TRIM59 is required for mouse GC-1 cell maintenance through modulating the ubiquitination of AXIN1.

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate ß-catenin signaling. Furthermore, activation of ß-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

Ionic titanium is expected to improve the nutritional quality of Tartary buckwheat sprouts through flavonoids and amino acid metabolism.

Tartary buckwheat sprouts are highly valued by consumers for their superior nutritional content. Ionic titanium (Ti) has been shown to enhance crop growth and improve nutritional quality. However, there is limited research on the impact of ionic Ti on the nutritional quality of Tartary buckwheat sprouts. This study cultivated Tartary buckwheat sprouts with ionic Ti and found that the high concentration of ionic Ti significantly increased the contents of chlorophyll a, chlorophyll b, and carotenoids (increased by 25.5%, 27.57%, and 15.11%, respectively). The lower concentration of ionic Ti has a higher accumulation of total flavonoids and total polyphenols. Metabolomics analysis by LC-MS revealed 589 differentially expressed metabolites and 54 significantly different metabolites, enriching 82 metabolic pathways, especially including amino acid biosynthesis and flavonoid biosynthesis. This study shows that ionic Ti can promote the growth of Tartary buckwheat sprouts, improve nutritional quality, and have huge development potential in food production.

Quinoa greens as a novel plant food: a review of its nutritional composition, functional activities, and food applications.

Quinoa (Chenopodium quinoa Willd) is widely regarded as a versatile pseudo-cereal native to the Andes Mountains in South America. It has gained global recognition as a superfood due to its rich nutritional profile. While quinoa grains are well-known, there is an undiscovered potential in quinoa greens, such as sprouts, leaves, and microgreens. These verdant parts of quinoa are rich in a diverse array of essential nutrients and bioactive compounds, including proteins, amino acids, bioactive proteins, peptides, polyphenols, and flavonoids. They have powerful antioxidant properties, combat cancer, and help prevent diabetes. Quinoa greens offer comparable or even superior benefits when compared to other sprouts and leafy greens, yet they have not gained widespread recognition. Limited research exists on the nutritional composition and biological activities of quinoa greens, underscoring the necessity for thorough systematic reviews in this field. This review paper aims to highlight the nutritional value, bioactivity, and health potential of quinoa greens, as well as explore their possibilities within the food sector. The goal is to generate interest within the research community and promote further exploration and wider utilization of quinoa greens in diets. This focus may lead to new opportunities for enhancing health and well-being through innovative dietary approaches.

The formation of volatiles in fruit wine process and its impact on wine quality.

Fruit wine is one of the oldest fermented beverages made from non-grape fruits. Owing to the differences in fruit varieties, growing regions, climates, and harvesting seasons, the nutritional compositions of fruits (sugars, organic acids, etc.) are different. Therefore, the fermentation process and microorganisms involved are varied for a particular fruit selected for wine production, resulting in differences in volatile compound formation, which ultimately determine the quality of fruit wine. This article reviews the effects of various factors involved in fruit wine making, especially the particular modifications differing from the grape winemaking process and the selected strains suitable for the specific fruit wine fermentation, on the formation of volatile compounds, flavor and aroma profiles, and quality characteristics of the wine thus produced. KEY POINTS: • The volatile profile and fruit wine quality are affected by enological parameters. • The composition and content of nutrients in fruit must impact volatile profiles. • Yeast and LAB are the key determining factors of the volatile profiles of fruit wines.

Application of C-InGAN Model in Interpretable Feature of Bearing Fault Diagnosis.

Although traditional fault diagnosis methods are proficient in extracting signal features, their diagnostic interpretability remains challenging. Consequently, this article proposes a conditionally interpretable generative adversarial network (C-InGAN) model for the interpretable feature fault diagnosis of bearings. Initially, the vibration signal is denoised and transformed into a frequency domain signal. The model consists of the two primary networks, each employing a convolutional layer and an attention module, generator (G) and discriminator (D), respectively. Latent code was incorporated into G to constrain the generated samples, and a discriminant layer was added to D to identify the interpretable features. During training, the two networks were alternately trained, and the feature mapping relationship of the pre-normalized encoder was learned by maximizing the information from the latent code and the discriminative result. The encoding that represents specific features in the vibration signal was extracted from the random noise. Ultimately, after completing adversarial learning, G is capable of generating a simulated signal of the specified feature, and D can assess the interpretable features in the vibration signal. The effectiveness of the model is validated through three typical experimental cases. This method effectively separates the discrete and continuous feature coding in the signal.

