Dabigatran-related serious medication errors: an analysis using data from VigiBase.

OBJECTIVE: To analyze the serious medication errors (MEs) on dabigatran, and their related factors, in order to avoid or reduce the occurrence of adverse events. METHODS: Serious MEs related to dabigatran were extracted from the WHO global database of reported potential side effects of medicinal products (VigiBase) by using "Medication errors and other product use errors and issues" High Level Group Term (HLGT) of the international Medical Dictionary for Regulatory Activities (MedDRA). Well-documented reports, vigiGrade completeness score ≥ 0.80, or with an informative narrative were analyzed with a focus on the clinical features of the cases. The PCNE Classification for drug-related problems (DRP) was used to classify medication errors in our analysis of cases. RESULTS: Until January 26, 2020, there were 453 cases with serious MEs related to dabigatran in VigiBase, and 113 were well-documented. Among these, 69 patients (61%) were hospitalized or had prolonged hospitalization, 16 (14%) had life-threatening events, and 12 (11%) died. The MEs occurred in the prescription phase in 77 cases, in administration in 35, and at the dispensing stage in one case. The MEs in prescription were related to a drug selection error in 44 cases (24 concerning contraindications and 20 drug interactions) and to dose error in 33 cases (17 with excessive dose; eight with insufficient frequency; four had an incorrect time; in three, the dose was too low; and in one, too frequent). The MEs in administration were medical-staff-related errors in five cases (three with wrong administration route, one administration omission, and one overdose), patient-related errors in 28 (14 insufficient dose or no administration, seven improper drug storage, four wrong administration method, and three over prescribed dose), and other errors in two (without efficacy monitoring). The dispensing error of a wrong drug strength occurred in a pharmacy. The main adverse events in the 113 patients were haemorrhage in 57 cases (50%) and ischemia in 29 cases (26%). CONCLUSION: Based on the analysis of reports in VigiBase, serious MEs related to dabigatran mainly occurred during prescription and administration. Although the incidence of MEs with clinical consequences in the use of dabigatran cannot be determined, attention should be paid to selection of the appropriate dose to a right patient in the prescription, and to patient compliance and storage in drug administration. The patient harm mainly manifested itself as bleeding or ischemia including fatal outcome in rare patients.

Pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 reinfections compared to those with a single infection: a retrospective cohort study.

BACKGROUND: To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. METHODS: This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission. RESULTS: We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms. CONCLUSION: Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes.

Genome-wide identification and expression analysis of the ALDH gene family and functional analysis of PaALDH17 in Prunus avium.

ALDH (Aldehyde dehydrogenase), as an enzyme that encodes the dehydroxidization of aldehydes into corresponding carboxylic acids, played an important role inregulating gene expression in response to many kinds of biotic and abiotic stress, including saline-alkali stress. Saline-alkali stress was a common stress that seriously affected plant growth and productivity. Saline-alkali soil contained the characteristics of high salinity and high pH value, which could cause comprehensive damage such as osmotic stress, ion toxicity, high pH, and HCO3-/CO32- stress. In our study, 18 PaALDH genes were identified in sweet cherry genome, and their gene structures, phylogenetic analysis, chromosome localization, and promoter cis-acting elements were analyzed. Quantitative real-time PCR confirmed that PaALDH17 exhibited the highest expression compared to other members under saline-alkali stress. Subsequently, it was isolated from Prunus avium, and transgenic A. thaliana was successfully obtained. Compared with wild type, transgenic PaALDH17 plants grew better under saline-alkali stress and showed higher chlorophyll content, Superoxide dismutase (SOD), Peroxidase (POD) and Catalase (CAT) enzyme activities, which indicated that they had strong resistance to stress. These results indicated that PaALDH17 improved the resistance of sweet cherries to saline-alkali stress, which in turn improved quality and yields. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01444-7.

Pnictogen-Bonding Enzymes.

