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1.
Foods ; 13(12)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38928870

ABSTRACT

To investigate the changes in phenols and antioxidant capacity in fermented grains during different stages of the fermentation process (Xiasha, Zaosha, and single-round stages) of Maotai-flavored liquor, the total phenolic contents of 61 samples, collected in different stages, were analyzed via the Folin-Ciocalteu method, and the phenolic compounds were then identified by high-performance liquid chromatography (HPLC). Subsequently, the antioxidant activities were determined using the DPPH free radical scavenging rate and ABTS and FRAP antioxidant capacities. The correlations among the total phenolic contents, individual phenolics, and three antioxidant activities of the samples were analyzed. The results show that the total phenolic contents of the fermented samples did not change significantly in the Xiasha and Zaosha stages but showed an upward trend in the single-round stage. A total of 12 phenol acids were identified in the fermented grains, including 5 phenolic acids (e.g., ferulic acid and caffeic acid), 4 flavonoids (e.g., luteolin and apigenin), and 3 proanthocyanidins (e.g., apigeninidin), for which the DPPH free radical scavenging rates and ABTS and FRAP antioxidant capacities of all of the fermented grain samples ranged from 78.91 ± 4.09 to 98.57 ± 1.52%, 3.23 ± 0.72 to 13.69 ± 1.40 mM Trolox, and 5.06 ± 0.36 to 14.10 ± 0.69 mM FeSO4, respectively. The total phenolic contents of the fermented grain samples were significantly and positively correlated with the ABTS and FRAP (p ≤ 0.05), while no significant correlations were found between total phenolic content and DPPH. In general, the total phenolic content, phenolic substances, and antioxidant capacity of the fermented grains exhibited changes during the fermentation process in liquor production, and the phenolic components contributed more to the antioxidant properties of the fermented grains. The present study provides a theoretical reference for analyzing the dynamic changes and antioxidant properties of functional phenolic components in fermented grains.

2.
Sci Adv ; 10(23): eadm9631, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38838154

ABSTRACT

Short-wavelength infrared (SWIR) light detection plays a key role in modern technologies. Emerging solution-processed organic semiconductors are promising for cost-effective, flexible, and large-area SWIR organic photodiodes (OPDs). However, the spectral responsivity (R) and specific detectivity (D*) of SWIR OPDs are restricted by insufficient exciton dissociation and high noise current. In this work, we synthesized an SWIR small molecule with a spectral coverage of 0.3 to 1.3 micrometers peaking at 1100 nanometers. The photodiode, with optimized exciton dissociation, charge injection, and SWIR transmittance, achieves a record high R of 0.53 ampere per watt and D* of 1.71 × 1013 Jones at 1110 nanometers under zero bias. The D* at 1 to 1.2 micrometers surpasses that of the uncooled commercial InGaAs photodiode. Furthermore, large-area semitransparent all-organic upconversion devices integrating the SWIR photodiode realized static and dynamic SWIR-to-visible imaging, along with excellent upconversion efficiency and spatial resolution. This work provides alternative insights for developing sensitive organic SWIR detection.

3.
Food Chem X ; 23: 101531, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38911472

ABSTRACT

To investigate the changes of phenolic metabolite during different grains fermentation stages of Chinse Baijiu, the ultra-performance liquid chromatography-quadrupole time of-flight mass spectrometry (UHPLC-QTOF-MS) was applied to identify and analyze the different phenolic metabolites, combined with principal component analysis and partial least squares discriminant analysis. Results indicated that significant differences in phenolic metabolites during different fermentation stages were found. Among the 231 phenolic metabolites detected, 36, 31, 19, 23, 14, and 50 differential phenolic metabolites were screened between different groups using partial least squares discriminant analysis. Twelve metabolic pathways with high correlation of differential phenolic metabolites and 23 main participating differential metabolites were identified through KEGG metabolic pathway enrichment analysis. The present study preliminarily revealed the differences of phenolic metabolites at different fermentation stages, and providing a theoretical basis for the further improving of the taste and quality of Chinese Baijiu.

