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Problems with silver carp protein (SCP) include a strong fishy odor, low gel strength of SCP surimi, and susceptibility to gel degradation. The objective of this study was to improve the gel quality of SCP. The effects of the addition of native soy protein isolate (SPI) and SPI subjected to papain-restricted hydrolysis on the gel characteristics and structural features of SCP were studied. The β-sheet structures in SPI increased after papain treatment. SPI treated with papain was crosslinked with SCP using glutamine transaminase (TG) to form a composite gel. Compared with the control, the addition of modified SPI increased the hardness, springiness, chewiness, cohesiveness, and water-holding capacity (WHC) of the protein gel (p < 0.05). In particular, the effects were most significant when the degree of SPI hydrolysis (DH) was 0.5% (i.e., gel sample M-2). The molecular force results demonstrated that hydrogen bonding, disulfide bonding, and hydrophobic association are important molecular forces in gel formation. The addition of the modified SPI increases the number of hydrogen bonds and the disulfide bonds. Scanning electron microscopy (SEM) analysis showed that the papain modifications allowed the formation of a composite gel with a complex, continuous, and uniform gel structure. However, the control of the DH is important as additional enzymatic hydrolysis of SPI decreased TG crosslinking. Overall, modified SPI has the potential to improve SCP gel texture and WHC.

Rosa roxburghii tratt (R. roxburghii) is an important plant resource that is widely distributed in the southwest of China and favored by consumers due to its high nutritional value and healthy functions. Meanwhile, it is a traditional edible and medicinal plant in China. With the deepening research of R. roxburghii, more and more bioactive components and its health care and medicinal value have been discovered and developed in recent years. This review summarizes and discusses the recent advances on main active ingredients such as vitamin, protein, amino acid, superoxide dismutase, polysaccharide, polyphenol, flavonoid, triterpenoid and mineral, and pharmacological activities including antioxidant activity, immunomodulatory activity, anti-tumor activity, glucose and lipid metabolism regulation, anti-radiation effect, detoxification effect, and viscera protection of R. roxbughii, as well as its development and utilization. The research status and existing problems of R. roxburghii development and quality control are also briefly introduced. This review ends with some suggestions on the perspectives and directions for future research and potential applications of R. roxbughii.

Microwave nondestructive testing (NDT) offers promising application prospects due to its advantages of non-contact inspection in detecting defects in non-metallic composites. However, the detection sensitivity of this technology is generally affected by the lift-off effect. To reduce this effect and highly concentrate electromagnetic fields on defects, a defect detection method using scanning instead of moving sensors in the microwave frequency range was proposed. Additionally, a novel sensor based on the programmable spoof surface plasmon polaritons (SSPPs) was designed for non-destructive detection in non-metallic composites. The unit structure of the sensor was made up of a metallic strip and a split ring resonator (SRR). A varactor diode was loaded between the inner and outer rings of the SRR, and by changing the capacitance of this diode using electronic scanning, the field concentration phenomenon of the SSPPs sensor can be moved along a specific direction for defect detection. By using this proposed method and sensor, the location of a defect can be analyzed without moving the sensor. The experimental results demonstrated that the proposed method and designed SSPPs sensor can be effectively applied in detecting defects in non-metallic materials.

Abstract Background Intraocular lens (IOL) calculation using traditional formulas for post-corneal refractive surgery eyes can yield inaccurate results. This study aimed to compare the clinical accuracy of the newly developed Zhang & Zheng (ZZ) formula with previously reported IOL formulas. Study design Retrospective study. Methods Post-corneal refractive surgery eyes were assessed for IOL power using the ZZ, Haigis-L, Shammas, Barrett True-K (no history), and ray tracing (C.S.O Sirius) IOL formulas, and their accuracy was compared. No pre-refractive surgery information was used in the calculations. Results This study included 38 eyes in 26 patients. ZZ IOL yielded a lower arithmetic IOL prediction error (PE) compared with ray tracing (P = 0.04), whereas the other formulas had values like that of ZZ IOL (P > 0.05). The arithmetic IOL PE for the ZZ IOL formula was not significantly different from zero (P = 0.96). ZZ IOL yielded a lower absolute IOL PE compared with Shammas (P

