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1.
Proc Natl Acad Sci U S A ; 118(41)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34620709

RESUMO

Germ cells possess the Piwi-interacting RNA pathway to repress transposable elements and maintain genome stability across generations. Transposable element mobilization in somatic cells does not affect future generations, but nonetheless can lead to pathological outcomes in host tissues. We show here that loss of function of the conserved zinc-finger transcription factor Hinfp causes dysregulation of many host genes and derepression of most transposable elements. There is also substantial DNA damage in somatic tissues of Drosophila after loss of Hinfp. Interference of transposable element mobilization by reverse-transcriptase inhibitors can suppress some of the DNA damage phenotypes. The key cell-autonomous target of Hinfp in this process is Histone1, which encodes linker histones essential for higher-order chromatin assembly. Transgenic expression of Hinfp or Histone1, but not Histone4 of core nucleosome, is sufficient to rescue the defects in repressing transposable elements and host genes. Loss of Hinfp enhances Ras-induced tissue growth and aging-related phenotypes. Therefore, Hinfp is a physiological regulator of Histone1-dependent silencing of most transposable elements, as well as many host genes, and serves as a venue for studying genome instability, cancer progression, neurodegeneration, and aging.

2.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

3.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

4.
Plant Dis ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569828

RESUMO

Acer pictum subsp. mono (Maxim.) H. Ohashi is a common deciduous tree species that is widely distributed in Northeast and Northern China, including all provinces of the Yangtze River Basin (Liu et al. 2014). A foliar disease, with an incidence of ~90% (19/21 trees), occurred on A. pictum subsp. mono in a community park, Nanjing, Jiangsu, China in July 2019. On average, ~80% of the leaves per individual tree were infected by this disease. The symptoms initially appeared as brown, necrotic lesions at leaf tips, and half the leaf would become dark brown with time, and finally almost all of leaves were infected. Small pieces of leaf tissue (3 to 5 mm2) cut from the lesion margins were surface-sterilized in 75% ethanol for 30 s and 1% NaClO for 90 s, rinsed with sterile H2O three times, and placed on potato dextrose agar (PDA) at 25°C in the dark. The same fungus was isolated from 92% of the samples. The pure cultures were obtained by single-spore isolation. Three representative isolates (WJF1, WJF3 and WJF4) were obtained, and WJF1 was deposited in China's Forestry Culture Collection Center (CFCC 54806), and WJF3 and WJF4 were deposited at the Nanjing Forestry University (NFU 083 and NFU 084). The culture on PDA was white, with white vigorous aerial mycelia at the edge. Black pycnidia developed on the alfalfa stems at 25°C under a 14/10 h light/dark cycle for 20 days. Conidiophores were hyaline, branched, septate, straight, 16.4-34.7 × 1.5-3.0 µm (n = 30). Conidiogenous cells were 9.0-24.6 × 1.3-2.3 µm (n = 30). Alpha conidia were 7.0 ± 0.6 × 2.2 ± 0.2 µm (n = 30), fusiform, hyaline, smooth and multi-guttulate. Beta conidia were 25.5 ± 4.3 × 1.3 ± 0.1 µm (n = 30), hyaline, smooth and hamate. Morphological characters of all three isolates matched those of Diaporthe spp. (Gomes et al. 2013). DNA of three isolates were extracted and the internal transcribed spacer region (ITS), partial sequences of elongation factor 1-alpha (EF1-α), calmodulin (CAL), beta-tubulin (ß-tub) and histone H3 (HIS) genes were amplified with primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R and CAL228F/CAL737R (Carbone et al. 1999), ßt2a/ßt2b and CYLH3F/H3-1b (Glass and Donaldson, 1995, Crous et al. 2004), respectively. The sequences of WJF1, WJF3 and WJF4 were deposited in GenBank (WJF1: Accession Nos. MW301339 for ITS, MW363932 to MW363935 for EF1-α, ß-tub, HIS, and CAL; WJF3: MW453062 and MW561566 to MW561569; WJF4: MW453063 and MW561570 to MW561573). BLAST results showed that the ITS, EF1-α, ß-tub, HIS, and CAL sequences of WJF1 were similar with sequences of Phomopsis liquidambari C.Q. Chang, Z.D. Jiang & P.K. Chi JQ676191 (identity = 540/540; 100%), D. huangshanensis H. Zhou & C.L. Hou MN224671 (identity = 291/292; 99%), D. pescicola Dissan., J.Y. Yan, Xing H. Li & K.D. Hyde MK691230 (identity = 438/438; 100%), D. spinosa Y.S. Guo & G.P. Wang MK726170 (identity = 437/438; 99%), D. cercidis C.M. Tian & Qin Yang MK691114 (identity = 452/452; 100%), respectively. BLAST results of WJF3 and WJF4 are list in Table 1. A maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed WJF1, WJF3 and WJF4 in the clade of D. cercidis. Based on the five-locus phylogeny and morphology, WJF1, WJF3 and WJF4 were identified as D. cercidis. The pathogenicity of three isolates were tested on potted 3-yr-old seedlings of A. pictum subsp. mono, grown in a greenhouse. Healthy leaves were wounded with a sterile needle and then inoculated with 10 µL of conidial suspensions (106 conidia/mL). Control leaves were treated with sterilized H2O. A total of twelve seedlings were used for the tests, 3 seedlings per treatment, and five leaves were inoculated per seedling. Each plant was covered with a plastic bag after inoculation and sterilized H2O was sprayed into the bag twice/day to maintain humidity and kept in a greenhouse at the day/night temperatures at 25 ± 2°C/16 ± 2°C. In 5 days, all the inoculated leaves had lesions similar to those observed in the field. D. cercidis was reisolated from the lesions of the inoculated leaves and was confirmed based on morphological characteristics and ITS sequence analysis. No symptoms were observed on the control leaves, and no fungus was isolated from them. D. cercidis was previously reported on twigs of Cercis chinensis (Yang et al. 2018) and causing pear shoot canker (Guo et al. 2020). This is the first report of D. cercidis causing leaf blotch on A. pictum subsp. mono. Identification of the pathogen is imperative for diagnosing and controlling this potentially high risk disease on A. pictum subsp. mono and also for the future studies.