Elevated ROS Levels Caused by Reductions in GSH and AsA Contents Lead to Grain Yield Reduction in Qingke under Continuous Cropping.

Continuous spring cropping of Qingke (Hordeum viilgare L. var. nudum Hook. f.) results in a reduction in grain yield in the Xizang autonomous region. However, knowledge on the influence of continuous cropping on grain yield caused by reactive oxygen species (ROS)-induced stress remains scarce. A systematic comparison of the antioxidant defensive profile at seedling, tillering, jointing, flowering, and filling stages (T1 to T5) of Qingke was conducted based on a field experiment including 23-year continuous cropping (23y-CC) and control (the first year planted) treatments. The results reveal that the grain yield and superoxide anion (SOA) level under 23y-CC were significantly decreased (by 38.67% and 36.47%), when compared to the control. The hydrogen peroxide content under 23y-CC was 8.69% higher on average than under the control in the early growth stages. The higher ROS level under 23y-CC resulted in membrane lipid peroxidation (LPO) and accumulation of malondialdehyde (MDA) at later stages, with an average increment of 29.67% and 3.77 times higher than that in control plants. Qingke plants accumulated more hydrogen peroxide at early developmental stages due to the partial conversion of SOA by glutathione (GSH) and superoxide dismutase (SOD) and other production pathways, such as the glucose oxidase (GOD) and polyamine oxidase (PAO) pathways. The reduced regeneration ability due to the high oxidized glutathione (GSSG) to GSH ratio resulted in GSH deficiency while the reduction in L-galactono-1,4-lactone dehydrogenase (GalLDH) activity in the AsA biosynthesis pathway, higher enzymatic activities (including ascorbate peroxidase, APX; and ascorbate oxidase, AAO), and lower activities of monodehydroascorbate reductase (MDHAR) all led to a lower AsA content under continuous cropping. The lower antioxidant capacity due to lower contents of antioxidants such as flavonoids and tannins, detected through both physiological measurement and metabolomics analysis, further deteriorated the growth of Qingke through ROS stress under continuous cropping. Our results provide new insights into the manner in which ROS stress regulates grain yield in the context of continuous Qingke cropping.

ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases. METHODS: Microarray, immunofluorescence, and Western blotting analyses were conducted to investigate the pathological role of ErbB3. Blood samples were collected for biomarker examination from healthy donors or patients with hypoxic PH. The pathological functions of ErbB3 were further validated in rodents subjected to chronic hypoxia- and Sugen-induced PH, with or without adeno-associated virus-mediated ErbB3 overexpression, systemic deletion, or endothelial cell-specific ErbB3 knockdown. Primary human pulmonary artery endothelial cells and pulmonary artery smooth muscle cells were used to elucidate the underlying mechanisms. RESULTS: ErbB3 exhibited significant upregulation in the serum, lungs, distal pulmonary arteries, and pulmonary artery endothelial cells isolated from patients with PH compared with those from healthy donors. ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated systolic pressure in the right ventricle, and promoted right ventricular hypertrophy in murine models of PH. Conversely, systemic deletion or endothelial cell-specific knockout of ErbB3 yielded opposite effects. Coimmunoprecipitation and proteomic analysis identified YB-1 (Y-box binding protein 1) as a downstream target of ErbB3. ErbB3 induced nuclear translocation of YB-1 and subsequently promoted hypoxia-inducible factor 1/2α transcription. A positive loop involving ErbB3-periostin-hypoxia-inducible factor 1/2α was identified to mediate the progressive development of this disease. MM-121, a human anti-ErbB3 monoclonal antibody, exhibited both preventive and therapeutic effects against hypoxia-induced PH. CONCLUSIONS: Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.

Residual behavior of dinotefuran and its metabolites during Huangjiu fermentation and their effects on flavor.