The objective of this study was to create artificial enzymes that capitalize on pnictogen bonding, a s-hole interaction that is essentially absent in biocatalysis.  For this purpose, stibine catalysts were equipped with a biotin derivative and combined with streptavidin mutants to identify an efficient transfer hydrogenation catalyst for the reduction of a fluorogenic quinoline substrate.  Increased catalytic activity from wild-type streptavidin to the best mutants coincides with the depth of the s hole on the Sb(V) center, and the emergence of saturation kinetic behavior.  Michaelis-Menten analysis reveals transition-state recognition in the low micromolar range, more than three orders of magnitude stronger than the millimolar substrate recognition.  Carboxylates preferred by the best mutants contribute to transition-state recognition by hydrogen-bonded ion pairing and anion-π interactions with the emerging pyridinium product.  The emergence of challenging stereoselectivity in aqueous systems further emphasizes compatibility of pnictogen bonding with higher order systems catalysis.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Wheat rhizosphere colonization by Bacillus amyloliquefaciens W10 and Pseudomonas protegens FD6 suppress soil and in planta abundance of the sharp eyespot pathogen Rhizoctonia cerealis.

AIMS: Develop quantitative assays (qPCR) to determine the wheat rhizosphere competence of inoculant strains Bacillus amyloliquefaciens W10 and Pseudomonas protegens FD6, and their suppressive efficacies against the sharp eyespot pathogen Rhizoctonia cerealis. METHODS AND RESULTS: Antimicrobial metabolites of strains W10 and FD6 decreased in vitro growth of R. cerealis. A qPCR assay for strain W10 was designed from a diagnostic AFLP fragment and the rhizosphere dynamics of both strains in wheat seedlings were compared by culture-dependent (CFU) and qPCR assays. The qPCR minimum detection limits for strains W10 and FD6 were log 3.04 and log 4.03 genome (cell) equivalents g-1 soil, respectively. Inoculant soil and rhizosphere abundance determined by CFU and qPCR were highly correlated (r > 0.91). In wheat bioassays, rhizosphere abundance of strain FD6 was up to 80-fold greater (P < 0.001) than strain W10 at 14 and 28 days postinoculation. Both inoculants reduced (P < 0.05) rhizosphere soil and root abundance of R. cerealis by up to 3-fold. CONCLUSIONS: Strain FD6 exhibited greater abundance in wheat roots and rhizosphere soil than strain W10 and both inoculants decreased the rhizosphere abundance of R. cerealis.

Activated Expression of Rice DMR6-like Gene OsS3H Partially Explores the Susceptibility to Bacterial Leaf Streak Mediated by Knock-Out OsF3H04g.

Downy Mildew Resistance 6-like (DMR6-like) genes are identified as salicylic acid (SA) hydroxylases and negative regulators of plant immunity. Previously, we identified two rice DMR6-like genes, OsF3H03g, and OsF3H04g, that act as susceptible targets of transcription activator-like effectors (TALEs) from Xanthomonas oryzae pv. oryzicola (Xoc), which causes bacterial leaf streak (BLS) in rice. Furthermore, all four homologs of rice DMR6-like proteins were identified to predominantly carry the enzyme activity of SA 5-hydroxylase (S5H), negatively regulate rice broad-spectrum resistance, and cause the loss of function of these OsDMR6s, leading to increased resistance to rice blast and bacterial blight (BB). Here, we curiously found that an OsF3H04g knock-out mutant created by T-DNA insertion, osf3h04g, was remarkedly susceptible to BLS and BB and showed an extreme reduction in SA content. OsF3H04g knock-out rice lines produced by gene-editing were mildly susceptible to BLS and reduced content of SA. To explore the susceptibility mechanism in OsF3H04g loss-of-function rice lines, transcriptome sequencing revealed that another homolog, OsS3H, had induced expression in the loss-of-function OsF3H04g rice lines. Furthermore, we confirmed that a great induction of OsS3H downstream and genomically adjacent to OsF3H04g in osf3h04g was primarily related to the inserted T-DNA carrying quadruple enhancer elements of 35S, while a slight induction was caused by an unknown mechanism in gene-editing lines. Then, we found that the overexpression of OsS3H increased rice susceptibility to BLS, while gene-editing mediated the loss-of-function OsS3H enhanced rice resistance to BLS. However, the knock-out of both OsF3H04g and OsS3H by gene-editing only neutralized rice resistance to BLS. Thus, we concluded that the knock-out of OsF3H04g activated the expression of the OsS3H, partially participating in the susceptibility to BLS in rice.

Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase.

PURPOSE: The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs. METHODS: The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed. RESULTS: By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one. CONCLUSIONS: Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

Damage Identification of Semi-Rigid Joints in Frame Structures Based on Additional Virtual Mass Method.

In civil engineering, the joints of structures are complex, and their damage is generally hard to be detected. Due to the insensitivity of structural modal information to local joint damage, this paper presents a method based on additional virtual mass for damage identification of a semi-rigid joint in a frame structure. Firstly, the modeling of a semi-rigid is described. Secondly, the frequency response of the virtual structure is constructed, and the natural frequency of the constructed virtual structure is extracted by the ERA method. By adding multiple values of virtual masses at different positions, the natural frequency information sensitive to joint damage for damage identification is effectively increased. Based on the above theory, qualitative identification of joint damage is proposed to detect the potential damage, and identification of both damage location and its extent is presented, using natural frequency. Improved Orthogonal Matching Pursuit (IOMP) algorithm is employed to improve the accuracy of the natural frequency-based method for damage identification. At last, numerical simulation of a three-story frame is performed to discuss and to verify the effectiveness of the proposed method.

Comparisons in the changes of clinical characteristics and cerebrospinal fluid cytokine profiles between varicella-zoster virus meningitis/encephalitis and other central nervous system infections. / 水痘-å¸¦çŠ¶ç–±ç–¹ç— æ¯’è„‘è†œç‚Ž/è„‘ç‚Žä¸Žå ¶ä»–ä¸­æž¢ç¥žç»ç³»ç»Ÿæ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾å’Œè„‘è„Šæ¶²ç»†èƒžå› å­æ¯”è¾ƒï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Varicella-zoster virus (VZV) is one of the most common etiologies of viral meningitis/encephalitis. The early clinical manifestations and cerebrospinal fluid (CSF) changes of VZV meningitis/encephalitis lack specificity, and it is easy to be misdiagnosed as other viral encephalitides or tuberculous meningitis. This study aims to investigate whether the clinical characteristics, CSF analysis findings, and CSF cytokine levels could distinguish VZV meningitis/encephalitis from central nervous system (CNS) herpes simplex virus (HSV) and Mycobacterium tuberculosis (MTB) infections. METHODS: The medical records from 157 CNS infections, including 49 HSV (45 HSV-1, 4 HSV-2), 55 VZV, and 53 MTB infections between January 2018 and June 2021 in the Cytology Laboratory, Department of Neurology, Third Xiangya Hospital of Central South University were retrospectively reviewed. The data of 3 groups included demographic characteristics, laboratory results, radiographic findings, and outcomes. The levels of 12 cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) in the CSF of 68 patients (13 HSV, 22 VZV, and 33 MTB infection cases) were quantified. Clinical and laboratory data were compared among the 3 groups. RESULTS: The most common clinical manifestations in the 3 groups were fever, headache, vomiting, and neck stiffness. The clinical manifestations of HSV and VZV CNS disease were similar, although fever and altered consciousness were less common in the VZV group than those in the HSV and MTB groups (63.6% vs 87.8% vs 96.2%, P<0.001, and 14.5% vs 26.5% vs 47.2%, P=0.004, respectively). Seven patients (7/55, 12.7%) presented cutaneous zoster in the VZV group. CSF leukocyte count was significantly higher in the VZV group (230×106 cells/mL) and MTB groups (276×106 cells/mL) than that in the HSV group (87×106 cells/mL, P=0.002). CSF protein level was significantly higher in the VZV than that in the HSV group (1 034 mg/L vs 694 mg/L, P=0.011) but lower than that in the MTB group (1 744 mg/L, P<0.001). IL-6 (VZV vs HSV vs MTB: 2 855.93 pg/mL vs 2 128.26 pg/mL vs 354.77 pg/mL, P=0.029) and IL-8 (VZV vs HSV vs MTB: 4 001.46 pg/mL vs 1 578.11 pg/mL vs 1 023.25 pg/mL, P=0.046) levels were significantly different among the 3 groups and were elevated in the VZV group.Post hoc analysis revealed that IL-6 and IL-8 were significantly higher in the VZV group than those in the MTB group (P=0.002 and P=0.035, respectively), but not in the HSV group (P>0.05). CONCLUSIONS: VZV meningitis/encephalitis presents with CSF hypercellularity and proteinemia, challenging the classical view of CSF profiles in viral encephalitis. CSF IL-6 and IL-8 levels are elevated in patients with VZV meningitis/encephalitis, indicating a more intense inflammatory response in these patients.

