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1.
Phys Chem Chem Phys ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35946223

RESUMO

The charge transfer (CT) interactions play a vital role in tuning the luminescence of organic crystals. The enhanced energy transfer (ET) effect in rare earth (RE) ions is a significant method to achieve long-lifetime fluorescence. These studies are of great significance in the fields of photoelectric functional materials. However, the effect of CT interactions on the process of ET from the cocrystal ligand group to RE ions is unknown. In this work, we have doped Eu3+ ions, Tb3+ ions and Eu3+/Tb3+ mixed ions on the surfaces of Phen-TCNB (Phen = 1,10-phenanthroline, and TCNB = 1,2,4,5-tetracyanobenzene) to construct organic cocrystal-type core-shell structures by the epitaxial growth method. The core-shell structures exhibited multiple photoluminescence depending on the types and proportions of RE3+ ions that are doped on the surfaces of the cocrystals. Experimental and theoretical investigations prove that the ET enhancements from ligand groups to Eu3+ ions originate from appropriate energy differences between the lowest triplet states of Phen-TCNB and the lowest excited state of RE3+ ions. In contrast, the reduced Tb3+ 5D4 lifetime is caused by the energy back transfer process since the energy difference becomes small. These results reveal that the multiple luminescences of the cocrystal-type core-shell structures can be adjusted by the CT and ET, and this study provides a new strategy for developing novel optoelectronic materials.

2.
Andrologia ; : e14542, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922383

RESUMO

The prevalence of varicoceles in male infertility is increasing; however, the exact mechanism is unknown, and no direct studies of varicose spermatic veins have been conducted. Three patients with varicocele infertility were included to explore the possible factors that cause varicocele infertility, and varicose and nearby normal veins were harvested by varicocelectomy. RNA sequencing was performed on six vascular samples, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the screened differential expressed genes which were validated by quantitative reverse transcription-polymerase chain reaction. The genomes of the patients were analysed using next-generation sequencing to screen for genetic factors behind varicocele infertility. 1171 genes were upregulated and 2772 were downregulated in varicose spermatic veins compared with those in normal veins. These genes were significantly enriched in the alcohol consumption pathway. HIST1H4C, HIST1H4F, HIST1H4K, TM9SF1, and TMEFF1 were significantly differentially expressed. The genomic results identified patients with mutations in CFTR, NANOS1, SRCAP, GATA4, GCM2, TUBB1, ALDH7A1, ANTXR1, and MAP3K1. In conclusion, our results indicated that Alcohol consumption may be a cause of varicoceles. Mutations in certain genes, such as CFTR, may be a cause of male infertility due to varicoceles.

3.
Anal Chim Acta ; 1221: 340026, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934334

RESUMO

State-of-the-art Tb-to-Eu energy transfer (TEET) efficiency (>90%) under ultralow Eu3+ proportion (<6%) has been achieved in Eu/Tb bimetallic lanthanide coordination polymers (LnCPs). The yellow-light-emitting sample as sensor exhibits micromolar l-phenylalanine (l-Phe) in water and serum via obvious yellow-to-green luminometric behavior, meanwhile nanomolar-level detection limits are determined in terms of an updated Stern-Volmer equation with high selectivity and competitiveness. Excited-state inter-ligand photon transfer (ESILPT) greatly contributes to superior TEET property and outstanding luminometric behavior. This work opens a window for developing sensitive and stable visualization sensing, being of values on monitoring biochemical markers.


Assuntos
Elementos da Série dos Lantanídeos , Luminescência , Colorimetria , Transferência de Energia , Európio/química , Elementos da Série dos Lantanídeos/química
4.
Neuropsychology ; 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35834208

RESUMO

Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. OBJECTIVE: In this context, we aimed to estimate the influence of participants' nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world's population. METHOD: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. RESULTS: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants' nationality from potential translation issues, which classically constitute a major limitation. CONCLUSIONS: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

