DELFMUT: duplex sequencing-oriented depth estimation model for stable detection of low-frequency mutations.

Duplex sequencing technology has been widely used in the detection of low-frequency mutations in circulating tumor deoxyribonucleic acid (DNA), but how to determine the sequencing depth and other experimental parameters to ensure the stable detection of low-frequency mutations is still an urgent problem to be solved. The mutation detection rules of duplex sequencing constrain not only the number of mutated templates but also the number of mutation-supportive reads corresponding to each forward and reverse strand of the mutated templates. To tackle this problem, we proposed a Depth Estimation model for stable detection of Low-Frequency MUTations in duplex sequencing (DELFMUT), which models the identity correspondence and quantitative relationships between templates and reads using the zero-truncated negative binomial distribution without considering the sequences composed of bases. The results of DELFMUT were verified by real duplex sequencing data. In the case of known mutation frequency and mutation detection rule, DELFMUT can recommend the combinations of DNA input and sequencing depth to guarantee the stable detection of mutations, and it has a great application value in guiding the experimental parameter setting of duplex sequencing technology.

JEBIN: analyzing gene co-expressions across multiple datasets by joint network embedding.

The inference of gene co-expression associations is one of the fundamental tasks for large-scale transcriptomic data analysis. Due to the high dimensionality and high noises in transcriptomic data, it is difficult to infer stable gene co-expression associations from single dataset. Meta-analysis of multisource data can effectively tackle this problem. We proposed Joint Embedding of multiple BIpartite Networks (JEBIN) to learn the low-dimensional consensus representation for genes by integrating multiple expression datasets. JEBIN infers gene co-expression associations in a nonlinear and global similarity manner and can integrate datasets with different distributions in linear time complexity with the gene and total sample size. The effectiveness and scalability of JEBIN were verified by simulation experiments, and its superiority over the commonly used integration methods was proved by three indexes on real biological datasets. Then, JEBIN was applied to study the gene co-expression patterns of hepatocellular carcinoma (HCC) based on multiple expression datasets of HCC and adjacent normal tissues, and further on latest HCC single-cell RNA-seq data. Results show that gene co-expressions are highly different between bulk and single-cell datasets. Finally, many differentially co-expressed ligand-receptor pairs were discovered by comparing HCC with adjacent normal data, providing candidate HCC targets for abnormal cell-cell communications.

Influence of the Au-Ti Active Site of the Titanosilicate MWW Zeolite on the Catalytic Activity of Ethane Dehydrogenation in the Presence of O2.

The titanosilicate zeolite with a MWW topology structure was synthesized by the atom-planting method through the dehydrochlorination of the hydroxyl group in the deboronated ERB-1 zeolite (D-ERB-1) and TiCl4, and Au was further loaded with the deposition precipitation method to apply for the ethane direct dehydrogenation (DH) and dehydrogenation of ethane in the presence of O2 (O2-DH). It was found that Au nanoparticles (NPs) below 5 nm exhibited good activity for ethane direct dehydrogenation and O2-DH. The addition of titanium can not only anchor more Au but also make Au have a more dispersed homogeneous distribution. The ethane O2-DH catalytic performances of Au-loaded Ti-incorporated D-ERB-1 (Ti-D-ERB-1) were compared to those of Au-loaded ZnO-D-ERB-1 and pure silicate D-ERB-1. The results confirm that ethane O2-DH catalyzed by Au-Ti paired active sites is a tandem reaction of catalytic ethane DH and selective H2 combustion (SHC) of generated H2. According to the experimental results and calculated kinetic parameters, such as the activation energy of DH and SHC reaction heat of O2-DH, SHC catalyzed by the Au/Ti-D-ERB-1 catalyst containing the Au-Ti active site can not only break the ethane dehydrogenation thermodynamic equilibrium limitation to improve the ethylene yield but also suppress the CO2 and CO selectivity.

Development of novel quinoline-NO donor hybrids inducing human breast cancer cells apoptosis via inhibition of topoisomerase I.

