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Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2–7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1–7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

The time-integrated polarization degree (PD) in the prompt optical band of a gamma-ray burst (GRB) was predicted to be less than 20%, while the time-resolved one can reach as high as 75% in the photosphere model. Polarizations in the optical band during the GRB prompt phase have not previously been studied in the framework of the magnetic reconnection model. Here, a three-segment power law of the energy spectrum is used to reconstruct the Stokes parameters of the magnetic reconnection model. Multiwavelength light curves and polarization curves from the optical band to MeV gamma rays in the GRB prompt phase are studied. We found that, depending mainly on the jet dynamics, there is a long-lasting high-PD phase in all calculated energy bands for the typical parameter sets. The time-resolved PD could be as high as 50%, while the time-integrated one is roughly 17% in the optical band. The time-resolved PD in X-rays can reach 60% and the time-integrated one is around 30%–40%. The evolution of polarization angle (PA) is random in both optical and gamma-ray bands for the photosphere model, while it is roughly constant in the synchrotron models. Therefore, future time-resolved PA observations in the prompt optical or gamma-ray band could distinguish between the photosphere and synchrotron models.

ObjectivesThis study was performed to investigate the changes and influencing factors of liver controlled attenuation parameter (CAP) in obese patients with polycystic ovary syndrome (PCOS), and to determine the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) in PCOS patients with obesity.MethodsForty-one PCOS patients with obesity and twenty age- and body mass index (BMI)-matched control women without PCOS were enrolled in this study. General data, body composition, biochemical parameters, sex hormones, and liver CAP in the two groups were collected and compared. Liver CAP was measured using transient elastography.ResultsNAFLD was more common in the Obese PCOS group than in the control group (75.61% vs. 45.00%, P=0.018). Compared to the control group, the obese PCOS group showed apparent increases in alanine transaminase (ALT), aspartate transaminase (AST), CAP, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), totle testosterone (TT), free androgen index (FAI), fasting insulin (FIns), and homeostasis model assessment-insulin resistance (HOMA-IR), along with lower high-density lipoprotein cholesterol (HDL-C) and sex hormone binding globulin (SHBG) levels. In addition, as shown by Spearman analysis, liver CAP in PCOS patients with obesity had a positive correlation with ALT, AST, TG, TT, FAI, FIns, and HOMA-IR, and a negative correlation with SHBG. Logistic regression analysis showed that TG, TT, FIns, and HOMA-IR were risk factors for NAFLD, while TT was an independent risk factor for NAFLD in PCOS patients with obesity.ConclusionPCOS patients with obesity had a significantly higher prevalence of NAFLD. Furthermore, in PCOS patients with obesity, liver CAP was associated with disorders of lipid metabolism, insulin resistance, and hyperandrogenemia, with elevated testosterone levels being an independent risk factor for NAFLD in PCOS patients with obesity.

A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey's analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the d- and once in the l-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.

The time-integrated polarization degree (PD) in the prompt optical band of a gamma-ray burst (GRB) was predicted to be less than 20%, while the time-resolved one can reach as high as 75% in the photosphere model. Polarizations in the optical band during the GRB prompt phase have not previously been studied in the framework of the magnetic reconnection model. Here, a three-segment power law of the energy spectrum is used to reconstruct the Stokes parameters of the magnetic reconnection model. Multiwavelength light curves and polarization curves from the optical band to MeV gamma rays in the GRB prompt phase are studied. We found that, depending mainly on the jet dynamics, there is a long-lasting high-PD phase in all calculated energy bands for the typical parameter sets. The time-resolved PD could be as high as 50%, while the time-integrated one is roughly 17% in the optical band. The time-resolved PD in X-rays can reach 60% and the time-integrated one is around 30%–40%. The evolution of polarization angle (PA) is random in both optical and gamma-ray bands for the photosphere model, while it is roughly constant in the synchrotron models. Therefore, future time-resolved PA observations in the prompt optical or gamma-ray band could distinguish between the photosphere and synchrotron models. [ABSTRACT FROM AUTHOR]

Eight new scalarane sesterterpenes, phyllofenones F–M (1–8), together with two known analogues, carteriofenones B and A (9–10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 μg/mL and 8 μg/mL, respectively. Compounds 1–10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 μM.

Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.

