Search

Many metabolic diseases in fish are often associated with lowered peroxisomal fatty acid (FA) β-oxidation. However, the physiological role of peroxisomal FA oxidation in lipid metabolism in fish still remains unclear. In the present study, a specific peroxisomal FA β-oxidation inhibitor, 10,12-tricosadiynoic acid (TDYA), was used to investigate the effects of impaired peroxisomal β-oxidation on growth performance, health status, and lipid metabolism in Nile tilapia. The results showed that the dietary TDYA treatment did not affect weight gain, but significantly decreased peroxisomal β-oxidation in the liver, and increased body fat accumulation. The fish with impaired peroxisomal β-oxidation exhibited higher contents of serum lipid and peroxidation products, and alanine aminotransferase activity, and significantly lowered hepatic activities of superoxide dismutase and catalase. The inhibited peroxisomal β-oxidation did not enhance mitochondrial β-oxidation activity, but compensatorily upregulated FA β-oxidation-related gene expression, and downregulated the gene expressions in lipolysis and lipogenesis. Taken together, TDYA treatment markedly induced lipid accumulation and hepatic oxidative damage via systemically depressing lipid catabolism and antioxidant capacity. Our findings reveal the pivotal roles of peroxisomal β-oxidation in maintaining health and lipid homeostasis in fish, and could be helpful in understanding metabolic diseases in fish.

In this paper, based on the theoretical study of tool wear and the systematic analysis of the main factors affecting the tool durability, four types of PVD and CVD-coated blades from three manufacturers were subjected to cutting tests using PCrNi3MoVA gun steel workpieces. The wear morphology, fatigue curves, and chip patterns of the tested blades were comparatively analyzed. The influence of the coating type on the tool durability was investigated using a scanning electron microscopy and energy dispersive spectroscopy. The results obtained strongly indicate that TiAlN coating deposited by the PVD technology has the best thermal stability, temperature oxidation resistance, and tool durability when cutting PCrNi3MoVA gun steel workpieces under semi-finishing conditions. The wear resistance of the other three types of blades was relatively lower due to less favorable coating compositions and structures. The study findings are instrumental in the substantiated selection of cutters for practical applications and provide a reference for the design optimization of indexable coated inserts.

This study mainly introduced the research on Chinese medicine toxicology funded by the National Natural Science Foundation of China(NSFC) in 2012-2021 and analyzed the research content. Furthermore, key research topics and characteristic research projects were discussed, such as the toxicity mechanism, relationship between toxicity and efficacy, toxicity-alleviating mechanisms, and new technology and methods. The review suggested that researchers should gain an in-depth understanding of thequot;toxicityquot; of Chinese me-dicine, turned to characteristic research topics, and build a toxicological research paradigm suited to the characteristics of Chinese medicine in project application.

Enhanced recovery after surgery strategies are increasingly implemented to improve the management of surgical patients.To evaluate the effects of new perioperative fasting protocols in children ≥ 3 mo of age undergoing non-gastrointestinal surgery.This prospective pilot study included children ≥ 3 mo of age undergoing non-gastrointestinal surgery at the Children's Hospital (Zhejiang University School of Medicine) from January 2020 to June 2020. The children were divided into either a conventional group or an ERAS group according to whether they had been enrolled before or after the implementation of the new perioperative fasting strategy. The children in the conventional group were fasted using conventional strategies, while those in the ERAS group were given individualized fasting protocols preoperatively (6-h fasting for infant formula/non-human milk/solids, 4-h fasting for breast milk, and clear fluids allowed within 2 h of surgery) and postoperatively (food permitted from 1 h after surgery). Pre-operative and postoperative fasting times, pre-operative blood glucose, the incidence of postoperative thirst and hunger, the incidence of perioperative vomiting and aspiration, and the degree of satisfaction were evaluated.The study included 303 patients (151 in the conventional group and 152 in the ERAS group). Compared with the conventional group, the ERAS group had a shorter pre-operative food fasting time [11.92 (4.00, 19.33)Optimizing fasting and clear fluid drinking before non-gastrointestinal surgery in children ≥ 3 mo of age is possible. It is safe and feasible to start early eating after evaluating the recovery from anesthesia and the swallowing function.

Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine formula used to invigorate blood circulation and resolve blood stasis. It consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H.Boissieu) PimenovKljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. THSWD is a common prescription for the treatment of ischemic stroke.To study the protective effect and mechanism of Taohong Siwu Decoction (THSWD) on PC12 cells damaged by oxygen glucose deprivation/reperfusion (OGD/R).OGD/R model of PC12 cells was used to simulate ischemia-reperfusion (I/R) injury of nerve cells in vitro. The experiment was grouped as follows: control, OGD/R and OGD/R + THSWD (5%, 10% and 15%) group. Oxygen and glucose was restored for 24 h after 4-6 h of deprivation. The severity of damage to PC12 cells was evaluated by CCK8, flow cytometry and lactate dehydrogenase (LDH). Mitochondrial morphology and function were examined by transmission electron microscopy (TEM), ATP and mitochondrial membrane potential (MMP) assay kits. Cellular autophagy and NLRP3 inflammasome-associated proteins were detected by Western blot and immunofluorescence staining.THSWD treatment improved the survival rate of PC12 cells injured by OGD/R, reduced cell damage and apoptosis. Moreover, ATP, MMP and the expression of autophagy marker proteins (LC3-II/LC3-I, Beclin1, Atg5) and mitophagy marker proteins (Parkin and PINK-1) was significantly elevated. The reactive oxygen species (ROS), NLRP3 inflammasome and pro-inflammatory cytokines induced by OGD/R were distinctly reduced. In contrast, these above beneficial effects of THSWD on mitochondrial autophagy and NLRP3 inflammasome were reversed by mitochondrial division inhibitory factor 1 (Mdivi-1).THSWD protects PC12 cells against OGD/R injury by heightening mitophagy and suppressing the activation of NLRP3 inflammasome.

Boreal forests with high carbon sequestration capacity play a crucial role in mitigating global climate change. Addressing dynamic changes of soil organic carbon (SOC) after wildfire helps in understanding carbon cycling. The objective of this study is to investigate changes in soil organic carbon after wildfires in a boreal forest. The post-fire soil chronosequence after 3 months, 17 years, and 25 years within a boreal forest was used to examine dynamic and stable SOC after wildfire at the decadal scale. Soils in genetic horizons were sampled and analyzed for dynamic and stable SOC, including water stable aggregates (WSA), WSA associated organic carbon (WSA-SOC), soil heavy fractions (HF) associated organic carbon (HF-SOC), and soil total organic carbon (TOC). The TOC and WSA-SOC content of the A horizon was the greatest in the control site. There was no significant difference for TOC between burned and unburned deep BC horizons. The TOC for the A and B horizons at the 17-year-old site was significantly lower compared to the other sites. TOC did not recover to the pre-fire levels (control site) in any of the burned areas. The lowest WSA was found in the A and B horizons of the 3-month-old site. The WSA at the 25-year-old site was higher compared to the 17-year-old site. WSA increased with time following fire, but the recovery rate differed among different sites. The lowest concentration of WSA-SOC for the A horizon occurred at the 17-year-old site, and no significant difference was observed between B and BC horizons. The HF content for the A horizon was the greatest at the 3-month-old site. There was no significant difference in HF-SOC between B and BC horizons in all sites. TOC and stable SOC (HF and WSA) increased over time in species-dominance relay stand areas, while self-replacement stands areas showed the opposite. The results indicate that overall, the ability of soil to sequester carbon decreased after wildfire disturbances. Stable SOC accumulated more in areas where species-dominance relay succession occurred compared to the self-replacement stands. These disturbances were more pronounced for surface soil horizons. This study provides a quantitative assessment of SOC changes after wildfires that are useful for forest management and modeling forecasts of SOC stocks, especially in boreal forests.

We analyze paradoxes embedded in long-term corporate development and conceptualize a new leadership approach: paradoxical leader behavior in long-term corporate development (PLB-CD). Paradoxical leader behaviors are characterized as seemingly both competing and interrelated. We posit that paradoxical leaders employ such behaviors to meet competing demands simultaneously and over time in the process of (a) maintaining both short-term efficiency and long-term development, (b) maintaining both organizational stability and flexibility, (d) focusing on both shareholders and stakeholder communities, and (d) conforming to and shaping collective forces in the environment. We conduct two studies with multiple samples to develop a measurement of PLB-CD. Our results demonstrate that long-term orientation is positively associated with paradoxical leader behavior, which in turn positively affects the increase of R&D investment, market share, and corporate reputation.

Intestinal lipases are fat-digesting enzymes, which play vital roles in lipid absorption in the intestine. To study the regulation of intestinal lipase activity in systemic lipid metabolism in fish, especially in the metabolic diseases caused by high-fat diet (HFD) feeding, we inhibited intestinal lipases in Nile tilapia to investigate the physiological consequences. In the present study, Nile tilapia were firstly fed with HFD (12% fat) for 6 weeks to establish a fatty fish model. Afterwards, Orlistat as a potent intestinal lipase inhibitor was added into the HFD for the following 5-week feeding trial, with two dietary doses (Orlistat16 group, 16 mg/kg body weight; Orlistat32 group, 32 mg/kg body weight). After the trial, both doses of Orlistat treatment significantly reduced intestinal lipase activity, fat absorption, hepatic lipid accumulation, and gene expression of lipogenesis, whereas increased gene expression of lipid catabolism. Moreover, intestinal lipase inhibition increased immune enzyme activities, antioxidant capacity, and gene expression of anti-inflammatory cytokines, whereas lowered gene expression of pro-inflammatory cytokines. Besides, Orlistat could also improve the structure of the intestine and increase expression of intestinal tight-coupling protein. Taken together, intestinal lipase inhibition alleviated the adverse effects caused by HFD in Nile tilapia. Thus, intestinal lipases played key roles in absorbing dietary lipid and could be a promising target in regulating systemic lipid metabolism in fish.

