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Leptin showed different apoptosis regulation effects on the chondrocytes from tibial and vertebral epiphyseal plates. However, the mechanism is still unclear. In this study, we tested the protein profile of tibial and vertebral epiphyseal plate chondrocytes with and without leptin stimulation by mass spectrometry and found that the histone acetylation level of tibial chondrocytes was decreased after leptin treatment, while increased in vertebral epiphyseal plates. COIP assay showed that leptin promoted H3, H4 histone acetylation by recruiting CREB binding protein (CBP)/P300 to activate histone acetyl transferases (HATs) activity in vertebral disc chondrocytes. But in tibial plate cartilage cells, leptin did not recruit CBP and p300, thus differently affect the apoptosis of epiphyseal plate chondrocytes. Through explored the mechanism of histone acetylation modulated by leptin, and its effect on cartilage cell apoptosis and cell cycle regulation, This provides a novel target therapy possibility therapeutic approach to for the related disease.

Abnormal microRNA (miR) expression has frequently been reported to be implicated in cancer-related drug resistance. Herein, we planned to investigate whether miR-381-3p contributes to doxorubicin (DOX) resistance in anaplastic thyroid carcinoma (ATC). DOX-resistant ATC tissues and cell lines were prepared to detect miR-381-3p and homeobox A9 (HOXA9) expression. CCK8, transwell and TUNEL assays were performed to evaluate cell proliferation, migration and invasion, and apoptosis in in vitro experiments. HOXA9 expression is intensively expressed in ATC tissues compared with benign thyroid tissues. Compared with parental ATC cell lines, HOXA9 protein expression is significantly up-regulated in DOX-resistant SW1736 and CAL62 cells. The knockdown of HOXA9 leads to growth inhibition and apoptosis of DOX-resistant SW1736 and CAL62 cells. Our results also indicate a significant decrease in miR-381-3p expression levels in DOX-resistant ATC tissues and cell lines. miR-381-3p may function as a tumour suppressor to impede proliferation, migration and invasion and induce apoptosis of DOX-resistant SW1736 and CAL62 cells by inhibiting HOXA9 protein expression. Our results present a novel signalling axis miR-381-3p/HOXA9 that mediates DOX resistance in ATC. miR-381-3p and HOXA9 may be promising molecular targets for preventing ATC progression and drug resistance.

Chemoresistance often causes treatment failure of B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase-1 (HO-1) was found in the bone marrow stromal cells (BMSCs) from B-ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B-ALL cell lines Super B15 and CCRF-SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO-1. Silencing HO-1 expression in BMSCs increased the apoptotic rates of B-ALL cell lines induced by VCR, whereas upregulating HO-1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B-ALL cells were arrested in the G0/G1 phase due to HO-1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment-associated chemoresistance, was also positively coexpressed with HO-1. VEGF secretion was markedly increased in BMSCs with HO-1 upregulation but decreased in BMSCs with HO-1 silencing. B-ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO-1 expression may promote the VCR resistance of B-ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO-1. In conclusion, this study clarifies a mechanism by which B-ALL is induced to resist VCR through HO-1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.

A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC-SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein. Tuning the QD surface mannose valency reveals that DC-SIGN binds more efficiently to densely packed mannosides. A FRET-based thermodynamic study reveals that the binding is enthalpy-driven. This work establishes QD FRET as a rapid, sensitive technique for probing structure and thermodynamics of multivalent protein-ligand interactions.

Objective To investigate the clinical features and risk factors for discerning the critical and predicting the outcome of patients with COVID‐19. Methods Patients who were admitted to the intensive care unit (ICU) department and general infection department of TaiKang Tongji (Wuhan) Hospital from February 10 to March 27, 2020, were included. Data on clinical features, complications, laboratory parameters, chest CT, nutrient requirement, and electrolyte imbalance were analyzed retrospectively. Results A total of 123 (50 critical and 73 non‐critical) patients were enrolled. 65% of patients with comorbidities, hypertension (45.5%), diabetes (21.9%), 36.5% of patients had more than one comorbidity. The proportion of lymphocytes in critical patients was significantly lower than that of non‐critical patients. The proportion of patients with increased NLR, PLR, IL‐6, CRP levels, and chest CT score was significantly higher in the critical than that of non‐critical patients. The logistic regression analysis identified low lymphocyte count, high NLR, PLR, IL‐6, CRP levels, and CT score as independent factors for discerning critical cases and high NLR, PLR, IL‐6, and CT score could predict poor clinical outcome. Furthermore, we identified patients who needed nutrition support (HR 16.99) and with correction of electrolyte imbalance (HR 18.24) via intravenous injection were more likely to have a poor outcome. Conclusions The potential risk factors of lower lymphocyte count, high levels of NLR, PLR, IL‐6, CRP, chest CT score, and the statue of nutrient requirement or electrolyte imbalance could assist clinicians in discerning critical cases and predict the poor outcome in patients with COVID‐19., The potential risk factors of lower lymphocyte count, high levels of NLR, PLR, IL‐6, CRP, chest CT score, and the statue of nutrient requirement or electrolyte imbalance could assist clinicians in discerning critical cases and predict the poor outcome in patients with COVID‐19.

