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1.
Artigo em Inglês | MEDLINE | ID: mdl-36659862

RESUMO

OBJECTIVES: The genus Streptococcus contains species of important zoonotic pathogens such as those that cause bovine mastitis. Unfortunately, many Streptococcus species have developed antibiotic resistance. Phage lysins are considered promising alternatives to antibiotics because it is difficult for bacteria to develop lysin resistance. However, there remains a lack of phage lysin resources for the treatment of streptococci-induced mastitis. METHODS: We identified the prophage lysin Lys0859 from the genome of the Streptococcus suis SS0859 strain. Lys0859 was subsequently characterized to determine its host range, MIC, bactericidal activity in milk, and ability to clear biofilms in vitro. Finally, to determine the effects of Lys0859 on the treatment of both bovine mastitis and S. suis infection in vivo, we established models of Streptococcus agalactiae ATCC 13813-induced mastitis and S. suis serotype 2 SC19 systemic infection. RESULTS: Our results demonstrate that Lys0859 possesses broad-spectrum lytic activity against Streptococcus and Staphylococcus species isolated from animals with bovine mastitis and 15 serotypes of S. suis isolated from swine. Intramammary and intramuscular injection of Lys0859 reduced the number of bacteria in mammary tissue by 3.75 and 1.45 logs compared with the PBS group, respectively. Furthermore, 100 µg/mouse of Lys0859 administered intraperitoneally at 1 h post-infection protected 83.3% (5/6) of mice from a lethal dose of S. suis infection. CONCLUSIONS: Overall, our results enhance the understanding and development of new strategies to combat both streptococci-induced mastitis and S. suis infection.

2.
CNS Neurosci Ther ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650666

RESUMO

INTRODUCTION: For investigating the mechanism of brain injury caused by chronic fluorosis, this study was designed to determine whether NRH:quinone oxidoreductase 2 (NQO2) can influence autophagic disruption and oxidative stress induced in the central nervous system exposed to a high level of fluoride. METHODS: Sprague-Dawley rats drank tap water containing different concentrations of fluoride for 3 or 6 months. SH-SY5Y cells were either transfected with NQO2 RNA interference or treated with NQO2 inhibitor or activator and at the same time exposed to fluoride. The enrichment of gene signaling pathways related to autophagy was evaluated by Gene Set Enrichment Analysis; expressions of NQO2 and autophagy-related protein 5 (ATG5), LC3-II and p62, and mammalian target of rapamycin (mTOR) were quantified by Western-blotting or fluorescent staining; and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) assayed biochemically and reactive oxygen species (ROS) detected by flow cytometry. RESULTS: In the hippocampal CA3 region of rats exposed to high fluoride, the morphological characteristics of neurons were altered; the numbers of autophagosomes in the cytoplasm and the levels of NQO2 increased; the level of p-mTOR was decreased, and the levels of ATG5, LC3-II and p62 were elevated; and genes related to autophagy enriched. In vitro, in addition to similar changes in NQO2, p-mTOR, ATG5, LC3 II, and p62, exposure of SH-SY5Y cells to fluoride enhanced MDA and ROS contents and reduced SOD activity. Inhibition of NQO2 with RNAi or an inhibitor attenuated the disturbance of the autophagic flux and enhanced oxidative stress in these cells exposed to high fluoride. CONCLUSION: Our findings indicate that NQO2 may be involved in regulating autophagy and oxidative stress and thereby exerts an impact on brain injury caused by chronic fluorosis.

3.
J Clin Med ; 12(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36615152

RESUMO

Hematocrit, a commonly used hematological indicator, is a simple and easily applicable test. As a marker of anisocytosis and anemia, it indicates the percentage of blood cells per unit volume of whole blood. This study aimed to evaluate the association between the level of the hematocrit at admission and preoperative deep vein thrombosis (DVT) in hip fractures of older people. We collected the demographic and clinical characteristics of patients with geriatric hip fractures between 1 January 2015, and 30 September 2019, at the largest trauma center in northwestern China. Doppler ultrasonography was used to diagnose DVT. The correlation between hematocrit levels at admission and preoperative DVT was assessed using linear and nonlinear multivariate logistic regression, according to the adjusted model. All analyzes were performed using EmpowerStats and R software. In total, 1840 patients were included in this study, of which 587 patients (32%) had preoperative DVT. The mean hematocrit level was 34.44 ± 5.64 vol%. Linear multivariate logistic regression models showed that admission hematocrit levels were associated with preoperative DVT (OR = 0.97, 95% CI: 0.95-0.99; p = 0.0019) after adjustment for confounding factors. However, the linear association was unstable, and nonlinearity was identified. An admission hematocrit level of 33.5 vol% was an inflection point for the prediction. Admission hematocrit levels <33.5 vol% were not associated with preoperative DVT (OR = 1.00, 95% CI: 0.97-1.04, p = 0.8230), whereas admission hematocrit levels >33.5 vol% were associated with preoperative DVT (OR = 0.94, 95% CI: 25 0.91-0.97, p = 0.0006). Hematocrit levels at admission were nonlinearly associated with preoperative DVT, and hematocrit at admission was a risk factor for preoperative DVT. However, the severity of a low hematocrit was not associated with preoperative DVT when the hematocrit was <33.5 vol%.