Catalytic Asymmetric Aza-Diels-Alder Reaction of Ketimines and Unactivated Dienes.

The enantioselective aza-Diels-Alder reaction is efficient for constructing chiral tetrahydropyridines, but the catalytic asymmetric aza-Diels-Alder reaction of ketimines with unactivated dienes is still a challenging topic. Herein, guided by computational screening, a highly enantioselective aza-Diels-Alder reaction of 2-aryl-3H-indol-3-ones with unactivated dienes was realized by using a B(C6 F5 )3 /chiral phosphoric acid catalyst system under mild conditions. The reaction has a broad scope with respect to both aza-Diels-Alder reaction partners and hence offers rapid access to an array of tetrahydropyridine derivatives with pretty outcomes (up to 99 % yield, >20:1 dr and 98:2 er). The reaction is very efficient: lowering catalyst loadings for the model reaction to 0.1 mol %, enantioselectivity is still maintained. The synthetic utility was confirmed by transformations of the products. DFT calculations provide convincing evidence for the interpretation of stereoselection.

Bridge Damage Identification Using Vehicle Bump Based on Additional Virtual Masses.

Structural damage identification plays an important role in providing effective evidence for the health monitoring of bridges in service. Due to the limitations of measurement points and lack of valid structural response data, the accurate identification of structural damage, especially for large-scale structures, remains difficult. Based on additional virtual mass, this paper presents a damage identification method for bridges using a vehicle bump as the excitation. First, general equations of virtual modifications, including virtual mass, stiffness, and damping, are derived. A theoretical method for damage identification, which is based on additional virtual mass, is formulated. The vehicle bump is analyzed, and the bump-induced excitation is estimated via a detailed analysis in four periods: separation, free-fall, contact, and coupled vibrations. The precise estimation of bump-induced excitation is then applied to a bridge. This allows the additional virtual mass method to be used, which requires knowledge of the excitations and acceleration responses in order to construct the frequency responses of a virtual structure with an additional virtual mass. Via this method, a virtual mass with substantially more weight than a typical vehicle is added to the bridge, which provides a sufficient amount of modal information for accurate damage identification while avoiding the bridge overloading problem. A numerical example of a two-span continuous beam is used to verify the proposed method, where the damage can be identified even with 15% Gaussian random noise pollution using a 1-degree of freedom (DOF) car model and 4-DOF model.

B(C6 F5 )3 /Chiral Phosphoric Acid Catalyzed Ketimine-Ene Reaction of 2-Aryl-3H-indol-3-ones and α-Methylstyrenes.

The enantioselective ketimine-ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine-ene reactions of 2-aryl-3H-indol-3-ones with α-methylstyrenes were achieved by utilizing a B(C6 F5 )3 /chiral phosphoric acid (CPA) catalyst. These ketimine-ene reactions proceed well with low catalyst loading (B(C6 F5 )3 /CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2-allyl-indolin-3-ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C6 F5 )3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen-bonding interactions, especially the enhanced N-H⋅⋅⋅O hydrogen-bonding interaction, differentiates the free energy of the transition states of CPA and B(C6 F5 )3 /CPA, thereby inducing the improvement of stereoselectivity.