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

BACKGROUND The common analysis methods of marine sediments, such as open digestion or high-pressure closed digestion combined with inductively coupled plasma-mass spectrometry (ICP-MS) or inductively coupled plasma-optical emission spectroscopy (ICP-OES) determination, and pressed powder pellet or fusion tablets combined with XRF determination, have a low efficiency of sample pretreatment and less detectable elements. The disadvantages of incomplete digestion, slow speed and high detection limit contribute to the inefficiency of the method. OBJECTIVES To develop a rapid method for the determination of 48 elements in marine sediments by ICP-MS. METHODS Lithium metaborate was used as a flux to decompose the sample. The obtained sample was leached with 5% nitric acid and determined by ICP-MS. An analytical method for the rapid determination of 48 elements in marine sediments was established. Using the national standard references materials of marine sediment as the high point, the standard working curve was drawn. The amount of flux LiBO2, dilution ratio, analytical isotope and internal standard elements of each element to be measured, instrument measurement mode and interference correction equation of individual elements were determined, an optimal decomposition conditions and measurement conditions were obtained. RESULTS The results showed that the accurate results of P, As, Se, Cd, Hg cannot be obtained due to high temperature loss, yet microwave digestion or other methods could be used for pretreatment to avoid loss before determination. The accurate results of 48 elements may be obtained by this method, the relative standard deviation (RSD) of each element was less than 9.7%. The measured values of the national standard references of marine sediments GBW07333, GBW07314, GBW07335 and GBW07336 were consistent with the certified values. The recoveries of each element in marine sediment samples ranged from 83.6% to 118.6%. CONCLUSIONS This method greatly improves the analysis efficiency, and can analyze more elements, suitable for the analysis of large numbers of samples.

Background and AimsHepatic ischemia–reperfusion injury (IRI) is a common phenomenon that occurs after liver transplantation and liver tumor surgery. It can cause liver dysfunction and recovery failure after liver surgery, even leading to acute liver failure. Our aim is to investigate the protective effect and related potential mechanism of [D-Ala2, D-Leu5] enkephalin (DADLE) treatment on hepatic IRI in cirrhotic livers of rats.MethodsThe models of liver cirrhosis and hepatic IRI were established with male Sprague–Dawley rats. DADLE at a dose series of 0.5, 1, or 5 mg·kg−1 was injected intravenously to rats 10 min prior hepatic ischemia, followed by a 6- h reperfusion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological changes, and liver cell apoptosis were used to assess liver IRI. The optimal dose of DADLE was assessed by using the Suzuki score and ALT and AST levels. We repeated the hepatic IRI procedure on the optimal dose of the DADLE group and the delta opioid receptor (DOR) antagonist natrindole hydrochloride (NTD) injection group. Serum ALT and AST levels, histological staining, hepatic apoptosis, and serum levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 β (IL-1β) were measured. The expression of protein kinase B (Akt) and its downstream proteins were evaluated by using quantitative real-time polymerase chain action (qRT-PCR) and Western blotting.ResultsCompared with the control group, DADLE treatment at a dose of 5 mg·kg−1 reduced the Suzuki score (mean: 5.8, range: 5.0–6.6 vs. mean: 8.0, range: 7.0–8.9), the ALT level (134.3 ± 44.7 vs. 247.8 ± 104.6), and the AST (297.1 ± 112.7 vs. 660.8 ± 104.3) level. DOR antagonist NTD aggravated hepatic IRI. Compared with the control group, DADLE treatment decreased the number of apoptosis cells and microphages and neutrophils, increased the expression of Akt and its mRNA to much higher levels, and upregulated the mRNA and protein expression of Bcl-2 and Bcl-2-associated death promoter (BAD).ConclusionDADLE treatment at a dose of 5 mg·kg−1 injected intravenously 10 min prior hepatic ischemia could contain rats’ hepatic IRI by activating DOR in cirrhotic livers. The effects of DADLE could be offset by NTD. The potential molecular mechanism seems to be involved in the phosphatidylinositol-3-kinase (PI3K)/Akt pathway.

Fusarium wilt of banana (Musa spp.), a typical vascular wilt disease caused by the soil-borne fungus, Fusarium oxysporum f. sp. cubense race 4 (Foc4), seriously threatens banana production worldwide. Pathogens, including vascular wilt fungi, secrete small cysteine-rich proteins during colonization. Some of these proteins are required for pathogenicity. In this study, 106 small secretory proteins that contain a classic N-terminal signal peptide were identified using bioinformatic methods in Foc4. Among them, 11 proteins were selected to show transient expressions in tobacco. Interestingly, transient expression of FoSsp1 in tobacco, an uncharacterized protein (of 145 aa), induced necrotic cell death reactive oxygen burst, and callous deposition. Furthermore, the expression of FoSSP1 in Foc4 wild type (WT) was up-regulated during the stage of banana roots colonization. A split-marker approach was used to knock out FoSSP1 in the Foc4 WT strain. Compared with the WT, the deletion mutant Fossp1 was normal in growth rate but increased in conidiation and virulence. RT-qPCR analysis showed that the expression of four conidiation regulator genes in the Fossp1 deletion mutant was significantly decreased compared to the WT strain. In addition, the expression of four pathogenesis-related genes of bananas infected with Fossp1 deletion mutant was down-regulated in comparison with that of the WT. In summary, these results suggested that FoSSP1 is a putative elicitor that negatively regulates conidiation and pathogenicity in Foc4.

