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1.
J Environ Manage ; 360: 121023, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733837

ABSTRACT

Solar-induced chlorophyll fluorescence (SIF) has been used since its discovery to characterize vegetation photosynthesis and is an effective tool for monitoring vegetation dynamics. Its response to meteorological drought enhances our comprehension of the ecological consequences and adaptive mechanisms of plants facing water scarcity, informing more efficient resource management and efforts in mitigating climate change. This study investigates the spatial and temporal patterns of SIF and examines how vegetation SIF in the Yellow River Basin (YRB) responds to meteorological drought. The findings reveal a gradual southeast-to-northwest decline in SIF across the Yellow River Basin, with an overall increase-from 0.1083 W m-2µm-1sr-1 in 2001 to 0.1468 W m-2µm-1sr-1 in 2019. Approximately 96% of the YRB manifests an upward SIF trend, with 75% of these areas reaching statistical significance. The Standardized Precipitation Evapotranspiration Index (SPEI) at a time scale of 4 months (The SPEI-4), based on the Liang-Kleeman information flow method, is identified as the most suitable drought index, adeptly characterizing the causal relationship influencing SIF variations. As drought intensified, the SPEI-4 index markedly deviated from the baseline, resulting in a decrease in SIF values to their lowest value; subsequently, as drought lessened, it gravitated towards the baseline, and SIF values began to gradually increase, eventually recovering to near their annual maximum. The key finding is that the variability of SIF with SPEI is relatively pronounced in the early growing season, with forests demonstrating superior resilience compared to grasslands and croplands. The responsiveness of vegetation SIF to SPEI can facilitate the establishment of effective drought early warning systems and promote the rational planning of water resources, thereby mitigating the impacts of climate change.

2.
Hell J Nucl Med ; 27(1): 55-57, 2024.
Article in English | MEDLINE | ID: mdl-38629817

ABSTRACT

The hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defect induced by intrapulmonary vascular dilatations in the setting of liver disease. We report a 57-year-old woman with a history of liver cirrhosis presented with progressive cyanosis, exertional dyspnea and a dry cough. Oxyhemoglobin saturation was 88.5% on room air. Contrast transthoracic echocardiography (cTTE) and technetium-99m-macroaggregated albumin (99mTc-MAA) scintigraphy showed an intrapulmonary shunting and confirmed HPS.


Subject(s)
Echocardiography , Hepatopulmonary Syndrome , Technetium Tc 99m Aggregated Albumin , Humans , Hepatopulmonary Syndrome/diagnostic imaging , Hepatopulmonary Syndrome/complications , Female , Middle Aged , Echocardiography/methods , Radionuclide Imaging/methods , Radiopharmaceuticals
3.
Front Biosci (Landmark Ed) ; 29(4): 157, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38682203

ABSTRACT

Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical during autoimmune responses, and the dysregulation of DC apoptosis could cause severe immune destruction in the host. For example, reduction of immunogenic DCs by increased apoptosis could lead to immune tolerance to pathogen infection that might allow exposure of nuclear autoantigens, whereas reduced apoptosis could result in long-term lymphocyte activation to break the immune tolerance for the development of autoimmune disease. Thus, keeping a balance between survival and apoptosis of DCs is crucial to maintain immune homeostasis. In this review, we summarize the recent development on the factors inducing DC apoptosis and their underlying mechanisms to provide insights into the immunopathogenesis of some autoimmune diseases, which could lead to effective therapeutic interventions in the clinics.


Subject(s)
Apoptosis , Autoimmune Diseases , Dendritic Cells , Dendritic Cells/immunology , Humans , Autoimmune Diseases/immunology , Apoptosis/immunology , Animals , Immune Tolerance/immunology
4.
Genes (Basel) ; 15(4)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38674348

ABSTRACT

The length of coleoptile is crucial for determining the sowing depth of oats in low-precipitation regions, which is significant for oat breeding programs. In this study, a diverse panel of 243 oat accessions was used to explore coleoptile length in two independent experiments. The panel exhibited significant variation in coleoptile length, ranging from 4.66 to 8.76 cm. Accessions from Africa, America, and the Mediterranean region displayed longer coleoptile lengths than those from Asia and Europe. Genome-wide association studies (GWASs) using 26,196 SNPs identified 34 SNPs, representing 32 quantitative trait loci (QTLs) significantly associated with coleoptile length. Among these QTLs, six were consistently detected in both experiments, explaining 6.43% to 10.07% of the phenotypic variation. The favorable alleles at these stable loci additively increased coleoptile length, offering insights for pyramid breeding. Gene Ontology (GO) analysis of the 350 candidate genes underlying the six stable QTLs revealed significant enrichment in cell development-related processes. Several phytochrome-related genes, including auxin transporter-like protein 1 and cytochrome P450 proteins, were found within these QTLs. Further validation of these loci will enhance our understanding of coleoptile length regulation. This study provides new insights into the genetic architecture of coleoptile length in oats.