4.
Surg Endosc ; 38(6): 3455-3460, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38755463

ABSTRACT

BACKGROUND: Laparoscopic anatomical resection of segment 7 (LARS7) remains a technically challenging procedure due to the deep anatomical location and the potential risk of injury to the right hepatic vein (RHV). Herein, we initiated an innovative technique of caudo-dorsal approach combined with the occlusion of the RHV and Pringle maneuver for LARS7 and presented the outcomes of our initial series. METHOD: Since January 2021, the patients who underwent LARS7 by using this novel technique were enrolled in this study. The critical aspect of this technique was the interruption of communication between the RHV and the inferior vena cava. Meanwhile, the Pringle maneuver was adopted to control the hepatic inflow. RESULT: A total of 11 patients underwent LARS7 by using this novel technique, which included 8 hepatocellular carcinoma, 2 bile duct adenocarcinoma and one focal nodular hyperplasia. The median operative time was 199 min (range of 151-318 min) and the median blood loss was 150 ml (range of 50-200 ml). The main trunk of the RHV was fully exposed on the cutting surface in all cases and no patient received perioperative blood transfusion. No procedure was converted to open surgery. Of note, no indications of CO2 gas embolism were observed in these cases after the introduction of double occlusion. Only one patient suffered from postoperative complications and healed after treatment. The median postoperative stay was 5 days (range of 4-7 days). The 90-day mortality was nil. At a median follow-up period of 19 months, all of the patients were alive without any evidence of tumor recurrence. CONCLUSION: The caudo-dorsal approach combined with the occlusion of RHV and the Pringle maneuver may be a feasible and expected technique for safe exposure of RHV in LARS7. Further validation of the feasibility and efficacy of this technique is needed.


Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Hepatic Veins , Laparoscopy , Liver Neoplasms , Humans , Laparoscopy/methods , Male , Hepatic Veins/surgery , Female , Middle Aged , Liver Neoplasms/surgery , Aged , Hepatectomy/methods , Carcinoma, Hepatocellular/surgery , Operative Time , Adult , Bile Duct Neoplasms/surgery , Blood Loss, Surgical/statistics & numerical data , Blood Loss, Surgical/prevention & control , Focal Nodular Hyperplasia/surgery , Adenocarcinoma/surgery
5.
ACS Nano ; 18(23): 14978-14988, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38805401

ABSTRACT

3D assembly technology is a cutting-edge methodology for constructing high-performance and multifunctional photodetectors since some attractive photodetection features such as light trapping effect, omnidirectional ability, and high spatial resolution can be introduced. However, there has not been any report of 3D-assembled multimode photodetectors owing to the lack of design and fabrication guideline of electrodes serving for 3D heterostructures. In this study, a 3D-assembled dual-mode photodetector (3DdmPD) was realized successfully via the clever electrical contact between the rolled-up tubular graphene/GaAs/InGaAs heterostructure and planar metal electrode. Arbitrary switching of three coplanar electrodes makes the as-fabricated tubular 3D photodetector work at the unbiased photodiode mode, which is suitable for energy conservation high-speed photodetection, or the biased photoconductive mode, which favors extremely weak light photodetection, fully showing the advantages of multifunctional detection. In more detail, the Ilight/Idark ratio reached as high as 2 × 104, and a responsivity of 42.3 mA/W, a detectivity of 1.5 × 1010 Jones, as well as a rising/falling time (τr/τf) of 360/370 µs were achieved under the self-driven photodiode mode. Excitingly, 3DdmPD shows omnidirectional photodetection ability at the same time. When 3DdmPD works at the photoconductive mode with 5 V bias, its responsivity is extremely high as 7.9 × 104 A/W and corresponding detectivity is increased to 1.0 × 1011 Jones. Benefiting from the totally independent coplanar electrodes, 3DdmPD is much more easily integrated as arrays that are expected to offer the function of high-speed omnidirectional image-sensing with ultralow power consumption than the planar counterparts which share communal bottom electrodes. We believe that our work can contribute to the progress of 3D-assembled optoelectronic devices.

