CRISPR-Cas13 Inhibitors Block RNA Editing in Bacteria and Mammalian Cells.

Cas13 has demonstrated unique and broad utility in RNA editing, nucleic acid detection, and disease diagnosis; however, a constantly active Cas enzyme may induce unwanted effects. Bacteriophage- or prophage-region-encoded anti-CRISPR (acr) gene molecules provide the potential to control targeting specificity and potency to allow for optimal RNA editing and nucleic acid detection by spatiotemporally modulating endonuclease activities. Using integrated approaches to screen acrVI candidates and evaluate their effects on Cas13 function, we discovered a series of acrVIA1-7 genes that block the activities of Cas13a. These VI-A CRISPR inhibitors substantially attenuate RNA targeting and editing by Cas13a in human cells. Strikingly, type VI-A anti-CRISPRs (AcrVIAs) also significantly muffle the single-nucleic-acid editing ability of the dCas13a RNA-editing system. Mechanistically, AcrVIA1, -4, -5, and -6 bind LwaCas13a, while AcrVIA2 and -3 can only bind the LwaCas13-crRNA (CRISPR RNA) complex. These identified acr molecules may enable precise RNA editing in Cas13-based application and study of phage-bacterium interaction.

DNA sensing via the cGAS/STING pathway activates the immunoproteasome and adaptive T-cell immunity.

The immunoproteasome is a specialized type of proteasome involved in MHC class I antigen presentation, antiviral adaptive immunity, autoimmunity, and is also part of a broader response to stress. Whether the immunoproteasome is regulated by DNA stress, however, is not known. We here demonstrate that mitochondrial DNA stress upregulates the immunoproteasome and MHC class I antigen presentation pathway via cGAS/STING/type I interferon signaling resulting in cell autonomous activation of CD8+ T cells. The cGAS/STING-induced adaptive immune response is also observed in response to genomic DNA and is conserved in epithelial and mesenchymal cells of mice and men. In patients with idiopathic pulmonary fibrosis, chronic activation of the cGAS/STING-induced adaptive immune response in aberrant lung epithelial cells concurs with CD8+ T-cell activation in diseased lungs. Genetic depletion of the immunoproteasome and specific immunoproteasome inhibitors counteract DNA stress induced cytotoxic CD8+ T-cell activation. Our data thus unravel cytoplasmic DNA sensing via the cGAS/STING pathway as an activator of the immunoproteasome and CD8+ T cells. This represents a novel potential pathomechanism for pulmonary fibrosis that opens new therapeutic perspectives.

The translational landscape of bread wheat during grain development.

The dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.

IL-17RA promotes pathologic epithelial inflammation in a mouse model of upper respiratory influenza infection.

The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of interleukin IL-17 recetor A (IL-17RA) as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings.

Diagnostic Utility of MOG Antibody Testing in Cerebrospinal Fluid.

OBJECTIVE: The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing. METHODS: We retrospectively identified patients for CSF MOG-IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG-IgG for testing including: controls, 282; serum MOG-IgG positive MOG antibody-associated disease (MOGAD), 74; serum MOG-IgG negative high-risk phenotypes, 73; serum false positive MOG-IgG with alternative diagnoses, 18. A live cell-based assay assessed CSF MOG-IgG positivity (IgG-binding-index [IBI], ≥2.5) using multiple anti-human secondary antibodies and end-titers were calculated if sufficient sample volume. Correlation of CSF MOG-IgG IBI and titer was assessed. RESULTS: The pan-IgG Fc-specific secondary was optimal, yielding CSF MOG-IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG-IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG-IgG positive MOGAD patients; and 9/73 (12%) serum MOG-IgG negative patients with high-risk phenotypes. Serum negative but CSF positive MOG-IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG-IgG low-positives revealed CSF MOG-IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG-IgG (3/15[20%]) (p = 0.01). CSF MOG-IgG IBI and CSF MOG-IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001). INTERPRETATION: CSF MOG-IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG-IgG, and those with low positive serum MOG-IgG results and diagnostic uncertainty. These findings support a role for CSF MOG-IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34-45.

Gut microbiome correlates with plasma lipids in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma metabolite correlations, which could identify robust disease biomarkers and potentially shed mechanistic insight. Here, gut microbiome changes were longitudinally profiled in ALS and correlated to plasma metabolome. Gut microbial structure at the phylum level differed in ALS versus control participants, with differential abundance of several distinct genera. Unsupervised clustering of microbe and metabolite levels identified modules, which differed significantly in ALS versus control participants. Network analysis found several prominent amplicon sequence variants strongly linked to a group of metabolites, primarily lipids. Similarly, identifying the features that contributed most to case versus control separation pinpointed several bacteria correlated to metabolites, predominantly lipids. Mendelian randomization indicated possible causality from specific lipids related to fatty acid and acylcarnitine metabolism. Overall, the results suggest ALS cases and controls differ in their gut microbiome, which correlates with plasma metabolites, particularly lipids, through specific genera. These findings have the potential to identify robust disease biomarkers and shed mechanistic insight into ALS.