ObjectivesIn this study, we analyzed the metabonomics of intermingled phlegm and blood stasis (IPBS) and its three concurrent syndromes in patients with stable angina pectoris of coronary heart disease.MethodsA total of 164 sera of separated outpatients from 12 national tradition Chinese medicine clinical research centers with IPBS or concurrent syndromes were collected for the study and assessed with LC-ESI-MS/MS (liquid chromatography—electrospray ionization tandem—mass spectrometry)-based metabolomics and multivariate statistical analysis.ResultsNon-differential metabolites between IPBS and its separate syndrome combined with the top 100 most abundant metabolites in four groups were screened to reflect the essence of IPBS. Amino acid and its metabolomics and glycerol phospholipids were screened for common metabolites, and these metabolites were mainly enriched in valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism. Principal component analysis revealed that the difference between IPBS and its separate concurrent syndromes was not distinct. Compared with IPBS, anserine, cytidine 5′-diphosphocholine, and 7,8-dihydro-L-biopterin separately significant increase in phlegm stasis and toxin (PST), phlegm stasis and Qi stagnation (PQS), and phlegm stasis and Qi deficiency (PQD). While these different metabolites were associated with histidine metabolism, beta-alanine metabolism, glycerophospholipid metabolism, and folate biosynthesis. Three accurate identification models were obtained to identify the difference between IPBS and its concurrent syndromes.ConclusionOur study indicated that valine, leucine, and isoleucine metabolism and glycerophospholipid metabolism could represent the essence of IPBS; dysregulated metabolites were valuable in identifying PST from IPBS.

Microbes play an essential role in the restoration of degraded coastal wetlands. However, few studies have focused on the role of key bacteria in the restoration process. Here, Suaeda salsa was planted to recover the biodiversity in the degraded Beidaihe coastal wetland. We monitored omics and soil environmental factors to understand the complex relationship between the bacterial community and wetland health during the restoration period. After planting S. salsa in the degraded area, the soil quality was improved in the later stage of restoration (LPR). Bacterial α-diversity increased with restoration and was positively correlated with TOC. Proteobacteria is the dominant bacterial phylum during the restoration period, and Bacteroidetes, Planctomycetes, Gemmatimonadetes, and Acidobacteria were sensitive to the planting restoration. Random forest analysis picked 30 key OTUs, showing the key bacterial variation of successful restoration. The result indicated that the sum of the relative abundances of key bacterial OTUs was more than 2% in the health wetland. The β-diversity showed that the growth of S. salsa reshaped the soil bacterial community structure and function in the LPR, which recovered to the level in the control area. Putative biogeochemical functions showed that symbionts and aromatic compound degradation were dominant bacterial functions in the growth period of S. salsa. Our study proposed a new indicator to assess wetland health and the planting restoration of S. salsa increased bacteria groups with the ability of symbionts and aromatic compound degradation in the Beidaihe coastal wetland. This study expanded our knowledge of coastal wetland restoration and its ecological contributions.

Electrospinning technology is widely used in the field of drug delivery due to its advantages of convenience, high efficiency, and low cost. To investigate the therapeutic effect of naringenin (Nar) on osteoarthritis (OA), the pH-responsive system of the polycaprolactone/polyethylene glycol-naringenin (PCL/PEG-Nar) nanofiber membrane was designed and used as drug delivery systems (DDS) in the treatment of OA. The PEG-Nar conjugate was constructed via ester linkage between mPEG-COOH and the carboxyl group of naringenin, and the PCL/PEG-Nar nanofiber membrane was prepared by electrospinning technology. When placed in the weak acid OA microenvironment, the PCL/PEG-Nar nanofiber membrane can be cleverly “turned on” to continuously release Nar with anti-inflammatory effect to alleviate the severity of OA. In this study, the construction and the application of the pH-responsive PCL/PEG-Nar nanofiber membrane drug delivery platform would throw new light on OA treatment.

BackgroundOsteosarcoma (OS) is a malignant bone tumor common in children and adolescents. The 5-year survival rate is only 67-69% and there is an urgent need to explore novel drugs effective for the OS. G protein-coupled receptors (GPCRs) are the common drug targets and have been found to be associated with the OS, but have been seldom used in OS.MethodsThe GPCRs were obtained from GPCRdb, and the GPCRs expression profile of the OS was downloaded from the UCSC Xena platform including clinical data. 10-GPCRs model signatures related to OS risk were identified by risk model analysis with R software. The predictive ability and pathological association of the signatures in OS were explored by bio-informatics analysis. The therapeutic effect of the target was investigated, followed by the investigation of the targeting drug by the colony formation experiment were.ResultsWe screened out 10 representative GPCRs from 50 GPCRs related to OS risk and established a 10-GPCRs prognostic model (with CCR4, HCRTR2, DRD2, HTR1A, GPR158, and GPR3 as protective factors, and HTR1E, OPN3, GRM4, and GPR144 as risk factors). We found that the low-risk group of the model was significantly associated with the higher survival probability, with the area under the curve (AUC) of the ROC greater than 0.9, conforming with the model. Moreover, both risk-score and metastasis were the independent risk factor of the OS, and the risk score was positively associated with the metastatic. Importantly, the CD8 T-cells were more aggregated in the low-risk group, in line with the predict survival rate of the model. Finally, we found that DRD2 was a novel target with approved drugs (cabergoline and bromocriptine), and preliminarily proved the therapeutic effects of the drugs on OS. These novel findings might facilitate the development of OS drugs.ConclusionThis study offers a satisfactory 10-GPCRs model signature to predict the OS prognostic, and based on the model signature, candidate targets with approved drugs were provided.