6.
J Agric Food Chem ; 72(20): 11381-11391, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38728113

ABSTRACT

RNA interference (RNAi)-based biopesticides offer an attractive avenue for pest control. Previous studies revealed high RNAi sensitivity in Holotrichia parallela larvae, showcasing its potential for grub control. In this study, we aimed to develop an environmentally friendly RNAi method for H. parallela larvae. The double-stranded RNA (dsRNA) of the V-ATPase-a gene (HpVAA) was loaded onto layered double hydroxide (LDH). The dsRNA/LDH nanocomplex exhibited increased environmental stability, and we investigated the absorption rate and permeability of dsRNA-nanoparticle complexes and explored the RNAi controlling effect. Silencing the HpVAA gene was found to darken the epidermis of H. parallela larvae, with growth cessation or death or mortality, disrupting the epidermis and midgut structure. Quantitative reverse transcription-polymerase chain reaction and confocal microscopy confirmed the effective absorption of the dsRNA/LDH nanocomplex by peanut plants, with distribution in roots, stems, and leaves. Nanomaterial-mediated RNAi silenced the target genes, leading to the death of pests. Therefore, these findings indicate the successful application of the nanomaterial-mediated RNAi system for underground pests, thus establishing a theoretical foundation for developing a green, safe, and efficient pest control strategy.


Subject(s)
Larva , RNA Interference , RNA, Double-Stranded , Animals , Larva/growth & development , Larva/genetics , RNA, Double-Stranded/genetics , RNA, Double-Stranded/metabolism , Hydroxides/chemistry , Hydroxides/metabolism , Vacuolar Proton-Translocating ATPases/genetics , Vacuolar Proton-Translocating ATPases/metabolism , Vacuolar Proton-Translocating ATPases/chemistry , Arachis/genetics , Arachis/chemistry , Arachis/growth & development , Arachis/metabolism , Pest Control, Biological , Coleoptera/genetics , Coleoptera/growth & development , Green Chemistry Technology , Biological Control Agents/chemistry , Biological Control Agents/metabolism , Nanoparticles/chemistry
7.
Aging Dis ; 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38607733

ABSTRACT

Numerous research works have emphasized the critical role that circadian rhythm plays in the tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment in clinical settings is a continuous endeavor. Consequently, to enhance the use of time-based pharmaceutical therapies in oncology, combining existing knowledge on circadian rhythms' roles within the TME is essential. This perspective elucidates the functions of circadian rhythms in the TME across various stages of cancer development, progression, and metastasis. Specifically, aging, angiogenesis, and inflammation are implicated in modulating circadian rhythm within the TME. Furthermore, circadian rhythm exerts a profound influence on current cancer treatments and thereby generates chronotheray to manage tumors. From a TME perspective, circadian rhythm offers promising opportunities for cancer prevention and treatment; nevertheless, further study is needed to address unanswered scientific problems.

8.
Molecules ; 29(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38675674

ABSTRACT

The water produced during the oxidative esterification reaction occupies the active sites and reduces the activity of the catalyst. In order to reduce the influence of water on the reaction system, a hydrophobic catalyst was prepared for the one-step oxidative esterification of methylacrolein (MAL) and methanol. The catalyst was synthesized by loading the active component Au onto ZnO using the deposition-precipitation method, followed by constructing the silicon shell on Au/ZnO using tetraethoxysilane (TEOS) to introduce hydrophobic groups. Trimethylchlorosilane (TMCS) was used as a hydrophobic modification reagent to prepare hydrophobic catalysts, which exhibited a water droplet contact angle of 111.2°. At a temperature of 80 °C, the hydrophobic catalyst achieved a high MMA selectivity of over 95%. The samples were characterized using XRD, N2 adsorption, ICP, SEM, TEM, UV-vis, FT-IR, XPS, and water droplet contact angle measurements. Kinetic analysis revealed an activation energy of 22.44 kJ/mol for the hydrophobic catalyst.

