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BACKGROUND: The exact role of sperm reactive oxygen species (ROS) in early embryo development has yet to be fully identified, and most of existing research did not differentiate female infertility factors, ignoring the importance of oocyte quality in embryo development and the large differences in oocyte quality in women with infertility of different etiologies. And there has been no relevant report on whether different types of sperm ROS have distinct effects on embryo development. This study aimed to study the impact of selected sperm ROS, namely, sperm mitochondrial ROS (mROS) and hydrogen peroxide, on human embryo development after conventional in vitro fertilization (IVF) cycles in patients with normo-ovulatory infertility vs. anovulatory infertility. METHODS: This was a prospective investigation including 393 couples underwent IVF cycles, among whom 90 patients had anovulatory infertility and 303 patients had normo-ovulatory infertility in a public university-affiliated in vitro fertilization center. Sperm mROS and hydrogen peroxide testing were performed by flow cytometry and analyzed for their relationship with embryo development indices on days 1-6 after IVF. Multivariate logistic regression analysis was used to control for female potential confounders. The nonlinear effects of sperm ROS on embryo development were analyzed by the Restricted cubic spline (RCS) method. RESULTS: 1. Multivariate linear logistic regression analysis showed that high proportion of mROS positive sperm improved the 2PN rate (OR = 1.325, 95% CI: 1.103-1.595), day 3 embryo utilization rate (OR = 1.362, 95% CI: 1.151-1.614) and good-quality day 3 embryo rate (OR = 1.391, 95% CI: 1.089-1.783) in patients with anovulatory infertility. High percentage of sperm mROS and hydrogen peroxide had adverse effects on cleavage-stage embryo and blastocyst development in patients with normo-ovulatory infertility. 2. For patients with polycystic ovarian syndrome (PCOS) anovulatory infertility, there were significant distinct effects on embryo development indices between sperm mROS and hydrogen peroxide, and the increased rate of sperm mROS improved the good-quality day 3 embryo rate (OR = 1.435, 95% CI: 1.045-1.981); however, high percentage of sperm hydrogen peroxide reduced the blastocyst utilization rate (OR = 0.555, 95% CI: 0.353-0.864) and the good-quality blastocyst rate (OR = 0.461, 95% CI: 0.292-0.718). 3. Multivariate RCS analysis revealed that sperm ROS had a nonlinear (such as a parabolic curve) effect on embryo development in patients with anovulatory infertility (P < 0.05), and either greatly increased or greatly decreased affected cleavage-stage embryo and blastocyst development. The effects of sperm ROS in patients with normo-ovulatory infertility were both linear and nonlinear. CONCLUSIONS: These findings indicate that contrary effects of sperm mROS on embryo development depending on whether patients treated with IVF cycles had normal ovulation. Regardless of whether the patients ovulated normally, increased sperm hydrogen peroxide rate damaged blastocyst development. It is necessary to evaluate male sperm ROS levels and the female ovulatory state to determine an individualized intervention plan before starting cycles, as this may be beneficial for infertile couples.
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Peróxido de Hidrogênio , Infertilidade Feminina , Humanos , Masculino , Feminino , Gravidez , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/farmacologia , Estudos Prospectivos , Sêmen , Fertilização in vitro/métodos , Desenvolvimento Embrionário , Espermatozoides , Infertilidade Feminina/terapia , Taxa de Gravidez , Estudos RetrospectivosRESUMO
In order to cut down on costs to the greatest possible extent, enterprises hope to distribute goods to different customers at the lowest costs possible. Based on this, this paper proposes an optimal location method for an intelligent transportation logistics warehouse. This scheme combines a variety of complex mechanisms to allow IoT devices to provide input. The scheme makes full use of the irreducibility of a blockchain system to promote the development and design of blockchain logistics applications. This method is aimed at tracking the progress of transportation of products in the whole supply chain. Experimental results show that, compared with traditional methods, the optimal positioning method has the advantages of fewer calculations, a high positioning accuracy, and a low overall cost, and it obtains the best warehouse positioning results. Based on the Internet of Things and blockchain technology, the application of intelligent logistics systems enables enterprises to intuitively understand their current inventory and the transportation status of goods, thus better controlling changes in enterprise resources.
