Search

Abstract Mutation of methylenetetrahydrofolate reductase (MTHFR) C677T leads to the decrease of folate utilization and the impairment of spermatogenesis. This study attempts to investigate the association between MTHFR C677T polymorphisms and nonobstructive oligozoospermia, asthenozoospermia or oligoasthenozoospermia in the Chinese population. The study cohort comprised 189 patients diagnosed with oligozoospermia, asthenozoospermia or oligoasthenozoospermia, and 626 controls based on clinical examinations. The MTHFR c.677 genotype of all subjects was determined by fluorescence staining in situ hybridization and the significance of different genotype frequencies was further analyzed by Chi-square test. The results showed that the frequency of MTHFR 677 CT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 33.3%, 38.3% and 44.0% respectively, whereas it was 47.3% in the control group. The P value of Chi-square test was 0.070, 0.103 and 0.654, respectively. The frequency of MTHFR 677 TT genotype in the oligozoospermia, asthenozoospermia and oligoasthenozoospermia group was 31.1%, 11.7% and 18.0% respectively, while that in the control group was 19.5%. The P value of Chi-square test was 0.061, 0.070 and 0.066, respectively. Collectively, there is a weak association between MTHFR C677T polymorphisms and oligozoospermia, asthenozoospermia or oligoasthenozoospermia within the current Chinese population cohort.

Background: Pancreatic cancer (PC) is a devastating human malignancy with a poor survival outcome (5-year survival less than 10 %). In recent years, the regulatory roles of long non-coding RNAs (lncRNAs) in various types of cancers have been widely reported. Based on bioinformatics analysis, LINC01857 is shown to be highly expressed in PC tissue. Nevertheless, the role of LINC01857 in PC is limitedly reported. Hence, this study aimed to explore the effects of lncRNA LINC01857 on PC cell process and the related mechanism. Methods: RT-qPCR and fluorescence in situ hybridization (FISH) assay were conducted to measure LINC01857 expression and distribution in PANC-1 and MIA PaCa-2 cells. Colony formation and wound healing assays as well as flow cytometry analyses were employed to estimate the proliferation, migration, and apoptosis of PC cells transfected with pcDNA3.1-LINC01857 or si-LINC01857 compared with the behavior of PC cells transfected with empty pcDNA3.1 vector (control) or si-negative control (NC). Furthermore, RNA pulldown and luciferase reporter assays were utilized to demonstrate the interaction of LINC01857 and miR-450b-5p or to validate the binding of miR-450b-5p and cell division cycle 42 effector protein 3 (CDC42EP3). Results: LINC01857 was highly expressed in PANC-1 and MIA PaCa-2 cells in contrast to its expression in pancreatic ductal epithelial cells (8.9 folds and 7.1 folds, p

Abstract Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Introduction: Rotator cuff tear (RCT) is a common shoulder injury impacting mobility and quality of life, while traditional surgeries often result in poor healing. Tissue engineering offers a promising solution, with poly (ε-caprolactone) (PCL) being favored due to its slow degradation, biocompatibility, and non-toxicity. However, PCL lacks sufficient compression resistance. Incorporating Mg, which promotes bone growth and has antibacterial effects, could enhance RCT repair.Methods: The Mg-incorporated PCL-based scaffolds were fabricated using a 3D printing technique. The scaffolds were incorporated with different percentages of Mg (0%, 5%, 10%, 15%, and 20%). The osteogenic activities and anti-inflammatory properties of the scaffolds were evaluated in vitro using human osteoblasts and macrophages. The tissue ingrowth and biocompatibility of the scaffolds were assessed in vivo using a rat model of RCT repair. The ability of the scaffolds to enhance macrophage polarization towards the M2 subtype and inhibit inflammation signaling activation was also investigated.Results: It was found that when incorporated with 10% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that the successfully constructed 10 Mg/PCL scaffolds enhance osteogenic activities and anti-inflammatory properties. Besides, the in vivo studies demonstrated that 10 Mg/PCL scaffolds promoted tissue ingrowth and enhanced biocompatibility compared to the control PCL scaffolds. Furthermore, the 10 Mg/PCL scaffolds enhanced the macrophages’ ability to polarize towards the M2 subtype and inhibited inflammation signaling activation.Discussion: These findings suggest that 3D-printed Mg-incorporated PCL scaffolds have the potential to improve RCT by enhancing osteogenesis, reducing inflammation, and promoting macrophage polarization. The incorporation of 10% Mg into PCL-based scaffolds provided the optimal combination of properties for RCT repair augmentation. This study highlights the potential of tissue engineering approaches in improving the outcomes of RCT repair and provides a foundation for future clinical applications.

The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

Stem cell-based therapy plays a significant role in the repair of bone defects. However, traditional stem cell transplantation strategies in bone tissue engineering are characterized by low survival rates and unstable treatment outcomes. In this study, we propose a timely delivery strategy for inflammatory changes in the setting of bone injury to improve the survival rate of transplanted cells and bone repair. The results of cell tracing in vivo showed that this strategy could effectively improve the survival rate of low-dose exogenous transplanted cells in bone defect areas, and CD31 immunofluorescence and histological sections suggested that this strategy effectively promoted vascularization and new bone formation in the calvarial defect area. Subsequently, we analyzed the mechanism of action of the “Two-step” strategy from the perspective of inflammatory microenvironment regulation, and the results suggested that the first batch transplanted stem cells caused localized and transient increases in tissue apoptosis levels and inflammatory factors, and recruited macrophage chemotaxis, and the second batch of cells may promote pro-inflammatory - anti-inflammatory transformation of the tissue. Finally, mRNA sequencing results suggest that the first batch cells in the “Two-step” strategy are important initiators in bone repair, which not only actively regulate the immune microenvironment at the bone defect, but also guide richer cellular activity and more positive biochemical responses. Therefore, the “Two-step” strategy leads to efficient inflammatory environment regulation and superior bone repair effects, which may provide an alternative option for the treatment of bone defects in the future.

