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1.
Cancer Commun (Lond) ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016057

ABSTRACT

BACKGROUND: Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. METHODS: In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. RESULTS: The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). CONCLUSIONS: This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

2.
Plants (Basel) ; 13(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38999627

ABSTRACT

In this study, the effects of soil conditioners on the growth and development of melons and the rhizosphere soil environment were explored. The optimal amount of added soil conditioner was screened to solve the practical production problems of high-quality and high-yield thin-skinned melon. The melon variety "Da Shetou" was used as the material. Under the conditions of conventional fertilization and cultivation technology management, different soil conditioners were set up for potted melons. The effects of Pastoral soil (CK), 95% Pastoral soil + 5% volcanic ash soil conditioner (KT1), 85% Pastoral soil + 15% volcanic ash soil conditioner (KT2), 75% Pastoral soil + 25% volcanic ash soil conditioner (KT3), 65% Pastoral soil + 35% volcanic ash soil conditioner (KT4), and 55% Pastoral soil + 45% volcanic ash soil conditioner (KT5) on melon yield, quality, and rhizosphere soil characteristics were investigated. The soil microbial community was analyzed using Illumina MiSeq technology. Compared to CK, KT1, KT3, KT4, and KT5, the KT2 treatment could improve the single fruit yield of melon, increasing it by 4.35%, 2.48%, 2.31%, 5.92%, and 2.92%. Meanwhile, the highest contents of soluble protein, soluble solid, and soluble sugar in the KT2 treatment were 1.89 mg·100 g-1, 16.35%, and 46.44 mg·g-1, which were significantly higher than those in the control treatment. The contents of organic matter, total nitrogen, alkali-soluble nitrogen, nitrate nitrogen, ammonium nitrogen, available potassium, and available phosphorus in melon rhizosphere soil were the highest in the KT2 treatment. Through Alpha diversity analysis, it was found that the Chao1 index, Shannon index, and ACE index were significantly higher in the KT1 treatment than in the control, while, among all groups, the Simpson index and coverage were not significantly different. The dominant bacteria in the six treated samples were mainly Actinobacteriota, Proteobacteria, Cyanobacteria, Chloroflexi, Acidobacteria, Bacteroidetes, Myxomycota, Firmicutes, Gemmatimonadota, Verrucomicrobia, and Planctomycetes, which accounted for 96.59~97.63% of the relative abundance of all bacterial groups. Through redundancy analysis (RDA), it was found that the organic matter, electrical conductivity, available phosphorus, and nitrate nitrogen of melon rhizosphere soil were the dominant factors of bacterial community change at the dominant genus level. In summary, 15% ash soil conditioner applied on melon was the selected treatment to provide a theoretical reference for the application of soil conditioner in facility cultivation.

3.
Open Life Sci ; 19(1): 20220893, 2024.
Article in English | MEDLINE | ID: mdl-38952718

ABSTRACT

This study aimed to explore the effects of different nitrogen, phosphorus, and potassium ratios on the yield and nutritional quality of greenhouse tomatoes under a water and fertilizer integration model. Greenhouse tomatoes were used as the research object, and the "3414" fertilizer trial design was employed to assess tomato growth, yield, quality, and soil indicators across various treatment combinations. The goal was to determine the optimal fertilization scheme and recommend appropriate fertilizer quantities for tomato cultivation and production. The results revealed that different fertilizer ratios significantly affected both the quality and yield of tomatoes. Overall, the tomato yield tended to increase with higher fertilization amounts, with potassium exhibiting the most pronounced effect on yield increase, followed by phosphorus and nitrogen. The comprehensive analysis of principal components indicated that the N2P2K1 treatment yielded the highest nutritional quality and yield. Therefore, the best fertilization combination identified in this study consisted of nitrogen fertilizer at 197.28 kg hm-2, phosphorus fertilizer at 88.75 kg hm-2, and potassium fertilizer at 229.80 kg hm-2. These findings provided the scientific basis for optimizing fertilization practices in greenhouse tomato cultivation and production in the Jilin Province.

