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1.
J Microbiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958871

RESUMO

Fleagrass, a herb known for its pleasant aroma, is widely used as a mosquito repellent, antibacterial agent, and for treating colds, reducing swelling, and alleviating pain. The antifungal effects of the essential oils of fleagrass and carvacrol against Candida albicans were investigated by evaluating the growth and the mycelial and biofilm development of C. albicans. Transmission electron microscopy was used to evaluate the integrity of the cell membrane and cell wall of C. albicans. Fleagrass exhibited high fungicidal activity against C. albicans at concentrations of 0.5% v/v (via the Ras1/cAMP/PKA pathway). Furthermore, transmission electron microscopy revealed damage to the cell wall and membrane after treatment with the essential oil, which was further confirmed by the increased levels of ß-1,3-glucan and chitin in the cell wall. This study showed that fleagrass exerts good fungicidal and hyphal growth inhibition activity against C. albicans by disrupting its cell wall, and thus, fleagrass may be a potential antifungal drug.

2.
BMC Nephrol ; 25(1): 209, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918687

RESUMO

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD. CASE PRESENTATION: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up. CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.


Assuntos
Rim Policístico Autossômico Recessivo , Humanos , Feminino , Rim Policístico Autossômico Recessivo/complicações , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Lactente , Miocárdio Ventricular não Compactado Isolado/complicações , Miocárdio Ventricular não Compactado Isolado/genética , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Ciliopatias/genética , Ciliopatias/complicações
3.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1711-1727, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38914487

RESUMO

Amino acids as the building blocks of proteins are widely applied in food, medicine, feed, and chemical industries. Amino acid production by microbial cell factories from renewable resources is praised for the environmental friendliness, mild reaction conditions, and high product purity, which helps to achieve the goal of carbon neutrality. Researchers have employed the methods of metabolic engineering and synthetic biology to engineer Escherichia coli and Corynebacterium glutamicum and optimized the culture conditions to construct the microbial cell factories with high performance for producing branched chain amino acids, amino acids of the aspartic acid and glutamic acid families, and aromatic amino acids. We review the engineering process of microbial cell factories for high production of amino acids, in the hope of providing a reference for the creation of high-performance microbial cell factories.


Assuntos
Aminoácidos , Corynebacterium glutamicum , Escherichia coli , Engenharia Metabólica , Engenharia Metabólica/métodos , Aminoácidos/biossíntese , Aminoácidos/metabolismo , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Biologia Sintética , Microbiologia Industrial
4.
J Mech Behav Biomed Mater ; 157: 106624, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38861785

RESUMO

OBJECTIVE: The purpose of this study was to synthesize Al-doped mesoporous silica spheres (Al-MSSs) and evaluate the effect of them as functional fillers on the mechanical properties and aging resistance of dental resin composites. METHODS: Al-MSSs were prepared by a two-step method. The effect of Al-MSSs on the performance of the composites was evaluated using neat resin matrix, commercial composites 3M Z350XT and samples containing mesoporous silica spheres (MSSs) and nonporous silica spheres (NSSs) as control. The neat resin matrix consisted of resin monomer (Bisphenol A glycerolate dimethacrylate/triethylene glycol dimethacrylate, 49.5/49.5, wt%) and photoinitiator (camphor quinone/Ethyl-4-dimethylaminobenzoate, 0.2/0.8, wt%). The mechanical properties (flexural strength, flexural modulus, compressive strength and microhardness) of them were evaluated by a universal testing machine and microhardness tester. The mechanical stabilities of the prepared composites in wet environment were evaluated by immersing them in deionized water at 37 °C. In addition, we evaluated the effect of Al-MSSs on other properties of the dental resin composites such as polymerization shrinkage, degree of conversion, curing depth, contact angle, water sorption and solubility according to ISO 4049: 2019. RESULTS: The synthesized Al-MSSs possessed good dispersibility with an average particle size of about 505 ± 16 nm. The mechanical properties of resin composites gradually increased with the increase of the loading amounts of inorganic fillers. The reinforcing effect of Al-MSSs was similar to that of MSSs and better than that of the NSSs groups at the same filler loading. After aging in deionized water at 37 °C for 30 days, the mechanical properties of all resin composites decreased. However, the decrease percentage of the composites filled with Al-MSSs was significantly lower than the other groups, indicating that the stability of the dental composites in wet environments was significantly improved by the Al-MSSs fillers. Furthermore, Al-MSSs had no obvious influence on the biocompatibility and other properties of dental resins. SIGNIFICANCE: The prepared Al-MSSs could effectively improve the mechanical properties and aging resistance without sacrificing other physic-chemical properties of dental resin composites.

