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The mechanisms for spinal cord stimulation (SCS) to alleviate chronic pain are only partially known. We aimed to elucidate the roles of adenosine A1 and A3 receptors (A1R, A3R) in the inhibition of spinal nociceptive transmission by SCS, and further explored whether 2′-deoxycoformycin (dCF), an inhibitor of adenosine deaminase, can potentiate SCS-induced analgesia. We used RNAscope and immunoblotting to examine the distributions of adora1 and adora3 expression, and levels of A1R and A3R proteins in the spinal cord of rats after tibial-spared nerve injury (SNI-t). Electrophysiology recording was conducted to examine how adenosine receptor antagonists, virus-mediated adora3 knockdown, and dCF affect SCS-induced inhibition of C-fibre-evoked spinal local field potential (C-LFP). Adora1 was predominantly expressed in neurones, whereas adora3 is highly expressed in microglial cells in the rat spinal cord. Spinal application of antagonists (100 μl) of A1R (8-cyclopentyl-1,3-dipropylxanthine [DPCPX], 50 μM) and A3R (MRS1523, 200 nM) augmented C-LFP in SNI-t rats (DPCPX: 1.39 [0.18] vs vehicle: 0.98 [0.05], P =0.046; MRS1523: 1.21 [0.07] vs vehicle: 0.91 [0.03], P =0.002). Both drugs also blocked inhibition of C-LFP by SCS. Conversely, dCF (0.1 mM) enhanced SCS-induced C-LFP inhibition (dCF: 0.60 [0.04] vs vehicle: 0.85 [0.02], P <0.001). In the behaviour study, dCF (100 nmol 15 μl−1, intrathecal) also enhanced inhibition of mechanical hypersensitivity by SCS in SNI-t rats. Spinal A1R and A3R signalling can exert tonic suppression and also contribute to SCS-induced inhibition of spinal nociceptive transmission after nerve injury. Inhibition of adenosine deaminase may represent a novel adjuvant pharmacotherapy to enhance SCS-induced analgesia. [ABSTRACT FROM AUTHOR]

To describe and analyze the current research status of life-space mobility of the older persons in community. The literature in PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost, Scopus, OpenGrey, SinoMed, CNKI, WanFang, and VIP databases was computer searched, and the time frame was build to May 23, 2023. A total of 42 literatures were included, including 35 in English and 7 in Chinese, 30 of which were cross-sectional studies. Theoretical models related to spatial mobility included the "concentric circles" model and the "cone" model. 33 literatures reported the prevalence or level of spatial mobility limitations, and 9 assessment instruments were used, The influencing factors can be divided into four categories. 9 literatures reported on the adverse effects, and 9 literatures reported on the prevention and intervention. The limitation of life-space mobility is a common and under-recognized phenomenon among the older persons in the community,with serious adverse effects, complex and diverse influencing factors. [ABSTRACT FROM AUTHOR]

• Of the total sample, 78% had in-hospital mortality. • Factors associated with in-hospital mortality from free wall rupture were first reported. • Pericardiocentesis, pericardial effusion at admission, the acute myocardial infarction to free wall rupture time, and previous myocardial infarction were associated factors. Free wall rupture is a fatal and emergency complication of acute myocardial infarction. The factors associated with in-hospital mortality from free wall rupture remain unclear. To investigate the factors associated with in-hospital mortality from free wall rupture. We performed a single-center, retrospective study. We enrolled 111 consecutive patients with free wall rupture following acute myocardial infarction who were admitted to Fuwai Hospital from January 2005 to May 2021. The primary endpoint was in-hospital death. Clinical characteristics, laboratory data, and treatment modalities associated with in-hospital mortality were analyzed. Eighty-seven of the 111 study participants died in hospital. Multivariate Cox regression analysis showed that pericardiocentesis (hazard ratio [HR] 0.296, 95% confidence interval [CI] 0.094–0.929, p = 0.037), pericardial effusion at admission (HR 0.083, 95% CI 0.025–0.269, p <0.001), time interval between acute myocardial infarction and free wall rupture (HR 0.670, 95% CI 0.598–0.753, p <0.001), and previous myocardial infarction (HR 0.046, 95% CI 0.010–0.208, p <0.001) were independently associated with in-hospital mortality. Pericardiocentesis, pericardial effusion at admission, the acute myocardial infarction to free wall rupture time, and previous myocardial infarction are associated with a lower rate of in-hospital mortality from free wall rupture after acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Drug response prediction is essential for drug development and disease treatment. One key question in predicting drug response is the representation of molecules, which has been greatly advanced by artificial intelligence (AI) techniques in recent years. In this review, we first describe different types of representation methods, pinpointing their key principles and discussing their limitations. Thereafter we discuss potential ways how these methods could be further developed. We expect that this review will provide useful guidance for researchers in the community. [ABSTRACT FROM AUTHOR]

