HIV-1 p17 matrix protein enhances type I interferon responses through the p17-OLA1-STING axis.

Stimulator of IFN genes (STING; also known as STING1) is an important adaptor protein for detecting cytosolic double-stranded DNA, which can come from HIV infection. Several HIV proteins, such as p6, Vpx and Vif, can influence STING-mediated innate immunity, but the function of p17 is still unknown. In this study, we find that HIV-1 p17, but not HIV-2 p17 or SIV p17, promotes STING signaling induced by cyclic GMP-AMP (cGAMP) treatment. Mechanistically, HIV-1 p17 binds to Obg-like ATPase 1 (OLA1) and inhibits the regulation of STING by OLA1. Here, OLA1 interacts with STING and inhibits the translocation and phosphorylation of STING upon cGAMP stimulation. Furthermore, compared with HIV-2 and SIV, the ATPase and GTPase activities of OLA1 are only promoted by HIV-1 p17. Our study shows that the p17 of HIV-1, but not HIV-2 or SIV, promotes STING-mediated innate immunity by interfering the interaction between OLA1 and STING, thus providing a new clue for specific immune activation of HIV-1.

IGCNSDA: unraveling disease-associated snoRNAs with an interpretable graph convolutional network.

Accurately delineating the connection between short nucleolar RNA (snoRNA) and disease is crucial for advancing disease detection and treatment. While traditional biological experimental methods are effective, they are labor-intensive, costly and lack scalability. With the ongoing progress in computer technology, an increasing number of deep learning techniques are being employed to predict snoRNA-disease associations. Nevertheless, the majority of these methods are black-box models, lacking interpretability and the capability to elucidate the snoRNA-disease association mechanism. In this study, we introduce IGCNSDA, an innovative and interpretable graph convolutional network (GCN) approach tailored for the efficient inference of snoRNA-disease associations. IGCNSDA leverages the GCN framework to extract node feature representations of snoRNAs and diseases from the bipartite snoRNA-disease graph. SnoRNAs with high similarity are more likely to be linked to analogous diseases, and vice versa. To facilitate this process, we introduce a subgraph generation algorithm that effectively groups similar snoRNAs and their associated diseases into cohesive subgraphs. Subsequently, we aggregate information from neighboring nodes within these subgraphs, iteratively updating the embeddings of snoRNAs and diseases. The experimental results demonstrate that IGCNSDA outperforms the most recent, highly relevant methods. Additionally, our interpretability analysis provides compelling evidence that IGCNSDA adeptly captures the underlying similarity between snoRNAs and diseases, thus affording researchers enhanced insights into the snoRNA-disease association mechanism. Furthermore, we present illustrative case studies that demonstrate the utility of IGCNSDA as a valuable tool for efficiently predicting potential snoRNA-disease associations. The dataset and source code for IGCNSDA are openly accessible at: https://github.com/altriavin/IGCNSDA.

Hypoxia-inducible factor prolyl hydroxylase inhibitor alleviates heatstroke-induced acute kidney injury by activating BNIP3-mediated mitophagy.

Hypoxia-induced inflammation and apoptosis are important pathophysiological features of heat stroke-induced acute kidney injury (HS-AKI). Hypoxia-inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF-PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF-PHI could alleviate HS-induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi-1, 3-MA, and Baf-A1 reversed the renoprotective effects of HIF-PHI. Mechanistically, HIF-PHI protects RTECs from inflammation and apoptosis by enhancing Bcl-2 adenovirus E18 19-kDa-interacting protein 3 (BNIP3)-mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF-PHI-induced mitophagy and abolished HIF-PHI-mediated renal protection. Thus, our results indicated that HIF-PHI protects renal function by upregulating BNIP3-mediated mitophagy to improve HS-induced inflammation and apoptosis of RTECs, suggesting HIF-PHI as a promising therapeutic agent to treat HS-AKI.

Artificial Funnel Nanochannel Device Emulates Synaptic Behavior.

Creating artificial synapses that can interact with biological neural systems is critical for developing advanced intelligent systems. However, there are still many difficulties, including device morphology and fluid selection. Based on Micro-Electro-Mechanical System technologies, we utilized two immiscible electrolytes to form a liquid/liquid interface at the tip of a funnel nanochannel, effectively enabling a wafer-level fabrication, interactions between multiple information carriers, and electron-to-chemical signal transitions. The distinctive ionic transport properties successfully achieved a hysteresis in ionic transport, resulting in adjustable multistage conductance gradient and synaptic functions. Notably, the device is similar to biological systems in terms of structure and signal carriers, especially for the low operating voltage (200 mV), which matches the biological neural potential (∼110 mV). This work lays the foundation for realizing the function of iontronics neuromorphic computing at ultralow operating voltages and in-memory computing, which can break the limits of information barriers for brain-machine interfaces.

