Research on the mechanism of government-industry-university-research collaboration for cultivating innovative talent based on game theory.

The assessment of colleges' effectiveness heavily relies on the employment status of graduates. Government-industry-university-research (GIUR) collaboration in cultivation talent is the key to improving the employment rate of college graduates. Based on the theoretical framework of the triple helix, this study develops a tripartite evolutionary game model that encompasses government, enterprises, and university research institutions. The research findings indicate (1) the evolutionary convergence of strategies among the subjects of the three-party game. (2) The attainment of a stable ideal evolution state for (1,1,1) is possible when the requisite conditions are met. This suggests that the cultivation of aligned talent in GIUR collaborations should coordinate the interests of various stakeholders. (3) Drawing inspiration from parameter-sensitive simulation, the problem of mismatch between talent cultivation and social demand can be effectively addressed through measures such as reducing the cost of cooperation, balancing the distribution of benefits, and implementing appropriate reward and punishment mechanisms. In response to these implications, we put forward some management insights and suggestions.

The down-regulation of STC2 mRNA may serve as a biomarker for death from mechanical asphyxia.

Death from mechanical asphyxia (DMA) is a common cause of death in forensic pathology. However, due to the lack of biomarkers, the authentication of DMA now relies on a series of non-specific signs, which may cause troubles in the judicial trials, especially when the criminal scene is not fully elucidated. To search for the potential biomarkers for DMA, brain samples of DMA and craniocerebral injury groups were screened by microarray. The obtained mRNAs were validated by animal and human samples. Primary cell culture was conducted to explore the biochemical changes under hypoxia. 415 differentially expressed mRNAs between two groups were discovered. Ten mRNAs were examined in both human and animal samples died of different causes of death. Stanniocalcin-2 (STC2) showed significant down-regulation in DMA samples compared to other groups, regardless of PMI, age, or temperature. Cellular experiments indicated that ROS level peaked after 15-min-hypoxic culture, when the expression level of STC2 was significant down-regulated simultaneously. The ER-stress-related proteins also showed potential connection with STC2. In general, it is indicated that the down-regulation of STC2 may serve as a biomarker for DMA.

Retrospective Analysis of Death Cases of Oral Diphenidol Hydrochloride Poisoning.

OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

Detection of dextran, maltodextrin and soluble starch in the adulterated Lycium barbarum polysaccharides (LBPs) using Fourier-transform infrared spectroscopy (FTIR) and machine learning models.

Due to the similar chemical structures and physicochemical properties, it is challenging to distinguish dextran, maltodextrin, and soluble starch from the polysaccharide products of plant origin, such as Lycium barbarum polysaccharides (LBPs). Using the first-order derivatives of Fourier-transformed infrared spectroscopy (FTIR, wave range 1800-400 cm-1), this study proposed a two-step pipeline to identify dextran, maltodextrin, and soluble starch from adulterated LBPs samples qualitatively and quantitatively. We applied principal component analysis (PCA) to reduce the dimensionality of FTIR features. For the qualitative step, a set of machine learning models, including logistic regression, support vector machine (SVM), Naïve Bayes, and partial least squares (PLS), were used to classify the adulterants. For the quantitative step, linear regression, LASSO, random forest, and PLS were used to predict the concentration of LBPs adulterants. The results showed that logistic regression and SVM are suitable for classifying adulterants, and random forests is superior for predicting adulterant concentrations. This would be the first attempt to discriminate the adulterants from the polysaccharide's product of plant origin. The proposed two-step methods can be easily extended to other applications for the quantitative and qualitative detection of samples from adulterants with similar chemical structures.

Research Progress on Molecular Changes in Pulmonary Hypoxia and Cause of Death Identification in Mechanical Asphyxia.

Lung is the largest organ of the respiratory system. During hypoxia, pulmonary cells undergo rapid damage changes and activate the self-rescue pathways, thus leading to complex biomacromolecule modification. Death from mechanical asphyxia refers to death due to acute respiratory disorder caused by mechanical violence. Because of the absence of characteristic signs in corpse, the accurate identification of mechanical asphyxia has always been the difficulty in forensic pathology. This paper reviews the biomacromolecule changes under the pulmonary hypoxia condition and discusses the possibility of application of these changes to accurate identification of death from mechanical asphyxia, aiming to provide new ideas for related research.

