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Purpose: Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen—polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty. Methods: A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software. Results: The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6–12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6–12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3–6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6–12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1–3 months) pain VAS score and postoperative (1–3 months) ODI score. Conclusions: Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence. [ABSTRACT FROM AUTHOR]

Background: Relevant evidence suggests that angiogenic factors contribute significantly to fibril matrix reconstruction following physical injuries to tendon ligaments. Vascular endothelial growth factor A (VEGFA), with its potent angiogenic effect, has been studied extensively, and its functional polymorphisms, including rs699947, rs1570360, and rs2010963, have been the focus of numerous investigations. Some scholars have explored the association between gene polymorphisms in the VEGFA and the risk of tendon ligament injury, but the findings are not entirely consistent. Objectives: The purpose of this study was to investigate the association between rs699947, rs1570360, and rs2010963 gene polymorphisms in VEGFA and the risk of tendon and ligament injuries. Methods: After including articles about the association of VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with tendon and ligament injuries according to the search strategy, we assessed their quality and conducted meta-analyses to examine the link between these polymorphisms and the risk of tendon and ligament injuries using odds ratios and 95% confidence intervals. Results: Of 86 related articles, six were included in the meta-analysis. Some of these suggest an association between VEGFA rs2010963 and the risk of tendon and ligament injury in the population, with the specific C allele being one of the adverse factors for knee injury. Some studies suggest that VEGFA rs699947 and VEGFA rs1570360 single-nucleotide polymorphisms are associated with anterior cruciate ligament rupture. The risk of non-contact anterior cruciate ligament rupture is nearly doubled in individuals with the rs699947 CC genotype compared to the control group. Our analysis did not find any significant relationship between VEGFA gene polymorphisms (rs699947, rs1570360, and rs2010963) and the chance of tendon and ligament injury without consideration of race. However, the European population reveals that the CC genotype of VEGFA rs699947 can result in a greater risk of tendon and ligament injury, whereas the AG genotype for rs1570360 provides some protection. Additionally, rs2010963 was significantly associated with tendon and ligament injury; individuals with the C allele and the CC genotype had higher risk. False-positive report probability confirmed the high credibility of our results. Conclusion: Overall, this study found no significant association between VEGFA rs699947, rs1570360, and rs2010963 polymorphisms and the risk of tendon ligament injury. However, in subgroup analysis, some genotypes of VEGFA rs699947, rs1570360, and rs2010963 were found to increase the risk of tendon ligament injury in European populations. [ABSTRACT FROM AUTHOR]

Summary: Immunogenic cell death (ICD) is a unique mode of cell death, which can release immunogenic damage‐associated molecular patterns (DAMPs) and tumor‐associated antigens to trigger long‐term protective antitumor immune responses. Thus, amplifying "eat me signal" during tumor ICD cascade is critical for cancer immunotherapy. Some therapies (radiotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), etc.) and inducers (chemotherapeutic agents, etc.) have enabled to initiate and/or facilitate ICD and activate antitumor immune responses. Recently, nanostructure‐based drug delivery systems have been synthesized for inducing ICD through combining treatment of chemotherapeutic agents, photosensitizers for PDT, photothermal transformation agents for PTT, radiosensitizers for radiotherapy, etc., which can release loaded agents at an appropriate dosage in the designated place at the appropriate time, contributing to higher efficiency and lower toxicity. Also, immunotherapeutic agents in combination with nanostructure‐based drug delivery systems can produce synergetic antitumor effects, thus potentiating immunotherapy. Overall, our review outlines the emerging ICD inducers, and nanostructure drug delivery systems loading diverse agents to evoke ICD through chemoradiotherapy, PDT, and PTT or combining immunotherapeutic agents. Moreover, we discuss the prospects and challenges of harnessing ICD induction‐based immunotherapy, and highlight the significance of multidisciplinary and interprofessional collaboration to promote the optimal translation of this treatment strategy. [ABSTRACT FROM AUTHOR]

This meta-analysis compared the efficacy of oblique lumbar interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of lumbar degenerative diseases. A computer search for the published literature on OLIF and MIS-TLIF for the treatment of lumbar degenerative diseases in the PubMed, Web of Science, Embase, CINAHL, MEDLINE, Cochrane Library, and other databases was performed, from which 522 related articles were retrieved and 13 were finally included. Two reviewers independently extracted data from the included studies and analyzed them using RevMan 5.4. The quality of the studies was assessed using the Cochrane systematic analysis and the Newcastle–Ottawa scale. Meta-analysis showed that the blood loss [95% confidence intervals (CI) (− 121.01, − 54.56), P < 0.001 ], hospital stay [95% CI (− 1.98, − 0.85), P < 0.001 ], postoperative fusion rate [95%CI (1.04, 3.60), P = 0.04 ], postoperative disc height [95% CI (0.50, 3.63), P = 0.01 ], and postoperative foraminal height [95% CI (0.96, 4.13), P = 0.002 ] were all better in the OLIF group; however, the complication rates were significantly lower in the MIS-TLIF group [95% CI (1.01, 2.06), P = 0.04 ]. However, there were no significant differences between the two in terms of surgery time, patient satisfaction, or postoperative functional scores. The OLIF group had the advantages of lower blood loss, a shorter hospital stay, a higher postoperative fusion rate, and better recovery of the disc and foraminal heights, whereas MIS-TLIF had a relatively lower complication rate. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future. [Display omitted] • Overview of metabolic reprogramming in esophageal carcinoma. • Functions and potential clinical application of exosomes in esophageal carcinoma. • Exosomes-mediated metabolic reprogramming in esophageal carcinoma progression. • Exosome-mediated metabolic reprogramming in the tumor microenvironment remodeling. [ABSTRACT FROM AUTHOR]

Introduction: This meta-analysis aimed to compare the differences in postoperative efficacy between oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative diseases. Materials and methods: Strictly based on the search strategy, we searched the published papers on OLIF and TLIF for the treatment of lumbar degenerative diseases in PubMed, Embase, CINAHL, and Cochrane Library. A total of 607 related papers were retrieved, and 15 articles were finally included. The quality of the papers was evaluated according to the Cochrane systematic review methodology, and the data were extracted and meta-analyzed using Review manager 5.4 software. Results: Through comparison, it was found that in the treatment of lumbar degenerative diseases, the OLIF group had certain advantages over the TLIF group in terms of intraoperative blood loss, hospital stay, visual analog scale (VAS) for leg pain (VAS-LP), Oswestry disability index (ODI), disc height (DH), foraminal height (FH), fused segmental lordosis (FSL), and cage height, and the differences were statistically significant. The results were similar in terms of surgery time, complications, fusion rate, VAS for back pain (VAS-BP) and various sagittal imaging indicators, and there was no significant difference. Conclusions: OLIF and TLIF can relieve low back pain symptoms in the treatment of lumbar degenerative diseases, but OLIF has certain advantages in terms of ODI and VAS-LP. In addition, OLIF has the advantages of minor intraoperative trauma and quick postoperative recovery. [ABSTRACT FROM AUTHOR]