5.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1185-1193, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856435

RESUMO

Optical systems with extended depth of field (EDOF) are crucial for observation and measurement applications, where achieving compactness and a substantial depth of field (DOF) presents a considerable challenge with conventional optical elements. In this paper, we propose an innovative solution for the miniaturization of EDOF imaging systems by introducing an ultra-thin annular folded lens (AFL). To validate the practical feasibility of the theory, we design an annular four-folded lens with an effective focal length of 80.91 mm and a total thickness of only 8.50 mm. Simulation results show that the proposed folded lens has a DOF of 380.55 m. We further developed an AFL-based test system exhibiting a resolution of 0.11 mrad across a wide wavelength range of 486-656 nm. Additionally, we present experimental results from a miniature compact prototype, which further highlights the promising potential of folded lenses for long-range EDOF imaging.

6.
bioRxiv ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895236

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Peripheral monocytes play a critical role in the secondary injury and recovery of damaged brain tissue after stroke, but the underlying mechanisms are largely unclear. To investigate transcriptome changes and molecular networks across monocyte subsets in response to T2DM and stroke, we performed single-cell RNA-sequencing (scRNAseq) from peripheral blood mononuclear cells and bulk RNA-sequencing from blood monocytes from four groups of adult mice, consisting of T2DM model db/db and normoglycemic control db/+ mice with or without ischemic stroke. Via scRNAseq we found that T2DM expands the monocyte population at the expense of lymphocytes, which was validated by flow cytometry. Among the monocytes, T2DM also disproportionally increased the inflammatory subsets with Ly6C+ and negative MHC class II expression (MO.6C+II-). Conversely, monocytes from control mice without stroke are enriched with steady-state classical monocyte subset of MO.6C+II+ but with the least percentage of MO.6C+II- subtype. Apart from enhancing inflammation and coagulation, enrichment analysis from both scRNAseq and bulk RNAseq revealed that T2DM specifically suppressed type-1 and type-2 interferon signaling pathways crucial for antigen presentation and the induction of ischemia tolerance. Preconditioning by lipopolysaccharide conferred neuroprotection against ischemic brain injury in db/+ but not in db/db mice and coincided with a lesser induction of brain Interferon-regulatory-factor-3 in the brains of the latter mice. Our results suggest that the increased diversity and altered transcriptome in the monocytes of T2DM mice underlie the worse stroke outcome by exacerbating secondary injury and potentiating stroke-induced immunosuppression. Significance Statement: The mechanisms involved in the detrimental diabetic effect on stroke are largely unclear. We show here, for the first time, that peripheral monocytes have disproportionally altered the subsets and changed transcriptome under diabetes and/or stroke conditions. Moreover, genes in the IFN-related signaling pathways are suppressed in the diabetic monocytes, which underscores the immunosuppression and impaired ischemic tolerance under the T2DM condition. Our data raise a possibility that malfunctioned monocytes may systemically and focally affect the host, leading to the poor outcome of diabetes in the setting of stroke. The results yield important clues to molecular mechanisms involved in the detrimental diabetic effect on stroke outcome.