The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway.

When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known about the maintenance of nascent hepatocytes in post-injured environments. Here, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a mutant containing a nonsense mutation in the gene nibrin (nbn), which encodes a component of the Mre11-Rad50-Nbn (MRN) complex that activates DNA damage response (DDR). The regenerated hepatocytes cannot be maintained and exhibit apoptosis in the mutant. Mechanistically, the nbn mutation results in the abrogation of ATR-Chk1 signaling and accumulations of DNA damage in nascent hepatocytes, which eventually induces p53-mediated apoptosis. Furthermore, loss of rad50 or mre11a shows similar phenotypes. This study reveals that the activation of DDR by the MRN complex is essential for the survival of BEC-derived hepatocytes, addressing how to maintain nascent hepatocytes in the post-injured environments.

Pax4-Ghrelin mediates the conversion of pancreatic ε-cells to ß-cells after extreme ß-cell loss in zebrafish.

Pancreatic ε-cells producing ghrelin are one type of endocrine cell found in islets, which have been shown to influence other intra-islet cells, especially in regulating the function of ß cells. However, the role of such cells during ß-cell regeneration is currently unknown. Here, using a zebrafish nitroreductase (NTR)-mediated ß-cell ablation model, we reveal that ghrelin-positive ε-cells in the pancreas act as contributors to neogenic ß-cells after extreme ß-cell loss. Further studies show that the overexpression of ghrelin or the expansion of ε-cells potentiates ß-cell regeneration. Lineage tracing confirms that a proportion of embryonic ε-cells can transdifferentiate to ß-cells, and that the deletion of Pax4 enhances this transdifferentiation of ε-cells to ß-cells. Mechanistically, Pax4 binds to the ghrelin regulatory region and represses its transcription. Thus, deletion of Pax4 derepresses ghrelin expression and causes producing more ghrelin-positive cells, enhancing the transdifferentiation of ε-cells to ß-cells and consequently potentiating ß-cell regeneration. Our findings reveal a previously unreported role for ε-cells during zebrafish ß-cell regeneration, indicating that Pax4 regulates ghrelin transcription and mediates the conversion of embryonic ε-cells to ß-cells after extreme ß-cell loss.

Adsorption of hydrogen sulfide by iron-based adsorbent derived from fly ash and iron slag.

In this article, an innovative sorbent (Fe-FA) is prepared from fly ash; ferrous sulfate-containing waste slag (FSS), which are industrial wastes; and NaOH by a hydrothermal method at 100 °C. As a result, in comparison to several conventional sorbents, such as ZnO, Fe2O3, 13X zeolite, and activated carbon, Fe-FA had the best adsorption performance for H2S adsorption. Fe-FA had not only a higher adsorption capacity (near 150 mg/g) but also a longer breakthrough time (near 400 min) when gas hourly space velocity was 8000 h-1. Then, characterizations of XRD, BET, NH3-TPD, FTIR, and XPS analyzed basic properties of Fe-FA and revealed reasons for the excellent adsorption performance. In general, the excellent adsorption performance of Fe-FA for H2S is mainly due to the high content of iron species (almost 50%) and suitable mesoporous structure in the Fe-FA.

Rngtt governs biliary-derived liver regeneration initiation by transcriptional regulation of mTORC1 and Dnmt1 in zebrafish.

