Cavomycins A-C, Linear Oligomer Depsipeptides from an Annelid-Associated Streptomyces cavourensis.

Three unique linear oligomeric depsipeptides, designated as cavomycins A-C (1-3), were identified from Streptomyces cavourensis, a gut bacterium associated with the annelid Paraleonnates uschakovi. The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including methanolysis, the modified Mosher's method, advanced Marfey's methods, and phenylglycine methyl ester derivatization. The unique dipeptidyl residue arrangements in compounds 1-3 indicate that they are not degradation products of valinomycin. Compound 2 and its methylation derivative 2a exhibited antiproliferative activity against PANC-1 pancreatic cancer cells with IC50 values of 1.2 and 1.7 µM, respectively.

Ulmus macrocarpa Hance trunk bark extracts inhibit RANKL-induced osteoclast differentiation and prevent ovariectomy-induced osteoporosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UmH) bark has been traditionally utilized for medicinal purposes. The bark extract of this plant has diverse health benefits, and its potential role in enhancing bone health is of distinct interest, particularly when considering the substantial health and economic implications of bone-related pathologies, such as osteoporosis. Despite the compelling theoretical implications of UmH bark in fortifying bone health, no definitive evidence at the in vivo level is currently available, thus highlighting the innovative and as-yet-unexplored potential of this field of study. AIM OF THE STUDY: Primarily, our study aims to conduct a meticulous analysis of the disparity in the concentration of active compounds in the UmH root bark (Umrb) and trunk bark (Umtb) extracts and confirm UmH bark's efficacy in enhancing bone health in vivo, illuminating the cellular mechanisms involved. MATERIALS AND METHODS: The Umrb and Umtb extracts were subjected to component analysis using high-performance liquid chromatography and then assessed for their inhibitory effects on osteoclast differentiation through the TRAP assay. An ovariectomized (OVX) mouse model replicates postmenopausal conditions commonly associated with osteoporosis. Micro-CT was used to analyze bone structure parameters, and enzyme-linked immunosorbent assay and staining were used to assess bone formation markers and osteoclast activity. Furthermore, this study investigated the impact of the extract on the expression of pivotal proteins and genes involved in bone formation and resorption using mouse bone marrow-derived macrophages (BMMs). RESULTS: The findings of our study reveal a significant discrepancy in the concentration of active constituents between Umrb and Umtb, establishing Umtb as a superior source for promoting bone health. I addition, a standardized pilot-scale procedure was conducted for credibility. The bone health benefits of Umtb were verified using an OVX model. This validation involved the assessment of various parameters, including BMD, BV/TV, and BS/TV, using micro-CT imaging. Additionally, the activation of osteoblasts was evaluated by Umtb by measuring specific factors such as ALP, OCN, OPG in blood samples and through IHC staining. In the same investigations, diminished levels of osteoclast differentiation factors, such as TRAP, NFATc1, were also observed. The observed patterns exhibited consistency in vitro BMM investigations. CONCLUSIONS: Through verification at both in vitro levels using BMMs and in vivo levels using the OVX-induced mouse model, our research demonstrates that Umtb is a more effective means of improving bone health in comparison to Umrb. These findings pave the way for developing health-functional foods or botanical drugs targeting osteoporosis and other bone-related disorders and enhance the prospects for future research extensions, including clinical studies, in extract applications.

Realizing a Superconducting Square-Lattice Bismuth Monolayer.

Interplay of crystal symmetry, strong spin-orbit coupling (SOC), and many-body interactions in low-dimensional materials provides a fertile ground for the discovery of unconventional electronic and magnetic properties and versatile functionalities. Two-dimensional (2D) allotropes of group 15 elements are appealing due to their structures and controllability over symmetries and topology under strong SOC. Here, we report the heteroepitaxial growth of a proximity-induced superconducting 2D square-lattice bismuth monolayer on superconducting Pb films. The square lattice of monolayer bismuth films in a C4 symmetry together with a stripey moiré structure is clearly resolved by our scanning tunneling microscopy, and its atomic structure is revealed by density functional theory (DFT) calculations. A Rashba-type spin-split Dirac band is predicted by DFT calculations to exist at the Fermi level and becomes superconducting through the proximity effect from the Pb substrate. We suggest the possibility of a topological superconducting state in this system with magnetic dopants/field. This work introduces an intriguing material platform with 2D Dirac bands, strong SOC, topological superconductivity, and the moiré superstructure.

