Asymmetric [3 + 3] cycloaddition of cinnamaldehyde-derived N-aryl nitrones with 2-indolemethanols enabled by chiral phosphoric acid.

We described a chiral phosphoric acid (CPA) catalyzed asymmetric [3 + 3] cycloaddition of cinnamaldehyde-derived N-aryl nitrones with 2-indolylmethanols to prepare various indole-fused 1,2-oxazines in high yields (up to 96%) with excellent enantioselectivity (>99% ee). Control experiments indicate that hydrogen bonding plays important roles in controlling the enantioselectivity of products. This strategy provides an efficient pathway to construct enantioenriched indole-fused 1,2-oxazines from N-aryl nitrones with 2-indolylmethanols.

Enhanced pediatric thyroid ultrasound image segmentation using DC-Contrast U-Net.

Early screening methods for the thyroid gland include palpation and imaging. Although palpation is relatively simple, its effectiveness in detecting early clinical signs of the thyroid gland may be limited, especially in children, due to the shorter thyroid growth time. Therefore, this constitutes a crucial foundational work. However, accurately determining the location and size of the thyroid gland in children is a challenging task. Accuracy depends on the experience of the ultrasound operator in current clinical practice, leading to subjective results. Even among experts, there is poor agreement on thyroid identification. In addition, the effective use of ultrasound machines also relies on the experience of the ultrasound operator in current clinical practice. In order to extract sufficient texture information from pediatric thyroid ultrasound images while reducing the computational complexity and number of parameters, this paper designs a novel U-Net-based network called DC-Contrast U-Net, which aims to achieve better segmentation performance with lower complexity in medical image segmentation. The results show that compared with other U-Net-related segmentation models, the proposed DC-Contrast U-Net model achieves higher segmentation accuracy while improving the inference speed, making it a promising candidate for deployment in medical edge devices in clinical applications in the future.

Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.

Metabolism-related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies.

Individualized and Biomarker-Based Prognosis of Longitudinal Cognitive Decline in Early Symptomatic Alzheimer's Disease.

Background: Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain. Objective: We aimed to develop prognostic models for individualized prediction of cognitive change in early AD. Methods: A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years. Results: A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R2 of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD. Conclusions: Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.

Effects of the interaction between body mass index and dietary patterns on severe NAFLD incidence: A prospective cohort study.

BACKGROUND: It remains unclear whether the associations between dietary patterns and non-alcoholic fatty liver disease (NAFLD) vary by body mass index (BMI). We aimed to explore the association between dietary patterns and severe NAFLD incidence, and further investigate the interaction of BMI with dietary patterns. METHODS: In a prospective cohort study using UK Biobank data, we included White participants with baseline food frequency questionnaire (FFQ) information. Principal component analysis (PCA) with varimax rotation was performed to identify major dietary patterns. The primary outcome was severe NAFLD, defined as hospitalization due to NAFLD or non-alcoholic steatohepatitis (NASH). We employed cause-specific Cox regression for competing risks to assess the association and calculated the relative excess risk due to interaction (RERI) to estimate the interaction of BMI. RESULTS: This study included 307,130 participants with a median follow-up of 12.68 years. 3104 cases of severe NAFLD were identified. PCA analysis revealed two primary dietary patterns: a prudent diet (RC1) and a meat-based diet (RC2). Multivariate analysis showed a standard deviation (SD) increase in RC1 was associated with lower severe NAFLD risk (HR 0.91 [95 % CI 0.88 to 0.94]), while a SD increase in RC2 was associated with higher risk (1.10 [1.05 to 1.14]). Significant interactions were observed between baseline BMI ≥25 kg/m2 and dietary patterns (RC1: RERI: -0.22 [95 % CI -0.43 to -0.003]; RC2: 0.29 [0.03 to 0.56]). CONCLUSIONS: Targeted dietary modifications are vital for specific populations at risk of severe NAFLD, considering the significant interaction observed between BMI and dietary patterns.

Gan-jiang-ling-zhu decoction improves steatohepatitis by regulating gut microbiota-mediated 12-tridecenoic acid inhibition.

Introduction: Gan-jiang-ling-zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated. Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction. Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression. Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC-CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

An Ensemble Learning Algorithm for Cognitive Evaluation by an Immersive Virtual Reality Supermarket.

