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1.
ACS Appl Mater Interfaces ; 16(5): 6548-6561, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38270085

RESUMEN

Much progress has been made toward the development of wearable flexible strain sensors with high sensing performance to monitor human motion, but continuous function in harsh aqueous environments remains a significant challenge. A promising strategy has been the design of sensors with highly durable superhydrophobicity and maintenance of unique sensing properties. Herein, an extremely durable superhydrophobic strain sensor with an ultrawide sensing range was simply fabricated by directly brushing conductive carbon black nanoparticles (CBNPs) onto an elastic silicone rubber sheet (SS) with poly(dimethylsiloxane) (PDMS) coatings (i.e., SS/PDMS-CBNPs sensors). First, this method avoided the use of toxic solvents and a conventional prestretching treatment. Second, considering the easily destroyed rough structures and surface chemistry for conventional superhydrophobic sensors during practical applications, the prepared SS/PDMS-CBNP sensors showed excellent mechanical durability of both superhydrophobicity and sensing as examined by harsh abrasion (300 cycles), stretching (up to 200%), and ultrasonication (40 min) treatments. Third, the prepared superhydrophobic strain sensor exhibited high sensitivity (gauge factor of 101.75), high stretchability (0.015-460%), low hysteresis (83 ms), and long-term stability (10000 cycles). Fourth, the high biocompatibility of the SS/PDMS-CBNP sensor was demonstrated by rabbit skin irritation tests. Finally, the remarkable water-repellent and sensing properties of the SS/PDMS-CBNP sensor allowed its application to monitor a swimmer's real-time situation and send distress signals when needed.


Asunto(s)
Dispositivos Electrónicos Vestibles , Animales , Humanos , Conejos , Movimiento (Física) , Agua , Conductividad Eléctrica , Interacciones Hidrofóbicas e Hidrofílicas
2.
Chem Commun (Camb) ; 60(2): 216-219, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38050725

RESUMEN

Herein, we present the first highly regio- and chemoselective C2 C-H acyloxylation of indole under rhodium catalysis and an N-quinolinyl auxiliary. This strategy accommodates a wide range of indoles and structurally diverse carboxylic acids with good reaction efficiencies to yield functionalized indoles. The utility of this logic was demonstrated by the concise synthesis of the functionalized 2-oxindole derivatives. Preliminary mechanistic studies indicate that catalyst turnover of RhIII-RhIV/V-RhII/III-RhIII might be involved in this catalytic C-H transformation.

3.
Appl Environ Microbiol ; 89(9): e0098323, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37655869

RESUMEN

The asexual sporulation of filamentous fungi is an important mechanism for their reproduction, survival, and pathogenicity. In Aspergillus and several filamentous fungi, BrlA, AbaA, and WetA are the key elements of a central regulatory pathway controlling conidiation, and MedA is a developmental modifier that regulates temporal expression of central regulatory genes; however, their roles are largely unknown in nematode-trapping (NT) fungi. Arthrobotrys oligospora is a representative NT fungus, which can capture nematodes by producing adhesive networks (traps). Here, we characterized the function of AoMedA and three central developmental regulators (AoBrlA, AoAbaA, and AoWetA) in A. oligospora by gene disruption, phenotypic comparison, and multi-omics analyses, as these regulators are required for conidiation and play divergent roles in mycelial development, trap formation, lipid droplet accumulation, vacuole assembly, and secondary metabolism. A combined analysis of phenotypic traits and transcriptome showed that AoMedA and AoWetA are involved in the regulation of peroxisome, endocytosis, and autophagy. Moreover, yeast one-hybrid analysis showed that AoBrlA can regulate AoMedA, AoAbaA, and AoWetA, whereas AoMedA and AoAbaA can regulate AoWetA. Our results highlight the important roles of AoMedA, AoBrlA, AoAbaA, and AoWetA in conidiation, mycelia development, trap formation, and pathogenicity of A. oligospora and provide a basis for elucidating the relationship between conidiation and trap formation of NT fungi. IMPORTANCE Conidiation is the most common reproductive mode for many filamentous fungi and plays an essential role in the pathogenicity of fungal pathogens. Nematode-trapping (NT) fungi are a special group of filamentous fungi owing to their innate abilities to capture and digest nematodes by producing traps (trapping devices). Sporulation plays an important role in the growth and reproduction of NT fungi, and conidia are the basic components of biocontrol reagents for controlling diseases caused by plant-parasitic nematodes. Arthrobotrys oligospora is a well-known NT fungus and is a routinely used model fungus for probing the interaction between fungi and nematodes. In this study, the functions of four key regulators (AoMedA, AoBrlA, AoAbaA, and AoWetA) involved in conidiation were characterized in A. oligospora. A complex interaction between AoMedA and three central regulators was noted; these regulators are required for conidiation and trap formation and play a pleiotropic role in multiple intracellular activities. Our study first revealed the role of AoMedA and three central regulators in conidiation, trap formation, and pathogenicity of A. oligospora, which contributed to elucidating the regulatory mechanism of conidiation in NT fungi and helped in developing effective reagents for biocontrol of nematodes.