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Blockchain , Internet das Coisas , Tecnologia , Meios de TransporteRESUMO
BACKGROUND: Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission. MAIN TEXT: Strategy 1: Intensive interventions within 2.5 km-wide perimeter along the border to prevent border-spill malaria. The area within 2.5 km along the international border is the travel radius of anopheline mosquitoes. Comprehensive interventions should include: (1) proactive and passive case detection, (2) intensive vector surveillance, (3) evidence-based vector control, and (4) evidence-based preventative treatment with anti-malarial drugs. Strategy 2: Community-based malaria detection and screening of migrants and travellers in frontier townships. Un-permitted travellers cross borders frequently and present in frontier townships. Maintenance of intensified malaria surveillance should include: (1) passive malaria detection in the township hospitals, (2) seek assistance from villager leaders and health workers to monitor cross border travellers, and refer febrile patients to the township hospitals and (3) the county's Centre for Disease Control and Prevention maintain regular proactive case detection. Strategy 3: Universal coverage of malaria surveillance to detect malaria cues. Passive detection should be consolidated into the normal health service. Health services personnel should remain vigilant to ensure universal coverage of malaria detection and react promptly to any malaria cues. Strategy + 1: Strong collaborative support with neighbouring countries. Based on the agreement between the two countries, integrated control strategies should be carried out to reduce malaria burden for both countries. There should be a clear focus on the border areas between neighbouring countries. CONCLUSION: The 3 + 1 strategy is an experience summary of border malaria control and elimination, and then contributed to malaria elimination in Yunnan's border areas, China. Nevertheless, Yunnan still has remaining challenges of re-establishment of malaria transmission in the border areas, and the 3 + 1 strategy should still be carried out.
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Transmissão de Doença Infecciosa/prevenção & controle , Malária/prevenção & controle , China , Emigração e Imigração , Humanos , Malária/diagnóstico , Malária/transmissãoRESUMO
We report the first examples of selective and regiodivergent opening of unsymmetrical phenonium ions with chloride ions. These reactions are enabled by the dual role of SnCl4 and TiCl4 as Lewis acids and chloride nucleophiles. Reagent control dictates addition of chloride at either the substituted internal position (SnCl4) or unsubstituted terminal position (TiCl4) of the phenonium ion. These reactions are highly selective, stereospecific, operationally simple, and proceed in good to excellent yields. Diverse product utility is demonstrated.
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Pyrimidine nucleosides are an important class of compounds with versatile applications across many fields, including biology and medicinal chemistry. Synthesis of nucleoside analogs in optically pure form via traditional glycosylation has always been a challenge, especially for unnatural carbohydrate motifs which do not have C2 substitution to dictate the stereochemical outcome of the newly formed glyosidic bond. Herein, we report an asymmetric Pd-catalyzed synthesis of nucleoside analogs enabled by the development of a series of chiral ligands. A variety of 5-substituted pyrimidine nucleobases, ranging from 5- to 12-membered ring nucleoside analogs, are generated in excellent yield (up to 96%) as well as diastereo- (>20:1) and enantioselectivity (up to 99.5% ee). These nucleoside analogs bearing an iodide functional group handle allow for rapid transformation to a variety of other interesting pyrimidine nucleoside structures.
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Carbono/química , Compostos Heterocíclicos/síntese química , Hidrocarbonetos Aromáticos/química , Oxigênio/química , Paládio/química , Nucleosídeos de Pirimidina/química , Catálise , Compostos Heterocíclicos/química , Ligantes , Estrutura Molecular , EstereoisomerismoRESUMO
The synthesis of des-epoxy-amphidinolide N was achieved in 22 longest linear and 33 total steps. Three generations of synthetic endeavors are reported herein. During the first generation, our key stitching strategy that highlighted an intramolecular Ru-catalyzed alkene-alkyne (Ru AA) coupling and a late-stage epoxidation proved successful, but the installation of the α,α'-dihydroxyl ketone motif employing a dihydroxylation method was problematic. Our second generation of synthetic efforts addressed the scalability problem of the southern fragment synthesis and significantly improved the efficiency of the atom-economical Ru AA coupling, but suffered from several protecting group-based issues that proved insurmountable. Finally, relying on a judicious protecting group strategy together with concise fragment preparation, des-epoxy-amphidinolide N was achieved in a convergent fashion. Calculations disclose a hydrogen-bonding bridge within amphidinolide N. Comparisons of 13C NMR chemical shift differences using our synthetic des-epoxy-amphidinolide N suggest that amphidinolide N and carbenolide I are probably identical.
