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1.
J Transl Med ; 22(1): 650, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997780

ABSTRACT

BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Multifactorial Inheritance , Polymorphism, Single Nucleotide , Humans , Polymorphism, Single Nucleotide/genetics , Male , Female , Multifactorial Inheritance/genetics , Risk Factors , Middle Aged , Fatty Liver/genetics , Fatty Liver/complications , Non-alcoholic Fatty Liver Disease/genetics , Metabolic Diseases/genetics , Metabolic Diseases/complications , Cohort Studies , Kaplan-Meier Estimate , Aged , Proportional Hazards Models , Genetic Risk Score
2.
Org Lett ; 26(30): 6424-6427, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39041637

ABSTRACT

The gem-difluoroalkene moiety is frequently found in medicinal chemistry. From α-keton sulfides and thioic acids, we were able to develop a universal approach for the synthesis of γ,γ-difluoroallylic ketones and δ,δ-difluoroallylic ketones via a desulfurative/defluorinative alkylation process. We expect that this mild and efficient method will be complementary to other known strategies.

3.
Front Pharmacol ; 15: 1281095, 2024.
Article in English | MEDLINE | ID: mdl-39011501

ABSTRACT

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

4.
Adv Sci (Weinh) ; : e2404047, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976552

ABSTRACT

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

6.
Front Genet ; 15: 1364944, 2024.
Article in English | MEDLINE | ID: mdl-38686025

ABSTRACT

Fructose-1, 6-bisphosphate aldolase (FBA) plays vital roles in plant growth, development, and response to abiotic stress. However, genome-wide identification and structural characterization of the potato (Solanum tuberosum L.) FBA gene family has not been systematically analyzed. In this study, we identified nine StFBA gene members in potato, with six StFBA genes localized in the chloroplast and three in the cytoplasm. The analysis of gene structures, protein structures, and phylogenetic relationships indicated that StFBA genes were divided into Class I and II, which exhibited significant differences in structure and function. Synteny analysis revealed that segmental duplication events promoted the expansion of the StFBA gene family. Promoter analysis showed that most StFBA genes contained cis-regulatory elements associated with light and stress responses. Expression analysis showed that StFBA3, StFBA8, and StFBA9 showing significantly higher expression levels in leaf, stolon, and tuber under blue light, indicating that these genes may improve photosynthesis and play an important function in regulating the induction and expansion of microtubers. Expression levels of the StFBA genes were influenced by drought and salt stress, indicating that they played important roles in abiotic stress. This work offers a theoretical foundation for in-depth understanding of the evolution and function of StFBA genes, as well as providing the basis for the genetic improvement of potatoes.

7.
Front Genet ; 15: 1381690, 2024.
Article in English | MEDLINE | ID: mdl-38650857

ABSTRACT

The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.

8.
Plants (Basel) ; 13(6)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38592751

ABSTRACT

Panicle type is one of the important factors affecting rice (Oryza sativa L.) yield, and the identification of regulatory genes in panicle development can provide significant insights into the molecular network involved. This study identified a large and dense panicle 1 (ldp1) mutant produced from the Wuyunjing 7 (WYJ7) genotype, which displayed significant relative increases in panicle length, number of primary and secondary branches, number of grains per panicle, grain width, and grain yield per plant. Scanning electron microscopy results showed that the shoot apical meristem (SAM) of ldp1 was relatively larger at the bract stage (BM), with a significantly increased number of primary (PBM) and secondary branch (SBM) meristematic centers, indicating that the ldp1 mutation affects early stages in SAM development Comparative RNA-Seq analysis of meristem tissues from WYJ7 and ldp1 at the BM, PBM, and SBM developmental stages indicated that the number of differentially expressed genes (DEGs) were highest (1407) during the BM stage. Weighted gene coexpression network analysis (WGCNA) revealed that genes in one module (turquoise) are associated with the ldp1 phenotype and highly expressed during the BM stage, suggesting their roles in the identity transition and branch differentiation stages of rice inflorescences. Hub genes involved in auxin synthesis and transport pathways, such as OsAUX1, OsAUX4, and OsSAUR25, were identified. Moreover, GO and KEGG analysis of the DEGs in the turquoise module and the 1407 DEGs in the BM stage revealed that a majority of genes involved in tryptophan metabolism and auxin signaling pathway were differentially expressed between WYJ and ldp1. The genetic analysis indicated that the ldp1 phenotype is controlled by a recessive monogene (LDP1), which was mapped to a region between 16.9 and 18.1 Mb on chromosome seven. This study suggests that the ldp1 mutation may affect the expression of key genes in auxin synthesis and signal transduction, enhance the size of SAM, and thus affect panicle development. This study provides insights into the molecular regulatory network underlying rice panicle morphogenesis and lays an important foundation for further understanding the function and molecular mechanism of LDP1 during panicle development.

