Confined Cu Single Sites in ZSM-5 for Photocatalytic Hydroxylation of Benzene to Phenol.

Zeolites with band-like charge transport properties have exhibited their potential activities in sensing, optics, and electronics. Herein, a precisely designed Cu@ZSM-5 catalyst is presented with an ultra-wide bandgap of 4.27 eV, showing excellent photocatalytic activity in hydroxylation of benzene with benzene conversion 27.9% and phenol selectivity 97.6%. The SXRD and Rietveld refinement results illustrate that Cu@ZSM-5 has an average of 0.8 Cu atoms per unit cell and the single Cu atoms located in the cross-section of the sinusoidal and straight channels. XANES and EXAFS further demonstrate that the Cu atoms have an oxidation state of +2, coordinated with three OMFI-framework atoms and one ─OH group. Detailed characterizations demonstrate that the Cu@ZSM-5 with tailored bandgap is able to enhance the photoinduced electron-hole separation and hence promote selective hydroxylation of benzene to phenol via the superoxide radical route. This work may open a new way for designing electrically conductive zeolite-supported photocatalysts.

AKAP95 regulates ubiquitination and degradation of cyclin Ds/Es, influencing the G1/S transition of lung cancer cells.

A-kinase anchoring protein 95 (AKAP95) functions as a scaffold for protein kinase A. Prior work by our group has shown that AKAP95, in coordination with Connexin 43 (Cx43), modulates the expression of cyclin D and E proteins, thus affecting the cell cycle progression in lung cancer cells. In the current study, we confirmed that AKAP95 forms a complex with Cx43. Moreover, it associates with cyclins D1 and E1 during the G1 phase, leading to the formation of protein complexes that subsequently translocate to the nucleus. These findings indicate that AKAP95 might facilitate the nuclear transport of cyclins D1 and E1. Throughout this process, AKAP95 and Cx43 collectively regulate the expression of cyclin D, phosphorylate cyclin E1 proteins, and target their specific ubiquitin ligases, ultimately impacting cell cycle progression.

LDHA deficiency inhibits trophoblast proliferation via the PI3K/AKT/FOXO1/CyclinD1 signaling pathway in unexplained recurrent spontaneous abortion.

Dysregulated trophoblast proliferation, invasion, and apoptosis may cause several pregnancy-associated complications, such as unexplained recurrent spontaneous abortion (URSA). Recent studies have shown that metabolic abnormalities, including glycolysis inhibition, may dysregulate trophoblast function, leading to URSA. However, the underlying mechanisms remain unclear. Herein, we found that lactate dehydrogenase A (LDHA), a key enzyme in glycolysis, was significantly reduced in the placental villus of URSA patients. The human trophoblast cell line HTR-8/SVneo was used to investigate the possible LDHA-mediated regulation of trophoblast function. LDHA knockdown in HTR-8/SVneo cells induced G0/G1 phase arrest and increased apoptosis, whereas LDHA overexpression reversed these effects. Next, RNA sequencing combined with Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the PI3K/AKT signaling pathway is potentially affected by downstream genes of LDHA. Especially, we found that LDHA knockdown decreased the phosphorylation levels of PI3K, AKT, and FOXO1, resulting in a significant downregulation of CyclinD1. In addition, treatment with an AKT inhibitor or FOXO1 inhibitor also verified that the PI3K/AKT/FOXO1 signaling pathway influenced the gene expression of CyclinD1 in trophoblast. Moreover, p-AKT expression correlated positively with LDHA expression in syncytiotrophoblasts and extravillous trophoblasts in first-trimester villus. Collectively, this study revealed a new regulatory pathway for LDHA/PI3K/AKT/FOXO1/CyclinD1 in the trophoblast cell cycle and proliferation.

Bafi A1 inhibits nano-copper oxide-induced mitochondrial damage by reducing the release of copper from lysosomes.

This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.

A Surface-Enhanced Raman Scattering Substrate with Tunable Localized Surface Plasmon Resonance Absorption Based on AgNPs.

In this paper, a three-layer structure of silver particle (AgNP)-dielectric-metal is proposed and constructed based on the characteristics of AgNPs that can excite LSPR (Localized Surface Plasmon Resonance) in free space. In order to overcome the problem of AgNPs easily oxidizing in the air, this paper synthesizes AgNPs using the improved Tollens method and effectively suppresses the coffee-ring effect by changing the solution evaporation conditions, so that the distribution of AgNPs in the deposition area is relatively uniform. The structure proposed in this paper takes advantage of the flexibility of nanoparticle application. The AgNPs deposited on the dielectric layer can effectively localize energy and regulate the LSPR of the device well. The structure can not only achieve precise regulation of the LSPR resonance peak of AgNPs but also can be used as a SERS substrate.