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Macrolídeos/síntese química , Alcenos/química , Alcinos/química , Catálise , Ciclização , Esterificação , Ligação de Hidrogênio , Conformação Molecular , Oxirredução , Rutênio/química , EstereoisomerismoRESUMO
In this study, we sequenced and annotated the complete mitochondrial genome of Loxocephala perpunctata (Jacobi, 1944) (Hemiptera: Eurybrachidae). The mitogenome of L. perpunctata is 15,017 bp long and includes 37 genes and a large control region. Consisting of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a D-loop. All protein-coding genes have the usual ATN start codons, except for ND5, which uses the noncanonical codon GTG. 22 tRNAs, the length ranging from 59 to 69 bp, having the clover-leaf structure except for the dihydrouridine (DHU) arm of trnS2 forming a simple loop.
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In the present study, the complete mitochondrial genome of Lophops carinata (Hemiptera: Lophopidae) was sequenced for the first time through next-generation sequencing. The complete mitogenome of L. carinata is 15,553 bp in length, with the typical gene content and arrangement usually observed in Hexapods. The mitogenome consisted of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 D-loop. The overall nucleotide composition of the mitogenome was 44.6% A, 14.0% C, 8.3% G, and 33.2% T, with an A + T bias of 77.8%. Phylogenetic analyses from 12 Fulgoroidea species by maximum likelihood were consistent and well supported the basal position of Delphacidae, a close affinity among the families Ricaniidae, Issidae, and Flatidae, and a close relationship between Achilidae and Fulgoridae. And L. carinata belong to a separate lineage, located in the middle of the phylogenetic tree.
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Today, the global exchange market has been the world's largest trading market, whose volume could reach nearly 5.345 trillion US dollars, attracting a large number of investors. Based on the perspective of investors and investment institutions, this paper combines theory with practice and creatively puts forward an innovative model of double objective optimization measurement of exchange forecast analysis portfolio. To be more specific, this paper proposes two algorithms to predict the volatility of exchange, which are deep learning and NSGA-II-based dual-objective measurement optimization algorithms for the exchange investment portfolio. Compared with typical traditional exchange rate prediction algorithms, the deep learning model has more accurate results and the NSGA-II-based model further optimizes the selection of investment portfolios and finally gives investors a more reasonable investment portfolio plan. In summary, the proposal of this article can effectively help investors make better investments and decision-making in the exchange market.
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Aprendizado Profundo , Algoritmos , Investimentos em SaúdeRESUMO
OBJECTIVE: To evaluate malaria situation in areas of Yunnan Province bordering with Myanmar, Laos and Vietnam. METHODS: Blood samples on filter paper were collected from the entry people in March to December of 2007 involving 19 national and provincial ports of entry. Indirect fluorescent antibody test (IFAT) was carried out by using the blood samples collected before June 30 as the first half year and after July 1 as the second half year. Analysis was made on the relationship of IFAT positive rate and GMRT to malaria incidence in the province reported by the China information system for disease control and prevention. RESULTS: IFAT positive rate in the first half year (5.6%) was 20.9% higher than that of second half year (4.4%) (chi2=12.95%, P<0.05). There was a positive correlation between IFAT positive rate and the number of malaria cases reported in 2007 from the 8 bordering prefectures (r=0.8124, P<.05). The highest IFAT positive rate was found in Dehong (8.7%), Baoshan (7.1%), and Lingcang (65%). Among the 19 entry ports, the highest IFAT positive rate was found in 5 entry ports: Lvliang, Laying, Jiegao, Houqiao, and Qingshuihe, all in China-Myanmar border. The IFAT positive rate in the Chinese entry people increased with their days of staying outside the border. Among the entry people, the highest antibody positive rate was from those of Myanmar nationality (11.7%) followed by those from Yunnan (3.7%). CONCLUSION: To certain extent, higher malaria incidence outside the border impacts that of Yunnan Province.
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Malária/sangue , Malária/prevenção & controle , Quarentena/estatística & dados numéricos , China , Humanos , Incidência , Malária/epidemiologia , Mianmar/epidemiologiaRESUMO
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. METHODS: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. RESULTS: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. CONCLUSION: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.
