Hybrid Functional Study Rationalizes the Simple Cubic Phase of Calcium at High Pressures

Simple cubic (SC) phase has been long experimentally determined as the high-pressure phase III of elemental calcium (Ca) since 1984. However, recent density functional calculations within semi-local approximation showed that this SC phase is structurally unstable by exhibiting severely imaginary phonons, and is energetically unstable with respect to a theoretical body-centered tetragonal I41/amd structure over the pressure range of phase III. These calculations generated extensive debates on the validity of SC phase. Here we have re-examined the SC structure by performing more precise density functional calculations within hybrid functionals of Heyd-Scuseria-Erhzerhof (HSE) and PBE0. Our calculations were able to rationalize fundamentally the phase stability of SC structure over all other known phases by evidence of its actual energetic stability above 33 GPa and its intrinsically dynamical stability without showing any imaginary phonons in the entire pressure range studied. We further established that the long-thought theoretical I41/amd structure remains stable in a narrow pressure range before entering SC phase and is actually the structure of experimental Ca-III' synthesized recently at low temperature 14 K as supported by the excellent agreement between our simulated X-ray diffraction patterns and the experimental data. Our results shed strong light on the crucial role played by the precise electron exchange energy in a proper description of the potential energy of Ca.Comment: submitted to Physical Review

Room-Temperature Structures of Solid Hydrogen at High Pressures

By employing first-principles metadynamics simulations, we explore the 300 K structures of solid hydrogen over the pressure range 150-300 GPa. At 200 GPa, we find the ambient-pressure disordered hexagonal close-packed (hcp) phase transited into an insulating partially ordered hcp phase (po-hcp), a mixture of ordered graphene-like H2 layers and the other layers of weakly coupled, disordered H2 molecules. Within this phase, hydrogen remains in paired states with creation of shorter intra-molecular bonds, which are responsible for the very high experimental Raman peak above 4000 cm-1. At 275 GPa, our simulations predicted a transformation from po-hcp into the ordered molecular metallic Cmca phase (4 molecules/cell) that was previously proposed to be stable only above 400 GPa. Gibbs free energy calculations at 300 K confirmed the energetic stabilities of the po-hcp and metallic Cmca phases over all known structures at 220-242 GPa and >242 GPa, respectively. Our simulations highlighted the major role played by temperature in tuning the phase stabilities and provided theoretical support for claimed metallization of solid hydrogen below 300 GPa at 300 K.Comment: Accepted in Journal of Chemical Physic

Ecological Protection Alone Is Not Enough to Conserve Ecosystem Carbon Storage: Evidence from Guangdong, China

The increase in atmospheric CO2 caused by land use and land cover change (LUCC) is one of the drivers of the global climate. As one of the most typical high-urbanization areas, the ecological conflicts occurring in Guangdong Province warrant urgent attention. A growing body of evidence suggests LUCC could guide the future ecosystem carbon storage, but most LUCC simulations are simply based on model results without full consistency with the actual situation. Fully combined with the territorial spatial planning project and based on the land use pattern in 2010 and 2020, we have used the Markov and Patch-generating Land Use Simulation (PLUS) model to simulate the future four land use scenarios: the Business as Usual (BU), Ecological Protection (EP), Farmland Protection (FP), and Economic Development (ED) scenario, and the ecosystem carbon storage was assessed by the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model. The results show that the built-up area experience further expansion in all scenarios, the largest scale happened in ED and the smallest in FP. Besides, the forest area in the EP scenario is the largest, while the land use pattern developed based on the previous circumstances in the BU scenario. Furthermore, the carbon storage plunged from 1619.21 Tg C in 2010 to 1606.60 Tg C in 2020, with a total decrease of 12.61 Tg C. Urban expansion caused 79.83% of total carbon losses, of which 31.56% came from farmland. In 2030, the carbon storage dropped in all scenarios, and their storage amount has a relationship of FP \u3e BU \u3e EP \u3e ED. To better resolve the ecological problems and conserve ecosystem carbon storage, not only ecological protection but also the protection of the land near the city such as farmland protection strategies must be considered

