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Bacteria-triggered sepsis is characterized by systemic, uncontrolled inflammation in affected individuals. Controlling the excessive production of pro-inflammatory cytokines and subsequent organ dysfunction in sepsis remains challenging. Here, we demonstrate that Spi2a upregulation in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages reduces the production of pro-inflammatory cytokines and myocardial impairment. In addition, exposure to LPS upregulates the lysine acetyltransferase, KAT2B, to promote METTL14 protein stability through acetylation at K398, leading to the increased m6A methylation of Spi2a in macrophages. m6A-methylated Spi2a directly binds to IKKβ to impair IKK complex formation and inactivate the NF-κB pathway. The loss of m6A methylation in macrophages aggravates cytokine production and myocardial damage in mice under septic conditions, whereas forced expression of Spi2a reverses this phenotype. In septic patients, the mRNA expression levels of the human orthologue SERPINA3 negatively correlates with those of the cytokines, TNF, IL-6, IL-1β and IFNγ. Altogether, these findings suggest that m6A methylation of Spi2a negatively regulates macrophage activation in the context of sepsis.

Cobalt (Co) ion is a common heavy metal ion and the main metal ion in nuclear wastewater. However, the study on the absorption for Co(II) is not sufficient. Herein, a novel ES-layered double hydroxide (LDH) is prepared by intercalated ethylenediaminetetraacetic acid disodium salt (EDTA) and sodium dodecylbenzene sulfonate (SDBS) in a magnesium, iron pristine LDH, which is subsequently used for ES-LDH@carboxymethyl cellulose (CMC) composite aerogel. The results of Fourier transform infrared spectroscopy, X-ray diffraction spectra and thermogravimetric analysis shows successfully preparation of intercalated LDH. The pore morphology, specific surface area and pore size distribution of the composite aerogels are characterized by scanning electron microscope and Nitrogen-BET curves. The significantly improved adsorption capacity, adsorption kinetics and isotherms the absorbents on Co(II) are systematically revealed. This study thus provides an important understanding and path for dealing with the threat of Co(II).

Reconstruction of severe bone defects in revision total knee arthroplasty (TKA) remains a challenge for orthopaedists. The progression of medical imaging and additive manufacturing technology has enabled the rapid manufacture of custom-made implants, and 3D-printed augments with interconnected pore structures have become an alternative approach for the reconstruction of bone defects in revision TKA, especially in patients with complex bone defects. The size and location of the bone defect were determined by thin-layer computed tomography (CT; layer thickness is 1 mm) after reduction of artifacts. The 3D reconstruction models of the host bone were obtained based on thin-layer CT imaging. The custom-made augmentation was designed according to the 3D reconstruction bone model. The augmentation had an interconnected porous structure on the bone-implant interface to achieve biological fixation. After the design was complete, the 3D model of augment was exported in STL format, and augments were fabricated with Ti6Al4V powder using electron beam melting. Thin-layer CT and 3D reconstruction bone models are accurate methods for evaluating periprosthetic bone loss after artifact reduction. The 3D-printed augments perfectly match the bone defects during surgery. 3D-printed augmentation is an effective approach for the reconstruction of bone defects in revision TKA. Thus, surgeons and engineers should carefully evaluate the bone defect during augment design to avoid a mismatch between the augment and host bone.

Patient-specific instrumentation (PSI) enables a more accurate alignment of the lower limbs in a high tibial osteotomy (HTO) than in traditional surgery; however, the current design of commercial PSIs is not perfect. Therefore, we designed a new patient-specific surgical guide to improve the accuracy of the osteotomy and verified its reliability through a clinical operation. Here, we describe a patient with isolated medial-compartment bilateral knee osteoarthritis, accompanied by a varus deformity of the proximal tibia. The patient was treated with HTO using a patient-specific 3D-printed surgical guide. We concluded that the patient-specific 3D-printed surgical guide improved the accuracy of the osteotomy and the alignment of the lower limb.