It is well known that opioid analgesics produce side effects including tolerance and constipation. Since neuropeptide FF (NPFF) receptor antagonists reversed opioid-induced hyperalgesia and analgesic tolerance, the present work was performed to synthetize two branched peptidomimetics, EKR and RKE, containing the opioid peptide endomorphin-2 (EM-2) and the NPFF receptor antagonist RF9. Our data obtained from the in vitro cyclic adenosine monophosphate experiment demonstrated that EKR functioned as a mixed mu-, delta-opioid receptors agonist and NPFF1 receptor antagonist/NPFF2 receptor partial agonist, whereas RKE acted as a multi-functional peptidomimetic with the mu-opioid agonism and the NPFF1 antagonism/NPFF2 partial agonism. Furthermore, EKR and RKE completely blocked the NPFF2 receptor-mediated neurite outgrowth of Neuro 2A cells. In vivo antinociception studies found that supraspinal administration of EKR and RKE dose-dependently produced potent antinociception via the mu-opioid receptor in the tail-flick test. In carrageenan inflammatory pain model, spinal administration of EKR and RKE induced dose-related analgesia, which was significantly reduced by the opioid antagonist naloxone and the NPFF antagonist RF9. Notably, compared with morphine, intracerebroventricular repeated administration of EKR and RKE maintained prolonged antinociceptive effectiveness. In addition, at the antinociceptive doses, these two branched peptidomimetics did not significantly inhibit gastrointestinal transit. Taken together, the present work suggest that EKR and RKE behave as multi-functional ligands with the opioid agonism and the NPFF1 antagonism/NPFF2 partial agonism, and produce prolonged antinociception with limited side effects. Moreover, our results imply that EKR and RKE might be interesting pharmacological tools for further investigating the biological function of the NPFF and opioid systems.

Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aβ) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H

Simple Summary Diapause is a type of seasonal polyphenism and is induced by multiple cues, such as light and temperature. However, the molecular mechanisms of how the environment induces diapause remains unclear. We are interested in the epigenetic regulation, especially the non-coding RNA, involved in environmentally induced diapause. The progeny eggs of bivoltine silkworm strains undergoing diapause or not depends on the incubation temperature during the maternal embryonic stage. In this research, we compared the differentially expressed microRNAs in embryos incubated under diapause-inducing temperature (25 °C) and non-diapause-inducing temperature (15 °C) in silkworm. Our results indicate that miRNAs respond to diapause-inducing temperature and regulate the expression of circadian clock genes. Our research not only provides reference for the study of the diapause induction process, but also gives insights into the role of epigenetic modification in diapause. Abstract Diapause is one of the survival strategies of insects for confronting adverse environmental conditions. Bombyx mori displays typical embryonic diapause, and offspring diapause depends on the incubation environment of the maternal embryo in the bivoltine strains of the silkworm. However, the molecular mechanisms of the diapause induction process are still poorly understood. In this study, we compared the differentially expressed miRNAs (DEmiRs) in bivoltine silkworm embryos incubated at diapause- (25 °C) and non-diapause (15 °C)-inducing temperatures during the blastokinesis (BK) and head pigmentation (HP) phases using transcriptome sequencing. There were 411 known miRNAs and 71 novel miRNAs identified during the two phases. Among those miRNAs, there were 108 and 74 DEmiRs in the BK and HP groups, respectively. By the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the predicted target genes of the DEmiRs, we found that aside from metabolism, the targets were also enriched in phototransduction-fly and insect hormone biosynthesis in the BK group and the HP group, respectively. Dual luciferase reporter assay illustrated that bmo-miR-6497-3p directly regulated Bmcycle and subsequently regulated the expression of circadian genes. These results imply that microRNAs, as vitally important regulators, respond to different temperatures and participate in the diapause induction process across species.

Widespread soil acidification due to atmospheric acid deposition and agricultural fertilization may greatly accelerate soil carbonate dissolution and CO2 release. However, to date, few studies have addressed these processes. Here, we use meta-analysis and nationwide-survey datasets to investigate changes in soil inorganic carbon (SIC) stocks in China. We observe an overall decrease in SIC stocks in topsoil (0–30 cm) (11.33 g C m–2 yr–1) from the 1980s to the 2010s. Total SIC stocks have decreased by ∼8.99 ± 2.24% (1.37 ± 0.37 Pg C). The average SIC losses across China (0.046 Pg C yr–1) and in cropland (0.016 Pg C yr–1) account for ∼17.6%–24.0% of the terrestrial C sink and 57.1% of the soil organic carbon sink in cropland, respectively. Nitrogen deposition and climate change have profound influences on SIC cycling. We estimate that ∼19.12%–19.47% of SIC stocks will be further lost by 2100. The consumption of SIC may offset a large portion of global efforts aimed at ecosystem carbon sequestration, which emphasizes the importance of achieving a better understanding of the indirect coupling mechanisms of nitrogen and carbon cycling and of effective countermeasures to minimize SIC loss.

