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.

Amolops wenshanensis Yuan & Jin & Li & Stuart & Wu 2018, sp. nov.

<i>Amolops wenshanensis</i> sp. nov. <p>(Fig. 3–8)</p> <p> <i>Amolops</i> sp. Stuart, Bain, Phimmachak and Spence, 2010: 57.</p> <p> <b>Holotype.</b> KIZ 0 21426, adult male, Wenshan National Nature Reserve, near Pingzai village, Xichou County, Wenshan city, Yunnan Province, China, 23.362°N, 104.839°E, 1,312 m asl., coll. 27 June 2016 by ZY (Fig. 1).</p> <p> <b>Paratypes.</b> KIZ 0 21425, KIZ 021428 - 30, KIZ 0 21435 (five adult males), same data as holotype. KU 292041 (one adult male), KU 292040, KU 292045 (two adult females), KU 292039, KU 292042 (two immature males), Diding village, Jingxi County, Guangxi Province, China, 23.1223°N, 105.9636°E, coll. 18-23 September 2004 by Juan Guayasamin, Luis Canseco, and Yunming Mo.</p> <p> <b>Diagnosis.</b> The genus <i>Amolops</i> is diagnosed primarily on the basis of the presence of a raised, sharply defined, abdominal sucker in the tadpole (Inger 1966). As the tadpole of the new species remains unknown, <i>Amolops wenshanensis</i> <b>sp. nov.</b> is placed here in the genus <i>Amolops</i> based on its morphological similarity to <i>A. cucae</i> and <i>A. compotrix</i> and by its phylogenetic position (Fig. 2). No mitochondrial DNA sequence of <i>A. monticola sensu stricto</i> is yet available, but <i>A. wenshanensis</i> <b>sp. nov.</b> is placed in the <i>A. monticola</i> group by having the combination of dorsolateral folds, smooth dorsal skin, and the side of head dark with a light-colored upper lip stripe extending to the axillary region (Stuart <i>et al</i>. 2010). <i>Amolops wenshanensis</i> <b>sp. nov.</b> is distinguished from other species in the <i>A. monticola</i> group by having the combination of small body size (adult males with SVL 35.7–39.9 mm; females with SVL 43.7–45.6 mm); smooth skin, without conspicuous glands, tubercles, warts or spinules on the dorsum; green dorsal coloration in life; immaculate venter; indistinct transverse bands on dorsal surfaces of limbs; distinct glandular dorsolateral folds; distinct tympanum; pineal body absent; all fingertips expanded with circummarginal grooves; two oblique vomerine teeth; vocal sac and white nuptial pad on the base of Finger I in adult males; supratympanic fold absent; outer metatarsal tubercle absent; glandular gold-white flank spot absent; and skin on venter not translucent.</p> <p> <b>Description of the holotype.</b> Adult male (Figs. 3–5), habitus moderately slender (SVL 35.7 mm); head slightly longer than wide (HW 92.0% of HL); snout obtusely pointed in dorsal view, projecting beyond lower jaw, rounded in profile, not depressed; nostril dorsolateral, closer to tip of snout than to eye; canthus rostralis distinct, internarial distance greater than interorbital distance (IOD 72.9% of IND); lores concave, sloping; eye diameter 73.3% of snout length; upper eyelid width 62.8% of interorbital distance; pineal body not visible; supratympanic fold absent; tympanum distinct, covered by layer of skin, 40.9% of eye diameter, not depressed relative to skin of temporal region, tympanic rim not elevated relative to tympanum; vomerine teeth on two oblique ridges; choanae oval. Tongue cordiform, with wide, U-shaped posterior notch; vocal sac opening on floor of mouth at each corner; sac-like gular pouch having anterior margin reaching center of orbit.</p> <p>Forearm robust (Fig. 4); relative lengths of fingers I<II<IV<III; all finger tips expanded with circummarginal grooves, Finger III equal to tympanum diameter; lateral fringes and webbing on fingers absent; one distinct subarticular tubercle on Fingers I and II, two distinct subarticular tubercles on Fingers III and IV; supernumerary tubercle indistinct; one thenar tubercle, oval; white glandular nuptial pad on Finger I, covering medial surface to base of finger disc.</p> <p>Hind limbs long, tibia (TFL 27.5 mm) longer than thigh (TIB 15.9 mm) and foot (FTL 15.8 mm); toes long and thin, relative lengths I<II<III<V<IV (Fig. 5); tips of all toes expanded with transversely oval disks and circummarginal grooves, relative width of toe disks 1<5<4<2<3; narrow, lateral fringes on all toes; subarticular tubercles all present, prominent, longitudinally ovoid; inner metatarsal tubercle prominent and oval; outer metatarsal absent; supernumerary tubercles absent.