Elevated pCO2 alleviates the toxic effects of polystyrene nanoparticles on the marine microalga Nannochloropsis oceanica.

Concerns about the environmental effects of nanoplastics on marine ecosystems are increasing. Ocean acidification (OA) has also become a global environmental problem. Plastic pollution occurs concomitantly with anthropogenic climate stressors such as OA. However, the combined effects of NP and OA on marine phytoplankton are still not well understood. Therefore, we have investigated the behavior of ammonia (NH2) polystyrene nanoparticles (PS NP) in f/2 medium under 1000 µatm pCO2 and discussed the toxicity of PS NP (100 nm; 0.5 and 1.5 mg/L) on Nannochloropsis oceanica under long and short-term acidification (LA and SA; pCO2 ~ 1000 µatm). We observed PS NP suspended in pCO2 1000 µatm f/2 medium aggregated to a size greater than nanoscale (1339.00 ± 76.10 nm). In addition, we found that PS NP significantly inhibited the growth of N. oceanica at two concentrations, which also produced oxidative stress. Whereas, the growth of algal cells under the coupling of acidification and PS NP was significantly better than that of single PS NP exposure. This indicated that acidification significantly alleviated the toxic effects of PS NP on N. oceanica, and long-term acidification can even promote the growth of N. oceanica under low-density NP. To further understand the mechanism, we analyzed a comparative transcriptome. The results showed that PS NP exposure inhibited the expression of genes involved in the TCA cycle. The acidification was possibly reflected in ribosomes and corresponding processes, which alleviated the negative effects of PS NP on N. oceanica by promoting the synthesis of related enzymes and proteins. This study provided a theoretical basis for assessing the damage of NP to marine phytoplankton under OA. We propose that future studies evaluating the toxicology of NP to marine ecology should consider the changing ocean climate.

CDC42 Might Be a Molecular Signature of DWI-FLAIR Mismatch in a Nonhuman Primate Stroke Model.

No definitive blood markers of DWI-FLAIR mismatch, a pivotal indicator of salvageable ischemic penumbra brain tissue, are known. We previously reported that CDC42 and RHOA are associated with the ischemic penumbra. Here, we investigated whether plasma CDC42 and RHOA are surrogate markers of DWI-FLAIR mismatch. Sixteen cynomolgus macaques (3 as controls and 13 for the stroke model) were included. Guided by digital subtraction angiography (DSA), a middle cerebral artery occlusion (MCAO) model was established by occluding the middle cerebral artery (MCA) with a balloon. MRI and neurological deficit scoring were performed to evaluate postinfarction changes. Plasma CDC42 and RHOA levels were measured by enzyme-linked immunosorbent assay (ELISA). The stroke model was successfully established in eight monkeys. Based on postinfarction MRI images, experimental animals were divided into a FLAIR (-) group (N = 4) and a FLAIR (+) group (N = 4). Plasma CDC42 in the FLAIR (-) group showed a significant decrease compared with that in the FLAIR (+) group (p < 0.05). No statistically significant difference was observed for plasma RHOA. The FLAIR (-) group showed a milder neurological function deficit and a smaller infarct volume than the FLAIR (+) group (p < 0.05). Therefore, plasma CDC42 might be a new surrogate marker for DWI-FLAIR mismatch.

Genetic basis of the early heading of high-latitude weedy rice.

Japonica rice (Oryza sativa L.) is an important staple food in high-latitude regions and is widely distributed in northern China, Japan, Korea, and Europe. However, the genetic diversity of japonica rice is relatively narrow and poorly adapted. Weedy rice (Oryza sativa f. spontanea) is a semi-domesticated rice. Its headings are earlier than the accompanied japonica rice, making it a potential new genetic resource, which can make up for the defects of wild rice that are difficult to be directly applied to japonica rice improvement caused by reproductive isolation. In this study, we applied a natural population consisting of weedy rice, japonica landrace, and japonica cultivar to conduct a genome-wide association study (GWAS) of the heading date and found four loci that could explain the natural variation of the heading date in this population. At the same time, we developed recombinant inbred lines (RILs) crossed by the early-heading weedy rice WR04-6 and its accompanied japonica cultivar ShenNong 265 (SN265) to carry out a QTL mapping analysis of the heading date and mapped four quantitative trait locus (QTLs) and three epistatic effect gene pairs. The major locus on chromosome 6 overlapped with the GWAS result. Further analysis found that two genes, Hd1 and OsCCT22, on chromosome 6 (Locus 2 and Locus 3) may be the key points of the early-heading character of weedy rice. As minor effect genes, Dth7 and Hd16 also have genetic contributions to the early heading of weedy rice. In the process of developing the RIL population, we introduced fragments of Locus 2 and Locus 3 from the weedy rice into super-high-yielding japonica rice, which successfully promoted its heading date by at least 10 days and expanded the rice suitable cultivation area northward by about 400 km. This study successfully revealed the genetic basis of the early heading of weedy rice and provided a new idea for the genetic improvement of cultivated rice by weedy rice.