Most of the constitutive model for liquefaction analysis cannot simulate the large post-liquefaction deformation of saturated sand, and there is little research on the nonlinear time-domain large deformation constitutive relationships suitable for seismic response analysis of saturated sand sites. In this paper, a feasible, simple and applicable large deformation constitutive model for time domain analysis is proposed through experimental analysis and theoretical research. The post-liquefaction stress-strain relationships of liquefied sand are obtained based on the undrained cyclic triaxial test data, then loading-reloading rules of large post-liquefaction deformation are proposed. Combined with the effective stress constitutive model based on logarithmic skeleton curve, a constitutive model that can quantitatively describe the large deformation of saturated sand liquefaction is proposed. According to the test results, the constitutive model can simulate small to large deformations from the pre-to post-liquefaction regime of sand. This constitutive model is also implemented to the program Soilresp1D for the dynamic response analysis of liquefiable soil sites. The results show that the time domain nonlinear large deformation unified constitutive model based on the logarithmic dynamic skeleton curve, effective stress-modified logarithmic dynamic skeleton constitutive model and liquefaction large deformation constitutive model can be directly applied to the dynamic response analysis of saturated sand.

A chemical investigation of the Arctic-derived fungus Eutypella sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds 1–3 and 11–12) from rice medium and eight cytosporins (compounds 2 and 4–11) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (1), cytosporin Y (2), cytosporin Z (3), cytosporin Y1 (4), cytosporin Y2 (5), cytosporin Y3 (6), and cytosporin E1 (7), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (4) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound 1 contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (12) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds 6 and 7 was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from Eutypella sp. D-1 were evaluated. Unfortunately, only compounds 3, 6, 8, and 10–11 displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 μg/mL.

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

The MAX phase of the ternary layered compound and the recently attracted attention of the MAB phase have become the research hotspots in the field of structural ceramics for more than 20 years because of their common characteristics of ceramics and metals. The high damage tolerance and high fracture toughness are different from the essential characteristics of traditional ceramics. The overall development of MAX phase and the latest research progress of MAB phase were briefly reviewed in this article, focusing on the analysis of the effect of multi-scale layered structure on macro-mechanical behavior and its internal mechanism. Based on the results of first-principles calculations,the bond stiffness model was established and the quantitative characterization of chemical bond strength was realized, and more importantly, it was clarified that "sufficiently" weak interlayer bonding is the root cause for the extraordinary mechanical properties of ternary layered ceramics. The magnetocaloric effect (MCE) of Fe2AlB2 near room temperature shows the good application prospects of MAB phase compounds in the functional field. After more than 20 years of continuous research, the structure and performance of MAX-phase compounds have gradually become clear. At present, application research for specific scenarios is vigorously carried out all over the world. However, the current knowledge of MAB phase compounds is still very limited. Therefore, synthesizing and characterizing the structure, mechanical properties, physical properties, and service behaviour of existing MAB phase compounds are the important tasks at this stage. First-principles numerical simulation based on density functional theory (DFT) can play an important role, just as in understanding the extraordinary properties of MAX phase compounds and discovering new compounds.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive disorder characterized by recurrent cholestasis. ATPase class I, type 8B, member 1 (ATP8B1) encodes familial intrahepatic cholestasis 1 (FIC1), which acts as a phosphatidylserine reversing enzyme in the tubule membrane of hepatocytes to mediate the inward translocation of phosphatidylserine (PS). At present, dozens of ATP8B1 pathogenic mutations have been identified that mainly cause BRIC1 and progressive familial intrahepatic cholestasis 1 (PFIC1). The diagnosis of BRIC1 is based on symptoms, laboratory tests, imaging, liver histology, and genetic testing. BRIC1 treatment seeks to prevent recurrence and reduce disease severity. At present, the main treatment methods include ursodeoxycholic acid (UDCA), rifampin, cholestyramine and haemofiltration, and endoscopic nasobiliary drainage (ENBD). Here, we report a 17-year-old patient with cholestasis who has a rare heterozygous ATP8B1 gene mutation (p.T888K). The patient was treated with UDCA, glucocorticoids and haemofiltration, after which bilirubin levels gradually returned to normal. This case was thought to be caused by an ATP8B1 heterozygous mutation, which may be related to haploinsufficiency (HI).

The rotations of the polarization angle (PA) with time (energy) can lead to the depolarization of the time-integrated (energy-integrated) polarization. However, we do not know how and when it will rotate. Here, we consider a magnetic reconnection model to investigate the polarizations, especially the PA rotations of gamma-ray burst (GRB) prompt emission. For a large-scale ordered aligned magnetic field configuration, we find that within T _50 PAs will rotate with time (energy) for slight off-axis observations. Our studies show that the rotations of the PAs are due to changes in the observed image of the emitting region before being averaged over the equal arrival time surface for the unresolved sources. We apply our model to the single-pulse bursts of GRB 170101A and GRB 170114A with time-resolved PA observations. We find it can interpret the violent PA variation of GRB 170101A, while the model could not predict the two 90° PA changes in GRB 170114A. A more detailed model should be considered.