Toward the synthesis of polycyclic aromatic compounds as nano-carbon cages

Under mild conditions, a key intermediate, diketone 51, for synthesis of buckybaskets was successfully synthesized through methylation of diketone 52. The Diels-Alder reaction between 2,5-dicarbomethoxy-3,4-diphenylcyclopentadienone (57) and 5,6-dimethoxy-2-norbornene (58) provided diester 56. Decarbonylation of 56 furnished diester 55, which on hydrolysis afforded diacid 54. Intramolecular acylation of diacid 54 furnished diketone 52

COVID-19 Outbreak Improves Attractiveness of Careers in Medicine in China: A Cross-Sectional Survey in High School Students and Parents

Background: The shortage of healthcare workers is becoming a serious global problem. The underlying reasons may be specific to the healthcare system in each country. Over the past decade, medicine has become an increasingly unpopular profession in China due to the heavy workload, long-term training, and inherent risks. The ongoing COVID-19 pandemic has placed the life-saving roles of healthcare professionals under the spotlight. This public health crisis may have a profound impact on career choices in the young generation of Chinese. Methods: We conducted a questionnaire-based online survey on high school students and their parents from 24 provinces (or municipalities) of China. We investigated the change of interest in medical study due to the outbreak of COVID-19 and the motivational factors. Pearson correlation analysis was used to assess the correlation of static or dynamic interest of medical career selection with the reported number of COVID-19 cases. Maslow’s Hierarchy of Needs was used to explore underlying motivations for selection of medical-related degrees. The logistic regression model was adopted to analyze the main factors associated with students’ choices. Findings: A total of 21,085 students and 21,009 parents were included in the study. We observed an increased preference for medical study since the outbreak of COVID-19 in both students (17·5% to 29·6%) and parents (37·1% to 47·3%). Contribution to society and interest in medicine was rated as the main motivations. Additionally, students who were female, in the resit of graduate year and outside of Hubei province were significantly associated with a keen interest in medical study. Interpretation: This first multi-center cross-sectional study explores the positive change and noble motivations of students’ preferences in medical study during the COVID-19 pandemic. A longitudinal study is required to determine the persistence of their choices. Funding Statement: The Local High Level University Construction Project of Shanghai, China. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional review board of the Fudan University School of Public Health. Informed consent was waived because the questions were answered anonymously

Functional characterization of solute carrier family 39 member 8 variant in relation to hypertension and coronary artery disease.

PhDHypertension and coronary artery disease are complex diseases with both environmental and genetic contributions. Genome-wide association studies (GWASs) have revealed a number of common genetic variants with modest effects on the disease susceptibility. One of the novel genetic variants (SNP rs13107325, C ! T, Ala391Thr) identified in GWASs has been associated with a number of CVD-related traits, including SBP, DBP, HDL-C, body mass index, and schizophrenia. This SNP is located at exon 8 of the solute carrier family 39 member 8 gene (SLC39A8), and results in an amino acid substitution from Alanine to Threonine at amino acid position 391. SLC39A8 was first found to be highly induced by Mycobacterium bovis BCG cell wall and TNF-α. The encoded protein ZIP8 is a divalent cation/bicarbonate cotransporter with different affinities for a number of metal ions. Recent studies revealed the major role of ZIP8 in the uptake of cadmium and manganese. The objective of this project is to investigate whether the Ala391Thr polymorphism has an impact on the structure or function of ZIP8, and the underlying mechanisms responsible for the deleterious cell events associated with cadmium exposure, that over time, may contribute to the development of hypertension. We showed that ZIP8 containing the Ala391 variant resulted in higher intracellular accumulation of Cd2+ at low dose and Zn2+ at physiological concentration. Lower cell proliferation and higher cell death were observed in transfected HEKs and HuVECs exposed to Cd2+. This was accompanied by stronger ERK1/2 and NF-ĸB activation in HEK293 possibly induced by Cd2+ uptake. We also showed some evidence of ZIP8 participation in HDL3-mediated cholesterol efflux, however this needs to be further validated in an improved experimental model. 6" " Bioinformatics analysis suggested a possible structural impact of Ala391Thr on ZIP8 function, which was supported by conservation analysis of the alanine amino acid. Membrane protein structure analysis predicted a shift of an α-helical domain possibly caused by the change of the amino acid hydrophillicity. The secondary structure predicted by the Robetta algorithm based on a similar homologue supported that this structural change may be caused by the Ala391Thr variation. Our data indicate that the amino acid substitution (Ala391Thr) caused by SNP rs13107325 alters the transport activity of ZIP8 on metal ions, leading to differential activation of ERK1/2 and NF-κB pathways, which subsequently results in different levels of cell death on human kidney and endothelial cells. This study sought to provide the preliminary mechanistic explanations for the association of rs1310725 with blood pressure and HDL-C following the GWAS. These observations have demonstrated a promising start for further investigation of SLC39A8 in the context of hypertensive mice or human populations. This may enable further pharmacological studies for the development of a potential therapeutic candidate for hypertension treatment.Chinese Scholarship Council William Harvey Research Institute British Heart Foundation Henry Lester Trust

