GraphCDR: a graph neural network method with contrastive learning for cancer drug response prediction.

Predicting the response of a cancer cell line to a therapeutic drug is an important topic in modern oncology that can help personalized treatment for cancers. Although numerous machine learning methods have been developed for cancer drug response (CDR) prediction, integrating diverse information about cancer cell lines, drugs and their known responses still remains a great challenge. In this paper, we propose a graph neural network method with contrastive learning for CDR prediction. GraphCDR constructs a graph neural network based on multi-omics profiles of cancer cell lines, the chemical structure of drugs and known cancer cell line-drug responses for CDR prediction, while a contrastive learning task is presented as a regularizer within a multi-task learning paradigm to enhance the generalization ability. In the computational experiments, GraphCDR outperforms state-of-the-art methods under different experimental configurations, and the ablation study reveals the key components of GraphCDR: biological features, known cancer cell line-drug responses and contrastive learning are important for the high-accuracy CDR prediction. The experimental analyses imply the predictive power of GraphCDR and its potential value in guiding anti-cancer drug selection.

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research.

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy.

Substantial accumulation of mercury in the deepest parts of the ocean and implications for the environmental mercury cycle.

Anthropogenic activities have led to widespread contamination with mercury (Hg), a potent neurotoxin that bioaccumulates through food webs. Recent models estimated that, presently, 200 to 600 t of Hg is sequestered annually in deep-sea sediments, approximately doubling since industrialization. However, most studies did not extend to the hadal zone (6,000- to 11,000-m depth), the deepest ocean realm. Here, we report on measurements of Hg and related parameters in sediment cores from four trench regions (1,560 to 10,840 m), showing that the world's deepest ocean realm is accumulating Hg at remarkably high rates (depth-integrated minimum-maximum: 24 to 220 µg ⋅ m-2 ⋅ y-1) greater than the global deep-sea average by a factor of up to 400, with most Hg in these trenches being derived from the surface ocean. Furthermore, vertical profiles of Hg concentrations in trench cores show notable increasing trends from pre-1900 [average 51 ± 14 (1σ) ng ⋅ g-1] to post-1950 (81 ± 32 ng ⋅ g-1). This increase cannot be explained by changes in the delivery rate of organic carbon alone but also need increasing Hg delivery from anthropogenic sources. This evidence, along with recent findings on the high abundance of methylmercury in hadal biota [R. Sun et al, Nat. Commun. 11, 3389 (2020); J. D. Blum et al, Proc. Natl. Acad. Sci. U. S. A. 117, 29292-29298 (2020)], leads us to propose that hadal trenches are a large marine sink for Hg and may play an important role in the regulation of the global biogeochemical cycle of Hg.

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Predicting drug-disease associations through layer attention graph convolutional network.

BACKGROUND: Determining drug-disease associations is an integral part in the process of drug development. However, the identification of drug-disease associations through wet experiments is costly and inefficient. Hence, the development of efficient and high-accuracy computational methods for predicting drug-disease associations is of great significance. RESULTS: In this paper, we propose a novel computational method named as layer attention graph convolutional network (LAGCN) for the drug-disease association prediction. Specifically, LAGCN first integrates the known drug-disease associations, drug-drug similarities and disease-disease similarities into a heterogeneous network, and applies the graph convolution operation to the network to learn the embeddings of drugs and diseases. Second, LAGCN combines the embeddings from multiple graph convolution layers using an attention mechanism. Third, the unobserved drug-disease associations are scored based on the integrated embeddings. Evaluated by 5-fold cross-validations, LAGCN achieves an area under the precision-recall curve of 0.3168 and an area under the receiver-operating characteristic curve of 0.8750, which are better than the results of existing state-of-the-art prediction methods and baseline methods. The case study shows that LAGCN can discover novel associations that are not curated in our dataset. CONCLUSION: LAGCN is a useful tool for predicting drug-disease associations. This study reveals that embeddings from different convolution layers can reflect the proximities of different orders, and combining the embeddings by the attention mechanism can improve the prediction performances.

Association between snoring and insulin levels in the US population: a cross-sectional study.