7.
Plant Cell Rep ; 43(6): 155, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814469

RESUMO

KEY MESSAGE: Remorin proteins could be positively related to salt and osmotic stress resistance in rapeseed. Remorins (REMs) play a crucial role in adaptations to adverse environments. However, their roles in abiotic stress and phytohormone responses in oil crops are still largely unknown. In this study, we identified 47 BnaREM genes in the B.napus genome. Phylogenetic relationship and synteny analysis revealed that they were categorized into 5 distinct groups and have gone through 55 segmental duplication events under purifying selection. Gene structure and conserved domains analysis demonstrated that they were highly conserved and all BnaREMs contained a conserved Remorin_C domain, with a variable N-terminal region. Promoter sequence analysis showed that BnaREM gene promoters contained various hormones and stress-related cis-acting elements. Transcriptome data from BrassicaEDB database exhibited that all BnaREMs were ubiquitously expressed in buds, stamens, inflorescences, young leaves, mature leaves, roots, stems, seeds, silique pericarps, embryos and seed coats. The qRT-PCR analysis indicated that most of them were responsive to ABA, salt and osmotic treatments. Further mutant complementary experiments revealed that the expression of BnaREM1.3-4C-1 in the Arabidopsis rem1.3 mutant restored the retarded growth phenotype and the ability to resistance to salt and osmotic stresses. Our findings provide fundamental information on the structure and evolutionary relationship of the BnaREM family genes in rapeseed, and reveal the potential function of BnaREM1.3-4C-1 in stress and hormone response.


Assuntos
Brassica napus , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Reguladores de Crescimento de Plantas , Proteínas de Plantas , Estresse Fisiológico , Brassica napus/genética , Brassica napus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Regiões Promotoras Genéticas/genética , Genoma de Planta/genética , Pressão Osmótica , Plantas Geneticamente Modificadas/genética
9.
Ren Fail ; 46(1): 2356022, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38803195

RESUMO

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.


Assuntos
Hiperparatireoidismo Secundário , Falência Renal Crônica , Hormônio Paratireóideo , Diálise Peritoneal , Humanos , Masculino , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Feminino , Diálise Peritoneal/efeitos adversos , Prognóstico , Fatores de Risco , Hormônio Paratireóideo/sangue , Adulto , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Progressão da Doença , Modelos de Riscos Proporcionais
10.
Front Endocrinol (Lausanne) ; 15: 1338683, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812812

RESUMO

Objective: To determine whether the late-follicular-phase progesterone to retrieved oocytes (P/O) ratio during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) impacts pregnancy outcomes. Design: 12,874 cycles were retrospectively categorized into four groups according to the P/O ratio percentile, with divisions at the 25th, 50th and 75th percentiles. Results: The clinical pregnancy and live birth rates of fresh cycle embryos in Group D were significantly lower than those in the other three groups (45.1% and 39.0%, 43.2% and 37.2%, 39.6% and 33.5%, 33.4% and 28.2% in Group A, B, C, D, respectively; both P < 0.008). Multivariate logistic regression analysis revealed a significant negative correlation between the P/O ratio and live birth, particularly when the P/O ratio was ≥0.22 (OR = 0.862, 95% CI [0.774-0.959], P = 0.006). Conclusions: The P/O ratio has certain predictive value for IVF/ICSI pregnancy outcomes and can be used for decision-making decision regarding fresh embryo transfer.


Assuntos
Transferência Embrionária , Fertilização in vitro , Recuperação de Oócitos , Oócitos , Indução da Ovulação , Taxa de Gravidez , Progesterona , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Transferência Embrionária/métodos , Indução da Ovulação/métodos , Fertilização in vitro/métodos , Oócitos/citologia , Recuperação de Oócitos/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Fase Folicular , Resultado da Gravidez
11.
BMC Genomics ; 25(1): 434, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693497