Asunto(s)
Ascomicetos , Nematodos , Animales , Metabolismo Secundario , Ascomicetos/fisiología , Saccharomyces cerevisiae
4.
iScience ; 26(8): 107404, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37609635

RESUMEN

Mitogen-activated protein kinase (MAPK) Fus3 is an essential regulator of cell differentiation and virulence in fungal pathogens of plants and animals. However, the function and regulatory mechanism of MAPK signaling in nematode-trapping (NT) fungi remain largely unknown. NT fungi can specialize in the formation of "traps", an important indicator of transition from a saprophytic to a predatory lifestyle. Here, we characterized an orthologous Fus3 in a typical NT fungus Arthrobotrys oligospora using multi-phenotypic analysis and multi-omics approaches. Our results showed that Fus3 plays an important role in asexual growth and development, conidiation, stress response, DNA damage, autophagy, and secondary metabolism. Importantly, Fus3 plays an indispensable role in hyphal fusion, trap morphogenesis, and nematode predation. Moreover, we constructed the regulatory networks of Fus3 by means of transcriptomic and yeast two-hybrid techniques. This study provides insights into the mechanism of MAPK signaling in asexual development and pathogenicity of NT fungi.

5.
J Org Chem ; 88(13): 9488-9495, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37338541

RESUMEN

A concise and efficient synthesis of fully substituted cyclobutane derivatives from 1,4-diyn-3-ols and anhydrides was developed. Mechanistic studies indicated that a tandem esterification, isomerization to give allenyl ester, and homointermolecular [2+2] cycloaddition might be involved. The features of this protocol are its operational practicality, mild reaction conditions, and high regio- and stereoselectivity, and it is a readily accessible gram-scale synthesis.


Asunto(s)
Ciclobutanos , Anhídridos , Catálisis , Estereoisomerismo , Ésteres
6.
J Fungi (Basel) ; 9(4)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37108952

RESUMEN

Malate dehydrogenase (MDH) is a key enzyme in the tricarboxylic acid (TCA) cycle and is essential for energy balance, growth, and tolerance to cold and salt stresses in plants. However, the role of MDH in filamentous fungi is still largely unknown. In this study, we characterized an ortholog of MDH (AoMae1) in a representative nematode-trapping (NT) fungus Arthrobotrys oligospora via gene disruption, phenotypic analysis, and nontargeted metabolomics. We found that the loss of Aomae1 led to a weakening of MDH activity and ATP content, a remarkable decrease in conidia yield, and a considerable increase in the number of traps and mycelial loops. In addition, the absence of Aomae1 also caused an obvious reduction in the number of septa and nuclei. In particular, AoMae1 regulates hyphal fusion under low nutrient conditions but not in nutrient-rich conditions, and the volumes and sizes of the lipid droplets dynamically changed during trap formation and nematode predation. AoMae1 is also involved in the regulation of secondary metabolites such as arthrobotrisins. These results suggest that Aomae1 has an important role in hyphal fusion, sporulation, energy production, trap formation, and pathogenicity in A. oligospora. Our results enhance the understanding of the crucial role that enzymes involved in the TCA cycle play in the growth, development, and pathogenicity of NT fungi.