The study aimed to explore the feasibility of an image registration technique for assessing the accuracy of intraoperative osteotomy of pelvic tumors by 3-dimensional (3D)-printed patient-specific templates. Patients with malignant pelvic tumors who were admitted to our hospital between March 2014 and December 2020 were retrospectively enrolled. Patients underwent hemi-pelvic resection and reconstruction by 3D-printed individualized prostheses. The registration between the designed model and the postoperative segmented model of the prosthesis was used to obtain the intraoperative osteotomy plane and reduce metal artifacts in postoperative computed tomography (CT) images. The distance and angle between the planned and actual osteotomy planes were then used to assess the accuracy of the intraoperative osteotomy. Eight patients with 13 osteotomy planes were enrolled, including four males and four females. The median age at the time of imaging examination was 44 years (range, 33–54 years). All intraoperative osteotomy planes were assessed successfully. The mean distance between the planned and true intraoperative osteotomy planes was −0.69 cm (−7.5–7.35 cm), and the mean angle was 6.57°±3.36° (1.05°–11.88°). This new assessment method of registering the designed model and the postoperative CT segmented model of the prosthesis may be used to assess the accuracy of intraoperative osteotomy for pelvic tumors, using 3D printed patient-specific templates.

The major aim of the present study was to determine the effects of quercetin, a well-known flavonoid, on attenuating cisplatin (CDDP)-induced fat loss and the possible mechanisms. Tumor-bearing nude mice and tumor-free BALB/c mice were administrated with CDDP alone or in combination with quercetin by a diet containing 0.1% or 1% quercetin (LQ or HQ) or by intraperitoneal injection (IQ) to determine the effects of quercetin on the anticancer effect of CDDP or CDDP-induced fat loss. The effects of quercetin on fat accumulation in CDDP-exposed 3T3-L1 cells were also determined. We first showed that HQ and IQ significantly enhanced the anticancer effect of CDDP by upregulating p53- and p21-associated pathways, while tended to attenuate CDDP-induced fat loss in tumor-bearing nude mice. The study in 3T3-L1 cells showed that CDDP decreased the fat accumulation accompanied by strong upregulation of the expression of six genes which are associated with fat metabolism, while quercetin completely suppressed such an effect. The tumor-free BALB/c mice study consistently showed a protective effect of HQ on CDDP-induced body weight and epididymal fat loss. HQ also increased the fat levels in liver and muscle tissues. In epididymal fat tissues, HQ consistently attenuated CDDP-induced changes in fat metabolism-associated gene expression. However, CDDP alone or in combination with HQ did not affect the food intake. This study demonstrates that quercetin possesses the potential to suppress CDDP-induced fat loss may partly through the regulation of the fat metabolism-associated gene expression.

Food protein-derived bioactive peptides have been recognized as a promising candidate for the development of functional foods or nutraceuticals. Peptides exhibiting antioxidant, anti-proliferative and anti-hypertensive activities have been characterized from corn proteins while the knowledge on the presence of immunomodulatory peptides in corn proteins is limited. The objective of this study was to identify the immunomodulatory peptides from corn proteins using interleukin 6 (IL-6) in human macrophage-like U937 cells as the marker. Results indicated that zein protein hydrolysate digested by thermolysin showed a high yield of peptides with potent activity, which was then used for further fractionation by RP-HPLC. We identified five peptides using LC–MS/MS, among which, peptide FLPFNQL showed the highest activity reducing IL-6 production by 57.7% ± 6.1%.

The cytotoxicity of phenolic antioxidants had attracted marked attention, posing serious challenges to food safety. This paper presented a screening method for two major phenolic antioxidants (butylated hydroxytoluene and tert-butylhydroquinone) added in edible oils. To specifically visualize the targeted compounds after developing with toluene/ethyl acetate/methanol 8:1:1 (v/v/v) to 70 mm solvent front, the plate was subjected to a standardized 1,1-diphenyl-2-picrylhydrazyl assay. In addition to synoptical eye inspection, accurate quantification was realized by modified densitometric measurements: fluorescence mode, excitation wavelength 530 nm (D2 and W lamp) without optical filter, which offered satisfactory sensitivity (8.5–17.5 mg/kg) and acceptable linearity (R2 > 0.999 within 50–200 ng/zone). Moreover, the established method was validated with edible oil samples, against EU Directive 2006/52/EC. Apart from that, the unambiguous confirmation of positive results was conveniently achieved by TLC-MS interface-mediated mass spectrometry. Featuring the merits of screening conception, the proposed method not only reached the goal of accurate quantification and conclusive identification of multi-phenolic antioxidants, but also excellently balanced the simplicity, detectability, and throughput of the screening workup. Therefore, it might be an attractive alternative to conventional methods.