Abstract In this study, sediments were collected from two different sites in the deep-sea hydrothermal region of the South Atlantic Ocean. Two microbial enrichment cultures (H7S and H11S), which were enriched from the sediments collected at two sample sites, could effectively degrade petroleum hydrocarbons. The bacterial diversity was analyzed by high-throughput sequencing method. The petroleum degradation ability were evaluated by gas chromatography–mass spectrometry and gravimetric analysis. We found that the dominant oil-degrading bacteria of enrichment cultures from the deep-sea hydrothermal area belonged to the genera Pseudomonas, Nitratireductor, Acinetobacter, and Brevundimonas. After a 14-day degradation experiment, the enrichment culture H11S, which was obtained near a hydrothermal vent, exhibited a higher degradation efficiency for alkanes (95%) and polycyclic aromatic hydrocarbons (88%) than the enrichment culture H7S. Interestingly, pristane and phytane as biomarkers were degraded up to 90% and 91% respectively by the enrichment culture H11S, and six culturable oil-degrading bacterial strains were isolated. Acinetobacter junii strain H11S-25, Nitratireductor sp. strain H11S-31 and Pseudomonas sp. strain H11S-28 were used at a density ratio of 95:4:1 to construct high-efficiency oil-degrading consortium H. After a three-day biodegradation experiment, consortium H showed high degradation efficiencies of 74.2% and 65.7% for total alkanes and PAHs, respectively. The degradation efficiency of biomarkers such as pristane and high-molecular-weight polycyclic aromatic hydrocarbons (such as CHR) reached 84.5% and 80.48%, respectively. The findings of this study indicate that the microorganisms in the deep-sea hydrothermal area are potential resources for degrading petroleum hydrocarbons. Consortium H, which was artificially constructed, showed a highly efficient oil-degrading capacity and has significant application prospects in oil pollution bioremediation.

Over the past decades, fault diagnosis of discrete event systems has many applications and attracts much attention from researchers and practitioners. With the increasingly high requirements on the reliability of cyber-physical systems such as automated manufacturing systems, fault detection technology has been unprecedentedly developed. Traditional approaches to diagnosability analysis of discrete event systems assume that all the communications between sensors and diagnosers work normally and correctly. However, communication failures may occur anytime, which may cause the loss of observations. This observation loss makes traditional diagnosers fail or report incorrect information. The problem of fault diagnosis against intermittent loss of observations is addressed, i.e., robust diagnosability. In this paper, an approach to robust diagnosability analysis based on labeled Petri nets is presented. A necessary and sufficient condition for robust diagnosability is proposed. We also introduce a verification procedure of robust diagnosability using robust reachability diagnosers.

Poloxamer is a thermo-sensitive synthetic polymer that can achieve sol-gel transition with temperature change, but its relative molecular mass is low, and the hydrogel structure is difficult to maintain for a long time. The thermo-sensitive sodium alginate/poloxamer composite hydrogel (SA/P407) was synthesized by mixing poloxamer with sodium alginate. The chemical structures, temperature sensitivity, microscopic morphology, dynamic viscoelasticity and in vitro drug release behaviors of sodium alginate/poloxamer composite hydrogels were investigated by FT-IR, test tube inversion, SEM, rheometer and UV-Vis spectroscopy. In addition, the swelling properties of sodium alginate/poloxamer composite hydrogels were also studied. These results show that the sodium alginate/poloxamer composite hydrogel is thermo-sensitive, and the gelation concentration (mass fraction is 6%) of poloxamer at body temperature can be reduced by adding sodium alginate. By controlling the mass ratio of sodium alginate and poloxamer, the sol-gel transition temperature can be kept between room temperature and body temperature (25-37 ℃), and the gelation time can be shortened to 84 s. The sodium alginate/poloxamer composite hydrogel has a structural feature of high porosity and interconnected pores, and its pore size ranges from 20 μm to 80 μm. With the increase of sodium alginate, the swelling rate of the sodium alginate/poloxamer composite hydrogel is gradually decreased. The sodium alginate/poloxamer composite hydrogel shows sustained release of the anticancer drug gemcitabine, and the drug release time can reach 72 hours. Sodium alginate/poloxamer composite hydrogel has an important application prospect in the field of injectable carriers for sustained drug release.