PURPOSE: Snoring may cause a number of problems such as tiredness, obesity, and even severe diseases, but the correlation between snoring and insulin secretion, which has important clinical significance, has rarely been studied. The objective of this study was to evaluate the correlation between snoring frequency and insulin secretion and discuss the potential mechanisms, thereby estimating the health condition of ß-cells of individuals who snore. METHODS: The analyses used data from National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018. A regression analysis was performed for snoring frequency and insulin concentration, and then multiple regression analyses excluded various factors related to insulin secretion, including age, sex, race, body mass index (BMI), factors indicating patients' nutritional condition, and symptoms possibly implying obstructive sleep apnea. Subsequently, three hierarchical multiple regression analyses were carried out respectively based on sex, race, and BMI. RESULTS: After adjusting for confounding variables, snoring frequency was correlated with insulin concentration especially when snoring was at relatively high frequencies (e.g., more than 5 nights per week) (ß = 1.77, 95%CI = 0.42-3.13, P = 0.010). The stratification analyses showed that high snoring frequency increased insulin secretion among women (ß = 1.83, 95%CI = 0.05-3.62, P = 0.044), Hispanics (ß = 3.28, 95%CI = 0.05-6.51, P = 0.047), and participants with BMI in the range > 30 kg/m2 (ß = 3.77, 95%CI = 0.52-7.03, P = 0.023). CONCLUSION: Our results suggest that snoring is likely to relate to an increase in insulin when severe, especially in women, Hispanics, and people with a BMI of more than 30 kg/m2.

Role of the tonsil-oropharynx ratio on lateral cephalograms in assessing tonsillar hypertrophy in children seeking orthodontic treatment.

OBJECTIVES: To analyze the diagnostic value of the tonsil-oropharynx (T/O) ratio on lateral cephalograms for evaluating tonsillar hypertrophy (TH). METHODS: A cross-sectional study was performed on 185 consecutive children (101 males, 84 females; mean age 7.3 ± 1.4 years) seeking orthodontic treatment. The T/O ratios on lateral cephalograms were calculated following Baroni et al.'s method. Tonsil sizes were clinically determined according to the Brodsky grading scale. Spearman correlation coefficients between the T/O ratio and clinical tonsil size were calculated with the total sample and subgroups and then compared between subgroups. Diagnostic value was analyzed using the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: There was a strong correlation between the T/O ratio and clinical tonsil size in children (ρ = 0.73; P < 0.001). A significantly higher correlation coefficient was found in the Class III children. The ROC curve revealed an area under the curve of 0.90 (95% CI, 0.86-0.94; P < 0.001). The optimal cutoff value of the T/O ratio for predicting TH was 0.58, with a sensitivity of 98.7% and specificity of 64.2%. Employing the cutoff value of 0.5, the sensitivity was 100% and the specificity was 45.9%. CONCLUSIONS: Measurement of the T/O ratio on lateral cephalograms may be helpful to initial screening in children for TH. Practitioners may combine the clinical examination of tonsil size with the cephalometric findings for a more comprehensive evaluation.

Enantioseparation of amino acid and mandelic acid enantiomers using Garphos derivatives as chiral extractants.

In this paper, Garphos with different substituents were employed as chiral extractants to enantioseparate racemic amino acid and mandelic acid. The influences of metal precursors, pH of aqueous solution, Garphos-metal concentration, extraction temperature, and substituent effect on extraction were investigated. The results indicated that the substituent groups significantly affected the π-π interaction between extractant and substrate. And the separation factors (α) for Garphos could be remarkably improved by regulating substituent groups. Garphos-II-Pd, Garphos-VI-Pd, Garphos-III-Pd, Garphos-I-Cu, Garphos-VI-Cu, and Garphos-V-Pd were the most efficient extractants for phenylalanine (Phe), homophenylalanine (Hphe), 4-nitrophenylalanine (Nphe), 3-chlorophenylglycine (Cpheg), mandelic acid (MA), and 2-chlormandelic acid (CMA) with α values of 2.40, 2.37, 5.37, 1.59, 5.98, and 3.69, respectively. This work provided an important reference for the design of efficient chiral extractants in future work.

Observation-Based Mercury Export from Rivers to Coastal Oceans in East Asia.

Globally, the consumption of coastal fish is the predominant source of human exposure to methylmercury, a potent neurotoxicant that poses health risks to humans. However, the relative importance of riverine inputs and atmospheric deposition of mercury into coastal oceans remains uncertain owing to a lack of riverine mercury observations. Here, we present comprehensive seasonal observations of riverine mercury and methylmercury loads, including dissolved and particulate phases, to East Asia's coastal oceans, which supply nearly half of the world's seafood products. We found that East Asia's rivers annually exported 95 ± 29 megagrams of mercury to adjacent seas, 3-fold greater than the corresponding atmospheric deposition. Three rivers alone accounted for 71% of East Asia's riverine mercury exports, namely: Yangtze, Yellow, and Pearl rivers. We further conducted a metadata analysis to discuss the mercury burden on seawater and found that riverine export, combined with atmospheric deposition and terrestrial nutrients, quantitatively elevated the levels of total, methylated, and dissolved gaseous mercury in seawater by an order of magnitude. Our observations support that massive amounts of riverine mercury are exported to coastal oceans on a continental scale, intensifying their spread from coastal seawater to the atmosphere, marine sediments, and open oceans. We suggest that the impact of mercury transport along the land-ocean aquatic continuum should be considered in human exposure risk assessments.