5.
Front Psychiatry ; 13: 855584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782425

RESUMO

Background: Workplace violence (WPV) in healthcare has received much attention worldwide. However, scarce data are available on its impact on turnover intention among psychiatrists, and the possible mechanisms between WPV and turnover intention have not been explored in China. Methods: A cross-sectional survey was conducted among psychiatrists in 41 tertiary psychiatric hospitals from 29 provinces and autonomous regions in China. A stress-strain-outcome (SSO) model was adopted to examine the effects of WPV on mental health and turnover intention. The association and mediation by burnout and stress were examined by multivariate logistic regression (MLR) and generalized structure equation modeling (GSEM). Results: We invited 6,986 psychiatrists to participate, and 4,520 completed the survey (64.7% response rate). The prevalence of verbal and physical violence against psychiatrist in China was 78.0 and 30.7%, respectively. MLR analysis showed that psychiatrists who experienced verbal violence (OR = 1.15, 95% CI = 1.10-1.21) and physical violence (OR = 1.15, 95% CI = 1.07-1.24) were more likely to report turnover intention. GSEM analysis showed that burnout (ß = 4.00, p < 0.001) and stress (ß = 1.15, p < 0.001) mediated the association between verbal violence and turnover intention; similarly, burnout (ß = 4.92, p < 0.001) and stress (ß = 1.80, p < 0.001) also mediated the association between physical violence and turnover intention. Conclusions: Experience of WPV is a significant contributor to turnover intention among psychiatrists. Mental health status, such as burnout and stress level significantly mediated the association. Policy makers and hospital administrators need to be aware of this association. Action is needed to promote mental health among the psychiatrists to improve morale and workforce sustainability.

6.
Hortic Res ; 9: uhac110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795394

RESUMO

The factors underlying the plant collapse of certain melon-pumpkin graft combinations are not fully understood. Our working hypothesis was that impairment of photoassimilates transport in incompatible combinations induces an imbalance in the homeostasis of root auxin (indole-3-acetic acid; IAA) and of cytokinins, probably triggering plant collapse. Root IAA and cytokinins levels in the presence and absence of fruit and changes in root and scion metabolites were investigated in compatible and incompatible combinations. We showed elevated levels of IAA, 2-oxoindole-3-acetic acid (IAA catabolite), indole-3-acetylaspartate (IAA conjugate), and cis-zeatin-type cytokinins, but low levels of trans-zeatin-type cytokinins in the roots of plants of the incompatible combination during fruit ripening. Similarly, during fruit ripening, the expression of the YUCCA genes, YUC2, YUC6, and YUC11 (required for auxin biosynthesis), the GRETCHEN-HAGEN3 gene (required for auxin conjugation), and the cytokinin oxidase/dehydrogenase 7 (CKX7) gene (regulates the irreversible degradation of cytokinin) was enhanced in the roots of plants of the incompatible combination. Moreover, in the incompatible combination the fruiting process restricted transport of photoassimilates to the rootstock and induces their accumulation in the scion. In addition, high levels of hydrogen peroxide and malondialdehyde and reduced activity of antioxidant enzymes were observed in the roots of the incompatible graft. Our results showed that the collapse of the incompatible graft combination during fruit ripening is closely associated with a dramatic accumulation of IAA in the roots, which probably elicits oxidative damage and disturbs the balance of IAA and cytokinins that is of critical importance in melon-pumpkin graft compatibility.

7.
Acta Pharmacol Sin ; 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835856

RESUMO

Aspirin as a chemopreventive agent is able to restrict the tumor growth. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme of glycolysis, playing an important role in the development of cancer. However, the underlying mechanism by which aspirin inhibits the proliferation of cancer cells is poorly understood. This study aims to identify the effects of aspirin on modulating PGAM1 enzymatic activities in liver cancer. Here, we found that aspirin attenuated the PGAM1 succinylation to suppress the PGAM1 enzymatic activities and glycolysis in hepatoma cells. Mechanically, aspirin remarkably reduced the global succinylation levels of hepatoma cells, including the PGAM1 succinylation, which led to the block of conversion from 3-phosphoglycerate (3-PG) to 2-phosphoglycerate (2-PG) in cells. Interestingly, RNA-seq analysis identified that aspirin could significantly decrease the levels of histone acetyltransferase 1 (HAT1), a writer of PGAM1 succinylation, in liver cancer. As a target of aspirin, NF-κB p65 could effectively up-regulate the expression of HAT1 in the system, resulting in the increase of PGAM1 enzymatic activities. Moreover, we observed that the PGAM1-K99R mutant failed to rescue the aspirin-induced inhibition of PGAM1 activities, glycolysis, and proliferation of hepatoma cells relative to PGAM1-WT. Functionally, aspirin down-regulated HAT1 and decreased the PGAM1 succinylation levels in the tumor tissues from mice treated with aspirin in vivo. Thus, we conclude that aspirin modulates PGAM1K99 succinylation to restrict the PGAM1 activities and glycolysis through NF-κB p65/HAT1/PGAM1 signaling in liver cancer. Our finding provides new insights into the mechanism by which aspirin inhibits glycolysis in hepatocellular carcinoma.