Effects of an antibacterial membrane on osteoblast-like cells in vitro

Infection around membranes is often found in guided bone regeneration (GBR). The excellent antibacterial properties of Ag-nHA-nTiO2/polyamide-66 (PA66) nanocomposite membranes have been demonstrated previously. The aim of this study was to observe the microstructure of an Ag-nHA-nTiO2/PA66 membrane and its effects on osteoblast-like cells in vitro. An Ag-nHA-nTiO2/PA66 membrane was used in the experimental group, and both nHA/PA66 and expanded poly tetrafluroethylene (e-PTFE) membranes were set as control. MG63 osteoblast-like cells were cultured on the three kinds of membrane and tissue culture polystyrene (TCP). The microstructure of the above membranes and the cells adhered on them were detected by scanning electronic microscope (SEM). Cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell viability with a cell viability analyzer, and alkaline phosphatase (ALP) activity and Ca2+ concentration of osteoblast-like cell matrix by enzyme-linked immunosorbent assay. SEM showed that both Ag-nHA-nTiO2/PA66 membranes and nHA/PA66 membranes were composed of porous obverse face and smooth opposite face. The e-PTFE membranes showed elliptic surface structure with many tiny lined cracks. The MG63 cells adhered and proliferated well on all three kinds of membranes. Though cell viability on Ag-nHA-nTiO2/PA66 membranes was significantly lower than that of the control groups (P < 0.05), MTT values, ALP activity, and Ca2+ concentration did not differ significantly among the three kinds of membranes (P > 0.05). From these findings, it can be concluded that Ag-nHA-nTiO2/PA66 membranes are as biocompatible as nHA/ PA66 membranes and TCP, thus may be applied safely in GBR

Characterization of two functional NKX3.1 binding sites upstream of the PCAN1 gene that are involved in the positive regulation of PCAN1 gene transcription

<p>Abstract</p> <p>Background</p> <p><it>NKX3.1 </it>and <it>PCAN1 </it>are both prostate-specific genes related to prostate development and prostate cancer. So far, little is known about the regulatory mechanisms of the expression of these two genes. In the present study, we found that NKX3.1 upregulated <it>PCAN1 </it>gene transcription in LNCaP prostate cancer cells. To understand the regulatory mechanisms, our work focused on identifying the functional NKX3.1 binding sites upstream of the <it>PCAN1 </it>gene, which might be involved in the positive regulation of <it>PCAN1 </it>expression by NKX3.1.</p> <p>Results</p> <p>We cloned and characterized a 2.6 kb fragment upstream of the <it>PCAN1 </it>gene. Analysis of the 2.6 kb sequence with MatInspector 2.2 revealed five potential binding sites of NKX3.1 transcription factor. Luciferase reporter assays, electrophoretic mobility shift assays, chromatin immunoprecipitation and RNA interference were performed to study the effects of NKX3.1 on <it>PCAN1 </it>gene expression in prostate cancer cells. Our results showed that <it>PCAN1 </it>promoter activity and mRNA expression were increased by transfection with the <it>NKX3.1 </it>containing plasmid (pcDNA3.1-<it>NKX3.1</it>) and that <it>PCAN1 </it>mRNA expression was decreased by RNA interference targeting human <it>NKX3.1 </it>in LNCaP prostate cancer cells. The results of electrophoretic mobility shift assays and chromatin immunoprecipitation showed that NKX3.1 bound to NBS1 (-1848 to -1836) and NBS3 (-803 to -791) upstream of the <it>PCAN1 </it>gene. The luciferase reporter assays showed that NBS1 and NBS3 enhanced the promoter activity in pGL₃-promoter vector with cotransfection of the <it>NKX3.1 </it>containing plasmid. Furthermore, the deletion of NBS1 or both NBS1 and NBS3 reduced <it>PCAN1 </it>promoter activity and abolished the positive regulation of <it>PCAN1 </it>expression by NKX3.1.</p> <p>Conclusion</p> <p>Our results suggested that two functional NKX3.1 binding sites located at -1848 to -1836 and -803 to -791 upstream of the <it>PCAN1 </it>gene were involved in the positive regulation of <it>PCAN1 </it>gene transcription by NKX3.1.</p