Investigation of Taniaphos as a chiral selector in chiral extraction of amino acid enantiomers.

Finding chiral selector with high stereoselectivity to a variety of amino acid enantiomers remains a challenge and warrants further research. In this work, Taniaphos, a chiral ligand with rotatable spatial configuration, was employed as a chiral extractant to enantioseparate various amino acid enantiomers. Phenylalanine (Phe), homophenylalanine (Hphe), 4-nitrophenylalanine (Nphe), and 3-chloro-phenylglycine (Cpheg) were used as substrates to evaluate the extraction efficiency. The results revealed that Taniaphos-Cu exhibited good abilities to enantioseparate Phe, Hphe, Nphe, and Cpheg with the highest separation factors (α) of 3.13, 2.10, 2.32, and 2.14, respectively. Taniaphos-Cu is more conducive to combine with D-amino acid in extraction. The influences of pH, Taniaphos-Cu, and concentration and extraction temperature on extraction were comprehensively evaluated. The highest performance factors (pf) for Phe, Hphe, Nphe, and Cpheg at optimal extraction conditions were 0.08892, 0.1250, 0.09621, and 0.08021, respectively. The recognition mechanism between Taniaphos-Cu and amino acid enantiomers was discussed. The coordination interaction between Taniaphos-Cu and COO- , π-π interaction between Taniaphos-Cu and amino acid enantiomers are important acting forces in chiral extraction. The steric-hindrance between NH2 and OH lead to Taniaphos-Cu-D-Phe is more stable than Taniaphos-Cu-L-Phe. This work provided a chiral extractant that has good abilities to enantioseparate various amino acid enantiomers.

Preparation of GO/Diatomite/Polyacrylonitrile Functional Separator and Its Application in Li-S Batteries.

Lithium-sulfur (Li-S) batteries have received extensive attention due to their numerous advantages, including a high theoretical specific capacity, high energy density, abundant reserves of sulfur in cathode materials, and low cost. Li-S batteries also face several challenges, such as the insulating properties of sulfur, volume expansion during charging and discharging processes, polysulfide shuttling, and lithium dendritic crystal growth. In this study, a composite of a porous multi-site diatomite-loaded graphene oxide material and a PAN fiber membrane is developed to obtain a porous and high-temperature-resistant GO/diatomite/polyacrylonitrile functional separator (GO/DE/PAN) to improve the electrochemical performance of Li-S batteries. The results show that the use of GO/DE/PAN helps to inhibit lithium phosphorus sulfide (LPS) shuttling and improve the electrolyte wetting of the separator as well as the thermal stability of the battery. The initial discharge capacity of the battery using GO/DE/PAN is up to 964.7 mAh g-1 at 0.2 C, and after 100 cycles, the reversible capacity is 683 mAh g-1 with a coulombic efficiency of 98.8%. The improved electrochemical performance may be attributed to the porous structure of diatomite and the layered composite of graphene oxide, which can combine physical adsorption and spatial site resistance as well as chemical repulsion to inhibit the shuttle effect of LPS. The results show that GO/DE/PAN has great potential for application in Li-S batteries to improve their electrochemical performance.

Strong linkage between benthic oxygen uptake and bacterial tetraether lipids in deep-sea trench regions.

Oxygen in marine sediments regulates many key biogeochemical processes, playing a crucial role in shaping Earth's climate and benthic ecosystems. In this context, branched glycerol dialkyl glycerol tetraethers (brGDGTs), essential biomarkers in paleoenvironmental research, exhibit an as-yet-unresolved association with sediment oxygen conditions. Here, we investigated brGDGTs in sediments from three deep-sea regions (4045 to 10,100 m water depth) dominated by three respective trench systems and integrated the results with in situ oxygen microprofile data. Our results demonstrate robust correlations between diffusive oxygen uptake (DOU) obtained from microprofiles and brGDGT methylation and isomerization degrees, indicating their primary production within sediments and their strong linkage with microbial diagenetic activity. We establish a quantitative relationship between the Isomerization and Methylation index of Branched Tetraethers (IMBT) and DOU, suggesting its potential validity across deep-sea environments. Increased brGDGT methylation and isomerization likely enhance the fitness of source organisms in deep-sea habitats. Our study positions brGDGTs as a promising tool for quantifying benthic DOU in deep-sea settings, where DOU is a key metric for assessing sedimentary organic carbon degradation and microbial activity.