Based on the CH-3 and WH-110A unmanned aerial vehicle (UAV) platforms, we independently developed aeromagnetic systems for fixed-wing UAVs (FUAV) and modified unmanned helicopters (MUH), respectively. These systems overcome key technological challenges in system integration, aeromagnetic compensation, and electromagnetic (EM) compatibility. We conducted a 1:100,000 aeromagnetic test using both systems in a tidal flat area in Jiangsu province, China. Both systems successfully completed 240 line km measurement lines and collected high-quality data with magnetic compensation accuracies of 0.01428 nT and 0.04690 nT, respectively. The dynamic noise was below 0.14 nT, accounting for 95.72% and 100% of the measurements. These results indicate that both systems offer high measurement accuracy, efficiency, low cost, convenience, and flexibility. We compared the two aeromagnetic systems based on their system parameters, integration modes, magnetic compensation methods and effects, and practical applications. By comprehensively analyzing their characteristics and application fields, we provide guidance for UAV-based aeromagnetic surveys in mineral exploration, basic geological survey and other related fields. And the FUAV and MUH aeromagnetic systems presented in this paper serve as a valuable reference for future research in this area. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. Methods: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. Results: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). Conclusion: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients. [ABSTRACT FROM AUTHOR]

To investigate the association of gene polymorphisms of TNF-α-308G/A rs1800629 with the susceptibility and severity of rheumatoid arthritis (RA), literature from PubMed, EMBASE, Web of Science and CNKI databases was searched. Two authors screened the literature independently, extracted data and evaluated the risk of bias of the included studies. According to the inclusion and exclusion criteria, five genetic models were established: The allelic model (A vs. G), dominant model (GA + AA vs. GG), recessive model (AA vs. GG + GA), co-dominant model (AA vs. GG) and super-dominant model (GG + AA vs. GA). Stata 17.0 software was used for the meta-analysis. A total of 34 eligible studies with 12,611 subjects were included, including 6,030 cases in the RA group and 6,581 controls. Meta-analysis calculations revealed that the genetic polymorphisms of TNF-α-308G/A rs1800629 were not significantly associated with susceptibility to RA, with an odds ratio and 95% confidence interval (CI) for each genetic model [A vs. G: 0.937 (0.762-1.152); GA + AA vs. GG: 0.918 (0.733-1.148); AA vs. GG + GA: 1.131 (0.709-1.802); AA vs. GG: 1.097 (0.664-1.813); and GG + AA vs. GA: 1.108 (0.894-1.373)]. For the association between TNF-α-308G/A rs1800629 gene polymorphisms and the severity of RA, the results of subgroup analysis calculations showed that TNF-α-308G/A rs1800629 gene polymorphisms were associated with the severity of RA in European populations, with the gene model and 95% CI [GA + AA vs. GG: 0.503 (0.297-0.853); and GG + AA vs. GA: 2.268 (1.434-3.590)]. When assessing the confidence in the positive results of the present study through the false-positive report probability, the positive results were observed to be reliable. No significant association was observed between genetic polymorphisms in TNF-α-308G/A rs1800629 and susceptibility to RA. However, a significant association exists with the severity of RA in European populations. [ABSTRACT FROM AUTHOR]

Rationale: Circular RNAs (circRNAs) have been demonstrated to contribute to esophageal cancer progression. CircBCAR3 (hsa_circ_0007624) is predicted to be differentially expressed in esophageal cancer by bioinformatics analysis. We investigated the oncogenic roles and biogenesis of circBCAR3 in esophageal carcinogenesis. Methods: Functions of circBCAR3 on cancer cell proliferation, migration, invasion, and ferroptosis were explored using the loss-of-function assays. A xenograft mouse model was used to reveal effects of circBCAR3 on xenograft growth and lung metastasis. The upstream and downstream mechanisms of circBCAR3 were investigated by bioinformatics analysis and confirmed by RNA immunoprecipitation and luciferase reporter assays. The dysregulated genes in hypoxia-induced esophageal cancer cells were identified using RNA-seq. Results: CircBCAR3 was highly expressed in esophageal cancer tissues and cells and its expression was increased by hypoxia in vitro. Silencing of circBCAR3 repressed the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro, as well as inhibited the growth and metastasis of esophageal xenograft in mice in vivo. The hypoxia-induced promotive effects on esophageal cancer cell migration and ferroptosis were rescued by circBCAR3 knockdown. Mechanistically, circBCAR3 can interact with miR-27a-3p by the competitive endogenous RNA mechanism to upregulate transportin-1 (TNPO1). Furthermore, our investigation indicated that splicing factor quaking (QKI) is a positive regulator of circBCAR3 via targeting the introns flanking the hsa_circ_0007624-formed exons in BCAR3 pre-mRNA. Hypoxia upregulates E2F7 to transcriptionally activate QKI. Conclusion: Our research demonstrated that splicing factor QKI promotes circBCAR3 biogenesis, which accelerates esophageal cancer tumorigenesis via binding with miR-27a-3p to upregulate TNPO1. These data suggested circBCAR3 as a potential target in the treatment of esophageal cancer. Hypoxia induces the upregulation of E2F7, which transcriptionally activates QKI in esophageal cancer cells. QKI increases the formation of circBCAR3 by juxtaposing the circularized exons. CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p. [ABSTRACT FROM AUTHOR]

