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1.
JACS Au ; 4(7): 2492-2502, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39055138

ABSTRACT

Illuminating synthetic pathways is essential for producing valuable chemicals, such as bioactive molecules. Chemical and biological syntheses are crucial, and their integration often leads to more efficient and sustainable pathways. Despite the rapid development of retrosynthesis models, few of them consider both chemical and biological syntheses, hindering the pathway design for high-value chemicals. Here, we propose BioNavi by innovating multitask learning and reaction templates into the deep learning-driven model to design hybrid synthesis pathways in a more interpretable manner. BioNavi outperforms existing approaches on different data sets, achieving a 75% hit rate in replicating reported biosynthetic pathways and displaying superior ability in designing hybrid synthesis pathways. Additional case studies further illustrate the potential application of BioNavi in a de novo pathway design. The enhanced web server (http://biopathnavi.qmclab.com/bionavi/) simplifies input operations and implements step-by-step exploration according to user experience. We show that BioNavi is a handy navigator for designing synthetic pathways for various chemicals.

2.
Poult Sci ; 103(9): 104032, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39003796

ABSTRACT

Egg production is an important economic trait in layer ducks and understanding the genetics basis is important for their breeding. In this study, a genome-wide association study (GWAS) for egg production traits in 303 female Longyan Shan-ma ducks was performed based on a genotyping-by-sequencing strategy. Sixty-two single nucleotide polymorphisms (SNPs) associated with egg weight traits were identified (P < 9.48 × 10-5), including 8 SNPs at 5% linkage disequilibrium (LD)-based Bonferroni-corrected genome-wide significance level (P < 4.74 × 10-6). One hundred and nineteen SNPs were associated with egg number traits (P < 9.48 × 10-5), including 13 SNPs with 5% LD-based Bonferroni-corrected genome-wide significance (P < 4.74 × 10-6). These SNPs annotated 146 target genes which contained known candidate genes for egg production traits, such as prolactin and prolactin releasing hormone receptor. This study identified that these associated genes were significantly enriched in egg production-related pathways (P < 0.05), such as the oxytocin signaling, MAPK signaling, and calcium signaling pathways. It was notable that 18 genes were differentially expressed in ovarian tissues between higher and lower egg production in Shan-ma ducks. The identified potential candidate genes and pathways provide insight into the genetic basis underlying the egg production trait of layer ducks.

3.
J Chem Theory Comput ; 20(14): 5882-5900, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38950345

ABSTRACT

A vibrational electronic-thermofield coupled cluster (VE-TFCC) approach is developed to calculate thermal properties of non-adiabatic vibronic coupling systems. The thermofield (TF) theory and a mixed linear exponential ansatz based on second-quantized Bosonic construction operators are introduced to propagate the thermal density operator as a "pure state" in the Bogoliubov representation. Through this compact representation of the thermal density operator, the approach is basis-set-free and scales classically (polynomial) as the number of degrees of freedoms (DoF) in the system increases. The VE-TFCC approach is benchmarked with small test models and a real molecular compound (CoF4- anion) against the conventional sum over states (SOS) method and applied to calculate thermochemistry properties of a gas-phase reaction: CoF3 + F- → CoF4-. Results shows that the VE-TFCC approach, in conjunction with vibronic models, provides an effective protocol for calculating thermodynamic properties of vibronic coupling systems.