Skeletal Editing of Benzene Motif: Photopromoted Transannulation for Synthesis of DNA-Encoded Seven-Membered Rings.

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Geochemical characteristics and implications of hydrocarbon in source rocks of Chagan Sag, Yin'e basin of Inner Mongolia.

Chagan Sag is one of the most significant tectonic unit in the Yin'e Basin. The special component of the organic macerals and biomarkers in the Chagan sag suggests great difference of its hydrocarbon generation process. In this paper, forty samples of source rocks are subjected to carry out on the geochemical characteristics by methods of rock-eval analysis, organic petrology and gas chromatography mass spectrometry (GC-MS) to reveal the origin, depositional environment and maturity of organic matter in Chagan Sag, Yin'e Basin of Inner Mongolia. The total organic matter of the analyzed samples ranges from 0.4 wt%∼3.89 wt% with an average of 1.12 wt%, indicating fair to excellent hydrocarbon generation potential. The rock-eval results show that the S1+S2 and hydrocarbon index range from 0.03 mg/g∼16.34 mg/g (avg.3.6 mg/g) and 6.24-521.32 mg/g (avg. 199.63 mg/g), suggesting most of the kerogen types are type II and III, with small amount of type I. The Tmax ranges from 428 to 496 °C, suggesting low mature to mature stage. The macerals component of morphological macerals presents with certain amount of vitrinite, liptinite and some inertinite. However, the amorphous component takes the dominant part of the macerals with account of 50%-80%. The amorphous components are dominated by sapropelite in the source rock, indicating bacteriolytic amorphous promote the organic generation process. Hopanes and sterane are widely distributed in the source rocks. The biomarker results suggest a mix of planktonic-bacterial and higher plant origins, with wide range of thermal maturity and relatively reducing depositional environment. Abnormal high content of hopanes were observed in the biomarkers, and some special biomarkers such as monomethylalkanes, long-chain-alkyl naphthalenes, aromatized de A-triterpenes, 8,14-seco-triterpenes, and A, B-cyclostane are detected in Chagan Sag. The presence of these compounds suggests that bacterial and microorganisms are of great significance to the generation of hydrocarbon in the source rock in Chagan Sag.

Lipidomic chemotaxonomy aligned with phylogeny of Halobacteria.

Archaea play an important role in global biogeochemical cycles and are considered ancestral to eukaryotes. The unique lipid composition of archaea, characterized by isoprenoid alkyl chains and ether linkage to glycerol-1-phosphate, offers valuable insights into archaeal phylogeny and evolution. However, comprehensive studies focusing on archaeal lipidomes, especially at the intact polar lipid level, are currently limited. Here, we built an in-house library of archaeal lipids by using high-performance liquid chromatography coupled with mass-spectrometry, which was integrated with bioinformatics and molecular network analyses. Seven halobacterial strains, representing three distinct orders, were cultured under identical conditions to investigate their lipidomes. A total of 162 features were identified, corresponding to 107 lipids that could be assigned to different strains. Clustering analyses of both core lipids and total lipids matched the phylogeny of Halobacteria at the order level. Notably, lipids such as triglycosyl diether-phosphatidyl acid and bis-sulfate glycosyl lipids were specific to particular groups and could serve as diagnostic intact lipid biomarkers for Halobacteria. Furthermore, the analysis of network-coordinated features facilitated the linkage of unknown lipid compounds to phylogeny, which promotes a lipidome to phylogeny matchup among three Haloferax strains, thereby expanding the knowledge of the halobacterial lipidome. Our study provides a comprehensive view of the lipidomes of the seven strains of Halobacteria and highlights the potential of lipidomics for studying archaeal phylogeny.

Spatial-temporal characteristics of mercury and methylmercury in marine sediment under the combined influences of river input and coastal currents.

Mercury, especially in the form of methylmercury (MeHg), is a global pollutant, and aquatic products are considered the main sources of Hg exposure to humans. The Bohai and Yellow seas are two important epicontinental seas for marine fisheries and aquaculture in China. A decreasing trend of the THg in the Yellow River Estuary toward the outer edge was reported according to 83 surface sediments (27.3 ± 15.0 ng g-1) and 3 sediment cores from the Bohai Sea and Yellow Sea. The relatively higher THg levels in the central Yellow Sea can be primarily attributed to higher organic carbon levels and finer-grained sediment sizes and partly to the particulates from the riverine input of the Yellow River driven by the currents. An increasing trend in THg levels since industrialization in north China around the Bohai and Yellow seas, and a decreasing trend of Yellow River THg input in recent years were recorded by sediment cores. The spatial distribution pattern of surface sediments MeHg (161 ± 130 pg g-1) was different from that of THg. A higher MeHg content and MeHg/THg ratio were found in the Bohai and Yellow seas compared to the East China Sea, and extremely high MeHg levels (714 pg g-1) were found in the Yellow Sea Cold Water Mass (YSCWM) area, which is considered an important region for fishery and marine breeding, suggesting that more attention should be paid to the potential ecological and human health risks in the region due to mercury exposure.