Objective. The mechanism of circRNA on M2 macrophage polarization, which contributes to esophageal cancer, remains unclear. This study is aimed at clarifying the mechanism of circRNA on esophageal cancer by regulating M2 macrophage polarization. Methods. The expression of circRNA TCFL5 and miR-543 was detected by qRT-PCR. Western blot was used to detect the expression of FMNL2 and CD163. CCK-8 and transwell assay was used to detect the proliferation, migration, and invasion of Eca109 and KYSE150, respectively. Flow cytometry was used to detect the CD163 positive cells. The contents of IL-10, TGF-β, TNF-α, IL-6, and IL-1β were detected by ELISA. A dual-luciferase reporter system was used to detect the regulation of miR-543 to circRNA TCFL5 and FMNL2. Results. 156 upregulated circRNAs and 91 downregulated circRNAs in esophageal cancer tissues were identified, and the expression of circRNA TCFL5 showed the most significant upregulation. Overexpression of circRNA TCFL5 promotes proliferation, invasion, and migration of Eca109 and KYSE150 and promotes tumor growth in vivo. circRNA TCFL5 served as a sponge of miR-543, and FMNL2 was a downstream target gene of miR-543. circRNA TCFL5 promotes cell proliferation, migration, and invasion of Eca109 and KYSE150 by modulating the miR-543/FMNL2 axis. Macrophage M2 polarization promoted proliferation, invasion, and migration of Eca109 and KYSE150 cells, and circRNA TCFL5 mediated macrophage M2 polarization by regulating the FMNL2/miR-543 axis. Conclusion. In the present study, we identified that circRNA TCFL5 was dramatically upregulated in esophageal cancer, and circRNA TCFL5 promotes esophageal cancer progression by modulating M2 macrophage polarization via the miR-543-FMNL2 axis, which provides a potential target for the treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Pelvic organ prolapse (POP) lowers the quality of life in elderly women, and there have been no studies on its role in the pathogenesis of POP. The purpose of this study is to investigate the effect of β‐catenin on proliferation and collagen anabolism in human vaginal fibroblasts (HVFs). Materials and Methods: The adherence and differential adherence methods were used to culture and purify HVFs. RNA interference was applied to knockdown β‐catenin and lithium chloride was used to activate Wnt/β‐catenin signaling pathway. β‐catenin nuclear translocation was tested by immunofluorescence, and HVF proliferation was detected by performing MTT assays. Results: The expression of β‐catenin, phosphorylated‐β‐catenin, phosphorylated‐glycogen synthase kinase 3β (p‐GSK3β), collagen I, matrix metalloproteinase 2 (MMP2), and tissue‐derived inhibitors of metalloproteinases 2 (TIMP2) was assessed by western blot analysis. The expression of β‐catenin and collagen I was lower in HVFs of POP group than that of control group. The proliferation rate of HVFs in POP group was lower than that in control group. Knockdown of β‐catenin decreased the cell proliferation rate and the expression of collagen I. Lithium chloride can activate the Wnt/β‐catenin signaling pathway. Conclusion: β‐catenin participates in the proliferation and collagen I synthesis of HVFs. The decrease of β‐catenin expression may be closely related to the occurrence, and development of POP. LiCl can activate the Wnt/β‐catenin signaling pathway in HVFs and thus increase HVFs proliferation and collagen synthesis. [ABSTRACT FROM AUTHOR]

The image in Figure 5C, A549, pcDNA3.1/PVT1+mimic control, has been duplicated with the image from Figure 2H, Cell invasion, si-NC, from Qian P et al (2020). The images in Figure 3D, H1299, si-NC and A549, si-nc, have been duplicated with the images from Figure 7D, A549, si-nc and H1299, si-nc, respectively. [Extracted from the article]

Purpose: This meta-analysis compared the efficacy and safety of Proximal Femoral Nail Antirotation (PFNA) and InterTan Nail in the treatment of intertrochanteric fractures. Given the high incidence of femoral intertrochanteric fractures in the elderly population and its impact on quality of life, choosing the most effective and safest surgical option is crucial. PFNA and InterTan are currently two commonly used techniques, but there is a lack of systematic evaluation comparing their safety and effectiveness. This study aims to fill this knowledge gap through Meta-analysis, providing clinicians with evidence-based treatment recommendations. Materials and methods: A computer search was used to search for published literature on PFNA and InterTan in the treatment of intertrochanteric fractures in PubMed (Medline), Web of Science, Embase, Cochrane Library (CENTRAL), Cinahl, CBM, and CNKI.A total of 853 related literatures were retrieved, and 15 literatures were finally included. Newcastle-Ottawa-Scale and Cochrane systematic review methodologies were used to assess the quality of the literature. Meta-analysis was performed using Review Manager 5.4 software, following data extraction. Results: The comparison found that during the surgical treatment of intertrochanteric fractures, the operation time, fluoroscopy time, and blood loss in the PFNA group were significantly shorter than those in the InterTan group, and the difference was statistically significant. In terms of postoperative complication rates, the InterTan group had a significant advantage over the PFNA group. Shaft fracture, varus collapse, cut out, screw migration, and pain of hip and thigh were the most likely to occur in the PFNA group, and the differences were all statistically significant. In terms of postoperative efficacy, the results of the PFNA group and the InterTan group were comparable, and there was no significant differences. Conclusions: When selecting surgical techniques for the treatment of femoral intertrochanteric fractures, it is necessary to conduct individualized assessments based on the patient's overall health status, surgical tolerance, and post-operative recovery needs. For patients who cannot tolerate long-term surgery or are in poor physical condition, PFNA may be more appropriate. While for patients who can tolerate long-term surgery or have more complex conditions, InterTan may be more suitable. [ABSTRACT FROM AUTHOR]

Objective: To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies. Materials and methods: Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset. Results: The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression. Conclusion: The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments. [ABSTRACT FROM AUTHOR]

Background. BMPER has been reported to be associated with the biological behavior of a few malignant tumors, but the mechanism is still unclear. We aimed to detect BMPER expression in ovarian epithelial tumor tissues and its effects on their biological behaviors, as well as to elucidate the possible mechanism. Methods. BMPER expression in ovarian epithelial tumor tissues was detected by immunohistochemistry. BMPER expression in ovarian cancer cell lines was inhibited via RNA interference. Changes in the malignant behaviors of ovarian cancer cells were detected by MTT, wound healing, Transwell, and flow cytometry assays. Changes in proteins in the MAPK and autophagy-related signaling pathways were detected by Western blot analysis. Results. The expression of BMPER was significantly upregulated in ovarian epithelial malignant tumors and was related to increased lymph node metastasis and lower survival rate. High BMPER expression is an independent risk factor for poor prognosis in patients. Inhibition of BMPER inhibited the proliferation, invasion, and migration of ovarian cancer cells and promoted apoptosis. In addition, BMPER downregulation decreased the expression of PCNA, Bcl-2, MMP2, and MMP9 and increased the expression of Bax. Moreover, the levels of p-ERK, p-MEK, and the autophagy-related protein p-mTOR were decreased, and Beclin 1 levels and the LC3II/I ratio were increased. Conclusions. Our findings indicated that BMPER is closely related to poor prognosis in ovarian cancer. BMPER plays a role in promoting the malignant biological behavior of tumor cells through the MAPK and autophagy-related signaling pathways. [ABSTRACT FROM AUTHOR]

