An Investigation of the Anisotropic Mechanical Properties of Additive-Manufactured 316L SS with SLM.

Selective laser melting (SLM) forms specimens that often exhibit anisotropic mechanical properties. Most existing research only explains that the mechanical properties of specimens perpendicular to the build direction are superior to those parallel to the build direction. In this paper, the mechanical properties of SLM 316L SS specimens with different surfaces and different directions are compared. Finally, it was found that the mechanical properties of specimens on Face 3 are stronger than those on Face 1 and Face 2, while the mechanical properties of specimens on Face 1 and Face 2 are similar. For specimens in different directions on the same surface, the mechanical properties of Face 1 and Face 2 exhibit clear anisotropy, while the mechanical properties of Face 3 tend to be isotropic. In this paper, the EBSD technique was used to analyze the specimens. It was found that the anisotropy of the mechanical properties of Face 1 and Face 2 are attributed to the presence of texture and columnar crystals in the sample. This paper can provide accurate and reliable material performance data for the practical application of SLM 316L SS, thereby guiding the optimization of engineering design and manufacturing processes.

Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-ß/TXNIP pathway.

OBJECTIVE: Intervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. METHODS: To confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. RESULTS: Macrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes' expression and the activation of pathways related to pyroptosis in the nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-ß)/ thioredoxin-interacting protein pathway. CONCLUSIONS: The absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds the potential for retarding intervertebral disc degeneration in the human body.

To Take a Risk or Not? The Effect of Perceived Scarcity on Risky Choices.

Studies suggest that resource scarcity leads to risky behaviors. From a cognitive perspective, a scarcity mindset affects the decision-making process. Does perceived scarcity therefore affect risk taking when making decisions? This study (N = 213) was conducted in western China to examine the effect of perceived scarcity on risky choices. Our results revealed that participants in the scarcity condition tended to be more risk averse than participants in the control condition when making a risky decision. Perceived scarcity increased the probability of choosing the safe option that offered a sure gain. The effect of psychological variables (emotion, risk attitude, personality, impulsivity, self-control and ego depletion) on risky choices was also tested. Risk attitude, urgency in impulsivity, and deliberate action in self-control also influence risky choices.

Outcomes of single- vs two-stage primary joint arthroplasty for septic arthritis: a systematic review and meta-analysis.

Purpose: Septic arthritis (SA) is an intra-articular infection caused by purulent bacteria and the only effective method is surgical intervention. Two-stage arthroplasty is considered the gold standard treatment for SA, but recent studies have found that single-stage arthroplasty can achieve the same efficacy as two-stage arthroplasty. This study aimed to compare the efficacy of single- vs two-stage arthroplasty in the treatment of (acute or quiescent) SA. Methods: The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, Medline, and Cochrane Library databases to identify all literature on the treatment of SA using single- and two-stage arthroplasty from the date of database inception to November 10, 2022. Data on reinfection rates were expressed as odds ratios and 95% CIs. Results: Seven retrospective studies with a total of 413 patients were included. Pooled analysis showed no difference in the reinfection rate between single- and two-stage arthroplasty. Subgroup analysis found no difference between the single- and two-stage arthroplasty groups in the incidence of purulent infection of the hip and knee. Cumulative meta-analysis showed gradual stabilization of outcomes. Conclusions: Based on our meta-analysis of available retrospective studies, we found no significant difference in reinfection rates between single- and two-stage arthroplasty for SA. Further prospective cohort studies are needed to confirm our results, although our meta-analysis provides important insights into the current literature on this topic.

Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways.

OBJECTIVES: Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD. METHODS: An IL-1ß-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc. KEY FINDINGS: Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model. CONCLUSIONS: Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.

Determination of selected glucocorticoids in healthy foods by ultra-performance convergence chromatography-triple quadrupole mass spectrometry.