Yellow rice wine (Huangjiu) is a traditional Chinese alcoholic beverage. However, there is a risk of pesticide residues in Huangjiu due to pesticide indiscriminate use. In this study, the residues of dinotefuran and its metabolites during Huangjiu fermentation and their effects on flavor substances were studied. The initial concentrations of dinotefuran ranged from 856.3 to 1874.9 µg/L, and its half-life was no more than 3.65 d. At 24 d of Huangjiu fermentation, the terminal residues of dinotefuran, 1-methyl-3-(tetrahydro-3-furylmethyl)urea (UF) and 1-methyl-3-(tetrahydro-3-furylmethyl)guanidine (DN) were 195.1-535.3 µg/L, 38.33-48.70 µg/L and 37.8-74.1 µg/L, respectively. Twenty potential degradation compounds were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), and their toxicity was evaluated. Finally, the effect of dinotefuran on physicochemical properties and total phenol content of Huangjiu were analyzed. The risk of rancidity was significantly increased and bitter amino acids were formed. These findings provide a guidance and the safe production of Huangjiu.

Mutation spectrum of thalassemia among pre-pregnant adults in the Jiangsu Province by capillary electrophoresis-based multiplex PCR assay.

BACKGROUND: Thalassemia is a common genetic disorder in southwestern China, and an increasing number of cases from eastern China have been recently reported. Here, we developed a rapid, convenient, and accurate assay to evaluate the mutation spectrum of thalassemia in eastern China. METHODS: A carrier screening assay for 61 hotspot variants among HBA1/HBA2 and HBB (OMIM: 141800, 141850, and 141900) genes was developed by SNaPshot/high-throughput ligation-dependent probe amplification (HLPA) technology. We used this assay to detect the mutation spectrum of thalassemia in individuals from eastern China and compared with the data collected from literatures focused on southern and northern China for variant distribution. RESULTS: Among 4276 tested individuals, 2.62% (112/4276) were α-thalassemia carriers, with 90 carrying one deletion or mutation and 22 carrying two deletions. 0.40% (17/4276) were ß-thalassemia carriers, and the most common variant of ß-thalassemia was c.126_129delCTTT (29.41%) followed by c.316-197C>T (23.53%). The genotype distribution in our study was similar to those from southern China populations. CONCLUSION: The Chinese population from different regions presented comparable mutation spectrum of thalassemia, and the SNaPshot/HLPA technique may serve as a capable assay for a routine genetic test in clinical practice with its accurate, rapid, and inexpensive advantage.

Residual risk of clinically significant copy number variations in fetuses with nasal bone absence or hypoplasia after excluding non-invasive prenatal screening-detectable findings.

BACKGROUND: It remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes. METHODS: This prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes. RESULTS: The overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028). CONCLUSIONS: The residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.

Evaluating the performance of four assays for carrier screening of spinal muscular atrophy.

BACKGROUND AND AIMS: Spinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular condition caused by biallelic mutations in the survival of motor neuron 1 (SMN1) gene. A homozygous deletion of the SMN1 gene accounts for approximately 95-98% of SMA patients. A highly homologous gene survival motor neuron 2 (SMN2) can partially compensate for SMN1 deletion, and its copy number is associated with disease severity. Population-based carrier screening by simultaneous quantification of SMN1 and SMN2 copy numbers is the best method to prevent SMA. MATERIALS AND METHODS: In this study, a total of 516 samples were re-tested for the SMN1 copy number by using quantitative polymerase chain reaction (qPCR), multiplex ligation probe amplification (MLPA), droplet digital PCR (ddPCR), high-resolution melting (HRM) analysis, and PCR-based capillary electrophoresis (PCR/CE) simultaneously. Then, the performance of these methods was compared by using MLPA results as the reference. RESULTS: The results of qPCR, ddPCR, HRM, and PCR/CE in detecting heterozygous deletion of SMN1 exon 7 and the results of ddPCR, HRM, and PCR/CE in detecting ≥2 copies of SMN1 exon7 are totally consistent with those of MLPA. The sensitivity and specificity of qPCR for detection of 2 copies of SMN1 exon 7 were 99.7% and 98.8%, respectively. The sensitivity and specificity of qPCR for detection of >2 copies of SMN1 exon 7 were 96.3% and 99.8%, respectively. Compared with the MLPA results, the sensitivity and specificity of qPCR and HRM for detection of heterozygous deletion of SMN1 exon 8 were 100% and 100%, respectively. They were 99.4% and 100%, respectively for detection of 2 copies, and 100% and 100%, respectively for detection of >2 copies. The results of PCR/CE in detecting SMN1 exon 8 were consistent with those of MLPA. CONCLUSION: All these four methods show excellent performance in detecting heterozygous deletion of SMN1 exon 7. All PCR/CE results are totally concordant with those of MLPA. As the most cost-effective method, qPCR also shows high sensitivity and specificity in detecting SMN1. Taken together, our study provides useful information to select appropriate methods for SMA carrier screening.