A number of NO-releasing quinoline derivatives have been designed and synthesized by introducing NO donor to quinoline carboxylic acid fragment. The anti-proliferation of all target compounds was evaluated against human cancer cell lines (HCT-116, MCF-7, and A549), MCF-7/ADR and normal cell (MCF-10A). Most compounds showed cytotoxic activity on cancer cells and drug-resistant cells with IC50 values in the range of 0.62-5.51 µM. Importantly, these compounds showed low toxicity to normal cells (4.21-34.08 µM). Further mechanism studies showed that the most potent compound 9 could release high concentration of NO and inhibit the activity of topoisomerase I. In addition, 9 regulated apoptosis-related proteins, generated ROS and blocked MCF-7 cells in G2/M phase to induce cell apoptosis. Furthermore, the P-gp-mediated transport was also influenced by 9. And 9 could significantly inhibit the growth of tumor in vivo without observable organ-related toxicities. Overall, as a novel NO-releasing quinoline derivative, 9 was worthy for further in-depth study.

Save lives or save livelihoods? A cross-country analysis of COVID-19 pandemic and economic growth.

This paper studies whether containing COVID-19 pandemic by stringent strategies deteriorates or saves economic growth. Since there are country-specific factors that could affect both economic growth and deaths due to COVID-19, we first start with a cross-country analysis on identifying risk and protective factors on the COVID-19 deaths using large across-country variation. Using data on 100 countries from 3 January to 27 November 2020 and taking into account the possibility of underreporting, we find that for deaths per million population, GDP per capita, population density, and income inequality are the three most important risk factors; government effectiveness, temperature, and hospital beds are the three most important protective factors. Second, inspired by the stochastic frontier literature, we construct a measure of pandemic containment effectiveness (PCE) after controlling for country-specific factors and rank countries by their PCE scores for deaths. Finally, by linking the PCE score with GDP growth data in Quarters 2 and 3 of 2020, we find that PCE is positively associated with economic growth in major economies. Countries with average PCE scores, such as Malaysia, would gain more GDP growth by 3.47 percentage points if they could improve their PCE scores for deaths to South Korea's level in Q2 of 2020. Therefore, there is not a trade-off between lives and livelihood facing by governments. Instead, to save economy, it is important to contain the pandemic first. Our conclusion is also mainly valid for infections due to COVID-19.

Right Heart Function of Fetuses and Infants with Large Ventricular Septal Defect: A Longitudinal Case-Control Study.

The objective of this study was to detect the effect of a large ventricular septal defect (VSD) on right ventricular function before and after birth. All consecutive children with large VSD who were born in our hospital between January 2013-February 2016 and followed up throughout early infancy, and who lacked malformations or chromosomal abnormalities, were identified by a retrospective review of the medical records and included in this retrospective longitudinal case-control study (n = 30). Thirty normal control cases with an equivalent gestational age and gender served as controls. Tricuspid annular plane systolic excursion (TAPSE), right ventricle (RV) Tei index, and tricuspid E/E m were measured in the fetal, neonatal (day 1-28), and infant (day 29-70) periods. In all periods, the VSD and control groups did not differ in TAPSE values, but VSD associated with higher Tei indices and tricuspid E/E m values (in the fetal period: VSD group RV Tei was 0.48 ± 0.12 and E/E m was 11.84 ± 1.53, control group RV Tei was 0.42 ± 0.16 and E/E m was 10.16 ± 1.61; in neonatal period: VSD group RV Tei was 0.41 ± 0.17 and E/E m was 12.21 ± 1.59, control group RV Tei was 0.30 ± 0.13 and E/E m was 7.20 ± 1.28; in the infant period: VSD group RV Tei was 0.39 ± 0.09 and E/E m was 11.89 ± 2.80, control group RV Tei was 0.28 ± 0.12 and E/E m was 5.26 ± 1.90, all p < 0.05). In the fetal and neonatal periods, TAPSE correlated negatively with Tei index and tricuspid E/E m in both groups. However, in the infant period, only the control group exhibited correlations between TAPSE and Tei index or tricuspid E/E m. Tei index correlated positively with tricuspid E/E m in both groups in all three periods. The VSD group had smaller correlation coefficients than the control group. Large VSD may already start to impair RV diastolic and global function before birth. This impairment continued and increased after birth. These changes did not associate with obvious RV longitudinal systolic function impairment. Large VSD mainly affected RV function by decreasing diastolic function and myocardial performance.

Damage assessment of two-way bending RC slabs subjected to blast loadings.