Subject(s)
Avena , Cotyledon , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Avena/genetics , Avena/growth & development , Genome-Wide Association Study/methods , Cotyledon/genetics , Cotyledon/growth & development , Phenotype , Genome, Plant , Plant Breeding
5.
Medicine (Baltimore) ; 103(14): e37537, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579066

ABSTRACT

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.


Subject(s)
Inflammatory Bowel Diseases , Mendelian Randomization Analysis , Humans , Inflammatory Bowel Diseases/genetics , Inflammation , CD4-Positive T-Lymphocytes , Causality , Genome-Wide Association Study
6.
BMC Infect Dis ; 24(1): 270, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429664

ABSTRACT

BACKGROUND: The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population. METHODS: A total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as "cases", and the mild and moderate patients were defined as "control". Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform. RESULTS: IFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008-0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746-8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045-15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant. CONCLUSION: Our study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.


Subject(s)
COVID-19 , Forkhead Transcription Factors , Polymorphism, Single Nucleotide , Humans , Male , Antibodies, Neutralizing , COVID-19/genetics , COVID-19/metabolism , Forkhead Transcription Factors/genetics , Genotype , Haplotypes , Interferons/metabolism , Myxovirus Resistance Proteins/metabolism
7.
Foods ; 13(3)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38338497

ABSTRACT

The Yellow-Bohai Sea is an important semi-enclosed continental shelf marginal seas with an intensive aquaculture industry in China. The current study analyzed the contamination status and the time variations of paralytic shellfish toxins (PSTs) in shellfish between 2019 and 2020 from the Yellow-Bohai Sea in the Dalian area and estimated the acute health risks to consumers in China. A total of 199 shellfish samples (including 34 Pacific oysters, 25 Mediterranean blue mussels, 34 Manila clams, 36 bay scallops, 34 veined rapa whelks and 36 bloody clams) were analyzed from four representative aquaculture zones around the Yellow-Bohai Sea in Dalian. Among the samples, scallops and blood clams were the shellfish species with the highest detection rate of PSTs (94.4%), and the highest level of PSTs was detected in scallops with 3953.5 µg STX.2HCl eq./kg (µg STX.2HCL equivalents per kg shellfish tissue), followed by blood clams with 993.4 µg STX.2HCl eq./kg. The contents of PSTs in shellfish showed a time variation trend, and autumn was the season of concern for PST contamination in Dalian. For general Chinese consumers, the probability of acute health risks to shellfish consumers from dietary exposure to PSTs was around 13%. For typical consumers in coastal areas of China, especially those with higher shellfish intake, there was an acute health risk associated with exposure to PSTs through shellfish consumption during the occurrence of harmful algal blooms. It is suggested that the government continue to strengthen the monitoring of the source of PSTs and the monitoring of harmful algal blooms and give reasonable advice on shellfish consumption for consumers in coastal areas, such as not eating scallop viscera.

8.
Hum Vaccin Immunother ; 20(1): 2300208, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38191194

ABSTRACT

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/prevention & control , COVID-19 Vaccines , Antibodies, Neutralizing , China/epidemiology
9.
Int J Biometeorol ; 68(2): 333-349, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38052751

ABSTRACT

Over the past three decades, there has been a significant global climate change characterized by an increase in the intensity and frequency of extreme climate events. The vegetation status in Qinghai Province has undergone substantial changes, which are more pronounced than other regions in the Qinghai-Tibet Plateau. However, a clear understanding of the response characteristics of plateau vegetation to extreme climate events is currently lacking. In this study, we investigated the response of net primary productivity (NPP) to different forms of extreme climate events across regions characterized by varying levels of aridity and elevation gradients. Specifically, we observed a significant increase in NPP in relatively arid regions. Our findings indicate that, in relatively arid regions, single episodes of high-intensity precipitation have a pronounced positive effect (higher correlation) on NPP. Furthermore, in high-elevation regions (4000-6000 m), both the intensity and frequency of precipitation events are crucial factors for the increase in regional NPP. However, continuous precipitation can have significant negative impacts on certain areas within relatively wet regions. Regarding temperature, a reduction in the number of frost days within a year has been shown to lead to a significant increase in NPP in arid regions. This reduction allows vegetation growth rate to increase in regions where it was limited by low temperatures. Vegetation conditions in drought-poor regions are expected to continue to improve as extreme precipitation intensifies and extreme low-temperature events decrease.