Early screening for Mild Cognitive Impairment (MCI) is crucial in delaying cognitive deterioration and treating dementia. Conventional neuropsychological tests, commonly used for MCI detection, often lack ecological validity due to their simplistic and quiet testing environments. To address this gap, our study developed an immersive VR supermarket cognitive assessment program (IVRSCAP), simulating daily cognitive activities to enhance the ecological validity of MCI detection. This program involved elderly participants from Chengdu Second People's Hospital and various communities, comprising both MCI patients (N=301) and healthy elderly individuals (N=1027). They engaged in the VR supermarket cognitive test, generating complex datasets including User Behavior Data, Tested Cognitive Dimension Game Data, Trajectory Data, and Regional Data. To analyze this data, we introduced an adaptive ensemble learning method for imbalanced samples. Our study's primary contribution is demonstrating the superior performance of this algorithm in classifying MCI and healthy groups based on their performance in IVRSCAP. Comparative analysis confirmed its efficacy over traditional imbalanced sample processing methods and classic ensemble learning voting algorithms, significantly outperforming in metrics such as recall, F1-score, AUC, and G-mean. Our findings advocate the combined use of IVRSCAP and our algorithm as a technologically advanced, ecologically valid approach for enhancing early MCI detection strategies. This aligns with our broader aim of integrating realistic simulations with advanced computational techniques to improve diagnostic accuracy and treatment efficacy in cognitive health assessments.

Endocytosis efficiency and targeting ability by the cooperation of nanoparticles.

Cooperative wrapping of nanoparticles (NPs) with small sizes is an important pathway for the uptake of NPs by cell membranes. However, the cooperative wrapping efficiency and the effects of NPs' rigidity remain ambiguous. With the aid of computer simulations, we show that the complete wrapping mechanism of cooperative endocytosis is that the aggregation of NPs leads to greater wrapping forces than the single NP case, which triggers the increase of the wrapping degree and in turn further increases the wrapping forces until they are finally fully taken up. The effects of the NP size, initial distance, interaction strength, arrangement and stiffness on cooperative endocytosis were systematically studied. The cooperative wrapping efficiency increases as the NP radius increases. Hexagonal close packed NPs have the highest internalization efficiency. When the interactions are strong, softer NPs exhibit higher endocytosis efficiency. We further propose two strategies by combining NPs with different wrapping properties for targeting applications. By combining two NPs decorated with different types of ligands, the combination NPs can only be fully endocytosed by the cell membrane with two cognate types of receptors and adhere to the normal cell membrane with only one type of receptor. We also design composite NPs using a large NP non-covalently decorated with several small NPs. By harnessing the competition between the ligand-receptor interactions and the excluded volume interactions between the small NPs and the lipid membrane, the composite NPs have targeting ability towards the cancer cell membrane. The design concept of combining NPs with different wrapping properties for drug targeting applications may be very promising in biomedicine.

Light footprint of microalgae cultivation system addressed by modified Cornet model.

The cultivation of microalgae is significantly influenced by light intensity and utilization efficiency. This study developed a modified Cornet (M-Cornet) model to assess the distribution of light intensity and flux in microalgae cultivation systems. Algal biofilm cultivation represents a more concentrated approach of algal suspension cultivation. Both follow the M-Cornet model and exhibit the same growth rates when cultured under identical conditions. Algal pigments and morphologies greatly impact the light absorption and scattering, resulting in light attenuation in intensity, penetration distance and light flux distribution. Algae varieties exhibit diverse light flux characteristics. 37% - 90% of the incident light is absorbed, of which, 80% to 90% is dissipated as heat. 10% to 63% of the incident light is scattered off the photobioreactor. The overall light utilization efficiency ranges 6% to 13%. The light footprint using the M-Cornet model offers valuable insights for photobioreactors designing and cultivation operating.

Oocyte-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early-growing follicles by mitochondrial fission defect-reactive oxygen species-DNA damage.