4.
BMC Public Health ; 24(1): 1818, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978025

ABSTRACT

BACKGROUND: As an innovative lipid parameter, NHHR (the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol) can serve as a valuable tool for assessing cardiovascular disease risk. Nevertheless, the relationship between NHHR and the risk of kidney stones remains unexplored. METHODS: A cross-sectional survey utilized data from the National Health and Population Survey (NHANES) database in the United States spanning from 2007 to 2018. Distinct statistical analyses were applied, including weighted logistic regression, stratified and interaction analysis and restricted cubic spline curve (RCS) models, to examine the correlation between NHHR and the incidence of kidney stones. RESULTS: This analysis encompassed 24,664 participants, with 9.63% reporting incidents of kidney stones. Following multivariate logistic regression and comprehensive adjustments, participants in NHHR quartile 4 (OR 1.34; 95% CI 1.12, 1.60, P < 0.01) exhibited a significantly increased risk of kidney stones compared to those in NHHR quartile 1 (Q1). The RCS result further illustrated a non-linear correlation between NHHR and the incidence of kidney stones. The result of subgroup analysis manifested that participants without diabetes had a higher risk of kidney stones when measured high NHHR levels compared those with diabetes (p for interaction < 0.05). CONCLUSION: Elevated NHHR levels were found to be associated with an increased risk of kidney stones. Based on these findings, NHHR appears to be a promising predictive indicator for the occurrence of kidney stones.


Subject(s)
Cholesterol, HDL , Kidney Calculi , Nutrition Surveys , Humans , Kidney Calculi/epidemiology , Kidney Calculi/blood , Cross-Sectional Studies , Male , Female , Middle Aged , United States/epidemiology , Adult , Cholesterol, HDL/blood , Risk Factors , Incidence , Aged , Cholesterol/blood
5.
Poult Sci ; 103(9): 103976, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-39024692

ABSTRACT

Pekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.

6.
PLoS One ; 19(7): e0307504, 2024.
Article in English | MEDLINE | ID: mdl-39028739

ABSTRACT

Recent research suggests that syntactic priming in language comprehension-the facilitated processing of repeated syntactic structures-arises from the expectation for syntactic repetition due to rational adaptation to the linguistic environment. To further evaluate the generalizability of this expectation adaptation account in cross-linguistic syntactic priming and explore the influence of second language (L2) proficiency, we conducted a self-paced reading study with Chinese L2 learners of English by utilizing the sentential complement-direct object (SC-DO) ambiguity. The results showed that participants exposed to clusters of SC structures subsequently processed repetitions of this structure more rapidly (i.e., larger priming effects) than those exposed to the same number of SC structures but spaced in time, despite the prime and target being in two different languages (Chinese and English). Furthermore, this difference in priming strength was more pronounced for participants with higher L2 (English) proficiency. These findings demonstrate that cross-linguistic syntactic priming is consistent with the expectation for syntactic repetition that rationally adapts to syntactic clustering properties in surrounding bilingual environments, and such adaptation is enhanced as L2 proficiency increases. Taken together, our study extends the expectation adaptation account to cross-linguistic syntactic priming and integrates the role of L2 proficiency, which can shed new light on the mechanisms underlying syntactic priming, bilingual shared syntactic representations and expectation-based sentence processing.


Subject(s)
Linguistics , Multilingualism , Humans , Male , Female , Young Adult , Adult , Comprehension/physiology , Reading , Language
7.
Ren Fail ; 46(2): 2367028, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39010723

ABSTRACT

BACKGROUND: Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous. METHODS: Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999-2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells' mediating roles in the FI-CKD relationship. RESULT: Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD. CONCLUSION: Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.


Subject(s)
Frailty , Mendelian Randomization Analysis , Nutrition Surveys , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/immunology , Frailty/immunology , Female , Male , Aged , Middle Aged , Risk Factors , Biomarkers/blood , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/complications , Logistic Models , Multiomics
8.
Front Nutr ; 11: 1408424, 2024.
Article in English | MEDLINE | ID: mdl-38946781