Bladder cancer is the most common malignant tumor of the urinary system. The intention of the present research is to explore the prognostic value and biological function of solute carrier family 12 member 8 (SLC12A8) in bladder cancer. The analysis based on the TCGA and ONCOMINE database revealed that the expression of SLC12A8 in bladder cancer was notably increased compared with the normal group. SLC12A8 expression was notably correlated with the age, pathological stage, T-stage, and lymph node metastasis of bladder cancer patients. Moreover, the patients’ overall survival was notably shorter in the high SLC12A8 group. Compared with the control, SLC12A8 upregulation enhanced the proliferative, invasive, and migratory capacities of bladder cancer cells and promoted the expression of epithelial–mesenchymal transition (EMT) protein markers including β-catenin, vimentin, snail, and slug, while reduced the expression of E-cadherin. In the case of downregulated SLC12A8 expression, the proliferative, invasive, and migratory capacities of bladder cancer cells and the expression of EMT protein markers presented the opposite trend. This study demonstrated that SLC12A8 was highly correlated with oncogenesis and progression of bladder cancer, indicating that SLC12A8 may be a meaningful biomarker for initial diagnosis and early treatment of bladder cancer.

Tobacco smoke exposure is a major environmental risk factor that facilitates the development and progression of asthma. Our previous study showed that CpG oligodeoxynucleotide (CpG-ODN) inhibits thymic stromal lymphopoietin (TSLP)-dendritic cells (DCs) to reduce Th2/Th17-related inflammatory response in smoke-related asthma. However, the mechanism underlying CpG-ODN -downregulated TSLP remains unclear. A combined house dust mite (HDM)/cigarette smoke extract (CSE) model was used to assess the effects of CpG-ODN on airway inflammation, Th2/Th17 immune response, and amount of IL-33/ST2 and TSLP in mice with smoke-related asthma induced by adoptive transfer of bone-marrow-derived dendritic cells (BMDCs) and in the cultured human bronchial epithelium (HBE) cells administered anti-ST2, HDM, and/or CSE. In vivo, compared to the HDM alone model, the combined HDM/CSE model had aggravated inflammatory responses, while CpG-ODN attenuated airway inflammation, airway collagen deposition, and goblet cell hyperplasia and reduced the levels of IL-33/ST2, TSLP, and Th2/Th17-cytokines in the combined model. In vitro, IL-33/ST2 pathway activation promoted TSLP production in HBE cells, which could be inhibited by CpG-ODN. CpG-ODN administration alleviated Th2/Th17 inflammatory response, decreased the infiltration of inflammatory cells into the airway, and improved the remodeling of smoke-related asthma. The underlying mechanism may be that CpG-ODN inhibits the TSLP-DCs pathway by downregulating the IL-33/ST2 axis.

The feedback control system with network-connected components is vulnerable to cyberattacks. We study a problem of attack detection in supervisory control of discrete-event systems. The scenario of a system subjected to actuator enablement attacks is considered in this article. We also consider that some unsafe places that should be protected from an attacker exist in the system, and some controllable events that are disabled by a supervisor might be re-enabled by an attacker. This article proposes a defense strategy to detect actuator enablement attacks and disable all controllable events after detecting an attack. We design algorithmic procedures to determine whether the system can be protected against damage caused by actuator enablement attacks, where the damage is predefined as a set of “unsafe” places. In this way, the system property is called “AE-safe controllability”. The safe controllability can be verified by using a basis diagnoser or a basis verifier. Finally, we explain the approach with a cargo system example.

Steel-fiber-reinforced concrete (SFRC) is a composite material made by randomly distributing short steel fibers in normal concrete (NC). In this study, central pull-out tests of 32 specimens were performed to investigate the bond behavior between high-strength rebar and SFRC under the influence of the fraction of steel fiber by volume (Vf = 0%, 0.5%, 1.0% and 1.5%) and temperature (T = 20, 200, 400 and 600 °C). The results show that in NC specimens, splitting failure occurs below 400 °C, while split-pullout failure occurs above 600 °C. Split-pullout failure occurs in all SFRC specimens at each tested temperature. The bond strength between rebar and SFRC was found to decay significantly between 400 and 600 °C. The effect of Vf on the improvement in bond strength was more obvious between 400 and 600 °C than between 20 and 400 °C. The positive contribution of steel fibers to bond behavior is the construction of a rigid skeleton with coarse aggregates that can play a bridging role and effectively retard the expansion of concrete cracks. This improves the bond strength between rebar and SFRC at high temperatures. The bond–slip curve can be divided into five stages, namely the initial micro-slide phase, slip phase, splitting failure phase, stress drop phase and residual pull-out phase. A model of the bond–slip relationship between rebar and SFRC considering temperature and Vf was developed by modifying the existing model of the bond–slip relationship between rebar and NC. The model calculation results agree well with those of testing.

The tower is the load-bearing structure of the overhead transmission line. Due to the complex operating environment and other factors, the transmission tower is prone to corrosion, which weakens the bearing capacity of the tower and affects the safe operation of the power grid. Through the investigation of the corrosion situation of the transmission towers in service, the angle steel members were removed from the in-service transmission towers, and the axial compression bearing capacity test was carried out. As the corrosion rate increases, the bearing capacity of components shows a decreasing trend, and due to the existence of corrosion, and at the same corrosion rate, due to the location of corrosion, The corrosion depth and corrosion area are different, and the axial compression bearing capacity of the components fluctuates greatly.