BACKGROUND: Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. METHODS AND RESULTS: We generated eukaryotic translation initiation factor 5 (Eif5) conditional knockout mice aiming to investigate the function of eIF5 during oocyte growth and follicle development. Here, we demonstrated that Eif5 deletion in mouse primordial and growing oocytes both resulted in the apoptosis of oocytes within the early-growing follicles. Further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission-related proteins (p-DRP1, FIS1, MFF and MTFR) and upregulated the levels of the integrated stress response-related proteins (AARS1, SHMT2 and SLC7A1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased adenosine triphosphate content and mtDNA copy numbers, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNA damage response proteins (γH2AX, p-CHK2 and p-p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti-apoptotic protein BCL-xL. CONCLUSION: These findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early-growing follicles via mitochondrial fission defects, excessive ROS accumulation and DNA damage. This study provides new insights into pathogenesis, genetic diagnosis and potential therapeutic targets for POI. KEY POINTS: Eif5 deletion in oocytes leads to arrest in oocyte growth and follicle development. Eif5 deletion in oocytes impairs the translation of mitochondrial fission-related proteins, followed by mitochondrial dysfunction. Depletion of Eif5 causes oocyte apoptosis via ROS accumulation and DNA damage response pathway.

Characterizing the clinical heterogeneity of early symptomatic Alzheimer's disease: a data-driven machine learning approach.

Introduction: Alzheimer's disease (AD) is highly heterogeneous, with substantial individual variabilities in clinical progression and neurobiology. Amyloid deposition has been thought to drive cognitive decline and thus a major contributor to the variations in cognitive deterioration in AD. However, the clinical heterogeneity of patients with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) already with evidence of amyloid abnormality in the brain is still unknown. Methods: Participants with a baseline diagnosis of mild cognitive impairment or mild dementia, a positive amyloid-PET scan, and more than one follow-up Alzheimer's Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) administration within a period of 5-year follow-up were selected from the Alzheimer's Disease Neuroimaging Initiative database (n = 421; age = 73±7; years of education = 16 ± 3; percentage of female gender = 43%; distribution of APOE4 carriers = 68%). A non-parametric k-means longitudinal clustering analysis in the context of the ADAS-Cog-13 data was performed to identify cognitive subtypes. Results: We found a highly variable profile of cognitive decline among patients with early AD and identified 4 clusters characterized by distinct rates of cognitive progression. Among the groups there were significant differences in the magnitude of rates of changes in other cognitive and functional outcomes, clinical progression from mild cognitive impairment to dementia, and changes in markers presumed to reflect neurodegeneration and neuronal injury. A nomogram based on a simplified logistic regression model predicted steep cognitive trajectory with an AUC of 0.912 (95% CI: 0.88 - 0.94). Simulation of clinical trials suggested that the incorporation of the nomogram into enrichment strategies would reduce the required sample sizes from 926.8 (95% CI: 822.6 - 1057.5) to 400.9 (95% CI: 306.9 - 516.8). Discussion: Our findings show usefulness in the stratification of patients in early AD and may thus increase the chances of finding a treatment for future AD clinical trials.

High dietary Fructose Drives Metabolic Dysfunction-Associated Steatotic Liver Disease via Activating ubiquitin-specific peptidase 2/11ß-hydroxysteroid dehydrogenase type 1 Pathway in Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver-related morbidity and mortality. Though high fructose intake is acknowledged as a metabolic hazard, its role in the etiology of MASLD requires further clarification. Here, we demonstrated that high dietary fructose drives MASLD development and promotes MASLD progression in mice, and identified Usp2 as a fructose-responsive gene in the liver. Elevated USP2 levels were detected in the hepatocytes of MASLD mice; a similar increase was observed following fructose exposure in primary hepatocytes and mouse AML12 cells. Notably, hepatocytes overexpressing USP2 presented with exaggerated lipid accumulation and metabolic inflammation when exposed to fructose. Conversely, USP2 knockdown mitigated these fructose-induced changes. Furthermore, USP2 was found to activate the C/EBPα/11ß-HSD1 signaling, which further impacted the equilibrium of cortisol and cortisone in the circulation of mice. Collectively, our findings revealed the role of dietary fructose in MASLD pathogenesis and identified the USP2-mediated C/EBPα/ 11ß-HSD1 signaling as a potential target for the management of MASLD.

Catalyst-Free, Zn-Mediated Decarboxylative Coupling of Chlorostibines to Access Alkylstibines with Stable C(sp3)-Sb Bonds.