4.
Sci Total Environ ; : 174839, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025147

ABSTRACT

The discovery of complete ammonia oxidizers (comammox) has dramatically altered our perception of nitrogen (N) biogeochemistry. However, their functional importance vs. the canonical ammonia oxidizers (i.e., ammonia oxidizing-archaea (AOA) and bacteria (AOB)) in agroecosystems is still poorly understood. Accordingly, a new assay, which involves the combined use of acetylene, 3,4-dimethylpyrazole phosphate (DMPP), and 1-octyne, was adopted to assess the ammonia (NH3) oxidation and nitrous oxide (N2O) production activity of these functional guilds in a subtropical Inceptisol subjected to long-term different fertilization regimes, namely CK (no fertilizer control), synthetic fertilizer only (NPK), organic manure only (M) and organic manure plus synthetic fertilizer (MNPK). AOA dominated the NH3 oxidation in M treatment, whereas AOB dominated all the NH3 oxidation and N2O production processes in all but M treatment, and comammox played a minor role in both NH3 oxidation and N2O production in all treatments. Both M and MNPK treatments significantly increased the activity and growth of comammox. Compared to NPK, comammox exhibited increases of 270 % and 326 % in the NH3 oxidation rates, and increases of 1472 % and 563 % in the N2O production rates in M and MNPK, respectively. Random forest model revealed that copper (Cu), comammox abundance, and dissolved organic nitrogen (DON) were the most important predictors for the NH3 oxidation rates of comammox. Redundancy analyses (RDA) showed that fertilizer treatments significantly altered the community composition of NH3 oxidizers, and pH was the overarching parameter underpinning the community shift of the NH3 oxidizers. Overall, this paper provides evidence that comammox play a minor yet unneglectable role in the nitrification of agroecosystems, and the long-term addition of organic manure stimulates the growth and activity of comammox in a subtropical Inceptisol.

5.
Open Life Sci ; 19(1): 20220882, 2024.
Article in English | MEDLINE | ID: mdl-38911928

ABSTRACT

A pot experiment was conducted to investigate the combined effects of different nitrogen fertilizer levels (5, 25, and 45 kg of pure nitrogen per 667 m²) and biochar concentrations (0, 0.7, 1.4, and 2.1%) on the growth, yield, and fruit quality of pepper. The findings indicated that a combination of 25 kg/667 m2 of nitrogen and either 0.7% or 1.4% biochar significantly enhanced plant growth, yield, and fruit quality. Specifically, the N2 treatment (25 kg of pure nitrogen per 667 m²) increased substrate porosity, alkali-hydrolyzed nitrogen content, and available phosphorus content. It also boosted root activity and superoxide dismutase activity in pepper leaves, resulting in increased yield and better fruit quality. Furthermore, the proper addition of biochar (0.7-1.4% by weight) enhanced the physical and chemical properties of the substrate, including increased chlorophyll content and enzyme activity in plants, thereby leading to improved overall plant growth, yield, and fruit quality.