The presence of glucocorticoids in healthy foods has recently become a topic of concern because of their side effects. In this study, we developed a method based on ultra-performance convergence chromatography-triple quadrupole mass spectrometry (UPC2-MS/MS) to detect 63 glucocorticoids in healthy foods. The analysis conditions were optimized, and the method was validated. We further compared the results of this method with those of the RPLC-MS/MS method. Glucocorticoids were separated on an Acquity Torus 2-picolylamine column (100 mm × 3.0 mm, 1.7 µm) and detected via MS/MS. CO2 and methanol (containing 0.1% formic acid) were used as mobile phases. The method demonstrated good linear relationships between 1 and 200 µg·L-1 (R2 ≥ 0.996). The limits of detection in different types of samples were 0.3-1.5 µg·kg-1 (S/N = 3). The average recoveries (n = 9) and RSDs in different types of samples were 76.6-118.2% and 1.1-13.1%, respectively. The matrix effect, calculated as the ratio between calibration curves built in matrix and pure solvent, was less than 0.21 for both a fish oil and a protein powder. This method exhibited better selectivity and resolution than RPLC-MS/MS method. Lastly, it could realize the baseline separation of 31 isomers of 13 groups, including four groups of eight epimers. This study provides new technical support for assessing the risk of exposure to glucocorticoids in healthy foods.

PD0325901, an ERK inhibitor, attenuates RANKL-induced osteoclast formation and mitigates cartilage inflammation by inhibiting the NF-κB and MAPK pathways.

Osteoarthritis (OA), a degenerative disease affecting the joint, is characterized by degradation of the joint edge, cartilage injury, and subchondral bone hyperplasia. Treatment of early subchondral bone loss in OA can inhibit subsequent articular degeneration and improve the prognosis of OA. PD0325901, a specific inhibitor of ERK, is widely used in oncology and has potential as a therapeutic agent for osteoarthritis In this study, we investigated the biological function of PD0325901 in bone marrow monocytes/macrophages (BMMs)treated with RANKL and found that it inhibited osteoclast differentiation in vitro in a time- and dose-dependent manner. PD0325901 restrained the expression of osteoclast marker genes, such as c-Fos and NFATc1 induced by RANKL. We tested the biological effects of PD035901 on ATDC5 cells stimulated by IL-1ß and found that it had protective effects on ATDC5 cells. In animal studies, we used a destabilization of the medial meniscus (DMM) model and injected 5 mg/kg or 10 mg/kg of PD0325901 compound into each experimental group of mice. We found that PD0325901 significantly reduced osteochondral pathological changes in post-OA subchondral bone destruction.Finally, we found that PD0325901 down-regulated the pyroptosis level in chondrocytes to rescue cartilage degeneration. Therefore, PD0325901 is expected to be a new generation alternative therapy for OA.

Bufei Decoction Improves Lung-Qi Deficiency Syndrome of Chronic Obstructive Pulmonary Disease in Rats by Regulating the Balance of Th17/Treg Cells.

Bufei decoction (BFD) has been applied to treat chronic obstructive pulmonary disease (COPD) for centuries as a recognized traditional Chinese herbal formula. However, mechanisms of BFD on COPD are unclear. This study conducts an inquiry into the underlying mechanisms of the therapeutic effect of BFD on COPD. A COPD rat model with qi deficiency in lungs was established through induction using cigarette and sawdust smoking combined with intratracheal instillation of lipopolysaccharide following BFD treatment for 28 days. Changes in Th17/Treg cells of COPD rats with the syndrome of lung qi deficiency after BFD administration were verified using pulmonary function, ELISA, flow cytometry, histopathology, and Western blotting assays. The findings showed that BFD protected COPD rats from decreased lung function and lung injury. BFD administration reduced proinflammatory cytokines IL-6 and IL-17 secretion, promoted inhibitory cytokines IL-10 and TGF-ß secretion, decreased Th17/Treg cell ratio, markedly downregulated the Th17 cell transcription factor ROR-γt expression, and upregulated transcription factor Foxp3 expression in Treg cells. We speculate that lung tonic soup improved pulmonary qi deficiency in rats with COPD by regulating the balance of Th17/Treg cells.

Neratinib exerts dual effects on cartilage degradation and osteoclast production in Osteoarthritis by inhibiting the activation of the MAPK/NF-κB signaling pathways.