Herein, decarboxylative C(sp3)-Sb coupling of aliphatic carboxylic acid derivatives with chlorostibines to access alkylstibines has been achieved. This catalyst-, ligand-, and base-free approach using zinc as a reductant affords various kinds of benzyldiarylstibines and other monoalkyldiarylstibines and tolerates various functional groups, including chlorine, bromine, hydroxyl, amide, sulfone, and cyano groups. The late-stage modification and the gram-scale experiments illustrate its potential application.

Premeiotic deletion of Eif2s2 causes oocyte arrest at the early diplotene stage and apoptosis in mice.

Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2), a subunit of the heterotrimeric G protein EIF2, is involved in the initiation of translation. Our findings demonstrate that the depletion of Eif2s2 in premeiotic germ cells causes oocyte arrest at the pachytene and early diplotene stages at 1 day postpartum (dpp) and 5 dpp, respectively, and eventually leads to oocyte apoptosis and failure of primordial follicle formation. Further studies reveal that Eif2s2 deletion downregulates homologous recombination-related and mitochondrial fission-related protein levels, and upregulates the integrated stress response-related proteins and mRNA levels. Consistently, Eif2s2 deletion significantly decreases the expression of dictyate genes and compromises mitochondrial function, characterized by elongated shapes, decreased ATP levels and mtDNA copy number, along with an excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, DNA damage response and proapoptotic protein levels increase, while anti-apoptotic protein levels decrease in Eif2s2-deleted mice. An increase in oocytes with positive cleaved-Caspase-3 and TUNEL signals, alongside reduced Lamin B1 intensity, further indicates oocyte apoptosis. Collectively, Eif2s2 deletion in premeiotic germ cells causes oocyte meiotic arrest at the early diplotene stage by impairing homologous recombination, and eventually leads to oocyte apoptosis mainly through the downregulation of mitochondrial fission-related proteins, ROS accumulation and subsequent DNA damage.

Hydrogel binding sodium alginate based optical fiber surface plasmon resonance for calcium ion trace detection.

A plasmonic tilted fiber Bragg grating (TFBG)-based sensor for the detection of calcium ion (Ca2+) was proposed and demonstrated experimentally. Hydrogel material was synthesized by utilizing hydrogen bond recombination between cellulose nanocrystals (CNC) and polyvinyl alcohol (PVA). Sodium alginate (SA) was incorporated into this hydrogel material, resulting in a composite membrane with specific binding properties for Ca2+. The membrane was applied as a coating on the surface of a gold-coated TFBG. The CNC/PVA-SA modified gold on the TFBG surface enhanced the localized refractive index changes caused by variations of Ca2+ concentrations. The experimental results demonstrated an impressive limit of detection (LOD) of approximately 0.025 fM, which is five orders of magnitude better than the current LODs of similar Ca2+ sensors. And the proposed Ca2+ sensor exhibited a wide dynamic range of 10-16 M to 10-6 M.

Efficient Microbubble Trajectory Tracking in Ultrasound Localization Microscopy Using a Gated Recurrent Unit-Based Multitasking Temporal Neural Network.

Ultrasound Localization Microscopy (ULM), an emerging medical imaging technique, effectively resolves the classical trade-off between resolution and penetration inherent in traditional ultrasound imaging, opening up new avenues for noninvasive observation of the microvascular system. However, traditional microbubble tracking methods encounter various practical challenges. These methods typically entail multiple processing stages, including intricate steps like pairwise correlation and trajectory optimization, rendering real-time applications unfeasible. Furthermore, existing deep learning-based tracking techniques neglect the temporal aspects of microbubble motion, leading to ineffective modeling of their dynamic behavior. To address these limitations, this study introduces a novel approach called the Gated Recurrent Unit (GRU)-based Multitasking Temporal Neural Network (GRU-MT). GRU-MT is designed to simultaneously handle microbubble trajectory tracking and trajectory optimization tasks. Additionally, we enhance the nonlinear motion model initially proposed by Piepenbrock et al. to better encapsulate the nonlinear motion characteristics of microbubbles, thereby improving trajectory tracking accuracy. In this study, we perform a series of experiments involving network layer substitutions to systematically evaluate the performance of various temporal neural networks, including Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), GRU, Transformer, and its bidirectional counterparts, on the microbubble trajectory tracking task. Concurrently, the proposed method undergoes qualitative and quantitative comparisons with traditional microbubble tracking techniques. The experimental results demonstrate that GRU-MT exhibits superior nonlinear modeling capabilities and robustness, both in simulation and in vivo dataset. Additionally, it achieves reduced trajectory tracking errors in shorter time intervals, underscoring its potential for efficient microbubble trajectory tracking. Model code is open-sourced at https://github.com/zyt-Lib/GRU-MT.

