A microbial knowledge graph-based deep learning model for predicting candidate microbes for target hosts.

Predicting interactions between microbes and hosts plays critical roles in microbiome population genetics and microbial ecology and evolution. How to systematically characterize the sophisticated mechanisms and signal interplay between microbes and hosts is a significant challenge for global health risks. Identifying microbe-host interactions (MHIs) can not only provide helpful insights into their fundamental regulatory mechanisms, but also facilitate the development of targeted therapies for microbial infections. In recent years, computational methods have become an appealing alternative due to the high risk and cost of wet-lab experiments. Therefore, in this study, we utilized rich microbial metagenomic information to construct a novel heterogeneous microbial network (HMN)-based model named KGVHI to predict candidate microbes for target hosts. Specifically, KGVHI first built a HMN by integrating human proteins, viruses and pathogenic bacteria with their biological attributes. Then KGVHI adopted a knowledge graph embedding strategy to capture the global topological structure information of the whole network. A natural language processing algorithm is used to extract the local biological attribute information from the nodes in HMN. Finally, we combined the local and global information and fed it into a blended deep neural network (DNN) for training and prediction. Compared to state-of-the-art methods, the comprehensive experimental results show that our model can obtain excellent results on the corresponding three MHI datasets. Furthermore, we also conducted two pathogenic bacteria case studies to further indicate that KGVHI has excellent predictive capabilities for potential MHI pairs.

Role of microfibril angle in molecular deformation of cellulose fibrils in Pinus massoniana compression wood and opposite wood studied by in-situ WAXS.

Upon tensile stress, the spiral cellulose fibrils in wood cell walls rotate like springs with decreasing microfibril angle (MFA), and the cellulose molecules elongate in the chain direction. Compression wood with high MFA and opposite wood with low MFA were comparatively studied by in-situ tensile tests combined with synchrotron radiation WAXS in the present study. FTIR spectroscopy revealed that compression wood had a higher lignin content and fewer acetyl groups. For both types of wood, the lattice spacing d004 increased and the MFA decreased gradually with the increase of tensile stress. At stresses beyond the yield point, cellulose lattice strain depended linearly on macroscopic stress, while the MFA depended linearly on macroscopic strain. The deformation mechanisms of compression wood and opposite wood are not essentially different but differ in their deformation behavior. Specifically, the contribution ratio of lattice strain and cellulose fibril reorientation to macroscopic strain was 0.25 and 0.53 for compression wood, and 0.40 and 0.33 for opposite wood, respectively. Due to the geometric effects of MFA, a greater contribution of cellulose fibril reorientation to the macroscopic deformation was detected in compression wood than in opposite wood.

Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. RESULTS AND DISCUSSION: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. CONCLUSION: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Ciprofol is primarily glucuronidated by UGT1A9 and predicted not to cause drug-drug interactions with typical substrates of CYP1A2, CYP2B6, and CYP2C19.

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent Km values of 345 and 412 µM, Vmax values of 2214 and 444 nmol min-1·mg protein-1, respectively. The in vitro intrinsic clearances (CLint = Vmax/Km) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 µL min-1·mg protein-1, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (Ki = 12 µM) and CYP2B6 (Ki = 4.7 µM), and noncompetitively inhibited CYP2C19 (Ki = 29 µM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

Prognostic implications of left ventricular ejection fraction trajectory changes in heart failure.

Aims: The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Methods: Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Results: Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. Conclusions: The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.

PTBGRP: predicting phage-bacteria interactions with graph representation learning on microbial heterogeneous information network.