Osteoarthritis (OA) is a degenerative disease caused by the progressive destruction of cartilage and subchondral bone [1]. Studies have shown that by inhibiting the degradation of cartilage cells and the loss of subchondral bone, OA can be prevented and treated. Neratinib, as a small molecule compound with anti-inflammatory and anti-tumor properties, is a very effective inhibitor of IL-1ß-induced chondrocyte inflammation and anabolic metabolism. By investigating the effect of neratinib in ATDC5 chondrocytes, the study finds that neratinib reduces inflammation by inhibiting the MAPK and NF-κB signaling pathways, and at the same time reduces pyrolysis (indicated by the results of reverse transcription quantitative PCR and western blotting). For anabolic metabolism, after high-density cell culture, IL-1ß-induced catalytic changes and degradation of the extracellular matrix were evaluated by toluidine blue staining. Since osteoclasts are key participants in the process of subchondral bone remodeling in OA, we also studied the effect of neratinib on the maturation of osteoclasts. The results showed that neratinib also acts as an anti-osteoclast agent in vitro. By inhibiting the NF-κB and MAPK pathways, it reduces the expression of osteoclast-related genes, thereby inhibiting RANKL-induced osteoclastogenesis. The results of in vivo animal experiments supported the conclusions from the experiments in vitro. Neratinib inhibited both the destruction of medial meniscus induced cartilage degradation and osteoclast formation, which proves that neratinib has a dual effect, protecting cartilage and inhibiting osteoclast formation. These results indicate that neratinib can be a brand-new latent strategy for the treatment of OA.

The Effector Protein CgNLP1 of Colletotrichum gloeosporioides Affects Invasion and Disrupts Nuclear Localization of Necrosis-Induced Transcription Factor HbMYB8-Like to Suppress Plant Defense Signaling.

Fungi secrete numerous effectors to modulate host defense systems. Understanding the molecular mechanisms by which fungal effectors regulate plant defense is of great importance for the development of novel strategies for disease control. In this study, we identified necrosis- and ethylene-inducing protein 1 (Nep1)-like protein (NLP) effector gene, CgNLP1, which contributed to conidial germination, appressorium formation, invasive growth, and virulence of Colletotrichum gloeosporioides to the rubber tree. Transient expression of CgNLP1 in the leaves of Nicotiana benthamiana induced ethylene production in plants. Ectopic expression of CgNLP1 in Arabidopsis significantly enhanced the resistance to Botrytis cinerea and Alternaria brassicicola. An R2R3 type transcription factor HbMYB8-like of rubber tree was identified as the target of CgNLP1.HbMYB8-like, localized on the nucleus, and induced cell death in N. benthamiana. CgNLP1 disrupted nuclear accumulation of HbMYB8-like and suppressed HbMYB8-like induced cell death, which is mediated by the salicylic acid (SA) signal pathway. This study suggested a new strategy whereby C. gloeosporioides exploited the CgNLP1 effector to affect invasion and suppress a host defense regulator HbMYB8-like to facilitate infection.

Wright's Technique with the Addition of Visualized Axial Cortical Windows in Odontoid Fractures.