ABSTRACT

Objective: There is suggestive data indicating a correlation among dietary protein intake and the progression of chronic kidney disease (CKD). Nonetheless, the exact associations between dietary protein intake and the incidence of CKD have remained uncertain. We performed the first meta-analysis to explore the correlation among total protein, plant protein, animal protein intake and CKD risk. Methods: The study conformed the PRISMA statement guidelines. We comprehensively searched PubMed, Web of Science, and Embase until to December 2023. The retrieved studies underwent rigorous evaluation for eligibility, and relevant data were meticulously extracted. The Newcastle-Ottawa Scale (NOS) tool was applied to evaluate the risk of bias. Subsequently, relevant data were extracted and pooled to evaluate the relations among dietary protein intake and CKD incidence. Results: Totally, 6,191 articles were identified, six studies were eligible. A total of 148,051 participants with 8,746 CKD cases were included. All studies had a low overall risk of bias. Higher total, plant and animal protein intake were all correlated with decreased CKD incidence, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were as follows: (RR = 0.82, 95% CI = 0.71-0.94, p = 0.005; I2 = 38%, p = 0.17); (RR = 0.77, 95% CI = 0.61-0.97, p = 0.03; I2 = 77%, p = 0.001); (RR = 0.86, 95% CI = 0.76-0.97, p = 0.02; I2 = 0%, p = 0.59), respectively. For fish and seafood within animal protein: RR = 0.84, 95% CI = 0.74-0.94. Subgroup analysis showed that geographical region, sample size, follow-up time, not assessing protein by food frequency questionnaire, using %energy as the measurement index, not adjusting for several covariates may be the sources of heterogeneity for plant protein. A significant non-linear relation among plant protein and incident CKD was observed by dose-response analysis. Conclusion: The data showed a lower CKD risk significantly associated higher-level dietary total, plant or animal protein (especially for fish and seafood) intake. Further prospective studies demonstrating the correlations of precise sources, intake and duration of dietary protein and incident CKD are warranted.

9.
World J Hepatol ; 16(6): 966-972, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38948434

ABSTRACT

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.

11.
Sci Rep ; 14(1): 16284, 2024 07 15.
Article in English | MEDLINE | ID: mdl-39009696

ABSTRACT

The purpose of present study was to examine the current prevalence and recent trends of overactive bladder (OAB) among US adult men and examine the correlations between OAB and several potential risk factors. The study used the nationally representative data between 2005 and 2020 from the National Health and Nutrition Examination Survey in the US. A total of 18,386 participants aged ≥ 20 years were included in the study. We divided the data into three groups: 2005-2008, 2009-2014 and 2015-2020 to investigate the trends in OAB prevalence. The weighted prevalence and corresponding 95% confidence intervals (CI) of OAB were calculated. The differences (95% CI) in prevalence between the surveys were calculated and multivariate-adjusted weighted logistic regression analysis was performed to determine the correlates of OAB. Among all US adult men, the overall prevalence of OAB increased slightly from 11.3% in 2005-2008 to 11.7% in 2009-2014 and significantly increased to 14.5% in 2015-2020 (difference, 3.2% [95% CI (1.9-4.4%)]; P < 0.05). Increases in OAB prevalence especially concentrated on those who were 40-59 years, non-Hispanic White, non-Hispanic Black and those who were overweight and obese. Older age, non-Hispanic Black, lower educational level and family poverty ratio, diabetes, depression, sleep disorder, other chronic comorbidities, less intense recreational activity, poorer health condition and unsafe food were independent risk factors of OAB. The contemporary prevalence of OAB was high, affecting 14.5% US men and the estimated overall prevalence significantly increased from 2005 to 2020. Therefore, future research should be focused to prevent and remedy this growing socioeconomic and individually troublesome malady.


Subject(s)
Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/epidemiology , Male , United States/epidemiology , Middle Aged , Adult , Prevalence , Risk Factors , Aged , Nutrition Surveys , Young Adult
12.
Comput Struct Biotechnol J ; 23: 2708-2716, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39035833

ABSTRACT

In the field of computational oncology, patient status is often assessed using radiology-genomics, which includes two key technologies and data, such as radiology and genomics. Recent advances in deep learning have facilitated the integration of radiology-genomics data, and even new omics data, significantly improving the robustness and accuracy of clinical predictions. These factors are driving artificial intelligence (AI) closer to practical clinical applications. In particular, deep learning models are crucial in identifying new radiology-genomics biomarkers and therapeutic targets, supported by explainable AI (xAI) methods. This review focuses on recent developments in deep learning for radiology-genomics integration, highlights current challenges, and outlines some research directions for multimodal integration and biomarker discovery of radiology-genomics or radiology-omics that are urgently needed in computational oncology.