RESUMO

BACKGROUND: WOX genes are a class of plant-specific transcription factors. The WUSCHEL-related homeobox (WOX) family is a member of the homeobox transcription factor superfamily. Previous studies have shown that WOX members play important roles in plant growth and development. However, studies of the WOX gene family in blueberry plants have not been reported. RESULTS: In order to understand the biological function of the WOX gene family in blueberries, bioinformatics were used methods to identify WOX gene family members in the blueberry genome, and analyzed the basic physical and chemical properties, gene structure, gene motifs, promoter cis-acting elements, chromosome location, evolutionary relationships, expression pattern of these family members and predicted their functions. Finally, 12 genes containing the WOX domain were identified and found to be distributed on eight chromosomes. Phylogenetic tree analysis showed that the blueberry WOX gene family had three major branches: ancient branch, middle branch, and WUS branch. Blueberry WOX gene family protein sequences differ in amino acid number, molecular weight, isoelectric point and hydrophobicity. Predictive analysis of promoter cis-acting elements showed that the promoters of the VdWOX genes contained abundant light response, hormone, and stress response elements. The VdWOX genes were induced to express in both stems and leaves in response to salt and drought stress. CONCLUSIONS: Our results provided comprehensive characteristics of the WOX gene family and important clues for further exploration of its role in the growth, development and resistance to various stress in blueberry plants.


Assuntos
Mirtilos Azuis (Planta) , Filogenia , Regiões Promotoras Genéticas , Mirtilos Azuis (Planta)/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Cromossomos de Plantas/genética , Evolução Molecular , Biologia Computacional/métodos
12.
Reprod Sci ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600416

RESUMO

The purpose of this study was to investigate the effect of G-CSF on the endometrial receptivity of implantation failure mice. Sixty female mice were treated mifepristone to establish an implant failure model. The treatment groups received different doses of G-CSF. Endometrial tissue and serum were collected on day 5 after mating. The abundance of pinopodes on the endometrium was observed by scanning electron microscopy. The expressions of LPAR3, COX2, and HOXA10 were detected by RT-qPCR and Western blotting. Serum levels of E2, P, VEGF, LIF, TNF-α and IL-10 were measured by ELISA. The expressions of VEGF, CD34, CD57, TNF-α, and IL-10 were assessed by immunohistochemistry. Immunofluorescence analysis was performed to determine the number of CD57, Treg, and Th17 cells. G-CSF increased implantation and pregnancy rates of mifepristone-induced implantation failure mice, with the most significant effect seen at the intermediate dose. G-CSF increased the serum levels of E2 and P, the abundance of endometrial pinopodes, and the level of LIF in the endometrium. It also promoted the expression of VEGF, HOXA10, LPAR3, and COX2. Moreover, G-CSF reduced the level of CD57 cells and the ratio of Th17/Treg cells in endometrium. G-CSF reduced the inflammatory factor TNF-α, but IL-10 did not change significantly. G-CSF can enhance embryo implantation rate and pregnancy rate and improve endometrial receptivity by attenuating degeneration of pinopodes, upregulating estrogen and progesterone, facilitating angiogenesis, maintaining immune cell homeostasis, and reducing the production of inflammatory cytokines in implantation failure mouse.

13.
iScience ; 27(4): 109522, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38585660

RESUMO

Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities. In this study, we unveil TDP-43 as a pivotal regulator of the circadian clock. TDP-43 knockdown induces intracellular arrhythmicity, disrupts transcriptional activation regulation, and diminishes clock genes expression. Moreover, our experiments in adult mouse reveal that TDP-43 knockdown, specifically within the suprachiasmatic nucleus (SCN), induces locomotor arrhythmia, arrhythmic c-Fos expression, and depression-like behavior. This observation offers valuable insights into the substantial impact of TDP-43 on the behavioral aberrations associated with ALS/FTD. In summary, our study illuminates the significance of TDP-43 in circadian regulation, shedding light on the circadian regulatory mechanisms that may elucidate the pathological underpinnings of ALS/FTD.