9.
Environ Toxicol ; 39(6): 3473-3480, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38450827

ABSTRACT

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.


Subject(s)
Cholelithiasis , Mendelian Randomization Analysis , Sarcopenia , Humans , Sarcopenia/epidemiology , Cholelithiasis/epidemiology , Prospective Studies , Female , Male , Middle Aged , Biomarkers/blood , Aged , Adult , Proportional Hazards Models , Risk Factors
10.
Org Lett ; 26(13): 2585-2589, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38517195

ABSTRACT

Unsymmetrical 1,6-dicarbonyl compounds are useful building blocks in organic synthesis. However, the synthetic methods are limited. Herein we report a three-component one-pot reaction for the synthesis of unsymmetrical 1,6-diketones. This reaction utilizes sulfides as radical precursors and enol ethers as building blocks. It takes advantage of photocatalysis and Lewis acid catalysis. Its synthetic utility was demonstrated in the modification of biorelevant compounds.

11.
Plants (Basel) ; 13(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38337940

ABSTRACT

Brassinazole resistant (BZR) genes act downstream of the brassinosteroid signaling pathway regulating plant growth and development and participating in plant stress responses. However, the BZR gene family has not systematically been characterized in potato. We identified eight BZR genes in Solanum tuberosum, which were distributed among seven chromosomes unequally and were classified into three subgroups. Potato and tomato BZR proteins were shown to be closely related with high levels of similarity. The BZR gene family members in each subgroup contained similar conserved motifs. StBZR genes exhibited tissue-specific expression patterns, suggesting their functional differentiation during evolution. StBZR4, StBZR7, and StBZR8 were highly expressed under white light in microtubers. StBZR1 showed a progressive up-regulation from 0 to 6 h and a progressive down-regulation from 6 to 24 h after drought and salt stress. StBZR1, StBZR2, StBZR4, StBZR5, StBZR6, StBZR7 and StBZR8 were significantly induced from 0 to 3 h under BR treatment. This implied StBZR genes are involved in phytohormone and stress response signaling pathways. Our results provide a theoretical basis for understanding the functional mechanisms of BZR genes in potato.

12.
Chemistry ; 30(16): e202303845, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38212866

ABSTRACT

SznF, a member of the emerging family of heme-oxygenase-like (HO-like) di-iron oxidases and oxygenases, employs two distinct domains to catalyze the conversion of Nω-methyl-L-arginine (L-NMA) into N-nitroso-containing product, which can subsequently be transformed into streptozotocin. Using unrestricted density functional theory (UDFT) with the hybrid functional B3LYP, we have mechanistically investigated the two sequential hydroxylations of L-NMA catalyzed by SznF's binuclear iron central domain. Mechanism B primarily involves the O-O bond dissociation, forming Fe(IV)=O, induced by the H+/e- introduction to the FeA side of µ-1,2-peroxo-Fe2(III/III), the substrate hydrogen abstraction by Fe(IV)=O, and the hydroxyl rebound to the substrate N radical. The stochastic addition of H+/e- to the FeB side (mechanism C) can transition to mechanism B, thereby preventing enzyme deactivation. Two other competing mechanisms, involving the direct O-O bond dissociation (mechanism A) and the addition of H2O as a co-substrate (mechanism D), have been ruled out.


Subject(s)
Iron , Oxygenases , Iron/chemistry , Hydroxylation , Streptozocin , Oxygenases/chemistry , Catalysis
13.
Osteoporos Int ; 35(4): 679-689, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38221591

ABSTRACT

Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE: Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS: Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS: After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION: No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.