Optimal Placement of Virtual Masses for Structural Damage Identification.

Adding virtual masses to a structure is an efficient way to generate a large number of natural frequencies for damage identification. The influence of a virtual mass can be expressed by Virtual Distortion Method (VDM) using the response measured by a sensor at the involved point. The proper placement of the virtual masses can improve the accuracy of damage identification, therefore the problem of their optimal placement is studied in this paper. Firstly, the damage sensitivity matrix of the structure with added virtual masses is built. The Volumetric Maximum Criterion of the sensitivity matrix is established to ensure the mutual independence of measurement points for the optimization of mass placement. Secondly, a method of sensitivity analysis and error analysis is proposed to determine the values of the virtual masses, and then an improved version of the Particle Swarm Optimization (PSO) algorithm is proposed for placement optimization of the virtual masses. Finally, the optimized placement is used to identify the damage of structures. The effectiveness of the proposed method is verified by a numerical simulation of a simply supported beam structure and a truss structure.

Development of a massively parallel sequencing assay for investigating sequence polymorphisms of 15 short tandem repeats in a Chinese Northern Han population.

Massively parallel sequencing (MPS) has been used in forensic genetics in recent years owing to several advantages, e.g. MPS can provide precise descriptions of the repeat allele structure and variation in the repeat-flanking regions, increasing the discriminating power among loci and individuals. However, it cannot be fully utilized unless sufficient population data are available for all loci. Thus, there is a pressing need to perform population studies providing a basis for the introduction of MPS into forensic practice. Here, we constructed a multiplex PCR system with fusion primers for one-directional PCR for MPS of 15 commonly used forensic autosomal STRs and amelogenin. Samples from 554 unrelated Chinese Northern Han individuals were typed using this MPS assay. In total, 313 alleles obtained by MPS for all 15 STRs were observed, and the corresponding allele frequencies ranged between 0.0009 and 0.5162. Of all 15 loci, the number of alleles identified for 12 loci increased compared to capillary electrophoresis approaches, and for the following six loci more than double the number of alleles was found: D2S1338, D5S818, D21S11, D13S317, vWA, and D3S1358. Forensic parameters were calculated based on length and sequence-based alleles. D21S11 showed the highest heterozygosity (0.8791), discrimination power (0.9865), and paternity exclusion probability in trios (0.7529). The cumulative match probability for MPS was approximately 2.3157 × 10-20 .

[Validation of GlobalFiler® PCR Amplification Kit and the STR Polymorphism].

OBJECTIVE: To test the technical parameters of GlobalFiler® PCR Amplification Kit for its application to forensic application value and to investigate the genetic polymorphisms. METHODS: The validation was conducted in sensitivity, mixed samples, species specificity, adaptability, survivability, consistency, peak height balance and stability. The amplification and detection of the genomic DNA from 373 unrelated individuals from Beijing Han nationality were extracted by automation workstation. RESULTS: Global-Filer® PCR Amplification Kit was adaptive to some mixed, degraded and inhibited samples. The power of sensitivity and adaptability and peak height balance showed well. The distributions of genotype frequencies for 21 STR loci in the population were all in accordance with Hardy-Weinberg equilibrium (P > 0.05). The PIC value of the 21 STR loci was among 0.536 to 0.940; the H value was among 0.558 to 0.933; the DP value was among 0.783 to 0.992; the PE value was among 0.243 to 0.874. CONCLUSION: GlobalFiler® PCR Amplification Kit is suitable for criminal cases and DNA database in forensic practice. And 21 STR loci in Beijing Han nationality have high polymorphism, which have application value in forensic practice and population genetics.

[Consistency study of PowerPlex 21 kit and Goldeneye 20A kit and forensic application].

