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2.
J Trace Elem Med Biol ; 84: 127437, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38564977

ABSTRACT

INTRODUCTION: Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (Ag@ZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer. METHODS: The process of generating bimetallic nanoparticles (NPs), namely Ag@ZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated. RESULTS: Bimetallic Ag@ZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90 nm, and their zeta potential was -14.70 mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24 hours of treatment, a dosage of 5 µg/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins. CONCLUSIONS: The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic Ag@ZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Nanocomposites , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Silver , TOR Serine-Threonine Kinases , Uterine Cervical Neoplasms , Zinc Oxide , Humans , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Silver/chemistry , Silver/pharmacology , TOR Serine-Threonine Kinases/metabolism , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Female , HeLa Cells , Phosphatidylinositol 3-Kinases/metabolism , Nanocomposites/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Metal Nanoparticles/chemistry , Drug Screening Assays, Antitumor , Signal Transduction/drug effects
3.
Dalton Trans ; 53(5): 2055-2064, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38179885

ABSTRACT

The development prospects of conventional Li-ion batteries are limited by the paucity of Li resources. Mg-Li hybrid batteries (MLIBs) combine the advantages of Li-ion batteries and magnesium batteries. Li+ can migrate rapidly in the cathode materials, and the Mg anode has the advantage of being dendrite-free. In this study, a type of Li4Ti5O12 composite material doped with Sn4+ and a conductive carbon skeleton (Li4Ti4.9Sn0.1O12/C, Sn0.1-LTO/C) was prepared by a simple one-pot sol-gel method. The doped Sn4+ replaces part of Ti4+ in the crystal lattice, which makes Ti3+ require charge compensation, thus improving the ionic conductivity. The intervention of the conductive carbon skeleton further improves the conductivity of the Sn0.1-LTO/C composite material. The performance of Sn0.1-LTO/C as the cathode of MLIBs is explored. The initial discharge capacity was 159.1 mA h g-1 at 0.5 C, and it was maintained at 105 mA h g-1 even after 500 cycles. The excellent electrochemical performance is attributed to a small amount of Sn doping and the involvement of the conductive carbon skeleton, which indicated that the Sn0.1-LTO/C composite material provides great potential application in MLIBs.

4.
IEEE Trans Cybern ; PP2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38198259

ABSTRACT

Observer-based disturbance rejection holds substantial theoretical and practical relevance in the field of control engineering, with numerous variants of disturbance observers already schemed. Nevertheless, the criteria for accuracy and avenues for enhancement remain areas warranting further investigation. This article introduces an integral compensation function observer (CFO) featuring a novel structure and efficient utilization of information for estimating disturbances in n th-order uncertain systems. This approach enhances estimation accuracy by addressing the inherent limitations of the linear extended state observer (LESO), such as low order, lacking usage of information, nonconvergence, and limited bandwidth. Through the derivation and quantification of the disturbance sensitivity transfer function (DSTF), this study examines the disturbance sensitivities of the CFO, LESO, and an improved ESO (IESO). The findings indicate that the CFO elevates the estimable order of disturbance and surpasses both LESO and IESO in bandwidth and disturbance estimation accuracy. In evaluating both the EAD of the CFO and the disturbance-rejection performance (DRP) of CFO-based control, nonlinear pole assignment controls (NPACs) employing 2nd/3rd-order CFO, IESO, LESO, and 4 th-order CFO are implemented in the context of attitude control for a quadrotor unmanned aerial vehicle (QUAV) that is exposed to prearranged disturbance torques. The results illustrate that the CFO outperforms the IESO and LESO in terms of accurately estimating the prearranged disturbing torques. Furthermore, the recorded magnitudes of attitude in response to disturbances underscore the superior DRP of CFO-NPAC relative to IESO-NPAC and LESO-NPAC.

