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Bone regeneration has been extensively studied over the past several decades. The surgically-induced mouse model is the key animal model for studying bone regeneration, of the various research strategies used. These mouse models mimic the trauma and recovery processes in vivo and serve as carriers for tissue engineering and gene modification to test various therapies or associated genes in bone regeneration. The present review introduces a classification of surgically induced mouse models in bone regeneration, evaluates the application and value of these models and discusses the potential development of further innovations in this field in the future. [ABSTRACT FROM AUTHOR]

Background: Ginkgo biloba L. (Ginkgoaceae) is one of the most distinctive plants. It possesses a suite of fascinating characteristics including a large genome, outstanding resistance/tolerance to abiotic and biotic stresses, and dioecious reproduction, making it an ideal model species for biological studies. However, the lack of a high-quality genome sequence has been an impediment to our understanding of its biology and evolution. Findings: The 10.61 Gb genome sequence containing 41,840 annotated genes was assembled in the present study. Repetitive sequences account for 76.58% of the assembled sequence, and long terminal repeat retrotransposons (LTR-RTs) are particularly prevalent. The diversity and abundance of LTR-RTs is due to their gradual accumulation and a remarkable amplification between 16 and 24 million years ago, and they contribute to the long introns and large genome. Whole genome duplication (WGD) may have occurred twice, with an ancient WGD consistent with that shown to occur in other seed plants, and a more recent event specific to ginkgo. Abundant gene clusters from tandem duplication were also evident, and enrichment of expanded gene families indicates a remarkable array of chemical and antibacterial defense pathways. Conclusions: The ginkgo genome consists mainly of LTR-RTs resulting from ancient gradual accumulation and two WGD events. The multiple defense mechanisms underlying the characteristic resilience of ginkgo are fostered by a remarkable enrichment in ancient duplicated and ginkgo-specific gene clusters. The present study sheds light on sequencing large genomes, and opens an avenue for further genetic and evolutionary research. [ABSTRACT FROM AUTHOR]

Study Design. Based on human disc surgical samples and isolated cells in vitro, we undertook a descriptive and mechanistic investigation of proinflammatory effects of interleukin (IL)-9 in intervertebral disc (IVD) degeneration. Objective. To investigate the proinflammatory role of IL-9 in the pathological process of IVD degeneration. Summary of Background Data. IL-9 is known as a pleiotropic cytokine that regulates the human pathogenesis of inflammatory and autoimmune diseases. However, whether IL-9 cytokine is involved in the immuno-inflammatory pathogenesis of IVD degeneration is unclear. Methods. The IVD samples were obtained from 45 patients. Immunohistochemistry, western blot, and real-time Polymerase Chain Reaction (PCR) were performed to detect the expression of IL-9 and tumor necrosis factor alpha (TNF-α) in the degenerated IVDs. Moreover, nucleus pulposus (NP) cells were treated with 0, 1, 10, and 100 ng/mL IL-9 cytokine and stimulated with IL-9 alone at 100 ng/mL for 0, 12, 24, and 48 hours. TNF-α expression was determined by immunofluorescence staining, western blot, and real-time PCR, respectively. The amounts of TNF-α and prostaglandin E2 (PGE2) in the supernatant were quantified by enzyme-linked immunosorbent assay. Additionally, Spearman correlation analyses were performed to analyze the correlation between Pfirrmann grading score of the involved degenerated IVDs and serum levels of IL-9. Results. The expressions of IL-9 and TNF-α in degenerated IVD tissues were dramatically elevated in comparison with the control. IL-9 significantly up-regulated the TNF-α and PGE2 secretion of NP cells in dose- and time-dependent manner. Moreover, there is a positive correlation between IL-9 serum level and severity of involved IVD degeneration. Conclusion. Our findings suggest that IL-9 may play a potential role in the inflammatory processes of IVD degeneration. IL-9 may be involved in the IVD degeneration, at least in part, though stimulating the release of TNF-α and PGE2 in NP cells. [ABSTRACT FROM AUTHOR]