UNLABELLED: To ensure the consistency of genotype results for PowerPlex 21 kit and Goldeneye 20A kit. METHODS: The STR loci were amplified in DNA samples from 205 unrelated individuals in Beijing Han population. And consistency of 19 overlap STR loci typing were observed. The genetic polymorphism of D1S1656 locus was obtained. RESULTS: All 19 overlap loci typing showed consistent. The proportion of peak height of heterozygous loci in two kits showed no statistical difference (P > 0.05). The observed heterozygosis of D1S1656 was 0.878. The discrimination power was 0.949. The excluding probability of paternity of triplet was 0.751. The excluding probability of paternity of diploid was 0.506. The polymorphism information content was 0.810. CONCLUSION: PowerPlex 21 kit and Goldeneye 20A kit present a good consistency. The primer design is reasonable. The polymorphism of D1S1656 is good. The two kits can be used for human genetic analysis, paternity test, and individual identification in forensic practice.

Multistage Supply Chain Channel Principal-Agent Model in the Context of e-Commerce With Fairness Preference.

This research aims to investigate information asymmetry in e-commerce supply chain channels and the impact of the fair preference model on the behavior and returns of channel members. Therefore, by contrasting it with the model in the completely rational case, this research establishes a more realistic principal-agent model and incorporates the fair preference model into the e-commerce supply chain channel. According to the model's analysis, the effort level of the retailer at each stage is positively correlated with the e-commerce efficiency coefficient, and the incentive coefficient of manufacturers is positively correlated with the e-commerce efficiency coefficient in the case where all rationality is assumed. Manufacturing companies' anticipated profits are positively correlated with the e-commerce efficiency coefficient. According to the fair preference model, retailers will put forth more effort to sell products when their fixed income from manufacturers is higher and their optimal effort level is positively correlated with that income. When e-commerce's efficiency coefficient is higher than 1, the retailer's revenue and effort exceeded those of traditional channels. Manufacturers and retailers both experience Pareto improvements in their earnings after the fair preference model is introduced.

Network Pharmacology and Molecular Docking Validation to Explore the Pharmacological Mechanism of Zhuling Decoction against Nephrotic Syndrome.

BACKGROUND: In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear. OBJECTIVE: This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets. RESULTS: Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2. CONCLUSION: In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.

Pre-phase transition of a Cu2-xS template enables polymorph selective synthesis of MS (M = Zn, Cd, Mn) nanocrystals via cation exchange reactions.

Utilization of copper-deficient Cu2-xS nanocrystals (NCs) with diverse crystal phases and stoichiometries as cation exchange (CE) templates is a potential route to overcome the current limitations in the polymorph selective synthesis of desired nanomaterials. Among the Cu2-xS NCs, covellite CuS is emerging as an attractive CE template to produce complicated and metastable metal sulfide NCs. The presence of a reducing agent is essential to induce a phase transition of CuS into other Cu2-xS phases prior to the CE reactions. Nevertheless, the effect of the reducing agent on the phase transition of CuS, especially into the hexagonal close packing (hcp) phase and the cubic close packing (ccp) phase, has been scarcely exploited, but it is highly important for the polymorphic production of metal sulfides with the wurtzite phase and zinc blende phase. Herein, we report a reducing agent dependent pre-phase transition of CuS nanodisks (NDs) into hcp and ccp Cu2-xS NCs. 1-Dodecanethiol molecules and oleylamine molecules selectively reduced CuS NDs into hcp djurleite Cu1.94S NDs and ccp digenite Cu1.8S NCs. Afterward, the hcp Cu1.94S NDs and ccp Cu1.8S NCs were exchanged by Zn2+/Cd2+/Mn2+, and the wurtzite phase and the zinc blende phase of ZnS, CdS, and MnS NCs were produced. Without the pre-phase transition, direct CE reactions of CuS NDs are incapable of synthesizing the above wurtzite and zinc blende metal sulfide NCs. Therefore, our findings suggest the importance of the pre-phase transition of the CE template in polymorphic syntheses, holding great promise in the fabrication of other polymorphic nanomaterials with novel physical and chemical properties.