Cyclodipeptide 2,5‐diketopiperazines (DKP) are privileged structural units present in drugs and natural alkaloids. This work reports a new method for the synthesis of biologically important DKP scaffolds based on an intramolecular nucleophilic α‐addition of general amides towards an alkynamide system. The utility of this umpolung cyclization mediated by trimethyl phosphine and l‐glutamic acid is highlighted by its application to the concise total syntheses of 6‐methoxyspirotryprostatin B (the first total synthesis), spirotryprostatin A, and spirotryprostatin B. Alkaloid synthesis: This work reports a concise and practical approach towards the synthesis of spirotryprostatins. This synthetic route features an organo‐mediated intramolecular umplolung cyclization to construct the DKP ring system, a Grignard addition‐dehydration‐Friedel–Crafts reaction procedure to establish the C‐ring and the prenyl moiety, and a regioselective oxidation and microwave‐assisted stereospecific rearrangement to afford the spiro‐oxindole system. [ABSTRACT FROM AUTHOR]

Abstract This paper addresses the longitudinal control problem of air-breathing hypersonic vehicles subject to actuator faults, full state constraints and backlash-like hysteresis. To accomplish the full state constraints, the modified nonlinear mappings are proposed to transform the altitude subsystem to a new system without state constraints. An adaptive backstepping controller is developed for this new system, in which the command filters are embedded to eliminate the problem of "explosion of terms". Then, the controller parameters are updated to compensate the dysfunction of failed actuators and attenuate the unfavorable effects resulted from the backlash-like hysteresis. It is proved that the proposed controller can guarantee that the tracking errors converge to an arbitrarily small residual set and the full state constraints are not violated. Simulation results are carried out to demonstrate the effectiveness of the proposed control scheme. [ABSTRACT FROM AUTHOR]

Introduction and Objective: The relationship between either paraoxonase 1 (PON1) gene promoter DNA methylation or genetic variations and bleeding or major adverse cardiac events after dual antiplatelet therapy has been incompletely characterized. We aimed to systematically investigate the role of genetic variations and DNA methylation of the PON1 CpG island promoter on the clinical outcomes of dual antiplatelet therapy for patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).Methods: This study included 653 patients with CAD undergoing PCI and receiving dual antiplatelet therapy. Genomic DNAs were isolated from whole blood and were genotyped for the three single nucleotide polymorphisms (SNPs) of the PON1 gene. The DNA methylation levels in the PON1 promoter region were determined by bisulfite sequencing or pyrosequencing at five CpG sites (positions -142, -161, -163, -170, and -184 from the transcription start site). Clopidogrel and its metabolites in plasma were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and platelet function analysis was performed using the VerifyNow assay.Results: Statistically significant associations between methylation levels at five PON1 CpG sites and bleeding were observed: -184 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00, p = 0.028]; -170 (OR 0.99, 95% CI 0.97-1.00, p = 0.048); -163 (OR 0.98, 95% CI 0.96-1.00, p = 0.029); -161 (OR 0.98, 95% CI 0.97-1.00, p = 0.026); and -142 (OR 0.98, 95% CI 0.97-1.00, p = 0.042) at a false discovery rate of <5%. Statistical analysis also revealed that aspirin reaction units (ARUs) were significantly associated with PON1 methylation level at CpG site -163 (p = 0.0342). The ARUs of patients with the PON1 126 CC genotype was 527 ± 94, which was higher than the ARUs (473 ± 89) of patients with the 126 CG genotype (p = 0.0163). Multivariate logistic regression analysis indicated that the PON1 methylation level at CpG site -161 (OR 0.95, 95% CI 0.92-0.98, p = 0.002) and the use of angiotensin-converting enzyme inhibitors (OR 0.48, 95% CI 0.26-0.89, p = 0.021) were associated with a decreased risk of bleeding events.Conclusions: Hypomethylation of CpGs in the PON1 promoter may be a weak, albeit statistically significant, risk factor of bleeding after dual antiplatelet therapy. Further large-scale studies are needed to verify our results. [ABSTRACT FROM AUTHOR]

An efficient protocol for the synthesis of 2-arylsulfonyl quinolines has been developed via a metal-free catalyzed cross-coupling reaction of chloroquinoline with sodium arylsulfinates in moderate-to-good yields under microwave irradiation. The reactions proceed with a wide range of substrates with good functional group tolerance. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is an invasive malignant neoplasm of the bones. The present study identified and analyzed key genes associated with OS. Expression profiling of the dataset GSE49003, which included 6 metastatic and 6 non‑metastatic OS cell lines and was obtained from the Gene Expression Omnibus, was performed. Following data preprocessing, the differentially expressed genes (DEGs) were selected using the limma package in R. Subsequently, bidirectional hierarchical clustering using the pheatmap package in R and an unpaired Students' t‑test was performed for the DEGs. Based on the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software, a protein‑protein interaction (PPI) network for the DEGs was constructed. Using Database for Annotation, Visualization and Integrated Discovery software and the Kyoto Encyclopedia of Genes and Genomes Orthology Based Annotation System server, functional and pathway enrichment analyses were performed for the DEGs corresponding to the proteins of the network. In addition, the transcription factors (TFs) and CpG islands of the gene promoter were searched for using the TRANSFAC database and CpG Island Searcher software, respectively. A total of 323 DEGs were identified between the metastatic and non‑metastatic samples. In the PPI network, upregulated epidermal growth factor receptor (EGFR) exhibits a high degree and was therefore highly interconnected with other proteins. Enrichment analysis revealed that EGFR was enriched in cytoskeleton organization, organic substance response and the signaling pathway of focal adhesion. The TFs early growth response 1, nuclear factor‑κB complex subunits, peroxisome proliferator activated receptor α, signal transducer and activator of transcription 3 and MYC proto‑oncogene were identified in the EGFR promoter region. Furthermore, multiple CpG islands, starting from the 400 bp of the EGFR promoter sequence, were predicted. Methylated modification of the CpG islands in the EGFR promoter may help to regulate EGFR expression. The TFs identified in the EGFR promoter may function in the progression of OS. [ABSTRACT FROM AUTHOR]