7.
Int J Hyg Environ Health ; 250: 114158, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36934548

RESUMEN

BACKGROUND: Experimental studies suggested that per- and polyfluoroalkyl substances (PFAS) may have endocrine-disrupting effects. However, the epidemiological evidence on the associations of PFAS with female reproductive hormones is sparse and limited to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). OBJECTIVE: To evaluate effects of legacy and emerging PFAS alternatives on female reproductive hormones. METHODS: A total of 433 reproductive-aged females were recruited from 2014 to 2016. Information on age, age at menarche, gravity, menstrual cycle, BMI, education, and income was obtained from medical records and questionnaires. Serum samples were collected for reproductive hormones, and plasma samples for PFAS measurement by ultraperformance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Multiple linear regression and quantile g-computation (q-gcomp) were used to examine the associations of individual PFAS and their mixture with reproductive hormones. RESULTS: Multiple linear regression analysis showed significant effects of certain PFAS on total testosterone (TT): adjusted estimate (ß) for perfluoroheptanoic acid (PFHpA) was 0.57 (95% CI: 0.18, 0.97). Moreover, a positive association was detected between PFAS mixture and TT in the q-gcomp model. Higher concentrations of 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) were associated with significantly lower prolactin level (ß = -0.07, 95% CI: -0.14, -0.001). CONCLUSION: Our study found that exposure to PFAS alternatives was associated with altered levels of reproductive hormones in women of childbearing age.


Asunto(s)
Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Humanos , Femenino , Adulto , Cromatografía Liquida , Espectrometría de Masas en Tándem , Ácidos Sulfónicos , Testosterona
8.
J Genet ; 1022023.
Artículo en Inglés | MEDLINE | ID: mdl-36722223

RESUMEN

The objective of the study was to perform the prenatal diagnosis of two foetuses with 22q11.2 duplication for 2.5 Mb after noninvasive prenatal testing (NIPT), and to explore the prenatal diagnosis and genetic characteristics of these foetuses. After amniocentesis, each foetus was diagnosed through karyotype analysis and single-nucleotide polymorphism array (SNP-array), and copy number variation using shotgun sequencing (CNV-seq) was carried out on each mother's peripheral blood for comparative analysis. Both pregnant woman 1 and pregnant woman 2 had foetal amniotic fluid chromosomal karyotypes of 46, XN. The SNP-array result for foetus 1 was arr[hg19] 22q11.21(18,648,856-21,800,471) x3; namely, 22q11.2 had a 3.1 Mb repeat, and the SNP-array result of foetus 2 was arr[hg19]22q11.2(18,648,855-21,464,764) x3; there was a 2.4 Mb repeat of 22q11.2. The CNV-Seq result of the peripheral blood of pregnant woman 1 was seq[hg19]22q11.2(18,953,139-21,449,967) x3; namely, in this mother's 22q11.2 region, there was ~2.5 Mb of duplicate fragment that was pathogenic to CNV. We confirmed that case 1 was inherited from the mother by CNV-seq. In both cases, however, there were key region deletions, including 41 OMIM genes such as CLTCL1, HIRA and TBX1. Both SNP-array and CNV-seq can effectively diagnose 22q11.2 duplication syndrome and clarify its fracture site and involved genes, which may facilitate understanding of the genotype and phenotype correlations.


Asunto(s)
Variaciones en el Número de Copia de ADN , Síndrome de DiGeorge , Femenino , Humanos , Embarazo , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Genotipo , Diagnóstico Prenatal
9.
Microbiol Spectr ; : e0395722, 2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36786575

RESUMEN

Nematode-trapping (NT) fungi are a unique group of carnivorous microorganisms that can capture and digest nematodes by producing ingenious trapping devices (traps). Arthrobotrys oligospora, a representative NT fungus, can develop adhesive three-dimensional networks for nematode predation. Hyphal fusion is indispensable for the trap formation of A. oligospora. Here, we characterized an orthologous Ste12 protein (AoSte12) in A. oligospora via gene disruption, DNA affinity purification sequencing (DAP-Seq), and multi-omics approaches. The disruption of the Aoste12 gene caused an increase in hyphal fusion and resulted in defects in mycelial growth, conidiation, trap morphology, and stress resistance, as well as reducing the number of nuclei and lipid droplet accumulation. Moreover, transcriptome and DAP-Seq analysis revealed that AoSte12 was involved in cellular processes associated with growth, cell fusion, the tricarboxylic acid cycle, vesicles, actin filaments, and lipid metabolism. In addition, combining metabolome with transcriptome and DAP-Seq analysis indicated that AoSte12 was involved in the mitogen-activated protein kinase signaling pathway, lipid metabolism, and secondary metabolites. A yeast two-hybrid assay revealed that AoSte12 can interact with diverse proteins, such as the MAK-2 orthologue protein Fus3, the vacuolar sorting protein Pep3, and UDP-glycosyltransferase. Our results suggest that AoSte12 plays an indispensable role in hyphal fusion and thus regulates sporulation and trap morphogenesis. These results provide deep insights into the connection between hyphal fusion and trap formation in NT fungi. IMPORTANCE Nematode-trapping (NT) fungi are an important natural enemy of nematodes and can capture their prey by producing traps. Hyphal anastomosis and fusion are important for mycelial growth and the colony morphological development of filamentous fungi and are also crucial for the trap morphogenesis of NT fungi. Arthrobotrys oligospora can form complex three-dimensional networks (traps) when sensing the presence of nematodes. This study revealed that AoSte12 is indispensable for hyphal fusion and that it regulates mycelial growth, conidiation, trap morphogenesis, stress resistance, the number of nuclei, and lipid droplet accumulation in A. oligospora. In addition, DNA affinity purification sequencing, transcriptome, and metabolome analyses further revealed that AoSte12 is involved in the mitogen-activated protein kinase pathway, lipid metabolism, and secondary metabolism. Overall, these findings expand the important role of AoSte12 in NT fungus A. oligospora and provide a broad foundation for elucidating the regulatory mechanism of trap development and the lifestyle transitions of pathogenic fungi.