Background Thoracoscopic-laparoscopic procedures have been used more in the operations of esophagus cancer; in most times we call it minimally invasive esophagectomy, which is becoming mature. However, the efficacy of minimally invasive esophagectomy is still unclear, especially about the dissection of lymph nodes and survival. Methods A retrospective review was performed. The development process of minimally invasive esophagectomy for esophageal cancer was divided into three stages: the first stage 20, the second stage 37, the third stage 50. Result Total 107 patients underwent minimally invasive esophagectomy between July 2010 and May 2015. The number of lymph node resected during the three stages increased significantly, with a mean of 12.65, 15.91, and 20.16 nodes, respectively (p = 0.0075). The number of lymph nodes dissection greater than or equal to 12 or 18 increased significantly (p = 0.000). The patients from the first and the second stages had the similar 2-year survival rate (p = 0.8618). There is no significant difference in the 2-year disease-free survival rate (p = 0.606). Conclusion Surgeons accumulate experience on lymphadenectomy during minimally invasive esophagectomy as time goes by, and experience on 50 to 60 cases is essential and necessary to accomplish an apparent progress. [ABSTRACT FROM AUTHOR]

Background: Abnormal serum lipid levels have been shown to be associated with the occurrence of atherosclerosis, but little is known about the relationships of them with the risk of developing intervertebral disc degeneration (IVDD) in Chinese population. Methods: We performed a case-control study to assess the relationship between serum lipid levels and lumbar disc degeneration. A total of 790 Chinese patients were recruited for this study at the time of hospitalization. We examined fasting serum lipid levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). 396 patients (235 men and 161 women; mean age: 41.07 years) underwent surgery for single-level lumbar disc herniation. A control group of 394 patients (225 men and 169 women; mean age: 42.1 years) underwent surgery for wounded lower limbs during the same period. Patients in the control group were collected randomly from among patients who were age- and sex-matched patients with the case group. Results: Patients with lumbar disc herniation had significantly higher TC and LDL-C serum concentrations (P < 0.001 for both) than controls. Percentage of High-TC, High-TG, High-LDL-C, borderline High-TC and borderline High-LDL-C were significantly higher in the disc herniation group (P = 0.017, P = 0.002, P = 0.039, P =0.002 and P < 0.001, respectively). Ratios of TC/HDL-C and LDL-C/HDL-C were significantly associated with disc herniation (P < 0.001 for both). Logistic regression revealed that patients with higher serum LDL-C levels had a higher risk of disc herniation, in which odds ratio (OR) was 1.462 and confidence interval (CI) was 1.179 ~ 1.813. Moreover, patients with High-TG and borderline High-LDL-C had a higher probability of disc herniation (OR: 2.974, CI: 1.488 ~ 5.945, statistical power: 100 %; OR: 1.626, CI: 1.012 ~ 2.612, statistical power: 61.4 %, respectively). However, hyperlipidaemia did not seem to be associated with the herniated segment of the lumbar intervertebral disc (p = 0.374). Conclusions: The present study suggests that dyslipidaemia may be associated with a higher risk of developing lumbar disc herniation. Serum lipid levels could be a useful predictor for intervertebral disc degeneration in Chinese population. [ABSTRACT FROM AUTHOR]

Analysis of networks and in particular discovering communities within networks has been a focus of recent work in several fields and has diverse applications. Most community detection methods focus on partitioning the entire network into communities, with the expectation of many ties within communities and few ties between. However, many networks contain nodes that do not fit in with any of the communities, and forcing every node into a community can distort results. Here we propose a new framework that extracts one community at a time, allowing for arbitrary structure in the remainder of the network, which can include weakly connected nodes. The main idea is that the strength of a community should depend on ties between its members and ties to the outside world, but not on ties between nonmenibers. The proposed extraction criterion has a natural probabilistic interpretation in a wide class of models and performs well on simulated and real networks. For the case of the block model, we establish asymptotic consistency of estimated node labels and propose a hypothesis test for determining the number of communities. [ABSTRACT FROM AUTHOR]