13.
Anal Methods ; 16(28): 4724-4732, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38949046

ABSTRACT

It has been well-elaborated that KIN17 protein is closely related to the expression, development and prognosis of liver cancer; however, till date, there has been no study about detecting the KIN17 protein in serum, which is important to developing clinical applications. The objective of this work is to detect serum KIN17 protein by the ELISA method and to explore the diagnostic significance of the KIN17 protein in liver cancer. First, we verified the ELISA method for serum KIN17 measurement according to five aspects: accuracy, precision, specificity, stability and detection limit. Results illustrate that the recovery rate of the ELISA method can be controlled between 90% and 110%, the variation coefficient of intra-assay can be controlled within 16%, and the variation coefficient of inter-assay can be controlled within 10%. There is no non-specific reaction with common tumor markers, and the detection limit can reach 0.125 ng mL-1. The results show that the KIN17 protein can be detected by ELISA, and there is a significant rise in KIN17 concentration in a liver cancer group compared with a healthy group, whose average concentrations are 1.730 ng mL-1 and 0.3897 ng mL-1, respectively. On this basis, we hypothesize that the serum KIN17 protein can serve as a potential biomarker of liver cancer and be measurable with the verified ELISA system after specific ultrafiltration and centrifugation, which is of great significance for the diagnosis and treatment of liver cancer.


Subject(s)
Biomarkers, Tumor , Enzyme-Linked Immunosorbent Assay , Liver Neoplasms , Humans , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Biomarkers, Tumor/blood , Male , Female , Limit of Detection , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Kininogens
14.
Infect Drug Resist ; 17: 2873-2882, 2024.
Article in English | MEDLINE | ID: mdl-39005855

ABSTRACT

Background: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.

15.
Imeta ; 3(1): e154, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38868520

ABSTRACT

Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan-genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan-genome together with high-depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE-derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan-genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

16.
Small Methods ; : e2400533, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874104

ABSTRACT

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight (MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

17.
BMC Infect Dis ; 24(1): 619, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909204

ABSTRACT

BACKGROUND: Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. METHODS: Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. RESULTS: Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06-1.26; P < 0.05). Multivariable analysis further substantiated PDW's robust association with mortality risk (OR 1.23; 95% CI, 1.03-1.48; P < 0.05). Conversely, our analysis did not uncover significant correlations between the genetic predispositions to other BCIs-including red blood cell count, erythrocyte distribution width, platelet count, mean platelet volume, white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, and lymphocyte percentage-and 28-day mortality in sepsis. Additionally, an inverse MR analysis did not establish a causal impact of 28-day mortality in sepsis on PDW (OR 1.00; 95% CI, 1.00-1.07; P = 0.29). Moreover, a similar result was observed in the retrospective study. CONCLUSIONS: The study underscores the independent causal role of PDW in predicting 28-day mortality in sepsis, suggesting its potential utility in early patient assessment, risk stratification, and tailoring of therapeutic interventions.


Subject(s)
Mendelian Randomization Analysis , Sepsis , Humans , Sepsis/mortality , Sepsis/blood , Retrospective Studies , Male , Female , Middle Aged , Genome-Wide Association Study , Aged , Blood Platelets
18.
Hum Cell ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935235

