Three new phenols and one new lignan from Clematis terniflora var. manshurica (Rupr.) Ohwi with their anti-inflammatory activity.

Three undescribed phenols, mandshusica C-E (1-3) and a new lignan, mandshusica F (5), along with six known compounds (4, 6-10) were isolated from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi. Their structures were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. Moreover, the possible biosynthetic pathways of compounds 1-3 were also discussed. All compounds were evaluated for their anti-inflammatory activities in LPS-induced RAW 264.7 cells. Compounds 1, 3, 4 significantly reduced the levels of NO and TNF-α, while compounds 2 and 8 significantly inhibited NO production in LPS-induced RAW264.7 cells.

Suberitolactams A-D and Suberitopyridines A-B: New γ-lactam and Pyridine Alkaloids Isolated from the South China Sea Sponge Pseudospongosorites suberitoides.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC50 values of 27.6 and 13.3 µM, respectively.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Melt-quenched glass formation of a family of metal-carboxylate frameworks.

Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.

The effect of air on oxidation decomposition of uranium-containing cationic exchange resins in Li2CO3-Na2CO3-K2CO3 molten-salt system.

With the development of nuclear energy, spent cationic exchange resins after purification of radioactive wastewater must be treated. Molten-salt oxidation (MSO) can minimize the disposal content of resins and capture SO2. In this work, the decomposition of uranium-containing resins in carbonate molten salt in N2 and air atmospheres was investigated. Compared to N2 atmosphere, the content of SO2 released from the decomposition of resins was relatively low at 386-454 °C in an air atmosphere. The SEM morphology indicated that the presence of air facilitated the decomposition of the resin cross-linked structure. The decomposition efficiency of resins in an air atmosphere was 82.6% at 800 °C. The XRD analysis revealed that uranium compounds had the reaction paths of UO3 → UO2.92 → U3O8 and UO3 → K2U2O7 → K2UO4 in the carbonate melt, and sulfur elements in resins were fixed in the form of K3Na(SO4)2. The XPS result illustrated that peroxide and superoxide ions accelerated the conversion of sulfone sulfur to thiophene sulfur and further oxidized to CO2 and SO2. Besides, the ion bond formed by uranyl ions on the sulfonic acid group was decomposed at high temperature. Finally, the decomposition of uranium-containing resins in the carbonate melt in an air atmosphere was explained. This study provided more theoretical guidance and technical support for the industrial treatment of uranium-containing resins.

Anticancer mechanisms on pyroptosis induced by Oridonin: New potential targeted therapeutic strategies.

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.

Controlled Synthesis, Chiral Assembly, and Circularly Polarized Luminescence of Poly(Phenyl Isocyanide)-Block-Polyfluorene Copolymers.

In this work, π-conjugated block copolymers consisting of poly(phenyl isocyanide) (PPI) and polyfluorene (PF) segments are facilely prepared by one-pot sequential polymerization of phenyl isocyanide (monomer 1) and 7-bromo-9,9-dioctylfluorene-2-boronic acid pinacol ester (monomer 2). The Pd(II)-terminated PPI is first prepared via polymerizing monomer 1 catalyzed with phenyl alkyne-Pd(II) complex and then utilized to initiate the controlled Suzuki cross-coupling polymerization of monomer 2, yielding various PPI-b-PF copolymers possessing controlled molar mass and narrow dispersity. Owing to the helical conformation of PPI segment and π-conjugated structure of PF segment, PPI-b-PF copolymers present distinctive optical property and fascinating chiral self-assembly behavior. During the self-assembly process, chirality transfer from helical PPI block to the supramolecular aggregates of helical nanofibers occurs to afford optically active helical nanofibers with high optical activity. Furthermore, the self-assembled helical nanofibers exhibit excellent circularly polarized luminescence performance.

Effect of copper ions on transformation of organic sulfur in cationic exchange resins in Li2CO3-Na2CO3-K2CO3 molten-salt system.