Subject(s)
Ecosystem , Models, Theoretical , China , Tibet , Temperature , Climate Change
10.
Exp Lung Res ; 49(1): 205-219, 2023 11 20.
Article in English | MEDLINE | ID: mdl-38044666

ABSTRACT

Objective: This study aimed to investigate the effects of stevioside (STE) on pulmonary fibrosis (PF) and the potential mechanisms. Methods: In this study, a mouse model of PF was established by a single intratracheal injection of bleomycin (BLM, 3 mg/kg). The experiment consisted of four groups: control group, BLM group, and STE treatment groups (STE 50 and 100 mg/kg). ELISA and biochemical tests were conducted to determine the levels of TNF-α, IL-1ß, IL-6, NO, hydroxyproline (HYP), SOD, GSH, and MDA. Histopathological changes and collagen deposition in lung tissues were observed by HE and Masson staining. Immunohistochemistry was performed to determine the levels of collagen I-, collagen III-, TGF-ß1- and p-Smad2/3-positive cells. Western blot analysis was used to measure the expression of epithelial-mesenchymal transition (EMT) markers, including α-SMA, vimentin, E-cadherin, and ZO-1, as well as proteins related to the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, nuclear transcription factor-κB (NF-κB) pathway, and TGF-ß1/Smad2/3 pathway in lung tissues. Results: STE significantly alleviated BLM-induced body weight loss and lung injury in mice, decreased HYP levels, and reduced the levels of collagen I- and collagen III-positive cells, thereby decreasing extracellular matrix (ECM) deposition. Moreover, STE markedly improved oxidative stress (MDA levels were decreased, while SOD and GSH activity were enhanced), the inflammatory response (the levels of TNF-α, IL-1ß, IL-6, and NO were reduced), and EMT (the expression of α-SMA and vimentin was downregulated, and the expression of E-cadherin and ZO-1 was upregulated). Further mechanistic analysis revealed that STE could activate the Nrf2 pathway and inhibit the NF-κB and TGF-ß1/Smad2/3 pathways. Conclusion: STE may alleviate oxidative stress by activating the Nrf2 pathway, suppress the inflammatory response by downregulating the NF-κB pathway, and inhibit EMT progression by blocking the TGF-ß1/Smad2/3 pathway, thereby improving BLM-induced PF.


Subject(s)
Pulmonary Fibrosis , Mice , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , NF-kappa B , Transforming Growth Factor beta1/metabolism , Bleomycin/adverse effects , Vimentin , NF-E2-Related Factor 2 , Tumor Necrosis Factor-alpha , Interleukin-6 , Collagen/metabolism , Collagen Type I/metabolism , Cadherins , Superoxide Dismutase
11.
Clin Nucl Med ; 48(12): e598-e599, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37801578

ABSTRACT

ABSTRACT: A 41-year-old woman with right papillary thyroid carcinoma underwent 131 I therapy (3.7 GBq). Posttherapy whole-body scintigraphy acquired 2 days later revealed a focus of intense activity in the anterior aspect of the left knee. The activity corresponding to the posttraumatic scab. Posttraumatic scab should be considerable a cause of false-positive whole-body scintigraphy findings.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Female , Humans , Adult , Thyroid Cancer, Papillary , Thyroid Neoplasms/diagnostic imaging , Carcinoma, Papillary/diagnostic imaging , Tomography, X-Ray Computed , Radionuclide Imaging , Iodine Radioisotopes
12.
BMC Nephrol ; 24(1): 293, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37794407

ABSTRACT

BACKGROUND: Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis. CASE PRESENTATION: A 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence. CONCLUSIONS: This is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy.