ABSTRACT

The limited response of hepatocellular carcinoma (HCC) to chemotherapy drugs has always been a bottleneck in therapy. DNA damage repair is a major reason for chemoresistance. Previous studies have confirmed that KIN17 affects chemosensitivity. In this study, we examined the impact of KIN17 on chemotherapy response and DNA repair in HCC cells treated with oxaliplatin (L-OHP). We evaluated the expression and biological roles of KIN17 in HCC using bioinformatic analysis. The correlation between KIN17 and RAD51, particularly their nuclear expression levels, was evaluated using immunofluorescence, immunoblotting after nucleocytoplasmic separation in HCC cells, and immunohistochemistry of mouse xenograft tumors and human HCC tissues. The results indicated a significant increase in KIN17 expression in HCC tissues compared to normal tissues. The GSEA analysis revealed that upregulation of KIN17 was significantly associated with DNA damage repair. Knockdown of KIN17 led to increased DNA damage and reduced cellular survival after exposure to L-OHP. On the other hand, overexpression of KIN17 was linked to decreased DNA damage and improved cell survival following L-OHP treatment. Further experiments indicated that KIN17 affects the expression of RAD51, particularly in the nucleus. KIN17 plays a crucial role in influencing the sensitivity of HCC to chemotherapy by triggering the DNA repair response. Increased expression of KIN17 is associated with a poor prognosis for HCC patients, indicating that KIN17 could serve as a prognostic marker and therapeutic target for HCC.

19.
Toxicology ; 506: 153872, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38924947

ABSTRACT

N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.


Subject(s)
Alcohol Drinking , Chemical and Drug Induced Liver Injury , Cytochrome P-450 CYP2E1 , Dimethylformamide , Ethanol , Liver , Animals , Dimethylformamide/toxicity , Ethanol/toxicity , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Mice , Male , Cytochrome P-450 CYP2E1/metabolism , Liver/drug effects , Liver/pathology , Liver/metabolism , Alcohol Drinking/adverse effects , Apoptosis/drug effects , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Hepatocytes/drug effects , Hepatocytes/pathology , Dose-Response Relationship, Drug , Inflammasomes/metabolism , Inflammasomes/drug effects , Mice, Inbred C57BL
20.
Sci Rep ; 14(1): 14551, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914606

ABSTRACT

This study compares postoperative visual outcomes and optical aberrations after Small Incision Lenticule Extraction (SMILE) in patients with both small (S-Kappa: Kappa angle < 0.2 mm) and large Kappa (L-Kappa: Kappa angle ≥ 0.2 mm) angles. The evaluated aberrations include total higher-order aberrations (HOAs), horizontal coma (HC), vertical coma (VC), and spherical aberrations (SA), with procedures incorporating intraoperative Kappa angle adjustments. We retrospectively analyzed patient records undergoing SMILE utilizing linear mixed models (LMM). We assessed adjusted mean uncorrected distance visual acuity (UDVA), Strehl ratio (SR), total HOAs, VC, and SA at pupils of 3 mm and 6 mm for both S-Kappa and L-Kappa. The disparities between S-Kappa and L-Kappa were evaluated by LMM's adjusted mean differences. The differences in optical metrics were also assessed in eyes grouped by myopia levels: low, moderate, and high. A sensitivity analysis was conducted on a threshold of Kappa angle at 0.3 mm. Eight-five patients (169 eyes) were analyzed, and no significant pre-operative difference was found in UDVA (p = .222) or spherical equivalent (p = .433). Post-operative differences were found in SR at 3 mm pupil size (-0.06, p = .022), total HOA 3 mm (0.15, p = .022), HC 3 mm (0.04, p = .042), VC 3 mm and 6 mm (-0.08, p = .041; 0.04, p = .041). The stratified analysis for high myopia revealed significant differences in UDVA (-0.04, p = .037), HC 3 mm (0.07, p = .03), VC 6 mm (-0.21, p = .001), and SA 3 mm and 6 mm (0.07, p = .037; -0.09, p = .037). Sensitivity analysis showed no significant difference using a 0.3 mm Kappa threshold. While some optical aberrations exhibited statistical differences between S-Kappa and L-Kappa, their clinical significance is limited. Thus, a large Kappa angle might not substantially influence post-operative optical aberrations when intraoperative Kappa angle adjustments are implemented.


Subject(s)
Myopia , Visual Acuity , Humans , Female , Male , Adult , Retrospective Studies , Myopia/surgery , Young Adult , Corneal Surgery, Laser/methods , Corneal Surgery, Laser/adverse effects , Corneal Wavefront Aberration/physiopathology , Treatment Outcome , Refraction, Ocular
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