The phenomenological interplay in the segregation of phosphorus (P) and transition metal (TM) elements at grain boundaries (GBs) in steels has long been suspected to be the main contributor to temper embrittlement. However, many of the details remain unclear. Here, we investigate the segregation, co-segregation and cohesion effects of TMs (Co, Cr, Cu, Mn, Mo, Ni, Nb, Ti, V, W) along with P in various ferritic iron (α -Fe) GBs utilising density functional theory and simulations of kinetics. Our findings demonstrate that P is unlikely to cause intergranular fracture via weakened interfacial bonding when segregated by itself. Nevertheless, the stronger segregation binding of P compared to TMs can explain the ubiquitous presence of P segregated at GBs. We find that most P-TM interactions at ferritic GBs are repulsive and differ significantly from the corresponding interactions in the bulk. Due to the repulsive interactions and strong segregation binding of P, the enrichment of P over time at GBs leads to the depletion of prior-segregated cohesion-enhancing solutes at general GBs. Additionally, certain P-TM co-segregation combinations that are cohesion-lowering are energetically favoured at such GBs. We posit these mechanisms act in tandem as critical causalities of P-induced temper embrittlement in alloyed steels. Finally, we reveal a contradiction in the predicted cohesion effects of segregated P calculated in the Rice–Thomson–Wang theory of interfacial embrittlement compared to that as assessed by chemical bonding strength, calculated in the DDEC6 bond-order framework. These findings have important implications for GB engineering for interfacial cohesion. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] The segregation of transition metal elements to grain boundaries in steels plays a critical role in determining their cohesion. Here, we investigate the segregation, co-segregation, and cohesion effects of various transition metals (Co, Cr, Cu, Mn, Mo, Ni, Nb, Ti, V and W) to different grain boundary characters in ferritic-iron (α -Fe) through a systematic, brute-force style configurational analysis utilising density functional theory calculations. We demonstrate that differing grain boundary characters change not only transition metal segregation and co-segregation behaviours, but also their effects on cohesion. The effects of co-segregated solutes on cohesion can be substantially different from their summed individual parts. We show that solute-solute interactions at grain boundaries vary significantly as a function of grain boundary character. These interactions are shown to be substantially different from those that occur in the bulk. We introduce a novel quantitative method for assessing effects of segregated elements on interfacial cohesion through calculating the strength of bonds at a grain boundary in the DDEC6 bond-order framework. It is shown that work of separation quantities calculated through rigid separation of surfaces better captures the strength of bonding in most cases, and thus more accurately depicts intergranular fracture. Collectively, these results offer valuable insight towards rational grain boundary engineering in steels. [ABSTRACT FROM AUTHOR]