Taxonomic uncertainties of rare species often hinder effective prioritization for conservation. One such taxonomic uncertainty is the 90-year-old enigma of Fagus chienii. F. chienii was previously only known from the type specimens collected in 1935 in Pingwu County of Sichuan Province, China, and has long been thought to be on the verge of extinction. However, morphological similarities to closely related Fagus species have led many to question the taxonomic status of F. chienii. To clarify this taxonomic uncertainty, we used the newly collected samples to reconstruct a molecular phylogeny of Chinese Fagus species against the phylogenetic backbone of the whole genus using seven nuclear genes. In addition, we examined nine morphological characters to determine whether F. chienii is morphologically distinct from its putatively closest relatives (F. hayatae, F. longipetiolata, and F. lucida). Both morphological and phylogenetic analyses indicated that F. chienii is conspecific with F. hayatae. We recommended that F. chienii should not be treated as a separate species in conservation management. However, conservation strategies such as in situ protection and ex situ germplasm preservation should be adopted to prevent the peculiar “F. chienii” population from extinction.

Abstract Family with sequence similarity three member (FAM3) plays a crucial role in the malignant development of various cancers of human. However, there remains doubtful what specific role of FAM3 family genes in pan-cancer. Our study aimed to investigate the role of FAM3 family genes in prognosis, immune subtype, tumor immune microenvironment, stemness score, and anticancer drug sensitivity of pan-cancer. We obtained data from UCSC Xena GDC and CellMiner databases, and used them to study the correlation of the expression, survival, immune subtype, tumor microenvironment, stemness score, and anticancer drug sensitivity between FAM3 family genes with pan-cancer. Furthermore, we investigated the tumor cellular functions and clinical prognostic value FAMC3 in pancreatic cancer (PAAD) using cellular experiments and tissue microarray. Cell Counting Kit-8 (CCK-8), transwell invasion, wound-healing and apoptosis assays were performed to study the effect of FAM3C on SW1990 cells’ proliferation, migration, invasion and apoptosis. Immunohistochemical staining was used to study the relationship between FAM3C expression and clinical characteristics of pancreatic cancer patients. The results revealed that FAM3 family genes are significantly differential expression in tumor and adjacent normal tissues in 7 cancers (CHOL, HNSC, KICH, LUAD, LUSC, READ, and STAD). The expression of FAM3 family genes were negatively related with the RNAss, and robust correlated with immune type, tumor immune microenvironment and drug sensitivity. The expression of FAM3 family genes in pan-cancers were significantly different in immune type C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-beta dominant). Meanwhile, overexpression FAM3C promoted SW1990 cells proliferation, migration, invasion and suppressed SW1990 cells apoptosis. While knockdown of FAM3C triggered opposite results. High FAM3C expression was associated with duodenal invasion, differentiation and liver metastasis. In summary, this study provided a new perspective on the potential therapeutic role of FAM3 family genes in pan-cancer. In particular, FAM3C may play an important role in the occurrence and progression of PAAD.

Dental age estimation is extensively employed in forensic medicine practice. However, the accuracy of conventional methods fails to satisfy the need for precision, particularly when estimating the age of adults. Herein, we propose an approach for age estimation utilizing orthopantomograms (OPGs). We propose a new dental dataset comprising OPGs of 27,957 individuals (16,383 females and 11,574 males), covering an age range from newborn to 93 years. The age annotations were meticulously verified using ID card details. Considering the distinct nature of dental data, we analyzed various neural network components to accurately estimate age, such as optimal network depth, convolution kernel size, multi-branch architecture, and early layer feature reuse. Building upon the exploration of distinctive characteristics, we further employed the widely recognized method to identify models for dental age prediction. Consequently, we discovered two sets of models: one exhibiting superior performance, and the other being lightweight. The proposed approaches, namely AGENet and AGE-SPOS, demonstrated remarkable superiority and effectiveness in our experimental results. The proposed models, AGENet and AGE-SPOS, showed exceptional effectiveness in our experiments. AGENet outperformed other CNN models significantly by achieving outstanding results. Compared to Inception-v4, with the mean absolute error (MAE) of 1.70 and 20.46 B FLOPs, our AGENet reduced the FLOPs by 2.7×. The lightweight model, AGE-SPOS, achieved an MAE of 1.80 years with only 0.95 B FLOPs, surpassing MobileNetV2 by 0.18 years while utilizing fewer computational operations. In summary, we employed an effective DNN searching method for forensic age estimation, and our methodology and findings hold significant implications for age estimation with oral imaging.

AbstractObjective The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma.Methods We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications.Results A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration. In this work, we assembled a biomimetic hyaluronic acid nanocomposite hydrogel (HA-BP hydrogel) by coordination bonds with bisphosphonates (BPs), which are antiosteoclastic drugs. The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment. Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP. Furthermore, the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts, which are considered essential during bone regeneration, whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP. The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone. Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.