5.
Plant Biotechnol J ; 22(5): 1113-1131, 2024 May.
Article in English | MEDLINE | ID: mdl-38038155

ABSTRACT

Self-incompatibility (SI) is a widespread prezygotic mechanism for flowering plants to avoid inbreeding depression and promote genetic diversity. Citrus has an S-RNase-based SI system, which was frequently lost during evolution. We previously identified a single nucleotide mutation in Sm-RNase, which is responsible for the loss of SI in mandarin and its hybrids. However, little is known about other mechanisms responsible for conversion of SI to self-compatibility (SC) and we identify a completely different mechanism widely utilized by citrus. Here, we found a 786-bp miniature inverted-repeat transposable element (MITE) insertion in the promoter region of the FhiS2-RNase in Fortunella hindsii Swingle (a model plant for citrus gene function), which does not contain the Sm-RNase allele but are still SC. We demonstrate that this MITE plays a pivotal role in the loss of SI in citrus, providing evidence that this MITE insertion prevents expression of the S-RNase; moreover, transgenic experiments show that deletion of this 786-bp MITE insertion recovers the expression of FhiS2-RNase and restores SI. This study identifies the first evidence for a role for MITEs at the S-locus affecting the SI phenotype. A family-wide survey of the S-locus revealed that MITE insertions occur frequently adjacent to S-RNase alleles in different citrus genera, but only certain MITEs appear to be responsible for the loss of SI. Our study provides evidence that insertion of MITEs into a promoter region can alter a breeding strategy and suggests that this phenomenon may be broadly responsible for SC in species with the S-RNase system.


Subject(s)
Citrus , DNA Transposable Elements , DNA Transposable Elements/genetics , Citrus/genetics , Plant Breeding , Mutation , Ribonucleases/metabolism
6.
PLoS Genet ; 19(6): e1010811, 2023 06.
Article in English | MEDLINE | ID: mdl-37339133

ABSTRACT

Conservation of crop wild relatives is critical for plant breeding and food security. The lack of clarity on the genetic factors that lead to endangered status or extinction create difficulties when attempting to develop concrete recommendations for conserving a citrus wild relative: the wild relatives of crops. Here, we evaluate the conservation of wild kumquat (Fortunella hindsii) using genomic, geographical, environmental, and phenotypic data, and forward simulations. Genome resequencing data from 73 accessions from the Fortunella genus were combined to investigate population structure, demography, inbreeding, introgression, and genetic load. Population structure was correlated with reproductive type (i.e., sexual and apomictic) and with a significant differentiation within the sexually reproducing population. The effective population size for one of the sexually reproducing subpopulations has recently declined to ~1,000, resulting in high levels of inbreeding. In particular, we found that 58% of the ecological niche overlapped between wild and cultivated populations and that there was extensive introgression into wild samples from cultivated populations. Interestingly, the introgression pattern and accumulation of genetic load may be influenced by the type of reproduction. In wild apomictic samples, the introgressed regions were primarily heterozygous, and genome-wide deleterious variants were hidden in the heterozygous state. In contrast, wild sexually reproducing samples carried a higher recessive deleterious burden. Furthermore, we also found that sexually reproducing samples were self-incompatible, which prevented the reduction of genetic diversity by selfing. Our population genomic analyses provide specific recommendations for distinct reproductive types and monitoring during conservation. This study highlights the genomic landscape of a wild relative of citrus and provides recommendations for the conservation of crop wild relatives.