Comparison of microbial communities and volatile profiles of wines made from mulberry and grape.

In this study, three kinds of wines separately made from mulberry (MW), grape (GW), or mulberry/grape (MGW) were developed and their enological parameters, sensory scores, volatile components, and microbiota were investigated and compared. Contrary to the order of residual sugar and acidity of the three kinds of wines, the order of alcohol content from high to low is GW, MW, and MGW. A total of 60 volatile components (VCs), including esters (17), alcohols (12), acids (6), aldehydes (7), ketones (3), alkenes (3), amines (3), alkanes (4), pyrazines (2), benzene (1), sulfide (1), and thiazole (1), were identified by gas chromatography-ion mobility spectrometer (GC-IMS). The fingerprint of VCs and principal component analysis revealed that the volatile profiles of MGW and GW were more similar in comparison to that of MW and were significantly correlated with the mass ratio of mulberry to grape. Lactobacillus, Weissella, Pantoea, Leuconostoc, Lactococcus, Paenibacillus, Pediococcus, and Saccharomyces were identified as the main microflora at the genus level shared by the MW, MGW, and GW, suggesting that the heterolactic bacteria may contribute more to the high content of volatile acids in MW and MGW. The heatmap of core microbiota and main VCs of MW, MGW, and GW suggested the complicated and significant correlation between them. The above data implied that the volatile profiles were more closely related to the raw materials of winemaking and markedly affected by the fermentation microorganisms. This study provides references for evaluation and characterization of MGW and MW and improvement of MGW and MW winemaking process. KEY POINTS: • Fruit wine enological parameters, volatile profile, and microbiota were compared. • Sixty volatile compounds were identified by GC-IMS in three types of fruit wines. • Winemaking materials and microbiota affect volatile profiles of the fruit wines.

DR region of NKAα1 is a target to ameliorate hepatic lipid metabolism disturbance in obese mice.

BACKGROUND: Na+/K+-ATPase (NKA), an ion pumping enzyme ubiquitously expressed in various cells, is critically involved in cellular ion homeostasis and signal transduction. However, the role of NKA in hepatic lipid homeostasis has yet to be fully characterized. METHODS: The activity of NKA and NKAα1 expression were determined in steatotic cells, mice and patients. The roles of NKAα1 in hepatosteatosis were detected using hepatocyte knockout or specific overexpression of NKAα1 in mice. RESULTS: Herein, we demonstrated that the expression and activity of α1 subunit of NKA (NKAα1) were lowered in the livers of nonalcoholic fatty liver disease (NAFLD) patients, high-fat diet (HFD)-induced obese mice, and genetically obese (ob/ob, db/db) mice, as well as oleic acid-induced hepatocytes. Hepatic deficiency of NKAα1 exacerbated, while adeno-associated virus-mediated liver specific overexpression of NKAα1 alleviated hepatic steatosis through regulation of fatty acid oxidation (FAO) and lipogenesis. Mechanistically, we revealed that NKAα1 upregulated sirtuin 1 (SIRT1) via interacting with ubiquitin specific peptidase 22 (USP22), a deubiquitinating enzyme for the stabilization and deubiquitination of SIRT1, thus activating the downstream autophagy signaling. Blockade of the SIRT1/autophagy signaling pathway eliminated the protective effects of NKAα1 against lipid deposition in hepatocytes. Importantly, we found that an antibody against the DR region (897DVEDSYGQQWTYEQR911) of NKAα1 subunit (DR-Ab) ameliorated hepatic steatosis through maintaining the membrane density of NKAα1 and inducing its activation. CONCLUSIONS: Collectively, this study renews the functions of NKAα1 in liver lipid metabolism and provides a new clue for gene therapy or antibody treatment of hepatic lipid metabolism disturbance by targeting NKAα1.

