A new machine learning model to predict the prognosis of cardiogenic brain infarction.

Cardiogenic cerebral infarction (CCI) is a disease in which the blood supply to the blood vessels in the brain is insufficient due to atherosclerosis or stenosis of the coronary arteries in the patient's heart, which leads to neurological deficits. To predict the pathogenic factors of cardiogenic cerebral infarction, this paper proposes a machine learning based analytical prediction model. 494 patients with CCI who were hospitalized for the first time were consecutively included in the study between January 2017 and December 2021, and followed up every three months for one year after hospital discharge. Clinical, laboratory and imaging data were collected, and predictors associated with relapse and death in CCI patients at six months and one year after discharge were analyzed using univariate and multivariate logistic regression methods, meanwhile established a new machine learning model based on the enhanced moth-flame optimization (FTSAMFO) and the fuzzy K-nearest neighbor (FKNN), called BITSAMFO-FKNN, which is practiced on the dataset related to patients with CCI. Specifically, this paper proposes the spatial transformation strategy to increase the exploitation capability of moth-flame optimization (MFO) and combines it with the tree seed algorithm (TSA) to increase the search capability of MFO. In the benchmark function experiments FTSAMFO beat 5 classical algorithms and 5 recent variants. In the feature selection experiment, ten times ten-fold cross-validation trials showed that the BITSAMFO-FKNN model proved actual medical importance and efficacy, with an accuracy value of 96.61%, sensitivity value of 0.8947, MCC value of 0.9231, and F-Measure of 0.9444. The results of the trial showed that hemorrhagic conversion and lower LVDD/LVSD were independent risk factors for recurrence and death in patients with CCI. The established BITSAMFO-FKNN method is helpful for CCI prognosis and deserves further clinical validation.

Electrical and magnetic properties of antiferromagnetic semiconductor MnSi2N4 monolayer.

Two-dimensional antiferromagnetic semiconductors have triggered significant attention due to their unique physical properties and broad application. Based on first-principles calculations, a novel two-dimensional (2D) antiferromagnetic material MnSi2N4 monolayer is predicted. The calculation results show that the two-dimensional MnSi2N4 prefers an antiferromagnetic state with a small band gap of 0.26 eV. MnSi2N4 has strong antiferromagnetic coupling which can be effectively tuned under strain. Interestingly, the MnSi2N4 monolayer exhibits a half-metallic ferromagnetic properties under an external magnetic field, in which the spin-up electronic state displays a metallic property, while the spin-down electronic state exhibits a semiconducting characteristic. Therefore, 100% spin polarization can be achieved. Two-dimensional MnSi2N4 monolayer has potential application in the field of high-density information storage and spintronic devices.

MicroRNA-190-5p confers chlorantraniliprole resistance by regulating CYP6K2 in Spodoptera frugiperda (Smith).

The fall armyworm Spodoptera frugiperda (Smith) (FAA) is responsible for considerable losses in grain production, and chemical control is the most effective strategy. However, frequent insecticide application can lead to the development of resistance. In insects, cytochrome P450 plays a crucial role in insecticide metabolism. CYP6K2 is related to FAA resistance to chlorantraniliprole. However, the regulatory mechanism of CYP6K2 expression is poorly understood. In this study, a conserved target of isolated miRNA-190-5p was located in the 3' UTR of CYP6K2 in FAA. A luciferase reporter analysis showed that in FAA, miRNA-190-5p can combine with the 3'UTR of CYP6K2 to suppress its expression. Injected miRNA-190-5p agomir significantly reduced CYP6K2 abundance by 54.6% and reduced tolerance to chlorantraniliprole in FAA larvae, whereas injected miRNA-190-5p antagomir significantly increased CYP6K2 abundance by 1.77-fold and thus improved chlorantraniliprole tolerance in FAA larvae. These results provide a basis for further research on the posttranscriptional regulatory mechanism of CYP6K2 and will facilitate further study on the function of miRNAs in regulating tolerance to chlorantraniliprole in FAA.