Bioactive Piperazic Acid-Bearing Cyclodepsipeptides, Lydiamycins E-H, from an Endophytic Streptomyces sp. Associated with Cinnamomum cassia.

A chemical investigation of the endophytic Streptomyces sp. HBQ95, associated with the medicinal plant Cinnamomum cassia Presl, enabled the discovery of four new piperazic acid-bearing cyclodepsipeptides, lydiamycins E-H (1-4), and one known compound (lydiamycin A). Their chemical structures, including absolute configurations, were defined by a combination of spectroscopic analyses and multiple chemical manipulations. Lydiamycins F-H (2-4) and A (5) exhibited antimetastatic activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

(+)-Usnic acid and its salts, inhibitors of SARS-CoV-2, identified by using in silico methods and in vitro assay.

The pandemic caused by severe acute respiratory Coronavirus-2 (SARS-CoV-2) has been ongoing for over two years, and treatment for COVID-19, other than monoclonal antibodies, is urgently required. Accordingly, we have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database. Considering the calculated molecular properties and availability of the compounds, (+)-usnic acid was selected as a suitable hit. In the in vitro antiviral assay of (+)-usnic acid by the immunofluorescence method, IC50 was 7.99 µM, which is similar to that of remdesivir used as a positive control. The generalized Born and surface area continuum solvation (MM/GBSA) method was performed to find the potent target of (+)-usnic acid, and the Mpro protein showed the most prominent value, -52.05 kcal/mol, among other SARS-CoV-2 protein targets. Thereafter, RMSD and protein-ligand interactions were profiled using molecular dynamics (MD) simulations. Sodium usnate (NaU) improved in vitro assay results with an IC50 of 5.33 µM and a selectivity index (SI) of 9.38. Additionally, when (+)-usnic acid was assayed against SARS-CoV-2 variants, it showed enhanced efficacy toward beta variants with an IC50 of 2.92 µM and SI of 11.1. We report the in vitro anti-SARS-CoV-2 efficacy of (+)-usnic acid in this study and propose that it has the potential to be developed as a COVID-19 treatment if its in vivo efficacy has been confirmed.

Role of tyrosine autophosphorylation and methionine residues in BRI1 function in Arabidopsis thaliana.

BACKGROUND: Brassinosteroids (BRs), a group of plant growth hormones, control biomass accumulation and biotic and abiotic stress tolerance, and therefore are highly relevant to agriculture. BRs bind to the BR receptor protein, brassinosteroid insensitive 1 (BRI1), which is classified as a serine/threonine (Ser/Thr) protein kinase. Recently, we reported that BRI1 acts as a dual-specificity kinase both in vitro and in vivo by undergoing autophosphorylation at tyrosine (Tyr) residues. OBJECTIVE: In this study, we characterized the increased leaf growth and early flowering phenotypes of transgenic lines expressing the mutated recombinant protein, BRI1(Y831F)-Flag, compared with those expressing BRI1-Flag. BRI1(Y831F)-Flag transgenic plants showed a reduction in hypocotyl and petiole length compared with BRI1-Flag seedlings. Transcriptome analysis revealed differential expression of flowering time-associated genes (AP1, AP2, AG, FLC, and SMZ) between BRI1(Y831F)-Flag and BRI1-Flag transgenic seedlings. We also performed site-directed mutagenesis of the BRI1 gene, and investigated the effect of methionine (Met) substitution in the extracellular domain (ECD) of BRI1 on plant growth and BR sensitivity by evaluating hypocotyl elongation and root growth inhibition. METHODS: The pBIB-Hyg+-pBR-BRI1-Flag construct(Li et al. 2002) was used as the template for SDM with QuickChange XL Site Directed Mutagenesis Kit (Stratagene, La Jolla, CA, USA) to make the SDM mutants. After PCR with SDM kit, add 1 µl of Dpn1 to PCR reaction. Incubate at 37 °C for 2 h to digest parental DNA and then transformed into XL10-gold competent cells. Transcriptome analysis was carried out at the University of Illinois (Urbana-Champaign, Illinois, USA). RNA was prepared and hybridized to the Affymetrix GeneChip Arabidopsis ATH1 Genome Array using the Gene Chip Express Kit (Ambion, Austin, TX, USA). RESULTS: Tyrosine 831 autophosphorylation of BRI1 regulates Arabidopsis flowering time, and mutation of methionine residues in the extracellular domain of BRI1 affects hypocotyl and root length. BRI1(M656Q)-Flag, BRI1(M657Q)-Flag, and BRI1(M661Q)-Flag seedlings were insensitive to the BL treatment and showed no inhibition of root elongation. However, BRI1(M665Q)-Flag and BRI1(M671Q)-Flag seedlings were sensitive to the BL treatment, and exhibited root elongation inhibition. the early flowering phenotype of BRI1(Y831F)-Flag transgenic plants is consistent with the expression levels of key flowering-related genes, including those promoting flowering (AP1, AP2, and AG) and repressing flowering (FLC and SMZ).