5.
Plant Dis ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569832

RESUMO

Acer palmatum Thunb. is an important colorful leaf ornamental tree species widely distributed in Japan, Korea and China (Carlos et al. 2016). In October 2019, powdery mildew was observed on leaves of A. palmatum planted at Qixia Mountain Park and the campus of Nanjing Forestry University, Nanjing, Jiangsu, China. The powdery mildew infected and colonized leaves, covering both leaf surfaces with white mycelia, giving affected plants an unsightly appearance. Nearly 17.4% of the plants (87/501) exhibited these signs and symptoms. Fresh specimens were collected and examined for the identification of the pathogen. Photos were taken with a ZEISS Axio Imager A2m microscope and a scanning electronic microscope. Chasmothecia were scattered or aggregated on the upper and lower surfaces of the leaves, blackish brown, oblate, 157.5 to 238.1 × 152.3 to 217.8 µm (n=30), with numerous appendages (100 to 200). Appendages were often (1-) 2 to 3 times branched from the middle of the stalk, uncinate to circinate at the apex, hyaline, aseptate, 30.0 to 70.8 × 4.1 to 8.2 µm (n=30). Asci were 11 to 21 per chasmothecium (n=30), long oval, oval, oblong, with short stalk or sessile, 80.6 ± 8.6 × 40.3 ± 4.0 um (n=30) in length, 6 to 8 spored (n=30). Ascospores were ovoid, 18.2 ± 1.6 × 11.1 ± 1.2 µm (n=30). Microconidiophores were 25 to 50 × 4.0 to 5.5 µm, producing microconidia in chains. Microconidia were ellipsoidal, subglobose, 8.7 ± 0.6 × 7.2 ± 0.6 µm (n=30). Macroconidia were not observed. Based on the morphological characteristics, the fungus was identified as Sawadaea polyfida (C.T. Wei) R.Y. Zheng & G. Q. Chen (Zheng and Yu 1987). To confirm the causative species identity, a representative voucher specimen collected and deposited at Nanjing Forestry University was used for a molecular analysis. Mycelia and conidia were collected from diseased leaves and genomic DNA of the pathogen was extracted and the internal transcribed spacer region (ITS) was amplified with primers ITS1/ITS4 (White et al. 1990). The resulting sequence of 461 bp was deposited in GenBank (accession no. MW255383). BLAST result showed that this sequence fully agreed with a sequence of S. polyfida [AB193381.1 (ITS), identities = 461/461 (100%)]. A maximum likelihood phylogenetic analyses using IQtree v. 1.6.8 with the ITS sequence placed this fungus in the S. polyfida clade. Based on the morphology and phylogeny, the fungus was identified as S. polyfida (Hirose et al. 2005; Zheng and Yu 1987). Pathogenicity was tested through inoculation by gently pressing the naturally infected leaves onto healthy ones of three potted A. palmatum seedlings wih five leaves. Healthy leaves from three other seedlings served as control. Inoculated and control seedlings were placed in separate growth chambers maintained at 20 ± 2°C, 70% humidity, with a 16 h/8 h light/dark period. Symptoms developed 8 days after inoculation. The powdery mildew developing on the inoculated seedlings was sequenced and confirmed as S. polyfida. The control leaves did not develop powdery mildew. S. polyfida has been reported on Acer catalpifolium in China (Zheng and Chen 1980), A. amoenum, A. australe, A. japonicum, A. palmatum, A. shirasawanum, and A. sieboldianum in Japan (Hirose et al. 2005; Meeboonet al. 2015), as well as A. takesimense in Korea (Lee et al. 2011). To the best of our knowledge, this is the first report of powdery mildew caused by S. polyfida on A. palmatum in China. These results form the basis for developing effective strategies for monitoring and managing this disease.