An in vitro fibrotic liver lobule model through sequential cell-seeding of HSCs and HepG2 on 3D-printed poly(glycerol sebacate) acrylate scaffolds.

Cirrhosis is a major cause of global morbidity and mortality, and significantly leads to a heightened risk of liver cancer. Despite decades of efforts in seeking for cures for cirrhosis, this disease remains irreversible. To assist in the advancement of understanding toward cirrhosis as well as therapeutic options, various disease models, each with different strengths, are developed. With the development of three-dimensional (3D) cell culture in recent years, more realistic biochemical properties are observed in 3D cell models, which have gradually taken over the responsibilities of traditional 2D cell culture, and are expected to replace some of the animal models in the near future. Here, we propose a 3D fibrotic liver model inspired by liver lobules. In the model, 3D-printed poly(glycerol sebacate) acrylate (PGSA) scaffolds facilitated the formation of 3D tissues and guided the deposition of fibrotic structures. Through the sequential seeding of hepatic stellate cells (HSCs), HepG2 and HSCs, fibrotic septum-like tissues were created on PGSA scaffolds. As albumin secretion is considered a rather important function of the liver and is found only among hepatic cells, the detection of albumin secretion up to 30 days indicates the mimicking of basic liver functions. Moreover, the in vivo fibrotic tissue shows a high similarity to fibrotic septa. Finally, via complete encapsulation of HSCs, a down-regulated albumin secretion profile was observed in the capped model, which is a metabolic indicator that is important for the prognosis for liver cirrhosis. Looking forward, the incorporation of the vasculature will further upgrade the model into a sound tool for liver research and associated treatments.

A Pilot Study: Favorable Effects of Clostridium butyricum on Intestinal Microbiota for Adjuvant Therapy of Lung Cancer.

Probiotics as medications have previously been shown to change intestinal microbial characteristics, potentially influencing cancer therapy efficacy. Patients with non-squamous non-small cell lung cancer (NS-NSCLC) treated by bevacizumab plus platinum-based chemotherapy were randomized to obtain Clostridium butyricum supplement (CBS) or receive a placebo as adjuvant therapy. Clinical efficacy and safety were assessed using progression-free survival (PFS), overall survival (OS), and adverse events (AE). Intestinal microbiota was longitudinally explored between CBS and placebo groups over time. Patients who took CBS had significantly decreased bacterial richness and abundance, as well as increased the total richness of the genus Clostridium, Bifidobacterium, and Lactobacillus compared to the placebo group (p < 0.05). Beta diversity and the interactional network of intestinal microbiota were distinctly different between CBS and placebo group. However, there were no significant variations between them in terms of microbial taxonomical taxa and alpha diversity. The potential opportunistic pathogen Shewanella was still detectable after treatment in the placebo group, while no distinguishing microbial markers were found in the CBS group. In terms of clinical efficacy, the CBS group had a significantly reduced AE compare to the placebo group (p < 0.05), although no significantly longer PFS and OS. Therefore, favorable modifications in intestinal microbiota and significant improvements in drug safety make probiotics be promising adjunctive therapeutic avenues for lung cancer treatment.

Recombinant Human Regenerating Gene 4 Attenuates the Severity of Osteoarthritis by Promoting the Proliferation of Articular Chondrocyte in an Animal Model.

INTRODUCTION: Osteoarthritis (OA) is a dominant cause of morbidity and disability. As a chronic disease, its etiological risk factors and most therapies at present, are empirical and symptomatic. Regenerating gene 4 (Reg4) is involved in cell growth, survival, regeneration, adhesion, and resistance to apoptosis, which are partially thought to be the pathogenic mechanisms of OA. However, the proper role of Reg4 in OA is still unknown. METHODS: In this study, a consecutive administration of rhReg4 was applied to normal Sprague- Dawley rats or rats after OA induction. Histological changes and chondrocyte proliferation in the articular cartilage were measured. RESULTS: We found that RhReg4 promotes chondrocyte proliferation in normal rats, and RhReg4 attenuated the severity of OA in rats by promoting chondrocytes' proliferation in OA rats. CONCLUSION: In conclusion, recombinant human regenerating gene 4 (rhReg4) attenuates the severity of osteoarthritis in OA animal models and may be used as a new method for the treatment of osteoarthritis.