In cases of end-stage liver diseases, the proliferation of existing hepatocytes is compromised, a feature of human chronic liver disease, in which most hepatocytes are dysfunctional. So far, liver transplantation represents the only curative therapeutic solution for advanced liver diseases, and the shortage of donor organs leads to high morbidity and mortality worldwide. The promising treatment is to prompt the biliary epithelial cells (BECs) transdifferentiation. However, the critical factors governing the initiation of BEC-derived liver regeneration are largely unknown. The zebrafish has advantages in large-scale genetic screens to identify the critical factors involved in liver regeneration. Here, we combined N-ethyl-N-nitrosourea screen, positional cloning, transgenic lines, antibody staining, and in situ hybridization methods and identified a liver regeneration defect mutant ( lrd ) using the zebrafish extensive liver injury model. Through positional cloning and genomic sequencing, we mapped the mutation site to rngtt . Loss of rngtt leads to the defects of BEC dedifferentiation, bipotential progenitor cell activation, and cell proliferation in the initiation stage of liver regeneration. The transdifferentiation from BECs to hepatocytes did not occur even at the late stage of liver regeneration. Mechanically, Rngtt transcriptionally regulates the attachment of mRNA cap to mTOR complex 1 (mTORC1) components and dnmt1 to maintain the activation of mTORC1 and DNA methylation in BECs after severe liver injury and prompt BEC to hepatocyte conversion. Furthermore, rptor and dnmt1 mutants displayed the same liver regeneration defects as rngtt mutation. In conclusion, our results suggest Rngtt is a new factor that initiates BEC-derived liver regeneration.

Comparative Study on the Structural Properties and Bioactivities of Three Different Molecular Weights of Lycium barbarum Polysaccharides.

The molecular weight, the triple-helix conformation, the monosaccharide content, the manner of glycosidic linkages, and the polysaccharide conjugates of polysaccharides all affect bioactivity. The purpose of this study was to determine how different molecular weights affected the bioactivity of the Lycium barbarum polysaccharides (LBPs). By ethanol-graded precipitation and ultrafiltration membrane separation, one oligosaccharide (LBPs-1, 1.912 kDa) and two polysaccharides (LBPs-2, 7.481 kDa; LBPs-3, 46.239 kDa) were obtained from Lycium barbarum. While the major component of LBPs-1 and LBPs-2 was glucose, the main constituents of LBPs-3 were arabinose, galactose, and glucose. LBPs-2 and LBPs-3 exhibited triple-helix conformations, as evidenced by the Congo red experiment and AFM data. Sugar residues of LBPs-2 and LBPs-3 were elucidated by NMR spectra. The polysaccharides (LBPs-2 and LBPs-3) exhibited much higher antioxidant capacities than oligosaccharide (LBPs-1). LBPs-3 showed higher oxygen radical absorbance capacity (ORAC) and superoxide dismutase (SOD) activity than LBPs-2, but a lower capability for scavenging ABTS+ radicals. In zebrafish, LBPs-2 and LBPs-3 boosted the growth of T-lymphocytes and macrophages, enhanced the immunological response, and mitigated the immune damage generated by VTI. In addition to the molecular weight, the results indicated that the biological activities would be the consequence of various aspects, such as the monosaccharide composition ratio, the chemical composition, and the chemical reaction mechanism.

Monitoring the fluctuations of cysteine activity in living cells using a near-infrared fluorescence probe.

Cysteine (Cys) is one of the most common cellular biothiols and is closely implicated in numerous diseases such as edema, psoriasis, Parkinson's disease, and liver damage. Therefore, detecting Cys activity in complex living organisms is highly necessary for diagnosing related diseases. This study synthesized a near-infrared (NIR) Cys-special probe (MCyA) by introducing an acrylate group to the MCyOH fluorophore. Consequently, Cys could precisely and quickly "light up" strong NIR fluorescence (711 nm) by transforming MCyA into MCyOH. Additionally, MCyA was applied to systematically detect dynamic fluctuations of Cys activity in living cells under different stimulation. The observations indicated that the endogenous Cys activity was depressed when HepG2 cells were under oxidative stress status; however, a dramatic expansion of Cys levels in HepG2 cells with omeprazole stimulation. In particular, MCyA has been successfully used to image the upregulation of Cys level in HepG2 cells in the presence of methionine (Met). Overall, MCyA would be a novel and practical tool to study Cys-related physiological and pathological processes.

Functional screening of congenital heart disease risk loci identifies 5 genes essential for heart development in zebrafish.