6.
Bioengineered ; 12(1): 6878-6890, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34519628

RESUMO

Recurrent spontaneous abortion (RSA) is a threat to human reproductive health worldwide. CircPUM1 has been reported to participate in the pathogenesis of various diseases. However, there has been no report on its association with RSA yet. In this study, gene expressions were examined by RT-qPCR. Protein levels of JUNB and cleaved caspases-3 were detected by Western blotting. ELISA was used to detect TNF-α, IL-6, and IL-8 levels. Cell viability, migration, invasion, and apoapsis were analyzed using CCK-8, transwell, and flow cytometry assays. The association between miR-30a-5p and circPUM1 or JUNB was identified by bioinformatics analysis, dual-luciferase reporter assay, and RIP assay. Herein, we found circPUM1 was significantly downregulated in RSA placental samples. CircPUM1 knockdown induced decreased proliferation, migration, and invasion, but increased apoptosis, pro-apoptotic protein (cleaved caspases-3) level, and proinflammatory factor (TNF-α, IL-6, and IL-8) secretion in trophoblast cells. Furthermore, we confirmed that circPUM1 was a sponge for miR-30a-5p, and JUNB was directly targeted by miR-30a-5p. It was demonstrated that miR-30a-5p inhibition could reverse trophoblast cell dysfunction and inflammation induced by circPUM1 knockdown. In addition, we found that JUNB expression was negatively modulated by miR-30a-5p and positively regulated by circPUM1. Moreover, circPUM1 inhibition exacerbated dysfunction and inflammation in trophoblast cells via targeting JUNB. To sum up, our study indicated that circPUM1 could impair RSA occurrence and development by facilitating trophoblast cellular processes and protecting against inflammation via the miR-30a-5p/JUNB axis, providing a new target for the improvement of RSA diagnosis and treatment.

7.
Talanta ; 234: 122651, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364460

RESUMO

Wide uses of azo dyes produce a great risk of high residuals of carcinogenic aromatic amines, and hence it is important to rapidly analyze these carcinogenic compounds in the textile products to guarantee product safety. In the present work, a surface enhanced Raman spectroscopic (SERS) method was developed for rapid detection of carcinogenic aromatic amines in textiles. In this method, target aromatic amines are extracted from textiles, and then gold nanoparticles are added to the organic extractant, which assemble into closely packed Au array at liquid interface in situ. Finally, fingerprint SERS signals of the target aromatic amines are detected on the generated Au array on the basis of strong chemical interaction between the aromatic amines and the Au surface. The proposed method provided good reproducibility with a relative standard deviation of 3.5% for ten parallel tests of benzidine. It was applied to analyze 70 textile products. To strengthen the spectroscopic data processing, a cluster analysis model was established with 50 samples to automatically identify the spectra based on the good signal reproducibility. The other 20 samples were used as test sets to validate this model. It was found that all the positive samples were successfully identified with false positive rate of 20%. With the addition of the Artificial Intelligence step, the reliability of the discriminant results can be ensured.