8.
Cancers (Basel) ; 14(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35884483

RESUMO

(1) Background: The role of radiotherapy (RT) in superficial esophageal squamous cell cancer (ESCC) remains unclear. The objective of our study was to perform a detailed outcome and safety analysis of RT as a definitive or adjuvant treatment for T1N0M0 staged ESCC patients. (2) Methods: A total of 55 patients treated with endoscopic resection (ER) + RT/concurrent chemoradiotherapy (CCRT) or RT/CCRT from January 2011 to June 2021 were included in this study. Eighteen patients with risk factors received ER + RT/CCRT, and thirty-seven patients solely received RT/CCRT. Kaplan-Meier curves were used to calculate the clinical outcomes, and toxicities were scored. (3) Results: The median follow-up time was 51.9 months. The estimated 5-year local recurrence-free survival (LRFS) and overall survival (OS) were 88.9% and 94.4% in the ER + RT/CCRT group and 91.8% and 91.7% in the RT/CCRT group. The predominant failure pattern was in-field local failure (5.5%, 3/55), with one patient in the ER + RT/CCRT group and two patients in the RT/CCRT group. One patient (1.8%, 1/55) had lung metastasis in the RT/CCRT group. The most common toxicities were Grades 1-2 in all patients, including esophagitis (74.5%, 41/55), myelosuppression (49.1%, 27/55) and esophageal stricture after RT (27.3%, 15/55). Two patients (11.1%, 2/18) and four patients (10.8%, 4/37) had Grade 3 esophageal stricture after RT in the ER + RT/CCRT group and RT/CCRT group, respectively. No patients experienced a Grade 4 or higher toxicity, and there were no treatment-related deaths. (4) Conclusions: Definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.

9.
J Dairy Sci ; 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35879161

RESUMO

Milk protein is one of the major food allergens. As an effective processing method, fermentation may reduce the potential allergenicity of allergens. This study aimed to evaluate the therapeutic potential of co-fermented milk protein using Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 in cow milk protein allergy (CMPA) management. This study determined the secondary and tertiary structures of the fermented versus unfermented proteins by Fourier-transform infrared spectroscopy and surface hydrophobicity to evaluate its conformational changes. Our results showed that different fermentation methods have significantly altered the conformational structures of the cow milk protein, especially the tertiary structure. Further, the potential allergenicity of the fermented cow milk protein was assessed in Balb/c mice, and mice treated with the unfermented milk and phosphate-buffered saline were used as a control. We observed a significant reduction in allergenicity via the results of the spleen index, serum total IgE, specific IgE, histamine, and mouse mast cell protease 1 in the mice treated with the co-fermented milk protein. In addition, we analyzed the cytokines and transcription factors expression levels of spleen and jejunum and confirmed that co-fermentation could effectively reduce the sensitization of cow milk protein by regulating the imbalance of T helper (Th1/Th2 and Treg/Th17). This study suggested that changes of conformational structure could reduce the potential sensitization of cow milk protein; thus, fermentation may be a promising strategy for developing a method of hypoallergenic dairy products.

10.
J Dairy Sci ; 105(8): 6405-6421, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35840401

RESUMO

Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.


Assuntos
Microbioma Gastrointestinal , Fórmulas Infantis , Animais , Ácidos Graxos Voláteis/análise , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Fórmulas Infantis/química , Camundongos , Leite Humano/química , RNA Ribossômico 16S/análise
11.
Carbohydr Polym ; 294: 119828, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35868775

RESUMO

In this study, we explored a novel approach to enhancing the production and bioactivities of Ganoderma exopolysaccharides. The homologous phosphomannomutase gene (PMM1) was cloned and overexpressed in Ganoderma for the first time. As a result, the maximum production of exopolysaccharides by the PMM1 transformant was 1.53 g/L, which was 1.41-fold higher than of a wild-type (WT) strain in a 5-L bioreactor. The transcription levels of PMM1 and PMM2 increased 40.5- and 2.4-fold, respectively, whereas the value of the GDP-D-mannose pyrophosphorylase gene did not change significantly in this transgenic strain. Furthermore, the major exopolysaccharide fractions from PMM1 transformants contained higher amounts of mannose (56.5 % and 21.1 %) than those from a WT strain (26.7 % and 9.3 %). Moreover, the major fractions from PMM1 transformants exhibited stronger regulation effects on macrophage. In conclusion, this study is helpful for the efficient production and application of Ganoderma exopolysaccharides and facilitates an understanding of polysaccharide biosynthesis regulation.