10.
BMC Med Genomics ; 16(1): 3, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36624491

RESUMEN

BACKGROUND: Pathogenic PAK1 variants were described to be causative of neurodevelopmental disorder with macrocephaly, seizures, and speech delay. Herein, we present a de novo PAK1 variant combine with a de novo terminal 1q microdeletion in a Chinese pediatric patient, aiming to provide more insights into the underlying genotype-phenotype relationship. METHODS: Enrolled in this study was a 6-year-old girl with clinical features of global developmental delay, severe intellectual disability, speech delay, and seizures from Quanzhou region of China. Karyotype and chromosomal microarray analysis (CMA) were performed to detect chromosome abnormalities in this family. Whole exome sequencing (WES) was performed to investigate additional genetic variants in this family. RESULTS: No chromosomal abnormalities were elicited from the entire family by karyotype analysis. Further familial CMA results revealed that the patient had a de novo 2.7-Mb microdeletion (arr[GRCh37] 1q44(246,454,321_249,224,684) × 1]) in 1q44 region, which contains 14 OMIM genes, but did not overlap the reported smallest region of overlap (SRO) responsible for the clinical features in 1q43q44 deletion syndrome. In addition, WES result demonstrated a de novo NM_002576: c.251C > G (p.T84R) variant in PAK1 gene in the patient, which was interpreted as a likely pathogenic variant. CONCLUSION: In this study, we identify a novel PAK1 variant associated with a terminal 1q microdeletion in a patient with neurodevelopmental disorder. In addition, we believe that the main clinical features may ascribe to the pathogenic variant in PAK1 gene in the patient.


Asunto(s)
Discapacidad Intelectual , Trastornos del Desarrollo del Lenguaje , Humanos , Aberraciones Cromosómicas , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Quinasas p21 Activadas/genética , Fenotipo , Convulsiones/genética , China
11.
Microbiol Res ; 268: 127299, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36599176

RESUMEN

The maintenance of cell-wall integrity (CWI) is important for mycelial growth, development, and pathogenicity in fungi. Arthrobotrys oligospora is a typical nematode-trapping (NT) fungus which can capture nematodes by producing adhesive networks. In this study, we characterized an orthologous MADS-box transcription factor RlmA (AoRlmA) downstream of the CWI regulatory pathway in A. oligospora. The deletion of AorlmA caused a reduction in mycelial growth, the number of nuclei, conidiation, and trap formation, as well as increased sensitivity to cell-wall synthesis-disrupting agents, osmotic agents, and oxidants; accordingly, the transcript levels of genes associated with sporulation, cell-wall biosynthesis, and DNA damage response were downregulated in the ΔAorlmA mutant. Furthermore, the absence of AorlmA resulted in a reduction in autophagy and endocytosis. Transcriptome analysis showed that differentially expressed genes in the absence of AorlmA were involved in membrane components, the oxidation-reduction process, transmembrane transport, metabolic processes, cellular components, organelles, cellular response to stress, and DNA damage response. In addition, metabolomic analysis showed that AoRlmA was involved in the regulation of secondary metabolites of A. oligospora. To summarize, our results highlighted the important roles of transcription factor RlmA in mycelial growth, conidiation, CWI, trap formation, stress response, autophagy, endocytosis, and secondary metabolism regulation in A. oligospora, providing a basis for elucidating the regulatory mechanism of the mycelial growth and development, pathogenicity, and stress response of NT fungi.