Endogenous neuroprotective mechanism of ATP2B1 in transcriptional regulation of ischemic preconditioning.

Ischemic stroke is the main cause of disability and mortality in the world. Clinical studies have shown that patients who undergo mild transient ischemic attack (TIA) before more severe ischemic stroke have lower clinical severity of stroke and better functional prognosis. This phenomenon is called ischemic preconditioning (IPC). IPC is a powerful intrinsic protection of the brain against ischemic injury, but the underlying mechanism of IPC-mediated endogenous protection of the brain is not clear. METHODS: Using transcriptome method, we sequenced the serum of 3 stroke patients with progenitor TIA and 3 stroke patients without prodromal TIA. We explored the expression profiles of miRNAs and mRNAs in response to IPC, and predicted the regulatory pathway of IPC related genes and their expression in cerebral neurons. The methylation consistent expression of IPC-related gene ATP2B1 in blood and brain and alternative polyadenylate (APA) analysis were used to identify the pathway and molecular mechanism of endogenous neuroprotection of IPC. RESULTS: We found that the brain protective effect of IPC was related to platelet homeostasis and Ca2+ concentration. IPC-related gene ATP2B1 was highly expressed in γ-aminobutyric acid (GABA)-containing neurons in the brain. From the mechanism, we speculated that ATP2B1 was representative of the same methylation in blood and brain and was affected by alternative polyadenylation. CONCLUSION: We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca2+ concentration in platelet homeostasis pathway and the activation of GABAB receptor.

Integrating Transcriptomics and Metabolomics to Characterize Metabolic Regulation to Elevated CO2 in Chlamydomonas Reinhardtii.

With atmospheric CO2 increasing, a large amount of CO2 is absorbed by oceans and lakes, which changes the carbonate system and affects the survival of aquatic plants, especially microalgae. The main aim of our study was to explore the responses of Chlamydomonas reinhardtii (Chlorophyceae) to elevated CO2 by combined transcriptome and metabolome analysis under three different scenarios: control (CK, 400 ppm), short-term elevated CO2 (ST, 1000 ppm), and long-term elevated CO2 (LT, 1000 ppm). The transcriptomic data showed moderate changes between ST and CK. However, metabolic analysis indicated that fatty acids (FAs) and partial amino acids (AAs) were increased under ST. There was a global downregulation of genes involved in photosynthesis, glycolysis, lipid metabolism, and nitrogen metabolism but increase in the TCA cycle and ß-oxidation under LT. Integrated transcriptome and metabolome analyses demonstrated that the nutritional constituents (FAs, AAs) under LT were poor compared with CK, and most genes and metabolites involved in C and N metabolism were significantly downregulated. However, the growth and photosynthesis of cells under LT increased significantly. Thus, C. reinhardtii could form a specific adaptive evolution to elevated CO2, affecting future biogeochemical cycles.

Hsp47 Inhibitor Col003 Attenuates Collagen-Induced Platelet Activation and Cerebral Ischemic-Reperfusion Injury in Rats.

Ischemic stroke is a major type of stroke worldwide currently without effective treatment, although antiplatelet therapy is an existing option for it. In previous studies, heat shock protein 47 (Hsp47) was found to be expressed on the surface of human and mice platelets and to strengthen the interaction between platelets and collagen. In recent years, Col003 was discovered to inhibit the interaction of Hsp47 with collagen. We evaluated whether the Hsp47 inhibitor Col003 is a promising therapeutic agent for ischemic stroke. Here, we first verified that Hsp47 is also expressed on the surface of rat platelets, and its inhibitor Col003 significantly inhibited thrombus formation in the FeCl3-induced rat carotid arterial thrombus model. Both Col003 and clopidogrel did not alter the bleeding time or coagulation parameters, while aspirin increased the tail-bleeding time (p < 0.05). The low cytotoxicity level of Col003 to rat platelets and human liver cells was similar to those of aspirin and clopidogrel. Col003 inhibited collagen-induced platelet aggregation, adhesion, [Ca2+]i mobilization, P-selectin expression, reactive oxygen species production and the downstream signal pathway of collagen receptors. The results of the middle cerebral artery occlusion model indicated that Col003 has a protective effect against cerebral ischemic-reperfusion injury in rats. The Hsp47 inhibitor Col003 exerted antiplatelet effect and protective effect against brain damage induced by ischemic stroke through the inhibition of glycoprotein VI (GPVI)and mitogen-activated protein kinase (MAPK) signaling events, which might yield a new antiplatelet agent and strategy to treat ischemic stroke.