Neutral lipases-mediated lipolysis and acid lipases-moderated lipophagy are two main processes for degradation of lipid droplets (LDs). However, the individual and interactive roles of these metabolic pathways are not well known across vertebrates. This study explored the roles of lipolysis and lipophagy from the aspect of neutral and acid lipases in zebrafish. We established zebrafish strains deficient in either adipose triglyceride lipase (atgl-/-; AKO fish) or lysosomal acid lipase (lal-/-; LKO fish) respectively, and then inhibited lipolysis in the LKO fish and lipophagy in the AKO fish by feeding diets supplemented with the corresponding inhibitors Atglistatin and 3-Methyladenine, respectively. Both the AKO and LKO fish showed reduced growth, swimming activity, and oxygen consumption. The AKO fish did not show phenotypes in adipose tissue, but mainly accumulated triacylglycerol (TAG) in liver, also, they had large LDs in the hepatocytes, and did not stimulate lipophagy as a compensation response but maintained basal lipophagy. The LKO fish reduced total lipid accumulation in the body but had high cholesterol content in liver; also, they accumulated small LDs in the hepatocytes, and showed increased lipolysis, especially Atgl expression, as a compensatory mechanism. Simultaneous inhibition of lipolysis and lipophagy in zebrafish resulted in severe liver damage, with the potential to trigger mitophagy. Overall, our study illustrates that lipolysis and lipophagy perform individual and interactive roles in maintaining homeostasis of TAG and cholesterol metabolism. Furthermore, the interactive roles of lipolysis and lipophagy may be essential in regulating the functions and form of mitochondria.

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

To explore the effects of Taohong Siwu decoction (, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion.Thirty-six pregnant female rats were administered mifepristone and misoprostol to induce abortion, and amounts of uterine bleeding were recorded. Pathological damage and collagen accumulation were detected by hematoxylin-eosin staining and Masson's trichrome staining in uterus, respectively. Myeloperoxidase was evaluated by immunohistochemistry.The expression levels of fibronectin, laminin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were quantified using western blotting.THSWD could promote endometrial protection in rats following drug-induced abortion. The contents of cellulose and myeloperoxidase were significantly decreased in uterine tissue of THSWD-treated groups. Moreover, THSWD significantly decreased the expression levels of fibronectin, laminin, and TIMP-1. THSWD also significantly increased MMP-9 expression and the MMP-9/TIMP1 ratio.THSWD plays a critical role in endometrial protection by reducing extracellular matrix deposition and uterine fibrosis. These effects may have been achieved by increasing MMP-9, reducing TIMP-1, and/or altering the ratio of MMP-9/TIMP-1.

Cellular energy production requires coordinated interactions between genetic components from the nuclear and mitochondrial genomes. This coordination results in coadaptation of interacting elements within populations. Interbreeding between divergent gene pools can disrupt coadapted loci and result in hybrid fitness breakdown. While specific incompatible loci have been detected in multiple eukaryotic taxa, the extent of the nuclear genome that is influenced by mitonuclear coadaptation is not clear in any species. Here, we used F2 hybrids between two divergent populations of the copepod Tigriopus californicus to examine mitonuclear coadaptation across the nuclear genome. Using developmental rate as a measure of fitness, we found that fast-developing copepods had higher ATP synthesis capacity than slow developers, suggesting variation in developmental rates is at least partly associated with mitochondrial dysfunction. Using Pool-seq, we detected strong biases for maternal alleles across 7 (of 12) chromosomes in both reciprocal crosses in high-fitness hybrids, whereas low-fitness hybrids showed shifts toward the paternal population. Comparison with previous results on a different hybrid cross revealed largely different patterns of strong mitonuclear coadaptation associated with developmental rate. Our findings suggest that functional coadaptation between interacting nuclear and mitochondrial components is reflected in strong polygenic effects on this life-history phenotype, and reveal that molecular coadaptation follows independent evolutionary trajectories among isolated populations.

Objectives To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. Materials and methods Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. Results Expression of tumour necrosis factor-α, interleukin-1β, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. Conclusions Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.