Genome-wide analysis and expression pattern of the ZoPP2C gene family in Zingiber officinale Roscoe.

BACKGROUND: Protein phosphatases type 2C (PP2C) are heavily involved in plant growth and development, hormone-related signaling pathways and the response of various biotic and abiotic stresses. However, a comprehensive report identifying the genome-scale of PP2C gene family in ginger is yet to be published. RESULTS: In this study, 97 ZoPP2C genes were identified based on the ginger genome. These genes were classified into 15 branches (A-O) according to the phylogenetic analysis and distributed unevenly on 11 ginger chromosomes. The proteins mainly functioned in the nucleus. Similar motif patterns and exon/intron arrangement structures were identified in the same subfamily of ZoPP2Cs. Collinearity analysis indicated that ZoPP2Cs had 33 pairs of fragment duplicated events uniformly distributed on the corresponding chromosomes. Furthermore, ZoPP2Cs showed greater evolutionary proximity to banana's PP2Cs. The forecast of cis-regulatory elements and transcription factor binding sites demonstrated that ZoPP2Cs participate in ginger growth, development, and responses to hormones and stresses. ZoERFs have plenty of binding sites of ZoPP2Cs, suggesting a potential synergistic contribution between ZoERFs and ZoPP2Cs towards regulating growth/development and adverse conditions. The protein-protein interaction network displayed that five ZoPP2Cs (9/23/26/49/92) proteins have robust interaction relationship and potential function as hub proteins. Furthermore, the RNA-Seq and qRT-PCR analyses have shown that ZoPP2Cs exhibit various expression patterns during ginger maturation and responses to environmental stresses such as chilling, drought, flooding, salt, and Fusarium solani. Notably, exogenous application of melatonin led to notable up-regulation of ZoPP2Cs (17/59/11/72/43) under chilling stress. CONCLUSIONS: Taken together, our investigation provides significant insights of the ginger PP2C gene family and establishes the groundwork for its functional validation and genetic engineering applications.

Atomic-Scale Cryo-TEM Studies of the Electrochemistry of Redox Mediator in Li-O2 Batteries.

Rechargeable aprotic lithium (Li)-oxygen battery (LOB) is a potential next-generation energy storage technology because of its high theoretical specific energy. However, the role of redox mediator on the oxide electrochemistry remains unclear. This is partly due to the intrinsic complexity of the battery chemistry and the lack of in-depth studies of oxygen electrodes at the atomic level by reliable techniques. Herein, cryo-transmission electron microscopy (cryo-TEM) is used to study how the redox mediator LiI affects the oxygen electrochemistry in LOBs. It is revealed that with or without LiI in the electrolyte, the discharge products are plate-like LiOH or toroidal Li2O2, respectively. The I2 assists the decomposition of LiOH via the formation of LiIO3 in the charge process. In addition, a LiI protective layer is formed on the Li anode surface by the shuttle of I3 -, which inhibits the parasitic Li/electrolyte reaction and improves the cycle performance of the LOBs. The LOBs returned to 2e- oxygen reduction reaction (ORR) to produce Li2O2 after the LiI in the electrolyte is consumed. This work provides new insight on the role of redox mediator on the complex electrochemistry in LOBs which may aid the design LOBs for practical applications.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

Altered gut mycobiome in patients with end-stage renal disease and its correlations with serum and fecal metabolomes.

BACKGROUND: The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored. METHODS: In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites. RESULTS: Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces. CONCLUSIONS: Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.

Metagenomic analysis of the gut virome in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, is recognized for its association with alterations in the gut microbiome and metabolome. This study delves into the largely unexplored domain of the gut virome in IBS patients. We conducted a comprehensive analysis of the fecal metagenomic data set from 277 IBS patients and 84 healthy controls to characterize the gut viral community. Our findings revealed a distinct gut virome in IBS patients compared to healthy individuals, marked by significant variances in between-sample diversity and altered abundances of 127 viral operational taxonomic units (vOTUs). Specifically, 111 vOTUs, predominantly belonging to crAss-like, Siphoviridae, Myoviridae, and Quimbyviridae families, were more abundant in IBS patients, whereas the healthy control group exhibited enrichment of 16 vOTUs from multiple families. We also investigated the interplay between the gut virome and bacteriome, identifying a correlation between IBS-enriched bacteria like Klebsiella pneumoniae, Fusobacterium varium, and Ruminococcus gnavus, and the IBS-associated vOTUs. Furthermore, we assessed the potential of gut viral signatures in predicting IBS, achieving a notable area under the receiver operator characteristic curve (AUC) of 0.834. These findings highlight significant shifts in the viral diversity, taxonomic distribution, and functional composition of the gut virome in IBS patients, suggesting the potential role of the gut virome in IBS pathogenesis and opening new avenues for diagnostic and therapeutic strategies targeting the gut virome in IBS management.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Efficient automated high dynamic range 3D measurement via deep reinforcement learning.