Assuntos
Ganoderma , Fosfotransferases (Fosfomutases) , Reatores Biológicos , Manose , Fosfotransferases (Fosfomutases)/genética
12.
Food Res Int ; 158: 111562, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35840251

RESUMO

Penicillium expansum is the causative fungus of blue mold decay in postharvest pears resulting in substantial economic losses. Investigating P. expansum-pear fruit interactions is necessary to help develop P. expansum control strategies for effective and safe pear production. Investigating the P. expansum gene expression alterations and essential gene functions during the infection process is indispensable. Based on our results, the necrosis-inducing protein (NIP) gene was closely associated with genes related to plant cell wall degrading enzymes (CWDEs) and involved in P. expansum virulence. The NIP has high homology with other already-known fungal NIPs. To evidence the role of NIP in P. expansum virulence, NIP mutant (including knockout (ΔNIP) and complementation mutant (cNIP)) P. expansum were generated. Despite the NIP deletion did not affect the basic morphology and structure of P. expansum, it slowed down the fungal growth and hyphal production, thus reducing P. expansum's sporulation and patulin (PAT) accumulation. Furthermore, the deletion of NIP reduced the pathogenicity of P. expansum in pear. The complementation of NIP (cNIP) restored the growth, conidia production, PAT accumulation, and virulence of ΔNIP to the level of wild-type P. expansum. In addition, PAT can cause decay and aggravate the disease severity of wild-type P. expansum and ΔNIP on pears. Our results confirmed NIP plays a crucial role in P. expansum's growth, hyphal production, and pathogenicity in pears.


Assuntos
Patulina , Penicillium , Pyrus , Necrose , Doenças das Plantas/microbiologia , Pyrus/metabolismo , Virulência/genética
13.
Acta Pharm Sin B ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35702321

RESUMO

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3Cpro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (Mpro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its activity. We demonstrate that targeting the active site cysteine of Mpro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

14.
Nat Chem Biol ; 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710616

RESUMO

Activated B cells increase central carbon metabolism to fulfill their bioenergetic demands, yet the mechanistic basis for this, as well as metabolic regulation in B cells, remains largely unknown. Here, we demonstrate that B-cell activation reprograms the tricarboxylic acid cycle and boosts the expression of fumarate hydratase (FH), leading to decreased cellular fumarate abundance. Fumarate accumulation by FH inhibition or dimethyl-fumarate treatment suppresses B-cell activation, proliferation and antibody production. Mechanistically, fumarate is a covalent inhibitor of tyrosine kinase LYN, a key component of the BCR signaling pathway. Fumarate can directly succinate LYN at C381 and abrogate LYN activity, resulting in a block to B-cell activation and function in vitro and in vivo. Therefore, our findings uncover a previously unappreciated metabolic regulation of B cells, and reveal LYN is a natural sensor of fumarate, connecting cellular metabolism to B-cell antigen receptor signaling.

15.
Radiother Oncol ; 174: 8-15, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35750106

RESUMO

BACKGROUND AND PURPOSE: To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS: This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n = 201) and internal validation sets (n = 101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n = 95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS: The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index: 0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation sets (C-index: 0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p < 0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p < 0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p < 0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index: 0.82), internal (Cindex: 0.78), and external validation sets (C-index: 0.76). Calibration curves showed good agreement. CONCLUSIONS: The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.

16.
World J Emerg Med ; 13(3): 175-181, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646207

RESUMO

BACKGROUND: Septic cardiomyopathy (SCM) occurs in the early stage of sepsis and septic shock, which has implications for treatment strategies and prognosis. Additionally, myocardial involvement in the early stages of sepsis is difficult to identify. Here, we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography (STE). METHODS: Emergency department patients diagnosed with sepsis or septic shock were included for analysis. Those with other causes of acute or pre-existing cardiac dysfunction were excluded. Transthoracic echocardiography (TTE), including conventional echocardiography and STE, were performed for all patients three hours after initial resuscitation. Samples for laboratory tests were taken around the time of TTE. RESULTS: Left ventricular functions of 60 patients were analyzed, including 21 septic shock patients and 39 sepsis patients. There was no significant difference in global longitudinal strain (GLS), global circumferential strain (GCS), or global radical strain (GRS) between patients with sepsis and septic shock (all with P>0.05). However, GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction (LVEF) values (all with P<0.05). There were also moderate correlations between GLS and levels of cTnI (r=0.40, P=0.002) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r=0.44, P=0.001) in sepsis and septic shock patients. CONCLUSION: Myocardial dysfunction, e.g., lower LVEF or less negative GLS in patients with sepsis or septic shock, is more affected by myocardial injury. GLS could be incorporated into mainstream clinical practice as a supplementary LVEF parameter, especially for those with elevated troponin levels.