Regardless of the advancement of synthetic bone substitutes, allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases. Nevertheless, the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure. Hence, improving osseointegration and transplantation efficiency remains important. The alteration of bone tissue microenvironment (TME) to facilitate osseointegration has been generally recognized. However, the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging. To address this concern, an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment. The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique. The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated. In the animal test, superior osseointegration between Mg-enriched graft and host bone was found, whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation. Furthermore, the bony in-growth appeared on magnesium-enriched allograft bone was significant higher. The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells. Lastly, our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.

Soil microorganisms are an important part of forest ecosystems, and their community structure and ecological adaptations are important for explaining soil material cycles in the fragile ecological areas. We used high-throughput sequencing technology to examine the species composition and diversity of soil bacterial and fungal communities in sea buckthorn forests at five sites in the water-wind erosion crisscross in northern Shaanxi (about 400 km long). The results are described as follows: (1) The soil bacterial community of the sea buckthorn forest in the study region was mainly dominated by Actinobacteria, Proteobacteria, and Acidobacteria, and the fungi community was mainly dominated by Ascomycota. (2) The coefficient of variation of alpha diversity of microbial communities was higher in the 0–10 cm soil layer than in the 10–20 cm soil layer. (3) Soil electrical conductivity (36.1%), available phosphorous (AP) (21.0%), available potassium (16.2%), total nitrogen (12.7%), and the meteorological factors average annual maximum temperature (33.3%) and average annual temperature (27.1%) were identified as the main drivers of structural changes in the bacterial community. Available potassium (39.4%), soil organic carbon (21.4%), available nitrogen (AN) (13.8%), and the meteorological factors average annual maximum wind speed (38.0%) and average annual temperature (26.8%) were identified as the main drivers of structural changes in the fungal community. The explanation rate of soil factors on changes in bacterial and fungal communities was 26.6 and 12.0%, respectively, whereas that of meteorological factors on changes in bacterial and fungal communities was 1.22 and 1.17%, respectively. The combined explanation rate of environmental factors (soil and meteorological factors) on bacterial and fungal communities was 72.2 and 86.6%, respectively. The results of the study offer valuable insights into the diversity of soil microbial communities in the water-wind erosion crisscross region and the mechanisms underlying their interaction with environmental factors.

Innate immunity plays an important role in viral keratitis. Recently, it has been found that surfactant proteins(SP)A and D in the innate immune system are essential in viral keratitis. SP can inhibit virus adhesion to host cells and further promote phagocytosis of virus through high affinity for virus ligands. In order to ensure the normal function of tissues in the early stage of virus infection, SP regulates immune cells to maintain a non-inflammatory state. However, when pathogen invasion increases, SP promoted inflammation and increased the immune cells to kill the pathogens. SP-A and SP-D could be expressed in cornea, conjunctiva. To play the role of anti-adenovirus, herpes simplex virus, cytomegalovirus and other major eye pathogenic viruses, SP-A and SP-D combine with the virus to prevent entry into cells, promote phagocytosis, and directly kill the virus. SP-A and SP-D may be used as clinical diagnostic tools for viral infection. In the future, recombinant SP is expected to be used as an important means for the treatment of viral keratitis. Here, we review the innate immune function of SP-A and SP-D in ocular viral infection.

BackgroundDepression is a common mental disorder and the diagnosis is still based on the descriptions of symptoms. Biomarkers can reveal disease characteristics for diagnosis, prognosis, and treatment. In recent years, many biomarkers relevant to the mechanisms of depression have been identified. This study uses bibliometric methods and visualization tools to analyse the literature on depression biomarkers and its hot topics, and research frontiers to provide references for future research.MethodsScientific publications related to depression biomarkers published between 2009 and 2022 were obtained from the Web of Science database. The BICOMB software was used to extract high-frequency keywords and to construct binary word-document and co-word matrices. gCLUTO was used for bicluster and visual analyses of high-frequency keywords. Further graphical visualizations were generated using R, CiteSpace and VOSviewer software.ResultsA total of 14,403 articles related to depression biomarkers were identified. The United States (34.81%) and China (15.68%), which together account for more than half of all publications, can be considered the research base for the field. Among institutions, the University of California, University of London, and Harvard University are among the top in terms of publication number. Three authors (Maes M, Penninx B.W.J.H., and Berk M) emerged as eminent researchers in the field. Finally, eight research hotspots for depression biomarkers were identified using reference co-citation analysis.ConclusionThis study used bibliometric methods to characterize the body of literature and subject knowledge in the field of depression biomarker research. Among the core biomarkers of depression, functional magnetic resonance imaging (fMRI), cytokines, and oxidative stress are relatively well established; however, research on machine learning, metabolomics, and microRNAs holds potential for future development. We found “microRNAs” and “gut microbiota” to be the most recent burst terms in the study of depression biomarkers and the likely frontiers of future research.

Abstract Objective To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA). Methods In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well. Results A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42–15.42) and the median duration of disease was 2.38 months (range, 1.53–49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores. Conclusions Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.