Subject(s)
Hyperparathyroidism, Primary , Hyperparathyroidism, Secondary , Parathyroid Neoplasms , Humans , Female , Middle Aged , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Hyperplasia/pathology , Parathyroid Glands/diagnostic imaging , Parathyroid Glands/surgery , Parathyroid Glands/pathology , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/surgery , Hyperparathyroidism, Secondary/complications , Hyperparathyroidism, Secondary/diagnostic imaging , Parathyroidectomy/adverse effects , Renal Dialysis/adverse effects , Pruritus , Recurrence , Parathyroid Hormone
13.
J Virol ; 97(10): e0082423, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37724880

ABSTRACT

IMPORTANCE: African swine fever (ASF) is an acute, hemorrhagic, and severe porcine infectious disease caused by African swine fever virus (ASFV). ASF outbreaks severely threaten the global pig industries and result in serious economic losses. No safe and efficacious commercial vaccine is currently available except in Vietnam. To date, large gaps in the knowledge concerning viral biological characteristics and immunoevasion strategies have hindered the ASF vaccine design. In this study, we demonstrate that pD129L negatively regulates the type I interferon (IFN) signaling pathway by interfering with the interaction of the transcriptional coactivator p300 and IRF3, thereby inhibiting the induction of type I IFNs. This study reveals a novel immunoevasion strategy employed by ASFV, shedding new light on the intricate mechanisms for ASFV to evade the host immune responses.


Subject(s)
African Swine Fever Virus , African Swine Fever , E1A-Associated p300 Protein , Interferon Regulatory Factor-3 , Interferon Type I , Animals , African Swine Fever/virology , Interferon Type I/metabolism , Interferon-beta/metabolism , Swine , Transcription Factors/metabolism , Vaccines/metabolism , E1A-Associated p300 Protein/metabolism , Interferon Regulatory Factor-3/metabolism , Immune Evasion
14.
Foods ; 12(16)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37628101

ABSTRACT

Tetrodotoxin (TTX) is an extremely potent marine biotoxin. An analytical method was developed for both trace contamination and extremely high levels of TTX in gastropods by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with clean-up of cation exchange solid phase extraction (SPE) in this study. The limit of detection (LOD) in the sample matrix was 0.5 µg/kg. With the calibration of a screened internal standard (validamycin, IS), the linear range was 0.1-100 ng/mL (1.5-1500 µg/kg in sample matrix) with a correlation coefficient of r2 > 0.999. The average recoveries at three spiking levels (1.5 µg/kg, 44 µg/kg, and 1500 µg/kg) were 82.6-94.4% with relative standard deviations (RSDs) less than 8.4%. TTX levels in seven gastropods (741 samples) were studied. The contamination and analogues in Neverita didyma (N. didyma, 565 samples collected in Zhejiang province, China, from 2016 to 2022) were first reported. The detection rate of TTX in N. didyma was 34.2%. The average concentration was 23.1 µg/kg, and the maximum value was 2327 µg/kg. The time distribution study indicated that high contaminations of TTX occurred from May to August for N. didyma.

15.
J Vis Exp ; (196)2023 06 30.
Article in English | MEDLINE | ID: mdl-37458458

ABSTRACT

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.


Subject(s)
Precancerous Conditions , Stomach Neoplasms , Rats , Animals , Stomach Neoplasms/genetics , Rats, Sprague-Dawley , Mitophagy , Precancerous Conditions/drug therapy , Precancerous Conditions/pathology , Cell Proliferation
16.
J Agric Food Chem ; 71(26): 10133-10143, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37350414

ABSTRACT

Linalool, a plant-derived high-value monoterpene, is widely used in the perfume, cosmetic, and pharmaceutical industries. Recently, engineering microbes to produce linalool has become an attractive alternative to plant extraction or chemical synthesis approaches. However, the low catalytic activity of linalool synthase and the shortage of precursor pools have been considered as two key factors for low yields of linalool. In this study, we rationally engineered the entrance of the substrate-binding pocket of linalool synthase (t67OMcLISM) and successfully increased the catalytic efficiency of this enzyme toward geranyl pyrophosphate. Specifically, F447E and F447A, with decreased entrance hydrophobicity and steric hindrance, increased linalool production by 2.2 and 1.9 folds, respectively. Subsequently, cytoplasm and peroxisomes were harnessed to boost linalool synthesis in Saccharomyces cerevisiae, achieving a high titer of linalool (219.1 mg/L) in shake-flask cultivation. Finally, the engineered diploid strain produced 2.6 g/L of linalool by 5 L fed-batch fermentation, which was the highest production in yeast to date. The protein engineering and biosynthetic pathway compartmentalization in the peroxisome provide references for the microbial production of other monoterpenes.