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Neoplasias Colorretais/genética , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Proteínas Ribossômicas/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HEK293 , Células HT29 , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/patologia , Isoformas de Proteínas , RNA Mensageiro/genéticaRESUMO
In the present study, the complete mitochondrial genomes (mitogenomes) of five Achilidae (Hemiptera: Fulgoroidea), Betatropis formosana, two new species (Magadhaideus luodiana sp. nov and Peltatavertexalis horizontalis sp. nov), Plectoderini sp. and Paracatonidia sp., were sequenced for the first time through next-generation sequencing. The five mitogenomes ranged from 15,214 to 16,216 bp in length, with the typical gene content and arrangement usually observed in Hexapods. The motif "ATGATAA" between atp8 and atp6 was found in all the analyzed species. An overlap "AAGCTTA" between trnW and trnC was observed in the mitogenomes of most Fulgoroidea. The structural and compositional analyses of 26 Fulgoroidea mitogenomes, including the gene rearrangement of five tRNAs (trnW, trnC and trnY; trnT and trnP), the A + T content and AT-skew of the whole mitogenomes, and the nuclear acid and amino acid compositions of the protein-coding genes (PCGs), revealed family-level differences between Delphacidae and other families (Achilidae, Flatidae, Fulgoridae, Issidae and Ricaniidae). Phylogenetic analyses of 13 protein-coding genes from 26 Fulgoroidea species by maximum likelihood and Bayesian Inference were consistent and well supported the basal position of Delphacidae, a close affinity among the families Flatidae, Issidae and Ricaniidae, and a close relationship between Achilidae and Fulgoridae.
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Two new species of the planthopper genus Magadhaideus Long & Chen, 2017 from China, Magadhaideusluchunensis sp. n. and Magadhaideuspingbianensis sp. n., are described and illustrated. Photographs of the new species are provided and a key to species of Magadhaideus is also given.
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Molecular identification and genetic analysis of cherry are necessary for solving the problem of synonyms and homonyms that occur in cherry production. In this study, capillary electrophoresis with fluorescent-labeled simple sequence repeat (SSR) primers was used to identify 63 cherry cultivars (varieties and rootstocks) planted in Shaanxi province, China. A total of 146 alleles were amplified by 10 SSR primer pairs, ranging from 10 to 20 per locus (mean: 14); among the SSR primer pairs, genotype number ranged from 12 to 26 (mean: 18). The mean values of gene diversity, heterozygosity, and polymorphism information content were 0.7549 (range 0.4011-0.8782), 0.5952 (range 0.3810-0.9683), and 0.7355 (range 0.3937-0.8697), respectively. An unweighted pair-group method with arithmetic average cluster analysis was used to separate the cherry cultivars. A model-based structure analysis separated the cultivars into three populations, which was consistent with the results of a phylogenic and principal component analysis. Based on Bayes' rule, the cultivars were further subdivided into seven populations. Some of the 63 cherry cultivars that are often confused in production were distinguished, and DNA fingerprinting of cherry cultivars was established. This research will significantly assist in the identification of cherry cultivars at the molecular level.
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OBJECTIVE: Locus and allellic heterogeneity in polycystic kidney disease (PKD) is a great challenge in precision diagnosis. We aim to establish comprehensive methods to distinguish the pathogenic mutations from the variations in PKD1, PKD2 and PKHD1 genes in a limited time and lay the foundation for precisely prenatal diagnosis, preimplantation genetic diagnosis and presymptom diagnosis of PKD. METHODS: Nested PCR combined with direct DNA sequencing were used to screen variations in PKD1, PKD2 and PKHD1 genes. The pathogenicity of de novel variations was assessed by the comprehensive methods including clinic data and literature review, databases query, analysis of co-segregation of the variants with the disease, variant frequency screening in the population, evolution conservation comparison, protein structure analysis and splice sites predictions. RESULTS: 17 novel mutations from 15 Chinese Han families were clarified including 10 mutations in PKD1 gene and 7 mutations in PKHD1 gene. The novel mutations were classified as 4 definite pathogenic, 2 highly likely pathogenic, 4 likely pathogenic, 7 indeterminate by the comprehensive analysis. The results were verified the truth by the follow-up visits. CONCLUSIONS: The comprehensive methods may be useful in distinguishing the pathogenic mutations from the variations in PKD1, PKD2 and PKHD1 genes for prenatal diagnosis and presymptom diagnosis of PKD. Our results also enriched PKD genes mutation spectrum and evolved possible genotype-phenotype correlations of Chinese Han population.