Subject(s)
Citrus , Citrus/genetics , Plant Breeding , Genome , Genomics , Crops, Agricultural/genetics , Genetic Variation
7.
Front Endocrinol (Lausanne) ; 14: 1110624, 2023.
Article in English | MEDLINE | ID: mdl-36742383

ABSTRACT

Background: Anlotinib may boost the efficacy of pancreatic cancer (PC) treatment if timely added to the GS regimen (Gemcitabine, Tegafur-gimeracil-oteracil potassium); however, no data has been published. This study evaluated the safety and efficacy of anlotinib in combination with the GS regimen(hereafter referred to as the A+GS regimen) in the first-line treatment of patients with unresectable or metastatic PC. Methods: Patients with unresectable or metastatic PC treated at Yueyang Central Hospital and Yueyang People's Hospital between October 2018 and June 2022 were enrolled in this retrospective real-world investigation. Treatment efficacy was evaluated based on the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR), while the treatment safety was assessed by the frequency of major adverse events (AEs). Results: Seventy-one patients were included in this study, 41 in the GS group and 30 in the A+GS group. The A+GS group had a longer mPFS than the GS group (12.0 months (95% CI, 6.0-18.0) and 6.0 months (95% CI, 3.0-8.1)), respectively (P = 0.005). mOS was longer in the GS+A group) when compared with the GS group (17.0 months (95%CI, 14.0-20.0) and 10.0 months (95% CI, 7.5-12.5)), respectively (P = 0.018). The GS+A group had higher ORR (50.0% vs 26.8%, P = 0.045) and DCR (83.3% vs 58.5%, P = 0.026). Furthermore, there were no grade 4-5 AEs and no treatment-related deaths, and no discernible increase in AEs in the GS+A group when compared with the GS group. Conclusion: The A+GS regimen therapy holds great promise in managing treatment-naive advanced PC, except that future prospective studies with larger sample sizes and multiple centers are required to determine its efficacy and safety.


Subject(s)
Pancreatic Neoplasms , Tegafur , Humans , Prospective Studies , Retrospective Studies , Tegafur/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms
8.
Natl Sci Rev ; 9(10): nwac114, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36415319

ABSTRACT

Apomixis, or asexual seed formation, is prevalent in Citrinae via a mechanism termed nucellar or adventitious embryony. Here, multiple embryos of a maternal genotype form directly from nucellar cells in the ovule and can outcompete the developing zygotic embryo as they utilize the sexually derived endosperm for growth. Whilst nucellar embryony enables the propagation of clonal plants of maternal genetic constitution, it is also a barrier to effective breeding through hybridization. To address the genetics and evolution of apomixis in Citrinae, a chromosome-level genome of the Hongkong kumquat (Fortunella hindsii) was assembled following a genome-wide variation map including structural variants (SVs) based on 234 Citrinae accessions. This map revealed that hybrid citrus cultivars shelter genome-wide deleterious mutations and SVs into heterozygous states free from recessive selection, which may explain the capability of nucellar embryony in most cultivars during Citrinae diversification. Analyses revealed that parallel evolution may explain the repeated origin of apomixis in different genera of Citrinae. Within Fortunella, we found that apomixis of some varieties originated via introgression. In apomictic Fortunella, the locus associated with apomixis contains the FhRWP gene, encoding an RWP-RK domain-containing protein previously shown to be required for nucellar embryogenesis in Citrus. We found the heterozygous SV in the FhRWP and CitRWP promoters from apomictic Citrus and Fortunella, due to either two or three miniature inverted transposon element (MITE) insertions. A transcription factor, FhARID, encoding an AT-rich interaction domain-containing protein binds to the MITEs in the promoter of apomictic varieties, which facilitates induction of nucellar embryogenesis. This study provides evolutionary genomic and molecular insights into apomixis in Citrinae and has potential ramifications for citrus breeding.