This meta-analysis was designed to systematically determine the effect of high-fidelity simulation teaching on nursing students' knowledge level, professional skill level and clinical ability. High-fidelity simulation is an increasingly popular pedagogical approach in nursing education. It provides students with opportunity to practice in a variety of simulations before entering clinical practice through a variety of real-life situational experiences and many institutions and educators have embraced this method for enhancing access to clinical skills. However, evidence for the effectiveness of the method in nursing teaching remains scarce. A meta-analysis and systematic review. The following Chinese and English databases were searched for relevant articles: PubMed, Embase, Cochrane library, Web of Science, CNKI (China National Knowledge Infrastructure) and Wangfang. The search encompassed the establishment of these databases up until November 2021. Two reviewers separately entered the data into Review Manager Software 5.3. A total of 15 studies were included in this study. High-fidelity simulation significantly increased nursing students' knowledge acquisition (SMD = 1. 37, 94％CI:0. 73–2. 00， P ＜0. 0001), enhanced nursing students'professional skills (SMD = 0. 90, 95％CI:0. 36–1. 44， P = 0. 0001). In terms of clinical practice ability outcomes, high-fidelity simulation significantly improved the levels of critical thinking ability (SMD = 0. 58, 95％CI:0. 09–1. 07， P ＜0. 00001), Clinical judgement ability (SMD = 1. 34, 95％CI:0. 38–2. 31， P ＝0. 006) and communication skills (SMD = 2. 62, 95％CI:1. 84–3. 40， P ＜0. 001) of nursing students. We found that high-fidelity simulation have strong educational effects in nursing education, helping nursing students to increase knowledge acquisition, enhance professional skills and cultivate their clinical practice ability (critical thinking ability, communication skills and clinical judgement ability). These findings can provide guidance for nursing educators, indicating that the use of High-fidelity simulation teaching represents an effective solution for transitioning students from the learning environment to clinical practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • GB character controls vulnerability to hydrogen segregation and embrittlement. • Low energy, highly coherent GBs minimise H-accumulation, embrittlement. • H-H interactions controls amount of H segregation, accumulation at a GB. • Bonding analysis reveals fundamental atomistic nature of H-embrittlement at GBs. Here, the segregation and accumulation of hydrogen in Ni grain boundaries, and its effects on cohesion and tensile mechanical strength were studied by means of density functional theory simulations. Three model grain boundaries were considered: the Σ 3 (1 1 ¯ 1) [ 110 ] , Σ 5 (120) [ 001 ] and Σ 11 (1 1 ¯ 0) [ 113 ] , as representatives for the highly coherent twin, high energy random high angle, and "special" low energy highly coherent grain boundaries, respectively. Hydrogen segregation was found to be favourable in the Σ 5 and Σ 11 grain boundaries, but not in the Σ 3. Hydrogen accumulation studied via a comprehensive site-permutation analysis revealed the mechanisms for how H accumulation capacity varies as a function of grain boundary character. We show that the interfacial cohesion of boundaries can diminish by between 6.7–37.5% at varying levels of H-accumulation. The cohesion of the grain boundaries was analysed using a novel chemical bond-order based approach, enabling a quantitative atomistic determination of the fracture paths arising from hydrogen embrittlement. These simulations explain the details of why grain boundary character is the principal determinant of the likelihood of hydrogen segregation and accumulation, and hence their vulnerability to hydrogen-enhanced decohesion. This knowledge can be used in the design of thermomechanical processes to achieve grain boundary engineering for resistance to hydrogen embrittlement. [ABSTRACT FROM AUTHOR]

Magnetic CoFe 2 O 4 serves as a promising photo-Fenton reagent, but its low adsorption ability and catalytic activity inhibit the effective removal of atrazine (ATZ). Herein, activated carbon fiber/cobalt ferrite (ACF/CoFe 2 O 4) composites were fabricated by hydrothermal deposition of CoFe 2 O 4 nanoparticles around ACFs. As compared with CoFe 2 O 4 nanoparticles, the ACF/CoFe 2 O 4 composites showed better adsorption ability due to the synergistic effect between CoFe 2 O 4 nanoparticles and ACF felts. The ATZ adsorption trend over the ACF/CoFe 2 O 4 composites matched well with pseudo-first-order and pseudo-second-order kinetics model, suggesting that the diffusion and adsorption reaction played equal contribution to the ATZ adsorption. Notably, the ACFs in the ACF/CoFe 2 O 4 composites decreased the band gap of CoFe 2 O 4 nanoparticles from 1.82 eV to 1.62 eV, facilitating the enhanced photocatalytic activity. In the reaction system of ATZ, H 2 O 2 and ACF/CoFe 2 O 4 composites, the remarkable changes of Co and Fe valence states demonstrated that both Co3+/Co2+ and Fe3+/Fe2+ circulations took part in the Fenton-like reaction. The hydroxyl radicals that were generated in the photo-Fenton system effectively induced the oxidative degradation of ATZ. Moreover, the photo-Fenton degradation pathway of ATZ was proposed according to LC-MS analyses. Hence, the ACF/CoFe 2 O 4 composite was a promising photo-Fenton catalyst to remove pesticide pollutants via physical adsorption and photo-Fenton degradation. [Display omitted] • CoFe 2 O 4 nanoparticles deposit hydrothermally on ACFs for atrazine removal. • Photo-Fenton degradation pathway of ATZ is proposed in this work. • ACFs improve the physical adsorption capacity of ACF/CoFe 2 O 4 composites. • ACF/CoFe 2 O 4 composites exhibit excellent photo-Fenton catalytic activity. [ABSTRACT FROM AUTHOR]