14.
Biotechnol Bioeng ; 121(7): 2017-2049, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38665008

RESUMO

Porous organic frameworks (POFs) represent a significant subclass of nanoporous materials in the field of materials science, offering exceptional characteristics for advanced applications. Covalent organic frameworks (COFs), as a novel and intriguing type of porous material, have garnered considerable attention due to their unique design capabilities, diverse nature, and wide-ranging applications. The unique structural features of COFs, such as high surface area, tuneable pore size, and chemical stability, render them highly attractive for various applications, including targeted and controlled drug release, as well as improving the sensitivity and selectivity of electrochemical biosensors. Therefore, it is crucial to comprehend the methods employed in creating COFs with specific properties that can be effectively utilized in biomedical applications. To address this indispensable fact, this review paper commences with a concise summary of the different methods and classifications utilized in synthesizing COFs. Second, it highlights the recent advancements in COFs for drug delivery, including drug carriers as well as the classification of drug delivery systems and biosensing, encompassing drugs, biomacromolecules, small biomolecules and the detection of biomarkers. While exploring the potential of COFs in the biomedical field, it is important to acknowledge the limitations that researchers may encounter, which could impact the practicality of their applications. Third, this paper concludes with a thought-provoking discussion that thoroughly addresses the challenges and opportunities associated with leveraging COFs for biomedical applications. This review paper aims to contribute to the scientific community's understanding of the immense potential of COFs in improving drug delivery systems and enhancing the performance of biosensors in biomedical applications.


Assuntos
Técnicas Biossensoriais , Portadores de Fármacos , Estruturas Metalorgânicas , Técnicas Biossensoriais/métodos , Estruturas Metalorgânicas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos
15.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673861

RESUMO

Plant-parasitic nematodes (PPNs) are among the most serious phytopathogens and cause widespread and serious damage in major crops. In this study, using a genome mining method, we identified nonribosomal peptide synthetase (NRPS)-like enzymes in genomes of plant-parasitic nematodes, which are conserved with two consecutive reducing domains at the N-terminus (A-T-R1-R2) and homologous to fungal NRPS-like ATRR. We experimentally investigated the roles of the NRPS-like enzyme (MiATRR) in nematode (Meloidogyne incognita) parasitism. Heterologous expression of Miatrr in Saccharomyces cerevisiae can overcome the growth inhibition caused by high concentrations of glycine betaine. RT-qPCR detection shows that Miatrr is significantly upregulated at the early parasitic life stage (J2s in plants) of M. incognita. Host-derived Miatrr RNA interference (RNAi) in Arabidopsis thaliana can significantly decrease the number of galls and egg masses of M. incognita, as well as retard development and reduce the body size of the nematode. Although exogenous glycine betaine and choline have no obvious impact on the survival of free-living M. incognita J2s (pre-parasitic J2s), they impact the performance of the nematode in planta, especially in Miatrr-RNAi plants. Following application of exogenous glycine betaine and choline in the rhizosphere soil of A. thaliana, the numbers of galls and egg masses were obviously reduced by glycine betaine but increased by choline. Based on the knowledge about the function of fungal NRPS-like ATRR and the roles of glycine betaine in host plants and nematodes, we suggest that MiATRR is involved in nematode-plant interaction by acting as a glycine betaine reductase, converting glycine betaine to choline. This may be a universal strategy in plant-parasitic nematodes utilizing NRPS-like ATRR to promote their parasitism on host plants.


Assuntos
Arabidopsis , Betaína , Peptídeo Sintases , Tylenchoidea , Betaína/metabolismo , Animais , Tylenchoidea/metabolismo , Tylenchoidea/genética , Arabidopsis/parasitologia , Arabidopsis/metabolismo , Arabidopsis/genética , Peptídeo Sintases/metabolismo , Peptídeo Sintases/genética , Interações Hospedeiro-Parasita , Doenças das Plantas/parasitologia , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética , Nematoides/metabolismo , Nematoides/genética
16.
Cell Rep ; 43(4): 114094, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38613784

RESUMO

The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for ß-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.


Assuntos
Camundongos Endogâmicos C57BL , Esqualeno Mono-Oxigenase , Animais , Esqualeno Mono-Oxigenase/metabolismo , Camundongos , Colesterol/metabolismo , Colesterol/biossíntese , Colesterol/análogos & derivados , Receptores X do Fígado/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Imunidade Inata/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral
17.
Org Lett ; 26(18): 3878-3882, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38678578

RESUMO

The synthesis of complex alkanes by the tetrafunctionalization of alkynes is limited and challenging. Herein, an unprecedented efficient geminal diazidation and dibromination of terminal alkynes is developed, which provides novel access to structurally diverse organic azides. The approach has exclusive chemo- and regioselectivity and features mild reaction conditions, good tolerance of various functional groups, and more crucially, no metal involved in the reaction, thereby benefiting the late-stage decoration of medicinal molecules. A mechanistic study showed that the current geminal diazidation and dibromination proceeds via a radical pathway.