This study sought to investigate and evaluate a modified axial translaminar screw fixation for treating odontoid fractures. We performed a retrospective study at Wenzhou Medical University Affiliated Second Hospital between March 2016 and June 2018. We retrospectively collected and analyzed the medical records of 23 cases with odontoid fractures. All patients were identified as type II odontoid fractures without neurological deficiency and serious diseases following the classification of Anderson. The average age, gender ratio, and body mass index (BMI) were 54.3 ± 11.1 years, 12 men to 11 women, and 22.6 ± 2.4 kg/m2 , respectively. Patients in this study accepted screw fixation using our modified axial translaminar screw fixation combined with atlas pedicle or lateral mass screw fixation. Within the technique, a small cortical "window" was dug in the middle of the axial contralateral lamina, such that the screws in the lamina were visualized to prevent incorrectly implanting the posterior spinal canal through the visualized "window." A total of 46 bone screws were accurately inserted into the axial lamina without using fluoroscopy. The length of all translaminar screws ranged between 26 and 30 mm, while the diameter was 3.5 mm. During the follow-up survey, the visual analog scale (VAS) and neck disability index (NDI) were measured. We provide a simple modification of Wright's elegant technique with the addition of "visualized windows" at the middle of the axial lamina. In all patients, screws were inserted accurately without bony breach and the screw angle was 56.1 ± 3.0°. Mean operative time was 102 ± 28 min with an average blood loss of 50 ± 25 mL. Postoperative hemoglobin and mean length of hospital stay were 12.0 ± 1.4 g/dL and 10.4 ± 3.4 days, respectively. The average follow-up time of all cases was 14.7 months and no internal fixation displacement, loosening, or breakage was found. All patients with odontoid fractures reported being satisfied with the treatment during the recheck period and good clinical outcomes were observed. At 1, 6, and 12 months, NDI and VAS showed that the symptoms of neck pain and limitations of functional disability improved significantly during follow-up. Our results suggest that the modified translaminar screw fixation technique can efficiently treat Anderson type II odontoid fracture, followed by the benefits of less soft tissue dissection, simple operation, no fluoroscopy, and accurate placement of screws.

Study on the Effect of Huanglian Jiedu Decoction on the Composition of Gut Microflora in SD Rats Based on 16S rRNA Sequencing.

OBJECTIVE: To study the effects of Huanglian Jiedu Decoction (HJD) on gut microflora of SD rats. METHOD: After 3 days of adaptive feeding, 36 rats were randomly divided into 4 groups, namely, the normal control group (NC, 10 mL/kg, distilled water), high_HJD dose group (H_HJD, 6.25 g/kg, weight ratio between crude drug and rat), medium_HJD dose group (M_HJD, 3.125 g/kg), and low_HJD dose group (L_HJD, 1.56 g/kg), and each group consisted of 9 mice. The HJD groups were then treated with orally administered HJD for 21 days, while the NC group was treated with distilled water. After 7 days, 14 days, and 21 days of the experiment and after 12 hours of fasting and water deprivation, 3 SD rats in each group were randomly sacrificed by cervical dislocation and sterile operation to collect stool faces. Sample DNA was extracted by Fecal total DNA extraction kit, sequenced using Illumina MiSeq platform, and analyzed. RESULTS: The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Coprobacillus, Blautia, Akkermansia, Klebsiella, Rhodococcus, Parabacteroides, Citrobacter, Enterococcus, Bacteroides, and Erysipelotrichaceae_incertae_sedis increased after using H_HJD. The abundance of Gemella, Turicibacter, Romboutsia, and Lactobacillus decreased, while that of Blautia, Akkermansia, Escherichia_Shigella, Thiobacillus, Rothia, Enterococcus, Lactobacillus, and Erysipelotrichaceae-incertae-sedis increased after using M_HJD. The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Bacteroides, Akkermansia, Enterococcus, Rhodococcus, Parabacteroides, Desulfovibrio, Blautia, Fusobacterium, Rothia, and Streptococcus increased after using L_HJD. CONCLUSION: HJD can regulate gut microbiota, and its effect varies with different dosage and duration of medication.

Inhibition of GPR17 with pranlukast protects against TNF-α-induced loss of type II collagen in ATDC5 cells.

Osteoarthritis (OA) is a common joint disease affecting millions of elderly people worldwide. However, the mechanism of OA is complicated and remains poorly understood. Thus, a safe and effective therapeutic strategy has yet to be developed. G protein-coupled receptor 17 (GPR17) is an orphan receptor that is widely distributed in the central nervous system (CNS). GPR17 has become a target for the treatment of inflammation in brain diseases. In this study, we demonstrate that GPR17 is expressed in ATDC5 cells and is increased in response to TNF-α exposure. We also found that antagonism of GPR17 with pranlukast significantly inhibited oxidative stress by downregulating the intracellular level of reactive oxygen species (ROS) and increasing the activity of super oxide dismutase (SOD) against TNF-α. Interestingly, treatment with pranlukast prevented TNF-α-induced reduction of type II collagen. Additionally, knockdown of GPR17 with siRNA ameliorated TNF-α-induced loss of type II collagen, suggesting the importance of the role of GPR17 in mediating the impairment of type II collagen. Blockage of GPR17 with pranlukast suppressed the expression of matrix metalloproteinases 3 (MMP-3) and matrix metalloproteinases 13 (MMP-13), which contribute to the degradation of type II collagen. Pranlukast also prevented the activation of the JAK2/STAT1/IRF-1 signaling pathway, thereby suppressing the expression of pro-inflammatory cytokines and enzymes. Furthermore, pranlukast rescued TNF-α-induced reduced SOX-9 expression. Together, our data indicate that GPR17 might be a potential target for the treatment of OA.