Terrible triad injury of the elbow (TTIE) is a severe high-energy injury to the elbow, mainly including elbow dislocation, coronoid fracture and radial head fracture. It is difficult to maintain the stability of the elbow joint using traditional conservative treatment, and there is a high risk of redislocation and various complications. Therefore, surgical treatment is currently advocated, mainly for repairing damaged ligaments and reconstructing bony structures, but there is still controversy about the treatment plan for the radial head. The current meta-analysis was conducted to compare the differences in efficacy of radial head arthroplasty (RHA) and open reduction internal fixation (ORIF) in the treatment of TTIE. Published literature related to the treatment (either ORIF or RHA) of TTIE was searched for in Embase, PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations and Theses, Cochrane Library and Chinese Biomedical Literature Database. According to the search strategy, a total of 1,928 related publications were retrieved. The patient must have been diagnosed with TTIE and required surgery on the radial head. The interventions were RHA and ORIF. Non-case-control studies, case reports, review articles, letters, duplicate reports and literature without sufficient relevant data were excluded. The quality of the literature was evaluated according to the Cochrane systematic review methodology and the Jadad scale. After data extraction, meta-analysis was performed using ReviewManager 5.4 software (Cochrane). A total of 15 studies involving 455 patients (189 who underwent RHA and 266 who underwent ORIF) were included. Range of motion (ROM) of the forearm (pronation-supination arc) after surgery in the RHA group [95% CI (0.28, 9.59); P=0.04] was found to be significantly superior to the ORIF group, with a lower incidence of complications [95% CI (0.22, 0.84); P=0.01]. However, there was no statistically significant difference for the Mayo Elbow Performance Score, Disabilities of the Arm, Shoulder and Hand Score nor for ROM of the elbow (flexion-extension arc). Overall, compared with the ORIF group, the RHA group had better forearm rotational ROM and fewer complications after surgery. Therefore, RHA was found to be superior to ORIF in the treatment of TTIE. [ABSTRACT FROM AUTHOR]

The authors proposed a quantum Prisoner's Dilemma (PD) game as a natural extension of the classic PD game to resolve the dilemma. Here, we establish a new Nash equilibrium principle of the game, propose the notion of convergence and discover the convergence and phase-transition phenomena of the evolutionary games on networks. We investigate the many-body extension of the game or evolutionary games in networks. For homogeneous networks, we show that entanglement guarantees a quick convergence of super cooperation, that there is a phase transition from the convergence of defection to the convergence of super cooperation, and that the threshold for the phase transitions is principally determined by the Nash equilibrium principle of the game, with an accompanying perturbation by the variations of structures of networks. For heterogeneous networks, we show that the equilibrium frequencies of super-cooperators are divergent, that entanglement guarantees emergence of super-cooperation and that there is a phase transition of the emergence with the threshold determined by the Nash equilibrium principle, accompanied by a perturbation by the variations of structures of networks. Our results explore systematically, for the first time, the dynamics, morphogenesis and convergence of evolutionary games in interacting and competing systems. [ABSTRACT FROM AUTHOR]

It was known that cooperation of evolutionary prisoner's dilemma games fails to emerge in homogenous networks such as random graphs. Here we proposed a quantum prisoner's dilemma game. The game consists of two players, in which each player has three choices of strategy: cooperator (C), defector (D) and super cooperator (denoted by Q). We found that quantum entanglement guarantees emergence of a new cooperation, the super cooperation of the quantum prisoner's dilemma games, and that entanglement is the mechanism of guaranteed emergence of cooperation of evolutionary prisoner's dilemma games on networks. We showed that for a game with temptation b, there exists a threshold arcoss √b/b for a measurement of entanglement, beyond which, (super) cooperation of evolutionary quantum prisoner's dilemma games is guaranteed to quickly emerge, giving rise to stochastic convergence of the cooperations, that if the entanglement degree γ is less than the threshold arcoss √b/b, then the equilibrium frequency of cooperations of the games is positively correlated to the entanglement degree γ, and that if γ is less than arcoss √b/b and b is beyond some boundary, then the equilibrium frequency of cooperations of the games on random graphs decreases as the average degree of the graphs increases. [ABSTRACT FROM AUTHOR]

Traditionally, fuzzy numbers with wide spread are always employed to solve fuzzy nonlinear programming problems with uncertain model parameters, which undoubtedly degrades the satisfaction level of the objective. Motivated by this challenge, sensitivity analysis was suggested to investigate how the objective is influenced by every fuzzy number. After finding out those which make dramatic impacts on the objective and decreasing their fuzziness, the corresponding solutions would be more reasonable. A simple searching algorithm was introduced to specify the optimum spread of fuzzy numbers, helping decision makers make deep insight into the uncertain parameters. A numerical example was employed to demonstrate the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis of the knee is an irreversible disease that causes great pain, and genetic factors play an important role in its occurrence and development. There have been many studies on the correlation between ADAM12 polymorphisms and genetic susceptibility to osteoarthritis, but the results remain inconclusive. Methods: Papers from PubMed, Web of Science, EMbase, Springer, SCOPUS, Google Scholar and other databases were systematically retrieved with a cut-off of January 2022. All case–control studies on ADAM12 rs3740199, rs1871054, rs1044122, and rs1278279 polymorphisms and osteoarthritis were searched. Fixed or random effects models were used for pooled analysis with OR values and 95% confidence intervals (CI), and publication bias was assessed. In addition, the false-positive reporting probability test was used to assess the confidence of a statistically significant association. Results: Eleven articles were included, which included 3332 patients with osteoarthritis and 5108 healthy controls. Meta-analysis showed that the rs1871054 polymorphism of ADAM12 was associated with osteoarthritis in dominant, recessive, allelic, and homozygote genetic models [C vs. T: OR = 1.34 95% CI (1.05, 1.71), P < 0.001]. Our subgroup analysis revealed an association between the ADAM12 polymorphism rs1871054 in Asians and osteoarthritis [C vs. T: OR = 1.61, 95% CI (1.25, 2.08), P < 0.001], albeit this was only for three studies. In addition, the ADAM12 polymorphism rs1871054 is associated with osteoarthritis in patients younger than 60 years of age [C vs. T: OR = 1.39, 95% CI (1.01, 1.92), P = 0.289]; however, the ADAM12 gene rs3740199, rs1044122, and rs1278279 site polymorphisms were not significantly. Furthermore, when assessing the confidence of the positive results, the positive results were found to be credible (except for Age < 60). Conclusion: Polymorphism at the rs1871054 site of ADAM12 is associated with genetic susceptibility to osteoarthritis, but rs3740199, rs1044122, and rs1278279 site polymorphisms are not. [ABSTRACT FROM AUTHOR]