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Mutação de Sentido Incorreto , Doenças Renais Policísticas/genética , Receptores de Superfície Celular/genética , Canais de Cátion TRPP/genética , China , Feminino , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Doenças Renais Policísticas/patologiaRESUMO
The first asymmetric total synthesis of the structurally unique Lycopodium alkaloid (-)-lycospidine A, containing an unprecedented five-membered ring, has been accomplished in only 10 steps with 21.6% overall yield from the known conveniently available sulfoxide. This protecting-group-free short synthesis relied on the use of a key amidation/aza-Prins domino cyclization reaction to rapidly construct the tricyclic skeleton and two continuous stereocenters (one of which is a bridged quaternary stereocenter). An intramolecular aldol condensation was successfully utilized to establish the unique five-membered ring, and a late-stage oxidation inspired by biosynthesis pathway was adopted to synthesize the diosphenol ring of (-)-lycospidine A.
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A protecting-group-free route for the total synthesis of (-)-lycopodine was demonstrated in only 8 steps from Wade's fawcettimine enone (12 steps from commercial availiable (R)-(+)-pulegone). The key core of this alkaloid was constructed through a phosphoric acid promoted and highly stereocontrolled alkyne aza-Prins cyclization reaction, synchronously establishing the bridged B-ring and the C13 quaternary stereocenter. Importantly, the synthesis further features a new efficient approach for the preparation of other lycopodine-type alkaloids.
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The first enantioselective total synthesis of the structurally unique nortriterpenoid (-)-walsucochin B has been accomplished through the cationic polyolefin cyclization initiated by chiral epoxide. The core framework and the stereocenters in the natural product were all constructed in this step. A site-selective, late-stage free-radical halogenation and Seyferth-Gilbert homologation was adopted to install the acetylene moiety to synthesize the phenylacetylene. The absolute configuration of walsucochin B was confirmed through enantioselective total synthesis.
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Produtos Biológicos/síntese química , Triterpenos/síntese química , Produtos Biológicos/química , Ciclização , Compostos de Epóxi/química , Radicais Livres , Estrutura Molecular , Estereoisomerismo , Triterpenos/químicaRESUMO
A 6-day-old female patient suddenly died of congestive heart failure, hepatomegaly and hypoglycemic encephalopathy. Tandem mass spectrometry (MS) analysis revealed a possibility of carnitine deficiency. However, many of the clinical symptoms had not yet occurred at that time, and the clinical data was incomplete. We aim to derive a systematic procedure of identifying pathogenic mutations for similar patients. Physicians could save patients' lives with effective treatment at a much earlier stage. Direct sequencing of the exons and exon-intron boundaries of GAA, SLC25A5, CPT1, CPT2, SLC25A20 and MUT genes were performed on the parents of the patient. DNA from the blood spots of the patient was analyzed for the MUT gene. The results revealed that the patient was a compound heterozygote with MUT. c. 729_730insTT and c. 1677-1G>A. cDNA sequence demonstrated MUT c. 1677-1G>A resulting in the deletion of eight nucleotides and the introduction of 13 novel amino acids before premature termination.
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Erros Inatos do Metabolismo dos Aminoácidos/genética , Metilmalonil-CoA Mutase/deficiência , Metilmalonil-CoA Mutase/genética , Mutação , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Carnitina/sangue , Carnitina/deficiência , China , Cromossomos Humanos Par 6 , Diagnóstico Diferencial , Evolução Fatal , Feminino , Deleção de Genes , Humanos , Recém-Nascido , Metilmalonil-CoA Mutase/metabolismo , Mutagênese Insercional , PaisRESUMO
Hemophilia A is an x-linked recessive inherited bleeding disorder. So far, more than 1,885 disease-causing mutations of factor VIII gene have been identified. Clinic confers a great challenge for the molecular diagnosis. We aim to make a better strategy for the molecular diagnosis in Hemophilia A. First, factor VIII intron 22 inversion and intron 1 inversion mutations were detected using Inversion-PCR and double-tube multiple PCRs. And then, non-inversion mutations were analyzed by denaturing high performance liquid chromatography and/or direct sequencing. Novel mutations were further analyzed the conservation and 3D structures by a B domain deleted crystallographic model and bioinformatics. Finally, we can indirectly confirm the diagnosis by linkage analysis for the patients with the confusing diagnosis by the techniques mentioned above. Eleven patients with the factor VIII Inv 22 were found, and the remaining 16 patients were found with 11 different mutations, of which 3 was novel mutations affecting A1, B domains and splicing site. Moreover, the prenatal diagnosis was performed on 14 fetuses. Ten fetuses were successfully confirmed to be normal, 1 fetus to be a heterozygote with factor VIII c.3275-3276 ins A and 3 fetuses to be hemizygotes with factor VIII Inv 22 mutation.