Terrorist attacks on vulnerable structures and their individual structural members may cause considerable damage and loss of life. However, the research work on response and damage analysis of single structural components, for example, a slab to blast loadings, is limited in the literature and this is necessary for assessing its vulnerability. This study investigates the blast response and damage assessment of a two-way bending reinforced concrete (RC) slab subjected to blast loadings. Numerical modeling and analysis are carried out using the commercial finite element code LS-DYNA 971. A damage assessment criterion for the two-way bending RC slab is defined based on the original and residual uniformly distributed load-carrying capacity. Parametric studies are carried out to investigate the effects of explosive weight and explosive position on the damage mode of the two-way RC slab. Some design parameters, such as the boundary conditions and the negative reinforcement steel bar length, are also discussed. The illustrated results show that the proposed criterion can apply to all failure modes. The damage assessment results are more accurate than the ones due to the conventional deformation criterion.

Thermoelectric Properties of Zn-Doped YbMg1.85-xZnxBi1.98.

Bi-based YbMg2Bi1.98 Zintl compounds represent promising thermoelectric materials. Precise composition and appropriate doping are of great importance for this complex semiconductor. Here, the influence of Zn substitution for Mg on the microstructure and thermoelectric properties of p-type YbMg1.85-xZnxBi1.98 (x = 0, 0.05, 0.08, 0.13, 0.23) was investigated. Polycrystalline samples were prepared using induction melting and densified with spark plasma sintering. X-ray diffraction confirmed that the major phase of the samples possesses the trigonal CaAl2Si2-type crystal structure, and SEM/EDS indicated the presence of minor secondary phases. The electrical conductivity increases and the lattice thermal conductivity decreases with more Zn doping in YbMg1.85-xZnxBi1.98, whereas the Seebeck coefficient has a large reduction. The band gap decreases with increasing Zn concentration and leads to bipolar conduction, resulting in an increase in the thermal conductivity at higher temperatures. Figure of merit ZT values of 0.51 and 0.49 were found for the samples with x = 0 and 0.05 at 773 K, respectively. The maximum amount of Zn doping is suggested to be less than x = 0.1.

Effects of DNA Immunoadsorption Combined with Medication on Immune Function and Renal Function in Patients with Systemic Lupus Erythematosus.

Objective. At present, glucocorticoids combined with cyclophosphamide are still used for the clinical treatment of systemic lupus erythematosus (SLE). However, long-term practice has shown that drug treatment currently has the phenomena of long treatment duration, uncontrollable conditions in a short period of time, and unsatisfactory efficacy. DNA immunoadsorption therapy is a newly developed therapy. The combination of drugs and DNA immunoadsorption has been reported for the treatment of SLEN in clinics for a long time. In this study, we observed the effects of DNA immunoadsorption combined with drug therapy on immune function and renal function in patients with systemic lupus erythematosus (SLE). The results showed that the DNA immunosorbent assay combined with medication in the treatment of SLE could quickly and specifically remove pathogenic substances from patients, improve renal function, immune function, and complement levels in patients, and help to relieve disease activity.

Tumor Microenvironment-Activated Theranostics Nanozymes for Fluorescence Imaging and Enhanced Chemo-Chemodynamic Therapy of Tumors.

Chemodynamic therapy (CDT) is widely explored for tumor-specific therapy by converting endogenous H2O2 to lethal ·OH to destroy cancer cells. However, ·OH scavenging by glutathione (GSH) and insufficient intratumoral H2O2 levels seriously hinder the application of CDT. Herein, we reported the fabrication of copper ion-doped ZIF-8 loaded with gold nanozymes and doxorubicin hydrochloride (DOX) for the chemotherapy and CDT synergistic treatment of tumors with the assistance of tumor microenvironment (TME)-activated fluorescence imaging. The Cu2+-doped ZIF-8 shell was gradually degraded to release DOX and gold nanoclusters responding to the acidic TME. The fluorescence signal of the tumor region was acquired after the quenched fluorescence of the gold nanoclusters by Cu2+ and DOX by aggregation-induced quenching was turned on because of the interaction of GSH with Cu2+ and the release of free DOX. The Cu2+ ions could deplete the GSH via redox reactions and the generated Cu+ could convert internal H2O2 to ·OH for tumor CDT. The chemotherapeutic effect of DOX was strengthened through drug efflux inhibition and drug sensitivity increase due to the consumption of GSH and ·OH burst. Moreover, DOX could raise the level of H2O2 and augment the effect of CDT. In addition, the fluorescent gold nanoclusters not only served as a peroxidase to convert H2O2 to ·OH but also employed as an oxidase to consume GSH, resulting in the amplification of chemotherapy and CDT. This work presents an approach to construct tumor microenvironment-activated theranostic probes without external stimuli and to achieve the tumor elimination through cascade reactions and synergistic treatment.