4.
J Trace Elem Med Biol ; 75: 127088, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36265321

RESUMO

BACKGROUND: Potential protection against the neurotoxic damages of high levels of fluoride on rats and SH-SY5Y cells by extract of Ginkgo biloba leaves, as well as underlying mechanisms, were examined. METHODS: The rats were divided randomly into 4 groups, i.e., control, treatment with the extract (100 mg/kg body weight, gavage once daily), treatment with fluoride (50 ppm F- in drinking water) and combined treatment with both; SH-SY5Y cells exposed to fluoride and fluoride in combination with the extract or 4-Amino-1,8-naphthalimide (4-ANI), an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1). Spatial learning and memory in the rats were assessed employing Morris water maze test; the contents of fluoride in brains and urine by fluoride ion-selective electrode; cytotoxicity of fluoride was by CCK-8 kit; the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) by appropriate kits; the level of 8-hydroxydeoxyguanosine (8-OHdG) was by ELISA; the content of ROS and frequency of apoptosis by flow cytometry; the expressions of phospho-histone H2A.X(Ser139), PARP-1, poly (ADP-ribose) (PAR) and Sirtuin-1 (SIRT1) by Western blotting or immunofluorescence. RESULTS: The rats with prolong treatment of fluoride exhibited dental fluorosis, the increased contents of fluoride in brains and urine and the declined ability of learning and memory. In the hippocampus of the rats and SH-SY5Y cells exposed to fluoride, the levels of ROS, MDA, apoptosis, 8-OHdG and the protein expressions of histone H2A.X(Ser139), PARP-1 and PAR were all elevated; the activities of SOD and GSH-Px and the protein expression of SIRT1 reduced. Interestingly, the treatment of Ginkgo biloba extract attenuated these neurotoxic effects on rats and SH-SY5Y cells exposed to fluoride and the treatment of 4-ANI produced a neuroprotective effect against fluoride exposure. CONCLUSION: Ginkgo biloba extract attenuated neurotoxic damages induced by fluoride exposure to rats and SH-SY5Y cells and the underlying mechanism might involve the inhibition of PARP-1 and the promotion of SIRT1.


Assuntos
Fluoretos , Neuroblastoma , Humanos , Animais , Ratos , Fluoretos/farmacologia , Histonas
5.
Drug Resist Updat ; 66: 100907, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527888

RESUMO

The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1 , Resistência a Medicamentos , Imunoterapia , Microambiente Tumoral
6.
Clin Cancer Res ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469563

RESUMO

PURPOSE: We investigated the safety and preliminary efficacy of anti-PD-L1 antibody (ZKAB001) as maintenance therapy for localized high-grade osteosarcoma patients to reduce the risk of recurrence and metastasis. PATIENTS AND METHODS: This open-label phase I/II study was divided into dose-escalation phase I and expansion phase II. Phase I utilized a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3. RESULTS: Between October 2018 and October 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The maximum tolerated dose (MTD) was not defined in phase I. All doses had a manageable safety profile. The recommended dose in phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only one (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year EFS and OS were not established, however, 24-month EFS was 71.4% (95% CI: 47.2-86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population. CONCLUSIONS: Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized osteosarcoma patients.

7.
ACS Appl Mater Interfaces ; 14(51): 56471-56482, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36519432

RESUMO

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.