Hydrogel Capacitors Based on MoS2 Nanosheets and Applications in Glucose Monitoring.

Non-invasive/minimally invasive continuous monitoring of blood glucose and blood glucose administration have a high impact on chronic disease management in diabetic patients, but the existing technology is yet to achieve the above two purposes at the same time. Therefore, this study proposes a microfluidic microneedle patch based on 3D printing technology and an integrated control system design for blood glucose measurement, and a drug delivery control circuit based on a 555 chip. The proposed method provides an improved preparation of a PVA-PEG-MoS2 nanosheet hydrogel, making use of its dielectric properties to fabricate a microcapacitor and then embedding it in a microfluidic chip. When MoS2 nanosheets react with interstitial liquid glucose (and during the calibration process), the permittivity of the hydrogel is changed, resulting in changes in the capacitance of the capacitor. By converting the capacitance change into the square-wave period change in the output of the 555 chip with the control circuit design accordingly, the minimally invasive continuous measurement of blood glucose and the controlled release of hypoglycemic drugs are realized. In this study, the cross-linking structure of MoS2 nanosheets in hydrogel was examined using infrared spectroscopy and scanning electron microscopy (SEM) methods. Moreover, the critical doping mass fraction of MoS2 nanosheets was determined to be 2% via the measurement of the dielectric constant. Meanwhile, the circuit design and the relationship between the pulse cycle and glucose concentration is validated. The results show that, compared with capacitors in series, the microcapacitors embedded in microfluidic channels can be connected in parallel to obtain better linearized blood glucose measurement results.

HDAC3 controls male fertility through enzyme-independent transcriptional regulation at the meiotic exit of spermatogenesis.

The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis.

Detection of polycyclic aromatic hydrocarbons using a high performance-single particle aerosol mass spectrometer.

The real-time detection of the mixing states of polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs in ambient particles is of great significance for analyzing the source, aging process, and health effects of PAHs and nitro-PAHs; yet there is still few effective technology to achieve this type of detection. In this study, 11 types of PAH and nitro-PAH standard samples were analyzed using a high performance-single particle aerosol mass spectrometer (HP-SPAMS) in lab studies. The identification principles 'parent ions' and 'mass-to-charge (m/z) = 77' of each compound were obtained in this study. It was found that different laser energies did not affect the identification of the parent ions. The comparative experiments of ambient atmospheric particles, cooking and biomass burning emitted particles with and without the addition of PAHs were conducted and ruled out the interferences from primary and secondary organics on the identification of PAHs. Besides, the reliability of the characteristic ions extraction method was evaluated through the comparative study of similarity algorithm and deep learning algorithm. In addition, the real PAH-containing particles from vehicle exhaust emissions and ambient particles were also analyzed. This study improves the ability of single particle mass spectrometry technology to detect PAHs and nitro-PAHs, and HP-SPAMS was superior to SPAMS for detecting single particles containing PAHs and nitro-PAHs. This study provides support for subsequent ambient observations to identify the characteristic spectrum of single particles containing PAHs and nitro-PAHs.

Genetic characterization of a missense mutation in the X-linked TAF7L gene identified in an oligozoospermic man†.

Although hundreds of knockout mice show infertility as a major phenotype, the causative genic mutations of male infertility in humans remain rather limited. Here, we report the identification of a missense mutation (D136G) in the X-linked TAF7L gene as a potential cause of oligozoospermia in men. The human aspartate (D136) is evolutionally conserved across species, and its change to glycine (G) is predicted to be detrimental. Genetic complementation experiments in budding yeast demonstrate that the conserved aspartate or its analogous asparagine (N) residue in yeast TAF7 is essential for cell viability and thus its mutation to G is lethal. Although the corresponding D144G substitution in the mouse Taf7l gene does not affect male fertility, RNA-seq analyses reveal alterations in transcriptomic profiles in the Taf7l (D144G) mutant testes. These results support TAF7L mutation as a risk factor for oligozoospermia in humans.