Laser speckle contrast imaging to monitor microcirculation: An effective method to predict outcome in patients with sepsis and septic shock

Background: This study examines the microcirculation of patients with sepsis and septic shock using Laser Speckle Contrast Imaging (LSCI) technology, to enhance monitoring and predict outcomes of sepsis and septic shock.Methods: From 01 July 2021, to 31 January 2022, 44 patients diagnosed with septic shock and sepsis were included in the study, their clinical data were collected, and LSCI was used to monitor the mean peripheral blood flow perfusion index (PI).Results: The average peripheral blood flow PI of septic shock patients was significantly lower than that of septic patients, with a cutoff value of 26.25. The average peripheral blood flow PI negatively correlated with acute physiology and chronic health evaluation (APACHE) Ⅱ score (p = .01 &lt; .05), sequential organ failure assessment (SOFA) score (p &lt; .01), and lactic acid levels (p = .01 &lt; .05). We report average peripheral blood flow no correlation with age, mean arterial pressure, body temperature, oxygen saturation, heart rate, and body mass index. There was no correlation with procalcitonin, C-reactive protein (CRP), red blood cell distribution width, or platelet distribution width (p &gt; .05). PI significantly correlated with the group sepsis and septic shock (p &lt; .001, r = −.865). And PI significantly correlated with the outcome or mortality (p = .007 &lt; .05, r = −.398). The ROC curve was calculated for PI and the sensitivity was 81.3%, and the specificity was 75% when PI cutoff value chooses 20.88.Conclusion: LSCI technology successfully detected the fingertip microcirculation of patients with septic shock. LSCI can reliably differentiate patients with sepsis vs patients with septic shock. Additionally, the average peripheral blood PI negatively correlated with APACHE Ⅱ, SOFA score, and lactate acid levels, providing useful and supplementary information for the diagnosis and monitoring of septic shock. Trial registration: Chictr2100046761. Registered on May 28, 2021.Clinical Trial Registration:clinicaltrials.gov, identifier Chictr210004676

Synthesis and biological evaluation of novel bi-gold mitocans in lung cancer cells

Mitochondria are promising drug target for cancer treatment. We previously demonstrated that a bi-gold compound BGC2a was more potent than the mono-gold drug auranofin in suppressing cancer cells due to increased gold atom number that led to higher drug accumulation in and thereby inhibition of mitochondria. To exploit the potential of this new strategy, we further designed and synthesized a series of bi-gold mitocans, the compounds targeting mitochondria. The results showed that most of the newly synthesized mitocans exhibited obviously lower IC50 than auranofin, an old drug that is repurposed in clinical trials for cancer treatment. The best mitocan C3P4 was nearly 2-fold more potent than BGC2a in human non-small cell lung cancer A549 cells and mantle cell lymphoma Jeko-1 cells, exhibiting substantial colony formation-suppressing and tumor-suppressing effects in A549 cells xenograft model. C3P4 induced apoptosis in a dose-dependent manner and arrested cell cycle at G0/G1 phase. The mechanistic study showed that C3P4 significantly increased the global reactive oxygen species and mitochondrial superoxide level, and reduced the mitochondrial membrane potential. C3P4 preferentially accumulated in mitochondria as measured by the gold content and substantially inhibited oxygen consumption rate and ATP production. These results further validated our hypothesis that targeting mitochondria would be promising to develop more potent anticancer agents. C3P4 may be further evaluated as a drug candidate for lung cancer treatment