Assuntos
Neoplasias Mamárias Animais , Nanopartículas , Neoplasias , Animais , Camundongos , Fototerapia/métodos , Terapia Fototérmica , Irídio , Espécies Reativas de Oxigênio , Linhagem Celular Tumoral , Neoplasias/terapia , Nanopartículas/uso terapêutico , Neoplasias Mamárias Animais/terapia , Microambiente Tumoral
8.
Heliyon ; 8(12): e12159, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36544837

RESUMO

To explore the hemodynamic changes of the superficial temporal artery in adult Moyamoya Disease (MMD) who underwent combined revascularization surgery. A number of 40 patients with MMD were enrolled, and all of them underwent a direct superficial temporal artery (STA)-middle cerebral artery (STA-MCA) bypass combined with an encephalo-duro-arterio-synangiosis (EDAS). Hemodynamic parameters were detected by Color Doppler Ultrasonography (CDUS) at the preoperative, perioperative and follow-up time, including peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI). The control group were selected randomly during the same period. Researchers applied the SPSS 21 to conduct the two-sample analysis, Chi-Squared test and one-way repeated measures ANOVA between groups. P < 0.05 was considered statistically significant. In this study, 21 males and 19 females with an average age of 44.9 years (Range 28 y-56 y) were enrolled in the MMD group. Among them, 21 patients (52.5%) had perioperative complications, and all symptoms were transient neurological dysfunctions. Intermittent speech disorder was the most common complication during the period of operation. The preoperative hemodynamic of STA showed no significant difference between MMD and the control group. The perioperative hemodynamics had significant carnages compared with preoperative, and there was a trend of fluctuation. The perioperative PSV in the group with complications was significantly higher than the group without complications, except for EDV and RI. In the follow-up ( X ¯ = 5 months), PSV (60.21 ± 22.24 cm/s, P = 0.712) showed no difference compared with baseline data, while EDV (25.12 ± 9.94 cm/s, P = 0.000) and RI (0.575 ± 0.092, P = 0.000) showed significant difference between MMD and control group. The blood flow spectrogram showed high resistance in preoperative, but most patients showed a low resistance pattern during the follow-up time. It was the first time to demonstrate that the hemodynamic changes of STA fluctuated significantly within one week and eventually remained stable after combined revascularization. The PSV may play a more important role in postoperative complications. In the follow-up, PSV had no significant difference, EDV increased significantly, and RI decreased significantly. The blood flow spectrogram mainly shows a low resistance pattern when the hemodynamic is stable.

9.
Br J Cancer ; 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526676

RESUMO

BACKGROUND: At present, the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) is gemcitabine combined with cisplatin, but a considerable portion of ICC patients exhibit resistance to gemcitabine. Therefore, finding sensitisers for gemcitabine chemotherapy in ICC patients and predicting molecular markers for chemotherapy efficacy have become urgent needs. METHODS: In this study, PDX models were established to conduct gemcitabine susceptibility tests. The selected PDX tissues of the chemotherapy-sensitive group and drug-resistant group were subjected to transcriptome sequencing and protein chip technology to identify the key genes. Sixty-one ICC patients treated with gemcitabine chemotherapy were recruited for clinical follow-up validation. RESULTS: We found that thrombospondin-1 (TSP1) can predict gemcitabine chemosensitivity in ICC patients. The expression level of TSP1 could reflect the sensitivity of ICC patients to gemcitabine chemotherapy. Functional experiments further confirmed that TSP1 can increase the efficacy of gemcitabine chemotherapy for ICC. A mechanism study showed that TSP1 may affect the intake of oleic acid by binding to the CD36 receptor. CONCLUSIONS: In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.

10.
Mol Genet Genomic Med ; : e2103, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36373990

RESUMO

BACKGROUND: Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain-of-function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left-sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. METHODS: A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease-causing variant. A literature review of Myhre syndrome was also performed. RESULTS: A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23-month follow-up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%-54.5%), finger and toe abnormalities (3.9%-48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). CONCLUSIONS: Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2-3 toe involvement, or more complicated as was observed in our patient.

11.
Curr Opin Biotechnol ; 78: 102845, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36403537

RESUMO

Diols are important bulk chemicals that are widely used in polymer, cosmetics, fuel, food, and pharmaceutical industries. The development of bioprocess to produce diols from renewable feedstocks has gained much interest in recent years and is contributing to reducing the carbon footprint of the chemical industry. Although bioproduction of some natural diols such as 1,3-propanediol and 2,3-butanediol has been commercialized, microbial production of most other diols is still challenging due to the lack of natural biosynthetic pathways. This review describes the recent efforts in the development of novel synthetic pathways and metabolic engineering strategies for the biological production of C2∼C5 diols. We also discussed the main challenges and future perspectives for the microbial processes toward industrial application.