Bmpr2 plays a central role in the regulation of reproductive development in mammals, but its role during ovarian development in fish is still unclear. To ascertain the function of bmpr2 in ovarian development in the ricefield eel, we isolated and characterized the bmpr2 cDNA sequence; the localization of Bmpr2 protein was determined by immunohistochemical staining; and the expression patterns of bmpr2 in ovarian tissue incubated with FSH and hCG in vitro were analyzed. The full-length bmpr2 cDNA was 3311 bp, with 1061 amino acids encoded. Compared to other tissues, bmpr2 was abundantly expressed in the ovary and highly expressed in the early yolk accumulation (EV) stages of the ovary. In addition, a positive signal for Bmpr2 was detected in the cytoplasm of oocytes in primary growth (PG) and EV stages. In vitro, the expression level of gdf9, the ligand of bmpr2, in the 10 ng/mL FSH treatment group was significantly higher after incubation for 4 h than after incubation for different durations. However, bmpr2 expression in the 10 ng/mL FSH treatment group at 2 h, 4 h and 10 h was significantly lower. Importantly, the expression level of bmpr2 and gdf9 in the 100 IU/mL hCG group had similar changes that were significantly decreased at 4 h and 10 h. In summary, Bmpr2 might play a pivotal role in ovarian growth in the ricefield eel, and these results provide a better understanding of the function of bmpr2 in ovarian development and the basic data for further exploration of the regulatory mechanism of gdf9 in oocyte development.

This paper, as a reference for the researchers of mixed reality(MR) and surgical educators, introduced concept of MR and its characteristics as a surgical teaching tool. The paper also reviewed the current application of MR in surgical training, and analyzed its application approaches and an expected development in future.

Carboxymethyl chitosan is an important chitosan derivative with good biocompatibility and degradability, and has a wide range of biomedical applications. In this study, water-soluble carboxymethyl chitosan derivative that can be photo-crosslinked by UV irradiation was synthesized. Methacrylated carboxymethyl chitosan (M-CMCS) was synthesized by N-methacrylation of carboxymethyl chitosan (CMCS). The chemical structures of M-CMCS were characterized by 1H NMR and FT-IR. The M-CMCS hydrogels with different degrees of crosslinking was prepared by UV-triggered photo-crosslinking. The microscopic morphology, mechanical properties, swelling properties, enzymatic degradation properties and in vitro drug release behaviors of M-CMCS hydrogels were investigated by SEM, rheometer, and UV-Vis spectroscopy, respectively. The results show that the degree of methacrylation is gradually increased as the molar ratio of glycidyl methacrylate to carboxymethyl chitosan increases. M-CMCS hydrogels have the structure of high porosity and interconnected pores with the pore size of 1-20 μm. The swelling ratio of M-CMCS hydrogels is decreased as the degree of crosslinking increases. M-CMCS hydrogel can be slowly degraded by lysozyme, and the degradation rate is decreased by increasing the degree of crosslinking. M-CMCS hydrogels show sustained release behavior for anticancer drug gemcitabine, and the drug release can be extended to 4 days. Photo-crosslinked M-CMCS hydrogels show great promise for drug release and tissue engineering.

Abstract Background Rhodotorula glutinis is recognized as a biotechnologically important oleaginous red yeast, which synthesizes numerous meritorious compounds with wide industrial usages. One of the most notable properties of R. glutinis is the formation of intracellular lipid droplets full of carotenoids. However, the basic genomic features that underlie the biosynthesis of these valuable compounds in R. glutinis have not been fully documented. To reveal the biotechnological potential of R. glutinis, the genomics and lipidomics analysis was performed through the Next-Generation Sequencing and HPLC-MS-based metabolomics technologies. Results Here, we firstly assemble the genome of R. glutinis ZHK into 21.8 Mb, containing 30 scaffolds and 6774 predicted genes with a N50 length of 14, 66,672 bp and GC content of 67.8%. Genome completeness assessment (BUSCO alignment: 95.3%) indicated the genome assembly with a high-quality features. According to the functional annotation of the genome, we predicted several key genes involved in lipids and carotenoids metabolism as well as certain industrial enzymes biosynthesis. Comparative genomics results suggested that most of orthologous genes have underwent the strong purifying selection within the five Rhodotorula species, especially genes responsible for carotenoids biosynthesis. Furthermore, a total of 982 lipids were identified using the lipidomics approaches, mainly including triacylglycerols, diacylglyceryltrimethylhomo-ser and phosphatidylethanolamine. Conclusion Using whole genome shotgun sequencing, we comprehensively analyzed the genome of R. glutinis and predicted several key genes involved in lipids and carotenoids metabolism. By performing comparative genomic analysis, we show that most of the ortholog genes have undergone strong purifying selection within the five Rhodotorula species. Furthermore, we identified 982 lipid species using lipidomic approaches. These results provided valuable resources to further advance biotechnological applications of R .glutinis.