In omics studies, different sources of information about the same set of genes are often available. When the group structure (e.g., gene pathways) within the genes are of interests, we combine the normal hierarchical model with the stochastic block model, through an integrative clustering framework, to model gene expression and gene networks jointly. The integrative framework provides higher accuracy in extensive simulation studies when one or both of the data sources contain noises or when different data sources provide complementary information. An empirical guideline in the choice between integrative versus separate clustering models is proposed. The integrative clustering method is illustrated on the mouse embryo single cell RNAseq and bulk cell microarray data, which identified not only the gene sets shared by both data sources but also the gene sets unique in one data source. [ABSTRACT FROM AUTHOR]

'General requirements for the production of extracellular vesicles derived from human stem cells' is the first guideline for stem cells derived extracellular vesicles in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the general requirements, process requirements, packaging and labelling requirements and storage requirements for preparing extracellular vesicles derived from human stem cells, which is applicable to the research and production of extracellular vesicles derived from stem cells. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardisation of extracellular vesicles derived from human stem cells. [ABSTRACT FROM AUTHOR]

In order to response to the “double carbon” strategy for reducing emissions, chemical production processes were optimized to lower the amount of utility work and equipment investment expenses with increasing the system’s capacity for heat recovery. A sensitivity analysis and the energy efficiency analysis with pinch technique were performed on the distillation and purification of the 30 kt/a isopropyl acetate (IPAC) production process by using process simulation software of Aspen Plus. The IPAC refining tower optimization results show that the purity of the refined IPAC could be reached 99.9% at circumstances of 44 theoretical plates, 19 feed plates, and 0.755 reflux ratio. According to the optimized energy consumption data from Aspen Energy Analyzer (AEA), the cold and heat logistics matching was performed. It can be seen that the heat exchange network was tuned to maximize energy recovery by reducing the amount of utility work. The optimized cold and heat utility usage were 734.69 and 727.81 kW, which meaning that compared with original process, the cold and heat utility usage energy can be save with 10.0%, respectively. The optimized results provide a certain theoretical basis and solution for improving energy saving and reducing investment costs. [ABSTRACT FROM AUTHOR]

Ridership prediction of urban rail transit stations is of great significance for the operation and management of rail transit and configuration of facilities around stations. This study used automatic fare collection (AFC) data of the rail transit in Nanjing, China, for a month to obtain station ridership. Based on the point of interest (POI) data (within 800 m around urban rail transit stations), built environment factors such as land type and station accessibility were extracted, and a variable set of built environment factors was then established. Multiple collinearity and spatial autocorrelation analyses were used to screen the variables used in the regression model. A geographically weighted regression (GWR) model was constructed to explore the spatial heterogeneity of the influence on ridership of the built environment around the urban rail stations and to predict ridership. The results show that the GWR model can effectively capture the spatial heterogeneity of the effect of built environment factors on station ridership, and its ridership prediction accuracy is significantly better than that of the ordinary least squares model. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has an atypical onset of clinical symptoms and a rapid tumor progression. The majority of patients with HCC are already in the late stages of the disease when they are diagnosed, limiting them to the best available treatments. Contrast-enhanced ultrasound (CEUS) has achieved significant advances in the diagnosis of HCC, including the detection of small lesions, the investigation of more beneficial contrast agents, and the use of CEUS-based radiomics. The purpose of this review is to discuss the relevant research and future challenges of CEUS in the early detection of HCC, to advise more accurate therapy. [ABSTRACT FROM AUTHOR]

