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Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. Ilex hainanensis Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of I. hainanensis extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD.
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With the imbalance of intestinal microbiota, the body will then face an inflammatory response, which has serious implications for human health. Bodily allergies, injury or pathogens infections can trigger or promote inflammation and alter the intestinal environment. Meanwhile, excessive changes in the intestinal environment cause the imbalance of microbial homeostasis, which leads to the proliferation and colonization of opportunistic pathogens, invasion of the body's immune system, and the intensification of inflammation. Some natural compounds and gut microbiota and metabolites can reduce inflammation; however, the details of how they interact with the gut immune system and reduce the gut inflammatory response still need to be fully understood. The review focuses on inflammation and intestinal microbiota imbalance caused by pathogens. The body reacts differently to different types of pathogenic bacteria, and the ingestion of pathogens leads to inflamed gastrointestinal tract disorders or intestinal inflammation. In this paper, unraveling the interactions between the inflammation, pathogenic bacteria, and intestinal microbiota based on inflammation caused by several common pathogens. Finally, we summarize the effects of intestinal metabolites and natural anti-inflammatory substances on inflammation to provide help for related research of intestinal inflammation caused by pathogenic bacteria.
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Few studies have considered bilingualism's impact on cognitive development within the sociolinguistic and cultural context of the immigrant communities where bilingualism is commonly practiced. In the United States, many Mexican-origin bilingual youth practice their bilingual skills by brokering (i.e., translating/interpreting between languages) for their immigrant parents who have low English proficiency. Meanwhile, these youth may also experience discrimination in their daily life. The present study focuses on Mexican-origin bilingual youth brokers (N=334) in order to examine how discriminatory experiences (i.e., daily and ethnic discrimination) and bilingual brokering experiences captured by profiles are related to cognitive control performance (i.e., attentional control and inhibition). We found no significant direct influence of either bilingual broker profiles or discriminatory experiences on cognitive control. However, the associations between discriminatory experiences and cognitive control performance depended upon brokering experiences. Specifically, greater discrimination was associated with lower cognitive control performance among moderate brokers (with moderate bilingual experiences), but the association was attenuated among efficacious brokers (with positive bilingual experiences). Findings highlight the need to consider the sociolinguistic heterogeneity of both discriminatory experiences and language use when investigating cognitive control performance in bilinguals.
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Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, accounting for 30%-40% of non-Hodgkin lymphoma in adults. The mechanisms underlying DLBCL occurrence are extremely complex, and involve the B-cell receptor (BCR) and Toll-like receptor (TLR) signaling pathways, as well as genetic abnormalities and other factors. With the development of high-throughput sequencing, an increasing number of abnormal genes have been identified in DLBCL. Among them, the tumor protein p53 (TP53/p53) gene is important in DLBCL occurrence. Patients with DLBCL carrying TP53 gene abnormalities generally have poor prognosis and studies of p53 have potential to provide a better basis for their treatment. Normally, p53 is maintained at low levels through its interaction with murine double minute 2 (MDM2), and prevents tumorigenesis by mediating cell cycle arrest, apoptosis, and repair of damaged cells, among other processes. Therefore, the prognosis of patients with DLBCL harboring TP53 gene abnormalities (mutations, deletions, etc.) is poor, and targeting p53 for tumor therapy has become a research hotspot, following developments in molecular biology technologies. Current treatments targeting p53 mainly act by restoring the function or promoting degradation of mutant p53, and enhancing wild-type p53 protein stability and activity. Based on the current status of p53 research, exploration of existing therapeutic methods to improve the prognosis of patients with DLBCL with TP53 abnormalities is warranted.
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[This corrects the article DOI: 10.3389/fphar.2020.586725.].
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Excessive alcohol exposure can cause neurobehavioral deficits and structural alterations in the brain. Emerging research evidence suggests that endoplasmic reticulum (ER) stress plays an important role in alcohol-induced neurotoxicity. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein and is responsible to maintain ER homeostasis. MANF is highly expressed in both the developing and mature brain. We have previously shown that MANF deficiency exacerbated alcohol induced neurodegeneration and ER stress in the developing brain. However, little is known regarding the role of MANF in alcohol induced neuronal damage in the adult brain. In this study, we used a neuron-specific MANF knockout (KO) mouse model to investigate the effect of MANF deficiency on acute binge alcohol exposure-induced neurobehavioral deficits and ER stress. Adult male and female MANF KO mice and littermate controls received daily alcohol gavage (5 g/kg) for 10 days and then subjected to a battery of neurobehavioral tests including rotarods, balance beam, DigiGait, open field, elevated plus maze, Barnes maze, and three-chamber sociability task. Female MANF KO animals were more susceptible to alcohol-induced body weight loss. Alcohol exposure did not affect motor function, however female but not male MANF KO mice exhibited an increased locomotor activity in open field test. Learning and memory was not significantly impaired, but it was altered by MANF deficiency in females while it was affected by alcohol treatment in males. Both alcohol-exposed male and female MANF KO mice displayed increased sociability. Alcohol induced the expression of ER chaperones GRP78 and GRP94 and altered the levels of several unfolded protein response (UPR) and neuroinflammation markers in MANF KO mice in a sex-specific manner. The expression of MANF interacting proteins neuroplastin, PDIA1, and PDIA6 was increased in MANF KO mice, and was further induced by alcohol. In conclusion, alcohol exposure and neuronal MANF deficiency interacted to alter neurobehavioral outcomes, ER homeostasis and neuroinflammation in a sex-specific manner.