Subject(s)
Diabetes Mellitus, Type 2 , Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Osteoporosis , Humans , Bone Density/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Nutrition Surveys , Osteoporosis/genetics
14.
Am J Cardiol ; 211: 239-244, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37979640

ABSTRACT

Excessive calcium-phosphorus product (Ca-P product) in patients with chronic kidney disease (CKD) is associated with coronary artery calcification and coronary artery disease, but the relation between Ca-P product and coronary artery disease in non-CKD populations has rarely been reported. Therefore, we designed a cross-sectional study to investigate the role of Ca-P product in total coronary artery occlusion (TCAO) in a non-CKD population. We reviewed 983 patients who underwent coronary angiography at Guangyuan Central Hospital from February 2018 to January 2020. Ca-P product (mg2/dl2) was calculated as Ca (mmol/L) × 4 × P (mmol/L) × 3.1 and was analyzed as a continuous and tertiary variable. TCAO was defined as complete occlusion of any coronary artery by coronary angiography (thrombolysis in myocardial infarction flow grade 0). Statistical analysis was performed using univariate and multivariate logistic regression models and restricted cubic splines. Univariate logistic regression analysis showed a statistically significant association between Ca-P product and TCAO (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95 to 0.99, p <0.001). After stepwise adjustment for covariates, the risk of TCAO was reduced by 40% in the high versus low Ca-P group (OR 0.6, 95% CI 0.38 to 0.95, p = 0.031), and the risk of TCAO was predicted to decrease by 4% (OR 0.96, 95% CI 0.94 to 0.99, p = 0.006) for each unit increase in Ca-P product. Restricted cubic splines showed a nonlinear relation between Ca-P product and TCAO, with a significant decrease in the risk of TCAO after reaching 27.46 (nonlinear p = 0.047). In conclusion, in non-CKD populations, a higher Ca-P product (≥27.46 mg2/dl2) may help avoid TCAO.


Subject(s)
Coronary Artery Disease , Coronary Occlusion , Renal Insufficiency, Chronic , Humans , Calcium , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/complications , Coronary Occlusion/complications , Coronary Occlusion/diagnosis , Coronary Occlusion/epidemiology , Cross-Sectional Studies , Phosphorus , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk Factors
15.
Prep Biochem Biotechnol ; 54(2): 239-246, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37578156

ABSTRACT

Secreted phospholipase A2s (sPLA2s) are a group of enzymes with 6-8 disulfide bonds that participate in numerous physiological processes by catalyzing the hydrolysis of phospholipids at the sn-2 position. Due to their high content of disulfide bonds and hydrolytic activity toward cell membranes, obtaining the protein of sPLA2s in the soluble and active form is challenging, which hampers their functional study. In this study, one member of recombinant human sPLA2s, tag-free group IIE (GIIE), was expressed in Pichia pastoris. The protein GIIE was purified from the crude culture supernatant by a two-step chromatography procedure, a combination of cation exchange and size-exclusion chromatography. In the shake flask fermentation, Protein of GIIE with higher purity was successfully obtained, using basal salts medium (BSM) instead of YPD medium. In the large-scale fermentation, each liter of BSM produced a final yield of 1.2 mg pure protein GIIE. This protocol will facilitate further research of GIIE and provide references for the production of other sPLA2 members.


Subject(s)
Phospholipases A2, Secretory , Saccharomycetales , Salts , Humans , Recombinant Proteins/chemistry , Pichia/genetics , Pichia/metabolism , Phospholipases A2, Secretory/genetics , Phospholipases A2, Secretory/metabolism , Disulfides/metabolism
16.
Anat Sci Int ; 99(1): 59-67, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37453991

ABSTRACT

The hypermobility of the first tarsometatarsal joint has been identified as a key factor in the development of hallux valgus. Previous research found a link between the tarsometatarsal joint obliquity and the hallux valgus angle. Nevertheless, most studies relied on radiographs that lack 3D evidence. This study used 3D analysis to investigate the morphological differences in the medial cuneiform between hallux valgus and normal feet. In this study, twenty-three hallux valgus feet and twenty-three normal feet were scanned with computed tomography and 3D models of medial cuneiforms were reconstructed. Medial cuneonavicular and the first tarsometatarsal joint surfaces of the medial cuneiform were manually extracted. To obtain the obliquity angle of the medial cuneiform and curvature of the medial cuneonavicular joint, the joint surfaces were approximated to planes and spheres. Furthermore, the orientations of two joint surfaces were accessed through a novel positioning method. No significant difference was found in the cuneiform obliquity between hallux valgus and normal feet. Hallux valgus and normal groups did not differ significantly in any of the medial cuneiform joint orientations. The medial cuneiform in hallux valgus had a larger curvature diameter of the medial cuneonavicular joint (P = 0.029), indicating a flatter surface. The results demonstrated that the generally supported atavism (i.e., tarsometatarsal joint obliquity) does not exist in the hallux valgus feet. A flatter medial cuneonavicular joint surface was found in hallux valgus feet. This study contributes to the comprehensive understanding of the etiological factors with hallux valgus.