In order to give an in-depth understanding of the contradictions arising from the land resource supply and demand, this study selected 30 provinces (some are autonomous regions or municipalities) in China to be the research unit, used the carbon emission as an undesirable output, and adopted the Super-SBM DEA model and ESDA-GWR method to research the evolution characteristics and influencing factors of land use efficiency in China in 2003–2013. The results indicated that: (1) The land use efficiency in China overall was moderately ineffective and the overall utilization level was low; (2) The Global Spatial Autocorrelation was instable and had maintained a high level; (3) The “hot spots” mainly being distributed in the southeast coastal regions and “cold spots” being found in the central and western regions, so that as time goes on, the pattern of “high in the east and low in the west” has been gradually formed and stabilized. (4) The GWR model analysis showed that the natural factors such as NDVI, DMSP/OLS and DEM have a significant impact on land use efficiency, thereby providing an important contribution to this study. For the eastern coastal areas, the emphasis should be improving their OT, PF and PGDP, for the western region, should focus on improving its comprehensive economic development level to improve the DMSP/OLS, while strengthening the ecological environment to improve the level of NDVI.

A novel fiber grating pair that consists of a conventional long-period fiber grating and a fiber Bragg cladding grating (FBCG) is proposed. The FBCG is a new type of fiber grating in which refractive index modulation is formed in the cladding. Through the coupled-mode theory, we accurately calculate the coupling coefficients between modes supported in the fibers. And some other mode coupling features in the fiber cladding gratings are analyzed in detail. The calculation of the modes involved in this paper is based on a model of three-layer step-index fiber geometry. Then, we have investigated the sensitivity characteristics for variation of the modulation strengths of the fiber Bragg cladding gratings’ resonance peaks and the long-period cladding gratings’ (LPCGs) dual resonant peaks. Finally, the modulation strength sensitivity of the grating pair’s three resonant peaks is demonstrated, and the results indicate that these grating pairs may find potential applications in optical fiber sensing.

Antioxidant peptides derived from food sources are considered as safer alternatives to commercially available antioxidant drugs. As one of the most abundant protein sources, hen’s egg proteins were extensively used to produce antioxidant peptides by enzymatic hydrolysis. Our previous work indicated that gastrointestinal digestion of cooked eggs significantly increased the antioxidant activity due to hydrolysis of egg proteins. To characterize the responsible antioxidant peptides, cooked eggs were digested in a simulated in vitro model of human gastro-intestinal digestion. Prepared digests were fractionated with FPLC (Fast Protein Liquid Chromatography) and RP-HPLC (Reverse-Phase High-Performance Liquid Chromatography) and the antioxidant activity was determined in A7r5 cells (vascular smooth muscle cell line). Further identification of peptides from peptide fractions with the highest antioxidant activity was carried out using LC-MS/MS. Four peptides derived from ovalbumin, DSTRTQ (48–53), DKLPG (61–65), DVYSF (96–100), and ESKPV (205–209), were identified; of which DKLPG did not show antioxidant activity in cells. Enzyme cleave analysis suggested that these four peptides were likely released from ovalbumin only by pepsin non-specific cleaves. It is postulated that egg consumption may exert protection against oxidative stress on human health due to release of antioxidant peptides during digestion., Antioxidant peptides from eggs: more active upon digestion Chicken eggs are a major source of dietary proteins, and can be used to produce antioxidant peptides, safer alternatives to synthetic antioxidant drugs. Jianping Wu and co-workers at University of Alberta, Canada, looked into how digestion of cooked eggs in the stomach and intestines could affect the antioxidant activity. Using a simulated model of human digestion, they separated the digests and identified the most active antioxidant peptides, likely released from ovalbumin—the main protein in egg white—by pepsin, the essential digestive enzyme in the stomach. These findings show that digestion of cooked eggs breaks down egg proteins to more potent antioxidant peptides, suggesting that consumption of eggs may help protect human body against oxidative stress.

Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function loss, renal tubular damage, and the induction of the apoptotic marker caspase-3 in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice. Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated cytochrome c release and the increase in the intrinsic apoptotic mediators Bax, Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator caspase-12, which is independent of calcium-dependent protease m-calpain activation. Taken together, KCa3.1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI.

Thermosensitive and magnetic nanoparticles as “smart” drug carriers have shown great potential in the field of controlled drug delivery owing to their unique properties. Previously, poly(N-isopropylacrylamide)-coated silica/magnetic nanoparticles (PNIPAM/SiO2/Fe3O4 nanoparticles) were synthesized using SiO2-coated Fe3O4 nanoparticles as a template. The properties of these nanoparticles such as the transition of the lower critical solution temperature (LCST), biocompatibility, drug loading efficiency, and drug release kinetics were investigated in vitro for both targeted and controlled drug delivery. The release profile and the in vitro cancer cell inhibition activity of vitamin D3 loading for PNIPAM/SiO2/Fe3O4 nanoparticles were systemically studied. The loading and release behavior of vitamin D3 were found to be dependent on the LCST of PNIPAM/SiO2/Fe3O4 nanoparticles. HepG2 liver cancer cells were incubated with PNIPAM/SiO2/Fe3O4 nanoparticles loaded with vitamin D3 for 5 days, and cell viability significantly decreased, as observed by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, which was further confirmed by transmission electron microscopy (TEM) images. In conclusion, the current study demonstrated that PNIPAM/SiO2/Fe3O4 nanoparticles can be used as potential drug delivery systems for controlled release. Open image in new window

Background KIT is a tyrosine kinase growth factor receptor. High expression of KIT has been found in several tumors including canine hemangiosarcoma (HSA). This study investigated the correlation of KIT expression and c-kit sequence mutations in canine HSAs and benign hemangiomas (HAs). Results Immunohistochemistry (IHC) staining confirmed KIT expression in 94.4 % (34/36) of HSAs that was significantly higher than 0 % in HAs (0/16). Sequencing the entire c-kit coding region of HSAs and normal canine cerebellums (NCCs) revealed GNSK-deletion in exon 9. As for exon 9 genotyping by TA-cloning strategy, GNSK-deletion c-kit accounted for 48.6 % (68/140) colonies amplified from12 KIT-positive HSAs, a significantly higher frequency than 14.1 % (9/64) of colonies amplified from six NCCs. Conclusions Due to the distinct expression pattern revealed by IHC, KIT might be used to distinguish benign or malignant vascular endothelial tumors. Moreover, the high incidence of GNSK-deletion c-kit in canine HSAs implicates KIT isoforms as possibly participating in the tumorigenesis of canine HSAs. Electronic supplementary material The online version of this article (doi:10.1186/s12917-016-0772-y) contains supplementary material, which is available to authorized users.

The pair of parallel combinative long-period fiber gratings can be used to add and drop higher-order core modes, serving as a key device in mode-division multiplexing (MDM) transmission. For higher-order modes EH2m multiplexing, the grating written in SMF need to be tilted, but the grating tilt is unnecessary in FMF. To minimize coupling interferences, the modes should be multiplexed in order from low to high and be de-multiplexed in order from high to low in MDM transmission.

The nanoparticles containing thermosensitive and magnetic properties were investigated for their potential use as a novel drug carrier for targeted and controlled release drug delivery system. These thermosensitive and magnetic nanoparticles were prepared by grafting thermosensitive poly (N-isopropylacrylamide) (PNIPAM) on the surface of silica (SiO2)-coated Fe3O4 nanoparticles with the particle size of 18.8 ± 1.6 nm. Adsorption and desorption behavior of bovine serum albumin (BSA) on the surface of PNIPAM-grafted SiO2/Fe3O4 nanoparticles was studied, and the results indicated that these nanoparticles were able to absorb protein at temperature above the lower critical solution temperature (LCST) and to be desorbed below the LCST. Cytotoxicity studies conducted on Chinese hamster ovary (CHO-K1) cells using methyl tetrazolium (MTT) assays revealed that cell viability of 1 mg/mL PNIPAM-grafted nanoparticles was slightly decreased after 24 h of incubation as compared to the lower concentration of nanoparticles. Furthermore, the concentration of 0.5 mg/mL PNIPAM-grafted nanoparticles was totally biocompatible for 48 h, but had low cytotoxicity after 72 h of incubation. These PNIPAM-grafted nanoparticles did not induce morphological change in their cellularity after exposure for 24 and 108 h. These results demonstrate that PNIPAM-grafted nanoparticles are biocompatible and have potential use as drug carriers.