Objectives: Cancer-associated fibroblast (CAF) is among the most important tumor-host microenvironment components by affecting tumor progression. This study explored the role of miR-224 in CAF-induced non-small cell lung cancer (NSCLC). Materials and methods: A CAF-NSCLC cell co-culture model was established, and the miR-224 expression in CAF was detected by reverse transcription-polymerase chain reaction (RT-PCR). Gain- and loss- of experiments of miR-224 were implemented to verify the effects of CAF on NSCLC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and endothelial cell (EC) angiogenesis. Overexpressing genetic or pharmacological interventions were performed to explore the potential mechanisms of Sirtuins 3/AMP-activated protein kinase/mammalian target of rapamycin/hypoxia-inducible factor-1α (SIRT3/AMPK/mTOR/HIF-1α). Results: CAF enhanced the malignant phenotype of NSCLC cells and induced EC angiogenesis. miR-224 was significantly altered in CAFs. miR-224 up-regulation exacerbated NSCLC development mediated by CAFs, while miR-224 inhibition mostly reversed CAF-induced effects. Mechanistically, miR-224 targeted the 3’-untranslated regions (UTR) of SIRT3 mRNA, thereby inhibiting SIRT3/AMPK and activating mTOR/HIF-1α. Forced overexpression of SIRT3 up-regulated AMPK and inactivated mTOR/HIF-1α, while inhibiting HIF-1α markedly up-regulated SIRT3/AMPK and reduced mTOR phosphorylation. Interestingly, both Sirt1 overexpression and HIF-1α inhibition repressed miR-224 levels and miR-224-mediated promotive effects in NSCLC. Conclusion: The miR-224-SIRT3/AMPK/mTOR/HIF-1α axis formed a positive feedback loop in modulating CAF-induced carcinogenic effects on NSCLC.

ObjectiveThe present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism.MethodsRats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis.In vitro, the calcium content and ALP activity were measured, and RT-PCR (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed.ResultsIn the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression.ConclusionLanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

OBJECTIVE To investigate the effectiveness of molding custom-made insoles for female patients with foot pain. METHODS The study included 20 patients whose insoles were prescribed according to biomechanical evaluations and molded by repositioning the subtalar joint in its neutral position using a simple set of tools. Plantar biomechanics were measured under the following conditions: static stand, walking at self-comfortable walking speed (CWS) barefoot, walking in patient owned running shoes, and walking in running shoes plus insoles. Each patient's upper arm isometric muscle strength and subjective feelings before and after the insole intervention were assessed. RESULTS The molded insoles increased plantar contact area both during static standing and walking at CWS compared to the barefoot condition. The insoles also had more evenly distributed plantar contact area and loading rate, with the changes in the medial arch area being most significant. Moreover, the custom-made insole intervention immediately increased maximum resistance and duration of bilateral upper arms, as well as improved foot comfort, especially at the medial arch area during single leg squat tests. CONCLUSION Molding custom-made insoles by repositioning the subtalar joint in its neutral position can be accomplished with a simple set of tools, making this method highly applicable for a majority of less developed regions. Insoles molded using this method are effective in immediately improving plantar biomechanics disorders and enhancing isometric upper muscle performance in female patients with foot pain.

Transnational ivory traffickers continue to smuggle large shipments of elephant ivory out of Africa, yet prosecutions and convictions remain few. We identify trafficking networks on the basis of genetic matching of tusks from the same individual or close relatives in separate shipments. Analyses are drawn from 4,320 savannah (Loxodonta africana) and forest (L. cyclotis) elephant tusks, sampled from 49 large ivory seizures totalling 111 t, shipped out of Africa between 2002 and 2019. Network analyses reveal a repeating pattern wherein tusks from the same individual or close relatives are found in separate seizures that were containerized in, and transited through, common African ports. Results suggest that individual traffickers are exporting dozens of shipments, with considerable connectivity between traffickers operating in different ports. These tools provide a framework to combine evidence from multiple investigations, strengthen prosecutions and support indictment and prosecution of transnational ivory traffickers for the totality of their crimes.

To establish a prospective cohort of kindergarten children and longitudinally study the causes of early childhood caries.Cluster random sampling was used to select a kindergarten in the urban and suburban areas of Pudong New District of Shanghai, a total of 240 small-class children joined the study. Chi-square test, analysis of variance, binomial logistic regression model and general linear regression model was used to analyze caries of the cohort children at baseline and 1 year after follow-up with SPSS 21.0 software package.In the first two years of this cohort study, the follow-up rate was 88.3%, the caries rate in the first year of baseline and follow-up were 58.3% and 69.8%, and the mean dmft values were 3.1±4.2 and 4.5±4.9, respectively. 56.1% of children had new caries. Logistic regression results showed that children who lived in the suburbs (P=0.010) and ate candy more frequently (P=0.036) had higher rates of new caries. The results of general linear regression equation showed that children in the suburbs (P0.001), those who did not use fluoridated toothpaste (P=0.003) and those who ate candy more frequently (P=0.002) had higher new mean dmft values.Living in the suburbs, not using fluoride toothpaste and eating candy more frequently are important risk factors for new caries in preschool children in Pudong New District of Shanghai.