[Determination of 15 3-chloro-1,2-propanediol fatty acid esters in vegetable oils and fritters by ultra performance convergence chromatography-tandem mass spectrometry].

The presence of 3-chloro-1,2-propanediol fatty acid esters (3-MCPDE) in food and processed materials has recently become a topic of concern because of the toxicity of their metabolites. 3-MCPDE structurally similar to glyceride, which makes it difficult to separate or extract them from oils and fritters. A method based on ultra performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS) was established for the determination of 15 3-MCPDE in vegetable oils and fritters. Amino-packed columns were used to purify the samples. The analytical conditions were optimized, and the matrix effect was investigated. The sample was treated by column chromatography to remove glyceride and free fatty acids, which induce strong matrix effects. The amino-packed column was eluted with hexane and hexane-ethyl acetate (6:4, v/v). Every 1 mL of the eluent was analyzed using a UPC2 and ACQUITY QDa detector. Elution curves were drawn based on the testing data and used to determine the collection volume. The collection volumes for 3-chloro-1,2-propanediol diesters and monoesters according to the elution curves were 7-14 mL and 3-9 mL. The collected eluent was mixed and dried under nitrogen flow at a temperature of 60℃. A hexane-isopropanol (98:2, v/v, 1 mL) mixture was used to dissolve the residue. The resulting solution was separated on a Viridis HSS C18 SB column (150 mm×2.1 mm, 1.8 µm) under gradient elution. Supercritical carbon dioxide and methanol (containing 40% acetonitrile and 0.1% formic acid) were used as the mobile phases, and the flow rate was 1 mL/min. The separated compounds were analyzed by tandem MS with an electrospray ionization (ESI) source in positive and multiple reaction monitoring modes. Water (containing 97% isopropanol and 0.2% ammonia water) was used as the auxiliary pump mobile phase, and the flow rate was 0.2 mL/min. The method showed good linear relationships in the range of 0.5-100 µg/L (r2 ≥ 0.9973). The limits of detection (LODs) and limits of quantification (LOQs) were 0.01-0.68 µg/L (S/N=3) and 0.04-1.74 µg/L (S/N=10), respectively. The average recoveries (n=9) at the three spiked levels were in the range of 81.6%-98.5%. The relative standard deviations were in the range of 1.8%-6.4%. The matrix effects in the case of the oils and fritters were weak. The developed method was used to detect 44 oil samples and eight fritter samples. Meanwhile, some suspect 3-MCPDE compounds outside the scope of the investigation were analyzed based on their primary and secondary mass spectra. The detection rates of 3-MCPDE in oils and fritters were 84.1% and 87.5%, and their amounts were in the range of 0.024-4.481 mg/kg and 0.018-1.144 mg/kg, respectively. The detection rates of 3-MCPDE in rapeseed oil were higher compared to those for other kinds of oil. The method is specific, fast, simple, accurate, reliable, and environmentally friendly, in addition to being more sensitive than other methods and showing better matrix compatibility for oils. This method has been successfully used to determine the types and amounts of 3-MCPDE in vegetable oils and fritters. The research findings provided accurate data to assess the exposure risk of 3-MCPDE. The results of our experiment also provided valuable information for elucidating the formation mechanism of 3-MCPDE. The proposed method can be used to analyze waste edible oil based on large amounts of analysis data. However, this method has some limitations. The resolution ratio of the mass spectrometer used in this method is too low for the qualitative analysis of unknown compounds. The qualitative results for the suspect 3-MCPDE compounds are not particularly accurate, and a large variety of monomer standards are required for the quantitative determination of 3-MCPDE. The 3-MCPDE standards are expensive, and there is limited choice of these standards; moreover, they are difficult to synthesize. The poor ionization yield of 3-chloro-1,2-propanediol monoesters under the ESI conditions resulted in high LODs. Hence, it is necessary to develop a method for increasing the ionization of monoesters, for example, via derivatization.