Asunto(s)
Ascomicetos , Nematodos , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ascomicetos/metabolismo , Micelio/genética
12.
Biochem Genet ; 61(4): 1625-1644, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36719624

RESUMEN

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.


Asunto(s)
MicroARNs , Proteínas Proto-Oncogénicas c-akt , ARN Circular , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Circular/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología
13.
Mol Genet Genomic Med ; 11(3): e2121, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36504312

RESUMEN

BACKGROUND: Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant, lethal male disorder caused by mutations to the NSDHL (NAD(P)H steroid dehydrogenase-like protein) gene. It primarily exhibits strictly unilateral congenital hemidysplasia with ichthyosiform erythroderma and ipsilateral limb defects in female individuals. METHODS: A Chinese couple suffering from recurrent spontaneous abortion in male fetuses was enrolled in this study. Chromosomal microarray analysis and whole-exome sequencing were performed for genetic etiological diagnosis. RESULTS: A 33-year-old pregnant woman with recurrent spontaneous abortion was experiencing her third pregnancy with a male embryo. In this pregnancy, a miscarriage occurred at a gestational age of 10+6  weeks with no copy number variants. However, a novel mutation c.790-6C>T in the NSDHL gene was observed in the fetus through whole-exome sequencing (WES). Parental verification indicated that the NSDHL gene variant was inherited from the mother. Additionally, the variant in the NSDHL gene was absent in her subsequent pregnancy with a female fetus. CONCLUSION: In this study, we detected c.790-6C>T, a novel variant in the NSDHL gene that results in recurrent miscarriage in males. Our study may broaden the scope of research on the NSDHL gene in CHILD syndrome and strengthens the application value of WES for the genetic etiological identification of recurrent miscarriage.


Asunto(s)
Anomalías Múltiples , Aborto Habitual , Nevo , Neoplasias Cutáneas , Adulto , Femenino , Humanos , Lactante , Masculino , Embarazo , 3-Hidroxiesteroide Deshidrogenasas/genética , Anomalías Múltiples/genética , Secuenciación del Exoma , Mutación , Nevo/genética , Resultado Fatal , Resultado del Embarazo
14.
Chem Commun (Camb) ; 58(98): 13620-13623, 2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36408627

RESUMEN

A palladium-catalyzed interannular C-H amination of biaryl amines with O-benzoylhydroxylamines is reported. This reaction undergoes smoothly with operational practicality and good tolerance of functional groups, thereby providing a concise synthesis of 2,2'-diaminobiaryls. Moreover, the readily accessible scale-up synthesis and the ability to transform the products into structurally diverse N-containing heterocycles demonstrate the synthetic potential of this catalytic protocol.


Asunto(s)
Aminas , Paladio
15.
Org Lett ; 24(42): 7784-7789, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36250597

RESUMEN

The first electrochemical rhodium-catalyzed C-H cyclodimerization of alkynes for the direct construction of functionalized naphthalenes was reported. The practicality and synthetic value of this strategy were demonstrated by the readily accessible scale-up synthesis and transformation of the products. Detailed mechanistic studies evidenced that electricity played an important role during the electrochemical disproportionation (ECD) process to generate and maintain the catalytically active RhIV/V and RhI species, which conducted the direct C-H activation.

16.
Colloids Surf B Biointerfaces ; 220: 112944, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36274398

RESUMEN

With the continuous increasing number of cancer patients worldwide, there has been great interest in developing the targeted delivery anti-cancer drugs. The drug concentration reaching the tumor site is not enough to achieve a good therapeutic effect if it relies only on passive targeted drug delivery. In a long-lasting effort to improve the anti-cancer effect of drugs, surface ligand modification to nanocarriers has been actively explored to greatly improve the targeting ability, induce apoptosis in tumor cells, and prolong the drug circulation time in blood. This present review provides an overview of the effects of surface ligand modifications on the properties of anti-tumor nanocarriers. The first part presents the targeting mechanisms of nanocarriers. The second part focuses on recent progress in types of surface modification ligands exploited for anti-tumor nanocarriers. And the third part encompasses the effect of surface modifications on the properties of nanocarriers. In addition, the perspective in this field is also discussed.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Portadores de Fármacos/uso terapéutico , Ligandos , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico
17.
J Org Chem ; 87(17): 11796-11804, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-35993485

RESUMEN

A copper-catalyzed three-component reaction of ynones, aryl iodides, and elemental sulfur via a syn-addition process is established. The reaction features operational practicality, broad substrate scope, and readily accessible scale-up synthesis by affording a series of (Z)-1,2-bis(arylthio)alkenes in good to excellent yield. Moreover, benzo[b][1,4]dithiines can be also constructed efficiently by using 1,2-diiodobenzene as the coupling partner.