17.
PLoS Biol ; 20(6): e3001684, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35727855

RESUMO

The ability to detect and respond to acute oxygen (O2) shortages is indispensable to aerobic life. The molecular mechanisms and circuits underlying this capacity are poorly understood. Here, we characterize the behavioral responses of feeding Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. While the behavioral responses to 1% O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome function inhibits escape from 1% O2 due to increased cGMP signaling. A primary source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP) receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+ decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial complex I (MCIII), which lead to persistently high reactive oxygen species (ROS), abrogate acute hypoxia responses. In particular, repressing the expression of isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1% O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia responses. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute responses to hypoxia by C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Hipóxia , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
18.
Angew Chem Int Ed Engl ; : e202205597, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35691826

RESUMO

Protein-protein coupling reactions under physiological conditions that do not impact the three-dimensional structures of the proteins are in high demand. Owing to the combination of phenylsulfonyl and aldehyde groups in 5-fluoro-4-(phenylsulfonyl)picolinaldehyde (FPPA), the fluorine substituent shows high reactivity toward free thiols. In FPPA, the fluorine is more reactive than phenylsulfonyl for free thiols. Thus the first quantitative nucleophilic substitution can be followed by selective substitution of phenylsulfonyl by an additional thiol or cyclization of aldehyde with a 1,2-aminothiol molecule. The FPPA mediated protein-protein coupling proceeds efficiently under mild conditions, resulting in stable protein conjugates. This coupling method has negligible 3D structural perturbations on the target proteins, and it produces overall intact, nearly traceless, and native structural folds of proteins. It is highly suitable for reconstruction of proteins that are difficult to make and segmental isotopic labeling of multidomain proteins.

19.
Biosens Bioelectron ; 210: 114287, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35500311

RESUMO

An "on-off" nonenzymatic and ultrasensitive electrochemiluminescence (ECL) biosensing platform has been constructed to detect BCR-ABL fusion gene based on CeO2/MXene heterojunction and configuration-entropy driven dual-toehold strand displacement reaction (DT-SDR) for signal amplification. The CeO2/MXene heterojunction were prepared via one-step hydrothermal method through in situ synthesis of CeO2 nanocubes on the surface of Ti3C2-MXene nanosheets. Surprisingly, the prepared CeO2/MXene heterojunction with good dispersion and excellent conductivity not only significantly enhanced ECL emission of S2O82-/O2 system, but also acted as good electrode modification materials to provide massive active sites for three-stranded ST/AS/BK complex immobilization. In the presence of target BCR-ABL fusion gene and Bio-FS, target BCR-ABL fusion gene bound to dual-toehold exposed at the ends of ST, replacing AS and BK and obtaining ST/target with a loop. Subsequently, Bio-FS bound to the loop (as toehold) in ST strand of ST/target to form ST/Bio-FS, replacing the target to further trigger a new SDA cycle. This configuration-entropy driven DT-SDR made three-stranded ST/AS/BK complex transform into dual-stranded ST/Bio-FS in the electrode interface. Ultimately, the quenching labels of streptavidin modified Pt nanoparticles functionalized polydopamine composites (SA-Pt@PDA) were introduced via biotin and streptavidin recognition, realizing ECL emission quenching of S2O82-/O2 system for "on-off" detection of BCR-ABL fusion gene. The developed ECL biosensor for BCR-ABL fusion gene detection achieves the wide concentration variation from 1 fM to 100 pM with low limit of detection down to 0.27 fM, which provides new enlightenment and basis for molecular diagnosis of chronic myelogenous leukemia in clinical practice.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Eletrodos , Medições Luminescentes , Fotometria , Estreptavidina
20.
Orphanet J Rare Dis ; 17(1): 209, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606856

RESUMO

BACKGROUND: Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias. RESULTS: A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias. CONCLUSION: Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.


Assuntos
Hipospadia , Proteínas Proto-Oncogênicas B-raf , Humanos , Hipospadia/genética , Sistema de Sinalização das MAP Quinases/genética , Masculino , Fenótipo , Fosforilação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Ativadoras de ras GTPase/genética
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