Progress in Chemical Recycling of Carbon Fiber Reinforced Epoxy Composites.

Carbon fiber reinforced polymer (CFRP) composites are indispensable in a variety of applications, because of their high specific strength. CFRPs are generally constructed by carbon fibers as reinforcements and crosslinked polymers as binders. Due to the irreversible nature of the crosslinked polymers, CFRPs are neither repairable nor recyclable. Once the material is damaged or out of service, landfill or incineration is the typical way to deal with the waste. These methods take no advantages of the residue value of the waste and add burdens to the environment. To reduce waste and cost, it is desirable to develop effective recycling technologies to reserve the residue value of carbon fiber and polymer matrix. In the past decade, chemical recycling by cleaving the covalent bonds in a solvent has been considered as an ideal path for the recycling of CFRP wastes, because it has the potential to recover both valuable CFs and polymer matrix. In this review, the discussion is focused on the progress in the chemical recycling of CFRP. The primary matrix resin of CFRP discussed in this review is epoxy resin which is the most widely used polymer matrix. In addition, the challenges and outlook are provided.

Sox30 initiates transcription of haploid genes during late meiosis and spermiogenesis in mouse testes.

Transcription factors of the Sox protein family contain a DNA-binding HMG box and are key regulators of progenitor cell fate. Here, we report that expression of Sox30 is restricted to meiotic spermatocytes and postmeiotic haploids. Sox30 mutant males are sterile owing to spermiogenic arrest at the early round spermatid stage. Specifically, in the absence of Sox30, proacrosomic vesicles fail to form a single acrosomal organelle, and spermatids arrest at step 2-3. Although most Sox30 mutant spermatocytes progress through meiosis, accumulation of diplotene spermatocytes indicates a delayed or impaired transition from meiotic to postmeiotic stages. Transcriptome analysis of isolated stage-specific spermatogenic cells reveals that Sox30 controls a core postmeiotic gene expression program that initiates as early as the late meiotic cell stage. ChIP-seq analysis shows that Sox30 binds to specific DNA sequences in mouse testes, and its genomic occupancy correlates positively with expression of many postmeiotic genes including Tnp1, Hils1, Ccdc54 and Tsks These results define Sox30 as a crucial transcription factor that controls the transition from a late meiotic to a postmeiotic gene expression program and subsequent round spermatid development.

Systematic review regulatory principles of non-coding RNAs in cardiovascular diseases.

Cardiovascular diseases (CVDs) continue to be a major cause of morbidity and mortality, and non-coding RNAs (ncRNAs) play critical roles in CVDs. With the recent emergence of high-throughput technologies, including small RNA sequencing, investigations of CVDs have been transformed from candidate-based studies into genome-wide undertakings, and a number of ncRNAs in CVDs were discovered in various studies. A comprehensive review of these ncRNAs would be highly valuable for researchers to get a complete picture of the ncRNAs in CVD. To address these knowledge gaps and clinical needs, in this review, we first discussed dysregulated ncRNAs and their critical roles in cardiovascular development and related diseases. Moreover, we reviewed >28 561 published papers and documented the ncRNA-CVD association benchmarking data sets to summarize the principles of ncRNA regulation in CVDs. This data set included 13 249 curated relationships between 9503 ncRNAs and 139 CVDs in 12 species. Based on this comprehensive resource, we summarized the regulatory principles of dysregulated ncRNAs in CVDs, including the complex associations between ncRNA and CVDs, tissue specificity and ncRNA synergistic regulation. The highlighted principles are that CVD microRNAs (miRNAs) are highly expressed in heart tissue and that they play central roles in miRNA-miRNA functional synergistic network. In addition, CVD-related miRNAs are close to one another in the functional network, indicating the modular characteristic features of CVD miRNAs. We believe that the regulatory principles summarized here will further contribute to our understanding of ncRNA function and dysregulation mechanisms in CVDs.

Carbon Fiber Reinforced Epoxy Vitrimer: Robust Mechanical Performance and Facile Hydrothermal Decomposition in Pure Water.