Effect of Magnesium Supplementation on Chronic Kidney Disease-Mineral and Bone Disorder in Hemodialysis Patients: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Research about the effects of magnesium (Mg) supplementation on chronic kidney disease-mineral bone disorder (CKD-MBD) among hemodialysis (HD) patients is controversial. Thus, we conducted a meta-analysis to examine Mg supplementation's effects on CKD-MBD in patients requiring dialysis. METHODS: The PubMed and EMBASE databases were searched for English language studies up to September 2020. The main indicators of our study were changes in serum Mg, calcium (Ca), phosphate, parathyroid hormone (PTH), and C-reactive protein levels, and carotid intima-media thickness (CIMT) after Mg supplementation. Mg efficacy was evaluated by weighted mean difference (WMD) and confidence intervals (CIs), and subgroup analyses of intervention type and intervention duration were also performed. RESULTS: Eight eligible studies comprising 309 HD patients were included in our meta-analysis. Mg supplementation alone produced a negative effect on serum PTH levels (WMD = -236.56; 95% CI -349.71 to -123.41) and CIMT (WMD = -0.18; 95% CI -0.34 to -0.01). A subgroup analysis based on intervention type showed a significant improvement in serum Mg (WMD = 1.08; 95% CI 0.51-1.64) and Ca (WMD = -0.50; 95% CI -0.77 to -0.23) levels when Mg was administered via dialysate and oral medication, respectively. Different intervention durations had no effect on serum Mg levels. Mg supplementation had no significant effect on serum phosphate (WMD = -0.25; 95% CI -0.64 to 0.14) and C-reactive protein levels (WMD = -0.02; 95% CI -2.80 to 2,76). CONCLUSIONS: Our results showed that Mg supplementation alone could improve CKD-MBD by regulating serum Ca and PTH metabolism and decreasing CIMT among HD patients.

[Effects of Heat Treatment Conditions on Shape Memory Recovery of NiTi Self-expanding Vascular Stents].

Effects of heat treatment conditions (including temperature and time) on the shape memory recovery and corrosion resistance of NiTi self-expanding vascular stents were studied based on working mechanism and clinical use. The Af temperature, dimensional recovery, crush resistance with radially applied load and point applied load of stents and corrosion resistance were characterized in diffident heat treatment conditions. The research results allow the conclusion that the stent treated at 500 ℃ for 10 min has optimum performance, and corrosion resistance meets the requirements.

Effect of local anti-vascular endothelial growth factor therapy to prevent the formation of stenosis in outflow vein in arteriovenous fistula.

BACKGROUND AND OBJECTIVES: Vascular stenosis and angiogenesis are the major causes of short expectancy of arteriovenous fistula (AVF). Increased expression of vascular endothelial growth factor-A (VEGF-A) has been suggested to play an important role in the pathophysiologic process. Anti-VEGF has been proved to be effective on anti-angiogenesis and applied in clinical practice, but its effect on anti-stenosis remains to be verified before it could be applied to prevent stenosis of AVF. This study was aimed to evaluate the effect of local anti-VEGF therapy to prevent the formation of stenosis in the outflow vein in AVF and its mechanism. METHODS: Bioinformatics of VEGF-A and its downstream-regulated molecules from the STRING PPI database were analyzed in this study. The biopsy samples from outflow veins of AVF in patients and C57BL/6 mouse models were analyzed to examine the mechanisms of pathologic vascular stenosis associated with VEGF pathways and their potential therapeutic targets. RESULTS: We found that the reduction of VEGF-A could downregulate downstream molecules and subsequently reduce the intimal hyperplasia and abnormal vascular remodeling by analyzing the STRING PPI database. Venous wall thickening, intimal neointima formation, and apoptosis of vascular endothelial cells in the proliferative outflow vein of the AVF were significantly more obvious, and upregulation of expression of VEGF was observed in dysfunctional AVF in patients. In mouse models, the expression of VEGF, Ephrin receptor B4 (EphB4), matrix metalloproteinase (MMP)2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, and caspase 3 in the control-shRNA surgical group was significantly higher than in the sham group (P < 0.05), and all of these indicators were significantly lower in lentiviral transfection group and Avastin group than in control-shRNA surgical group (P < 0.05) on the 14th day after AVF operation. CONCLUSION: VEGF expression is significantly increased in vascular endothelial cells in stenosed or occluded outflow veins of dysfunctional AVF. Local injection of Avastin into the adventitia of the proximal outflow vein in autologous AVF procedure has an excellent potential to prevent the subsequent local stenosis of the proximal outflow vein.

MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host.

The arms race between entomopathogenic bacteria and their insect hosts is an excellent model for decoding the intricate coevolutionary processes of host-pathogen interaction. Here, we demonstrate that the MAPK signaling pathway is a general switch to trans-regulate differential expression of aminopeptidase N and other midgut genes in an insect host, diamondback moth (Plutella xylostella), thereby countering the virulence effect of Bacillus thuringiensis (Bt) toxins. Moreover, the MAPK cascade is activated and fine-tuned by the crosstalk between two major insect hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH) to elicit an important physiological response (i.e. Bt resistance) without incurring the significant fitness costs often associated with pathogen resistance. Hormones are well known to orchestrate physiological trade-offs in a wide variety of organisms, and our work decodes a hitherto undescribed function of these classic hormones and suggests that hormonal signaling plasticity is a general cross-kingdom strategy to fend off pathogens.