12.
Hortic Res ; 9: uhac200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382226

RESUMO

Fruit shape is an essential agronomic feature in many crops. We identified and functionally characterized an auxin pathway-related gene, VvSUN. VvSUN, which belongs to the SUN/IQ67-DOMAIN (IQD) family, localizes to the plasma membrane and chloroplast and may be involved in controlling fruit shape through auxin. It is highly expressed in the ovary, and the expression level 1 week before the anthesis stage is positively correlated with the fruit shape index. Functional analyses illustrated that VvSUN gene overexpression in tomato and tobacco plants changed fruit/pod shape. The VvSUN promoter directly bound to VvARF6 in yeast and activated ß-glucuronidase (GUS) activity by indole-3-acetic acid (IAA) treatments in grapevine leaves, indicating that VvSUN functions are in coordination with auxin. Further analysis of 35S::VvSUN transgenic tomato ovaries showed that the fruit shape changes caused by VvSUN were predominantly caused by variations in cell number in longitudinal directions by regulating endogenous auxin levels via polar transport and/or auxin signal transduction process variations. Moreover, enrichment of the 35S::VvSUN transgenic tomato differentially expressed genes was found in a variety of biological processes, including primary metabolic process, transmembrane transport, calcium ion binding, cytoskeletal protein binding, tubulin binding, and microtubule-based movement. Using weighted gene co-expression network analysis (WGCNA), we confirmed that this plant hormone signal transduction may play a crucial role in controlling fruit shape. As a consequence, it is possible that VvSUN acts as a hub gene, altering cellular auxin levels and the plant hormone signal transduction pathway, which plays a role in cell division patterns, leading to anisotropic growth of the ovary and, ultimately, an elongated fruit shape.

13.
BMC Med Genomics ; 15(1): 241, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401330

RESUMO

Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.


Assuntos
Surdez , Perda Auditiva , Humanos , Linhagem , Miosinas/genética , Surdez/genética , Perda Auditiva/genética , Fenótipo , Família , Genótipo
14.
Sci Adv ; 8(47): eade3431, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36417504

RESUMO

The catalytic asymmetric geminal bis-nucleophilic addition to nonreactive functional groups is a type of highly desirable yet challenging transformation in organic chemistry. Here, we report the first catalytic asymmetric reductive/deoxygenative alkynylation of secondary amides. The method is based on a multicatalysis strategy that merges iridium/copper relay catalysis with organocatalysis. A further combination with the palladium-catalyzed alkyne hydrogenation allows the one-pot enantioselective reductive alkylation of secondary amides. This versatile protocol allows the efficient synthesis of four types of α-branched chiral amines, which are prevalent structural motifs of active pharmaceutical ingredients. The protocol also features excellent enantioselectivity, chemoselectivity, and functional group tolerance to be compatible with more reactive functional groups such as ketone and aldehyde. The synthetic utility of the method was further demonstrated by the late-stage functionalization of two drug derivatives and the concise, first catalytic asymmetric approach to the κ-opioid antagonist aticaprant.

15.
Cancers (Basel) ; 14(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36358727

RESUMO

BACKGROUND: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. METHODS: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. RESULTS: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02-1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3'RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3'UTR of CHURC1 isoforms. CONCLUSION: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3'UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3'UTR lengths of CHURC1 that regulate LUAD development.

16.
Genomics ; 114(6): 110518, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347326

RESUMO

The Muscovy duck (Cairina moschata) is an economically important poultry species, which is susceptible to fatty liver. Thus, the Muscovy duck may serve as an excellent candidate animal model of non-alcoholic fatty liver disease. However, the mechanisms underlying fatty liver development in this species are poorly understood. In this study, we report a chromosome-level genome assembly of the Muscovy duck, with a contig N50 of 11.8 Mb and scaffold N50 of 83.16 Mb. The susceptibility of Muscovy duck to fatty liver was mainly attributed to weak lipid catabolism capabilities (fatty acid ß-oxidation and lipolysis). Furthermore, conserved noncoding elements (CNEs) showing accelerated evolution contributed to fatty liver formation by down-regulating the expression of genes involved in hepatic lipid catabolism. We propose that the susceptibility of Muscovy duck to fatty liver is an evolutionary by-product. In conclusion, this study revealed the potential mechanisms underlying the susceptibility of Muscovy duck to fatty liver.