High dynamic range 3D measurement technology, utilizing multiple exposures, is pivotal in industrial metrology. However, selecting the optimal exposure sequence to balance measurement efficiency and quality remains challenging. This study reinterprets this challenge as a Markov decision problem and presents an innovative exposure selection method rooted in deep reinforcement learning. Our approach's foundation is the exposure image prediction network (EIPN), designed to predict images under specific exposures, thereby simulating a virtual environment. Concurrently, we establish a reward function that amalgamates considerations of exposure number, exposure time, coverage, and accuracy, providing a comprehensive task definition and precise feedback. Building upon these foundational elements, the exposure selection network (ESN) emerges as the centerpiece of our strategy, acting decisively as an agent to derive the optimal exposure sequence selection. Experiments prove that the proposed method can obtain similar coverage (0.997 vs. 1) and precision (0.0263 mm vs. 0.0230 mm) with fewer exposures (generally 4) compared to the results of 20 exposures.

Tensor Network Message Passing.

When studying interacting systems, computing their statistical properties is a fundamental problem in various fields such as physics, applied mathematics, and machine learning. However, this task can be quite challenging due to the exponential growth of the state space as the system size increases. Many standard methods have significant weaknesses. For instance, message-passing algorithms can be inaccurate and even fail to converge due to short loops, while tensor network methods can have exponential computational complexity in large graphs due to long loops. In this Letter, we propose a new method called "tensor network message passing." This approach allows us to compute local observables like marginal probabilities and correlations by combining the strengths of tensor networks in contracting small subgraphs with many short loops and the strengths of message-passing methods in globally sparse graphs, thus addressing the crucial weaknesses of both approaches. Our algorithm is exact for systems that are globally treelike and locally dense-connected when the dense local graphs have a limited tree width. We have conducted numerical experiments on synthetic and real-world graphs to compute magnetizations of Ising models and spin glasses, and have demonstrated the superiority of our approach over standard belief propagation and the recently proposed loopy message-passing algorithm. In addition, we discuss the potential applications of our method in inference problems in networks, combinatorial optimization problems, and decoding problems in quantum error correction.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Dynamically or Kinetically Controlled? Computational Study of the Mechanisms of Electrophilic Aminoalkenylation of Heteroaromatics with Keteniminium Ions.

Quantum chemical calculations and molecular dynamics simulations were applied to study the electrophilic aminoalkenylation of heteroaromatics with keniminium ions. Post-transition state bifurcation (PTSB) was found in the electrophilic addition step for the aminoalkenylation of pyrroles and indoles, and the selectivity for these reactions was dynamically controlled. However, the aminoalkenylation of furan was kinetically controlled because no apparent PTSB was found in the electrophilic addition step. The substituents on the keteniminium ions can also affect the dynamic results for the aminoalkenylations to pyrroles: the C2-aminoalkenylated product is much more favored over the C3-aminoalkenylated product for keteniminium ions with electron-donating substituents, while the product ratio (C2 product/C3 product) decreased when stronger electron-withdrawing substituents were applied.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Efficient Catalytic Elimination of Toxic Volatile Organic Compounds via Advanced Oxidation Process Wet Scrubbing with Bifunctional Cobalt Sulfide/Activated Carbon Catalysts.

Advanced oxidation process (AOP) wet scrubber is a powerful and clean technology for organic pollutant treatment but still presents great challenges in removing the highly toxic and hydrophobic volatile organic compounds (VOCs). Herein, we elaborately designed a bifunctional cobalt sulfide (CoS2)/activated carbon (AC) catalyst to activate peroxymonosulfate (PMS) for efficient toxic VOC removal in an AOP wet scrubber. By combining the excellent VOC adsorption capacity of AC with the highly efficient PMS activation activity of CoS2, CoS2/AC can rapidly capture VOCs from the gas phase to proceed with the SO4•- and HO• radical-induced oxidation reaction. More than 90% of aromatic VOCs were removed over a wide pH range (3-11) with low Co ion leaching (0.19 mg/L). The electron-rich sulfur vacancies and low-valence Co species were the main active sites for PMS activation. SO4•- was mainly responsible for the initial oxidation of VOCs, while HO• and O2 acted in the subsequent ring-opening and mineralization processes of intermediates. No gaseous intermediates from VOC oxidation were detected, and the highly toxic liquid intermediates like benzene were also greatly decreased, thus effectively reducing the health toxicity associated with byproduct emissions. This work provided a comprehensive understanding of the deep oxidation of VOCs via AOP wet scrubber, significantly accelerating its application in environmental remediation.