Development of Dibenzothiazepine Derivatives as Multifunctional Compounds for Neuropathic Pain.

Neuropathic pain is a chronic and sometimes intractable condition caused by lesions or diseases of the somatosensory nervous system. Many drugs are available but unfortunately do not provide satisfactory effects in patients, producing limited analgesia and undesirable side effects. Thus, there is an urgent need to develop new pharmaceutical agents to treat neuropathic pain. To date, highly specific agents that modulate a single target, such as receptors or ion channels, never progress to the clinic, which may reflect the diverse etiologies of neuropathic pain seen in the human patient population. Therefore, the development of multifunctional compounds exhibiting two or more pharmacological activities is an attractive strategy for addressing unmet medical needs for the treatment of neuropathic pain. To develop novel multifunctional compounds, key pharmacophores of currently used clinical pain drugs, including pregabalin, fluoxetine and serotonin analogs, were hybridized to the side chain of tianeptine, which has been used as an antidepressant. The biological activities of the hybrid analogs were evaluated at the human transporters of neurotransmitters, including serotonin (hSERT), norepinephrine (hNET) and dopamine (hDAT), as well as mu (µ) and kappa (κ) opioid receptors. The most advanced hybrid of these multifunctional compounds, 17, exhibited multiple transporter inhibitory activities for the uptake of neurotransmitters with IC50 values of 70 nM, 154 nM and 2.01 µM at hSERT, hNET and hDAT, respectively. Additionally, compound 17 showed partial agonism (EC50 = 384 nM) at the µ-opioid receptor with no influence at the κ-opioid receptor. In in vivo pain animal experiments, the multifunctional compound 17 showed significantly reduced allodynia in a spinal nerve ligation (SNL) model by intrathecal administration, indicating that multitargeted strategies in single therapy could considerably benefit patients with multifactorial diseases, such as pain.

Flavonoid Glycosides from Ulmus macrocarpa Inhibit Osteoclast Differentiation via the Downregulation of NFATc1.

The aim of this study was to isolate and identify chemical components with osteoclast differentiation inhibitory activity from Ulmus macrocarpa Hance bark. Spectroscopic analyses, including nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD), resulted in the unequivocal elucidation of active compounds such as (2S)-naringenin-6-C-ß-d-glucopyranoside (1), (2R)-naringenin-6-C-ß-d-glucopyranoside (2), (2R,3S)-catechin-7-O-ß-d-xylopyranoside (3), (2R,3S)-catechin-7-O-ß-d-apiofuranoside (6), (2R,3R)-taxifolin-6-C-ß-d-glucopyranoside (7), and (2S,3S)-taxifolin-6-C-ß-d-glucopyranoside (8). Mechanistically, the compounds may exhibit osteoclast differentiation inhibitory activity via the downregulation of NFATc1, a master regulator involved in osteoclast formation. This is the first report of their inhibitory activities on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in murine bone marrow-derived macrophages. These findings provide further scientific evidence for the rational application of the genus Ulmus for the amelioration or treatment of osteopenic diseases.

Enhanced Berry Curvature Dipole and Persistent Spin Texture in the Bi(110) Monolayer.