This study examined the anti-metastatic effects of oxythiamine (OT) both in cell culture and in vivo. Cell culture results revealed that OT (0-20 microM) significantly inhibited the invasion and migration (IC(50) = 8.75 microM) of Lewis lung carcinoma (LLC) cells. These effects of OT were accompanied by the inhibition of metalloproteinases-2 and -9 (MMP-2, MMP-9), urokinase-type plasminogen activator (uPA) activities and by the increases in protein expression of tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1, TIMP-2). We then implanted (s.c.) C57BL/6 mice with LLC cells and supplemented the mice with a low- or a high-dose of OT (250 or 500 mg/kg BW) daily for 5 wk. During the 5-wk period, OT supplementation decreased plasma MMP-2 activity in a dose-dependent manner, and this effect was significant after 4 wk of tumor cell implantation. Tumor metastasis was found to confine to the lungs of mice injected with the tumor cells. High-OT supplementation strongly lowered the number and area of tumors and inhibited protein expression of MMP-2 and MMP-9 in the lungs. In addition, high-OT supplementation markedly decreased the extent of proliferating cell nuclear antigen (PCNA) staining in the lungs. By contrast, OT supplementation increased TIMP-1 and -2 protein expression in the lungs. These results demonstrate that OT supplementation attenuates tumor cell metastasis, possibly via inhibition of protein expression of MMPs, extent of PCNA staining and via increase of proteins expression of TIMPs.

Background Systematic analysis of cancer gene-expression patterns using high-throughput transcriptional profiling technologies has led to the discovery and publication of hundreds of gene-expression signatures. However, few public signature values have been cross-validated over multiple studies for the prediction of cancer prognosis and chemosensitivity in the neoadjuvant setting. Methods To analyze the prognostic and predictive values of publicly available signatures, we have implemented a systematic method for high-throughput and efficient validation of a large number of datasets and gene-expression signatures. Using this method, we performed a meta-analysis including 351 publicly available signatures, 37,000 random signatures, and 31 breast cancer datasets. Survival analyses and pathologic responses were used to assess prediction of prognosis, chemoresponsiveness, and chemo-drug sensitivity. Results Among 31 breast cancer datasets and 351 public signatures, we identified 22 validation datasets, two robust prognostic signatures (BRmet50 and PMID18271932Sig33) in breast cancer and one signature (PMID20813035Sig137) specific for prognosis prediction in patients with ER-negative tumors. The 22 validation datasets demonstrated enhanced ability to distinguish cancer gene profiles from random gene profiles. Both prognostic signatures are composed of genes associated with TP53 mutations and were able to stratify the good and poor prognostic groups successfully in 82%and 68% of the 22 validation datasets, respectively. We then assessed the abilities of the two signatures to predict treatment responses of breast cancer patients treated with commonly used chemotherapeutic regimens. Both BRmet50 and PMID18271932Sig33 retrospectively identified those patients with an insensitive response to neoadjuvant chemotherapy (mean positive predictive values 85%-88%). Among those patients predicted to be treatment sensitive, distant relapse-free survival (DRFS) was improved (negative predictive values 87%-88%). BRmet50 was further shown to prospectively predict taxane-anthracycline sensitivity in patients with HER2-negative (HER2-) breast cancer. Conclusions We have developed and applied a high-throughput screening method for public cancer signature validation. Using this method, we identified appropriate datasets for cross-validation and two robust signatures that differentiate TP53 mutation status and have prognostic and predictive value for breast cancer patients. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1102-7) contains supplementary material, which is available to authorized users.