In this study, the performance of manganese oxide nanorods/reduced graphene oxide (MnOx/rGO) composite papers as anode for lithium-ion battery is investigated. The self-supporting and flexible composite papers are fabricated via traditional vacuum filtration. The crystal structure, chemical state and morphology are determined by XRD, XPS and SEM, respectively. And the electrochemical performance is measured by means of cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD) techniques. It is proved that the MnOx/rGO papers exhibit layer-by-layer structure in which rod-shaped MnOx is sandwiched among the rGO sheets. As anode for lithium-ion batteries, the capacity of MnOx/rGO paper can be stabilized at 518 mAh g−1 for 1500 charge/discharge cycles.

The adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)-mediated lipolysis play important roles in lipid catabolism. ATGL is considered the central rate-limiting enzyme in the mobilization of fatty acids in mammals. Currently, severe fat accumulation has been commonly detected in farmed fish globally. However, the ATGL-mediated lipolysis and the potential synergy among ATGL, HSL, and autophagy, which is another way for lipid breakdown, have not been intensively understood in fish. In the present study, we added Atglistatin as an ATGL-specific inhibitor into the zebrafish diet and fed to the fish for 5 weeks. The results showed that the Atglistatin-treated fish exhibited severe fat deposition, reduced oxygen consumption, and fatty acid β-oxidation, accompanied with increased oxidative stress and inflammation. Furthermore, the Atglistatin-treated fish elevated total and phosphorylation protein expressions of HSL. However, the free fatty acids and lipase activities in organs were still systemically reduced in the Atglistatin-treated fish, and the autophagy marker LC3 was also decreased in the liver. On the other hand, glycogenolysis was stimulated but blood glucose was higher in the Atglistatin-treated fish. The transcriptomic analysis also provided the hint that the protein turnover efficiency in Atglistatin-treated fish was likely to be accelerated, but the protein content in whole fish was not affected. Taken together, ATGL plays crucial roles in energy homeostasis such that its inhibition causes loss of lipid-sourced energy production, which cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients.

To compare the differences of influence of mothers' different socio-demographic background, their oral health status and feeding behavior on their one-month-old infants' risk of dental caries between Shanghai and Kunming, and to explore the factors affecting infants' risk of dental caries in different regions.One-month-old infants and their mothers from Huangpu district of Shanghai and Xishan district of Kunming were recruited in the study. Oral plaque samples of mothers and their infants were collected to assess their risk of dental caries. Statistical analysis was performed using SPSS 22.0 software package, and multivariate logistic regression analysis was used to screen the factors affecting the risk of infantile rickets in Shanghai and Kunming.A total of 165 mother-child pairs in Shanghai and 161 mother-child pairs in Kunming participated in the survey, and the proportion of infants who were at high risk of caries was 10.3% and 6.2%, respectively. The result of multivariate logistic analysis indicated that the infants whose mother smoked before pregnancy (OR=6.9, P=0.030) and attained lower education level (OR=6.1, P=0.035) had higher risk of caries in Shanghai; while in Kunming, the infants whose mother had higher DMFS values were at higher risk of caries (OR=1.1, P=0.031).Factors affecting one-month-old infants' risk of caries in Shanghai and Kunming were pre-pregnancy maternal cigarette smoking, mother's lower education level and mother's dental caries status, respectively.

Key points In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown. Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation. Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β-oxidation or autophagy weakened the fasting-induced cold resistance. Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting-induced cold resistance in fish. Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress. Abstract In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild-type or specific gene knock-out zebrafish models (carnitine palmitoyltransferase-1b-deficient strain, CPT1b-/- , or autophagy-related protein 12-deficient strain, ATG12-/- ), we verified that fasting-stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.

The projects which supported by National Natural Science Foundation of China(NSFC) including General Program, Young Scientist Fund, and Fund for Less Developed Regions, in field of pharmacology of traditional Chinese medicine in 2019 were reviewed. Based on these research items, the main contents and characteristics, as well as the main problems from academic and non-academic point of view, were summarized for reference.