Assuntos
Ouro , Nanopartículas Metálicas , Aminas , Inteligência Artificial , Compostos Azo , Reprodutibilidade dos Testes , Análise Espectral Raman , Têxteis
8.
Hum Gene Ther ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376056

RESUMO

Huntington's disease (HD) is a devasting, autosomal dominant neurodegenerative disease caused by a trinucleotide repeat expansion in the HTT gene. Inactivation of the mutant allele by CRISPR-Cas9 based gene editing offers a possible therapeutic approach for this disease, but permanent disruption of normal HTT function might compromise adult neuronal function. Here, we use a novel HD mouse model to examine allele-specific editing of mutant HTT (mHTT), with a BAC97 transgene expressing mHTT and a YAC18 transgene expressing normal HTT. We achieve allele-specific inactivation of HTT by targeting a protein coding sequence containing a common, heterozygous single nucleotide polymorphism (SNP). The outcome is a marked and allele-selective reduction of mutant HTT (mHTT) protein in a mouse model of HD. Expression of a single CRISPR-Cas9 nuclease in neurons generated a high frequency of mutations in the targeted HD allele that included both small insertion/deletion (InDel) mutations and viral vector insertions. Thus, allele-specific targeting of InDel and insertion mutations to heterozygous coding region SNPs provides a feasible approach to inactivate autosomal dominant mutations that cause genetic disease.

10.
Proc Natl Acad Sci U S A ; 118(32)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34353903

RESUMO

Vertebrate mammals express a protein called Ki-67 which is most widely known as a clinically useful marker of highly proliferative cells. Previous studies of human cells indicated that acute depletion of Ki-67 can elicit a delay at the G1/S boundary of the cell cycle, dependent on induction of the checkpoint protein p21. Consistent with those observations, we show here that acute Ki-67 depletion causes hallmarks of DNA damage, and the damage occurs even in the absence of checkpoint signaling. This damage is not observed in cells traversing S phase but is instead robustly detected in mitotic cells. The C-terminal chromatin-binding domain of Ki-67 is necessary and sufficient to protect cells from this damage. We also observe synergistic effects when Ki-67 and p53 are simultaneously depleted, resulting in increased levels of chromosome bridges at anaphase, followed by the appearance of micronuclei. Therefore, these studies identify the C terminus of Ki-67 as an important module for genome stability.

11.
J Int Med Res ; 49(8): 3000605211027739, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34435925

RESUMO

BACKGROUND: Recent studies have reported associations between, human bocavirus (HBoV), and respiratory tract diseases in children. However, there is limited information on the epidemiology of HBoV in infants. This prospective study investigated the prevalence and clinical characteristics of HBoV infection in infants with acute lower respiratory tract infection (ALRTI) in eastern China. METHODS: Nasopharyngeal aspirates and throat swab samples were collected from infants with ALRTI and age-matched healthy infants between January 2016 and December 2019. HBoV was identified by polymerase chain reaction. Laboratory data and clinical characteristics were analyzed. RESULTS: Of 2510 infants, 145 tested positive for HBoV. The highest prevalence of HBoV was detected during the winter. Co-infection was frequently observed during this period of high viral transmission. There were no HBoV-positive infants in the control group. Clinical signs and symptoms included cough, wheezing, fever, nasal discharge, vomiting, diarrhea, hypoxemia, and tachypnea. Co-infections included: Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydophila pneumoniae, respiratory syncytial virus, and adenovirus. CONCLUSIONS: HBoV was frequently detected in infants with ALRTI in China. The prevalence of HBoV was highest in winter. Co-infection was common, especially in infants requiring intensive care unit admission. Comprehensive clinical evaluation may facilitate optimal treatment.