18.
Plant Physiol Biochem ; 210: 108594, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581808

RESUMO

Populus cathayana (C) grafted onto P. deltoides (D) (C/D) can promote growth better than self-grafting (C/C and D/D). However, the mechanisms underlying growth and resistance to drought stress are not clear. In this study, we performed physiological and RNA-seq analysis on the different grafted combinations. It was found that C/D plants exhibited higher growth, net photosynthetic rate, IAA content and intrinsic water use efficiency (WUEi) than C/C and D/D plants under both well-watered and drought-stressed conditions. However, most growth, photosynthetic indices, and IAA content were decreased less in C/D, whereas ABA content, WUEi and root characteristics (e.g., root length, volume, surface area and vitality) were increased more in C/D than in other grafting combinations under drought-stressed conditions. Transcriptomic analysis revealed that the number of differentially expressed genes (DEGs) in leaves of C/D vs C/C (control, 181; drought, 121) was much lower than that in the roots of C/D vs D/D (control, 1639; drought, 1706), indicating that the rootstocks were more responsive to drought resistance. KEGG and GO functional enrichment analysis showed that the enhanced growth and drought resistance of C/D were mainly related to DEGs involved in the pathways of ABA and IAA signaling, and secondary metabolite biosynthesis, especially the pathways for lignin and dopamine synthesis and metabolism. Therefore, our results further demonstrated the dominant role of rootstock in drought resistance, and enriched our knowledge on the mechanism of how interspecific grafting enhanced the growth and drought resistance in poplar.


Assuntos
Secas , Reguladores de Crescimento de Plantas , Populus , Transdução de Sinais , Populus/genética , Populus/metabolismo , Populus/crescimento & desenvolvimento , Populus/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Fotossíntese , Resistência à Seca
19.
Food Chem Toxicol ; 188: 114632, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583503

RESUMO

PFOA is one of the most representative compounds in the family of perfluorinated organic compounds. Due to its varying toxicity, alternatives to PFOA are beginning to emerge. HFPO-TA is an alternative for PFOA. It is currently unclear whether HFPO-TA affects glucose and lipid metabolism. In this study, rats were used as an animal model to investigate the effects of HFPO-TA on liver glucose and lipid metabolism. We found that HFPO-TA can affect glucose tolerance. Through omics analysis and molecular detection, it was found that HFPO-TA mainly affects the PPAR signaling pathway in the liver of rats, inhibiting liver glycolysis while promoting glucose production. HFPO-TA not only promotes the synthesis of fatty acids in the liver, but also promotes the breakdown of fatty acids, which ultimately leads to the disruption of hepatic glucose and lipid metabolism. The effects of HFPO-TA on metabolism are discussed in this paper to provide a reference for the risk assessment of this PFOA substitute.


Assuntos
Glucose , Metabolismo dos Lipídeos , Fígado , Metaboloma , Receptores Ativados por Proliferador de Peroxissomo , Transdução de Sinais , Transcriptoma , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ratos , Masculino , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Transcriptoma/efeitos dos fármacos , Glucose/metabolismo , Metaboloma/efeitos dos fármacos , Ratos Sprague-Dawley , Fluorocarbonos
20.
Org Lett ; 26(17): 3509-3513, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38652867

RESUMO

Five-carbon (C5) units are the fundamental building blocks that constitute a multitude of natural products. Herein we report an unprecedented unusual C5 functionalization of indole regioselectively at the C-2-position enabled by a (2-pyridyl)sulfonyl-directing palladium-catalyzed dehydrogenative strategy with a bulk chemical 2-methyl-2-butene as a C5 source. Compared to typical C5 functionalization using pentenyl alcohols, carbonates, borates, or halides as the C5 source, the protocol not only has a low cost advantage but also is of atom and step economy.

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