Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair ...growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4–20.0 μm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding.
•Chancelloriids from the Balang Biota are revised as a new and an undetermined taxa.•Archiasterella acuminata had an acuminate basal end and a pronounced apical tuft.•Chancelloriids likely reached a ...high diversification in the early Cambrian.
Chancelloriids are an enigmatic group of Cambrian animals characterized by radially symmetrical bodies equipped with spiny sclerites. Although they were major components of many benthic communities, current understanding on how this group diversified during the Cambrian remains limited. Clarifying these confusions about the diversification of chancelloriids requires new information provided by new studies of previously described and/or new material. Considering the emerging scenario of chancelloriids, the sack-like chancelloriids from the Stage 4 Balang Lagerstätte are restudied on the basis of previous collections, which are herein separated from Chancelloria eros Walcott, 1920, and revised as Archiasterella acuminata nov. sp. and Chancelloriidae gen. et sp. indet. The Ar. acuminata specimen is well preserved and does show its scleritome and sclerite characters, while the Chancelloriidae gen. et sp. indet. specimen is poorly preserved and its scleritome and sclerite characters are difficult to distinguish. By combining information from previous studies and the present research, data on chancelloriid occurrences in South China indicate that chancelloriids had once diversified in the Cambrian South China, evidenced by high-level richness of sclerite-based taxa during the late Fortunian to the middle Stage 3, and of sclerite formulas during the late Stage 2 to the Wuliuan. The result is inconsistent with the recent viewpoint that there were two flourishing ages of chancelloriids in South China. Although more evidence is needed to support our results, the present study offers insights in understanding the evolutionary dynamics of chancelloriids.
Recently, a series of studies have been conducted to investigate the association of the common biochemical biomarkers, such as serum lactate and creatinine, with clinical outcomes in cardiac arrest ...patients treated with extracorporeal membrane oxygenation (ECMO), however, the results were not consistent and the sample size of primary studies is limited. In the present study, we performed a systematic review and meta-analysis to summarize the associations.
Relevant studies in English databases (PubMed, ISI web of science, and Embase) and Chinese databases (Wanfang and CNKI) up to January 2018 were systematically searched. Crude ORs or HRs from the included studies were extracted and pooled to summarize the associations of lactate and creatinine with clinical outcomes including survival and neurological outcomes in ECMO treated cardiac arrest patients.
17 papers containing 903 cases were included in the present meta-analysis study. After pooling all the eligible studies, we identified the significant associations of high lactate level with poor survival (N=13, OR=1.335, 95%CI=1.167–1.527, P<0.001) and poor neurological outcome (N=2, HR=1.058, 95%CI=1.020–1.098, P=0.002) in CA patients treated with ECMO and a slight significant association of high creatinine with poor survival was also found (N=7, OR=1.010, 95%CI=1.002–1.018, P=0.015).
High serum lactate level was associated with poor survival and poor neurological outcome in CA patients treated with ECMO. Further well-designed studies with larger sample size should be conducted to confirm the results.
Src Homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) interacts specifically with GluN2A subunit of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors in spinal cord dorsal ...horn. This molecular interaction is involved in the development of GluN2A-dependent spinal sensitization of nociceptive behaviors. Intrathecal application of a GluN2A-derived polypeptide (short for pep-GluN2A) has been shown to disturb spinal GluN2A/SHP1 interaction and inhibit inflammatory pain. Here we found that SHP1 was also located at dorsal root ganglion (DRG) neurons and formed complexes with GluN2A subunit. Peripheral inflammation activated SHP1 in DRG neurons, which promoted GluN2A tyrosine phosphorylation. The SHP1 binding to GluN2A facilitated the glutamate release from primary afferent fibers and exaggerated nociceptive synaptic transmission onto postsynaptic spinal cord neurons. Our data showed that intradermal application of pep-GluN2A disrupted GluN2A/SHP1 interaction in DRG neurons, attenuated the ability of GluN2A subunit-containing NMDA receptors to regulate the presynaptic glutamate release and more importantly, alleviated the pain hypersensitivity caused by carrageenan, complete Freund's adjuvant and formalin. The neuropathic pain induced by spared nerve injury was also ameliorated by intradermal pep-GluN2A application. These data suggested that disruption of GluN2A/SHP1 interaction in DRG neurons generated an effective analgesic action against pathological pain.
Background: Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional ...cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA).
Methods: Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test.
Results: All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng2/ml2 vs. 1.18 ± 0.38 ng2/ml2, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng2/ml2 vs. 3.00 ± 0.44 ng2/ml2, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group.
Conclusions: Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney.
Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino ...acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino-acid insert within the TM3-TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission.
Extracorporeal membrane oxygenation (ECMO) could increase survival rate and neurological outcomes of cardiac arrest (CA) patients compared with conventional cardiopulmonary resuscitation (CCPR). ...Currently, the underlying mechanisms how ECMO improves neurological outcomes of CA patients compared with CCPR have not been revealed. A pig model of CA was established by ventricular fibrillation induction and then underwent CCPR or ECMO. Survival and hemodynamics during the 6 h after return of spontaneous circulation (ROSC) were compared. The levels of inflammatory cytokines and Ca
-ATPase and NA
-K
-ATPase activities were detected. Brain tissues histology and ultra-microstructure in CCPR and ECMO groups were also examined. Results suggested that ECMO significantly improved the survival of pigs compared with CCPR. Heart rate (HR) decreased while cardiac output (CO) increased along with the time after ROSC in both ECMO and CCPR groups. At each time point, HR in ECMO groups was lower than that in CCPR group while CO and mean arterial pressure in ECMO group was higher than CCPR group. In ECMO group, lower levels of IL-1, IL-1β, IL-6, TNFα, and TGFβ, especially IL-1, IL-6, TNFα, and TGFβ, were found compared that in CCPR group while no difference of IL-10 between the two groups was observed. Similar with the results from enzyme-linked immunosorbent assay, decreased expressions of IL-6 and TGFβ were also identified by Western blotting. And Ca
-ATPase and NA
-K
-ATPase activities were increased by ECMO compared with CCPR. Hematoxylin and eosin staining and ultra-microstructure examination also revealed an improved inflammation situation in ECMO group compared with CCPR group.
The solvothermal self‐assembly reaction of CuCl
2
, LaCl
3
, and H
2
tdc afforded a new heterometallic compound, namely CuLa
2
(tdc)
4
(H
2
O)(DMA)
2
n
(
1
) (H
2
tdc = thiophene‐2,5‐dicarboxylic ...acid, DMA =
N
,
N
′‐dimethylacetamide). Single crystal X‐ray diffraction analysis revealed that compound
1
features a 3D framework based on 1D heterometallic rod‐shaped Cu
II
‐La
III
‐carboxylate chains. The porous framework of the desolvated samples (denoted as
1′
) can be easily obtained via the heat treatment process at 200°C for 2 h. Gas adsorption investigations revealed that
1′
exhibits good light hydrocarbons adsorption performance. In addition, the anticancer activities of this heterometallic complex were evaluated via the MTT assay.
PDF