Congenital heart disease (CHD) is the most common birth defect worldwide and a main cause of perinatal and infant mortality. Our previous genome-wide association study identified 53 SNPs that associated with CHD in the Han Chinese population. Here, we performed functional screening of 27 orthologous genes in zebrafish using injection of antisense morpholino oligos. From this screen, 5 genes were identified as essential for heart development, including iqgap2, ptprt, ptpn22, tbck and maml3. Presumptive roles of the novel CHD-related genes include heart chamber formation (iqgap2 and ptprt) and atrioventricular canal formation (ptpn22 and tbck). While deficiency of maml3 led to defective cardiac trabeculation and consequent heart failure in zebrafish embryos. Furthermore, we found that maml3 mutants showed decreased cardiomyocyte proliferation which caused a reduction in cardiac trabeculae due to inhibition of Notch signaling. Together, our study identifies 5 novel CHD-related genes that are essential for heart development in zebrafish and first demonstrates that maml3 is required for Notch signaling in vivo.

Notch-Sox9 Axis Mediates Hepatocyte Dedifferentiation in KrasG12V-Induced Zebrafish Hepatocellular Carcinoma.

Liver cancer is one of the most prevalent cancers in humans. Hepatocytes normally undergo dedifferentiation after the onset of hepatocellular carcinoma, which in turn facilitates the progression of cancer. Although the process of hepatocellular carcinoma dedifferentiation is of significant research and clinical value, the cellular and molecular mechanisms underlying it are still not fully characterized. We constructed a zebrafish liver cancer model based on overexpression of the oncogene krasG12V to investigate the hepatocyte dedifferentiation in hepatocellular carcinoma. We found that, after hepatocarcinogenesis, hepatocytes dedifferentiated and the Notch signaling pathway was upregulated in this progress. Furthermore, we found that inhibition of the Notch signaling pathway or deficiency of sox9b both prevented hepatocyte dedifferentiation following hepatocellular carcinoma induction, reducing cancer metastasis and improving survival. In conclusion, we found that hepatocytes undergo dedifferentiation after hepatocarcinogenesis, a process that requires Notch signaling and likewise the activation of Sox9.

Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration.

Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.

[Analysis of spectrum-activity relationship among antioxidant parts of Lycii Fructus using three different chemometrics methods].

The chemical components of Lycii Fructus were analyzed by liquid chromatography( LC) and mass spectrometry( MS for the establishment of spectrum-activity relationship,on the basis of which its antioxidant active ingredients were determined. In this experiment,Lycii Fructus was extracted with different solvents and then separated into 80 samples by macroporous adsorption resin and reversed-phase chromatography,respectively. The antioxidant components were enriched into 11 samples and their scavenging abilities against DPPH free radical and ferric ion reducing antioxidant power( FRAP) were significantly stronger than those before the treatment( P<0. 05). The spectrum-activity relationship regarding the antioxidant activity in vitro of Lycii Fructus was established by Pearson correlation analysis,orthogonal partial least squares( OPLS) and elastic net regression. Six chromatographic peaks greatly contributing to the antioxidant activity in vitro of Lycii Fructus were identified as rutin( P6),quercetin( P35),scopoletin( P14),N-cis-feruloyl-4-O-ß-D-glucopyranosyl-tyramine or N-( 4-O-ß-D-glucopyranosyl-trans-feruloyl)-tyramine( P8), ferulic acid( P13) and1,3,5-dihydroxy-2-isoprenyl-3-xanthone( P23). The active components associated with free radical scavenging were rutin and quercetin both belonging to flavonoids. The reduction of Fe3+was based on phenylpropanoids such as ferulic acid,scopoletin,xanthone and phenolic amides. These results indicated that the antioxidant activity of Lycii Fructus was ascribed to the synergistic action of different products through different ways. Besides,the data analysis model should be chosen carefully for the establishment of spectrum-activity relationship,thus ensuring the reliability of results.

Model for the prediction of mechanical asphyxia as the cause of death based on four biological indexes in human cardiac tissue.