Identifying the potential bacteriophages (phage) candidate to treat bacterial infections plays an essential role in the research of human pathogens. Computational approaches are recognized as a valid way to predict bacteria and target phages. However, most of the current methods only utilize lower-order biological information without considering the higher-order connectivity patterns, which helps to improve the predictive accuracy. Therefore, we developed a novel microbial heterogeneous interaction network (MHIN)-based model called PTBGRP to predict new phages for bacterial hosts. Specifically, PTBGRP first constructs an MHIN by integrating phage-bacteria interaction (PBI) and six bacteria-bacteria interaction networks with their biological attributes. Then, different representation learning methods are deployed to extract higher-level biological features and lower-level topological features from MHIN. Finally, PTBGRP employs a deep neural network as the classifier to predict unknown PBI pairs based on the fused biological information. Experiment results demonstrated that PTBGRP achieves the best performance on the corresponding ESKAPE pathogens and PBI dataset when compared with state-of-art methods. In addition, case studies of Klebsiella pneumoniae and Staphylococcus aureus further indicate that the consideration of rich heterogeneous information enables PTBGRP to accurately predict PBI from a more comprehensive perspective. The webserver of the PTBGRP predictor is freely available at http://120.77.11.78/PTBGRP/.

Efomycine U, a new C2-asymmetric elaiophylin derivative from Streptomyces malaysiensis DSM 4137.

Chemical examination of an actinomycete strain Streptomyces malaysiensis DSM 4137 derived from a soil sample derived isolate Streptomyces sp. DSM 3816, yielded a new C2-asymmetric elaiophylin derivative efomycine U (1) and a known analogue halichoblelide D (2). These structures were unambiguously elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. All compounds isolated were subjected to antimicrobial, cytotoxic and immnosuppressive activities evaluation.

The Influence of Interface Design and External Frame on the Energy Absorption Performance of the Semi-Auxetic Structure.

In this article, four new semi-auxetic structures are designed by changing the way of interface connection and adding external frames. These structures were fabricated by fused deposition modeling, which is an additive manufacturing technology. The effects of interface design and external frame on deformation mode and energy absorption performance of semi-auxetic structure under quasi-static compression are studied. It was found that the deformation modes of framed and frameless structures are different. The specific energy absorption of the semi-auxetic structure is increased by ∼52% compared with the frameless hexagonal honeycomb structure. In addition, Abaqus was used to establish finite element models of the four new semi-auxetic structures and the frameless hexagonal honeycomb structure. It can be found that the simulation results were consistent with the experimental results.

Migration and Transformation of Arsenic in Rice and Soil under Different Nitrogen Sources in Polymetallic Sulfide Mining Areas.

Nitrogen (N) fertilizer affects the migration and transformation of arsenic (As) in soil and rice. We conducted pot experiments and studied the effects of 0.1, 0.2, and 0.4 g∙kg−1 N levels of NH4Cl, (NH4)2SO4, and NH4NO3 fertilizers on the As bioavailability in the As-contaminated inter-rhizosphere soil and As accumulation in the rice organs. The results showed that the concentration of bioavailable As in the rice rhizosphere soil was significantly negatively correlated with pH under the 0.4 g∙kg−1 N level of each fertilizer. At the same N level, while the As concentration was maturity stage > tillering stage in rice stems and leaves treated with NH4Cl and (NH4)2SO4, it was the opposite in roots. This suggests that the transfer of As from roots to stems and leaves mainly occurs in the late stage of rice growth under the condition of only NH4+-N fertilizer applying. The As concentration in rice aboveground organ (grains and stems−leaves) decreased with the increasing N application under the same N fertilizer treatment condition during the mature stage. In addition, the As concentration in rice grains treated with (NH4)2SO4 was the lowest. This result indicated that SO42− and NH4+-N had a significant synergistic inhibition on the As accumulation in rice grains. It was concluded that appropriate (NH4)2SO4 levels for As-contaminated paddy soils with high sulfur (S) contents would obtain rice grains with inorganic As concentrations below 0.2 mg·kg−1.

Carotane sesquiterpenoids A-G from the desert endophytic fungus Fusarium sp. HM 166.

Seven undescribed carotane sesquiterpenoids named fusanoids A-G (1-7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4-9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1R132h mutant.