Cationic exchange resins (CERs) were applied for purification and clarifying process of radioactive wastewater in nuclear industry, which was a kind of sulfur-containing organic material. Molten-salt oxidation (MSO) method can be applied for the treatment of spent CERs and the absorption of acid gas (such as SO2). The experiments about the molten salt destruction of the original resin and Cu ions doped resin were conducted. The transformation of organic sulfur in Cu ions doped resin was investigated. Compared with the original resin, the content of tail gas (such as CH4, C2H4, H2S and SO2) released from the decomposition of Cu ions doped resin was relatively high at 323-657 °C. Sulfur elements in the form of sulfates and copper sulfides were fixed in spent salt through XRD analysis. The XPS result revealed that the portion of functional sulfonic acid groups (-SO3H) in Cu ions doped resin was converted into sulfonyl bridges (-SO2-) at 325 °C. With the enhancement of temperature, sulfonyl bridges (-SO2-) were further decomposed to sulfoxides sulfur (-SO-) and organic sulfide sulfur. The destruction of thiophenic sulfur to H2S and CH4 was prompted by copper ions in copper sulfide. Sulfoxide were oxidized to the sulfone sulfur in molten salt. Sulfones sulfur consumed by reduction of Cu ions at 720 °C was more than it produced by oxidation of sulfoxide through XPS analysis, and the relative proportion of sulfone sulfur was 16.51%.

[Research Progress on the Application of Goel Technique in Craniovertebral Junction Anomalies].

Craniovertebral junction anomalies are a group of diseases characterized by the pathological changes of occipital bone,atlantoaxial bone,cerebellar tonsil,surrounding soft tissue,and nervous system,which are caused by a variety of factors.Chiari malformation is a common type of craniovertebral junction anomalies,the conventional surgical therapy of which is posterior fossa decompression.Currently,scholars represented by Goel have proposed a new theory on the classification,pathogenesis,and treatment of Chiari malformation based on posterior atlantoaxial fixation (Goel technique).This article introduces the progress in Goel technique,aiming to provide reference for the clinical work.

Sinudenoids A-E, C19-Norcembranoid Diterpenes with Unusual Scaffolds from the Soft Coral Sinularia densa.

Five new furanobutenolide-derived C19-norcembranoid diterpenes, sinudenoids A-E (1-5, respectively), were isolated from the soft coral Sinularia densa. Sinudenoid A (1) possesses an uncommon 5/5/11-fused tricyclic ring system. Sinudenoids B-D (2-4, respectively) share the same tetracyclic 5/5/6/6 ring system but represent two kinds of new skeletons. Sinudenoid E (5) is the second compound with the rare 8/8 bicyclic carbon core. A plausible biosynthesis pathway for compounds 1-6 is proposed. Compound 5 exhibits strong anti-inflammatory activity in the zebrafish model.

[Recurrence Rate and Risk Factors of Atypical Meningioma:a Meta-analysis].

Objective To systematically review the overall status of postoperative recurrence in patients with atypical meningiomas. Methods China National Knowledge Infrastructure,Wanfang Database,Chinese Biomedical Literature Database,VIP Database,PubMed,Embase,Web of Science,and Cochrane Library were searched for collection of the relevant literature on the recurrence of atypical meningioma from database establishment to July 2021.Two investigators independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and then performed a meta-analysis by using R 5.0. Results A total of 29 studies involving 3122 patients were included in this study.The meta-analysis showed that the overall postoperative recurrence rate of atypical meningioma was 38%.The subgroup analysis showed that the tumor recurrence rate of patients ≥60 years old and<60 years old was 51% and 40%,respectively,with no significant difference.The tumor recurrence rates in male and female patients were 42% and 44%,respectively,which showed no significant difference.The recurrence rates of the patients with parasagittal meningiomas,brain tissue infiltration,Ki-67>8%,mitotic count ≥6/10 high-power fields,and tissue necrosis were 52%,47%,63%,53%,and 69%,respectively.The recurrence rate after subtotal tumor resection was as high as 58%,and the patients who received radiotherapy had higher tumor recurrence rate than that those who did not receive radiotherapy (38% vs.29%,P=0.007). Conclusions The current evidence demonstrates that atypical meningioma has a high recurrence rate after surgery.It is essential to pay more attention and take corresponding measures to improve the tumor-free survival rate of the patients.