6.
Front Cell Infect Microbiol ; 14: 1347345, 2024.
Article in English | MEDLINE | ID: mdl-38828262

ABSTRACT

Background: To date, more than 770 million individuals have become coronavirus disease 2019 (COVID-19) convalescents worldwide. Emerging evidence highlights the influence of COVID-19 on the oral microbiome during both acute and convalescent disease phases. Front-line healthcare workers are at an elevated risk of exposure to viral infections, and the effects of COVID-19 on their oral microbiome remain relatively unexplored. Methods: Oropharyngeal swab specimens, collected one month after a negative COVID-19 test from a cohort comprising 55 healthcare workers, underwent 16S rRNA sequencing. We conducted a comparative analysis between this post-COVID-19 cohort and the pre-infection dataset from the same participants. Community composition analysis, indicator species analysis, alpha diversity assessment, beta diversity exploration, and functional prediction were evaluated. Results: The Shannon and Simpson indexes of the oral microbial community declined significantly in the post-COVID-19 group when compared with the pre-infection cohort. Moreover, there was clear intergroup clustering between the two groups. In the post-COVID-19 group, the phylum Firmicutes showed a significant increase. Further, there were clear differences in relative abundance of several bacterial genera in contrast with the pre-infection group, including Streptococcus, Gemella, Granulicatella, Capnocytophaga, Leptotrichia, Fusobacterium, and Prevotella. We identified Gemella enrichment in the post-COVID-19 group, potentially serving as a recovery period performance indicator. Functional prediction revealed lipopolysaccharide biosynthesis downregulation in the post-COVID-19 group, an outcome with host inflammatory response modulation and innate defence mechanism implications. Conclusion: During the recovery phase of COVID-19, the oral microbiome diversity of front-line healthcare workers failed to fully return to its pre-infection state. Despite the negative COVID-19 test result one month later, notable disparities persisted in the composition and functional attributes of the oral microbiota.


Subject(s)
Bacteria , COVID-19 , Health Personnel , Microbiota , Oropharynx , RNA, Ribosomal, 16S , SARS-CoV-2 , Humans , COVID-19/microbiology , Oropharynx/microbiology , Oropharynx/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/genetics , Adult , RNA, Ribosomal, 16S/genetics , Male , Female , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Middle Aged , Cohort Studies
7.
Article in English | MEDLINE | ID: mdl-38839575

ABSTRACT

AIM: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer (RPR-OC) patients. METHODS: This study retrieved 67 RPR-OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. RESULTS: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression-free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5-6.3) months in apatinib + chemo group and 3.8 (2.0-5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5-24.5) months in apatinib + chemo group and 13.6 (8.6-18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). CONCLUSION: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR-OC patients.

8.
Sci Total Environ ; 942: 173681, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38844210

ABSTRACT

Soil microbial food web is crucial for maintaining crop production, while its community structure varies among fertilization regimes. Currently, the mechanistic understanding of the relationships between microbial food web and crop production under various nutrient fertilizations is poor. This knowledge gap limits our capacity to achieve precision agriculture for ensuring yield stability. In this study, we investigated the abiotic (i.e., soil chemical properties) and biotic factors (i.e., microbial food web, including bacteria, fungi, archaea and nematodes) that were closely associated with rice (Oryza sativa L.) production, using soils from seven fertilization regimes in distinct sampling locations (i.e., bulk vs rhizosphere soil) at a long-term experimental site. Organic manure alone fertilization (M) and integrated fertilization (NPKM) combining manure with inorganic fertilizers increased soil pH by 0.21-0.41 units and organic carbon content by 49.1 %-65.2 % relative to the non-fertilization (CK), which was distinct with inorganic fertilization. The principal coordinate analysis (PCoA) revealed that soil microbial and nematode communities were primarily shaped by fertilization rather than sampling locations. Organic fertilization (M, NPKM) increased the relative abundance of both r-strategist bacteria, specific taxa within the fungal (i.e., Pezizales) and nematode communities (i.e., omnivores-predators), whereas inorganic fertilization increased K-strategist bacteria abundances relative to the CK. Correspondingly, network analysis showed that the keystone taxa in the amplicon sequence variants (ASVs) enriched by organic manure and inorganic fertilization were mainly affiliated with r- and K-strategist bacteria, respectively. Structural equation modeling (SEM) analysis found that r- and K-strategist bacteria were positively correlated with rice production under organic and inorganic fertilization, respectively. Our results demonstrate that the response patterns of r/K-strategists to nutrient fertilization largely regulate rice yield, suggesting that the enhanced soil fertility and r-strategists contribute to the highest crop production in NPKM fertilization.