Abstract Background Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. Results We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. Conclusions C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

Abstract Background To protect and maintain the positivity of self-concept, normal people usually show a self-serving bias (internal attribution of positive events and external attribution of negative events) by the motives of self-enhancement and self-protection. Additionally, self-serving assessments predominantly activate the subcortical-cortical midline structures (CMS) in healthy individuals. However, little is known about self-serving bias and its underlying neural correlates among individuals with Internet gaming disorder (IGD). Methods Twenty-four participants with IGD and 25 recreational Internet gaming users (RGUs) were scanned while attributing the causes of positive/negative self- and other-related events that could occur in both the game-world and real-world contexts. Region-of-interest (within CMS regions) and parametric analysis were performed to investigate the neural correlates of self-serving bias in IGD. Results Behaviorally, the IGD participants attributed more negative and fewer positive events to themselves than RGU participants in both contexts. Neurally, during the attributions of negative events, the IGD participants exhibited increased ventromedial prefrontal cortex (vmPFC) activation in both contexts compared with RGU participants. Higher vmPFC activation was associated with weaker self-protective motivation in the IGD group. Meanwhile, during the attributions of positive events, the IGD participants exhibited decreased precuneus/posterior cingulate cortex activation in the real world compared with RGU participants. Parametric analysis showed a reduced positive correlation between precuneus activation and self-attribution ratings of positive events in the real world in the IGD group relative to the RGU group. Conclusion These results suggest that individuals with IGD show an attenuated self-serving bias and altered brain activity within CMS regions involved in self-attribution, providing evidence for the negative self-concept and weakened abilities in both self-enhancement and self-protection in IGD.

Objective: With the rapid rising prevalence, gestational diabetes mellitus (GDM) has become one of the leading causes of maternal and child mortality and morbidity worldwide. The present study aimed to analyze GDM-related risk factors for early intervention. Materials and methods: From January to June 2018, a total of 250 pregnant women from Chengdu Second People's Hospital were enrolled in the study. According to the diagnostic criteria for GDM, they were assigned into GDM group (n = 48) and non-GDM group (n = 202). The clinical data and biochemical indicators were compared between GDM group and non-GDM group, and Logistic regression analysis was performed to analyze the risk factors of GDM. Results: GDM group was significantly higher than non-GDM group in the age, pregnancy times, pre-pregnancy body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) level, history of diabetes mellitus in first-degree relatives, incidence of subclinical hypothyroidism (SCH) and the positive rate of thyroid peroxidase antibody (TPOAb) (P

Abstract Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal − organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA .

Abstract Background The differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology. Methods To identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early stages, the gene expression profiles with temporal series were downloaded to reveal the distinct fates when BMSCs adopt a committed lineage. For both OS and AD lineages, the profiles of days 2–4 were compared with day 0 to screen the differentially expressed genes (DEGs), respectively. Next, the functional enrichment analysis was utilized to find out the biological function, and protein-protein interaction network to predict the central genes. Finally, experiments were performed to verify our finding. Results FoxO signaling pathway with central genes like FoxO3, IL6, and CAT is the crucial mechanism of OS, while Rap1 signaling pathway of VEGFA and FGF2 enrichment is more significant for AD. Besides, PI3K-Akt signaling pathway might serve as the latent mechanism about the initiation of differentiation of BMSCs into multiple lineages. Conclusion Above hub genes and early-responder signaling pathways control osteogenic and adipogenic fates of BMSCs, which maybe mechanistic models clarifying the changes of bone metabolism in the clinical progress of osteoporosis. The findings provide a crucial reference for the prevention and therapy of osteoporosis.

Acute respiratory distress syndrome (ARDS) is an uncontrollable, progressive pulmonary inflammatory disease, and as a common clinical critical disease, there is no effective treatment available. Electroacupuncture (EA) therapy is a type of traditional Chinese medicine physiotherapy that can alleviate the inflammatory response. However, the potential mechanism of EA in the treatment of ARDS is not yet clear. Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation. Recently, emerging evidence has shown that ferroptosis is closely related to the occurrence and development of ARDS caused by various pathological factors. Here, we further investigated whether EA-mediated inhibition of ferroptosis in lung tissue could attenuate lipopolysaccharide (LPS)-induced ARDS and explored its underlying mechanisms. In this study, mice were administered LPS intraperitoneally to establish a model of LPS-induced ARDS. We found that EA stimulation could not only reduce the exudation of inflammatory cells and proteins in the alveolar lumen but also significantly alleviate the pathological changes of lung tissue, inhibit the production of proinflammatory cytokines and improve the survival rate of mice. Concurrently, we also found that ferroptosis events occurred in the lung tissue of LPS-induced ARDS mice, manifested by elevated iron levels, ROS production and lipid peroxidation. Intriguingly, our results showed that EA stimulation at the Zusanli (ST36) acupoint activated α7 nicotinic acetylcholine receptor (α7nAchR) in lung tissue mainly through the sciatic nerve and cervical vagus nerve, thus exerting anti-ferroptosis and pulmonary protective effects. Additionally, these effects were eliminated by methyllycaconitine (MLA), a selective antagonist of α7nAchR. In vitro experiments, activation of α7nAchR protected alveolar epithelial cells from LPS-induced ferroptosis. Furthermore, our experiments showed that the pulmonary protective effects of EA stimulation were effectively reversed by erastin, a ferroptosis activator. Collectively, we demonstrated that EA stimulation could alleviate LPS-induced ARDS by activating α7nAchR to inhibit LPS-induced ferroptosis in alveolar epithelial cells. Targeting and regulating ferroptosis in alveolar epithelial cells may be a potential intervention approach for the treatment of LPS-induced ALI/ARDS in the future.