Abstract Background The precise etiology of anterior inferior cerebellar artery (AICA) infarction is difficult to identify because of the high anatomic variability of vertebrobasilar arteries and the limitations of conventional vascular examinations. Basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) can reveal the outer contour of the intracranial vertebrobasilar arteries, which may be helpful to distinguish the arteriosclerosis from congenital dysplasia and dissection. Case presentation In this study, we reported 3 cases of AICA infarction and discussed the diagnostic value of BPAS-MRI in the evaluation of vascular etiology. Conclusions The BPAS-MRI could be considered as an important supplementary in the diagnosis of vascular etiology of infarction in AICA territory.

Abstract Objectives To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. Methods The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. Results The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47–10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P

Nanocomposite hydrogels consist of polymeric network embedded with functional nanoparticles or nanostructures, which not only contribute to the enhanced mechanical properties but also exhibit the bioactivities for regulating cell behavior. Bisphosphonates (BPs) are capable of coordinating with various metal ions and modulating bone homeostasis. Thanks to the inherent dynamic properties of metal–ligand coordination bonds, BP-based nanocomposite hydrogels possess tunable mechanical properties, highly dynamic structures, and the capability to mediate controlled release of encapsulated therapeutic agents, thereby making them highly versatile for various biomedical applications. This review presents the comprehensive overview of recent developments in BP-based nanocomposite hydrogels with an emphasis on the properties of embedded nanoparticles (NPs) and interactions between hydrogel network and NPs. Furthermore, various challenges in the biomedical applications of these hydrogels are discussed to provide an outlook of potential clinical translation.

The integrated use of molecular marker-assisted selection (MAS) and anther culture has potential to significantly increase efficiency in plant breeding; however, reports on this kind of practical use are very limited. In the present study, we report the development of cytoplasmic male sterile (CMS) maintainers with aroma, disease resistance and red-brown hulls, as an example of integration of MAS and anther culture in rice breeding. A high-resolution melting (HRM)-based functional molecular marker was developed for the red-brown hull trait caused by a unique mutation (rbh1) in OsCAD2. Functional molecular markers for genes of rice blast resistance (Pi2), aroma (fgr) and red-brown hull (rbh1) were used for precise genotyping of individual plants in the BC1 and BC2F2 populations derived from a cross between CMS maintainers Huaxiang B (pi2–/rbh1–/fgr–) and Rong 3B (Pi2+/RBH1+/Fgr+). A total of 89 doubled haploid (DH) lines were generated from selected BC2F2 plants (Pi2+/rbh1–/fgr–) by anther culture. Seven DH lines were subsequently selected as the potential new CMS maintainers based on their overall performance and high resistance to blast. Our study demonstrated that integration of MAS and anther culture significantly accelerated the development of CMS maintainers with multiple stacked genes.

Pyrabactin resistance 1-like proteins (PYLs) are direct receptors of abscisic acid (ABA). For the redundant and polymorphic functions, some members of the PYL family interact with components of other signaling pathways. Here, 253 positive colonies from a maize cDNA library were screened as interacting proteins with the members of ZmPYL family. After sequencing and function annotation, 17 of 28 interaction combinations were verified by yeast two-hybrid (Y2H). The germination potential, taproot length and proline content of a quartet mutant of Arabidopsis PYL genes were significantly deceased comparing to the wild type (WT) under alkaline stress (pH 8.5) and 100 µmol L−1 methyl jasmonate (MeJA) induction. The malondialdehyde (MDA) content was significantly increased. After germinating in darkness, the characteristics of dark morphogenesis of the quartet mutant seedlings were more obvious than those of the WT. The differential expression of the related genes of photomorphogenesis in the mutant was much more than that in the WT. Three light and two JA responsive cis-affecting elements were identified during the promoter sequences of the AtPYL1 and AtPYL2 genes. These results suggested that functional polymorphism has evolved among the members of ZmPYL family. In response to developmental and environmental stimuli, they not only function as direct ABA receptors but also interact with components of other signaling pathways mediated JA, brassinosteroid (BR), auxin, etc., and even directly regulate downstream stress-related proteins. These signaling pathways can interact at various crosstalk points and different levels of gene expression within a sophisticated network.

Abstract Background Dexamethasone intravitreal implants (0.7 mg) (Ozurdex®, Allergan Inc., Madison, NJ) are FDA approved for managing macular oedema (ME) of retinal vein occlusion (RVO). The major complications associated with intravitreal Ozurdex® implant include increased intraocular pressure and cataract progression. In regard to the occurrence of retinal complications, we report an unusual intravitreal Ozurdex® implantation-related acute retinal necrosis (ARN). Case presentation A 45-year-old immunocompetent woman with a history of encephalitis presented with photophobia, redness, floaters, and rapidly decreased vision in her left eye. Three and six months ago, she received two doses of intravitreal Ozurdex® implant for ME of RVO. Clinical evaluation, including slit-lamp biomicroscopy, retinal photography, and fluorescein angiography, revealed anterior chamber cells, granulomatous keratic precipitates, cells in the vitreous, optic disc oedema, occlusive retinal vasculitis, scattered retinal haemorrhages, one quadrant of peripheral white areas with retinal necrosis, optic disc and vessels fluorescein staining, and retinal nonperfusion zones. All the above clinical manifestations showed an ARN. Herpes simplex virus was detected in the aqueous and vitreous humour by quantitative polymerase chain reaction testing. Intravenous acyclovir 500 mg tid for 7 days followed by oral valcyclovir was immediately performed for ARN. At 4 months, the patient’s condition improved without retinal detachment, and the best-corrected visual acuity remained stable at 0.3. Conclusions ARN might represent a risk of Ozurdex® administration.