Subject(s)
Agriculture , Bacteria , Fertilizers , Food Chain , Oryza , Soil Microbiology , Fertilizers/analysis , Bacteria/classification , Agriculture/methods , Soil/chemistry , Manure , Fungi , Rhizosphere
9.
Environ Sci Pollut Res Int ; 31(30): 42547-42573, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38884935

ABSTRACT

Volatile organic compounds (VOCs) have been extensively studied because of their significant roles as precursors of atmospheric ozone and secondary organic aerosol pollution. The research aims to comprehend the current advancements in domestic and international VOC emission accounting. The study utilized the CiteSpace software to represent the pertinent material from Web of Science visually. The hot spots and future development trends of VOC emission calculation are analyzed from the perspectives of thesis subject words, cooperative relationships, co-citation relationships, journals, and core papers. According to the statistics, the approaches most often employed in VOC accounting between 2013 and 2023 are source analysis and emission factor method. Atmospheric environment is the journal with the most publications in the area. The Chinese Academy of Sciences and the University of Colorado System are prominent institutions in VOC emission accounting research, both domestically and internationally. The primary research focuses on the realm of VOC emission accounting clusters, which are "emission factor," "source analysis," "model," "air quality," and "health." A current trend in VOC emission accounting involves the construction of a VOC emission inventory using a novel model that combines emission factors and source analysis. This study reviews the progress made in calculating volatile organic compound (VOC) emissions over the past decade. It aims to provide researchers with a new perspective to promote the development of this field.


Subject(s)
Air Pollutants , Air Pollution , Bibliometrics , Volatile Organic Compounds , Volatile Organic Compounds/analysis , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Environmental Monitoring/methods
10.
Chem Commun (Camb) ; 60(56): 7180-7183, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38904415

ABSTRACT

A novel process using N-benzylhydroxylamine hydrochloride as a "C1N1 synthon" in [2+2+1] cyclization for the construction of 1,2,5-trisubstituted imidazoles has been described for the first time. The key to realizing this process lies in capturing arylamines by in situ generated novel acyl ketonitrone intermediates. Subsequent tautomerization activates the α-C(sp3)-H of N-benzylhydroxylamines, and thus breaks through its inherent reaction mode and achieves N, α-C site-selective cyclization. Furthermore, this method enables scale-up synthesis and late-stage modification of complex molecules.

11.
Anal Biochem ; 692: 115571, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38796119

ABSTRACT

Markers of myocardial injury, such as myoglobin (Mb), are substances swiftly released into the peripheral bloodstream upon myocardial cell injury or altered cardiac activity. During the onset of acute myocardial infarction, patients experience a significant surge in serum Mb levels. Given this, precise detection of Mb is essential, necessitating the development of innovative assays to optimize detection capabilities. This study introduces the synthesis of a three-dimensional hierarchical nanocomposite, Cubic-ZIF67@Au-rGOF-NH2, utilizing aminated reduced graphene oxide and zeolite imidazolium ester framework-67 (ZIF67) as foundational structures. Notably, this novel material, applied in a label-free electrochemical immunosensor, presents a groundbreaking approach for detecting myocardial injury markers. Experimental outcomes revealed ZIF67 and AuNPs exhibit enhanced affinity and growth on the 3D-rGOF-NH2 matrix, thus amplifying electrical conductivity while preserving the inherent electrochemical attributes of ZIF67. As a result, the Cubic-ZIF67@Au-rGOF-NH2 label-free electrochemical immunosensor exhibited a broad detection range and high sensitivity for Mb. The derived standard curve was ΔIp = 16.67552lgC+275.245 (R = 0.993) with a detection threshold of 3.47 fg/ml. Moreover, recoveries of standards spiked into samples ranged between 96.3% and 108.7%. Importantly, the devised immunosensor retained notable selectivity against non-target proteins, proving its potential clinical utility based on exemplary sample analysis performance.