Assuntos
Bocavirus Humano , Infecções por Parvoviridae , Infecções Respiratórias , Criança , Bocavirus Humano/genética , Humanos , Lactente , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Estudos Prospectivos , Sons Respiratórios , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia
12.
J Obstet Gynaecol Res ; 47(10): 3471-3479, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34235813

RESUMO

AIM: To investigate the expression of formyl peptide receptor 2 (FPR2) in maternal blood, umbilical blood, and placenta of patients with gestational diabetes mellitus (GDM), and to analyze the changes of other pro-inflammatory cytokines in blood, including interleukin 33 (IL-33), IL-1ß, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP), so as to reveal the pathogenesis of GDM. METHODS: FPR2, IL-33, IL-1ß, T TNF-α, and CRP in maternal blood and umbilical cord blood of 50 pregnant women with GDM and 30 normal pregnant women were analyzed by ELISA method to explore the correlation between inflammatory factors and blood glucose. The expression of FPR2 in placental tissues was analyzed by PCR and immunohistochemistry. RESULTS: The expression of FPR2 in maternal blood of gestational diabetes patients was significantly higher than that of normal pregnant women, and other inflammatory factors IL-33 and IL-1ß in maternal blood were also significantly increased. The expression of FPR2 in umbilical cord blood of gestational diabetes was higher than that of normal pregnant women, but the difference was not significant. Other inflammatory factors IL-33, IL-1ß, and CRP in umbilical cord blood were also significantly increased. The expression of FPR2mRNA and protein in placental tissues of gestational diabetes was significantly higher than that of normal pregnant women. CONCLUSIONS: The level of FPR2, IL-33, and IL-1ß in maternal blood was related to the pathogenesis of GDM and these inflammatory factors could be used as special candidate direction of marks for the prevention, clinical treatment and drug design of GDM, laying a new theoretical foundation for the treatment of GDM.


Assuntos
Diabetes Gestacional , Placenta , Receptores de Formil Peptídeo/sangue , Receptores de Lipoxinas/sangue , Diabetes Gestacional/sangue , Feminino , Sangue Fetal , Humanos , Gravidez , Fator de Necrose Tumoral alfa
13.
Prog Mol Biol Transl Sci ; 181: 31-43, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34127199

RESUMO

The clustered, regularly interspersed, short palindromic repeats (CRISPR) technology is revolutionizing biological studies and holds tremendous promise for treating human diseases. However, a significant limitation of this technology is that modifications can occur on off-target sites lacking perfect complementarity to the single guide RNA (sgRNA) or canonical protospacer-adjacent motif (PAM) sequence. Several in vivo and in vitro genome-wide off-target profiling approaches have been developed to inform on the fidelity of gene editing. Of these, GUIDE-seq has become one of the most widely adopted and reproducible methods. To allow users to easily analyze GUIDE-seq data generated on any sequencing platform, we developed an open-source pipeline, GS-Preprocess, that takes standard base-call output in bcl format and generate all required input data for off-target identification using bioconductor package GUIDEseq for off-target identification. Furthermore, we created a Docker image with GS-Proprocess, GUIDE-seq, and all its R and system dependencies already installed. The bundled pipeline will empower end users to streamline the analysis of GUIDE-seq data and motivate their use of higher throughput sequencing with increased multiplexing for GUIDE-seq experiments.

14.
Int J Biol Macromol ; 184: 955-966, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153360

RESUMO

Hemoglobin-based oxygen carriers have long been pursued to meet clinical needs by using native hemoglobin (Hb) from human or animal blood, or recombinantly produced Hb, but the development has been impeded by safety and toxicity issues. Herewith we report the successful production of human fetal hemoglobin (HbF) in Nicotiana benthamiana through Agrobacterium tumefaciens-mediated transient expression. HbF is a heterotetrameric protein composed of two identical α- and two identical γ-subunits, held together by hydrophobic interactions, hydrogen bonds, and salt bridges. In our study, the α- and γ-subunits of HbF were fused in order to stabilize the α-subunits and facilitate balanced expression of α- and γ-subunits in N. benthamiana. Efficient extraction and purification methods enabled production of the recombinantly fused endotoxin-free HbF (rfHbF) in high quantity and quality. The transiently expressed rfHbF protein was identified by SDS-PAGE, Western blot and liquid chromatography-tandem mass spectrometry analyses. The purified rfHbF possessed structural and functional properties similar to native HbF, which were confirmed by biophysical, biochemical, and in vivo animal studies. The results demonstrate a high potential of plant expression systems in producing Hb products for use as blood substitutes.