Nonvanishing Berry curvature dipole (BCD) and persistent spin texture (PST) are intriguing physical manifestations of electronic states in noncentrosymmetric 2D materials. The former induces a nonlinear Hall conductivity while the latter offers a coherent spin current. Based on density-functional-theory (DFT) calculations, we demonstrate the coexistence of both phenomena in a Bi(110) monolayer with a distorted phosphorene structure. Both effects are concurrently enhanced due to the strong spin-orbit coupling of Bi while the structural distortion creates internal in-plane ferroelectricity with inversion asymmetry. We further succeed in fabricating a Bi(110) monolayer in the desired phosphorene structure on the NbSe2 substrate. Detailed atomic and electronic structures of the Bi(110)/NbSe2 heterostructure are characterized by scanning tunneling microscopy/spectroscopy and angle-resolved-photoemission spectroscopy. These results are consistent with DFT calculations which indicate the large BCD and PST are retained. Our results suggest the Bi(110)/NbSe2 heterostructure as a promising platform to exploit nonlinear Hall and coherent spin transport properties together.

Engineering Domain Wall Electronic States in Strongly Correlated van der Waals Material of 1T-TaS2.

Although a few physical methods were demonstrated for domain wall engineering in various electronic or ferroic materials with broken discrete symmetries, the direct control over the electronic properties of individual domain walls has been extremely limited. Here, we introduce a chemical method to tune the electronic property of domain walls in 1T tantalum disulfide. By using scanning tunneling microscopy and spectroscopy techniques, we find that indium adatoms on 1T-TaS2 have distinct behaviors on the domains with different bulk terminations. Moreover, the adatoms form their own chains along the edges of neighboring domains. The density functional theory calculations reveal a 1D Mott insulating state on a modified domain wall, resulting from the degenerated spin-polarized bands with electron doping from adsorbates and charge transfer from neighboring domains. This work suggests that chemical decoration by adsorbates can be widely used to tune local electronic states of domain walls and various 2D materials.

Phosphorylation of BIK1 is critical for interaction with downstream signaling components.

BACKGROUND: Botrytis-induced Kinase 1 (BIK1) is a receptor-like cytoplasmic kinase (RLCK) involved in the defense, growth, and development of higher plants. It interacts with various receptor-like kinases (RLKs) such as Brassinosteroid Insensitive 1 (BRI1), Flagellin Sensitive 2 (FLS2), and Perception of the Arabidopsis Danger Signal Peptide 1 (PEPR1), but little is known about signaling downstream of BIK1. OBJECTIVE: In this study, we aimed to identify Arabidopsis thaliana BIK1 (AtBIK1) and Brassica rapa BIK1 (BrBIK1) interacting proteins, which is downstream signaling components in Arabidopsis. In addition, the effect of BIK1 phosphorylation on their interaction were examined. METHODS: For yeast two hybrid (Y2H) screening, a B. rapa cDNA activation domain (AD) library and an A. thaliana cDNA library were used. Reverse reaction (LR) recombinations of appropriate open reading frames (AtBIK1, BrBIK1, AtRGP2, AtPATL2, AtPP7) in either pDONR207 or pDONR/zeo were performed with the split-YFP destination vectors pDEST-GWVYNE and pDEST-GWVYCE to generate N- or C-terminal fusions with the N- and C-terminal yellow fluorescent protein (YFP) moieties, respectively. Recombined vectors were transformed into Agrobacterium strain GV3101. The described GST-AtBIK1, Flag-AtBIK1, and Flag-BrBIK1 constructs were used as templates for site-directed mutagenesis with a QuikChange XL Site-Directed Mutagenesis Kit (Stratagene). RESULTS: In results, A. thaliana BIK1 (AtBIK1) displays strong autophosphorylation kinase activity on tyrosine and threonine residues, whereas B. rapa BIK1 (BrBIK1) does not exhibit autophosphorylation kinase activity in vitro. Herein, we demonstrated that four proteins (RGP2, PATL2, PP7, and SULTR4.1) interact with BrBIK1 but not AtBIK1 in a Y2H system. To confirm interactions between BIK1 and protein candidates in Nicotiana benthamiana, BiFC analysis was performed and it was found that only BrBIK1 bound the three proteins tested. Three phosphosites, T90, T362, and T368, based on amino acid sequence alignment between AtBIK1 and BrBIK1, and performed site-directed mutagenesis (SDM) on AtBIK1 and BrBIK. S90T, P362T, and A369T mutations in BrBIK1 restored autophosphorylation kinase activity on threonine residues comparable to AtBIK1. However, T90A, T362P, and T368A mutations in AtBIK1 did not alter autophosphorylation kinase activity on threonine residues compared with wild-type AtBIK1. BiFC results showed that BIK1 mutations restored kinase activity led to the loss of the binding activity to RGP2, PATL2, or PP7 proteins. CONCLUSION: Phospho-BIK1 might be involved in plant innate immunity, while non-phospho BIK1 may regulate plant growth and development through interactions with RGP2, PATL2, and PP7.