Subject(s)
Electrochemical Techniques , Gold , Graphite , Metal-Organic Frameworks , Myoglobin , Myoglobin/analysis , Electrochemical Techniques/methods , Graphite/chemistry , Metal-Organic Frameworks/chemistry , Gold/chemistry , Humans , Biosensing Techniques/methods , Nanocomposites/chemistry , Zeolites/chemistry , Imidazoles/chemistry , Limit of Detection , Metal Nanoparticles/chemistry
12.
Org Lett ; 26(20): 4340-4345, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38743916

ABSTRACT

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

13.
Article in English | MEDLINE | ID: mdl-38763304

ABSTRACT

OBJECTIVE: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer remains clinically challenging. In this study, we investigated the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase 2 trial. METHODS: Blood samples were prospectively collected from 45 patients with stage IIIA (N2) non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the computed tomography-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. RESULTS: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 mutations/megabase was associated with significantly greater MPR rates (77.8% vs 38.5%, P = .042), and longer disease-free survival (P = .043), but not overall survival (P = .131), compared with bTMB <11 mutations/megabase in 35 patients with bTMB available. The developed DL model achieved an area under the curve of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an area under the curve of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathologic response and survival. Compared with ctDNA residual, ctDNA clearance before surgery was associated with significantly greater MPR rates (88.2% vs 11.1%, P < .001) and improved disease-free survival (P = .010). CONCLUSIONS: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

14.
J Hazard Mater ; 472: 134468, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38703680

ABSTRACT

The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater.


Subject(s)
Anti-Bacterial Agents , Charcoal , Soil Pollutants , Soil , Anti-Bacterial Agents/chemistry , Charcoal/chemistry , Adsorption , Soil/chemistry , Soil Pollutants/chemistry , Water Pollutants, Chemical/chemistry , Water Movements , Groundwater/chemistry , Thiamphenicol/analogs & derivatives , Thiamphenicol/chemistry
15.
Am J Otolaryngol ; 45(4): 104305, 2024.
Article in English | MEDLINE | ID: mdl-38653085

ABSTRACT

AIM: Iatrogenic acute spinal cord injury with tetraplegia is a serious consequence of non-spinal surgery.We report a case of acute spinal cord injury with tetraplegia after thyroid surgery. METHOD: The patient was pathologically diagnosed with papillary carcinoma, underwent left thyroidectomy, and developed tetraplegia after surgery. RESULT: The patient was diagnosed with acute spinal cord injury with tetraplegia and cured after anti-inflammatory and dehydrating treatment. CONCLUSION: Iatrogenic spinal cord injuries after elective non-spinal surgery can have catastrophic consequences, and clinicians must be alert to this possibility in clinical practice.


Subject(s)
Iatrogenic Disease , Quadriplegia , Spinal Cord Injuries , Thyroid Neoplasms , Thyroidectomy , Humans , Quadriplegia/etiology , Thyroidectomy/adverse effects , Spinal Cord Injuries/complications , Spinal Cord Injuries/etiology , Spinal Cord Injuries/surgery , Thyroid Neoplasms/surgery , Male , Postoperative Complications/etiology , Middle Aged , Carcinoma, Papillary/surgery , Female , Magnetic Resonance Imaging
16.
Nat Cell Biol ; 26(4): 552-566, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38561547

ABSTRACT

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.


Subject(s)
Blood Glucose , Lipolysis , Phosphatidylinositol Phosphates , Animals , Humans , Mice , Fatty Acids/metabolism , Glucose , Lipase/genetics , Lipase/metabolism , Lipolysis/genetics , Ubiquitin-Protein Ligases/metabolism
17.
J Obstet Gynaecol ; 44(1): 2338235, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38619096

ABSTRACT

BACKGROUND: Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. METHODS: A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. RESULTS: The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2-2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5-2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. CONCLUSION: The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.


Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.


Subject(s)
Abortion, Spontaneous , Pregnancy Outcome , Pregnancy , Female , Humans , Pregnancy Outcome/epidemiology , Single Embryo Transfer , Retrospective Studies , Blastocyst , Embryo, Mammalian , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology
18.
Sci Total Environ ; 929: 172622, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38642761

ABSTRACT

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.