Targeting the Na+/K+ ATPase DR-region with DR-Ab improves doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a potent chemotherapeutic drug for various cancers. Yet, the cardiotoxic side effects limit its application in clinical uses, in which ferroptosis serves as a crucial pathological mechanism in DOX-induced cardiotoxicity (DIC). A reduction of Na+/K + ATPase (NKA) activity is closely associated with DIC progression. However, whether abnormal NKA function was involved in DOX-induced cardiotoxicity and ferroptosis remains unknown. Here, we aim to decipher the cellular and molecular mechanisms of dysfunctional NKA in DOX-induced ferroptosis and investigate NKA as a potential therapeutic target for DIC. A decrease activity of NKA further aggravated DOX-triggered cardiac dysfunction and ferroptosis in NKAα1 haploinsufficiency mice. In contrast, antibodies against the DR-region of NKAα-subunit (DR-Ab) attenuated the cardiac dysfunction and ferroptosis induced by DOX. Mechanistically, NKAα1 interacted with SLC7A11 to form a novel protein complex, which was directly implicated in the disease progression of DIC. Furthermore, the therapeutic effect of DR-Ab on DIC was mediated by reducing ferroptosis by promoting the association of NKAα1/SLC7A11 complex and maintaining the stability of SLC7A11 on the cell surface. These results indicate that antibodies targeting the DR-region of NKA may serve as a novel therapeutic strategy to alleviate DOX-induced cardiotoxicity.

Reproductive outcomes in couples with sporadic miscarriage after embryonic chromosomal microarray analysis.

OBJECTIVES: Chromosomal microarray analysis (CMA) has been widely applied to genetic diagnosis in miscarriages in clinical practice. However, the prognostic value of CMA testing of products of conception (POCs) after the first clinical miscarriage remains unknown. The aim of this study was to evaluate the reproductive outcomes after embryonic genetic testing by CMA in SM couples. METHODS: In this retrospective study, a total of 1142 SM couples referred for embryonic genetic testing by CMA, and 1022 couples were successfully followed up after CMA. RESULTS: Among 1130 cases without significant maternal cell contamination, pathogenic chromosomal abnormalities were detected in 680 cases (60.2%). The subsequent live birth rate did not differ significantly between couples with chromosomally abnormal and normal miscarriage (88.6% vs. 91.1%, p = .240), as well as the cumulative live birth rate (94.5% vs. 96.7%, p = .131). Couples with partial aneuploid miscarriage had a higher likelihood of spontaneous abortion both in the subsequent pregnancy (19.0% vs. 6.5%, p = .037) and cumulative pregnancies (19.0% vs. 6.8%, p = .044) when compared with couples with chromosomally normal miscarriage. CONCLUSIONS: SM couples with chromosomally abnormal miscarriage manifested with a similar reproductive prognosis to couples with chromosomally normal miscarriage. Key messagesCMA testing of POCs could provide an accurate genetic diagnosis for couples with SM.The live birth rate of couples with partial aneuploid miscarriage was as high as couples with chromosomally normal miscarriage, despite a higher risk of adverse pregnancy event.Among couples with the most common single aneuploid miscarriage, the cumulative live birth rates of couples with trisomy 16, sex chromosomal abnormalities and trisomy 22 were 94.1%, 95.8% and 84.0%, respectively.

Current attitudes toward carrier screening for spinal muscular atrophy among pregnant women in Eastern China.

Spinal muscular atrophy (SMA) is an autosomal recessive and often fatal neurological disease. However, very little is known about the attitudes toward SMA carrier screening among Chinese pregnant people. In this study, pregnant women in Eastern China who were undergoing routine chromosomal screening programs were invited to view an educational video about SMA and complete a 26-item survey regarding their attitudes toward SMA screening by scanning a specific quick response code. A total of 1673 questionnaires were collected, and 81.1% of respondents were willing to undergo self-funded screening. If the screening program were included in the medical insurance, 97.8% of respondents were willing to accept screening. The important reasons for supporting SMA screening were a belief that it could help them make better reproductive decisions and avoid having a child with SMA. The key reason for declining SMA screening was not having a family history of genetic diseases. A higher score for SMA genetics knowledge was associated with a greater willingness to undergo SMA screening. We concluded that pregnant women in Eastern China had positive attitudes toward SMA carrier screening. Improving genetic knowledge and including the screening program in medical insurance would support the widespread implementation of SMA carrier screening. Steps should be taken to offer SMA carrier screening along with pre- and posttest education and genetic counseling to raise awareness and reduce misconceptions regarding SMA.