A joint power and rate optimisation for multihop relay networks adopting different hybrid automatic repeat request (HARQ) schemes are investigated. Specifically, Type‐I HARQ, chase‐combining‐based HARQ and schemes without HARQ are considered with practical system parameters. The optimisation problem is to adjust transmission power and rate of each node to maximise spectral efficiency under the limitations of total power consumption. However, this problem is not always mathematically tractable for three HARQ schemes. Hence, low‐complexity iterative algorithms are proposed to obtain the optimisation strategies. Numerical results demonstrate that joint optimisation strategy outperforms conventional separate optimisation strategies significantly. The impact of the path loss conditions is also investigated. It is found that performance improvement increases with increase in link unbalance. [ABSTRACT FROM AUTHOR]

The aim of this study was to retrospectively analyze and evaluate the effect of treatment employing pedicle subtraction osteotomy for chronic, posttraumatic thoracolumbar kyphosis. This study included 19 patients, 11 males and 8 females, with chronic, posttraumatic thoracolumbar kyphosis. Pre-operative kyphosis ranged from 31° to 63°. The history of trauma ranged from 8 to 63 months. All patients were treated with pedicle subtraction osteotomy. A mean 40.2° improvement in sagittal alignment was achieved with a mean correction rate of 85.8 %. Perioperative complications were encountered in two patients, one with cerebrospinal fluid leakage followed by encephalitic infection and one with a wound infection. Both were treated conservatively with antibiotics and local wound care. There were no other severe complications. The average follow-up period was 15 months (range 6-41 months). At the last follow-up, clinical symptoms and neurological function were significantly improved. Of 14 patients presenting with intractable back pain, VAS scores improved from a preoperative mean of 6.7 (range 5.0-8.0) to an average 2.0 (range 0-3.0) at final follow-up. No significant loss of correction was observed (loss of 1.7°), and solid fusion was achieved in all 19 patients. A single-stage posterior pedicle subtraction osteotomy is a safe and effective procedure for correction of posttraumatic thoracolumbar kyphosis. Using this technique, it is possible to safely obtain no greater than 55° of correction at a single level. [ABSTRACT FROM AUTHOR]

Highlights: [•] A cost-effective method of producing succinic acid was created. [•] Corn steep liquor powder was used as nitrogen source to replace yeast extract. [•] Heme was added to the medium and the culture was agitated at a low speed. [Copyright &y& Elsevier]

The navigating pose of underwater vehicle is difficult to be controlled because there exist coupling between pitching, yawing, rolling and uncertain disturbance caused by varying ocean current, so traditional control technology cannot obtain controlling objective. For solving the difficulty existed in underwater vehicle's pose decoupling controlling, the subsystem status equation of pose controller of underwater vehicle adopting variable structure control is constructed through constructing state equation of underwater vehicle pose moving subsystems. Theory analysis and simulation show that the designed controller makes pose angle track course angle of trajectory steadily and has good robustness for uncertain disturbance caused by varying ocean current, and achieves decoupling controlling between underwater vehicle pose moving subsystems. [ABSTRACT FROM AUTHOR]

Abstract: A minimal chemically defined medium (CDM) was created and used to study the effect of biotin on the metabolism of Actinobacillus succinogenes NJ 113. The medium contained four amino acids and vitamins as key growth factors. To gain insight into the effect of biotin, different concentrations of this compound were added, and glucose utilisation, cell growth, and the succinic acid concentration were investigated. Anaerobic batch fermentation was carried out at optimised conditions in a 3L fermentor with a succinic acid concentration of 45.2g/L and a yield of 90.4%. A metabolic pathway was proposed after further study of the mechanism underlying the metabolism of biotin. The same results were obtained when 5-aminolevulinate (5-ALA) was used instead of biotin. We suggest that 5-ALA is a great alternative to biotin for the preparation of succinic acid by biological fermentation. [Copyright &y& Elsevier]

Compared with genetic factors, drug interactions are largely unexplored in pharmacogenetic studies. This study sought to systematically investigate the effects of VKORC1, STX4A, CYP2C9, CYP4F2, CYP3A4, and GGCX gene polymorphisms and interacting drugs on warfarin maintenance dose.A retrospective study of 845 Chinese patients after heart valve replacement receiving long-term warfarin maintenance therapy was conducted. Thirteen polymorphisms in the six genes were genotyped, and 36 drugs that may interact with warfarin were investigated.Single-nucleotide polymorphism association analysis showed that VKORC1, CYP2C9 and CYP4F2 variations were highly associated with the warfarin maintenance dose. Among 36 drugs that may interact with warfarin, fluconazole, amiodarone, and omeprazole were associated with the requirement for 45.8, 16.7, and 16.7% lower median warfarin dose (all P<0.05 with a false discovery rate <0.05). The final pharmacogenetic equation explained 43.65% of interindividual variation of warfarin maintenance dose with age, body surface area, VKORC1 g.3588G>A, CYP2C9∗3, CYP4F2 c.1297G>A, amiodarone, fluconazole, and diltiazem accounting for 1.97, 2.74, 24.12, 3.94, 1.64, 5.92, 2.47, and 0.84% of variation.The present study indicated that VKORC1, CYP4F2, and CYP2C9 genotypes and interacting drugs had a significant impact on the warfarin maintenance dose in Chinese patients with heart valve replacement and demonstrated that integrating interacting drugs can largely improve the predictability of the dose algorithm. [ABSTRACT FROM AUTHOR]

The culture conditions in CO fixation by Actinobacillus succinogenes for succinic acid production were investigated by a model of available CO in a 3-l fermentor. The results from the model analysis showed that the available CO for succinic acid production in the fermentation broth is the sum of HCO, CO, and CO influenced by external culture conditions such as medium components, CO partial pressures, and temperature. The optimized conditions for CO supply in a 3-l fermentor were determined as follows: CO partial pressure and stirring speed were maintained at 0.1 MPa and 200 r min, respectively, with a pH of 6.8 and a temperature of 37°C; 0.15 mol l NaHCO was added. Under the optimized conditions, a CO fixation rate of 0.57 g l h was obtained, and a succinic acid concentration of 51.6 g l with a yield of 75.8% was reached. These results suggest that optimized conditions of CO supply are effective in high succinic acid production and thus have potential applications in succinic acid production and CO fixation. [ABSTRACT FROM AUTHOR]

Background: Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. Methods: 83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. Results: Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. Conclusions: Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2. [ABSTRACT FROM AUTHOR]