Actinidia macrosperma (AM) is a medicinal plant in China and has been well known for its activities against cancers, especially of lung, liver and digestive system. The immunomodulatory effects of AM aqueous extract were examined using S180-bearing mice. Young adult (20 ± 2 g) ICR mice inoculated with SI80 cells were divided randomly into six groups: S l80-bearing control group, normal control group, positive control group (Ginseng Radix Rubra 2000 mg/kg) and 50, 100, 250 mg/kg AM treatment groups. Each group consisted of ten mice. Body and tumor weights were obtained after 12 consecutive days, and their humoral, cellular and nonspecific immune functions were also determined by relative assays. The results showed that the aqueous extract of AM was lack of significant inhibit on transplantable sarcoma SI80, with a inhibit rate of 1.5%-14.8% (dose at 250 mg/kg was the best), but significantly increased the overall immune functions (especially at 100 and 250 mg/kg). The immunomodulatory effect was dose-dependent in a nonlinear fashion with the optimal dose of 100 mg/kg. The AM-induced antitumor effects were at least partially indirect and were associated with the modulation of immune functions. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11), a key member of the TGF-β superfamily, plays critical roles in various medical conditions. Recently, GDF11 was found to suppress the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and protect against inflammation. This study aimed to investigate the role of GDF11 in the development of rheumatoid arthritis (RA). We demonstrated that GDF11 treatment antagonized TNF-α-induced inflammation in macrophages. Moreover, GDF11 inhibited the development of arthritis in the collagen-induced arthritis and collagen antibody-induced arthritis models. Local gene transfer of GDF11 via adeno-associated virus exerted therapeutic effects, while local knockdown of GDF11 exaggerated inflammation in our collagen-induced arthritis model, as detected by expression levels of inflammatory biomarkers and the destruction of joint structures. Additionally, the results from both in vitro experiments and luciferase reporter gene mouse experiments implied that the NF-κB pathway might play a critical role in the therapeutic effect of GDF11 in RA. This study presents GDF11 as a potential target for the treatment of inflammatory arthritis, including RA. [ABSTRACT FROM AUTHOR]

Cardamine occulta, recently reported also as 'Asian C. flexuosa', is originally a native East Asian weed of paddy fields and other open habitats. It has been recorded throughout the world and is now also spreading widely in Europe. However, how this species differs morphologically from European C. flexuosa and its closest relatives in Asia (C. kokaiensis and C. scutata) is not fully known, particularly because it became widely recognized as a new taxon only recently. We used chromosome counting and flow cytometry to determine ploidies and genome size variation in these four species and morphometric analyses to ascertain their morphological differentiation. A uniformly octoploid level (2n = 64) is confirmed here for C. occulta and a tetraploid level for C. flexuosa and C. scutata (2n = 32). Here we formally describe C. kokaiensis, which is restricted to East Asia (Japan, Honshu; eastern China, Zhejiang Province; perhaps also the Russian Far East) and determine it to be a tetraploid. Considerable differences in monoploid genome size were revealed between these taxa, suggesting their mostly allopolyploid origins. Morphological differences between the species are demonstrated, and detailed morphological descriptions and an identification key are provided. [ABSTRACT FROM AUTHOR]

Background: At the end of the Pliocene and the beginning of Pleistocene glaciation and deglaciation cycles Ginkgo biloba went extinct all over the world, and only few populations remained in China in relict areas serving as sanctuary for Tertiary relict trees. Yet the status of these regions as refuge areas with naturally existing populations has been proven not earlier than one decade ago. Herein we elaborated the hypothesis that during the Pleistocene cooling periods G. biloba expanded its distribution range in China repeatedly. Whole plastid genomes were sequenced, assembled and annotated, and sequence data was analyzed in a phylogenetic framework of the entire gymnosperms to establish a robust spatio-temporal framework for gymnosperms and in particular for G. biloba Pleistocene evolutionary history. Results: Using a phylogenetic approach, we identified that Ginkgoatae stem group age is about 325 million years, whereas crown group radiation of extant Ginkgo started not earlier than 390,000 years ago. During repeated warming phases, Gingko populations were separated and isolated by contraction of distribution range and retreated into mountainous regions serving as refuge for warm-temperate deciduous forests. Diversification and phylogenetic splits correlate with the onset of cooling phases when Ginkgo expanded its distribution range and gene pools merged. Conclusions: Analysis of whole plastid genome sequence data representing the entire spatio-temporal genetic variation of wild extant Ginkgo populations revealed the deepest temporal footprint dating back to approximately 390,000 years ago. Present-day directional West-East admixture of genetic diversity is shown to be the result of pronounced effects of the last cooling period. Our evolutionary framework will serve as a conceptual roadmap for forthcoming genomic sequence data, which can then provide deep insights into the demographic history of Ginkgo. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common chronic degenerative disease characterized by degeneration in the joints and subsequent destruction of cartilage and bone, yet much remains to be elucidated regarding its molecular mechanism. Ghrelin is a recently discovered neuropeptide with anti-inflammatory actions, but it is unknown whether ghrelin is involved in OA. Human primary chondrocyte and cartilage samples were collected from patients with OA, and the expression pattern of ghrelin was assessed. Human chondrocyte and cartilage samples were stimulated with IL-1β and TNF-α, and exogenous ghrelin-alleviated disorganization of catabolism and anabolism were mediated by IL-1β and TNF-α. Destabilization of the medial meniscus and anterior cruciate ligament transection models were established in wild-type mice that were administered ghrelin or PBS. Severity of inflammation and degeneration in the joints were determined by measuring the levels of various inflammatory cytokines and degeneration-associated molecules. Ghrelin down-regulated the production of various inflammatory cytokines, inhibited apoptosis of chondrocytes, decreased the levels of metalloproteinases (including matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motif-5), and maintained the expression of critical matrix components, such as aggrecan and collagen 2. Moreover, suppression of the Akt signaling pathway and activation of NF-μB signaling in chondrocytes during OA development was antagonized by ghrelin administration. This supports the assessment of ghrelin as a potential therapeutic approach to treat degenerative cartilage diseases, including OA. [ABSTRACT FROM AUTHOR]