Conventional carbon fiber reinforced thermosetting polymers (CFRPs) are neither recyclable nor repairable due to their crosslinked network. The rapid growing CFRP market raises a serious concern of the waste management. In this work, a viable method to develop a readily recyclable CFRP based on epoxy vitrimer is introduced. First, a self-catalytic epoxy prepolymer with built-in hydroxy and tertiary amine groups is designed, which upon reaction with an anhydride formed a catalyst-free epoxy vitrimer. The epoxy prepolymer is synthesized from a diamine and an excess of bisphenol A epoxy resin. The hydroxyls and tertiary amines of the epoxy prepolymer efficiently catalyze both curing and the dynamic transesterification of the crosslinked polymer without the need of a catalyst. Then, the epoxy vitrimer is used as the matrix resin to prepare CFRP. The resulting CFRP exhibited a tensile strength as high as 356 MPa. More interestingly, the matrix of the CFRP is efficiently degraded in pure water at above 160 °C. This is because the built-in tertiary amines catalyze the hydrolysis of the ester bonds of the crosslinked network. The simple method developed in this work provides a framework for the development of recyclable CFRP.

Structure, Distribution, Chemical Composition, and Gene Expression Pattern of Glandular Trichomes on the Leaves of Rhus potaninii Maxim.

Rhus potaninii Maxim is an economically and medicinally important tree species in China. It produces galls (induced by aphids) with a high abundance of tannins. Here, we discuss the histology, cellular structures and their distribution, and the macromolecular components of secretive glandular trichomes on the leaves of R. potaninii. A variation in the density of glandular trichomes and tomenta was found between the adaxial and abaxial sides of a leaf in different regions and stages of the leaf. The glandular trichomes on R. potaninii trees comprise a stalk with no cellular structure and a head with 8-15 cells. Based on staining, we found that the secretion of glandular trichomes has many polysaccharides, phenolic compounds, and acidic lipids but very few neutral lipids. The dense glandular trichomes provide mechanical protection for young tissues; additionally, their secretion protects the young tissues from pathogens by a special chemical component. According to transcriptome analysis, we found enhanced biosynthetic and metabolism pathways of glycan, lipids, toxic amino acids, and phenylpropanoids. This shows a similar tendency to the staining. The numbers of differentially expressed genes were large or small; the averaged range of upregulated genes was greater than that of the downregulated genes in most subpathways. Some selectively expressed genes were found in glandular trichomes, responsible for the chitinase activity and pathogenesis-related proteins, which all have antibacterial activity and serve for plant defense. To our knowledge, this is the first study showing the components of the secretion from glandular trichomes on the leaf surface of R. potaninii.

Combinatorial epigenetic regulation of non-coding RNAs has profound effects on oncogenic pathways in breast cancer subtypes.

Although systematic genomic studies have identified a broad spectrum of non-coding RNAs (ncRNAs) that are involved in breast cancer, our understanding of the epigenetic dysregulation of those ncRNAs remains limited. Here, we systematically analysed the epigenetic alterations of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in two breast cancer subtypes (luminal and basal). Widespread epigenetic alterations of miRNAs and lncRNAs were observed in both cancer subtypes. In contrast to protein-coding genes, the majority of epigenetically dysregulated ncRNAs were shared between subtypes, but a subset of transcriptomic and corresponding epigenetic changes occurred in a subtype-specific manner. In addition, our findings suggested that various types of epi-modifications might synergistically modulate ncRNA transcription. Our observations further highlighted the complementary dysregulation of epi-modifications, particularly of miRNA members within the same family, which produced the same directed alterations as a result of diverse epi-modifications. Functional enrichment analysis revealed that epigenetically dysregulated ncRNAs were significantly involved in several hallmarks of cancers. Finally, our analysis of epigenetic modification-mediated miRNA regulatory networks revealed that cancer progression was associated with specific miRNA-gene modules in two subtypes. This study enhances understanding of the aberrant epigenetic patterns of ncRNA expression and provides new insights into the functions of ncRNAs in breast cancer subtypes.

Glycerol Induced Catalyst-Free Curing of Epoxy and Vitrimer Preparation.

Epoxy vitrimers prepared from anhydride-cured epoxies exhibit, repairable and reprocessable properties; however, they generally rely on a large amount of catalyst for accelerating the dynamic transesterification (DTER). If the catalyst loading is not enough, the vitrimer properties will be limited. In this work, a preparation method of catalyst-free epoxy vitrimer is demonstrated by adding glycerol to an epoxy-anhydride curing system. The hydroxyls of glycerol first react with the anhydride to induce the ring-opening of anhydride and form a carboxylic acid, and the latter attacks the epoxy and form a ß-hydroxyester linkage, so the curing can be performed in the absence of catalyst. A significant amount of hydroxy groups are preserved in the crosslinked network, and they serve as both reacting moiety and catalyst for the DTER, which imparts fast relaxation and satisfactory repairability to the materials. By taking advantage of this mechanism, a catalyst-free and self-healing coating is demonstrated. These findings provide a solution to avoid using catalyst in vitrimer preparation and advance the application of vitrimer in coating. However, the addition of glycerol produces a decrease of the T g of the final materials, which needs to be further addressed in the future study.