Determination of mechanical asphyxia as the cause of death has always been difficult for forensic pathologists, particularly when signs of asphyxia are not obvious on the body. Currently, depending on only physical examination of corpses, pathologists must be cautious when making cause-of-death appraisals. In a previous study, four biomarkers-dual-specificity phosphatase 1 (DUSP1), potassium voltage-gated channel subfamily J member 2 (KCNJ2), miR-122, and miR-3185-were screened in human cardiac tissue from cadavers that died from mechanical asphyxia compared with those that died from craniocerebral injury, hemorrhagic shock, or other causes. Expression of the markers correlated with death from mechanical asphyxia regardless of age, environmental temperature, and postmortem interval. However, a single biological index is not an accurate basis for the identification of the cause of death. In this study, receiver operating characteristic curves of the ΔCq values of the four indexes were generated. The diagnostic accuracy of the indexes was judged according to their area under the curve (DUSP1: 0.773, KCNJ2: 0.775, miR-122: 0.667, and miR-3185: 0.801). Finally, a nomogram was generated, and single blind experiment was conducted to verify the cause of death of mechanical asphyxia.

Fixation stability of glass matrix co-existent with crystal phases for heavy metals formed by high-temperature vitrification.

Vitrification is an effective solidification method for heavy metal-containing wastes. However, most investigations focused on the formation of glass matrix. Seldom report discussed the influence of co-existing crystals on heavy metal stabilizations. In this work, Ca-Al-Si phase was formed in the glass matrix by adjusting the composition of feeding ingredient and melting temperature. As a result, when molar ratio of CaO/(SiO2+Al2O3) was lower than 0.97 and reaction temperature was bigger than 1300 °C, small-size Ca-Al-Si phase (Ca2Al2SiO7 and CaAl2Si2O8) was homogeneously distributed in vitreous matrix. At the same time, Cr, Zn, and Pb leaching concentrations were the lowest, far lower than the leaching standard values. According to theoretical calculations, Zn and Pb replaced Ca atom; Cr replaced Al atom in Ca-Al-Si phase under thermal conditions. These replacements resulted in the fixation and stabilization of heavy metals. When the CaO/(SiO2+Al2O3) molar ratio was bigger than 1.00, neither glass nor Ca-Al-Si was formed. Similarly, when the melting temperature was decreased, Ca-Al-Si phase formed a bigger size. Both these went against the stabilization, resulting in high leaching concentrations of heavy metals. The main of this work will help the development of high-temperature melting for the treatment of hazardous wastes.

Synthesis of Acryl Group-Modified Adsorption Resins and Their Adsorption Properties for Matrine and Oxymatrine in Aqueous Solutions.

Three series of resins with different functional groups (PS-EA, PS-MP, and PS-BA) based on D101 copolymer were prepared via the atom transfer radical polymerization method. The adsorption capacities of functionalized resins toward matrine (MT) and oxymatrine (OM) depended on the specific surface area, the surface chemistry, and the good polarity match between the target compound and porous material. It is noted that the accumulation of functional groups uploaded on the surface of resins increased the adsorption affinity difference between the MT-functionalized resin system and OM-modified copolymer system. The selectivity of modified resins to MT and OM would attribute to polarity matching. The results could provide a possible strategy for the design of efficient adsorbents applied for the isolation the bioactive compound from complex natural products.

Rational design of a near-infrared fluorescence probe for highly selective sensing butyrylcholinesterase (BChE) and its bioimaging applications in living cell.

In the current work, a near-infrared (NIR) fluorescent probe (CyClCP) was developed for fast (35 min), highly sensitive (LOD of 3.75 U/L) and selective response to BChE in vitro and in vivo. Upon the addition of BChE, CyClCP could be efficiently activated with remarkable NIR (λem = 708 nm) fluorescence enhancement and obvious absorbance red shift (581 nm-687 nm). Specifically, according to the subtle differences structural features and substrate preference between BChE and its sister enzyme AChE, CyClCP was constructed by introducing chlorine atom at the ortho-position of the phenolic hydroxyl in the previous reported probe (CyCP). Fortunately, CyClCP exhibited better selectivity towards BChE over AChE compared with CyCP. This molecular design strategy was further rationalized by docking molecular of fluorescence probes (CyClCP and CyCP) and enzymes (BChE and AChE). Finally, CyClCP was membrane permeable and successfully applied to image endogenous BChE level in HepG2 and LO2 cells. Therefore, CyClCP could serve as a promising tool for BChE-related physiological function studies in complex biological systems.