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BACKGROUND: The Naples Prognostic Score (NPS) is a novel indicator of inflammatory and nutritional status, but its relationship to lung health is unknown. OBJECTIVE: To evaluate the relationship of NPS to lung health problems. METHODS: A total of 15,600 participants aged 20 years or older with an available assessment of chronic lung diseases were enrolled from the National Health and Nutrition Examination Survey 2007-2012. The NPS was calculated based on serum albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Associations of NPS with chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), and spirometric measurements (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated. Kaplan-Meier survival analysis and multiple Cox regressions were used to assess the significance of NPS in relation to all-cause mortality and chronic lower respiratory diseases mortality in participants. Furthermore, to comprehensively assess the association between NSP and chronic lower respiratory diseases mortality, Fine-Gray subdistribution hazards model was performed to analyze non-chronic lower respiratory diseases mortality as a competitive risk. RESULTS: People with a higher NPS score were associated with greater odds of asthma, chronic bronchitis, respiratory symptoms (including phlegm production, wheeze, and exertional dyspnea), and a greater risk of obstructive and restrictive spirometry. A higher NPS score was significantly associated with decreased FEV1 and FVC in both overall participants and those with lung health problems. Longitudinally, we found that those in the category with highest NPS were at greater risk of all-cause mortality and chronic lower respiratory diseases mortality in those with chronic lung disease, and respiratory symptoms. CONCLUSIONS: An elevated NPS is associated with a host of adverse pulmonary outcomes. Prospective studies to define NPS as a biomarker for impaired lung health are warranted.
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Dual control policies aim to effectively reduce energy consumption and carbon emission by setting targets for total volume and intensity control. With global climate change becoming increasingly serious. China, as a large energy-consuming and carbon-emitting country, faces a huge challenge to reduce carbon emissions. The transition from the "dual control of energy consumption" to the "dual control of carbon emissions" in China is necessary to optimize energy structures, promote energy conservation, reduce carbon emissions, and reach carbon neutrality. This study utilizes multi-regional input-output models to evaluate the results toward both goals from production-based, consumption-based, and income-based perspectives. The findings indicate that "dual control of carbon emissions" is a more precise approach than "dual control of energy consumption". Some provinces have met the latter goal while still falling short of the former. Provinces having met their production-based energy intensity and carbon emission intensity targets, but having failed their consumption-based and income-based targets, are identified to develop a comprehensive and accurate assessment of these targets. A net outflow of embodied energy and carbon emissions is observed among provinces in less-developed central and southern regions to more-developed eastern and northern regions. Suggestions and policy implications based on these findings include establishing a comprehensive evaluation of energy and carbon intensity, considering both consumption-based and income-based perspectives, as well as facilitating enhanced cooperation among developed and developing provinces.
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Carbono , Mudança Climática , ChinaRESUMO
The dopamine D2 receptor (DRD2) represents a pivotal target for therapeutic intervention in the treatment of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and Parkinson's disease. The successful discovery of numerous effective DRD2 inhibitors has led to their clinical application and ongoing evaluation in various clinical trials. This review explores the synthetic approaches and clinical applications of prototypical small-molecule DRD2 inhibitors that have received approval or are currently undergoing clinical trials, highlighting their therapeutic potential and challenges. The synthesis of these inhibitors employs various chemical strategies, including modifications of phenothiazine and butyrophenone structures, which have yielded significant antipsychotic agents like chlorpromazine and haloperidol. Additionally, newer classes of inhibitors, such as aripiprazole, exhibit partial agonist activity at DRD2, offering a unique therapeutic profile. Clinically, DRD2 inhibitors demonstrate efficacy in managing positive symptoms of schizophrenia, manic episodes in bipolar disorder, and dopaminergic imbalance in Parkinson's disease. However, the emergence of adverse effects, including tardive dyskinesia, extrapyramidal symptoms and metabolic syndrome, presents substantial challenges. Advances in the development of second-generation antipsychotics aim to balance efficacy with a better side effect profile by targeting additional neurotransmitter receptors. This review aims to deliver an overview of the synthesis and clinical applications of representative small-molecule DRD2 inhibitors across various clinical phases, thereby offering strategic insights for the advancement of DRD2 inhibitor development.