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells (HSCs) transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases (PIDs). Despite of some pitfalls at early stage clinical trials, the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety, preparatory regime for manufacturing high quality virus, automated CD34 cell purification. Hence, the overall outcome from the clinical trials for the different PIDs has been very encouraging. In addition to the viral vector based gene therapy, the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of PIDs. This review provides an overall outcome and progress in gene therapy clinical trials for SCID-X, ADA-SCID, WAS, X- CGD, and the recent developments in genome editing technology applied in HSCs for developing potential therapy, particular in the key studies for PIDs. Keywords: Adenosine deaminase deficient, Chronic granulomatous disease, Gene therapy, Genome editing, Hematopoietic progenitor stem cells, Primary immunodeficiency diseases, Wiskott-Aldrich syndrome, X-liked severe combined immunodeficiency

With the rise of green concept, shared bikes are booming. The accompanying unbalanced scheduling problem is a scientific problem that needs to be solved urgently. Aiming at the problem of shared bikes scheduling with travel uncertainty, a multi-objective integer programming model is established based on the consideration of static demand of fix time period, station capacity limit, penalty cost and other practical factors. In addition, this paper gives the basic formula to calculate the parameters in the model. An algorithm based on “ant colony algorithm” is then given to solve the model. Taking the massive data provided by the “Mobike” company in 2017 as an example, this paper uses the program analysis data to prove the feasibility and effectiveness of the model and get the initial optimization plan. Finally, the data simulation is carried out to verify the feasibility and accuracy of the optimization scheme and the optimization scheme is adjusted accordingly to obtain the final optimization scheme. The research results show that the final optimization scheme proposed in this paper has certain reference value for the scheduling problem of Shanghai “Mobike”.

Soil materials can exhibit strongly dispersive properties in the operating frequency range of a physical system, and the uncertain parameters of the dispersive materials introduce uncertainties in the simulation result of propagating waves. It is essential to quantify the uncertainty in the simulation result when the acceptability of these calculation results is considered. To avoid performing thousands of full-wave simulations, an efficient surrogate model based on artificial neural networks (ANNs) is proposed in this paper, to imitate the concerned ground penetrating radar (GPR) calculation. With the autoencoder neural network to reduce the dimensionality of data, the surrogate model successfully predicts the outputs of the GPR calculation using a small number of training samples. The finite-difference time-domain method with the uniaxial perfectly matched layer is used to collect sampling data for the surrogate model. The process of constructing the surrogate model is presented in detail in this paper. The proposed surrogate model is demonstrated to be an attractive alternative to the full-wave GPR calculation due to its considerable advantage in terms of computational expense and speed.

Casting technology of thin-wall TiAl alloy turbochargers was studied by investment casting and numerical simulation. Misruns and gas holes were the main defects observed in preliminary work due to the poor fluidity of alloy, and to gas entrapment. In order to eliminate these defects, cast parameters, such as centrifugal rotation rate and mould preheating temperature, were optimized by numerical simulation, meanwhile, the structure of the shell mould was optimized to improve the filling capacity of TiAl alloy. Pouring experiments were carried out by vacuum induction melting furnace equipped with a water-cooled copper crucible based on the above optimization. The quality of the TiAl alloy casting was analyzed by fluorescent penetrant inspection and X-ray detection. The results show that a centrifugal rotation rate of 200 rpm, mould preheating temperature of 600 °C, shell preparation through organic fiber addition can dramatically improve the mould filling capacity, and integrated turbochargers were finally prepared.

High level of carbohydrate in aquafeed could achieve cost-sparing effect, but it may cause adverse effects on flesh quality of aquatic products. An eight-week trial was conducted to investigate whether oligosaccharides-supplementation, including Galacto-oligosaccharides (GOS) and xylo-oligosaccharide (XOS), could systematically improve the growth performance, texture characteristics and nutrition composition of Nile tilapia fed with high-carbohydrate diet. The results indicated that GOS-supplementation improved the amino acid composition, while XOS-supplementation showed beneficial effects on growth performance. High-carbohydrate diet had adverse effects on fillet texture, while oligosaccharide-supplementation regulated the expression of muscle development-related genes to help restoring muscle texture properties. Furthermore, either high-carbohydrate or addition of oligosaccharides could change the intestinal microbiota composition and their metabolites. Further correlation analysis suggested that intestinal microbiota may account for the improvement in fish growth condition and texture characteristics. Application of oligosaccharides may be an innovative strategy for flesh quality modulation in aquaculture.