Tumor-derived exosomal hyaluronidase 1 induced M2 macrophage polarization and promoted esophageal cancer progression.

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

In Situ Sodium Chloride Cross-Linked Fish Skin Collagen Scaffolds for Functional Hemostasis Materials.

Current fish collagen hemostasis for wound healing products is commonly obtained by electrospinning or artificial cross-linking fish collagen fibers which lacks mechanical properties, and biofunctions. Here, a new bio-active fish skin scaffold (FSS) is shown using in situ cross-linked scaleless freshwater fish skin adding adipose-derived stem cells (ASCs)-produced exosomes for hemostasis and wound healing. The structure, pore size, and the thickness of FSS is studied by swelling test, Fourier-transform infrared (FT-IR) spectra, scanning electron microscope (SEM) images, and histological analysis. The biofunctions of the FSS are also tested in vitro and in vivo. FSS keeps two functional layers: The dermis layer collagen forms a sponge like structure after swelling and in situ cross-linking treatments. The pore size of the FSS is ≈152 ± 23.54 µm, which is suitable for cells growing, angiogenesis and ASCs exosomes accelerate wound healing. The fat-rich epidermis layer can keep the wound moisty and clean before completely healed. In vitro and in vivo experimental results indicate that FSS+Exosomes enhances rat skin cavity wound healing. In situ sodium chloride cross-linked FSS+Exosomes provides a new strategy as functional hemostatic dressing scaffold for wound healing.

Polarization motivating high-performance weak targets' imaging based on a dual-discriminator GAN.

High-level detection of weak targets under bright light has always been an important yet challenging task. In this paper, a method of effectively fusing intensity and polarization information has been proposed to tackle this issue. Specifically, an attention-guided dual-discriminator generative adversarial network (GAN) has been designed for image fusion of these two sources, in which the fusion results can maintain rich background information in intensity images while significantly completing target information from polarization images. The framework consists of a generator and two discriminators, which retain the texture and salient information as much as possible from the source images. Furthermore, attention mechanism is introduced to focus on contextual semantic information and enhance long-term dependency. For preserving salient information, a suitable loss function has been introduced to constrain the pixel-level distribution between the result and the original image. Moreover, the real scene dataset of weak targets under bright light has been built and the effects of fusion between polarization and intensity information on different weak targets have been investigated and discussed. The results demonstrate that the proposed method outperforms other methods both in subjective evaluations and objective indexes, which prove the effectiveness of achieving accurate detection of weak targets in bright light background.

Dynamically manipulating long-wave infrared polarized thermal radiation by a vanadium dioxide metasurface.

Dynamically manipulating the spectra and polarization properties of thermal radiation is the key to counter an infrared polarization imaging system (IPIS) under the different background environments. In this Letter, we propose a phase-change metasurface thermal emitter (PCMTE) composed of vanadium dioxide (VO2) dipole antenna arrays to dynamically manipulate polarized radiation spectra in the long-wave infrared (LWIR) region of 8-14 µm. During the thermally induced and reversible insulator-to-metal transition (IMT) in VO2, by simulating the LWIR images at different polarization angles for the PCMTE and background plates, the PCMTE can realize dynamically tunable LWIR camouflage; then, their degree of linear polarization (DoLP) can be calculated, which can demonstrate that the PCMTE can also achieve dynamically tunable LWIR polarization camouflage at the specific radiation angles and backgrounds. Our proposed PCMTE provides an effective scheme for adaptive IR polarization camouflage.

Compact mode converters in thin-film lithium niobate integrated platforms.

Mode converters, crucial elements within photonic integrated circuits (PICs) designed for multimode optical transmission and switching systems, present a challenge due to their bulky structures in thin-film lithium niobate (TFLN) integrated platforms, which are incompatible with the compact and efficient nature desired for dense PICs. In this work, we propose TE1-TE0, TE2-TE0, and TE3-TE0 mode converters in shallowly etched TFLN, within small footprints. The experimental results show that the insertion loss is 0.4 dB, 0.6 dB, and 0.5 dB for the compact TE1-TE0, TE2-TE0, and TE3-TE0 mode converters, respectively, and these devices can be operated within a wide 1 dB bandwidth (BW) over 100 nm. This work facilitates the development of low-loss, broadband, and compact monolithically integrated photonic devices for future multimode communication networks in TFLN integrated platforms.

Quantum Light Generation Based on GaN Microring toward Fully On-Chip Source.

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

Pyridinethiolate-Capped CdSe Quantum Dots for Red-Light-Driven H2 Production in Water.