Identify QTLs and candidate genes underlying source-, sink-, and grain yield-related traits in rice by integrated analysis of bi-parental and natural populations.

The source-sink relationship determines the ultimate grain yield of rice. In this study, we used a set of reciprocal introgression lines (ILs) derived from Xuishui09 × IR2061 to map quantitative trait loci (QTLs) that were associated with sink-, source-, and grain yield-related traits. A total of 95 QTLs influencing eight measured traits were identified using 6181 high-quality single nucleotide polymorphism markers. Nine background-independent QTLs were consistently detected in seven chromosomal regions in different genetic backgrounds. Seven QTLs clusters simultaneously affected sink-, source-, and grain yield-related traits, probably due to the genetic basis of significant correlations of grain yield with source and sink traits. We selected 15 candidate genes in the four QTLs consistently identified in the two populations by performing gene-based association and haplotype analyses using 2288 accessions from the 3K project. Among these, LOC_Os03g48970 for qTSN3b, LOC_Os06g04710 for qFLL6a, and LOC_Os07g32510 for qTGW7 were considered as the most likely candidate genes based on functional annotations. These results provide a basis for further study of candidate genes and for the development of high-yield rice varieties by balancing source-sink relationships using marker-assisted selection.

Pleiotropic Effect of GNP1 Underlying Grain Number per Panicle on Sink, Source and Flow in Rice.

Rice yield potential is largely determined by the balance among source capacity, sink strength, and flow fluency. Our previous study indicated that the gene GNP1 encoding gibberellin biosynthesis gene GA20ox1 affects grain number per panicle (GNP) in rice, thus resulting in increase of grain yield. To clarify GNP1 effect on sink, source and flow in regulating rice grain yield, we compared Lemont, a japonica (geng) cultivar, with its near-isogenic line (NIL-GNP1 TQ) in Lemont background with introgression of the allele at GNP1 from Teqing, a high-yielding indica (xian) cultivar. NIL-GNP1 TQ exhibited averagely 32.8% more GNP than Lemont with the compensation by reduced seed setting rate, panicle number and single-grain weight. However, NIL-GNP1 TQ still produced averagely 7.2% higher grain yield than Lemont in two years, mainly attributed to significantly more filled grain number per panicle, and greater vascular system contributing to photoassimilates transport to spikelets. The significantly decreased grain weight of superior spikelets (SS) in NIL-GNP1 TQ was ascribed to a significant decrease of grain size while the significantly decreased grain weight of inferior spikelets (IS) ascribed to both grain size and poor grain-filling as compared with Lemont. The low activities of key enzymes of carbon metabolism might account for the poor grain-filling in IS, which resulted in more unfilled grains or small grain bulk density in NIL-GNP1 TQ. In addition, low seed setting rate and grain weight of IS in NIL-GNP1 TQ might be partially resulted from significantly lower carbohydrate accumulation in culms and leaf sheath before heading compared with Lemont. Our results indicated that significantly increased GNP from introgression of GNP1 TQ into Lemont did not highly significantly improve grain yield of NIL-GNP1 TQ as expected, due primarily to significant low sink activities in IS and possible insufficient source supply which didn't fully meet the increased sink capacity. The results provided useful information for improving rice yield potential through reasonably introgressing or pyramiding the favorable alleles underlying source-related or panicle number traits by marker-assisted selection.

The effect of elevated pCO2 on cadmium resistance of a globally important diatom.