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Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.
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Doping of polycyclic conjugated hydrocarbons (PCHs) with sulfur atoms is becoming more and more important as a means of creating unique functional materials. Recently, thiophene-containing multiple helicenes have garnered enormous attention due to their intriguing electronic and (chir)optical properties compared with carbohelicenes. However, the efficient synthesis of thiopyran-containing multiple helicenes and the underlying sulfur doping mechanisms are rather unexplored. Herein, the synthesis and structural analysis of a thiopyran-containing double [7]helicene 3 are reported. X-ray crystallographic analysis reveals 3 and its dication with C2-symmetric propeller-shape structure and compact p-p interaction in the solid state. 3 exhibits deep-red to near-infrared (NIR) fluorescence emission. Tunable aromaticity of the central benzene ring and thiopyran rings is found by chemical oxidation, which is further confirmed by nucleus-independent chemical shift (NICS), anisotropy of the induced current density (AICD) and harmonic oscillator model of aromaticity (HOMA) analysis. Furthermore, the chiral and photosensitizing characters of 3 are investigated. The excellent deep-red to NIR fluorescence, circularly polarized luminescence (CPL) and photosensitizing activities suggest that 3 can be used as an outstanding photosensitizer in photodynamic therapy (PDT) and bioimaging, especially paving the way for future CPL-PDT and CPL-bio-probe applications.
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BACKGROUND: In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. AIM: To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. METHODS: This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. RESULTS: The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). CONCLUSION: In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.
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Background: In recent years, with the rapid advancement of fundamental ultrasonography research, the application of ultrasound in disease treatment has progressively increased. An increasing body of research indicates that microbubbles serve not only as contrast agents but also in conjunction with ultrasound, enhancing cavitation effects and facilitating targeted drug delivery, thereby augmenting therapeutic efficacy. The objective of this study is to explore the current status and prevailing research trends in this field from 2009 to 2023 through bibliometric analysis and to forecast future developmental trajectories. Methods: We selected the Science Citation Index Expanded (SCI-Expanded) from the Web of Science Core Collection (WOSCC) as our primary data source. On 19 January 2024, we conducted a comprehensive search encompassing all articles and reviews published between 2009 and 2023 and utilized the bibliometric online analysis platform, CiteSpace and VOSviewer software to analyze countries/regions, institutions, authors, keywords, and references, used Microsoft Excel 2021 to visualize the trends of the number of articles published by year. Results: Between 1 January 2009, and 31 December 2023, 3,326 publications on ultrasound combined with microbubble therapy technology were included. There were a total of 2,846 articles (85.6%) and 480 reviews (14.4%) from 13,062 scholars in 68 countries/regions published in 782 journals. China and the United States emerged as the primary contributors in this domain. In terms of publication output and global institutional collaboration, the University of Toronto in Canada has made the most significant contribution to this field. Professor Kullervo Hynynen has achieved remarkable accomplishments in this area. Ultrasound in Medicine and Biology is at the core of the publishing of research on ultrasound combined with microbubble therapy technology. Keywords such as "sonodynamic therapy," "oxygen," "loaded microbubbles" and "Alzheimer's disease" indicate emerging trends in the field and hold the potential to evolve into significant areas of future investigation. Conclusion: This study provides a summary of the key contributions of ultrasound combined with microbubble therapy to the field's development over the past 15 years and delves into the historical underpinnings and contemporary trends of ultrasound combined with microbubble therapy technology, providing valuable guidance for researchers.
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BACKGROUND: Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer. METHODS: Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis. RESULT: The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5. CONCLUSION: In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC.