Objectives: Both coronavirus disease 2019 (COVID-19) pneumonia and influenza A (H1N1) pneumonia are highly contagious diseases. We aimed to characterize initial computed tomography (CT) and clinical features and to develop a model for differentiating COVID-19 pneumonia from H1N1 pneumonia.Methods: In total, we enrolled 291 patients with COVID-19 pneumonia from January 20 to February 13, 2020, and 97 patients with H1N1 pneumonia from May 24, 2009, to January 29, 2010 from two hospitals. Patients were randomly grouped into a primary cohort and a validation cohort using a seven-to-three ratio, and their clinicoradiologic data on admission were compared. The clinicoradiologic features were optimized by the least absolute shrinkage and selection operator (LASSO) logistic regression analysis to generate a model for differential diagnosis. Receiver operating characteristic (ROC) curves were plotted for assessing the performance of the model in the primary and validation cohorts.Results: The COVID-19 pneumonia mainly presented a peripheral distribution pattern (262/291, 90.0%); in contrast, H1N1 pneumonia most commonly presented a peribronchovascular distribution pattern (52/97, 53.6%). In LASSO logistic regression, peripheral distribution patterns, older age, low-grade fever, and slightly elevated aspartate aminotransferase (AST) were associated with COVID-19 pneumonia, whereas, a peribronchovascular distribution pattern, centrilobular nodule or tree-in-bud sign, consolidation, bronchial wall thickening or bronchiectasis, younger age, hyperpyrexia, and a higher level of AST were associated with H1N1 pneumonia. For the primary and validation cohorts, the LASSO model containing above eight clinicoradiologic features yielded an area under curve (AUC) of 0.963 and 0.943, with sensitivity of 89.7 and 86.2%, specificity of 89.7 and 89.7%, and accuracy of 89.7 and 87.1%, respectively.Conclusions: Combination of distribution pattern and category of pulmonary opacity on chest CT with clinical features facilitates the differentiation of COVID-19 pneumonia from H1N1 pneumonia.

To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM)-induced liver damage, we investigated the protective effects of punicalagin, a major component in pomegranate peel, on the liver of mice with T2DM. After five weeks of punicalagin treatment, blood and liver samples were obtained for the subsequent analyses. Western blotting, reverse transcription polymerase chain reaction, and immunohistochemical staining were performed to determine the expression of endoplasmic reticulum (ER) stress markers in the liver tissue. The results showed that punicalagin alleviated glucose and insulin resistance, increased insulin sensitivity, and reduced serum free fatty acids levels and hepatic steatosis in the mice with T2DM. Furthermore, punicalagin down-regulated the elevated mRNA expression of the ER stress markers eIF2α, GRP78, ATF4, and CHOP in the liver of mice with T2DM. Our results suggest that punicalagin is a potential natural agent for the prevention of T2DM-induced liver damage.

After publication of this article (Zhang et al., 2019), it is noticed the article contains some error:

Abstract Quantifying the palaeoclimates of Qinghai–Tibetan Plateau is vital for understanding the uplift history of plateau and the evolution of Asian monsoon since Cenozoic. Recently, the Coexistence Approach (CA) has been employed to reconstruct the palaeoelevation and palaeoclimate of the plateau by several studies. However, the application of CA in mountainous areas and the realism of climate reconstructions via this method are seldom discussed, although the complexity of reconstructions is speculated. Here we reevaluated the realism of climate reconstruction using the CA with modern pollen samples from the Qinghai–Tibetan Plateau, and try to explore the possible factors influencing the precipitation and temperature reconstructions by CA. We suggest that the long-distance transport pollen as a result of the Asian summer monsoon potentially significantly affects the reconstructions both for precipitation and temperature. The precipitation complexly interacting with snowmelt and permafrost thaw leads to the discrepancy between the reconstructed precipitation and the real value. The response temperature for blossoming of dwarfed plants on the plateau is mostly likely higher than the air temperature (usually measured at 1.5 m above ground) due to energy flux or morphological adaptation of inflorescences during the growing season, causing the distortion of temperature reconstructions. Precipitation reconstruction is notoriously difficult as the establishers of CA have already suggested, but reconstructing the low temperatures may be even more challenging on Qinghai–Tibetan Plateau. Though all of the explorations in current paper are in a qualitative way, it offers an inspiration of how appropriately interpret the disagreements between CA results and the observations, and of how to obtain a reasonable reconstruction of palaeoclimate of the plateau.

Glucagon-like peptide-1 (GLP-1) is easily degraded by dipeptidyl peptidase-4 (DPP-4) in the human body, limiting its therapeutic effect on type II diabetes. Therefore, improving GLP-1 receptor agonist (GLP-1RA) stability is a major obstacle for drug development. We analyzed human GLP-1, DPP-4, and GLP-1 receptor structures and designed three GLP-1RAs, which were introduced into fusion protein fragments and changed in the overall conformation. This modification effectively prevented GLP-1RAs from entering the DPP-4 active center without affecting GLP-1RAs’ ability to bind to GLP-1R, the new GLP-1RA hypoglycemic effect lasting for >24 h. Through molecular modeling, molecular dynamics calculation, and simulation, possible tertiary structure models of GLP-1RAs were obtained; molecular docking with DPP-4 and GLP-1R showed access to the fusion protein. The overall conformational change of GLP-1RAs prevented DPP-4 binding, without affecting GLP-1RAs’ affinity to GLP-1R. This study provides important drug design ideas for GLP-1RA development and a new example for application of structural biology-based protein design in drug development.