L.acidophilus HSCC LA042 and HKL suspension ameliorate DSS-induced ulcerative colitis in mice by improving the intestinal barrier inhibiting the NLRP3 inflammasome and pathogenic bacteria.

Ulcerative Colitis(UC) is a chronic intestinal inflammation affecting the intestines, yet its underlying causes remain unclear. In recent decades, the global prevalence of UC has been on the rise, leading to an increasing demand for therapeutic drugs with minimal side effects. Huan Kui Le (HKL), a traditional Chinese medicine compound, has demonstrated promising efficacy when combined with Lactobacillus acidophilus (Lac.) for UC intervention. However, the precise therapeutic mechanism of this combination remains unknown. The study focused on understanding the mechanisms of UC by examining the effects of Lac. and HKL (LH) treatment. The outcomes discovered that the disruption of gut microbiota, triggered by the activation of the NLRP3 inflammasome, plays a crucial role in UC development. This disruption exacerbates UC symptoms by causing disturbances in inflammatory cytokines and mucosal permeability. We investigated the dynamic changes following the application of this treatment using 16S rRNA sequencing, HE, WB, IHC, and ELISA. Compared with the UC group, LH treatment reduced colon pathological injury, improved colon length, and decreased IL-1 ß serum levels. Furthermore, it restored the expression of TJs and preserved mucosal barrier integrity. LH treatment also mitigated colon injury by attenuating the expression of pyroptosis-related genes and proteins, such as NLRP3 and Caspase-1. Additionally, LH treatment altered the gut microbiota's microecology, characterized by a reduction in pathogenic bacteria abundance like Escherichia-shigella and an increase in beneficial bacteria abundance like Akkermansia and Erysipelatoclostridium. Overall, our findings indicate that LH therapy may be associated with intestinal barrier repair, inflammasome inhibition, and gut microbiota regulation, suggesting its potential as a UC treatment.

Serum Metabolomics Uncovers the Mechanisms of Inulin in Preventing Non-Alcoholic Fatty Liver Disease.

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD.

Base-Promoted Annulated Aromatization of Aryl Acetylenes with Dimethyl Sulfoxide to Access Symmetrical/Unsymmetric m-Terphenyl.

A protocol for selective and efficient synthesis of symmetrical and unsymmetrical m-terphenyls is presented among aryl acetylene and DMSO in the presence of KOH and methanol. In this reaction, two molecules of aryl acetylene contribute four carbons, and DMSO, as a dual carbon donor, provides two carbons to a new aromatic ring. This protocol can be tolerated for the electron-donating or disubstituted phenylacetylenes as well as the heterocyclic acetylene derivatives.

Mutagenesis and fluorescence-activated cell sorting of oleaginous Saccharomyces cerevisiae and the multi-omics analysis of its high lipid accumulation mechanisms.

Acquiring lipid-producing strains of Saccharomyces cerevisiae is necessary for producing high-value palmitoleic acid. This study sought to generate oleaginous S. cerevisiae mutants through a combination of zeocin mutagenesis and fluorescence-activated cell sorting, and then to identify key mutations responsible for enhanced lipid accumulation by multi-omics sequencing. Following three consecutive rounds of mutagenesis and sorting, a mutant, MU310, with the lipid content of 44%, was successfully obtained. Transcriptome and targeted metabolome analyses revealed that a coordinated response involving fatty acid precursor biosynthesis, nitrogen metabolism, pentose phosphate pathway, ethanol conversion, amino acid metabolism and fatty acid ß-oxidation was crucial for promoting lipid accumulation. The carbon fluxes of acetyl-CoA and NADPH in lipid biosynthesis were boosted in these pathways. Certain transcriptional regulators may also play significant roles in modulating lipid biosynthesis. Results of this study provide high-quality resource for palmitoleic acid production and deepen the understanding of lipid synthesis in yeast.