Shell thickness-induced thermal dependence: highly sensitive core-shell CdSe/ZnS/POSS-based temperature probes.

Fluorescence nanothermometry based on quantum dots is a current research hotspot for novel non-contact temperature monitoring, and is of vital significance for the modulation and design of the sensing properties of sensors. Herein, a design strategy to modulate the temperature-sensing characteristics of quantum dots based on the thickness of a shell is proposed. In this study, CdSe/ZnS quantum dot/POSS-based temperature probe films with varying fluorescence characteristics were developed, and the influence of the ZnS shell on temperature sensing was examined by varying the thickness of the ZnS shell. The temperature dependency, linearity, range of applications, and reversibility of quantum dot thin film probes were all considerably regulated by the ZnS shell, according to research on quantum dot/POSS-based films coated with various shell thicknesses. The CdSe/ZnS temperature probe with 4 monolayers (MLs) stood out among the rest due to its strong thermal stability (at least 5 cycles), large usable temperature range (20-80 °C), and excellent temperature sensitivity (R2 > 0.994). The results demonstrated that the temperature sensing performance of quantum dots was the consequence of the combined effect of multiple temperature response properties induced by the thickness of the shell, and the shell control of quantum dots to optimize the temperature sensing performance was an essential approach for the design of temperature probes. This work demonstrates the great potential of the shell in tuning the temperature sensing performance of quantum dots and provides a viable approach for the design of quantum dot temperature probes.

Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

Unveiling unconventional CH4-Xe compounds and their thermodynamic properties at extreme conditions.

Inert gases (e.g., He and Xe) can exhibit chemical activity at high pressure, reacting with other substances to form compounds of unexpected chemical stoichiometry. This work combines first-principles calculations and crystal structure predictions to propose four unexpected stable compounds of CH4Xe3, (CH4)2Xe, (CH4)3Xe, and (CH4)3Xe2 at pressure ranges from 2 to 100 GPa. All structures are composed of isolated Xe atoms and CH4 molecules except for (CH4)3Xe2, which comprises a polymerization product, C3H8, and hydrogen molecules. Ab initio molecular dynamics simulations indicate that pressure plays a very important role in the different temperature driving state transitions of CH4-Xe compounds. At lower pressures, the compounds follow the state transition of solid-plastic-fluid phases with increasing temperature, while at higher pressures, the stronger Xe-C interaction induces the emergence of a superionic state for CH4Xe3 and (CH4)3Xe2 as temperature increases. These results not only expand the family of CH4-Xe compounds, they also contribute to models of the structures and evolution of planetary interiors.

Knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney.

BACKGROUND: Sepsis is a life-threatening, systemic inflammatory disease that can lead to a variety of conditions, including septic acute kidney injury (AKI). Recently, multiple circular Rnas (circRNAs) have been implicated in the development of this disease. METHODS: In this study, we aimed to elucidate the role of circ-Gatad1 in sepsis induced AKI and its potential mechanism of action. High-throughput sequencing was used to investigate abnormal expression of circRNA in AKI and healthy volunteer. Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. HK2 cells were employ to analysis the ROS, inflammatory cytokines expression, proliferation and apoptosis under LPS condition. RESULTS: The result show that the expression of circ-Gatad1 was increased in septic acute kidney patients. Downregulation circ-Gatad1 suppressed LPS-treated induced HK2 cells injury including apoptosis, proliferation ability, ROS and inflammatory cytokines level. Bioinformatics and luciferase report analysis confirmed that both miR-22-3p and TRPM7 were downstream targets of circ-Gatad1. Overexpression of TRPM7 or downregulation of miR-22-3p reversed the protective effect of si-circ-Gatad1 to HK2 after exposure to LPS (5 µg/ml) microenvironment. CONCLUSION: In conclusion, knockdown of circ-Gatad1 alleviates LPS induced HK2 cell injury via targeting miR-22-3p/TRPM7 axis in septic acute kidney.