9.
J Thorac Oncol ; 17(10): 1205-1215, 2022 10.
Article in English | MEDLINE | ID: mdl-35659581

ABSTRACT

INTRODUCTION: Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. METHODS: This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. RESULTS: From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred. CONCLUSIONS: Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. CLINICAL TRIAL INFORMATION: NCT03502850.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Exanthema , Lung Neoplasms , Acrylamides , Aniline Compounds/therapeutic use , Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Diarrhea/chemically induced , ErbB Receptors , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/adverse effects
10.
Hortic Res ; 8(1): 199, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34465762

ABSTRACT

Self-incompatibility (SI) substantially restricts the yield and quality of citrus. Therefore, breeding and analyzing self-compatible germplasm is of great theoretical and practical significance for citrus. Here, we focus on the mechanism of a self-compatibility mutation in 'Guiyou No. 1' pummelo (Citrus maxima), which is a spontaneous mutant of 'Shatian' pummelo (Citrus maxima, self-incompatibility). The rate of fruit set and the growth of pollen tubes in the pistil confirmed that a spontaneous mutation in the pistil is responsible for the self-compatibility of 'Guiyou No. 1'. Segregation ratios of the S genotype in F1 progeny, expression analysis, and western blotting validated that the reduced levels of S2-RNase mRNA contribute to the loss of SI in 'Guiyou No. 1'. Furthermore, we report a phased assembly of the 'Guiyou No. 1' pummelo genome and obtained two complete and well-annotated S haplotypes. Coupled with an analysis of SV variations, methylation levels, and gene expression, we identified a candidate gene (CgHB40), that may influence the regulation of the S2-RNase promoter. Our data provide evidence that a mutation that affects the pistil led to the loss of SI in 'Guiyou No. 1' by influencing a poorly understood mechanism that affects transcriptional regulation. This work significantly advances our understanding of the genetic basis of the SI system in citrus and provides information on the regulation of S-RNase genes.

11.
Nonlinear Dyn ; 106(2): 1411-1424, 2021.
Article in English | MEDLINE | ID: mdl-34511722

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been causing an outbreak of a new type of pneumonia globally, and repeated outbreaks have already appeared. Among the studies on the spread of the COVID-19, few studies have investigated the repeated outbreaks in stages, and the quantitative condition of a controllable spread has not been revealed. In this paper, a brief compartmental model is developed. The effective reproduction number (ERN) of the model is interpreted by the ratio of net newly infectious individuals to net isolation infections to assess the controllability of the spread of COVID-19. It is found that the value of the ERN at the inflection point of the pandemic is equal to one. The effectiveness of the quarantine, even the treatment, is parametrized in various stages with Gompertz functions to increase modeling accuracy. The impacts of the vaccinations are discussed by adding a vaccinated compartment. The results show that the sufficient vaccinations can make the inflection point appear early and significantly reduce subsequent increases in newly confirmed cases. The analysis of the ERNs of COVID-19 in the United States, Spain, France, and Peru confirms that the condition of a repeated outbreak is to relax or lift the interventions related to isolation and quarantine interventions to a level where the ERN is greater than one.

12.
Plant J ; 108(3): 705-724, 2021 11.
Article in English | MEDLINE | ID: mdl-34398993

ABSTRACT

Ethylene-responsive factors (ERFs) are plant-specific transcription factors involved in cold stress response, and raffinose is known to accumulate in plants exposed to cold. However, it remains elusive whether ERFs function in cold tolerance by modulating raffinose synthesis. Here, we identified a cold-responsive PtrERF108 from trifoliate orange (Poncirus trifoliata (L.) Raf.), a cold-tolerant plant closely related to citrus. PtrERF108 is localized in the nucleus and has transcriptional activation activity. Overexpression of PtrERF108 conferred enhanced cold tolerance of transgenic lemon, whereas virus-induced gene silencing (VIGS)-mediated knockdown of PtrERF108 in trifoliate orange greatly elevated cold sensitivity. Transcriptome profiling showed that PtrERF108 overexpression caused extensive reprogramming of genes associated with signaling transduction, physiological processes and metabolic pathways. Among them, a raffinose synthase (RafS)-encoding gene, PtrRafS, was confirmed as a direct target of PtrERF108. RafS activity and raffinose content were significantly increased in PtrERF108-overexpressing transgenic plants, but prominently decreased in the VIGS plants under cold conditions. Meanwhile, exogenous replenishment of raffinose could recover the cold tolerance of PtrERF108-silenced plants, whereas VIGS-mediated knockdown of PtrRafS resulted in cold-sensitive phenotype. Taken together, the current results demonstrate that PtrERF108 plays a positive role in cold tolerance by modulation of raffinose synthesis via regulating PtrRafS. Our findings reveal a new transcriptional module composed of ERF108-RafS underlying cold-induced raffinose accumulation in plants.