[Progress in Research and Application of Drug-Device Combination Product].

Drug-device combination product, which comprises at least a drug and a medical device, has been proved to effectively reduce the risk of complications accompanied with conventional medical devices implantation, and has a great clinical success especially in implantable therapeutics. Herein, we firstly elaborated the definitions and requirements of drug-device combination product in different countries, then summarized the market application and research development of typical drug-device combination products. Technical problems and the trend of future development had also been analyzed.

Reduced Expression of a Novel Midgut Trypsin Gene Involved in Protoxin Activation Correlates with Cry1Ac Resistance in a Laboratory-Selected Strain of Plutella xylostella (L.).

Bacillus thuringiensis (Bt) produce diverse insecticidal proteins to kill insect pests. Nevertheless, evolution of resistance to Bt toxins hampers the sustainable use of this technology. Previously, we identified down-regulation of a trypsin-like serine protease gene PxTryp_SPc1 in the midgut transcriptome and RNA-Seq data of a laboratory-selected Cry1Ac-resistant Plutella xylostella strain, SZ-R. We show here that reduced PxTryp_SPc1 expression significantly reduced caseinolytic and trypsin protease activities affecting Cry1Ac protoxin activation, thereby conferring higher resistance to Cry1Ac protoxin than activated toxin in SZ-R strain. Herein, the full-length cDNA sequence of PxTryp_SPc1 gene was cloned, and we found that it was mainly expressed in midgut tissue in all larval instars. Subsequently, we confirmed that the PxTryp_SPc1 gene was significantly decreased in SZ-R larval midgut and was further reduced when selected with high dose of Cry1Ac protoxin. Moreover, down-regulation of the PxTryp_SPc1 gene was genetically linked to resistance to Cry1Ac in the SZ-R strain. Finally, RNAi-mediated silencing of PxTryp_SPc1 gene expression decreased larval susceptibility to Cry1Ac protoxin in the susceptible DBM1Ac-S strain, supporting that low expression of PxTryp_SPc1 gene is involved in Cry1Ac resistance in P. xylostella. These findings contribute to understanding the role of midgut proteases in the mechanisms underlying insect resistance to Bt toxins.

Comprehensive analysis of Cry1Ac protoxin activation mediated by midgut proteases in susceptible and resistant Plutella xylostella (L.).

Insecticidal Cry toxins produced by Bacillus thuringiensis (Bt) have been widely used to control agricultural pests in both foliage sprays and transgenic crops. Nevertheless, rapid evolution of insect resistance to Cry toxins requires elucidation of the molecular mechanisms involved in Cry resistance. Two proposed models have been described to explain the toxicity of Cry proteins, the classic model states that Cry protoxin is activated by midgut proteases resulting in activated toxin that binds to receptors and forms a pore in the midgut cells triggering larval death, and the newly proposed dual model of the mode of action of Bt Cry toxins states that protoxin and activated toxins may have different mechanisms of action since several resistant strains to activated Cry toxins are still susceptible to the same Cry-protoxin. Protoxin activation by midgut proteases is a key step in both models. Herein, we evaluated Cry1Ac protoxin activation in a susceptible Plutella xylostella (L.) strain (DBM1Ac-S) and in the near-isogenic strain (NIL-R) with high field-evolved Cry1Ac resistance. Previous work showed that Cry1Ac resistance in NIL-R correlates with reduced binding to midgut receptors due to enhanced MAPK signaling pathway and down regulation of ABCC2 receptor. However, reduced midgut trypsin levels and altered midgut protease gene transcription were also observed in the Cry1Ac-resistant field isolated strain that is parent of the NIL-R strain. Therefore, we analyzed the midgut protease activities in both DBM1Ac-S and NIL-R strains. Detection of enzymatic activities showed that caseinolytic protease, trypsin and chymotrypsin activities were not significantly different between the susceptible and resistant strains. Furthermore, treatment with different trypsin or chymotrypsin inhibitors, such as Nα-tosyl-l-lysine chloromethyl ketone (TLCK) or Np-tosyl-L-phenylalanine chloromethyl ketone (TPCK) did not affect the susceptibility to Cry1Ac protoxin of the DBM1Ac-S and NIL-R larvae. Bioassay results indicated that the NIL-R larvae showed similar resistant levels to both Cry1Ac protoxin and trypsin-activated toxin. Taken together, our results demonstrated that high-level field-evolved Cry1Ac resistance in the NIL-R strain is independent of Cry1Ac protoxin activation and the specific protoxin mechanism of action. This discovery will strengthen our comprehensive understanding of the complex mechanistic basis of Bt resistance in different insects.