Arthroscopy-assisted surgery: The management of posterolateral tibial plateau depression fracture accompanying ligament injury: A case series and review of the literature.

Tibial plateau fractures are multiple fracture patterns associated with soft-tissue injuries. Among which, the combined existence of posterolateral tibial plateau depression fracture with anterior cruciate ligament (ACL) rupture has been reported rarely. Meanwhile, surgical method for the treatment of depression fracture is fairly complex. The aim of this article is to show a case series of this unusual injury pattern and the therapy of posterolateral tibial plateau depression fracture accompanying ACL rupture. In our treatment, arthroscopy assisted reduction of depression fracture and ACL reconstruction reduces surgical trauma and leads to good functional recovery. We also review the current literature.

LINC01436, regulating miR-585 and FBXO11, is an oncogenic lncRNA in the progression of gastric cancer.

Accumulating studies have indicated that long non-coding RNAs (lncRNAs) are crucial modulators in cancer biology. In this work, we investigated the function and related mechanisms of LINC01436 in the progression of gastric cancer (GC). We demonstrated that LINC01436 was significantly up-regulated in cancerous tissues of GC samples, and its overexpression was correlated with a worse prognosis for the patients. In the GC cell line BGC823 cells, LINC01436 knockdown repressed the proliferation and metastasis of cancer cells; conversely, in GC cell line AGS cells, overexpression of LINC01436 showed the opposite effects. We then demonstrated that miR-585, a tumor suppressor, could bind to both LINC01436 and the 3'-UTR of F-box protein 11 (FBOX11), and LINC01436 was proved to sponge miR-585 and repress it, and indirectly promoted the expression of FBOX11. Collectively, these results suggested that LINC01436 was an oncogenic lncRNA in GC and promoted proliferation and metastasis of GC cell via regulating miR-585 and FBOX11.

Qishen Yiqi Dropping Pills Ameliorates Doxorubicin-induced Cardiotoxicity in Mice via Enhancement of Cardiac Angiogenesis.

BACKGROUND Qishen Yiqi Dropping Pills (QYDP) is a Chinese traditional medicine that has been applied to treat coronary heart disease and ischemic heart failure in China. However, few studies have explored whether QYDP exerted an effect on doxorubicin (Doxo)-induced cardiotoxicity. Hence, in this study we investigated the effect of QYDP on cardiotoxicity induced by doxorubicin (Doxo) and its potential mechanism. MATERIAL AND METHODS Male C57BL/6 mice (20-25 g, 8-10 weeks old) were randomly assigned to 4 groups: Control group, QYDP group, Doxo group, and QYDP+Doxo group. The mice were intraperitoneal injected with Doxo weekly for 4 weeks to mimic the chronic toxicity. Four weeks after Doxo injection, echocardiography was applied to evaluate the left ventricular (LV) function, and the structure of the cardiac muscle fibers was analyzed with anti-actinin-2 antibody staining by immunofluorescence. Moreover, TUNEL staining and western blot analysis of Bax protein, Bcl-2 protein, and cleaved caspase-3 protein expression levels were conducted to explore whether QYDP exerted effect on cardiac apoptosis. In addition, Masson trichrome staining and western blot analysis of alpha-SMA protein expression levels were used to evaluate whether QYDP exerted an effect on cardiac fibrosis. Western blots and quantitative real-time polymerase chain reaction were applied to detect the vascular endothelial growth factor (VEGF) protein and mRNA levels in the myocardial tissue, and anti-CD31 antibody staining by immunohistochemistry was employed to explore whether QYDP exerted an effect on cardiac angiogenesis. RESULTS QYDP effectively attenuated cardiac dysfunction and cardiac muscle fibers disruption in Doxo treated mice. Moreover, QYDP reduced myocardial apoptosis and myocardial fibrosis in Doxo treated mice, accompanied with elevated protein levels of VEGF and enhancement of myocardial microvessel density. CONCLUSIONS QYDP could protect against Doxo-induced cardiotoxicity, which may be closely associated with enhanced cardiac angiogenesis. Hence, QYDP could be a promising alternative for the treatment of Doxo-induced cardiotoxicity.