Assuntos
Hemoglobina Fetal/genética , Oxigênio/metabolismo , Tabaco/genética , Hemoglobina Fetal/isolamento & purificação , Hemoglobina Fetal/metabolismo , Humanos , Ligação de Hidrogênio , Proteínas de Plantas/isolamento & purificação , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Tabaco/crescimento & desenvolvimento , Tabaco/metabolismo
15.
Plant Dis ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34058841

RESUMO

Salix matsudana Koidz. (Chinese willow) is an important landscaping tree species widely grown in China (Zhang et al. 2017). In October 2019, a characteristic leaf spot disease of S. matsudana was found on the campus of Nanjing Forestry University. Most 25-year-old S. matsudana trees (13 out of 21, approximately 62%) on campus showed the leaf spot disease. On average, 70% of the leaves per individual tree were affected by this disease. Foliar symptoms began as dark brown, irregular spots and the centers were gray-white, gradually enlarging with time. Leaf spot symptomatic leaves were collected from three infected S. matsudana trees (10 leaves/tree), and small infected tissues (3-4 mm2) were surface-sterilized in 75% ethanol for 30 s, 1% NaClO for 90 s, rinsed in ddH2O, dried on sterilized filter paper, and plated on potato dextrose agar (PDA), and then incubated at 25°C. Three isolates (NHY1-1, NHY1-2, and NHY1-3) of the same fungus were obtained in 85% of the samples and deposited in China's Forestry Culture Collection Center (NHY1-1: cfcc55354, NHY1-2: cfcc55355, NHY1-3: cfcc55359). The colonies of three isolates were white, but the reverse side was grayish-white. The conidia of NHY1-1 were one-celled, straight, subcylindrical, hyaline, 14.4 ± 0.9 × 5.4 ± 0.4 µm (n = 50), with a rounded end. Conidiophores were hyaline to pale brown, septate, and branched. Appressoria were one-celled, ellipsoidal, brown or dark brown, thick-walled, 8.0 ± 0.9 × 5.9 ± 0.5 µm (n = 50). The conidia and appressoria of the other two isolates weralmost identical to NHY1-1. The morphological characters of the three isolates were matched with those of the Colletotrichum gloeosporioides complex (Weir et al. 2012). For accurate identification, the DNA of the three isolates was extracted. The internal transcribed spacer region (ITS), actin (ACT), calmodulin (CAL), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), superoxide dismutase (SOD2), and ß-tubulin 2 (TUB2) genes were amplified using the primer pairs ITS1/ITS4, ACT-512F/ACT-783R, CL1C/CL2C, CHS-79F/CHS-345R, GDF1/GDR1, SODglo2-F/SODglo2-R, and Bt2a/Bt2b, respectively (Weir et al. 2012). The sequences were deposited in GenBank [Accession Nos. MW784679 and MW808959 to MW808964 for NHY1-1; MW784726 and MW808965 to MW808970 for NHY1-2; MW784729 and MW808971 to MW808976 for NHY1-3]. A BLAST search of GenBank showed that ITS, ACT, CAL, GAPDH, SOD2, and TUB2 sequences of the three isolates were identical to Colletotrichum siamense at a high level (>99%), and CHS-1 sequences of three isolates were consistent with Colletotrichum fructicola at a high level (>99%). A maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences (ITS, ACT, CAL, CHS-1, GAPDH, SOD2, and TUB2) placed NHY1-1, NHY1-2, and NHY1-3 in the clade of C. siamense with high bootstrap support values (ML/BI = 93/1). The pathogenicity of three isolates were tested on potted 2-yr-old seedlings (50-cm tall) of S. matsudana, which were grown in a greenhouse. Healthy leaves were wounded with a sterile needle and then inoculated with 10 µL of conidial suspension (106 conidia/mL). Controls were treated with ddH2O (Zhu et al. 2019). In total, 12 seedlings were inoculated including controls. Three seedlings/isolate and 10 leaves/seedling were used for each treatment. The plants were covered with plastic bags after inoculation and sterilized H2O was sprayed into the bags twice/day to maintain humidity and kept in a greenhouse at the day/night temperatures at 25 ± 2 / 16 ± 2°C. Within 7 days, all the inoculated points showed lesions similar to those observed in field, whereas controls were asymptomatic. The infection rate of each of the three isolates is 100%. C. siamense was re-isolated from the lesions, whereas no fungus was isolated from control leaves. The diseases caused by C. siamense often occur in tropical and subtropical regions of China, with a wide range of hosts, such as Hevea brasiliensis and Coffea arabica, etc. (Cao et al. 2019; Liu et al. 2018). This is the first report of C. siamense causing leaf spot of S. matsudana in China and the world. These data will help to develop effective strategies for managing this newly emerging disease.