Designing Optimal Implementations of Linear Layers (Full Version)

Linear layer is a fundamental primitive for computer science, electronic engineering, and telecommunication. The performance of a linear layer depends on two aspects: diffusion ability and implementation cost, where the latter is usually measured by the number of XORs needed to implement it. For many years, linear layers have been implemented by computing co-ordinates of the output independently. With this method, costs are determined only by the matrices representing linear layers. However, we note that the implementation cost of a given linear layer depends not only on its matrix but also on the ways with which we implement it. So, in this paper, we focus on another implementation method: modifying input vectors to output step by step (MIOSS). This method uses fewer XORs than previous methods do and needs no extra temporary register. Besides, this method makes the implementation cost of a linear layer same as that of its inverse. With the new implementation method, we first clarify the measurement of implementation cost and the optimal implementation procedure of linear layers. Here, ``optimal\u27\u27 means using fewest XORs. Then, to find the optimal implementation procedure of a given linear layer, we construct a graph-theoretical model and transfer the problem to the shortest path problem in graph theory. Although there has been several algorithms for the shortest path problem, they do not perform best for the graph that we construct in this paper because of its regularity. Therefore, we adopt a new ``double-direction\u27\u27 algorithm that uses less storage and makes the search for a shortest path more efficient in a regular graph. Unfortunately, this algorithm is not practical for large size linear layers because of its high space/time complexity. So, we finally construct another algorithm for finding efficient implementations of linear layers. An important advantage of this last algorithm is its extremely low complexity. We conduct it to the linear layer of AES and get very efficient implementations

On Constructions of a Sort of MDS Block Diffusion Matrices for Block Ciphers and Hash Functions

Many modern block ciphers use maximum distance separate (MDS) matrices as their diffusion layers. In this paper, we propose a new method to verify a sort of MDS diffusion block matrices whose blocks are all polynomials in a certain primitive block over the finite field $\mathbb F_2$. And then we discover a new kind of transformations that can retain MDS property of diffusion matrices and generate a series of new MDS matrices from a given one. Moreover, we get an equivalence relation from this kind of transformation. And MDS property is an invariant with respect to this equivalence relation which can greatly reduce the amount of computation when we search for MDS matrices. The minimal polynomials of matrices play an important role in our strategy. To avoid being too theoretical, we list a series of MDS diffusion matrices obtained from our method for some specific parameters. Furthermore, we talk about MDS recursive diffusion layers with our method and extend the corresponding work of M. Sajadieh et al. published on FSE 2012 and the work of S. Wu published on SAC 2012

Correlation study between advanced age and inferior prognosis in stage Ⅱ colorectal cancer patients

Background and purpose: With the aging population, the number of elderly patients with colorectal cancer (CRC) is increasing. To date, elderly patients with stage Ⅱ CRC often receive a weakened chemotherapy regimen or even no chemotherapy after radical surgery, and It is still unclear whether this will lead to adverse oncological outcomes. This study aimed to explore the prognostic impact of advanced age on stage Ⅱ CRC patients after removing bias through a multivariate COX regression approach. Methods: We retrospectively collected data of 3314 colorectal cancer patients with postoperative pathology of stage Ⅱ, no history of previous tumors, no secondary primary tumors within 5 years after surgery and no preoperative neoadjuvant therapy. This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center (ethics number: 050432-4-2108*). The optimal threshold for calculating age relative to survival using survminer package of R software (version 3.0) (surv_cutpoint algorithm) was 73 years. We compared the clinical and pathological characteristics, overall survival (OS) and disease-free survival (DFS) between the older group (age>73 years) and the younger group (age≤73 years). The alignment diagram prediction model was drawn using the survival package and RMS package. Results: The elderly and non-elderly groups were evenly comparable in terms of gender, tumor location, differentiation, vascular invasion, perineural invasion and pT stage. Multivariate COX regression showed that advanced age was an independent prognostic risk factor for OS [hazard ratio (HR)=3.725 (3.051-4.549), P<0.001] and DFS [HR=2.431 (2.029-2.912), P<0.001]. The nomogram (alignment diagram) prediction model constructed based on multivariate COX regression could effectively evaluate the prognosis of stage Ⅱ CRC patients and provide guidance for practical clinical work. Conclusion: In stage Ⅱ CRC patients, older age is associated with shorter OS and DFS. Adequate intensity of adjuvant chemotherapy may be necessary. Treatment decisions can be adjusted based on the predicted model scores of the patient’s alignment diagram