Ethnopharmacological relevance Tao Hong Si Wu Decoction (THSWD) is a traditional prescription for blood management in traditional Chinese medicine, THSWD consists of Paeoniae Radix Alba (Paeonia lactiflora Pall.), Rehmanniae Radix Praeparata (Rehmannia glutinosa (Gaertn.) DC.), Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels), Chuanxiong Rhizoma (Conioselinum anthriscoides 'Chuanxiong'), Persicae Seman (Prunus persica (L.) Batsch) and Carthami Flos (Carthamus tinctorius L.) at a weight ratio of 3: 4: 3: 2: 3: 2. THSWD is a commonly used prescription in the treatment of postpartum blood stasis disease. Aim of the study To explore the potential mechanism of THSWD for the treatment of postpartum blood stasis using network pharmacology and experimental research. Materials and methods We extracted the active ingredients and targets in THSWD from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and constructed a herbs-ingredients-targets-disease-network, devised a protein-protein interaction (PPI) network, performed GO enrichment analysis, and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to discover potential treatment mechanisms. A postpartum blood stasis model was established in rats, and the results of network pharmacology were verified by in vivo experiments. Results The results showed that 69 potential active ingredients and 207 THSWD target genes for the treatment of postpartum blood stasis disease were obtained after ADME filtering analysis. The targets were enriched in multiple gene functions and different signaling pathways. By exploring various different signaling pathways, it was found that mitochondrial regulation of oxidative stress plays a potentially important role in the treatment of postpartum blood stasis with THSWD. Compared to model group, THSWD alleviated mitochondrial damage, decreased levels of oxidative stress in the rat model of postpartum blood stasis and reduced apoptosis in uterine cells. Conclusion The therapeutic effect of THSWD on postpartum blood stasis is likely related to mitochondrial regulation of oxidative stress, which paves the way for further research investigating its mechanisms.

In recent years, alongside with the convergence of In-vehicle network (IVN) and wireless communication technology, vehicle communication technology has been steadily progressing. Furthermore, communication with various external networks—such as cloud, vehicle-to-vehicle (V2V), and vehicle-to-infrastructure (V2I) communication networks—further reinforces the connectivity between the inside and outside of a vehicle. On the contrary, this means that the functions of existing vehicles using computer-assisted mechanical mechanisms can be manipulated and controlled by a malicious packet attack. Therefore, diversified and advanced architectures of vehicle systems can significantly increase the accessibility of the system to hackers and the possibility of an attack. This paper proposes an intrusion detection method for vehicular networks based on the survival analysis model. Our main aims were to identify malicious CAN messages and accurately detect the normality and abnormality of a vehicle network without semantic knowledge of the CAN ID function. To this end, normal and abnormal driving data were extracted from three different types of vehicles and we evaluated the performance of our proposed method by measuring the accuracy and the time complexity of anomaly detection by considering three attack scenarios and the periodic characteristics of CAN IDs. Based on the results, we concluded that a CAN ID with a long cycle affects the detection accuracy and the number of CAN IDs affects the detection speed. The difference in the detection accuracy between applying all CAN IDs and CAN IDs with a short cycle is not considerable with some differences observed in the detection accuracy depending on the chunk size and the specific attack type. High detection accuracy and low computational cost will be the essential factors for real-time processing of IVN security. Taken together, the results of the present study contribute to the current understanding of how to correctly manage vehicle communications for vehicle security and driver safety.

We recently characterized a novel bifunctional agonist for opioid and neuropeptide FF receptors, named BN-9, which exhibited potent analgesia in the mouse tail-flick test when given centrally. To further evaluate its potential therapeutic efficacy for translational-medical development, the current work was performed to explore the antinociceptive activities of intraperitoneal (i.p.) administration of BN-9 in mouse models of tail-flick assay, formalin pain, visceral pain and post-operative pain. In the tail-flick test, BN-9 induced a dose-related antinociceptive effect, which was fully blocked by systemic pretreatment with the peripheral acting opioid receptor antagonist naloxone methiodide, but not supraspinal naloxone methiodide, implying the involvement of the peripheral opioid receptors. In addition, the systemic antinociception of BN-9 was antagonized by the selective antagonists of the μ- and κ-opioid receptors, independently of the δ-opioid and neuropeptide FF receptors. Similarly, dose-dependent analgesia was also produced by systemic BN-9 in different pain models via the peripheral opioid receptors, independently of the neuropeptide FF receptors. Furthermore, the side-effects of systemic BN-9 on motor performance, tolerance development and gastrointestinal transit inhibition were also evaluated. Repeated systemic injection of BN-9 produced non-tolerance analgesia over 8 days. Compared with morphine, intraperitoneal administration of BN-9 exerted less inhibition of gastrointestinal transit. These data show that BN-9 induced systemic analgesia with reduced side-effects on tolerance and constipation. This article suggests that systemic injection of BN-9 causes effective antinociception in different preclinical pain models via the peripheral opioid receptors, providing an attractive approach to develop peripherally acting opioid analgesics with multiple targeting properties.

Basic oxygen furnace (BOF) slag contains a significant amount of iron-containing species, which is considered to be iron resources and therefore need to be recovered. In this work, the oxidation be ...