Dl-3-n-butylphthalide prevents the disruption of blood-spinal cord barrier via inhibiting endoplasmic reticulum stress following spinal cord injury.

After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear. Here, we show that NBP prevented BSCB disruption after SCI via inhibition of ER stress. Following a moderate contusion injury of the T9 level of spinal cord, NBP was administered by oral gavage and further treated once a day. NBP significantly attenuated BSCB permeability and breakdown of adherens junction (AJ) and tight junction (TJ) proteins, then improved locomotion recovery following SCI. The protective role of NBP on BSCB disruption is associated with the restrain of ER stress caused by SCI. Furthermore, NBP considerably constrained the expression of ER stress-associated proteins and degradation of TJ and AJ in human brain microvascular endothelial cells (HBMECs) treated with TG. In conclusion, our results indicate that ER stress is associated with the disruption of BSCB integrity after injury, NBP attenuates BSCB disruption via inhibiting ER stress and improve functional recovery following SCI.

[Construction and panning of scFv phage display library against recombinant interleukin 4 receptor].

Objective To construct the recombinant human interleukin 4 receptor (rhIL-4R) single-chain Fv (scFv) antibody library by phage display technique to obtain the anti-IL-4R scFv clones selected from the library. Methods Total RNA was extracted from splenocytes of the BALB/c mice immunized with rhIL-4R. Complementary DNA fragments of variable heavy (VH) and variable light (VL) chains of the antibodies were prepared by reverse transcription PCR and assembled into scFv by splice overlap extension PCR (SOE-PCR). Both scFv and the pCANTAB5E vector were respectively double-digested with restriction endonuclease Sfi I and Not I, connected with T4 ligase, and then transformed into the competent cells E.coli TG1; it was cultured in medium to obtain the phage scFv antibody library; after three rounds of enrichment and panning, the specific antigen scFv with high affinity was selected for the sequencing. Results After three rounds of panning, we obtained a diversity of approximately 2×10(8) anti-rhIL-4R scFv antibody library. Sequencing analysis of one positive clone showed that the anti-rhIL-4R scFv was 741 bp and coded 247 amino acids. The analysis of VBASE2 database indicated that VH and VL gene sequences of anti-rhIL-4R protein all had three complementarity determining regions and four backbone areas.Conclusion The anti-rhIL-4R scFv was obtained from the scFv antibody library.

A knowledge generation model via the hypernetwork.

The influence of the statistical properties of the network on the knowledge diffusion has been extensively studied. However, the structure evolution and the knowledge generation processes are always integrated simultaneously. By introducing the Cobb-Douglas production function and treating the knowledge growth as a cooperative production of knowledge, in this paper, we present two knowledge-generation dynamic evolving models based on different evolving mechanisms. The first model, named "HDPH model," adopts the hyperedge growth and the hyperdegree preferential attachment mechanisms. The second model, named "KSPH model," adopts the hyperedge growth and the knowledge stock preferential attachment mechanisms. We investigate the effect of the parameters (α,ß) on the total knowledge stock of the two models. The hyperdegree distribution of the HDPH model can be theoretically analyzed by the mean-field theory. The analytic result indicates that the hyperdegree distribution of the HDPH model obeys the power-law distribution and the exponent is γ = 2 + 1/m. Furthermore, we present the distributions of the knowledge stock for different parameters (α,ß). The findings indicate that our proposed models could be helpful for deeply understanding the scientific research cooperation.