18.
Org Lett ; 24(28): 5143-5148, 2022 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-35815481

RESUMEN

Herein, we present the Pd(II)-catalyzed atroposelective C-H acyloxylation strategy for the assembly of biaryl aldehyde atropoisomers using readily available amino acids as the catalytic auxiliary and chiral pool. This strategy exhibits a broad substrate scope with a good yield (≤90%) and excellent enantioselectivity (≤99%), furnishing functionalized aldehydes through direct asymmetric C-H oxidation. The application utility of this method was demonstrated by the concise synthesis of a kind of atropoisomeric amino-phenol organocatalyst, which enables good enantiocontrol in catalyzing asymmetric addition of diethylzinc to aldehydes.


Asunto(s)
Paladio , Fenol , Aldehídos/química , Catálisis , Fenoles , Estereoisomerismo
19.
Sci China Life Sci ; 65(12): 2455-2471, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35829807

RESUMEN

Predatory fungi possess intricate signal transduction systems that regulate their development and support successful infection of the host. Herein, we characterized three components of the cell wall integrity-controlling pathway, namely protein kinase C (AoPKC), SLT2-MAPK (AoSLT2), and SWI6 (AoSWI6), in a representative nematode-trapping fungus Arthrobotrys oligospora, using gene disruption and multi-omics approaches. The phenotypic traits (such as mycelia development, conidiation, stress response, and trap morphogenesis) and metabolic profiles of ΔAopkc and ΔAoswi6 mutants were similar but differed from those of the ΔAoslt2 mutants. Transcriptomic analysis indicated that the genes differentially expressed in the absence of Aoswi6 were involved in DNA replication, repair, and recombination during trap formation. Moreover, the yeast two-hybrid assay showed that AoPKC interacted with AoSWI6, suggesting that in A. oligospora, PKC can directly regulate SWI6, bypassing the SLT2 signaling cascade. Conclusively, our findings deepen our understanding of the regulatory mechanism of asexual development and lifestyle switching in nematode-trapping fungi.


Asunto(s)
Ascomicetos , Nematodos , Animales , Ascomicetos/fisiología , Nematodos/genética , Nematodos/microbiología , Transducción de Señal , Pared Celular
20.
Sci China Life Sci ; 65(2): 412-425, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34031812

RESUMEN

Autophagy is an evolutionarily conserved process in eukaryotes, which is regulated by autophagy-related genes (ATGs). Arthrobotrys oligospora is a representative species of nematode-trapping (NT) fungi that can produce special traps for nematode predation. To elucidate the biological roles of autophagy in NT fungi, we characterized an orthologous Atg protein, AoAtg5, in A. oligospora. We found that AoATG5 deletion causes a significant reduction in vegetative growth and conidiation, and that the transcript levels of several sporulation-related genes were significantly downregulated during sporulation stage. In addition, the cell nuclei were significantly reduced in the ΔAoATG5 mutant, and the transcripts of several genes involved in DNA biosynthesis, repair, and ligation were significantly upregulated. In ΔAoATG5 mutants, the autophagic process was significantly impaired, and trap formation and nematocidal activity were significantly decreased. Comparative transcriptome analysis results showed that AoAtg5 is involved in the regulation of multiple cellular processes, such as autophagy, nitrogen metabolism, DNA biosynthesis and repair, and vesicular transport. In summary, our results suggest that AoAtg5 is essential for autophagy and significantly contributes to vegetative growth, cell nucleus development, sporulation, trap formation, and pathogenicity in A. oligospora, thus providing a basis for future studies focusing on related mechanisms of autophagy in NT fungi.


Asunto(s)
Ascomicetos/fisiología , Ascomicetos/patogenicidad , Proteína 5 Relacionada con la Autofagia/metabolismo , Núcleo Celular/metabolismo , Proteínas Fúngicas/metabolismo , Nematodos/microbiología , Animales , Ascomicetos/clasificación , Autofagosomas/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Núcleo Celular/genética , ADN de Hongos/metabolismo , Proteínas Fúngicas/genética , Perfilación de la Expresión Génica , Hifa/crecimiento & desarrollo , Hifa/metabolismo , Mutación , Nitrógeno/metabolismo , Filogenia , Esporas Fúngicas/fisiología , Transcripción Genética , Virulencia
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