AimThe study aimed to develop a scalable dual-fluorescence assay in cells to enable the functional interpretation of HNF-4α missense variants identified in exome sequencing, which can be used to guide clinical diagnosis.MethodsUsing mOrange2 and GFP fluorescence proteins to track the expression of HNF-4α (HNF-4α-mOrange2) and reporter activity under the control of the HNF-1α promoter (pHNF1A-GFP), respectively, we designed a dual-fluorescence assay to evaluate the expression level, cellular localization, and transcriptional function of HNF-4α simultaneously in live cells. To assess the scalable characteristic of the assay, a small library containing five previously reported mutations and wild-type HNF-4α was constructed. Cells infected with this library were sorted into different populations through fluorescence-activated cell sorting (FACS) according to the transcription activity and expression abundance. Cloning and Sanger sequencing were used to detect the mutations of the different groups. High content screening (HCS) assay was used for the validation of individual mutants in the function and expression point of view.ResultsHNF-4α-mOrange2 exhibited nuclear localization and transactivation capability on the HNF-1α promoter as physical HNF-4α does. The expression of HNF-4α-mOrange2 shows a 6-fold induction of GFP expression compared to the control without HNF-4α-mOrange2, which was significantly abolished by the known loss-of-function mutant M373R. The different performances of wild-type and mutant M373R made them distinguishable in the FACS system, empowering the scalable capability of this assay for classifying large numbers of variants combining functional stratification and sequencing. Further application of the assay in the small library showed that three cell populations were seen grouped as Normal (same transactivation as wild type), Reducedexp_nor (reduced transactivation with normal or higher expression), and Reducedexp_low (reduced transactivation with lower expression). Subsequently, Sanger sequencing showed that wild-type HNF-4α was in the Normal group, two mutations (M373R and G79C) were enriched in the Reducedexp_nor group, and three mutations (C115S, L272P, and F83C) belonged to the Reducedexp_low group. These results were validated by further imaging data using HCS assay for individual mutation.ConclusionsOur study proposes a scalable and informative approach for the characterization of the variants in HNF-4α genes in a quantitative and high-throughput manner.

Background: Genome-wide association studies have identified many Alzheimer’s disease (AD) genetic-risk single nucleotide polymorphisms (SNPs) and indicated the important role of the cholesterol/lipid metabolism pathway in AD pathogenesis. This study aims to investigate the effects of cholesterol and genetic risk factors on progression of mild cognitive impairment (MCI) to AD.Methods: We prospectively followed 316 MCI participants aged ≥50 years with a baseline cholesterol profile and SNP genotyping data for 4.5 years on average in a sub-cohort of the Shanghai Aging Study. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol in serum were measured at baseline. SNP genotyping was performed using a MassARRAY system. At follow-up, consensus diagnosis of incident dementia and AD were established based on medical, neurological, and neuropsychological examinations. Cox regression models were used to assess the association of cholesterol and SNP with incident AD.Results: The AG/AA genotypes of PVRL2 rs6859 were significantly associated with increased incident AD in MCI participants, compared with GG genotype (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.32–5.76, p = .007, false discovery rate–adjusted p = .030). In PVRL2 rs6859 AG/AA carriers, each-1 mmol/L higher level of LDL-C was significantly associated with a 48% decreased risk of AD (adjusted HR 0.52, 95%CI 0.33–0.84, p = .007). Consistent results were obtained when using LDL-C as the categorical variable (P for trend = 0.016).Conclusion: The relationship between LDL-C and progression of MCI may be influenced by genetic variants.

Abstract Introdction Previous studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., “I hit Tom”) or a passive recipient (e.g., “Paul hits me”). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression. Methods The present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events. Results Compared with healthy controls, depressed patients showed more self‐attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self‐related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients’ self‐attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self‐related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients’ reaction time when they played recipient role in selfrelated negative events. Conclusion These results implicated that depressed patients manifested the negative self‐view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.

Since illegal wildlife trade poses challenges to biodiversity and public security, improving people’s wildlife conservation through environmental education has become an important issue. This study analyzes the intervention effect of labeling in wildlife conservation education and explores the underlying mechanism by targeting adolescents. Specifically, it is found that (1) the labeling in wildlife conservation education can improve teenagers’ willingness to protect wildlife; (2) the environmental self-identity is highly correlated with wildlife conservation.