Subject(s)
Cold-Shock Response/physiology , Galactosyltransferases/genetics , Plant Proteins/genetics , Poncirus/physiology , Raffinose/biosynthesis , Cell Nucleus/genetics , Cell Nucleus/metabolism , Citrus/genetics , Citrus/physiology , Galactosyltransferases/metabolism , Gene Expression Regulation, Plant , Gene Silencing , Plant Proteins/metabolism , Plants, Genetically Modified , Poncirus/drug effects , Promoter Regions, Genetic , Raffinose/genetics , Raffinose/pharmacology , Transcription Factors/genetics , Transcription Factors/metabolism
13.
Chaos ; 31(1): 013101, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33754774

ABSTRACT

In this paper, a four-dimensional conservative system of Euler equations producing the periodic orbit is constructed and studied. The reason that a conservative system often produces periodic orbit has rarely been studied. By analyzing the Hamiltonian and Casimir functions, three invariants of the conservative system are found. The complete integrability is proved to be the mechanism that the system generates the periodic orbits. The mechanism route from periodic orbit to conservative chaos is found by breaking the conservation of Casimir energy and the integrability through which a chaotic Hamiltonian system is built. The observed chaos is not excited by saddle or center equilibria, so the system has hidden dynamics. It is found that the upgrade in the Hamiltonian energy level violates the order of dynamical behavior and transitions from a low or regular state to a high or an irregular state. From the energy bifurcation associated with different energy levels, rich coexisting orbits are discovered, i.e., the coexistence of chaotic orbits, quasi-periodic orbits, and chaotic quasi-periodic orbits. The coincidence between the two-dimensional diagram of maximum Lyapunov exponents and the bifurcation diagram of Hamiltonian energy is observed. Finally, field programmable gate array implementation, a challenging task for the chaotic Hamiltonian conservative system, is designed to be a Hamiltonian pseudo-random number generator.

14.
3 Biotech ; 11(2): 90, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33520576

ABSTRACT

The aim of this work was to rapidly and efficiently insert target DNA sequences into predetermined genomic sites in Saccharomyces cerevisiae. In this study, we designed two technical routes for gene insertion in the S. cerevisiae genome based on the CRISPR/Cas9 system, and a CRISPR array was inserted into the Amp site and the crRNA site of the pCRCT plasmid, respectively. The CRISPR array consists of a 100 bp donor sequence, the target gene and guide sequence. A 100 bp donor sequence was designed to have two 50 bp homology arms flanking the Cas9 cutting site and incorporate 8 bp or 1000 bp deletions including the PAM sequence, where the target gene was also inserted. The results showed that using only one pCRCTG plasmid and a 100 bp dsDNA mutagenizing homologous recombination donor, we can successfully insert a 2.9 kb gene fragment at the target site of the S. cerevisiae genome. However, inserting the CRISPR array into the crRNA site has a higher recombination efficiency than inserting into the Amp site. This recombination strategy represents a powerful tool for creating yeast strains with target gene inserts.