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Processamento Alternativo , Apoptose , Movimento Celular , Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteína de Replicação C , Fatores de Processamento de Serina-Arginina , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Apoptose/genética , Linhagem Celular Tumoral , Proteína de Replicação C/genética , Proteína de Replicação C/metabolismo , Técnicas de Silenciamento de Genes , Proteínas Repressoras , Proteínas de Ciclo CelularRESUMO
Understanding of how different grasslands types respond to climate change and human activities across different spatial and temporal dimensions is crucial for devising effective strategies to prevent grasslands degradation. In this study, we developed a novel vulnerability assessment model for grasslands that intricately evaluates the combined impact of climate change and human activities. We then applied this model to analyze the vulnerability and driving mechanism of four representative Chinese grasslands to climate change and human activities. Our findings indicate that the vulnerability of the four grasslands would show a pattern of higher in the west and lower in the east under the influence of climate change alone. However, when human activities are factored in, the vulnerability across the four grasslands tends to homogenize, with human activities notably reducing the vulnerability of alpine grasslands in the west and, conversely, increasing the vulnerability of grasslands in the east. Furthermore, our study reveals distinct major environmental drivers of grasslands vulnerability across different regions. The two western alpine grasslands exhibit higher vulnerability to annual mean temperature and isothermality compared to the eastern temperate grasslands, while their vulnerability to precipitation of the coldest quarter is lower than that of the eastern temperate grasslands. These findings are helpful for understanding the multifaceted causes and mechanisms of grasslands degradation, providing a scientific foundation for the sustainable management and conservation of grassland resources.
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BACKGROUND: Post-burn anxiety and depression affect considerably the quality of life and recovery of patients; however, limited research has demonstrated risk factors associated with the development of these conditions. AIM: To predict the risk of developing post-burn anxiety and depression in patients with non-mild burns using a nomogram model. METHODS: We enrolled 675 patients with burns who were admitted to The Second Affiliated Hospital, Hengyang Medical School, University of South China between January 2019 and January 2023 and met the inclusion criteria. These patients were randomly divided into development (n = 450) and validation (n = 225) sets in a 2:1 ratio. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with post-burn anxiety and depression diagnoses, and a nomogram model was constructed. RESULTS: Female sex, age < 33 years, unmarried status, burn area ≥ 30%, and burns on the head, face, and neck were independent risk factors for developing post-burn anxiety and depression in patients with non-mild burns. The nomogram model demonstrated predictive accuracies of 0.937 and 0.984 for anxiety and 0.884 and 0.923 for depression in the development and validation sets, respectively, and good predictive performance. Calibration and decision curve analyses confirmed the clinical utility of the nomogram. CONCLUSION: The nomogram model predicted the risk of post-burn anxiety and depression in patients with non-mild burns, facilitating the early identification of high-risk patients for intervention and treatment.
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This paper introduces a novel digital triangular-trapezoidal double-channel shaping algorithm to enhance the counting rate of resistive anode detectors. The algorithm is based on the trapezoidal shaping algorithm and improves it. At the extreme counting rate, the trapezoidal shaping algorithm cannot alleviate the pulse pileup, so the counting rate cannot meet the requirements of a high performance detector. The triangular-trapezoidal double-channel shaping algorithm is introduced in the resistance anode detector, which can replace the trapezoidal shaping filtering algorithm to process the output signal of the resistance anode detector and obtain the single photon position information. This improvement improves the counting rate of the resistor anode detector and reduces the resolution degradation caused by pulse pileup. The algorithm is simulated by System Generator software and implemented on FPGA (field programmable gate array). The triangular-trapezoidal double-channel shaping algorithm presented in this paper plays an important role in reducing electronic noise and pulse pileup. The algorithm is subjected to simulation testing, and it can recognize signals with a minimum pulse interval of 1 µs and counting rate up to 1000 kcps.
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Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.
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Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.
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Background: Congenital scoliosis and congenital anomalies of the kidney and urinary tract are distinct genetic disorders with differing clinical manifestations. Clinically, their coexistence is not rare, but the etiologies of these complex diseases remain largely unknown, especially their shared genetic basis. Methods: We sequenced the genomes of 40 individuals diagnosed with both CS and CAKUT, alongside 2,764 controls from a Chinese Han population cohort. Our analyses encompassed gene-based and pathway-based weighted rare variant association tests, complemented by copy number variant association analyses, aiming to unravel the shared genomic etiology underlying these congenital conditions. Results: Gene-based analysis identified PTPN11 as a pivotal gene influencing both skeletal and urinary system development (P = 1.95E-21), participating in metabolic pathways, especially the MAPK/ERK pathway known to regulate skeletal and urinary system development. Pathway-based enrichment showed a significant signal in the MAPK/ERK pathway (P = 3E-04), reinforcing the potential role of PTPN11 and MAPK/ERK pathway in both conditions. Additionally, CNV analysis pinpointed IGFLR1 haploinsufficiency as a potential influential factor in the combined CS-CAKUT phenotypic spectrum. Conclusion: This study enriches our understanding of the intricate genomic interplay underlying congenital scoliosis and kidney and urinary tract anomalies, emphasizing the shared genetic foundations between these two disorders.