Cadmium (Cd) pollution is a widespread threat to marine life, and ongoing ocean acidification (OA) is predicted to impact bio-toxicity of Cd compounds. However, the cascading effects of changed Cd toxicity to marine primary producers are not well characterized. Here, we studied the impact of OA on Cd toxicity responses in a globally important diatom Phaeodactylum tricornutum under both ambient and elevated pCO2 conditions. We found that increased pCO2 alleviated the impact of additive Cd toxicity on P. tricornutum not only under controlled indoor experiments but also in outdoor mesocosm experiments that reflect more natural growth conditions. Transcriptome analysis suggested that genes involved in Cd efflux and phytochelatin production were up-regulated and genes involved in Cd influx were down-regulated in long-term selected lineages under elevated pCO2. We further found a significant reduction of Cd transfer across trophic level, when the scallop Argopecten irradians was fed with Cd-exposed P. tricornutum previously cultured under elevated pCO2. Our results indicate that after long-term selection of P. tricornutum exposed to future OA conditions (i.e. elevated pCO2), the diatom alters its Cd detoxification strategy, which could have broader impacts on the bio-geochemical cycle of Cd in the marine ecosystem.

Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty.

BACKGROUND This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). MATERIAL AND METHODS We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and ß-amyloid (Aß) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. RESULTS The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aß expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. CONCLUSIONS CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA.

Groundwater Vulnerability Assessment of the Pingtung Plain in Southern Taiwan.

In the Pingtung Plain of southern Taiwan, elevated levels of NO3--N in groundwater have been reported. Therefore, efforts for assessing groundwater vulnerability are required as part of the critical steps to prevent and control groundwater pollution. This study makes a groundwater vulnerability assessment for the Pingtung Plain using an improved overlay and index-based DRASTIC model. The improvement of the DRASTIC model is achieved by reassigning the weighting coefficients of the factors in this model with the help of a discriminant analysis statistical method. The analytical results obtained from the improved DRASTIC model provide a reliable prediction for use in groundwater vulnerability assessment to nitrate pollution and can correctly identify the groundwater protection zones in the Pingtung Plain. Moreover, the results of the sensitivity analysis conducted for the seven parameters in the improved DRASTIC model demonstrate that the aquifer media (A) is the most sensitive factor when the nitrate-N concentration is below 2.5 mg/L. For the cases where the nitrate-N concentration is above 2.5 mg/L, the aquifer media (A) and net recharge (R) are the two most important factors.

Defective autophagy leads to the suppression of stem-like features of CD271+ osteosarcoma cells.

BACKGROUND: As an important stress-response mechanism, autophagy plays crucial role in the tumor formation and drug resistance of cancer cells including osteosarcoma (OS). OS cancer stem cells (CSCs) also are considered a key factor of tumorigenesis, drug resistance and tumor recurrence. However, the relationship between autophagy and OS CSCs still remains unclear. METHODS: CD271+ OS CSCs and CD271- OS cells were isolated by magnetic activated cell sorting. The autophagy level was evaluated by the mRNA expression of autophagy genes, the protein level of LC3II and p62, and the mean number of GFP-LC3 dot per cell. Lentivirus-delivered specific shRNA was utilized to inhibit the corresponding gene expression. The cell viability was examined with CCK8 assay. The cell proliferation level was detected with BrdU staining assay. Cell death was determined by Annexin V/PI double staining of fluorescence activated cell sorting, lactate dehydrogenase release and caspase-3 activity. Tumorigenicity ability was evaluated by colony and sphere formation assay, the protein expression of stemness markers and tumor formation in nude mice. RESULTS: Our data indicated that CD271+ OS CSCs had a similar basic autophagy level with CD271- OS cells. Autophagy deficiency had no observable effects on the levels of cell proliferation and death both in CD271+ and CD271- OS cells under normal condition. However, CD271+ OS cells showed a higher autophagy activity than CD271- OS cells under hypoxia and low nutrient (LH) condition. Moreover, autophagy-deficient CD271+ OS cells lost the advantage of tolerance to LH condition compared to CD271- OS cells. Meanwhile, autophagy deficiency enhanced the sensitivity to chemotherapeutics in the CD271+ cells to the comparable level in the CD271- cells. More importantly, deficient-autophagy decreased the protein expression of stemness markers and caused the disappearance of the superiority in tumorigenicity in vitro and vivo in CD271+ OS cells. CONCLUSION: The results above demonstrated that autophagy contributes to the stem-like features of CD271+ OS CSCs. Inhibition of autophagy is a promising strategy in the CSCs-targeting OS therapy.

Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma.

In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients.

Efficacies of surgical treatments based on Harris hip score in elderly patients with femoral neck fracture.