15.
Top Curr Chem (Cham) ; 379(1): 4, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33428032

ABSTRACT

COVID-19 has broken out rapidly in nearly all countries worldwide, and has blossomed into a pandemic. Since the beginning of the spread of COVID-19, many scientists have been cooperating to study a vast array of old drugs and new clinical trial drugs to discover potent drugs with anti-COVID-19 activity, including antiviral drugs, antimalarial drugs, immunosuppressants, Chinese medicines, Mpro inhibitors, JAK inhibitors, etc. The most commonly used drugs are antiviral compounds, antimalarial drugs and JAK inhibitors. In this review, we summarize mainly the antimalarial drugs chloroquine and hydroxychloroquine, the antiviral drugs Favipiravir and Remdesivir, and JAK inhibitor Ruxolitinib, discussing their biological activities, clinical trials and synthesis progress.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Small Molecule Libraries , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Drug Repositioning , Humans , Janus Kinase Inhibitors/therapeutic use
16.
Nonlinear Dyn ; 106(2): 1149-1167, 2021.
Article in English | MEDLINE | ID: mdl-33071458

ABSTRACT

At present, more and more countries have entered the parallel stage of fighting the epidemic and restoring the economy after reaching the inflection point. Due to economic pressure, the government of India had to implement a policy of relaxing control during the rising period of the epidemic. This paper proposes a compartment model to study the development of COVID-19 in India after relaxing control. The Sigmoid function reflecting the cumulative effect is used to characterize the model-based diagnosis rate, cure rate and mortality rate. Considering the influence of the lockdown on the model parameters, the data are fitted using the method of least squares before and after the lockdown. According to numerical simulation and model analysis, the impact of India's relaxation of control before and after the inflection point is studied. Research shows that adopting a relaxation policy prematurely will have disastrous consequences. Even if the degree of relaxation is only 5% before the inflection point, it will increase the number of deaths by 15.03%. If the control is relaxed after the inflection point, the higher degree of relaxation, the more likely a secondary outbreak will occur, which will extend the duration of the pandemic, leading to more deaths and put more pressure on the health care system. It is found that after the implementation of the relaxation policy, medical quarantine capability and public cooperation are two vital indicators. The results show that if the supply of kits and detection speed can be increased after the control is relaxed, the secondary outbreak can be effectively avoided. Meanwhile, the increase in public cooperation can significantly reduce the spread of the virus, suppress the second outbreak of the pandemic and reduce the death toll. It is of reference significance to the government's policy formulation.

17.
J Colloid Interface Sci ; 536: 149-159, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30366180

ABSTRACT

HYPOTHESIS: Bionic superhydrophobicity including high contact angle, low sliding angle and nonstick property, combined with both strong pH and ultraviolet (UV) resistance, is difficult to simultaneously achieve for large-scale preparation of superhydrophobic surfaces by blending polymer with a nonreactive inorganic nanofiller. EXPERIMENTS: A series of high pH and UV-irradiation-resistant superhydrophobic nanocomposite films were prepared through UV-light-assisted chemical cross-linking among ternary components under nitrogen protection. Ethoxylated bisphenol A diacrylate, 2-(perfluorooctyl) ethyl acrylate, reactive thiol-coupled graphene nanosheets and photoinitiator were evenly mixed, followed by UV-irradiation curing. FINDINGS: Abundant 3D networks could be formed. A robust self-wrinkling surface morphology was formed due to a UV-curing-induced inner tension in the composites, 2D morphology-induced flexibility for graphene nanosheets and fluorine-bearing component-induced phase separation at the wetted surfaces. High roughness and use of the fluorine element endows the surfaces with superhydrophobicity and oleophobicity. A favorable nonstick performance was obtained. Superhydrophobicity could be maintained despite changing the film-forming substrate, pH of soaking solutions from 1 to 12, or use of a prolonged UV-irradiation time reaching 120 h. Therefore, both superhydrophobicity/oleophobicity and strong pH/UV resistance are finely balanced. This work might open up the way for large-scale fabrication of promising superhydrophobic surfaces.