Reduced expression of the P-glycoprotein gene PxABCB1 is linked to resistance to Bacillus thuringiensis Cry1Ac toxin in Plutella xylostella (L.).

BACKGROUND: Rapid evolution of pest resistance has seriously threatened the sustainable use of Bacillus thuringiensis (Bt). The diamondback moth, Plutella xylostella (L.), is the first pest to develop resistance to Bt biopesticides in the open field, which renders it an excellent model to explore the molecular basis of Bt resistance in insects. Our previous midgut transcriptome and RNA-Seq profiles showed that the P-glycoprotein gene PxABCB1 was down-regulated in two Cry1Ac-resistant P. xylostella strains, suggesting its potential involvement in Cry1Ac resistance in P. xylostella. RESULTS: In this study, the bona fide full-length cDNA sequence of the PxABCB1 gene was cloned and analyzed, and the expression of the PxABCB1 gene was detected in all tissues and developmental stages, with the highest expression in midgut tissue and the female adult stage. Although no consistent non-synonymous mutations were identified between the susceptible and resistant strains, PxABCB1 gene expression was remarkably decreased in all resistant strains, and the association was further validated by Cry1Ac selection in the moderately resistant SZ-R strain. Moreover, knockdown of the PxABCB1 gene expression resulted in significantly reduced larval susceptibility to Cry1Ac toxin in the DBM1Ac-S strain, and decreased expression of the PxABCB1 gene was tightly linked to Cry1Ac resistance in P. xylostella. CONCLUSION: Our results demonstrated that down-regulation of the PxABCB1 gene is associated with both laboratory-selected and field-evolved Cry1Ac resistance in P. xylostella. This knowledge will be conducive to further elucidating the complicated molecular basis of Bt resistance and developing new insect resistance management tactics. © 2019 Society of Chemical Industry.

CRISPR/Cas9-mediated knockout of both the PxABCC2 and PxABCC3 genes confers high-level resistance to Bacillus thuringiensis Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.).

Rapid evolution of resistance by insect pests severely jeopardizes the sustainable utilization of biopesticides and transgenic crops that produce insecticidal crystal proteins derived from the entomopathogenic bacterium Bacillus thuringiensis (Bt). Recently, high levels of resistance to Bt Cry1 toxins have been reported to be genetically linked to the mutation or down-regulation of ABC transporter subfamily C genes ABCC2 and ABCC3 in seven lepidopteran insects, including Plutella xylostella (L.). To further determine the causal relationship between alterations in the PxABCC2 and PxABCC3 genes and Cry1Ac resistance in P. xylostella, the novel CRISPR/Cas9 genome engineering system was utilized to successfully construct two knockout strains: the ABCC2KO strain is homozygous for a 4-bp deletion in exon 3 of the PxABCC2 gene, and the ABCC3KO strain is homozygous for a 5-bp deletion in exon 3 of the PxABCC3 gene, both of which can produce only truncated ABCC proteins. Bioassay results indicated that high levels of resistance to the Cry1Ac protoxin were observed in both the ABCC2KO (724-fold) and ABCC3KO (413-fold) strains compared to the original susceptible DBM1Ac-S strain. Subsequently, dominance degree and genetic complementation tests demonstrated that Cry1Ac resistance in both the knockout strains was incompletely recessive, and Cry1Ac resistance alleles were located in the classic BtR-1 resistance locus that harbored the PxABCC2 and PxABCC3 genes, similar to the near-isogenic resistant NIL-R strain. Moreover, qualitative toxin binding assays revealed that the binding of the Cry1Ac toxin to midgut brush border membrane vesicles (BBMVs) in both knockout strains was dramatically reduced compared to that in the susceptible DBM1Ac-S strain. In summary, our CRISPR/Cas9-mediated genome editing study presents, for the first time, in vivo reverse genetics evidence for both the ABCC2 and ABCC3 proteins as midgut functional receptors for Bt Cry1 toxins in insects, which provides new insight into the pivotal roles of both the ABCC2 and ABCC3 proteins in the complex molecular mechanism of insect resistance to Bt Cry1 toxins.