9.
Phys Rev Lett ; 132(7): 076503, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38427879

ABSTRACT

Transition metal dichalcogenide superlattices provide an exciting new platform for exploring and understanding a variety of phases of matter. The moiré continuum Hamiltonian, of two-dimensional jellium in a modulating potential, provides a fundamental model for such systems. Accurate computations with this model are essential for interpreting experimental observations and making predictions for future explorations. In this work, we combine two complementary quantum Monte Carlo (QMC) methods, phaseless auxiliary field quantum Monte Carlo and fixed-phase diffusion Monte Carlo, to study the ground state of this Hamiltonian. We observe a metal-insulator transition between a paramagnet and a 120° Néel ordered state as the moiré potential depth and the interaction strength are varied. We find significant differences from existing results by Hartree-Fock and exact diagonalization studies. In addition, we benchmark density-functional theory, and suggest an optimal hybrid functional which best approximates our QMC results.

11.
Heliyon ; 10(1): e23495, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38187257

ABSTRACT

Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.

13.
Heliyon ; 9(11): e22186, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38045189

ABSTRACT

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, ß-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

14.
Food Chem X ; 20: 100933, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38144804

ABSTRACT

Dipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography - mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from -25.71 % to 24.19 % and -14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.

15.
Molecules ; 28(22)2023 Nov 09.
Article in English | MEDLINE | ID: mdl-38005214

ABSTRACT

Distiller's grains (DGs) are solid mixtures that remain after the production of alcoholic beverages. A large amount of DGs is produced each year during the brewing process. Currently, they are mostly used as a feedstock or substrate in the feed industry. However, the lack of a comprehensive understanding of the chemical composition of DGs is a major constraint on their further development and application for high-value-added usages. Some studies were published on the bioactive constituents of DGs in several different types of journals. Data were therefore collated to provide a comprehensive overview of these natural products. DGs are rich in phenols, phytosterols, and fatty acids, in addition to general lipid and protein constituents. These compounds and their related extracts possess diverse biological activities, including antioxidant, anti-inflammatory, and anti-hyperglycaemic effects. We hope that this review will provide research incentives for the further development and utilisation of DGs to develop high-value-added products.


Subject(s)
Alcoholic Beverages , Proteins , Antioxidants/pharmacology , Edible Grain , Plant Structures , Animal Feed
16.
Foods ; 12(17)2023 Sep 03.
Article in English | MEDLINE | ID: mdl-37685247

ABSTRACT

Polyphenols, as common components with various functional activities in plants, have become a research hotspot. However, researchers have found that the bioavailability and bioactivity of plant polyphenols is generally low because they are usually in the form of tannins, anthocyanins and glycosides. Polyphenol-rich fermented foods (PFFs) are reported to have better bioavailability and bioactivity than polyphenol-rich foods, because polyphenols are used as substrates during food fermentation and are hydrolyzed into smaller phenolic compounds (such as quercetin, kaempferol, gallic acid, ellagic acid, etc.) with higher bioactivity and bioavailability by polyphenol-associated enzymes (PAEs, e.g., tannases, esterases, phenolic acid decarboxylases and glycosidases). Biotransformation pathways of different polyphenols by PAEs secreted by different microorganisms are different. Meanwhile, polyphenols could also promote the growth of beneficial bacteria during the fermentation process while inhibiting the growth of pathogenic bacteria. Therefore, during the fermentation of PFFs, there must be an interactive relationship between polyphenols and microorganisms. The present study is an integration and analysis of the interaction mechanism between PFFs and microorganisms and is systematically elaborated. The present study will provide some new insights to explore the bioavailability and bioactivity of polyphenol-rich foods and greater exploitation of the availability of functional components (such as polyphenols) in plant-derived foods.