Mercury and methylmercury in China's lake sediments and first estimation of mercury burial fluxes.

Lake sediments are key materials for mercury deposition and methylation. To understand the mercury concentrations in China's lakes, 100 lake surface sediment samples were collected from 35 lakes in 2014. Total mercury (THg), methylmercury (MeHg) concentrations and the annual Hg burial rates in lake sediments were measured. THg and MeHg concentrations in the sediment ranged from 13.6 to 1488 ng‧g-1 and 0.05 to 1.70 ng‧g-1, respectively, and urban lakes reported most high values, indicating direct anthropogenic inputs. The Inner Mongolia-Xinjiang Region (MX) and Qinghai-Tibet Plateau Region (QT) reported relatively lower mercury burial rates, while the Eastern Plain Region (EP), Northeast Mountain and Plain Region (NE), and Yunnan-Guizhou Plateau Region (YG) reported higher mercury burial rates. Regional variances of THg burial fluxes were dominated by atmospheric deposition, terrestrial input, and sediment accumulation rates in different lakes. In 2014, the estimated average THg burial rate in China's lakes was 139 µg‧m-2‧yr-1, comparable to the average in mid-latitude North America in recent years; however, due to China's much smaller lake area relative to NA, the annual THg burial flux in China was much lower than that in North America. EP and NE, where most freshwater aquatic products in China are harvested, accounted for 58.2% and 22.9%, respectively, of the THg burial flux. High sedimentary MeHg concentrations and MeHg:THg ratios were reported in most of the NE but low MeHg concentrations and MeHg:THg ratios were reported in EP. MeHg concentrations and MeHg:THg ratios were positively correlated with water COD levels and negatively correlated with average temperature. The results of this study indicate that in addition to the adjacent seas, lake sediments are an important mercury sink in China's aquatic environment, which could cause health risks due to MeHg intake, especially in NE.

Diet change of hadal amphipods revealed by fatty acid profile: A close relationship with surface ocean.

The diet of hadal organisms remains elusive because of the difficulty in sampling and monitoring at the great water depths (6-11 km). Here we analyzed fatty acids of the amphipods collected from three Pacific trenches, namely New Britain Trench (NBT; 8.2-8.9 km), Mariana Trench (MT; 11 km) and Massau Trench (MS; 6.9 km). A total of 35 fatty acids including saturated, monounsaturated and polyunsaturated compounds were identified. The principal component analysis (PCA) divides major fatty acids into three groups indicative of carrion (C20:4ω6, C22:5ω6, C22:6ω3, C16:1ω7, and C18:1ω9), algae (C18:2ω6 and C20:5ω3) and bacteria (C15:0, isoC15:0, isoC17:0, anteisoC17:0 and C17:0), respectively. The predominance of C18:1ω9, high C18:1ω9/C18:1ω7 and high δ15N values suggest that hadal amphipods are necrophagous. The inter-trench comparisons based on C18:1ω9/C18:1ω7, C22:6ω3/C20:5ω3, ∑polyunsaturated/∑saturated fatty acids, ∑branched fatty acids and PCA show that the amphipods in the NBT are more dependent on high-quality organic matter (i.e., carrion), whereas those in the MT and MS utilize detritus and bacterial organic matter as supplementary food. This inter-trench difference has been attributed to a bottom-up effect of food availability that the NBT has higher net primary productivity (NPP) and a strong terrestrial influence, whereas the MT and MS have lower NPP and insignificant terrestrial influences. Our study demonstrates that the diet of hadal animals is closely related to surface ocean biogeochemical property.

New secondary metabolites from the endophytic fungus Fusarium sp. HP-2 isolated from "Qi-Nan" agarwood.

A novel pyrone derivative (1) bearing two fused five-member rings, together with two new naphthalenone derivatives (2, 3), as well as two known compounds (4, 5) were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from "Qi-Nan" agarwood. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR, and by HRESIMS spectra, as well as by comparison with the literature. Bioactivity results indicated that compound 3 showed weak acetylcholinesterase inhibitory activity.