Background: Cetuximab (CTX) has been approved to be administered concurrently with radiotherapy (RT) to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study was to assess the efficacy and safety of concurrent CTX with RT (ExRT). Method: The PubMed, Cochrane Library, EMBASE databases were systematically searched to find relevant articles. The combined hazard ratio (HR), risk ratio (RR) and 95% confidence interval were calculated to assess the efficacy and safety of ExRT in contrast to concurrent platinum-based chemotherapy with RT (ChRT). Results: In total, 32 articles with 4556 patients were included. The pooled HRs indicated that ExRT achieved an unfavorable overall survival (HR: 1.86, p

Abstract Background At present, many laboratories and hospitals all over the world are attempting and exploring the clinical transformation of this tissue engineered bone graft (TEBG) strategy. Many successful cases of bone tissue engineering (BTE) repair were based on young individuals. But there are little studies about the effectiveness of TEBG strategy in physiological aged individuals. Methods In this research, we studied whether aging factor has influence on the skull repair effect of Fetal-TEBG, at the level of the large animal models. We used the fetal bone marrow stromal cells (Fetal-BMSCs) as the seed cells, combining the decalcified bone matrix (DBM) scaffolds, to repair the skull defects of the aged goats and the young goats. The repair effects on both aged goat and young goat were compared by Micro-CT and histology examination. Results The skull defects of the young goats could be repaired better than that of the aged goats after 6 months by Fetal-TEBG; In the aged goats, although not completely repaired, the defects repaired by Fetal-TEBG was better than that repaired by the Control DBM scaffold. Conclusions Aging factor has impact on the bone repair effect of Fetal-TEBG; and the BTE strategy is still efficacious even in the aged individuals. The improvement of the aged state may promote the repair effect of the BTE in the aged individuals.

Abstract Background Bone tissue engineering is not widely used in clinical treatment. Two main reasons hide behind this: (1) the seed cells are difficult to obtain and (2) the process of tissue engineering bone construction is too complex and its efficiency is still relatively low. It is foreseeable that in the near future, the problem of seed cell sources could be solved completely in tissue engineering bone repair. As for the complex process and low efficiency of tissue engineering bone construction, usually two strategies would be considered: (1) the construction strategy based on injectable bone tissue and (2) the construction strategy based on osteogenic cell sheets. However, the application of injectable bone tissue engineering (iBTE) strategy and osteogenic cell sheet strategy is limited and they could hardly be used directly in repairing defects of large segmental bone, especially load-bearing bone. Methods In this study, we built an osteogenic micro-tissue with simple construction but with a certain structure and composition. Based on this, we established a new iBTE repair strategy—osteogenic micro-tissue in situ repair strategy, mainly targeting at solving the problem of large segmental bone defect. The steps are as follows: (1) Build the biodegradable three-dimensional scaffold based on the size of the defect site with 3D printing rapid prototyping technology. (2) Implant the three-dimensional scaffold into the defect site. This scaffold is considered as the “steel framework” that could provide both mechanical support and space for bone tissue growth. (3) Inject the osteogenic micro-tissue (i.e., the “cell-extracellular matrix” complex), which could be considered as “concrete,” into the three-dimensional scaffold, to promote the bone tissue regeneration in situ. Meanwhile, the digested cells were injected as the compared group in this experiment. After 3 months, the effect of in situ bone defect repair of osteogenic micro-tissue and digested cells was compared. Results It is confirmed that osteogenic micro-tissue could achieve a higher efficiency on cell usage and has a better repair effect than the digested cells. Conclusions Osteogenic micro-tissue repairing strategy would be a more promising clinical strategy to solve the problem of large segmental bone defect.

Background: Wallerian degeneration (WD) of bilateral middle cerebellar peduncles (MCPs) can occur following pontine infarction, but its characteristics have not yet been clarified because of the low incidence. Thus, the present study discussed the clinical and radiological features to improve the awareness of this disease. Methods: Clinical and radiological information from consecutive individuals diagnosed with WD of bilateral MCPs following pontine infarction in three hospitals over the past 4 years between October 2012 and October 2016 were retrospectively investigated and compared with a control group (patients with pontine infarction had no secondary WD). Results: This study involved 30 patients with WD of MCPs, with a detection rate of only 4.9%. The primary infarctions (χ2 =24.791, P = 0.001, vs. control group) were located in the paramedian pons in 21 cases (70.0%), and ventrolateral pons in nine cases (30.0%). WD of the MCPs was detected 8–24 weeks after pons infarction using conventional magnetic resonance imaging (MRI); all secondary WDs were asymptomatic and detected incidentally. All WD lesions exhibited bilateral, symmetrical, and boundary blurring on MRI. The signal features were hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging and fluid-attenuated inversion recovery, and slightly hyperintense or isointense on diffusion-weighted imaging and apparent diffusion coefficient maps. Secondary brainstem atrophy was found in six (20.0%) cases. A Modified Rankin Scale score 0–2 was found in 10 (33.3%) cases and score >2 in 20 (66.7%) cases at 90 days after discharge, and the short-term prognosis was worse than that in control group (χ2 =12.814, P = 0.001). Conclusions: Despite the rarity of bilateral and symmetrical lesions of MCPs, secondary WD should be highly suspected if these lesions occur within 6 months after pontine infarction, particularly paramedian pons. Conventional MRI appears to be a relatively sensitive method for detecting WD of MCPs, which might affect the short-term prognosis.