Austalide K from the Fungus Penicillium rudallense Prevents LPS-Induced Bone Loss in Mice by Inhibiting Osteoclast Differentiation and Promoting Osteoblast Differentiation.

Osteoporosis is a chronic disease that has become a serious public health problem due to the associated reduction in quality of life and its increasing financial burden. It is known that inhibiting osteoclast differentiation and promoting osteoblast formation prevents osteoporosis. As there is no drug with this dual activity without clinical side effects, new alternatives are needed. Here, we demonstrate that austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling. Austalide K inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and improves bone morphogenetic protein (BMP)-2-mediated osteoblast differentiation in vitro without cytotoxicity. The nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK) osteoclast-formation-related genes were reduced and alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) (osteoblast activation-related genes) were simultaneously upregulated by treatment with austalide K. Furthermore, austalide K showed good efficacy in an LPS-induced bone loss in vivo model. Bone volume, trabecular separation, trabecular thickness, and bone mineral density were recovered by austalide K. On the basis of these results, austalide K may lead to new drug treatments for bone diseases such as osteoporosis.

Tunable high-temperature itinerant antiferromagnetism in a van der Waals magnet.

Discovery of two dimensional (2D) magnets, showing intrinsic ferromagnetic (FM) or antiferromagnetic (AFM) orders, has accelerated development of novel 2D spintronics, in which all the key components are made of van der Waals (vdW) materials and their heterostructures. High-performing and energy-efficient spin functionalities have been proposed, often relying on current-driven manipulation and detection of the spin states. In this regard, metallic vdW magnets are expected to have several advantages over the widely-studied insulating counterparts, but have not been much explored due to the lack of suitable materials. Here, we report tunable itinerant ferro- and antiferromagnetism in Co-doped Fe4GeTe2 utilizing the vdW interlayer coupling, extremely sensitive to the material composition. This leads to high TN antiferromagnetism of TN ~ 226 K in a bulk and ~210 K in 8 nm-thick nanoflakes, together with tunable magnetic anisotropy. The resulting spin configurations and orientations are sensitively controlled by doping, magnetic field, and thickness, which are effectively read out by electrical conduction. These findings manifest strong merits of metallic vdW magnets as an active component of vdW spintronic applications.

Golden Gate Cloning-Compatible DNA Replicon/2A-Mediated Polycistronic Vectors for Plants.

The expression of multiple proteins and high-throughput vector assembly system are highly relevant in the field of plant genetic engineering and synthetic biology. Deployment of the self-cleaving 2A peptide that mediates polycistronic gene expression has been an effective strategy for multigene expression, as it minimizes issues in coordinated transgene regulation and trait staking in plants. However, efficient vector assembly systems optimized for 2A peptide-mediated polycistronic expression are currently unavailable. Furthermore, it is unclear whether protein expression levels are influenced by the transgene position in the polycistronic expression cassette. In this article, we present Golden Gate cloning-compatible modular systems allowing rapid and flexible construction of polycistronic expression vectors applicable for plants. The genetic modules comprised 2A peptides (T2A and P2A)-linked tricistron expression cassette and its acceptor backbones, named pGO-DV1 and pGO-DV2. While both acceptor backbones were binary T-DNA vectors, pGO-DV2 was specially designed to function as a DNA replicon enhancing gene expression levels. Using the Golden Gate cloning, a set of six tricistronic vectors was constructed, whereby three transgenes encoding fluorescent proteins (mCherry, eYFP, and eGFP) were combinatorially placed along the expression cassette in each of the binary vectors. Transient expression of the construct in tobacco leaves revealed that the expression levels of three fluorescent proteins were comparable each other regardless of the gene positions in the tricistronic expression cassette. pGO-DV2-based constructs were able to increase protein expression level by up to 71%, as compared to pGO-DV1-based constructs.

A New Thiopeptide Antibiotic, Micrococcin P3, from a Marine-Derived Strain of the Bacterium Bacillus stratosphericus.