16.
Chem Asian J ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34156156

RESUMO

Nanostructures of the multimetallic catalysts offer great scope for fine tuning of heterogeneous catalysis, but clear understanding of the surface chemistry and structures is important to enhance their selectivity and efficiency. Focussing on a typical Pt-Pd-Ni trimetallic system, we comparatively examined the Ni/C, Pt/Ni/C, Pd/Ni/C and Pt-Pd/Ni/C catalysts synthesized by impregnation and galvanic replacement reaction. To clarify surface chemical/structural effect, the Pt-Pd/Ni/C catalyst was thermally treated at X=200, 400 or 600 °C in a H2 reducing atmosphere, respectively termed as Pt-Pd/Ni/C-X. The as-prepared catalysts were characterized complementarily by XRD, XPS, TEM, HRTEM, HS-LEIS and STEM-EDS elemental mapping and line-scanning. All the catalysts were comparatively evaluated for benzaldehyde and styrene hydrogenation. It is shown that the "PtPd alloy nanoclusters on Ni nanoparticles" (PtPd/Ni) and the synergistic effect of the trimetallic Pt-Pd-Ni, lead to much improved catalytic performance, compared with the mono- or bi- metallic counterparts. However, with the increase of the treatment temperature of the Pt-Pd/Ni/C, the catalytic performance was gradually degraded, which was likely due to that the favourable nanostructure of fine "PtPd/Ni" was gradually transformed to relatively large "PtPdNi alloy on Ni" (PtPdNi/Ni) particles, thus decreasing the number of noble metal (Pt and Pd) active sites on the surface of the catalyst. The optimum trimetallic structure is thus the as synthesised Pt-Pd/Ni/C. This work provides a novel strategy for the design and development of highly efficient and low-cost multimetallic catalysts, e. g. for hydrogenation reactions.

17.
DNA Cell Biol ; 40(5): 643-651, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33902329

RESUMO

Mitochondria play a critical role in cell function and embryo development. Recently, increasing studies have investigated whether mitochondrial DNA (mtDNA) can be used as a predictive biomarker of embryo implantation. However, the results of its effect on implantation are still controversial. To further understand the clinical application value of mtDNA content for reproductive potential, we analyzed the influence of relative mtDNA quantity on embryo quality and transfer outcomes based on the results of second-generation sequencing of preimplantation genetic testing patients in our center. Biopsied trophectoderm (TE) from aneuploid blastocysts contained much larger amounts of mtDNA than those from euploid blastocysts (p < 0.000). In an analysis of only euploid blastocysts (n = 769), female age had no effect on mtDNA content (p = 0.216). TE cells biopsied on day 5 (n = 355) contained significantly higher amounts of mtDNA compared to those biopsied on day 6 (n = 388) or day 7 (n = 26) (p < 0.000). Higher quality trophoblast was associated with lower mtDNA content (p = 0.026), but quality of inner cell mass was not correlated with quantity of mtDNA (p = 0.112). For transferred embryos, the biopsied date and mtDNA content were significantly associated with embryo implantation and live birth outcomes. Day-5 euploid blastocysts with lower quantities of mtDNA exhibited higher implantation rate and live birth rate. However, our data indicated that mtDNA content may not be considered an independent predictive marker, it may be a useful reference for the selection of day-5 transferred euploid blastocysts.