Osteoclasts (OCs) play an essential role in bone destruction in patients with multiple myeloma (MM). Bortezomib can ameliorate bone destruction in patients with MM, but advanced MM often resists bortezomib. We studied the molecular mechanisms of bortezomib tolerance in MM. The expression of the MM-related genes in newly diagnosed patients with MM and normal donors were studied. C-C motif chemokine ligand 3 (CCL3) is a cytokine involved in the differentiation of OCs, and its expression is closely related to APRIL (a proliferation-inducing ligand). We found that bortezomib treatment inhibited APRIL and CCL3. But the heme oxygenase-1 (HO-1) activator hemin attenuated the inhibitory effects of bortezomib on APRIL and CCL3. We induced mononuclear cells to differentiate into OCs, and the enzyme-linked immunosorbent assay showed that the more OCs differentiated, the higher the levels CCL3 secretions detected. Animal experiments showed that hemin promoted MM cell infiltration in mice. The weight and survival rate of tumor mice were associated with HO-1 expression. Immunohistochemical staining showed that HO-1, APRIL, and CCL3 staining were positively stained in the tumor infiltrating sites. Then, MM cells were transfected with L-HO-1/si-HO-1 expression vectors and cultured with an nuclear factor (NF)-kappa B (κB) pathway inhibitor, QNZ. The results showed that HO-1 was the upstream gene of APRIL, NF-κB, and CCL3. We showed that HO-1 could attenuate the inhibitory effect of bortezomib against the APRIL-NF-κB-CCL3 signaling pathways in MM cells, and the tolerance of MM cells to bortezomib and the promotion of bone destruction are related to HO-1.

Spinal cord injury (SCI) is a major disability requiring more effective treatment than is currently available. MicroRNAs have been shown to effectively regulate gene expression at the translational level. The aim of the present study was to explore the potential role of miR-30-5p and possible mechanism in SCI. We found that miR-30-5p was notably down-regulated, while Neurod 1 expression was highly elevated in microglia from the mouse model of SCI. Additionally, overexpression of miR-30a-5p significantly suppressed inflammatory responses as reflected by a decrease in the secretion of the cytokines TNF-α, IL-1β and IL-10 triggered by SCI. Furthermore, introduction of miR-30a-5p strengthened the scavenging of oxygen free radicals accompanied by an increase in the expression of SEPN1, TXNL1 and GPX1. More importantly, our study explored that Neurod 1 was a direct and functional target of miR-30a-5p, which was validated by the dual luciferase reporter assay. qRT-PCR and western blot analysis further validated that miR-30a-5p negatively regulated the expression of Neurod 1. Mechanistically, overexpression of miR-30a-5p or silencing of the Neurod 1 gene prevented the MAPK/ERK signalling and inhibited inflammatory responses, meanwhile activated SEPN1, TXNL1 and GPX1. These findings indicate that miR-30a-5p ameliorates inflammatory responses and oxidative stress by targeting Neurod 1 through MAPK/ERK signalling.

Osteoarthritis (OA) is a common chronic degenerative disease that affects all joints. At present, the pathological processes and mechanisms of OA are still unclear. Innate immunity, a key player in damage to the structure of the joint and the mechanism by which the host attempts to repair OA, affects all pathological stages of the disease. In the present study, our aim was to assess changes in innate immunity during the pathological processes of OA in articular cartilage (AC) and the synovial membrane (SM), which are the major structures in joints, and to systematically examine the histological changes in AC and SM in mild, moderate and severe cases of OA, in order to further speculate about the manner in which the interactions of AC and SM are facilitated by innate immunity. Histological methods (including HE and Safranin O-fast green staining), immunofluorescent double staining, TUNEL stain, and Western blots were used to assess the morphological changes within AC and SM tissues in healthy and mild, moderate, or severe OA rats. Our results showed that the damage to AC and SM within the joints progressively worsened in different degrees during the course of the disease, and that the innate immune system was closely involved in the AC and SM during each stage of OA. These findings also confirmed that SM may affect the pathological changes in AC through the innate immune system, and therefore affect the progress of OA.

Background Several indices have been developed to predict survival of brain metastases (BM) based on prognostic factors. However, such models were designed for general brain metastases from different kinds of cancers, and prognostic factors vary between cancers and histological subtypes. Recently, studies have indicated that epidermal growth factor receptor (EGFR) mutation status may be a potential prognostic biological factor in BM from lung adenocarcinoma. Thus, we sought to define the role of EGFR mutation in prognoses and introduce a prognostic model specific for BM from lung adenocarcinoma. Methods Data of 256 patients with BM from lung adenocarcinoma identified with EGFR mutations were collected. Independent prognostic factors were confirmed using a Cox regression model. The new prognostic model was developed based on the results of multivariable analyses. The score of each factor was calculated by six-month survival. Prognostic groups were divided into low, medium, and high risk based on the total scores. The prediction ability of the new model was compared to the three existing models. Results EGFR mutation and Karnofsky performance status were independent prognostic factors and were thus integrated into the new prognostic model. The new model was superior to the three other scoring systems regarding the prediction of three, six, and 12-month survival by pairwise comparison of the area under the curve. Conclusion Our proposed prognostic model specific for BM from lung adenocarcinoma incorporating EGFR mutation status was valid in predicting patient survival. Further verification is warranted, with prospective testing using large sample sizes.