</p> <p>Skin on dorsal and ventral surfaces of head, body, limbs and flanks smooth, except granular on posterior surface of thigh around vent; one rictal gland; dorsolateral fold distinct, glandular, extending from rear of tympanum to inguinal region.</p> <p> <b>Coloration of holotype.</b> In life, dorsum light green (Fig. 3); side of head dark brown from snout tip to axilla; white upper lip stripe extending to slightly posterior of axilla; narrow, white stripe in loreal region from tip of snout to anterior margin of eye; flank dark brown anteriorly, diffusing to yellowish-brown posteriorly; narrow, gold stripe on edge of canthus from tip of snout along margin of upper eyelid, continuing along upper edge of dorsolateral fold; upper one-fourth of iris bronze, lower three-fourths gold, black reticulations throughout; dorsal surfaces of limbs olive brown, with irregular, narrow, incomplete grey-brown bands and irregular black spots; immaculate venter; subarticular tubercles on fingers and expanded finger tips grey, subarticular tubercles on toes and expanded toe tips dark brown; inner metatarsal tubercle dark brown; foot webbing yellowish-gray with dark gray spots.</p> <p>In preservative (Fig. 6), dorsum faded to light gray; posterior portion of flank and surface of limbs faded to whitish-gray with dark marbling; ventral surface of throat, chest and belly faded to creamy-white; ventral surfaces of limbs faded to creamy-white with dark brown speckling; foot webbing gray with dark gray spots.</p> <p> <b>Morphological variation.</b> Measurements of holotype and paratypes are given in Table 2. Paratype KIZ 0 21428 has several irregular, black spots on ventral surfaces of lower limbs.</p> <p> <b>Etymology.</b> The specific epithet is named for the type locality, Wenshan National Nature Reserve, in Xichou county, Wenshan city, Yunnan Province, China.</p> <p> <b>Distribution and ecology.</b> Currently, <i>A. wenshanensis</i> <b>sp. nov.</b> is known only from the holotype and paratype localities, which are separated by approximately 300 km straight-line distance, in Yunnan and Guangxi Provinces, China (Fig. 1). The species was collected at night (20:15–22:00 h) on the bank or on low vegetation (grasses or branches 0.5–1 m above the ground) along small streams (Fig. 7). The stream at the holotype locality was in forest, 1-2 m wide, and had slow current. Males were observed calling from small branches (0.5–1 m above the ground) along the stream. The call (not recorded) generally resembled a bird song (e.g. <i>Tarsiger indicus</i>) with multiple, long, high frequency notes. Other frog species observed along the stream at the holotype locality included <i>Xenophrys major</i>, <i>Ophryophryne microstoma</i>, <i>Leptolalax</i> sp., <i>Limnonectes bannaensis</i>, <i>Odorrana graminea</i>, and <i>Sylvirana</i> sp. Paratype KIZ 0 21425 had an aberrantly-colored patch of skin on its dorsum and inguinal region, possibly caused by infection from a fungus or other microorganism (Fig. 8).</p> <p> <b>Comparisons.</b> <i>Amolops wenshanensis</i> <b>sp. nov.</b> differs from all other species of <i>Amolops</i>, except those in the <i>A. monticola</i> group, by having the combination of dorsolateral folds, smooth skin, and side of head dark with a lightcolored upper lip stripe extending to the shoulder.</p> <p> Morphological characters for the <i>A. monticola</i> group are summarized in Table 4. <i>Amolops wenshanensis</i> <b>sp. nov.</b> differs from all other species in the <i>A. monticola</i> group by having an immaculate venter (spots on throat and/or belly in these species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. akhaorum</i>, <i>A. archotaphus</i>, <i>A. bellulus</i>, <i>A. compotrix</i>, <i>A. cucae</i>, <i>A. daorum</i>, <i>A. iriodes</i>, and <i>A. vitreus</i> by having an uncorrected <i>p</i> -distance> 6.7% in sequences of the ND2 gene and portions of flanking tRNA gene (Table 3; molecular data remain unavailable for <i>A. aniqiaoensis</i>, <i>A. mengyangensis</i>, <i>A. monticola</i>, <i>A. gerbillus</i>, and <i>A. nyingchiensis</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. akhaorum</i>, <i>A. archotaphus</i>, <i>A. bellulus</i>, <i>A. chunganensis</i>, <i>A. cucae</i>, <i>A. compotrix</i>, <i>A. daorum</i>, <i>A. gerbillus</i>, <i>A. iriodes</i>, <i>A. mengyangensis</i>, <i>A. monticola</i>, <i>A. nyingchiensis</i>, and <i>A. vitreus</i> by lacking distinct transverse bands on the dorsal surfaces of limbs (present in these species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. aniqiaoensis</i>, <i>A. archotaphus</i>, <i>A. bellulus</i>, <i>A. chakrataensis</i>, <i>A. chunganensis</i>, <i>A. gerbillus</i>, <i>A. iriodes,</i> and <i>A. nyingchiensis</i> by having green dorsal coloration in life (olive green in <i>A. aniqiaoensis</i>, <i>A. archotaphus</i>, and <i>A. bellulus</i>; grayish-brown in <i>A. chakrataensis</i>; dark gray in <i>A. gerbillus</i>; reddish-brown in <i>A. chunganensis</i>; iridescent green in <i>A. iriodes</i>; light brown or yellowish brown in <i>A. nyingchiensis</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. akhaorum</i>, <i>A. archotaphus</i>, <i>A. bellulus</i>, <i>A. chunganensis</i>, <i>A. cucae</i>, <i>A. compotrix</i>, <i>A. daorum</i>, <i>A. gerbillus</i>, <i>A. iriodes</i>, <i>A. mengyangensis</i>, <i>A. monticola</i>, <i>A. nyingchiensis</i> and <i>A. vitreus</i> by lacking dorsal spots (present in these species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. daorum</i> and <i>A. iriodes</i> by lacking a glandular gold-white flank spot (present in both species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. akhaorum</i>, <i>A. archotaphus</i>, <i>A. bellulus</i>, <i>A. chakrataensis</i>, <i>A. cucae</i>, <i>A. compotrix</i>, <i>A. daorum</i>, <i>A. mengyangensis</i>, <i>A. monticola</i>, and <i>A. nyingchiensis</i> by lacking a pineal body (present in these species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. archotaphus</i>, <i>A. cucae</i>, <i>A. compotrix</i>, and <i>A. vitreus</i> by lacking an outer metatarsal tubercle (present in both species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. aniqiaoensis</i>, <i>A. bellulus</i>, <i>A. chakrataensis</i>, and <i>A. nyingchiensis</i> by having smaller body size (SVL 35.7–39.9 mm in males, 43.7–45.6 mm in females of <i>A. wenshanensis</i> <b>sp. nov.</b>; SVL 52.0 mm in the single known male of <i>A. aniqiaoensis</i>; SVL 46.0–50.0 mm in males, SVL 64.0 mm in the single known female of <i>A. bellulus</i>; SVL 55.0 mm in the single known female of <i>A. chakrataensis</i>; and SVL 52.3–58.3 mm in males, 57.6–70.7 mm in females of <i>A. nyingchiensis</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. akhaorum</i> and <i>A. iriodes</i> by having males with nuptial pads (absent in both species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. daorum</i> and <i>A. iriodes</i> by having two oblique vomerine teeth (vomerine teeth absent in <i>A. daorum</i>, vomerine teeth crescent-shaped in <i>A. iriodes</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. vitreus</i> by having non-translucent skin on the venter (present in <i>A. vitreus</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. bellulus</i> and <i>A. nyingchiensis</i> by having males with gular sacs (absent in both species). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. chakrataensis</i> and <i>A. monticola</i> by lacking a supratympanic fold (present in <i>A. chakrataenis</i> and <i>A. monticola</i>). <i>Amolops wenshanensis</i> <b>sp. nov.</b> further differs from <i>A. aniqiaoensis</i> and <i>A. gerbillus</i> by having a distinct tympanum (indistinct in both species).</p> <p> <i>Amolops wenshanensis</i> <b>sp. nov.</b> is most similar in morphology, and most closely related in mitochondrial DNA (Fig. 2), to <i>A. compotrix</i> and <i>A. cucae</i> from Vietnam and Laos. However, as above, <i>A. wenshanensis</i> <b>sp. nov.</b> is readily distinguished from these two species by lacking distinct transverse bands on dorsal surfaces of limbs, an outer metatarsal tubercle, pineal body, spots on dorsum, and spots on throat and belly (all present in <i>A. compotrix</i> and <i>A. cucae</i>).</p> <p>literature.</p> <p> <i>……continued on the next page</i></p>Published as part of <i>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, pp. 498-512 in Zootaxa 4415 (3)</i> on pages 504-509, DOI: 10.11646/zootaxa.4415.3.5, <a href="http://zenodo.org/record/1242166">http://zenodo.org/record/1242166</a&gt

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