The distribution pattern of vegetation on Qinghai–Tibetan Plateau is fundamentally influenced by the plateau climate, which is mainly controlled by Indian monsoon during summer. The long distance transportation of pollen (mostly anemophilous taxa) produced by trees on the plateau has been recorded by modern pollen samples in previous studies, and hypothesized to be a good indicator of monsoon dynamics. Here we use 270 surface pollen samples from Qinghai–Tibetan Plateau to test the distribution patterns of the anemophilous tree pollen. Meanwhile factors related to Indian monsoon affecting pollen transportation are simulated and analyzed. Results show that depositional patterns of anemophilous tree pollen, especially Abies, Pinus, Quercus and Betula are completely controlled by the pathways of Indian monsoon. This is reflected by climatic indicators of the atmospheric pressure pattern over June–July–August, by the precipitation pattern over June–July–August and by the topographic feature of the plateau. The spatial interpolation of thin plate spline results also display two depositional centers (ca. 30°N, 95°E and 30°N, 105°E) of the anemophilous tree pollen. In contrast to previous conclusion that pollen distributional pattern is determined by mean annual precipitation, we argue that Indian monsoon is the essential controller because of the synchronization between timing of monsoon wind and timing of plants flowering. Our finding strongly suggests that distributional pattern of anemophilous tree pollen on the plateau is a good proxy of Indian monsoon.

A hybrid linear ion trap-quadrupole-Orbitrap high-resolution mass spectrometry (LTQ-Orbitrap-HRMS) was used to qualitatively and quantitatively analyse the myriocin in Isaria cicadae and its allies. The samples were prepared with 95% methanol for 30 min by ultrasonic-assisted extraction. The target compound was purified by ODS solid-phase extraction (SPE) column. The enriched samples were identified by mass spectrometry. The results showed that the contents of myriocin in both wild and artificial Isaria cicadae were below the detection limit, while a strain of Ophiocordyceps longissima and Cordyceps cicadae Shing (Dujiaolong), both closely related to the Isaria cicadae, and its asexual mycelia are rich in myriocin. It suggests that it may be wrong to consider C. cicadae as I. cicadae’s teleomorph in Genbank or Mycobank in many published reports based on chemical classification, and the species rich in myriocin is probably not Isaria cicadae.

The deflectable nose missile has a longer range by deflecting its nose to improve its aerodynamic feature. Based on detached eddy simulation (DES), the supersonic flow fields of a missile with deflectable nose are simulated numerically and its aerodynamic force coefficients are calculated under the condition of the deflection angles vary from 0° to 8°, angles of attack, 0°–8°, and mach numbers, 2 to 5. Coupling these aerodynamic coefficients with the plumb plane ballistic equations, the extended flight range has been calculated. Furthermore, the genetic algorithm (GA) is employed for the solution of maximum range of the deflected missile.

Summary: The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. : Chen et al. show SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. This study uncovers a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and sequence-specific DNA-binding factors and also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. Keywords: TET2, SNIP1, c-MYC, DNA demethylation, transcription, DNA damage, cell death

The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

Icariin had been reported as a potential agent for osteogenesis, but the dose-effect relationship needed further research to realize the clinical application of icariin. We isolated and purified human bone mesenchymal stem cells (hBMSCs) and stimulated them with different concentrations of icariin. The cytotoxicity of icariin was evaluated by the methylthiazolytetrazolium (MTT) assay method. The proliferation and osteogenic differentiation of such hBMSCs were investigated for different concentrations of icariin. We found that icariin had a dose-dependent effect on the proliferation and osteogenic differentiation of hBMSCs in a suitable concentration range from 10−9 M to 10−6 M, but at concentrations above 10−5 M, the cytotoxicity limited its use. The extremely low cost of icariin and its high abundance make it appealing for bone regeneration.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.

Autologous platelet-rich plasma (PRP) has been extensively investigated for large bone defect treatment, but its clinical application is harassed by controversial outcome, due to highly variable PRP quality among patients. Alternatively, allogeneic PRP from well-characterized donors cannot only generate more consistent and reliable therapeutic effect but also avoid harvesting large quantities of blood, an additional health burdens to patients. However, the use of allogeneic PRP for bone defect treatment is generally less investigated, especially for its immunogenicity in such application. Here, we meticulously investigated the immunogenicity of allogeneic PRP and evaluated its healing efficacy for critical-sized defect treatment. Allogeneic PRP contained 4.1-fold and 2.7- to 4.9-fold higher amount of platelets and growth factors than whole blood, respectively. The intramuscular injection of allogeneic PRP to rabbits did not trigger severe and chronic immunoresponse, evidenced by little change in muscular tissue microstructure and CD4 + /CD8 + T lymphocyte subpopulation in peripheral blood. The implantation of allogeneic PRP/deproteinized bone matrix (DPB) constructs (PRP + DPB) successfully bridged 1.5-cm segmental radial defects in rabbits, achieving similar healing capacity as autologous MSC/DPB constructs (MSC + DPB), with greater bone formation (1.1–1.5x, p < 0.05) and vascularization (1.3–1.6x, p < 0.05) than DPB alone, shown by histomorphometric analysis, bone mineral density measurement, and radionuclide bone imaging. Furthermore, the implantation of both allogeneic PRP- and autologous MSC-mediated DPB constructs (PRP + MSC + DPB) resulted in the most robust bone regeneration (1.2–2.1x, p < 0.05) and vascularization (1.3–2.0x, p < 0.05) than others (PRP + DPB, MSC + DPB, or DPB alone). This study has demonstrated the promising use of allogeneic PRP for bone defect treatment with negligible immunogenicity, great healing efficacy, potentially more consistent quality, and no additional health burden to patients; additionally, the synergetic enhancing effect found between allogeneic PRP and autologous MSCs may shed a light on developing new therapeutic strategies for large bone defect treatment.