Assuntos
Blastocisto/metabolismo , DNA Mitocondrial/metabolismo , Ectoderma/metabolismo , Transferência Embrionária , Trofoblastos/metabolismo , Biópsia , Cromossomos Humanos/genética , Implantação do Embrião , Dosagem de Genes , Humanos , Nascido Vivo , Modelos Logísticos , Idade Materna , Curva ROC
18.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760220

RESUMO

Breast cancer (BCa) is the most common malignancy threatening the health of women worldwide, and the incidence rate has significantly increased in the last 10 years. Mammalian STE20­like protein kinase 1 (MST1) is involved in the development of various types of malignant tumor. The present study aimed to investigate the role of MST1 in BCa and its potential involvement in the poor prognosis of patients with BCa. Reverse transcription­quantitative PCR and immunohistochemistry were used to analyze the expression levels of MST1 in BCa, and the clinicopathological characteristics and prognosis of patients with BCa were further analyzed by statistical analysis. MST1 was overexpressed in BCa cell lines (MCF­7, MDA­MB­231 and SKBR3). Cell Counting Kit­8, 5­ethynyl­2'­deoxyuridine and flow cytometry assays were used to analyze cell proliferation and apoptosis, respectively, and a wound healing assay was used to analyze cell migration. The results of the present study revealed that the downregulated expression levels of MST1 in BCa were closely associated with the poor prognosis of patients, and MST1 may be an independent risk factor for BCa. The overexpression of MST1 significantly inhibited the proliferation and migration, and promoted the apoptosis of BCa cells. In addition, the overexpression of MST1 significantly activated the Hippo signaling pathway. Treatment with XMU­MP­1 downregulated the expression levels of MST1 and partially reversed the inhibitory effects of MST1 on proliferation, migration and apoptosis­related proteins, and inhibited the Hippo signaling pathway. In conclusion, the results of the present study suggested that MST1 expression levels may be downregulated in BCa and closely associated with tumor size and clinical stage, as well as the poor prognosis of affected patients. Furthermore, MST1 may inhibit the progression of BCa by targeting the Hippo signaling pathway.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Apoptose , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/genética
19.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33729889

RESUMO

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Assuntos
COVID-19 , Medição de Risco/métodos , COVID-19/epidemiologia , COVID-19/mortalidade , China , Hospitalização/estatística & dados numéricos , Humanos , Itália , Fatores de Risco
20.
Medicine (Baltimore) ; 100(6): e24597, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578561

RESUMO

ABSTRACT: Adenomyosis and endometriosis are common causes of pelvic pain in women of reproductive age. Furthermore, adenomyosis is a major cause of menorrhagia. This study aimed to evaluate the effects of Etonogestrel implants on pelvic pain and menstrual flow in women requiring long-acting reversible contraception and suffering from adenomyosis or endometriosis.One hundred women with adenomyosis or endometriosis and asking for contraception with Etonogestrel implants were enrolled in this study and were followed-up for 24 months. Patients were interviewed on pelvic pain by visual analog scale (VAS) pain score, menstrual flow by the number of sanitary napkins, menstrual bleeding pattern, weight gain, breast pain, and any other treatment side effects.Seventy four patients who were treated with Etonogestrel implants completed the 24-month follow-up in which we found a significant decrease in pelvic pain VAS scores comparing baseline scores to 6, 12, and 24 months (baseline: 6.39 ±â€Š2.35 to 24-month: 0.17 ±â€Š0.69, P < 0.05). The menstrual volume decreased significantly compared with that at baseline ((40.69 ±â€Š30.92) %, P < 0.05). However, vaginal bleeding, amenorrhea, weight gain, and acne occurred after treatment in some patients.Etonogestrel implants were effective in reducing pelvic pain and menstrual flow of adenomyosis or endometriosis.


Assuntos
Adenomiose/tratamento farmacológico , Contraceptivos Hormonais/administração & dosagem , Desogestrel/administração & dosagem , Endometriose/tratamento farmacológico , Menorragia/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Adenomiose/complicações , Adulto , Implantes de Medicamento , Endometriose/complicações , Feminino , Humanos , Contracepção Reversível de Longo Prazo , Menorragia/etiologia , Pessoa de Meia-Idade , Dor Pélvica/etiologia , Estudos Prospectivos , Adulto Jovem
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