AIM: To compare the efficacies of four surgical treatments, i.e., total hip arthroplasty (THA), internal fixation (IF), hemiarthroplasty (HA), and artificial femoral head replacement (artificial FHR), by performing a network meta-analysis based on Harris hip score (HHS) in elderly patients with femoral neck fracture. METHODS: In strict accordance with specific inclusion and exclusion criteria, randomized controlled trails (RCTs) were screened and selected from a larger group of studies that were retrieved through a comprehensive search of scientific literature databases, further complimented by manual search. The resultant high-quality data from final selected studies were analyzed using Stata 12.0 software. RESULTS: A total of 3680 studies were initially retrieved from database search, and 15 RCTs were eventually incorporated into this meta-analysis, containing 1781 elderly patients who had undergone various surgical treatments for femoral neck fracture (THA group = 604; HA group = 604; IF group = 495; artificial FHR group = 78). Our major result revealed a statistically significant difference in HHS of femoral neck fracture when HA and IF groups were compared with THA. No differences were detected in the HHS of femoral neck fracture undergoing artificial FHR and THA. The surface under the cumulative ranking curves (SUCRA) value of HHS, in elderly patients with femoral neck fracture after surgery, revealed that IF has the highest value. CONCLUSIONS: The current network meta-analysis results suggest that IF is the superlative surgical procedure for femoral neck fracture patients, and IF significantly improves the HHS in femoral neck fracture patients.

Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway.

Naringin exhibits antiinflammatory activity and is shown to induce bone formation. Yet the impact of naringin on inflammation-affected bone marrow-derived mesenchymal stem cell (BM-MSC), a promising tool for the regenerative treatment of bone injury, remained to be investigated. We first cultured and characterized the BM-MSCs in vitro and observe the effects of treatments of TNF-α, naringin, or the combination of both on osteogenic differentiation. TNF-α administered at the concentration of 20 ng/ml results in significant reductions in MSC's cell survival, alkaline phosphatase activity and expressions of two osteogenic genes, Runx2 and Osx. Simultaneous treatment of both TNF-α and naringin is able to rescue such reductions. Further mechanistic studies indicate that TNF-α treatment activates the NF-кB signaling pathway, evidenced by elevated p-IкBα level as well as the increased nuclear fraction of NF-кB subunit, p65. Finally, treatment with both TNF-α and naringin decreases expressions of p-IкBα and nuclear p65, and thus represses NF-кB pathway activated by sole TNF-α treatment. Our findings provide a molecular basis by which naringin restores the TNF-α-induced damage in MSCs and provide novel insights into the application of naringin in the MSC-based treatments for inflammation-induced bone injury.

The involvement of PDGF/VEGF related factor in regulation of immune and neuroendocrine in Chinese mitten crab Eriocheir sinensis.

Members of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family have been implicated in cell proliferation, cell differentiation, and cell migration, vascular development, angiogenesis and neural development. In the present study, a novel PDGF/VEGF related factor gene was cloned and identified in Chinese mitten crab Eriocheir sinensis (designated as EsPVF1). The full-length cDNA of EsPVF1 was of 1173 bp, consisting a 5' untranslated region (UTR) of 54 bp, a 3' UTR of 1131 bp with a poly (A) tail, and an open reading frame (ORF) of 588 bp encoding 196 amino acid residues. A signal peptide of 20 amino acid residues, a PDGF/VEGF homology growth factor domain of 81 amino acids, and a typical cysteine knot motif (CXCXC) were identified in the deduced amino acid sequence of EsPVF1. By fluorescent quantitative real-time PCR, the EsPVF1 mRNA was detected ubiquitously in the select tissues of hemocytes, gonad, heart, muscle, hepatopancreas and gill, with the high abundance in hemocytes and gonad. The mRNA expression level of EsPVF1 was up-regulated and reached the highest at 24 h after Vibrio anguillarum challenge, while it was induced at 3 h, 6 h, 12 h, 24 h and 48 h compared with the untreated group after Pichia pastoris GS115 challenge. Tissue injury also induced the mRNA expression of EsPVF1 in hemocytes of crabs, and the expression level increased obviously at 8 h. The cDNA fragment encoding mature peptide of EsPVF1 was recombined and expressed in Escherichia coli BL21 (DE3) pLysS. Biogenic amine in hemolymph pre-incubated with recombinant protein of EsPVF1 (rEsPVF1) was detected by fluorimetric method. Norepinephrine and dopamine in hemolymph incubated with rEsPVF1 were higher than that in the blank group. Therefore, EsPVF1 could significantly provoke the release of norepinephrine and dopamine. The results collectively indicated that EsPVF1 was involved in regulation of the immune response and neuroendocrine system in crabs.