Chicken primordial germ cells (PGCs) are important cells with significant implications in preserving genetic resources, chicken breeding and production, and basic research on genetics and development. Currently, chicken PGCs can be cultured long-term in vitro to produce single-cell clones. However, systematic exploration of the cellular characteristics of these single-cell clonal lines has yet to be conducted. In this study, single-cell clonal lines were established from male and female PGCs of Rugao Yellow Chicken and Shouguang Black Chicken, respectively, using a micropipette-based method for single-cell isolation and culture. Analysis of glycogen granule staining, mRNA expression of pluripotency marker genes (POUV , SOX2 , NANOG), germ cell marker genes (DAZL , CVH), and SSEA-1, EMA-1, SOX2, C -KIT, and CVH protein expression showed positive results, indicating that PGCs maintain normal cellular properties after single-cell cloning. Furthermore, tests on proliferation ability and gene expression levels in PGC single-cell clonal lines showed high expression of the pluripotency-related genes and TERT compared to control PGCs, and PGC single-cell clonal lines demonstrated higher proliferation ability. Finally, green fluorescent protein (GFP)-PGC single-cell clonal lines were established, and it was found that these single-cell clonal lines could still migrate into the gonads of recipients, suggesting their potential for germ-line transmission. This study systematically validated the normal cellular characteristics of PGC single-cell clonal lines, indicating that they could be applied in genetic modification research on chickens. • PGC single-cell clonal lines were created from two breeds of chickens. • PGCs maintain their normal cellular properties after single-cell cloning. • Single-cell clonal lines of PGCs could still migrate into the gonads of recipients. [ABSTRACT FROM AUTHOR]

Purpose: This study was to test the hypothesis that intramedullary (IM) nailing fixation of midshaft clavicle fractures could result in better clinical outcomes and lower complications rates than plating fixation.Methods: PubMed, Embase, and the Cochrane Library database were used to search all English language published randomized controlled trials (RCTs) of midshaft clavicle fractures using plating versus IM nailing. The characteristics of the study participants were collected. Outcomes of postoperative shoulder functional measurements, operative data and complications rates were meta-analyzed.Results: Eight hundred and ninety-five patients in ten RCTs and three quasi-RCTs were involved in the meta-analysis. The results of meta-analysis of these studies showed that the functional outcome evaluated by the Constant Shoulder and Disabilities of the Arm, Shoulder and Hand (DASH) scores after accepting IM nailing was significantly better than that of plating fixation at one year post-operatively (P < 0.01), with the heterogeneity of 43% and 91%, respectively. Sensitivity analyses of the pooled results of Constant and DASH scores displayed that the functional advantage of IM nailing fixation comes from the subgroup of locked IM nailing. Further, regarding the operative statistics, operative time, blood loss and wound length were significantly less in the IM nailing group than the plating group (P < 0.001). The rates of infection, major complications and complications-related revision surgery were significantly higher in the plating group than the IM nailing group; however, there were no significantly statistical differences in other complications, e.g., nonunion, refracture after hardware removal, implant failure, symptomatic hardware, etc. (P > 0.05).Conclusion: The observations in this review suggested that IM nailing, especially locked IM nailing, could provide better shoulder functional outcome at one-year follow-up. Moreover, IM nailing fixation could effectively reduce operative time, blood loss, rates of infection, major complications, and revision surgery than plating. Further high-quality clinical trials with large samples and consistent designs are still needed to verify the long-term functional advantage of locked and unlocked IM nailing for midshaft clavicle fractures.Level Of Evidence: Level II. [ABSTRACT FROM AUTHOR]

The understanding of intrinsic kinetics was crucial in guiding reactor design. However, the intrinsic kinetics of catalytic hydrogenation of p-nitroanisole (PNA) to p-aminoanisole remains obscure. In this work, the kinetic characteristics were experimentally and theoretically investigated under various experimental conditions. From the power law analysis of the initial reaction rate, the reaction order was found to be from 0.34 (at 343 K) to 0.53 (at 353 K) for hydrogen and 0.31∼ 0.34 for PNA (at concentrations less than 90 g·L−1), while the reaction was considered to be zero-order under higher PNA concentration (>90 g·L−1). The data was also used to fit Eley-Rideal and Langmuir-Hinshelwood-Hougen-Watson (LHHW) models. It was found that the rate-controlling step was the adsorption of dual-site dissociative H 2 based on LHHW model. The accuracy of the screened model was verified by correlation, between the predicted data and experimental data. This study could provide significant guidance for the hydrogenation reaction and reactor. • The intrinsic kinetics of hydrogenation of PNA to PA was experimentally studied. • The parameters of power law rate model were obtained. • The absorption of dual-site dissociative H 2 was the rate-controlling step. [ABSTRACT FROM AUTHOR]