17.
J Food Sci ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36353794

RESUMO

Soybean is a protein-rich material for plant-based products, and its application in soymilk products is limited due to its off-odor such as beany. In order to explore a solution to address this issue, composition, formation mechanism, and removal methods of the off-odor produced in the processing of soymilk products are comprehensively described in this paper. The main off-odor compounds in soymilk products include hexanal, hexanol, 1-octene-3-ol, (E,E)-2, 4-decadienal, 2-pentylfuran, (E,E)-2,4-nonadienal, (E)-2-nonenal, (E) -2-hexenal, and so on. These odor compounds are mainly produced by the enzymatic and nonenzymatic oxidation of unsaturated fatty acids. At present, physical methods are used to remove off-odor in the industrial production of soymilk products, of which heat treatment is still the most effective. With the development of no beany soybean breeding technology, the combination of multiple methods will become a technical trend for removing off-odor. Some new research directions are also explored about removal methods, which can provide a theoretical reference for the production and technical research of soymilk products.

18.
Chem Sci ; 13(38): 11320-11329, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36320582

RESUMO

Rechargeable Zn batteries hold great practicability for cost-effective sustainable energy storage but suffer from irreversibility of the Zn anode in aqueous electrolytes due to parasitic H2 evolution, corrosion, and dendrite growth. Herein, we report a non-flammable, dilute, and hydrous organic electrolyte by dissolving low-cost hydrated Zn(ClO4)2·6H2O in trimethyl phosphate (TMP), which homogenizes plating/stripping and enables in situ formation of a Zn3(PO4)2-ZnCl2-rich interphase to stabilize the Zn anode. A dilute 0.5 m Zn(ClO4)2·6H2O/TMP electrolyte featuring a H2O-poor Zn2+-solvation sheath and low water activity enables significantly enhanced Zn reversibility and a wider electrochemical window than the concentrated counterpart. In this formulated electrolyte, the Zn anode exhibits a high efficiency of 99.5% over 500 cycles, long-term cycling for 1200 h (5 mA h cm-2 at 5 mA cm-2) and stable operation at 50 °C. The results would guide the design of hydrous organic electrolytes for practical rechargeable batteries employing metallic electrode materials.

19.
PLoS Biol ; 20(11): e3001856, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318514

RESUMO

Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.


Assuntos
Microcefalia , Peixe-Zebra , Animais , Proteína Proto-Oncogênica N-Myc , Peixe-Zebra/metabolismo , Microcefalia/genética , Serina-Treonina Quinases TOR/metabolismo , Leucina
20.
Genes (Basel) ; 13(11)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36421777

RESUMO

One of the most prominent transcription factors in higher plants, the WRKY gene family, is crucial for secondary metabolism, phytohormone signaling, plant defense responses, and plant responses to abiotic stresses. It can control the expression of a wide range of target genes by coordinating with other DNA-binding or non-DNA-binding interacting proteins. In this study, we performed a genome-wide analysis of the EfWRKY genes and initially identified 89 members of the EfWRKY transcription factor family. Using some members of the OsWRKY transcription factor family, an evolutionary tree was built using the neighbor-joining (NJ) method to classify the 89 members of the EfWRKY transcription factor family into three major taxa and one unclassified group. Molecular weights ranged from 22,614.82 to 303,622.06 Da; hydrophilicity ranged from (-0.983)-(0.159); instability coefficients ranged from 40.97-81.30; lipid coefficients ranged from 38.54-91.89; amino acid numbers ranged from 213-2738 bp; isoelectric points ranged from 4.85-10.06. A signal peptide was present in EfWRKY41 but not in the other proteins, and EfWRK85 was subcellularly localized to the cell membrane. Chromosome localization revealed that the WRKY gene was present on each chromosome, proving that the conserved pattern WRKYGQK is the family's central conserved motif. Conserved motif analysis showed that practically all members have this motif. Analysis of the cis-acting elements indicated that, in addition to the fundamental TATA-box, CAAT-box, and light-responsive features (GT1-box), there are response elements implicated in numerous hormones, growth regulation, secondary metabolism, and abiotic stressors. These results inform further studies on the function of EfWRKY genes and will lead to the improvement of sugarcane.


Assuntos
Perciformes , Saccharum , Animais , Saccharum/genética , Saccharum/metabolismo , Proteínas de Plantas/metabolismo , Família Multigênica , Biologia Computacional , Fatores de Transcrição/metabolismo , Perciformes/genética
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