Subject(s)
Fertilizers , Fungi , Nitrogen , Oryza , Oryza/microbiology , Fungi/physiology , Mycobiome , Agriculture , Microbiota , Plant Leaves/microbiology
19.
Microb Pathog ; 190: 106633, 2024 May.
Article in English | MEDLINE | ID: mdl-38554778

ABSTRACT

Interferon-stimulated gene product 15 (ISG15) can be conjugated to substrates through ISGylation. Currently, the E3 ligase for porcine ISGylation remains unclear. Here, we identified porcine HERC5 and HERC6 (pHERC5/6) as ISGylation E3 ligases with pHERC6 acting as a major one by reconstitution of porcine ISGylation system in HEK-293 T cell via co-transfecting E1, E2 and porcine ISG15(pISG15) genes. Meanwhile, our data demonstrated that co-transfection of pISG15 and pHERC5/6 was sufficient to confer ISGylation, suggesting E1 and E2 of ISGylation are interchangeable between human and porcine. Using an immunoprecipitation based ISGylation analysis, our data revealed pHERC6 was a substrate for ISGylation and confirmed that K707 and K993 of pHERC6 were auto-ISGylation sites. Mutation of these sites reduced pHERC6 half-life and inhibited ISGylation, suggesting that auto-ISGylation of pHERC6 was required for effective ISGylation. Conversely, sustained ISGylation induced by overexpression of pISG15 and pHERC6 could be inhibited by a well-defined porcine ISGylation antagonist, the ovarian tumor (OTU) protease domain of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-nsp2 and PRRSV-nsp1ß, further indicating such method could be used for identification of virus-encoded ISG15 antagonist. In conclusion, our study contributes new insights towards porcine ISGylation system and provides a novel tool for screening viral-encoded ISG15 antagonist.


Subject(s)
Ubiquitin-Protein Ligases , Ubiquitins , Animals , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Swine , Humans , HEK293 Cells , Ubiquitins/metabolism , Ubiquitins/genetics , Porcine respiratory and reproductive syndrome virus/metabolism , Porcine respiratory and reproductive syndrome virus/genetics , Cytokines/metabolism , Ubiquitination , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/genetics
20.
Front Public Health ; 12: 1364579, 2024.
Article in English | MEDLINE | ID: mdl-38463156

ABSTRACT

Introduction: Many women experience fear toward pregnancy, which can impact their desire to have children and the national birth rate. Thus, assessing women's fear of pregnancy is of great importance. However, there is currently no specialized tool for assessing women's fear of pregnancy in China. The purpose of this study is to translate the Fear of Pregnancy Scale into Chinese and test its reliability and validity among women of childbearing age. Methods: Using convenience sampling combined with a snowballing method, a cross-sectional survey was conducted on 886 women of childbearing age in two cities in China. The translation was strictly carried out according to the Brislin model. Item analysis, validity analysis, and reliability analysis were employed for psychometric assessment. Results: The Chinese version of the Fear of Pregnancy Scale comprises 28 items. Exploratory factor analysis extracted four factors with a cumulative variance contribution rate of 72.578%. Confirmatory factor analysis showed: NFI = 0.956, CFI = 0.986, GFI = 0.927, IFI = 0.986, TLI = 0.985, RMSEA = 0.032, and χ2/df = 1.444. The scale's Cronbach's α coefficient is 0.957, split-half reliability is 0.840, and test-retest reliability is 0.932. Conclusion: The Chinese version of the Fear of Pregnancy Scale possesses robust psychometric properties and can assess the degree of pregnancy fear among Chinese women of childbearing age. It provides a reference for formulating relevant policies in the prenatal care service system and implementing targeted intervention measures.


Subject(s)
Fear , Pregnancy , Child , Humans , Female , Surveys and Questionnaires , Psychometrics , Cross-Sectional Studies , Reproducibility of Results
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