Objective: To study the expression of spleentyrosine kinase (Syk) gene in non--small--cell lung cancer and the relationship between Syk mRNA and microvessel density (MVD) in the tumor cells. Materials and Methods: The expression of Syk gene in 70 cases of lung tumor tissues, adjacent tissues, and normal lung tissues were examined with reverse transcription polymerase chain reaction (RT--PCR). The expression of MVD was examined with immunohistochemical streptavidin--biotin complex (SABC). The relation between them was analyzed. Results: Syk mRNA expression rates were 5.7, 95.7, and 100% in tumor, adjacent lung cells, and normal lung cells, respectively. The expression rate in tumor cells was significantly lower compared with those in normal lung tissue and adjacent lung tissue (P < 0.05), expression rate among different pathologic types, differentiation and clinical stages did not reveal any statistically significant differences (P > 0.05). The positive rate of CD34 in tumor was higher than that in adjacent tissues and normal lung tissues. The expression of Syk mRNA and MVD were negatively correlated. Conclusions: The lack of Syk mRNA expression in lung cancer play an important role in angiogenesis. [ABSTRACT FROM AUTHOR]

Background and Aims: Lung cancer has become one of the most dangerous malignant tumors in the world nowadays, whose pathogenesis is complex involving multi-genes and multi-elements. This study aims to investigate the values of spleen tyrosine kinase (Syk) and vascular endothelial growth factor-C (VEGF-C) in lymphangiogenesis and metastasis of lung adenocarcinoma A549 cells. Materials and Methods: The pcDNA3.1-VEGF-C and pLNCX-syk were constructed and transfected into A549 cells. After cells with stable expression were sorted, the level of VEGF-C was tested by RT-PCR and immunohistochemistry and the mRNA of syk was tested by RT-PCR. The cell invasion assay was investigated by transwell chamber in vitro. Restriction enzyme digestion and gel electrophoresis demonstrated successful construction of the pcDNA3.1-VEGF-C. Results: RT-PCR and immunohistochemistry revealed higher expression of VEGF-C in VEGFC-construct-transfected A549 cells than that in controls (P < 0.05). Successful construction of the pLNCX-syk was demonstrated by restriction enzyme electrophoresis and sequencing. RT-PCR revealed Syk expression higher in syk-construct-transfected cells than in controls (P < 0.05). Conclusions: The results indicate a potential link between the upregulation of Syk and VEGF-C expression and lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Our previous research has shown that the spliced isoform of XBP1 (XBP1s) is an important downstreammediator ofBMP2 and is involved in BMP2-stimulated chondrocyte differentiation. Herein, we report that ATF6 and its cleaved N-terminal cytoplasmic domain (known as ATF6a) are expressed in growth plate chondrocytes.We find that these proteins are differentially induced during BMP2-triggered chondrocyte differentiation. This differential expression probably results from the activation of the ATF6 gene by Runx2 and its repression by the Sox6 transcription factor. Runx2 and Sox6 act through their respective binding elements on the ATF6 gene. When overexpressed, ATF6 and ATF6a intensify chondrogenesis; our studies demonstrate that under the stimulation of ATF6 and ATF6a, chondrocytes tend to be hypertrophied and mineralized, a process leading to bone formation. By contrast, lowering expression of ATF6a by use of its specific siRNA suppresses chondrocyte differentiation. Moreover, ATF6a interacts with Runx2 and augments the Runx2-mediated hypertrophication of chondrocytes. Importantly, overexpression and knockdown of ATF6a during the chondrocyte hypertrophy process also led to altered expressions of IHH and PTHrP (also known as PTHLH). Taken together, these findings indicate that ATF6a favorably controls chondrogenesis and bone formation (1) by acting as a co-factor of Runx2 and enhancing Runx2-incited hypertrophic chondrocyte differentiation, and (2) by affecting IHH and PTHrP signaling. [ABSTRACT FROM AUTHOR]