18.
Materials (Basel) ; 11(11)2018 Nov 14.
Article in English | MEDLINE | ID: mdl-30441847

ABSTRACT

High discharged energy density and charge⁻discharge efficiency, in combination with high electric breakdown strength, maximum electric displacement and low residual displacement, are very difficult to simultaneously achieve in single-component polymer dielectrics. Plenty of researches have reported polymer based composite dielectrics filled with inorganic fillers, through complex surface modification of inorganic fillers to improve interface compatibility. In this work, a novel strategy of introducing environmentally-friendly biological polyester into fluoropolymer matrix has been presented to prepare all-organic polymer composites with desirable high energy storage properties by solution cast process (followed by annealing or stretching post-treatment), in order to simplify the preparation steps and lower the cost. Fluoropolymer with substantial ferroelectric domains (contributing to high dielectric response) as matrix and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) with excellent linear polarization property (resulting in high breakdown strength) as filler were employed. By high-temperature annealing, the size of ferroelectric domains could be improved and interfacial air defects could be removed, leading to elevated high energy storage density and efficiency in composite. By mono-directional stretching, the ferroelectric domains and polyester could be regularly oriented along stretching direction, resulting in desired high energy storage performances as well. Besides, linear dielectric components could contribute to high efficiency from their strong rigidity restrain effect on ferroelectric component. This work might open up the way for a facile fabrication of promising all-organic composite dielectric films with high energy storage properties.

19.
Materials (Basel) ; 11(9)2018 Sep 13.
Article in English | MEDLINE | ID: mdl-30216980

ABSTRACT

Promising comprehensive properties, including high permittivity, low dielectric loss, high breakdown strength, low electrical conductivity, and high thermal conductivity, are very hard to simultaneously obtain in high-frequency applicable polymer nanocomposite dielectrics. Instead of traditional electric percolation, in this work, a novel route based on a synergy between electric percolation and induced polarization has been raised to prepare 0⁻3 type nanocomposites with an enhanced high permittivity (high-k) property and low loss at high frequency. This work aimed at optimizing that synergy to achieve the favorable properties mentioned above in composite dielectrics used at high frequencies such as 1 MHz and 1 GHz. Conductive beta-SiC nanoparticles with a particle size of ~30 nm were employed as filler and both insulating poly(vinyl alcohol) and polyvinyl chloride were employed as polymer matrices to construct two composite systems. Utilizing polyvinyl chloride rather than poly(vinyl alcohol) realizes higher comprehensive electrical properties in composites, ascribed to optimization of that synergy. The optimization was achieved based on a combination of mild induced polarization and polarization-assisted electric percolation. Therefore, this work might open the way for large-scale production of high-frequency applicable composite dielectrics with competitive comprehensive electrical properties.

20.
Materials (Basel) ; 11(7)2018 Jun 29.
Article in English | MEDLINE | ID: mdl-29966239

ABSTRACT

High overall performance, including high dielectric constant, low loss, high breakdown strength, fine flexibility, and strong tensile properties, is difficult to achieve simultaneously in polymer nanocomposites. In our prior work, we modified the surfaces of alpha-SiC nanoparticles and chemically cross-linked the polymeric matrix to simultaneously promote the dielectric and mechanical properties of composites. In this work, a novel strategy of high-temperature plastification towards a polymeric matrix has been proposed to fabricate ternary nanocomposites with balanced dielectric and mechanical characteristics by the solution cast method in order to reduce costs and simplify steps during large-scale preparation. Poly(vinylidene fluoride-chlorotrifluoroethylene) with inner double bonds as matrix, unfunctionalized alpha-SiC nanoparticles (NPs) as filler, and dibutyl phthalate (DBP) as plasticizer were employed. By introducing DBP and high-temperature treatment, the dispersion of NPs and the degree of compactness of the interface regions were both improved due to the reduced cohesion of the fluoropolymer, resulting in an increase in the dielectric constant (by 30%) and breakdown strength (by 57%) as well as the lowering of loss (by 30%) and conductivity (by 16%) in nanocomposites. Moreover, high-temperature plastification contributed to the promotion of flexible and tensile properties. This work might open the door to large-scale fabrication of nanocomposite dielectrics with high overall properties through the cooperation of the plasticizer and high temperature.

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