Antimicrobial Dolabellanes and Atranones from a Marine-Derived Strain of the Toxigenic Fungus Stachybotrys chartarum.

Three new dolabellane-type diterpenoids (1-3) and three new atranones (4-6) were isolated and identified from a marine-derived strain of the toxigenic fungus Stachybotrys chartarum. The planar and relative structures of 1-6 were elucidated using extensive spectroscopic methods, and their absolute configurations were fully confirmed via single-crystal X-ray diffraction analysis. Structurally, compounds 2 and 3 have a 1,14-seco dolabellane-type diterpenoid skeleton; compound 4 is the first C23 atranone featuring a propan-2-one motif linked to a dolabellane-type diterpenoid by a carbon-carbon bond; compound 5 represents the first example of a C24 atranone with a 2-methyltetrahydrofuran-3-carboxylate motif fused to a dolabellane-type diterpenoid at C-5-C-6. In an in vitro antimicrobial activity assay, compound 2 was active against Acinetobacter baumannii and Enterococcus faecalis with MIC values of 16 and 32 µg/mL, respectively, while compound 4 exhibited significant inhibitory activities against Candida albicans, Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 8, 16, and 32 µg/mL, respectively.

Antibacterial activity against drug-resistant microbial pathogens of cytochalasan alkaloids from the arthropod-associated fungus Chaetomium globosum TW1-1.

By feeding 1-methyl-l-tryptophan (1-MT) into cultures of the arthropod-associated fungus Chaetomium globosum TW1-1, three novel cytochalasan alkaloids, termed as armochaetoglosins A-C (1-3), together with five known analogues, namely prochaetoglobosin I (4), chaetoglobosin T (5), chaetoglobosin C (6), armochaetoglobin Y (7), and chaetoglobosin Vb (8), were isolated and characterized. Their structures including absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of the experimental electronic circular dichroism (ECD) spectra. Structurally, compounds 1-3 represented the first examples of 1'-N-methyl-chaetoglobosins, which were possibly biosynthesized from the additive 1-MT rather than tryptophan. Additionally, compound 3 showed the highest antibacterial activity against K. pneumoniae and ESBL-E. coli with MIC values of 4.0 µg/mL and 16.0 µg/mL, respectively, wherein the inhibitory effect of 3 against K. pneumoniae was stronger than that of the clinically used antibiotic meropenem, with an MIC value of 8 µg/mL. Our findings may provide new chemical templates for the development of new antibacterial agents against drug-resistant microbial pathogens.

Comparative QTL analysis for yield components and morphological traits in maize (Zea mays L.) under water-stressed and well-watered conditions.

Drought significantly influences maize morphology and yield potential. The elucidation of the genetic mechanisms of yield components and morphological traits, and tightly linked molecular markers under drought stress are thus of great importance in marker assisted selection (MAS) breeding. Here, we identified 32 QTLs for grain weight per ear, kernel ratio, and ear height-to-plant height ratio across two F2:3 populations under both drought and non-drought conditions by single-environment mapping with composite interval mapping (CIM), of which 21 QTLs were mapped under water-stressed conditions. We identified 29 QTLs by joint analysis of all environments with mixed-linear-model-based composite interval mapping (MCIM), 14 QTLs involved in QTL-by-environment interactions, and 11 epistatic interactions. Further analysis simultaneously identified 20 stable QTLs (sQTLs) by CIM and MCIM could be useful for genetic improvement of these traits via QTL pyramiding. Remarkably, bin 1.07-1.10/6.05/8.03/8.06 exhibited four pleiotropic sQTLs that were consistent with phenotypic correlations among traits, supporting the pleiotropy of QTLs and playing important roles in conferring growth and yield advantages under contrasting watering conditions. These findings provide information on the genetic mechanisms responsible for yield components and morphological traits that are affected by different watering conditions. Furthermore, these alleles provide useful targets for MAS.

New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus.

Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 µM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 µM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.