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Summary: Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.

ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/β-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

The mismatch in the conserved structure but different expression levels of C-reactive protein (CRP) in distinct species is reconciled by functional selection on hidden activities of unfolded CRPs.

Background and aims: C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). Methods: The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice. Results: CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. Conclusion: Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in various effector cells and have been proved to play vital roles in smooth muscle contraction and digestive secretion. However, there are relatively few literatures revealing the roles of mAChRs in inflammatory processes, and its underlying regulatory mechanisms have not been elucidated. Taking the advantages of live imaging of zebrafish, we found that inhibition of mAChRs resulted in increased neutrophils recruitment and proinflammatory cytokines expression, whereas activation of mAChRs led to opposite outcome. Subsequently, we found that mAChRs regulated the expression of arginases (args), and pharmacological intervention of args level could reverse the effects of mAChRs on neutrophils migration and cytokines expression, suggesting that args are important downstream proteins of mAChRs that mediate the regulation of inflammatory response. In this study, we identified args as novel downstream proteins of mAChRs in inflammatory responses, providing additional evidence for system immune regulation of cholinergic receptors.

In this study, the optimum spraying performance of a pressurized vortex atomizer using water as the working fluid was investigated experimentally by modifying the geometry of auxiliary air holes via the Taguchi method. The experimental results were also examined by CFD simulations. The four control factors of the auxiliary air holes are their numbers, areas, inclination angles, and lengths. With five levels for each control factor, an L25 orthogonal table was selected. Each case of the L25 orthogonal table was test repeatedly three times to obtain key average results. The auxiliary air holes were designed by a KISSlicer CAD tool and fabricated by 3D printing. The 3D printing was carried out by fused deposition of PLA with a resolution of about 30 μm. In the experiments, the spraying jet patterns were recorded, and the water droplet weights were measured. By using the signal to noise ratios and the smaller-the-better quality characteristic, the effect of the control factors of the auxiliary air holes in descending order is the numbers, areas, inclination angles, and hole lengths, respectively. The optimum air hole configuration is the one with six holes, an inclination angle of 20°, an area of 18 mm2, and a length of 8 mm. The optimum condition was confirmed by a signal to noise ratio of 20.5 dB with 95% confidence interval. The resulting smaller jet opening angle is about 42°, close to the simulated angle of 45°. That is, by the novelty of combining 3D printing with the Taguchi method, this study obtains the optimum design with fast prototyping and relatively few experiments.

Background: Patients with recalcitrant frozen shoulder traditionally undergo arthroscopic capsular release. Some patients may have a concomitant partial-thickness rotator cuff tear (PTT). There is limited evidence if these PTT require repair at the same setting. We aim to compare if patients undergoing concomitant rotator cuff repair do better than patients undergoing capsular release alone. Secondarily, we aim to determine if outcomes after arthroscopic capsular release differ for patients with and without PTT. Methods: A retrospective review of patients with frozen shoulders undergoing arthroscopic capsular release between 2012 and 2016 was performed. Patients with partial-thickness tears and patients without rotator cuff tears were included. Clinical outcomes were collected preoperatively and at 3, 6, 12 months after operation. Results: There were 33 patients with PTT—15 underwent capsular release without repair (CR group), whereas 18 underwent capsular release with rotator cuff repair (RCR group). A total of 62 control patients without rotator cuff tears (No Tear) underwent arthroscopic capsular release only. For patients with PTT, there were no significant differences in preoperative demographics and function between the CR and RCR group. The CR group had significantly worse preoperative pain. At 1-year follow-up, the RCR group had significantly better internal rotation, lesser pain, and better function than the CR group. For patients undergoing capsular release only, the No Tear group had better internal rotation, lesser pain, and better function at 1 year compared with the CR group. Conclusion: Patients with a stiff, frozen shoulder and concomitant PTT do benefit from arthroscopic rotator cuff repair with capsular release. The benefit is evident at 1-year follow-up.

The fur color of mammals is mainly determined by melanin synthesized by melanocytes. Cell staining includes melanocyte development, melanin synthesis and metabolism, and signal pathways regulating melanin synthesis. Melanocytes can be classified into many types, and these types can be identified by a variety of melanocyte markers. Fur color can judge the physical condition and nutritional status of animals, and different fur colors may have certain influence on animal production. This paper reviews the structural basis and development cycle of mammalian fur color formation, describes the cytochrome process from neural crest to mature melanocytes residing in several tissues, summarizes the types of melanocytes and the markers of each type of melanocytes, and discusses the application of animal coat color in animal production, providing help for analyzing the genetic mechanism of mammalian fur color formation and providing effective suggestions for animal production affected by fur color. [ABSTRACT FROM AUTHOR]