In mammals, E2 factor (E2F) acts as a cell cycle regulator. E2F transcription factor 4 (E2F4) is a member of the E2F family of transcription factors and usually represents predominant E2F activity in cells. The E2F4 gene has been extensively studied in animals and is associated with multiple functions, such as cell cycle regulation and apoptosis; however, little is known about its role during embryonic development. In this study, we investigated the function of E2F4 and its mechanism of action in porcine embryo development. For this purpose, we knocked down E2F4 by microinjecting double-stranded RNA of E2F4 at the 1-cell stage. The results showed that E2F4 knockdown in porcine embryos led to a significant decrease in the blastocyst rate and total cell number. Defective E2F4 expression reduced the level of G1/S checkpoints (cyclin E-cyclin-dependent kinase 2) and cell cycle-related gene expression at the 4-cell embryo stage and blastocyst. Moreover, a decrease in E2F4 expression increased phosphorylated H2A.X variant histones and activated ataxia telangiectasia mutated (ATM) and p53-p21 pathway. In addition, E2F4 depletion caused a significant decrease in histone acetylation. Taken together, E2F4 plays a critical role as a transcriptional activator in the development of porcine embryos, an observation that contradicts its well-established role as a transcription repressor. • E2F4 affected porcine embryonic development. • E2F4 induced DNA damage and G1/S arrest in porcine embryos. • E2F4 decreased histone acetylation in porcine embryos. [ABSTRACT FROM AUTHOR]

Although it is well known that myxomatous mitral valve disease stage B2 (MMVD stage B2) is predominantly characterized by ECM remodeling of the mitral valve, ECM-related proteomics alterations in plasma from dogs with this disease have yet to be elucidated. To determine whether the differentially expressed protein (DEP) associated with ECM are potential biomarkers of MMVD stage B2. Tandem mass tag (TMT) quantitative proteomics analysis was performed to determine the DEPs in plasma samples from a discovery cohort (5 dogs with MMVD stage B2 and 3 healthy controls, poodle). Candidate proteins were identified using DEPs and ECM-related protein network analysis and confirmed by enzyme-linked immunosorbent assay (ELISA) and western blotting in a validation cohort (52 dogs with MMVD stage B2 and 56 healthy controls, multi-breed). The diagnostic potential of a candidate biomarker DEP was evaluated using receiver operating characteristic (ROC) curve analysis. A total of 90 DEPs were identified between healthy and MMVD stage B2 dogs, and of these 90 DEPs, 16 were ECM-related proteins. One ECM-related DEP, serpin family H member 1 (SERPINH1), was significantly overabundance at the protein level in MMVD stage B2 dog plasma, and SERPINH1 expression had an area under the ROC curve (AUC) value of 0.885 (95% CI = 0.814–0.956, P < 0.0001) that allowed discrimination of MMVD stage B2 dogs from healthy dogs. Plasma SERPINH1 has good predictive and diagnostic value at dog with MMVD stage B2, suggesting that SERPINH1 may be used as a biomarker for early prediction and diagnosis of stage B2 of MMVD. MMVD is the most acquired cardiac disease in dogs. MMVD stage B2, is when the heart valve structure begins to change significantly but there are no clinical symptoms; it is a critical time during which to slow progression of the disease, so timely diagnosis is extremely important. This study suggests that plasma SERPINH1 levels might differentiate MMVD progression in dogs during the early stage. It is also the first study to consider SERPINH1 as a diagnostic biomarker in dogs with stage B2 MMVD. Another advantage is that dogs in the validation cohort were recruited from six breeds to reduce the impacts of breed factors and partly reflect the universality of SERPINH1 for diagnosing MMVD stage B2. [Display omitted] • Serum SERPINH1 is potential diagnostic biomarker in canine with MMVD stage B2. • Significant difference abundance of ECM-related proteins were notable molecular features of MMVD stage B2. • Actin and cytoskeletal protein binding signaling are modulated in canine with MMVD stage B2. [ABSTRACT FROM AUTHOR]