Why Do Bamboo Parenchyma Cells Show Higher Nanofibrillation Efficiency than Fibers: An Investigation on Their Hierarchical Cell Wall Structure.

The cell walls of parenchyma cells and fibers in bamboo are both highly lignified with secondary thickening. However, the former were found to have much higher nanofibrillation efficiency than fibers via both protocols of ultrasonication and high pressure homogenization. To elucidate the inherent mechanism, detailed comparisons of chemical composition, cell morphology, cell wall density, pore structures, and structural organization of cell wall polymers were performed on native and pretreated cell walls of both parenchyma cells and fibers. Chemical compositional analysis showed that fibers have much higher cellulose (49.8% to 35.5%) but lower xylan content (21.1% to 36.2%) than parenchyma, while their lignin contents were similar (24.9% vs 22.9%). Polarized FTIR further revealed clear differences in the structural organization of polymers between the two types of cells, with all the polymers of fibers being more orderly assembled than those of parenchyma cells. The compact arrangement of polymers in the fibers was also supported by the much higher cell wall density (1.52 vs 1.28 g/cm3) and lower porosity (0.007 vs 0.013 cc/g after chemical pretreatments), as compared to the parenchyma cells. The study provides evidence that the anatomical characteristics of huge cavity-wall ratio, higher cell wall porosity, and less ordered arrangement of cell wall matrix polymers (mainly lignin) in parenchyma cells contribute to their higher nanofibrillation efficiency compared to fibers.

Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.

Three new cytochalasins, phomoparagins A-C (1-3), along with five known analogs (4-8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4-6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.

[Impact of Land Use Types at Different Scales on Surface Water Environment Quality and Its Driving Mechanism].

As an important carrier of human activities, the spatial type of land use has an important impact on the surface water environment. Taking the Ruoergai wetland as an example, based on object-oriented remote sensing interpretation of land use types combined with water quality examination data, this study analyzed the impact and driving mechanism of land use types at different scales on the surface water environment at the small watershed and buffer scale. ① It was found that the water quality of the Ruoergai wetland could been classified as water grade V, and it was slightly eutrophic as a whole. The main pollutants were total nitrogen(TN) and phosphorus(TP), and the pollution originated from domestic sewage and grazing. ② The environmental quality of surface water was closely related to land use types. There was a negative correlation between chemical oxygen demand(COD) and the proportion of water area, a positive correlation between TN and the proportion of swamp area, and a negative correlation between total TP. ③ There was a significant correlation between spatial land use types at different scales and surface water environment. The land use type within a buffer of 1000 m had the highest interpretation degree for all factors, the land use type within a buffer of 200 m had the greatest interpretation degree for COD, the land use type within a buffer of 500 m zone had the greatest interpretation degree for TP and TN, and the land use type within a buffer of 800 m had the greatest explanation for Chl-a. The results of this study showed that the Ruoergai wetland wetland had a certain purification effect on pollutants and eutrophication. However, different land use types had different effects on different pollutants. The water body had a purification effect on Fe2+, COD, and Chl-a, and the swamp had a purification effect on TP but a cumulative effect on TN. Thus, the small-buffer zone(≤ 1000 m) land use type should be controlled, the water body and swamp areas should be controlled, the self-purification capacity of wetland waters should be improved, and the surface water environment of the Ruoergai wetland should be further protected and repaired.

A Comparative Investigation on Structural and Chemical Differences between the Pith and Rind of Sunflower Stalk and Their Influences on Nanofibrillation Efficiency.