Paeonol Derivatives and Pharmacological Activities: A Review of Recent Progress.

Paeonol, 2-hydroxy-4-methoxy acetophenone, is one of the main active ingredients of traditional Chinese medicine such as Cynanchum paniculatum, Paeonia suffruticosa Andr and Paeonia lactiflora Pall. Modern medical research has shown that paeonol has a wide range of pharmacological activities. In recent years, a large number of studies have been carried out on the structure modification of paeonol and the mechanism of action of paeonol derivatives has been studied. Some paeonol derivatives exhibit good pharmacological activities in terms of antibacterial, anti-inflammatory, antipyretic analgesic, antioxidant and other pharmacological effects. Herein, the research progress on paeonol derivatives and their pharmacological activities were systematically reviewed.

A new indole alkaloid with anti-inflammatory from the branches of Nauclea officinalis.

A new indole alkaloid, 17-oxo-19-(Z)-naucline, and six known alkaloids 2-7 were isolated from the branches of Nauclea officinalis. The structure of the new compound 1 was characterised mainly by analysing its physical data including IR, 1 D, 2 D NMR, and HR-ESI-MS. Other compounds were identified by comparisons their data with those reported in the literature. Compound1, 4, 5, 6, 7 showed in vitro anti-inflammatory activity decrease the LPS-stimulated production of nitric oxide in RAW264.7 cell, while all compounds exhibited weak cytotoxicity against human tumour cell lines (LOVO, A549 and HepG2).

Preparation and Characterization of Graphene Oxide-Modified Sapium sebiferum Oil-Based Polyurethane Composites with Improved Thermal and Mechanical Properties.

Bio-based polyurethane (PU) composites with superior thermal and mechanical properties have received wide attention. This is due to the recent rapid developments in the PU industry. In the work reported here, novel nano-composites with graphene oxide (GO)-modified Sapium sebiferum oil (SSO)-based PU has been synthesized via in situ polymerization. GO, prepared using the improved Hummers method from natural graphene (NG), and SSO-based polyol with a hydroxyl value of 211 mg KOH/g, prepared by lipase hydrolysis, were used as raw materials. The microstructures and properties of GO and the nano-composites were both characterized using Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and tensile tests. The results showed that GO with its nano-sheet structure possessed a significant number of oxygen-containing functional groups at the surface. The nano-composites containing 1 wt % GO in the PU matrix (PU1) exhibited excellent comprehensive properties. Compared with those for pure PU, the glass transition temperature (Tg) and initial decomposition temperature (IDT) of the PU1 were enhanced by 14.1 and 31.8 °C, respectively. In addition, the tensile strength and Young's modulus of the PU1 were also improved by 126% and 102%, respectively, compared to the pure PU. The significant improvement in both the thermal stability and mechanical properties for PU/GO composites was attributed to the homogeneous dispersion and good compatibility of GO with the PU matrix. The improvement in the properties upon the addition of GO may be attributable to the strong interfacial interaction between the reinforcing agent and the PU matrix.

Lipase-Catalyzed Synthesis, Properties Characterization, and Application of Bio-Based Dimer Acid Cyclocarbonate.

Dimer acid cyclocarbonate (DACC) is synthesized from glycerol carbonate (GC) and Sapium sebiferum oil-derived dimer acid (DA, 9-[(Z)-non-3-enyl]-10-octylnonadecanedioic acid). Meanwhile, DACC can be used for synthetic materials of bio-based non-isocyanate polyurethane (bio-NIPU). In this study, DACC was synthesized by the esterification of dimer acid and glycerol carbonate using Novozym 435 (Candida antarctica lipase B) as the biocatalyst. Via the optimizing reaction conditions, the highest yield of 76.00% and the lowest acid value of 43.82 mg KOH/g were obtained. The product was confirmed and characterized by Fourier transform-infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Then, the synthetic DACC was further used to synthesize bio-NIPU, which was examined by FTIR, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC), indicating that it possesses very good physio-chemical properties and unique material quality with a potential prospect in applications.