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea.

Four new polyhydroxylated steroids lobophysterols E-H (1-4), together with three known compounds (5-7), were isolated from the soft coral Lobophytum pauciflorum collected at Xisha Island, China. The structures of the new compounds were elucidated by extensive spectroscopic analysis and comparison with NMR data of structurally related compounds reported in the literature. The absolute configuration of 1-3 was determined by X-ray diffraction. All the compounds have assessed the cytotoxicity against HL-60, K562, and Hela cells. Compound 1 showed weak cytotoxicity against K562 cells with an IC50 value of 19.03 µM. In addition, compound 1 also showed a moderate anti-inflammatory effect in zebrafish.

Secondary metabolites from marine sponges of the genus Agelas: a comprehensive update insight on structural diversity and bioactivity.

As one of the most common marine sponges in tropical and subtropical oceans, the sponges of the genus Agelas, have emerged as unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities. The present review highlights the chemical structure and biological activity of 355 compounds that have been isolated and characterized from the members of Agelas sponges, over the period of about five decades (from 1971 to November 2021). For a better understanding, these numerous compounds are firstly classified and presented according to their carbon skeleton as well as their biosynthetic origins. Relevant summaries focusing on the source organism and the associated bioactivity of these compounds belonging to different chemical classes are also provided. This review highlights sponges of the genus Agelas as exciting source for discovery of intriguing natural compounds.

Synthesis of heterocyclic ring-fused analogs of HMG499 as novel degraders of HMG-CoA reductase that lower cholesterol.

HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol de novo biosynthesis and its degradation may bring therapeutic benefits for the treatment of cardiovascular disease (CVD) and nonalcoholic steatohepatitis (NASH). Before, we disclosed compound HMG499 as a potent HMGCR degrader, which could be a promising agent for treating CVD, however its side-effect of promoting cholesterol accumulation in cells should be eliminated before progression. Herein, a series of novel heterocyclic ring-fused analogs of HMG499 were synthesized and investigated for their activities of stimulating HMGCR degradation using a HMGCR (TM1-8)-GFP reporting system. Among them, the most active compound 29 (QH536) showed an EC50 of 0.22 µΜ in promoting HMGCR degradation, which was about 2 times more potent than HMG499 (EC50 = 0.43 µM). Interestingly, 29 was different from HMG499, it had no side-effect of inducing cholesterol accumulation in cells. Mechanistic studies disclosed that 29 could significantly decrease statin-induced accumulation of HMGCR protein via ubiquitination and degradation of HMGCR through ubiquitin-proteasome pathway and inhibit the cholesterol biosynthesis in cells. Therefore, these heterocyclic ring-fused analogs could be used as promising leads for the development of new types of agents against CVD. Furthermore, 29 also lowered cholesterol levels and suppressed TGFß1-induced proliferation of LX-2 hepatic stellate cells in a dose-dependent manner. In particular, 29 not only decreased the NASH associated fibrotic mRNA and protein expression of α-SMA, COL1A1, TIMP1 and TGFß1 but also suppressed cholesterol levels and inflammatory genes of TNF-α, IL-6 an IL-1ß in RAW264.7 macrophage cells, indicating that 29 may bring therapeutic benefit to treat NASH.

MOF-supported crystalline ionic liquid: new type of solid electrolyte for enhanced and high ionic conductivity.