The utilization of low-energy sunlight to produce renewable fuels is a subject of great interest. Here we report the first example of metal chalcogenide quantum dots (QDs) capped with a pyridinethiolate carboxylic acid (pyS-COOH) for red-light-driven H2 production in water. The precious-metal-free system is robust over 240 h, and achieves a turnover number (TON) of 43910 ± 305 (vs Ni) with a rate of 31570 ± 1690 mmol g-1 h-1 for hydrogen production. In contrast to the inactive QDs capped with other thiolate ligands, the CdSe-pyS-COOH QDs give a significantly higher singlet oxygen quantum yield [ΦΔ (1O2)] in solution.

M2 macrophage-derived exosomes carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-ß1.

Radiotherapy is essential to cancer treatment, while it inevitably injures surrounding normal tissues, and bone tissue is one of the most common sites prone to irradiation. Bone marrow mesenchymal stem cells (BMMSCs) are sensitive to irradiation and the irradiated dysfunction of BMMSCs may be closely related to irradiation-induced bone damage. Macropahges play important role in regulating stem cell function, bone metabolic balance and irradiation response, but the effects of macrophages on irradiated BMMSCs are still unclear. This study aimed to investigate the role of macrophages and macrophage-derived exosomes in restoring irradiated BMMSCs function. The effects of macrophage conditioned medium (CM) and macrophage-derived exosomes on osteogenic and fibrogenic differentiation capacities of irradiated BMMSCs were detected. The key microribonucleic acids (miRNAs) and targeted proteins in exosomes were also determined. The results showed that irradiation significantly inhibited the proliferation of BMMSCs, and caused differentiation imbalance of BMMSCs, with decreased osteogenic differentiation and increased fibrogenic differentiation. M2 macrophage-derived exosomes (M2D-exos) inhibited the fibrogenic differentiation and promoted the osteogenic differentiation of irradiated BMMSCs. We identified that miR-142-3p was significantly overexpressed in M2D-exos and irradiated BMMSCs treated with M2D-exos. After inhibition of miR-142-3p in M2 macrophage, the effects of M2D-exos on irradiated BMMSCs differentiation were eliminated. Furthermore, transforming growth factor beta 1 (TGF-ß1), as a direct target of miR-142-3p, was significantly decreased in irradiated BMMSCs treated with M2D-exos. This study indicated that M2D-exos could carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-ß1. These findings pave a new way for promising and cell-free method to treat irradiation-induced bone damage.

Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

The Substitution of Rare-Earth Gd in BaScCuTe3 Realizing the Band Degeneracy and the Point-Defect Scattering toward Enhanced Thermoelectric Performance.

Zintl compounds have continuously received significant attention, primarily due to their structural characteristics that align with the properties of the electron crystal and phonon glass. In this study, the crystal structure and thermoelectric properties of the quaternary Zintl chalcogenide BaScCuTe3 are investigated. The band structure calculations for BaScCuTe3 reveal a slight energy split of 0.08 eV between the second valence band and the valence band maximum, suggesting the presence of multiband-transport behaviors. Substitution of rare earth Gd for Sc is conducted, which significantly increases the hole concentration from 4.1 × 1019 cm-3 to 8.2 × 1019 cm-3 at room temperature. Meanwhile, the Seebeck coefficient increases because of the participation of the second valence band. A maximum power factor of 6.56 µW/cm·K2 at 773 K is obtained, which is 72% higher than that of the pristine sample. Moreover, the lattice thermal conductivity decreases from 0.57 W/m·K for BaScCuTe3 to 0.48 W/m·K for BaSc0.97Gd0.03CuTe3 at 773 K, owing to the introduction of point-defect scattering. As a result, there is a noteworthy improvement in the thermoelectric figure of merit zT, increasing from 0.44 for the undoped sample to 0.85 for BaSc0.98Gd0.02CuTe3. Considering these findings, BaScCuTe3 exhibits great potential and holds promise for further investigation in the field of thermoelectric materials.

Thiocyanate promoted difunctionalization and cyclization of unsaturated C-C bonds to construct 1-sulfur-2-nitrogen-functionalized alkenes and 2-thiocyanate indolines.

An unprecedented one-pot route to achieve highly regioselective 1-sulfur-functionalized 2-nitrogen-functionalized alkenes and 2-thiocyanate indolines from unsymmetrical ynamides (readily and generally available amides) using the commercially available inexpensive iodobenzene diacetate (PIDA) as the oxidant and potassium thiocyanate (KSCN) as the thiocyanate (SCN) source has been developed. The interconversion of thiocyanate (SCN) and isothiocyanate (NCS) groups simultaneously forms C-N and C-S bonds in this metal-free approach, while introducing important functional groups into homemade alkynes. A radical-chain mechanism, involving competing kinetically controlled chain transfer at the S atom and sterically-controlled chain transfer at the N atom of the thiocyanogen molecule in this mild approach, is proposed.

Unusual immunosuppressive pyridine-containing bisnor- (c23), tetranor- (c21) and pentanor- (c20) sesterterpenoids from Tibetan Leucosceptrum canum.

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

Swieteliacates S-U, phragmalin limonoids, from the leaves of Swietenia macrophylla.

Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.