Subject(s)
Monoterpenes , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Acyclic Monoterpenes/metabolism , Monoterpenes/metabolism , Proteins/metabolism , Organelles/metabolism , Metabolic Engineering
17.
BMC Gastroenterol ; 23(1): 161, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37208605

ABSTRACT

INTRODUCTION: Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic. OBJECTIVES: The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics. METHODS: Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student's t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients. RESULTS: By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9. CONCLUSIONS: In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.


Subject(s)
Gastritis , Metabolome , Humans , Metabolomics/methods , Biomarkers/metabolism , Amino Acids , Gastritis/diagnosis
18.
Cancer Sci ; 114(7): 2860-2870, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37094904

ABSTRACT

High-risk neuroblastoma (HR-NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5-year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR-NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR-NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box-binding protein-associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR-NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN-amplified, high-risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN-amplified NB cells compared with MYCN-non-amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN-amplified NB. RNA-seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell-cycle regulator, cell-cycle-dependent kinase 1 (CDK1), resulting in cell-cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN-amplified HR-NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR-NB patients by blocking cell-cycle progression and the proliferation of tumor cells.


Subject(s)
Neuroblastoma , Humans , Animals , Mice , N-Myc Proto-Oncogene Protein/genetics , Neuroblastoma/pathology , Cell Proliferation/genetics , Cell Division , G2 Phase , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
19.
Article in English | MEDLINE | ID: mdl-37058093

ABSTRACT

Polycyclic aromatics hydrocarbons (PAHs) are ubiquitous in foods and environment and possess carcinogenic and mutagenic potential. Foods are the main source of exposure to PAHs in the general population. In this study, we determined the concentrations of 16 European Union priority PAHs in 1,564 foodstuffs acquired from nine provinces and commonly consumed by the Chinese population. The most predominant PAH was chrysene (16.7%), followed by benz[a]anthracene (12.4%) and benzo[b]fluoranthene (11.7%). Edible vegetable oils (17.89 µg/kg) and fruits (1.97 µg/kg) had the highest and lowest concentrations of total PAHs, respectively. Suitable indicators of PAH contamination in foods were assessed based on the occurrence of other PAHs in samples negative for benzo[a]pyrene and the correlation for the PAHs and their combinations. According to our results, PAH4 was a suitable indicator, better than PAH8 and benzo[a]pyrene alone. PAH exposure in the Chinese population was estimated by combining contamination data with national individual food consumption data, based on the middle bound approach. The overall average dietary exposures for BaP and PAH4 were 3.08 and 17.61 ng/kg bw/day, respectively. The major contributors to the total dietary exposure of PAHs were cereals (39%), edible vegetable oils (28%), and vegetables (20%). We used the margin of exposure (MOE) approach to assess health risk for consumers. MOEs of the mean estimated dietary exposures were >10,000, indicating a low concern for the health of the general population and of consumers of smoked, grilled, or barbecued foods. For high consumers and children, the MOEs were <10,000, indicating potential concerns.


Subject(s)
Polycyclic Aromatic Hydrocarbons , Humans , Benzo(a)pyrene/analysis , Diet , East Asian People , Food Contamination/analysis , Plant Oils , Polycyclic Aromatic Hydrocarbons/analysis , Risk Assessment , Vegetables
20.
Int J Mol Sci ; 24(6)2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36982656

ABSTRACT

Groat protein content (GPC) is a key quality trait attribute in oat. Understanding the variation of GPC in oat germplasms and identifying genomic regions associated with GPC are essential for improving this trait. In this study, the GPC of 174 diverse oat accessions was evaluated in three field trials. The results showed a wide variation in GPC, ranging from 6.97% to 22.24% in this panel. Hulless oats displayed a significantly higher GPC compared to hulled oats across all environments. A GWAS analysis was performed based on 38,313 high-quality SNPs, which detected 27 non-redundant QTLs with 41 SNPs significantly associated with GPC. Two QTLs on chromosome 6C (QTL16) and 4D (QTL11) were consistently detected in multiple environments, with QTL16 being the most significant and explaining the highest proportion of the phenotypical variation in all tested environments except in CZ20. Haplotype analysis showed that the favorable haplotypes for GPC are more prevalent in hulless oats. These findings provide a foundation for future efforts to incorporate favorable alleles into new cultivars through introgression, fine mapping, and cloning of promising QTLs.


Subject(s)
Avena , Genome-Wide Association Study , Avena/genetics , Chromosome Mapping , Quantitative Trait Loci , Phenotype , Edible Grain/genetics , Polymorphism, Single Nucleotide
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