The activation of transient receptor potential canonical 6 (TRPC6) channel participates in the glomerulosclerosis. The TRPC6 also participates in the mechanical or pressure sensation in various cel...

The strategies of combining photodynamic therapy (PDT) with other therapeutics are considered to be the most suitable methods in improving the antitumor therapeutic efficiency. Herein, a "Linkage Mechanism" strategy based on thermal controllable multishell nanoparticles (CuS@SiO2 -l-Arg (l-arginine)@PCM (phase-change material)-Ce6 (chiorin e6)) is proposed for combing PDT and NO-based gas therapy. Upon 1060 nm laser irradiation, the PCMs will melt under the photothermal effect induced by CuS and the loaded Ce6 and l-Arg can accurately release from the nanoparticles. Under further 660 nm laser irradiation, the released Ce6 will produce plenty of singlet oxygen (1 O2 ) for PDT, while the generated 1 O2 can oxidize l-Arg to release NO for the synergy of PDT and gas therapy. The "Linkage Mechanism" can achieve precise release of the payloads under the control of photothermal effect at tumor site, and the chain reaction of PDT and gas therapy overcomes the problem of premature release of gas during transportation. Benefiting from the guidance of fluorescence imaging and second near infrared photoacoustic imaging by Ce6 and CuS, both in vitro and in vivo experiments present effective antitumor efficiencies. The nanoparticles provide new ideas for controllable release of drugs and the synergistic effect of multiple treatments, possessing great application prospects.

This study was conducted to understand patients' experiences of nursing support, to identify gaps between patients' expected needs and the nursing support they received, and to explore reasons for such disparity. A qualitative study with a phenomenological approach was used. A purposive sample of 22 patients with different types of cancer was recruited and interviewed using semistructured guidelines. The data were analyzed using phenomenological analytic methods. Several needs regarding nursing support were expressed, including informational, psychological, clinical, care coordination and communication needs, and there were some unmet or partially-met needs. Reasons for the disparities covered both patient- and nurse-related factors, including patients' lack of awareness regarding how to acquire professional assistance and reluctance to express their needs, and nurses' lack of active communication with patients, inability to provide specific support, and limited resources for coordination. The expectations of nursing support did not always correspond with the actual delivery of nursing care. A tailored intervention is warranted to meet patients' expectations, which might contribute to quality-of-care improvements.

A highly efficient cap‐exchange approach for preparing compact, dense polyvalent mannose‐capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC‐SIGN and DC‐SIGNR (collectively termed as DC‐SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC‐SIGN, but not its closely related receptor DC‐SIGNR, which is further confirmed by its specific blocking of DC‐SIGN engagement with the Ebola virus glycoprotein. Tuning the QD surface mannose valency reveals that DC‐SIGN binds more efficiently to densely packed mannosides. A FRET‐based thermodynamic study reveals that the binding is enthalpy‐driven. This work establishes QD FRET as a rapid, sensitive technique for probing structure and thermodynamics of multivalent protein–ligand interactions.

Aims To describe the self-reported frequency of Chinese nurses’ interventions to help smokers quit, using the 5 As (i.e. Ask, Advise, Assess, Assist, Arrange), attitudes towards tobacco control and differences in consistency interventions by demographic and professional characteristics prior to an educational intervention to increase nurses’ support for quit efforts. Background Tobacco use is the leading cause of preventable death in China; quitting smoking reduces health risks and premature death. The China Tobacco Cessation Treatment Guideline supports the 5 As model for intervention, but nurses’ frequency of delivering smoking cessation interventions is unknown. Design Descriptive survey using a convenience sample. Methods Nurses from eight hospitals in Beijing and Hefei, China completed a web-based survey in 2012. Differences in consistency of the 5 As by nurse characteristics were determined using multivariate logistic regression. Overall importance of nurses in tobacco control was evaluated on a 1-5 scale (5 = most important). Results Nurses (N = 2440; 1404 Beijing, 1036 Hefei) participated. 64% consistently asked about smoking status, 85% advised patients to quit, 52% assessed readiness to quit and assisted with smoking cessation and 17% arranged for follow-up. Interventions varied by nurses’ education and clinical setting. Nurses positively viewed involvement in tobacco control (4·3/5) and thought nurses should be smoke-free role models (4·8/5·0). Conclusions This study demonstrates that the majority of nurses asked about smoking status, but few assisted patients with quitting. Further efforts are needed to help nurses actively promote smoking cessation interventions.

Boron nitride nanotubes (BNNTs)/alumina composites were fabricated by hot pressing. The effect of BNNTs on the mechanical properties, including ambient and high-temperature flexure strength and fracture toughness was investigated. As a result of sufficient physical and chemical bonding between BNNTs and alumina, the pullout and fracture of BNNTs concurrent with the suppression of BNNTs on abnormal growth of grains contributes to the excellent ambient and high-temperature mechanical properties.