Solid-state electrolyte (SSE) is crucial for a high-performance all-solid-state battery. Here, a new solid sodium electrolyte based on the ionic liquid EIMS-NaTFSI and one metal-organic framework (MOF) UiO-67-MIMS functionalized with zwitterion groups MIMS was obtained (UiO-67 and was assembled with 4,4'-biphenyldicarboxylate linker and cluster Zr6O4(OH)4) (EIMS = 1-(1-ethyl-3-imidazolio)propane-3-sulfonate, NaTFSI = sodium bis(trifluoromethanesulfonyl)imide, MIMS = 1-(1-mthyl-3-imidazolio)propane-3-sulfonate). By contacting and pairing EIMS-NaTFSI (abbreviated as EN-1) to the MIMS group on the framework, EN-1 was directed and arranged along the channels within UiO-67-MIMS, forming a solid composite EN-1@UiO-67-MIMS with Bragg scatter, i.e., a crystalline ionic liquid containing Na+ salts (NaTFSI). Such an ionic liquid EN-1@UiO-67-MIMS bearing crystalline MOF matrix showed and preserved fast ion conduction (1.02 × 10-2 S cm-1) at 150 °C even after 30 days, and exhibited 1-2 orders of magnitude higher conductivities than the bulk ionic liquid EN-1 within a wide temperature range, although the ion content in the latter was higher. The infinite pathway paved by the EN-1 arranged and contacted the MIMS along the channels within MOF well accounts for the fast ion transmission and the stability of the solid-state electrolyte. Such MOF-based crystalline ionic liquid provides a new strategy for developing high-performance solid-state electrolytes for ions.

Photolysis of free chlorine and production of reactive radicals in the UV/chlorine system using polychromatic spectrum LEDs as UV sources.

Recently, ultraviolet light-emitting diodes (UV-LEDs) and chlorine combined system has been employed as an emerging advanced oxidation process. However, UV-LEDs were commonly considered as monochromatic UV sources. In this study, the obvious quantum yields of chlorine photolysis under 265 nm and 280 nm LEDs irradiations were investigated with treating LEDs as polychromatic UV sources. Particularly, Φobs-poly of HOCl and OCl⁻ for 265 nm LED were found to be 1.50 and 0.70 mol E-1, respectively, whereas Φobs-poly of HOCl and OCl⁻ for 280 nm LED were 1.28 and 0.64 mol E-1, respectively. It was identified that Φobs-poly were 5.66-14.63 % lower than Φobs-mono. This suggests that obvious quantum yield using peak emission wavelength would overestimate the true quantum yield. The production of radical species in LED UV/chlorine systems were determined by the degradation of BA, and illustrated by a mathematical model. Different trends were observed for 265 nm and 280 nm LED UV/chlorine systems as pH increased from 5.0 to 10.0. As pH increased, the formation of OH continuously decreased in both 265 nm and 280 nm LED systems. The formation of Cl increased at neutral pH and more Cl and OH were formed due to the higher molar absorbance coefficient at 280 nm. The chlorine dose-dependent effects on radical productions at pH of 5.0, 7.5 and 10.0 were also assessed. At pH of 5.0, OH was the main radical product and had linear correlation with chlorine dose. At pH of 7.5, the productions of OH and Cl showed similar profiles that increased rapidly at low chlorine dosage and then slowed down.

Investigation on the Performance of Partial Penetration Welds in Multicell Concrete Filled Steel Tubes.

This paper presents an experimental and analytical investigation on the performance of partial penetration welds used to adjoin steel plates in irregular shaped multicell concrete filled steel tubes. The experimental program of this study is designed based on an actual implementation of such members as mega columns in a super high rise building in China. A total of six specimens are designed with different plate arrangements for the purpose of testing the performance of the partial penetration welds at different locations of the specimen. The designed specimens are tested under different load procedures and directions; this is achieved by placing them in vertical and slantwise manners between two loading plates which impose monotonic and cyclic actions. The failure conditions of each of the tested specimens are presented and discussed in detail and are based on the conclusions drawn from the experimental observations; the partial penetration weld at the corner of the tested specimens is found to be the most vulnerable. To facilitate large scale analysis, a finite element model constructed by the finite element analysis program ABAQUS is verified against experimental results. The evaluation of the stress at the partial penetration welded corner is carried out following an empirical procedure, which is adopted due to the complexity of the problem domain. The adopted procedure consists of two steps: the first one is to initially evaluate the stress based on an existing method in the literature, and the second one is to fit the results of the initial evaluation with the finite element model results based on parametric and regression analysis. After performing regression analysis, a formula to predict the weld stress is concluded, and the results of the proposed equation are found to be satisfactory when compared with the finite element model results.

Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis.

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

NAD+-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin.

Rationale: Nicotinamide adenine dinucleotide+ (NAD+)-boosting therapy has emerged as a promising strategy to treat various health disorders, while the underlying molecular mechanisms are not fully understood. Here, we investigated the involvement of fibronectin type III domain containing 5 (Fndc5) or irisin, which is a novel exercise-linked hormone, in the development and progression of nonalcoholic fatty liver disease (NAFLD). Methods: NAD+-boosting therapy was achieved by administrating of nicotinamide riboside (NR) in human and mice. The Fndc5/irisin levels in tissues and blood were measured in NR-treated mice or human volunteers. The therapeutic action of NR against NAFLD pathologies induced by high-fat diet (HFD) or methionine/choline-deficient diet (MCD) were compared between wild-type (WT) and Fndc5-/- mice. Recombinant Fndc5/irisin was infused to NALFD mice via osmotic minipump to test the therapeutic action of Fndc5/irisin. Various biomedical experiments were conducted in vivo and in vitro to know the molecular mechanisms underlying the stimulation of Fndc5/irisin by NR treatment. Results: NR treatment elevated plasma level of Fndc5/irisin in mice and human volunteers. NR treatment also increased Fndc5 expression in skeletal muscle, adipose and liver tissues in mice. In HFD-induced NAFLD mice model, NR displayed remarkable therapeutic effects on body weight gain, hepatic steatosis, steatohepatitis, insulin resistance, mitochondrial dysfunction, apoptosis and fibrosis; however, these actions of NR were compromised in Fndc5-/- mice. Chronic infusion of recombinant Fndc5/irisin alleviated the NAFLD pathological phenotypes in MCD-induced NAFLD mice model. Mechanistically, NR reduced the lipid stress-triggered ubiquitination of Fndc5, which increased Fndc5 protein stability and thus enhanced Fndc5 protein level. Using shRNA-mediated knockdown screening, we found that NAD+-dependent deacetylase SIRT2, rather than other sirtuins, interacts with Fndc5 to decrease Fndc5 acetylation, which reduces Fndc5 ubiquitination and stabilize it. Treatment of AGK2, a selective inhibitor of SIRT2, blocked the therapeutic action of NR against NAFLD pathologies and NR-induced Fndc5 deubiquitination/deacetylation. At last, we identified that the lysine sites K127/131 and K185/187/189 of Fndc5 may contribute to the SIRT2-dependent deacetylation and deubiquitination of Fndc5. Conclusions: The findings from this research for the first time demonstrate that NAD+-boosting therapy reverses NAFLD by regulating SIRT2-deppendent Fndc5 deacetylation and deubiquitination, which results in a stimulation of Fndc5/irisin, a novel exerkine. These results suggest that Fndc5/irisin may be a potential nexus between physical exercise and NAD+-boosting therapy in metabolic pathophysiology.

Terpenoids from the South China Sea soft coral Sinularia multiflora.

A rare sinulariane-type norcembranoid sinulariadiolide B (1) with a unique cyano group, and a eunicellin-based diterpenoid multifloralin (2), along with two known related analogues, sinulariadiolide (3) and sclerophytin E (4), were isolated from the extract of the South China Sea soft coral Sinularia multiflora. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with previously reported data. Compounds 2 and 4 showed potent antifouling activity against barnacle Balanus albicostatus.