Abstract: Diabetic hyperglycemia result in cardiovascular complications, but the mechanisms by which high levels of glucose (HG) cause diabetic cardiomyopathy are not known. We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. HG also induced apoptosis of H9C2 cells. The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter–p53 complex. In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. These studies may help delineate the complex pathways regulating diabetic cardiomyopathy, and have implications for the development of novel therapeutic strategies to prevent diabetic cardiomyopathy by epigenetic regulation of IGF-1R. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, selective and highly sensitive high performance liquid chromatography–tandem mass spectrometry method (LC–MS/MS) was developed and validated for the determination and pharmacokinetic investigation of eptifibatide in human plasma. Eptifibatide and the internal standard (IS), EPM-05, were extracted from plasma samples using solid phase extraction. Chromatographic separation was performed on a C18 column at a flow rate of 0.5mL/min. Detection of eptifibatide and the IS was achieved by tandem mass spectrometry with an electrospray ionization (ESI) interface in positive ion mode. Traditional multiple reaction monitoring (MRM) using the transition of m/z 832.6→ m/z 646.4 and m/z 931.6→ m/z 159.4 was performed to quantify eptifibatide and the IS, respectively. The calibration curves were linear over the range of 1–1000ng/mL with the lower limit of quantitation validated at 1ng/mL. The intra- and inter-day precisions were within 13.3%, while the accuracy was within ±7.6% of nominal values. The validated LC–MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of eptifibatide after intravenous (i.v.) administration of a 45μg/kg bolus of eptifibatide to 8 healthy volunteers. [Copyright &y& Elsevier]

Natal dispersal is common among many bird species with females usually dispersing farther than males. We examined postfledging and natal dispersal ecology of Crested Ibis (Nipponia nippon) in the Qinling Mountains, China by marking nestlings with either color bands or radio transmitters. Family groups, consisting of juveniles alter fledging and their parents, dispersed progressively farther from nest sites after fledging in a southerly direction with a mean (± SD) direction of 189.2 ± 46.5° and a mean distance of 20.3 ± 7.0 km. Mean natal dispersal distance of females (9.6 km) was significantly greater than for males (5.9 km) (t = 2.14, P = 0.03). Most individuals moved southeasterly from natal areas and dispersal movements of individual ibis were concentrated at the mean direction (µ = 185.6°, š = 86.1°). First reproduction by females (3.64 ± 1.36 years) was not significantly earlier than for males (4.17 ± 1.47 years). The results of this study will be useful for reintroduction programs for critically endangered species. [ABSTRACT FROM AUTHOR]

1. Ketamine is widely used for the induction of anaesthesia in high-risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L-type Ca2+ (ICa), transient outward K+ (Ito), ultra-rapid delayed rectifier K+ (IKur) and inward rectifier potassium (IK1) currents, as well as on action potentials, in human isolated atrial myocytes. 2. Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current- and voltage-clamp modes using the patch-clamp technique. 3. Ketamine inhibited ICa with an IC50 of 1.8 µmol/L. In addition, 10 µmol/L ketamine decreased the ICa peak current at +10 mV from 5.1 ± 0.3 to 2.1 ± 0.4 pA/pF ( P < 0.01), but did not change the threshold potential, peak current potential and reverse potential. 4. Ketamine had no effect on Ito, IKur or IK1, but it reversibly shortened the duration of the action potential in human atrial myocytes. 5. In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting ICa. [ABSTRACT FROM AUTHOR]

Abstract: Glucose toxicity is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The present study investigated whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9C2 through microRNA regulated insulin-like growth factor (IGF-1) signaling pathway. Our data showed that H9C2 cells exposed to high glucose have increased miR-1 expression level, decreased mitochondrial membrane potential, increased cytochrome-c release, and increased apoptosis. Glucose induced mitochondrial dysfunction, cytochrome-c release and apoptosis was blocked by IGF-1. Using prediction algorithms, we identified 3′-untranslated regions of IGF-1 gene are the target of miR-1. miR-1 mimics, but not mutant miR-1, blocked the capacity of IGF-1 to prevent glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. In conclusion, our data demonstrate that IGF-1 inhibits glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis and IGF-1’s effect is regulated by miR-1. [Copyright &y& Elsevier]

Abstract Purpose  Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models. Materials and Methods  Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(−/−) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method. Results  The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 � 0.09% at 1 min to 9.27 � 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Co-perfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6−142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(−/−) mice was 6.0-fold higher than the wild-type mice. Conclusions  These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drug-glabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The apelin receptor APJ is a putative receptor protein related to angiotensin (Ang) type 1 receptor. The apelin-APJ system has been implicated in diabetes, but its role in the diabetic vasculature and the mechanisms involved remain unclear. Our aim here was to explore the regulatory role of apelin in the aortic vascular tone in diabetic mice. Methods: A Multi Myograph system was used to determine the isometric vessel tone in aortic rings from diabetic db/db and control db/m+ mice. The mRNA, phosphorylation, and protein levels of APJ, Akt, and endothelial nitric oxide synthase (eNOS) were analyzed by reverse transcription–polymerase chain reaction and Western blotting, respectively. Results: There is depressed expression of APJ, enhanced contractile response to Ang II, and reduced relaxation response to acetylcholine in aortas from db/db mice. Apelin treatment strikingly reversed the altered aortic vascular responsiveness to Ang II and acetylcholine in db/db mice, both of which were abolished by the eNOS inhibitor N G-nitro-l-arginine methyl ester. Finally, in db/db mice, considerable increases in phosphorylation of Akt on serine 473 and of eNOS on serine 1177 were found in aortas pretreated with apelin. Conclusions: Apelin treatment modulates the abnormal aortic vascular tone in response to Ang II and acetylcholine by potentiating phosphorylation of Akt and eNOS in diabetic mice, suggesting that the apelin-APJ system might be an important regulator of vascular function in diabetes. [Copyright &y& Elsevier]

Abstract: Tanshinone IIB (TSB) is a major active constituent of the root of Salvia miltiorrhiza (Danshen) used in the treatment of acute stroke. Danshen extracts and TSB have shown marked neuron-protective effects in mouse studies but there is a lack of clinical evidence for the neuron-protective effects of Danshen and its active ingredients. This study investigated the neuron-protective effects of TSB in experimentally stroked rats. TSB at 5 and 25mg/kg by intraperitoneal injection significantly reduced the focal infarct volume, cerebral histological damage and apoptosis in rats subjected to middle cerebral artery occlusion (MCAO) compared to MCAO rats receiving vehicle. This study demonstrated that TSB was effective in reducing stroke-induced brain damage and may represent a novel drug candidate for further development. Further mechanistic studies are needed for the neuron-protective activity of TSB. [Copyright &y& Elsevier]