Effect of potassium simplex optimization medium (KSOM) and embryo screening on the production of human lactoferrin transgenic cloned dairy goats

In this study, we produced cloned transgenic dairy goat based on dairy goat ear skin fibroblast as donor cells for nuclear transfer (NT), which were modified by human lactoferrin (hLF) gene. The developmental competence of NT embryos was compared with either between different embryo culture medium, potassium simplex optimization medium (KSOM) and tissue culture medium (TCM 199), or different classification of NT embryos (48 h after fusion). First we cultured NT embryos to cleavage stage (48 h after fusion) by TCM 199 supplemented with 1 mg/ml bovine serum albumin BSA and KSOM, then used TCM 199 supplemented with 10% FBS to culture them to blastula stage. The results show that the NT embryos in KSOM (19.5%) were superior to TCM 199 (10.6%) in blastulation. In the second experiment, we found that the growth rate of NT embryos (48 h after fusion) was different, then we divided them into four groups: 2-cell, 3- to 4-cell, 5- to 8-cell and >8-cell in stereo microscope and cultured them in vitro respectively. The results show day-2 embryos at 3-4cell and 5-8cell stage (31.9 and 28.2%, P < 0.05) had higher blastocyst formation rates than those at both 2-cell (9.1%) and >8-cell (8.3%) stage, and finally three healthy cloned transgenic goat were successfully produced using 3-8 cell embryos at Day-2 (82%). Using Hoechst 33342 staining, we also found that the >8 cells embryos at Day- 2 demonstrated higher frequency of fragmentation, which may be the one cause of the low blastocyst formation rate. This study therefore demonstrates that KSOM medium could be selected as the early embryo culture medium, and 3-8 cell embryos at day-2 (48 h after fusion) may be the suitable embryos for transplantation, which could reduce the nuclei fragmentation and result in good quality blastocysts that may also enhance the efficiency of transgenic cloned dairy goats production, as well as decrease the economic loss due to embryonic mortality when embryos are transferred to synchronized recipients.Key words: Nuclear transfer, KSOM, transgenic, human lactoferrin, dairy goat

A blood pressure-associated variant of the SLC39A8 gene influences cellular cadmium accumulation and toxicity.

Genome-wide association studies have revealed a relationship between inter-individual variation in blood pressure and the single nucleotide polymorphism rs13107325 in the SLC39A8 gene. This gene encodes the ZIP8 protein which co-transports divalent metal cations, including heavy metal cadmium, the accumulation of which has been associated with increased blood pressure. The polymorphism results in two variants of ZIP8 with either an alanine (Ala) or a threonine (Thr) at residue 391. We investigated the functional impact of this variant on protein conformation, cadmium transport, activation of signalling pathways and cell viability in relation to blood pressure regulation. Following incubation with cadmium, higher intracellular cadmium was detected in cultured human embryonic kidney cells (HEK293) expressing heterologous ZIP8-Ala391, compared with HEK293 cells expressing heterologous ZIP8-Thr391. This Ala391-associated cadmium accumulation also increased the phosphorylation of the signal transduction molecule ERK2, activation of the transcription factor NFκB, and reduced cell viability. Similarly, vascular endothelial cells with the Ala/Ala genotype had higher intracellular cadmium concentration and lower cell viability than their Ala/Thr counterpart following cadmium exposure. These results indicate that the ZIP8 Ala391-to-Thr391 substitution has an effect on intracellular cadmium accumulation and cell toxicity, providing a potential mechanistic explanation for the association of this genetic variant with blood pressure

Potentially Functional Variants of PLCE1 Identified by GWASs Contribute to Gastric Adenocarcinoma Susceptibility in an Eastern Chinese Population

BACKGROUND: Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P(trend) = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05). CONCLUSIONS/SIGNIFICANCES: Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population