A new thiopeptide (micrococcin P3, 1) and a known one (micrococcin P1, 2) were isolated from the culture broth of a marine-derived strain of Bacillus stratosphericus. The structures of both compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR analysis, high resolution mass spectrometry (HRMS), and tandem mass spectrometry. Both compounds exhibited potent antibacterial activities against Gram-positive strains with minimum inhibitory concentration (MIC) values of 0.05-0.8 µg/mL and did not show cytotoxicity in the MTT assay up to a concentration of 10 µM. This study adds a new promising member, micrococcin P3, to the family of thiopeptide antibiotics, which shows potential for the development of new antibiotics targeting Gram-positive bacteria.

Defect-Selective Charge-Density-Wave Condensation in 2H-NbSe_{2}.

Defects have been known to substantially affect quantum states of materials including charge density wave (CDW). However, the microscopic mechanism of the influence of defects is often elusive due partly to the lack of atomic scale characterization of defects themselves. We investigate native defects of a prototypical CDW material 2H-NbSe_{2} and their microscopic interaction with CDW. Three prevailing types of atomic scale defects are classified by scanning tunneling microscope, and their atomic structures are identified by density functional theory calculations as Se vacancies and Nb intercalants. Above the transition temperature, two distinct CDW structures are found to be induced selectively by different types of defects. This intriguing phenomenon is explained by competing CDW ground states and local lattice strain fields induced by defects, providing a clear microscopic mechanism of the defect-CDW interaction.

Benzophenone Compounds, from a Marine-Derived Strain of the Fungus Pestalotiopsis neglecta, Inhibit Proliferation of Pancreatic Cancer Cells by Targeting the MEK/ERK Pathway.

Pancreatic cancer, which has an extremely poor prognosis, is one of the most fatal human cancers. Chemotherapy is the main palliative treatment for advanced cancer patients and also plays an indispensable role in postoperative treatments for surgical patients. Therefore, there is an urgent need to develop more innovative anticancer drugs to fight against this fatal disease. Here, we investigate the potential of benzophenone derivatives, obtained from a marine-derived strain of the fungus Pestalotiopsis neglecta, as antiproliferative lead compounds for the treatment of pancreatic cancer. The compounds, seven new (1-7) and two known (8 and 9) halogenated benzophenone derivatives, were obtained by bioactivity-guided fractionation from the cultures of Pestalotiopsis neglecta. The structures were defined by spectroscopic methods including X-ray crystallographic analysis. Using the commonly used pancreatic cancer cell line PANC-1, 2 and 4 were found to suppress cell proliferation and induce apoptosis in the low micromolar range of 7.6 and 7.2 µM, respectively. Mechanistically, benzophenone derivatives not only inhibit MEK activity in the cytoplasm but also suppress ERK activity in the cytoplasm and nucleus. An in silico study suggests that benzophenone derivatives could potentially inhibit MEK activity by binding to the allosteric pocket in MEK. Benzophenones could serve as new lead compounds for the treatment of pancreatic cancer.

Austalides, Osteoclast Differentiation Inhibitors from a Marine-Derived Strain of the Fungus Penicillium rudallense.

Four new meroterpenoids, austalides V-X (1-3) and a farnesylated phthalide derivative (4), were isolated from the culture of the marine fungus Penicillium rudallense, together with eight known meroterpenoids derivatives (5-12). Their structures, including absolute configurations, were determined by spectroscopic methods. All of the isolated compounds were evaluated for their inhibitory activities on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation. Compounds 1, 2, 5-7, and 10 exhibited potent osteoclast differentiation inhibitory activity with ED50 values of 1.9-2.8 µM.

Topological Landscape of Competing Charge Density Waves in 2H-NbSe_{2}.

Despite decades of studies of the charge density wave (CDW) of 2H-NbSe_{2}, the origin of its incommensurate CDW ground state has not been understood. We discover that the CDW of 2H-NbSe_{2} is composed of two different, energetically competing, structures. The lateral heterostructures of two CDWs are entangled as topological excitations, which give rise to a CDW phase shift and the incommensuration without a conventional domain wall. A partially melted network of topological excitations and their vertices explain an unusual landscape of domains. The unconventional topological role of competing phases disclosed here can be widely applied to various incommensuration or phase coexistence phenomena in materials.