The material-labeling method presented in this paper, coupled with X-ray computed tomography (XRCT), allows in situ non-invasive 3D characterization of certain pharmaceutical processes using relevant materials and process geometry. Microcrystalline cellulose (MCC, Celphere) particles were used in experiments, and lead (II) acetate trihydrate was used to label the MCC particles because it has both high water solubility and high X-ray attenuation coefficient. A 0.5-M lead acetate solution was used to impregnate the Celphere particles, and thus to deliver sufficient contrast in the XRCT shadow images. Selected physical properties of the impregnated particles were examined and found to be similar to the as-received material. The mixture of Pb-impregnated and as-received Celphere particles constituted a model pharmaceutical system to investigate die compaction and blending.Lead impregnation allows particles of low atomic weight to become visually traceable on XRCT by enhancing their X-ray absorption. For the compaction study, the in-die positions of Pb-impregnated particles were monitored as a function of compaction pressure. For the mixing study, a linear correlation between the gray scale of the cross-section images and the percentage of Pb-impregnated particles in the mixture was demonstrated. Two different initial fill configurations were compared: column-filling and layer-filling. Results show that the layer-filled configuration leads to better mixing than the column-filled configuration. [Copyright &y& Elsevier]

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA‐seq, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs‐Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA‐seq, bulk RNA‐seq, and bioinformatic approaches, and found the highly expressed miR‐27b‐3p in CPPs‐Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1‐CREB1 axis via exosomal miR‐27b‐3p. Our study offers a novel insight into the role of CPPs‐Exo in heart repair and highlights the potential of CPPs‐Exo as a promising therapeutic strategy for MI. [ABSTRACT FROM AUTHOR]

The sliding behavior of metallic glass (MG) was studied using pin-on-disk tests and molecular dynamics (MD) simulations. Friction coefficients and wear rates of a Zr–Ti–Cu–Ni–Be alloy were similar to those reported for ductile materials, e.g., normal crystalline metals; i.e., exceptional friction and wear characteristics of bulk MG were not observed. Sliding caused plastic deformation, transfer, mechanical mixing and reamorphizing of devitrified material. In vacuum, a softer layer developed adjacent to the interface. In air, an additional harder layer appeared when oxidation products were incorporated into the near-surface material. MD simulations involved a two-component 2D amorphous system. Simulations of tensile tests showed elastic/perfectly plastic response, strain rate dependence, void formation and shear bands. Simulations of sliding showed decreased density near the interface, suggesting an increase in free volume during shear, but neither voids nor shear bands. Subsurface displacement profiles were similar to those reported in experiments on crystalline materials and were consistent with flow patterns expected for flow near a boundary. The MD results on mechanical mixing suggest relevance to other processes, including mechanical alloying, friction welding, formation of nanocrystals, erosion and deformation at high strain rates. [Copyright &y& Elsevier]

A folding wing aircraft can autonomously change its configuration in flight to respond to different flying environments. Hinge moment during morphing process is an important basis for driving mechanism design and structural strength check, and its calculation depends on the simulation of the morphing process. Existing studies mostly use the simplified lifting surface method for aerodynamic modeling. In this paper, the CFD-based simulation method is studied, and the results are compared with those by the lifting surface method. First, the unsteady aerodynamic modeling method of the folding wing based on the CFD method is studied, an effective description method is given to define the wall mesh motion caused by wing folding and aileron deflection, and an unfolding–refolding strategy is proposed to improve the quality of the internal mesh in the case of large folding angles. Then, the CFD aerodynamic model is coupled through a developed coupling calculation program with the flexible multibody structure model for the simulation of a flight-morphing process. The comparison with the results of the lifting surface method shows that hinge moments obtained according to the two aerodynamic models are markedly different. Analysis of the difference shows that airfoil thickness considerably affects aerodynamic loading distributions and hinge moments of folding wing aircraft. The lifting surface method ignores airfoil thickness, which will cause large simulation errors in hinge moments. [ABSTRACT FROM AUTHOR]

The chemo‐regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer. In this work, the proteolysis targeting chimera (PROTAC) of BRD4 (dBET57) is found to downregulate colorectal cancer glycolysis through the transcription inhibition of c‐Myc, which also inhibits the expression of programmed death ligand 1 (PD‐L1) to reverse immune evasion and avoid adaptive immune resistance. Based on this, self‐delivery nano‐PROTACs (designated as DdLD NPs) are further fabricated by the self‐assembly of doxorubicin (DOX) and dBET57 with the assistance of DSPE‐PEG2000. DdLD NPs can improve the stability, intracellular delivery, and tumor targeting accumulation of DOX and dBET57. Meanwhile, the chemotherapeutic effect of DdLD NPs can efficiently destroy colorectal cancer cells to trigger a robust immunogenic cell death (ICD). More importantly, the chemo‐regulation effects of DdLD NPs can inhibit colorectal cancer glycolysis to reduce the lactate production, and downregulate the PD‐L1 expression through BRD4 degradation. Taking advantages of the chemotherapy and chemo‐regulation ability, DdLD NPs systemically activated the antitumor immunity to suppress the primary and metastatic colorectal cancer progression without inducing any systemic side effects. Such self‐delivery nano‐PROTACs may provide a new insight for chemotherapy‐enabled tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. Methods and results: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. Conclusions: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD. [ABSTRACT FROM AUTHOR]

Under the repeated action of aircraft taxiing load, the subgrade plastic deformation becomes the key factor affecting the service performance of the airfields when salinized silt is used to fill the subgrade. In this study, the dynamic triaxial tests were carried out on a region in the northern part of China to study the effects of different salt contents on the dynamic characteristics of silt under cyclic loading. A prediction model for the salinized silt dynamic strength with a plastic strain of 4% as the failure criterion for the subgrade was thus proposed. It is found that with the increase of dynamic stress amplitude, the salinized silt plastic deformation transforms gradually from plastic deformation to incremental failure. The salt contents significantly influence the plastic strain and critical dynamic stress of silt. The strength of the salinized silt specimen is related to the ion concentration in the soil pores and the arrangement pattern of soil particles, as indicated by the progressive strength increase of the salinized silt at the low salt content of 1% and a further gradual decrease at high salt content. [ABSTRACT FROM AUTHOR]