[Advances in platform compounds and polymers from vegetable oils].

Vegetable oil is one of the most potential alternatives of petroleum and has become a hot issue in recent years. This review focuses on the influence of vegetable oil structure on platform compounds and polymers properties, and further systematically introduces their developments and the latest progress. Meanwhile, we also summarized the main confronting problems and the future development directions in the research of oil-based platform compounds and polymers. The review provides useful information for readers to fully understand biochemical engineering of vegetable oils and their prospects.

[Study of the disease burden of patients with drug-resistant and drug-sensitive tuberculosis in Guangdong and Zhejiang provinces].

OBJECTIVE: To investigate the disease burden of drug-resistant and drug-sensitive tuberculosis (TB) patients in Guangdong and Zhejiang provinces. METHODS: Three hundred and two patients with TB, who had been involved in the project for drug resistance surveillance and completed the full course of treatment, were enrolled for this study. The proportion method for drug susceptibility was used. The method of disability adjusted life year (DALY) was applied to assess the disease burden of TB patients. RESULTS: The average DALYs of initial cases with drug-sensitive and drug-resistant TB, and retreated cases with drug-sensitive and drug-resistant TB, were 0.26, 0.68, 0.49, and 1.04, respectively. The average DALY loss of drug-resistant TB patients was 0.86 and that of drug-sensitive TB patients was 0.44. CONCLUSIONS: The values of DALY for initial and retreated cases with drug-resistant TB were 2 times higher than those for patients with drug-sensitive TB, indicating the higher disease burden in drug-resistant TB patients. Therefore, to reduce the disease burden of patients with drug-resistant TB, standardized protocols must be applied in the treatment of TB.

The Influence of Pelvic Ramus Fracture on the Stability of Fixed Pelvic Complex Fracture.

This study aims to evaluate the biomechanical mechanism of pelvic ring injury for the stability of pelvis using the finite element (FE) method. Complex pelvic fracture (i.e., anterior column with posterior hemitransverse lesion) combined with pelvic ramus fracture was used to evaluate the biomechanics stability of the pelvis. Three FE fracture models (i.e., Dynamic Anterior Plate-Screw System for Quadrilateral Area (DAPSQ) for complex pelvic fracture with intact pubic ramus, DAPSQ for complex pelvic fracture with pubic ramus fracture, and DAPSQ for complex pelvic fracture with fixed pubic ramus fracture) were established to explore the biomechanics stability of the pelvis. The pubic ramus fracture leads to an unsymmetrical situation and an unstable situation of the pelvis. The fixed pubic ramus fracture did well in reducing the stress levels of the pelvic bone and fixation system, as well as displacement difference in the pubic symphysis, and it could change the unstable situation back to a certain extent. The pelvic ring integrity was the prerequisite of the pelvic stability and should be in a stable condition when the complex fracture is treated.

Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine ß-hydroxylase.

BACKGROUND: Disulfiram has been an effective cocaine addiction pharmacotherapy, and one of its possible mechanisms of efficacy is through copper chelation and inhibition of an enzyme involved in catecholamine metabolism, dopamine ß-hydroxylase (DßH), which converts dopamine to norepinephrine. A variant in the gene encoding DßH leads to reduced DßH activity, and as such, disulfiram might not be an effective treatment of cocaine dependence for individuals with this variant. This study explored that potential matching. METHODS: Seventy-four cocaine- and opioid-codependent (DSM-V) subjects were stabilized on methadone for 2 weeks and subsequently randomized into disulfiram (250 mg/day, n = 34) and placebo groups (n = 40) for 10 weeks. We genotyped the DBH gene polymorphism, -1021C/T (rs1611115), that reduces DßH enzyme levels and evaluated its role for increasing cocaine free urines with disulfiram. RESULTS: With repeated measures analysis of variance, corrected for population structure, disulfiram pharmacotherapy reduced cocaine-positive urines from 80% to 62% (p = .0001), and this disulfiram efficacy differed by DBH genotype group. Patients with the normal DßH level genotype dropped from 84% to 56% on disulfiram (p = .0001), whereas those with the low DBH level genotype showed no disulfiram effect. CONCLUSIONS: This study indicates that the DBH genotype of a patient could be used to identify a subset of individuals for which disulfiram treatment might be an effective pharmacotherapy for cocaine dependence.