Deficiency of HtrA3 Attenuates Bleomycin-Induced Pulmonary Fibrosis Via TGF-ß1/Smad Signaling Pathway.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by excessive extracellular matrix deposition. No effective treatments are currently available for IPF. High-temperature requirement A3 (HtrA3) suppresses tumor development by antagonizing transforming growth factor ß (TGF-ß) signaling; however, little is known about the role of HtrA3 in IPF. This study investigated the role of HtrA3 in IPF and underlying mechanisms. METHODS: Lung tissues were collected from patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis, and HtrA3 expression was measured in tissue samples. Then, HtrA3 gene knockout mice were treated with BLM to induce pulmonary fibrosis and explore the effects and underlying mechanism of HtrA3 on pulmonary fibrosis. RESULTS: HtrA3 was up-regulated in the lung tissues of patients with IPF and the pulmonary fibrotic mouse model compared to corresponding control groups. HtrA3 knockout decreased pulmonary fibrosis-related protein expression, alleviated the symptoms of pulmonary fibrosis, and inhibited epithelial-mesenchymal transition (EMT) in BLM-induced lung tissue compared with BLM-induced wild-type mice. The TGF-ß1/Smad signaling pathway was activated in fibrotic lung tissue, whereas HtrA3 knockout inhibited this pathway. CONCLUSION: The expression level of HtrA3 is increased in fibrotic lungs. HtrA3 knockout alleviates the symptoms of pulmonary fibrosis probably via the TGF-ß1/Smad signaling pathway. Therefore, HtrA3 inhibition is a potential therapeutic target for pulmonary fibrosis.

Effect of Pathogenic Fungal Infestation on the Berry Quality and Volatile Organic Compounds of Cabernet Sauvignon and Petit Manseng Grapes.

The effect of pathogenic fungal infestation on berry quality and volatile organic compounds (VOCs) of Cabernet Sauvignon (CS) and Petit Manseng (PM) were investigated by using biochemical assays and gas chromatography-ion mobility spectrometry. No significant difference in diseases-affected grapes for 100-berry weight. The content of tannins and vitamin C decreased significantly in disease-affected grapes, mostly in white rot-affected PM, which decreased by 71.67% and 66.29%. The reduced total flavonoid content in diseases-affected grape, among which the least and most were anthracnose-affected PM (1.61%) and white rot-affected CS (44.74%). All diseases-affected CS had much higher titratable acid, a maximum (18.86 g/100 ml) was observed in the gray mold-affected grapes, while only anthracnose-affected grapes with a higher titratable acid level (21.8 g/100 mL) were observed in PM. A total of 61 VOCs were identified, including 14 alcohols, 13 esters, 12 aldehydes, 4 acids, 4 ketones, 1 ether, and 13 unknown compounds, which were discussed from different functional groups, such as C6-VOCs, alcohols, ester acetates, aldehydes, and acids. The VOCs of CS changed more than that of Petit Manseng's after infection, while gray mold-affected Cabernet Sauvignon had the most change. C6-VOCs, including hexanal and (E)-2-hexenal were decreased in all affected grapes. Some unique VOCs may serve as hypothetical biomarkers to help us identify specific varieties of pathogenic fungal infestation.

A Novel Fluorescent Aptasensor Based on Real-Time Fluorescence and Strand Displacement Amplification for the Detection of Ochratoxin A.

It is urgently necessary to develop convenient, reliable, ultrasensitive and specific methods of ochratoxin A determination in food safety owing to its high toxicity. In the present study, an ultrasensitive and labeled-free fluorescent aptamer sensor combining real-time fluorescence with strand displacement amplification (SDA) was fabricated for the determination of OTA. In the presence of OTA, the OTA-aptamer combines with OTA, thus opening hairpins. Then, SDA primers specifically bind to the hairpin stem, which is used for subsequent amplification as a template. SDA amplification is initiated under the action of Bst DNA polymerase and nicking endonuclease. The amplified products (ssDNA) are dyed with SYBR Green II and detected with real-time fluorescence. The method has good linearity in the range of 0.01-50 ng mL-1, with the lowest limit of detection of 0.01 ng mL-1. Additionally, the fluorescent aptamer sensor shows outstanding specificity and reproducibility. Furthermore, the sensor shows excellent analytical performance in the artificial labeled detection of wheat and oat samples, with a recovery rate of 96.1~100%. The results suggest that the developed sensor has a promising potential application for the ultrasensitive detection of contaminants in food.