Subject(s)
Hallux Valgus , Metatarsophalangeal Joint , Tarsal Bones , Humans , Hallux Valgus/diagnostic imaging , Hallux Valgus/etiology , Radiography , Tomography, X-Ray Computed/methods , Tarsal Bones/diagnostic imaging
17.
Clin Endocrinol (Oxf) ; 100(2): 116-123, 2024 02.
Article in English | MEDLINE | ID: mdl-38146598

ABSTRACT

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD. PATIENTS AND MEASUREMENTS: This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60. RESULTS: We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073-1.628, p = .005, respectively). CONCLUSION: Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.


Subject(s)
Cystatin C , Fatty Liver , Male , Humans , Prospective Studies , Creatinine , Cross-Sectional Studies , Biological Specimen Banks , UK Biobank
18.
J Med Chem ; 66(23): 16032-16050, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38031326

ABSTRACT

Cytochrome P450 1B1 (CYP1B1) is induced during the early stage of cancer and is universally overexpressed in tumors. Thus, it was considered as a potential biomarker for the monitoring of cancer. In this study, we designed and synthesized CYP1B1-targeted near-infrared (NIR) fluorescence molecular probes based on the latest reported open conformation of the CYP1B1-α-naphthoflavone (ANF) complex. According to the architecture of the open channel, we introduced linkers and a Cy5.5 fragment at the 5' position of ANF derivatives with strong CYP1B1 inhibitory activity to obtain probes 19-21. Then, in vitro cell-based studies showed that the probes could be enriched in tumor cells by binding to CYP1B1. During in vivo and ex vivo imaging in a xenograft mouse model, probe 19 with the best binding affinity was proven to be able to identify tumor sites in both fluorescence imaging and photoacoustic imaging modes.


Subject(s)
Colorectal Neoplasms , Humans , Animals , Mice , Cytochrome P-450 CYP1B1/chemistry , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Molecular Probes , Molecular Imaging
19.
J Org Chem ; 88(22): 15761-15766, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37890077

ABSTRACT

ß,γ-Unsaturated carbonyl compounds serve as versatile building blocks in organic synthesis and medicinal chemistry. Herein we reported the synthesis of ß,γ-unsaturated carbonyl compounds from tetrafluoropyridine sulfides with vinyl halides. This cross-coupling reaction takes the advantage of photocatalysis, as well as zinc catalysis, which is preferred due to its less-toxic, earth abundant, and cost-effective nature.

20.
Microorganisms ; 11(8)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37630658

ABSTRACT

Staphylococcus aureus (S. aureus) is a major foodborne pathogen. Rapid and specific detection is crucial for controlling staphylococcal food poisoning. This study reported a Staphylococcus phage named LSA2302 showing great potential for applications in the rapid detection of S. aureus. Its biological characteristics were identified, including growth properties and stability under different pH and temperature conditions. The genomic analysis revealed that the phage has no genes associated with pathogenicity or drug resistance. Then, the phage-functionalized magnetic beads (pMB), serving as a biological recognition element, were integrated with ATP bioluminescence assays to establish a biosensing method for S. aureus detection. The pMB enrichment brought high specificity and a tenfold increase in analytical sensitivity during detection. The whole detection process could be completed within 30 min, with a broad linear range of 1 × 104 to 1 × 108 CFU/mL and a limit of detection (LOD) of 2.43 × 103 CFU/mL. After a 2 h pre-cultivation, this method is capable of detecting bacteria as low as 1 CFU/mL. The recoveries of S. aureus in spiked skim milk and chicken samples were 81.07% to 99.17% and 86.98% to 104.62%, respectively. Our results indicated that phage-based biosensing can contribute to the detection of target pathogens in foods.

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