Background Surgical treatment of extensive tracheal lesions remains a major challenge because of lack of an ideal airway substitute that is well vascularized, rigid, and autologous. We describe a novel surgical technique of tracheal reconstruction using a combination of a polypropylene mesh material and anterior cervical myocutaneous flap in a dog model. Materials and methods A 3.5-4 cm length of cervical trachea was resected in 16 dogs and replaced with a myocutaneous cervical neck flap wrapped around the plain polypropylene tube (group 1, n = 7) or wrapped around a composite of polypropylene tube with an implanted Z-type metallic-covered stent (group 2, n = 9). The cervical tracheal defect was repaired with the previously mentioned substitute that was directly sutured to the remaining tracheal ends. Dogs were followed up using bronchoscopy and x-rays and euthanized at predetermined times for histologic examination. Results In group 1, four dogs died within 2 wk from respiratory failure with varying degrees of airway collapse and difficulties in expectoration. In group 2, eight dogs survived, whereas one died of anastomotic dehiscence 1 wk after surgery. Necropsy and histologic examination of the anastomotic sites revealed good healing tissue. Pathologic examination also revealed excellent healing of the squamous epithelium of the neotrachea and the columnar epithelium of the native tracheal mucosa. Conclusions The tissue compatibility of the polypropylene mesh material and anterior cervical myocutaneous skin flap makes this a promising therapeutic substitute for treatment of patients with extensive tracheal lesions. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone receptor 2 (CRHR2) plays a role in both the central nervous system (CNS) and the peripheral nervous system. CRHR2 together with its ligands, urocortins (Ucns) and corticotropin-releasing hormone (CRH), functions as a mediator of inflammatory response and inhibitor of angiogenesis. Recently, it has been reported to be expressed in many human cancers. An association between rs2267716 polymorphism in the CRHR2 gene and susceptibility to hepatocellular carcinoma (HCC) was found in patients with chronic hepatitis C virus (HCV) infection. In the present study we analyzed, using a polymerase chain reaction–ligation detection reaction (PCR–LDR), the rs2267716 polymorphism in 364 hepatitis B virus (HBV)-related HCC patients, 196 non-HCC patients with HBV infection, and 404 healthy controls. The aim was to detect the possible association of this single-nucleotide polymorphism (SNP) with susceptibility to HBV-related HCC. Significant differences of rs2267716 allele were detected between HBV-related HCC patients and healthy controls (OR = 1.55, 95% CI 1.13–2.15, P = 0.007) or non-HCC patients with HBV infection (OR = 1.61, 95% CI 1.13–2.31, P = 0.009). These results suggest that the rs2267716 polymorphism in the CRHR2 gene might influence the risk of developing HCC in patients with HBV infection in Chinese population. [ABSTRACT FROM AUTHOR]