17.
Int J Mol Sci ; 24(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37239852

ABSTRACT

Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.


Subject(s)
Extracellular Vesicles , Melanoma , Humans , Glycosaminoglycans/metabolism , Hyaluronic Acid/metabolism , Melanoma/diagnosis , Melanoma/metabolism , Polysaccharides/metabolism , Extracellular Vesicles/metabolism
18.
Urol Oncol ; 41(7): 327.e9-327.e18, 2023 07.
Article in English | MEDLINE | ID: mdl-37208228

ABSTRACT

PURPOSE: To explore the role of circadian clock gene NR1D1 (REV-erbα) in bladder cancer (BC). METHODS: Firstly, the association of NR1D1 level with clinical characteristics and prognosis was investigated among patients diagnosed with BC. Secondly, CCK-8, transwell, and colony formation experiments were performed among BC cells treated with Rev-erbα agonist (SR9009), as well as lentivirus and siRNA, for which NR1D1 were overexpressed (OE) and knocked down (KD), respectively. Thirdly, cell cycle and apoptosis were tested by flowcytometry. PI3K/AKT/mTOR pathway proteins were determined in OE-NR1D1 cells. Finally, OE-NR1D1 and OE-Control BC cells were subcutaneously implanted in BALB/c nude mice. The tumor size and protein levels were compared between groups. A P < 0.05 was considered as statistically significant. RESULTS: Patients with NR1D1 positive status had a longer disease-free survival than those with negative expression. The cell viability, migration, and colony formation of BC cells after treated with SR9009 were significantly suppressed. OE-NR1D1 cells had obviously inhibited cell viability, migration, and colony formation, while those were found strengthened in KD-NR1D1 cells. Besides, KD-NR1D1 cells were observed with a lower proportion of dead cells and G0/G1 cells, but a higher ratio of G2/M. The changes of p-AKT, p-S6, p-4EBP1, and FASN involved in PI3K/AKT/mTOR pathway were detected in OE- and KD-NR1D1 BC cells. Finally, in vivo data demonstrated that overexpression of NR1D1 suppressed the tumorigenicity of BC cells. CONCLUSION: NR1D1 played a role of tumor suppressor and it might become a novel target for the treatment of BC.


Subject(s)
Nuclear Receptor Subfamily 1, Group D, Member 1 , Urinary Bladder Neoplasms , Animals , Mice , Mice, Nude , Nuclear Receptor Subfamily 1, Group D, Member 1/genetics , Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine Kinases , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Humans
19.
Chem Commun (Camb) ; 59(36): 5403-5406, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37060141

ABSTRACT

Through the catalysis system design of in situ Ru SACs (single atoms) anchored on a rGO/NC two-dimensional interface, we successfully realized the SA-Ru@rGO/NC electrocatalyst with high metal loading density at a relatively low temperature. The largest NH3 yield of 110.1 µg h-1 mgcat-1 and FE of 17.9% were achieved at -0.3 V under ambient conditions. The electronic environment of the catalyst was regulated by the electronic metal-support interaction, and the use of SACs had the advantages of inhibiting the hydrogen evolution reaction (HER) and enhancing N2 adsorption, which effectively improved the performance of electrocatalytic nitrogen fixation.

20.
Phys Rev Lett ; 130(7): 076102, 2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36867819

ABSTRACT

We survey the phase diagram of high-pressure molecular hydrogen with path integral molecular dynamics using a machine-learned interatomic potential trained with quantum Monte Carlo forces and energies. Besides the HCP and C2/c-24 phases, we find two new stable phases both with molecular centers in the Fmmm-4 structure, separated by a molecular orientation transition with temperature. The high temperature isotropic Fmmm-4 phase has a reentrant melting line with a maximum at higher temperature (1450 K at 150 GPa) than previously estimated and crosses the liquid-liquid transition line around 1200 K and 200 GPa.

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