The structure and chemical composition of cell walls play a vital role in the bioconversion and utilization of plants. In the present study, the cell wall structure and chemical composition of pith and rind from sunflower stalks were compared and correlated to their nanofibrillation efficiency with ultrasonic treatment. Mild chemical pretreatment using 1% or 4% NaOH without any bleaching process were applied prior to ultrasonication nanofibrillation. Significant structural and chemical differences were demonstrated between the pith and rind, with the former exhibiting a much lower lignin and hemicellulose contents, higher pectin, much looser cell structure and higher cell wall porosity than the latter. Alkaline treatment alone was sufficient to eliminate most of the hemicellulose and pectin from stalk pith, whereas only partial removal of hemicellulose and lignin was achieved for the woody rind part. After 30 min of ultrasonic treatment, the stalk pith exhibited fully defibrillated fibrils with a continuous and entangled micro/nanofibrillated network, whereas numerous micron-sized fiber and fragments remained for the rind. The results indicated that stalk pith is less recalcitrant and easier to be fibrillated with ultrasonication than rind, which must be correlated to their distinct differences in both structure and chemical composition.

Nitrite- and N2O-reducing bacteria respond differently to ecological factors in saline lakes.

The distribution of nitrite- and N2O-reducing bacteria is key to potential N2O emission from lakes. However, such information in highland saline lakes remains unknown. Here, we investigated the abundance and community composition of nitrite- and N2O-reducing bacteria in the sediments of six saline lakes on the Qing-Tibetan Plateau. The studied lakes covered a wide range of salinity (1.0-340.0 g/L). Results showed that in the studied saline lake sediments, nitrite-reducing bacteria were significantly more abundant than N2O-reducing bacteria, and their abundances ranged 7.14 × 103-8.26 × 108 and 1.18 × 106-6.51 × 107 copies per gram sediment (dry weight), respectively. Nitrite-reducing bacteria were mainly affiliated with α-, ß- and γ-Proteobacteria, with ß- and α-Proteobacteria being dominant in low- and high-salinity lakes, respectively; N2O-reducing bacterial communities mainly consisted of Proteobacteria (α-, ß-, γ- and δ-subgroups), Bacteroidetes, Verrucomicrobia, Actinobacteria, Chloroflexi, Gemmatimonadetes and Balneolaeota, with Proteobacteria and Bacteroidetes/Verrucomicrobia dominating in low- and high-salinity lakes, respectively. The nitrite- and N2O-reducing bacterial communities showed distinct responses to ecological factors, and they were mainly regulated by mineralogical and physicochemical factors, respectively. In response to salinity change, the community composition of nitrite-reducing bacteria was more stable than that of N2O-reducing bacteria. These findings suggest that nitrite- and N2O-reducing bacteria may prefer niches with different salinity.

Aspergichromones A-E, Five Chromone Derivatives with Complicated Polycyclic Architecture from Aspergillus deflectus.

Five unprecedented chromone derivatives involving a 6/6/5/5/5/6 hexacyclic scaffold (1, 2), 6/6/5/6/6/6/6 heptacyclic scaffold (3), and 6/6/6/5/5/6 hexacyclic scaffold (4, 5) were obtained from the fungus Aspergillus deflectus NCC0415. Their structures were identified using comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Except for 3, the other compounds, especially the 6/6/6/5/5/6 hexacyclic derivatives (4 and 5), exhibited potent inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitory activities.

Structural Evolution of Cellulose from Bamboo Fibers and Parenchyma Cells during Ionic Liquid Pretreatment for Enhanced Hydrolysis.

Bamboo fibers and parenchyma cells, the two dominant types of cells in bamboo, exhibit some interesting differences in cellulose crystalline structures. In the present investigation, we further demonstrated that these structural differences affect their response during ionic liquid (IL) pretreatment and the sugar conversion yield, by tracking their changes in morphology, chemical, and crystalline structures. All of the results pointed to the fact that the cellulose from bamboo fibers exhibited higher recalcitrance to IL pretreatment, with a significantly lower change in crystallinity index, d spacings from the (110) and (11̅0) planes, crystallite sizes, and easier transformation from cellulose I to cellulose II after pretreatment, as compared to that from parenchyma cells. Furthermore, the crystalline parameters of (110) and (11̅0) lattice planes exhibited more changes compared to the (200) direction. This investigation highlights the significance of parenchyma cell wastes from bamboo processing plants as a competitive candidate for the biorefinery industry.

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus.

Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.