Estimation of carbon and nitrogen stocks is important for quantifying carbon and nitrogen sequestration as well as greenhouse gas emissions and inventorying national carbon and nitrogen balances. For Liaoning province of China, we estimated the vertical distribution of soil organic carbon (SOC), soil total nitrogen (STN), bulk density (BD), and mapped their spatial distribution at five standard soil depth intervals (0–5, 5–15, 15–30, 30–60 and 60–100 cm) using nine environmental variables as predictors including precipitation, temperature, land use, elevation, system for automated geoscientific analyses (SAGA) wetness index, and Normalized Difference Vegetation Index (NDVI). The highest average contents of SOC and STN were 15.2 g kg − 1 and 1.6 g kg − 1 in the 0–5 cm soil layer, and 1.5 g kg − 1 SOC and 0.4 g kg − 1 STN in the 60–100 cm soil layer, respectively. The prediction precision for SOC, STN and BD all decreased with soil depth. Average SOC and STN stocks for 0–30 cm were 3.1 kg m − 2 and 0.5 kg m − 2 , respectively. For the top 1 m, SOC and STN were 4.5 kg m − 2 and 0.9 kg m − 2 , respectively. In total, the soils stored approximately 588 Tg SOC and 128 Tg STN within the top 1 m. The soils under forest had the highest amount of carbon (356 Tg) and nitrogen (58 Tg) followed by agriculture and wetland that contributed 34% and 48% of the total stock, respectively. > 91% of the total SOC and STN stocks were in Argosols and Cambosols. We adopted a digital soil mapping method to map the spatial distribution of SOC and STN stocks and predict their uncertainties. The estimation was validated with a 10-fold cross-validation procedure. The data and high-resolution maps from this study can be used for future soil carbon and nitrogen assessment and inventorying.

A steel slag has been treated by air granulation, in order to enhance cementitious properties of the slag. Two samples with sizes ranged 1.68-2.38mm and 212-297μm and coded as Slag A and Slag B, respectively, were chosen from the granulated slag for investigations. A sample of the original steel slag was also studied. XRD analyses indicated the formations of α-C2S, β-C2S, C2F, C2MS2, f-MgO and α-C2S, C2F, f-MgO in Slag A and Slag B, respectively. The phases in the two slag samples were quite different from the phases found in steel slag. The SEM results show a reduction of C2S sizes from 10-20μm for the steel slag to nano-scales by air quenching for Slag B. This treatment of air quenching has increased the cumulative heat of hydration to 105.35J/g measured for Slag B, almost two times greater than that of the steel slag. The study results demonstrate a high potential for utilizations of the steel slag in cement and concrete applications after the slag treatment by air quenching. The treatment may thus lead to an environmental friendly and cost-effective recycling for the steel slag. This can also contribute to the sustainable developments in the steel and cement/concrete industries.

Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. Moreover, hemopressin and its truncated peptides were also reported to produce a slight modulatory effect on opioid system. In the present work, based on the amino acid sequence analyses of hemoglobin subunit α, rat VD-hemopressin(α) [(r)VD-Hpα] was predicted as a cannabinoid peptide derived from rat α-hemoglobin. Furthermore, (r)VD-Hpα was synthesized and characterized in a series of in vitro and in vivo assays. Our results demonstrated that (r)VD-Hpα induced neurite outgrowth in Neuro 2A cells via CB1 receptor. In the tail-flick assay, (r)VD-Hpα dose-dependently exerted central antinociception through CB1 receptor, but not CB2 and opioid receptors. In mice, supraspinal administration of (r)VD-Hpα produced dose-dependent hypothermia, which was partially reduced by the CB1 receptor antagonist AM251, but not by the antagonists of CB2 and opioid receptors. In addition, (r)VD-Hpα caused hypoactivity after intracerebroventricular injection, and this effect was insensitive to the antagonists of cannabinoid and opioid receptors. Further assessment of the side-effects demonstrated that (r)VD-Hpα evoked the limited effects on gastrointestinal transit at antinociceptive doses, but repeated i.c.v. injection of (r)VD-Hpα induced development of antinociceptive tolerance. Taken together, these data suggest that the predicted peptide (r)VD-Hpα produces antinociception, hypothermia and hypoactivity via different pharmacological mechanisms, at least partially, which may offer an attractive strategy for separating cannabinoid analgesia from hypoactivity. Moreover, it implies that (r)VD-Hpα has therapeutic potential in pain management with limited side-effects.

The production of belite-calcium sulfoaluminate-ferrite (BCSAF) cement with the addition of industrial wastes as feedstock has been studied for many years. The preparation of clinkers is essential in cement production, in which all raw materials react with each other to generate key phases in cement under some specified conditions. The objective of this study was to investigate the sintering characteristics of BCSAF cement clinkers. Four BCSAF clinkers with different compositions were examined. High-temperature microscopy, quantitative x-ray powder diffraction analysis and scanning electron microscopy were used to analyse sintering features and phase composition. The results show that the use of wastes from the production of manganese and magnesium metals, which were added to the raw materials to make clinker pellets, can significantly reduce the firing temperature of BCSAF clinker. The firing temperatures of clinkers with added wastes were below 1300°C, much lower than the temperature used for convention...