Unveiling the effect of Ni on the formation and structure of Earth's inner core.

Ni is the second most abundant element in the Earth's core. Yet, its effects on the inner core's structure and formation process are usually disregarded because of its electronic and size similarity with Fe. Using ab initio molecular dynamics simulations, we find that the bcc phase can spontaneously crystallize in liquid Ni at temperatures above Fe's melting point at inner core pressures. The melting temperature of Ni is shown to be 700 to 800 K higher than that of Fe at 323 to 360 GPa. hcp, bcc, and liquid phase relations differ for Fe and Ni. Ni can be a bcc stabilizer for Fe at high temperatures and inner core pressures. A small amount of Ni can accelerate Fe's crystallization at core pressures. These results suggest that Ni may substantially impact the structure and formation process of the solid inner core.

Mapping stress inside living cells by atomic force microscopy in response to environmental stimuli.

The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. The efficiency of such a feedback mechanism is closely related to the most challenging human diseases, including cancer. Since cellular responses are implemented through physical forces exerted on intracellular components, more detailed knowledge of force distribution through modern imaging techniques is needed to ensure a mechanistic understanding of these forces. In this work, we mapped these intracellular forces at a whole-cell scale and with submicron resolution to correlate intracellular force distribution to the cytoskeletal structures. Furthermore, we visualized dynamic mechanical responses of the cells adapting to environmental modulations in situ. Such task was achieved by using an informatics-assisted atomic force microscope (AFM) indentation technique where a key step was Markov-chain Monte Carlo optimization to search for both the models used to fit indentation force-displacement curves and probe geometry descriptors. We demonstrated force dynamics within cytoskeleton, as well as nucleoskeleton in living cells which were subjected to mechanical state modulation: myosin motor inhibition, micro-compression stimulation and geometrical confinement manipulation. Our results highlight the alteration in the intracellular prestress to attenuate environmental stimuli; to involve in cellular survival against mechanical signal-initiated death during cancer growth and metastasis; and to initiate cell migration.

Eremophilane and cadinane sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities.

The fruits of Alpinia oxyphylla have been used for centuries in China as both edible resources and traditional Chinese medicine. In order to identify structurally interesting and bioactive constituents from the fruits of A. oxyphylla, bioassay-guided fractionation and purification of the crude extracts were performed, which led to the isolation of 38 sesquiterpenoids, including six previously undescribed eremophilane sesquiterpenoids (1-6), six new cadinane sesquiterpenoids (23-24, 26-29), and 26 known analogues (7-22, 25 and 31-38). The structures of these compounds were elucidated by comprehensive spectroscopic data analysis, single crystal X-ray diffraction, quantum chemistry calculations (13C-NMR and ECD), and Mo2(OAc)4 reaction. Several of the isolated compounds (8, 13, 17, 18, 30, 31 and 35) showed moderate to strong inhibition of the secretion of cytokines (NO, TNF-α and IL-6) in LPS-stimulated BV-2 cells. Furthermore, western blot, immunofluorescence, and real-time PCR assays indicated that 18 could down-regulate the mRNA levels of TNF-α, IL-6, COX-2, and iNOS and the protein expression of COX-2 and iNOS. Meanwhile, 18 was able to partially inhibit the phosphorylation of ERK1/2, JNK, and p38. Thus, the discovery of structurally diverse anti-inflammatory sesquiterpenoids from the fruits of A. oxyphylla in this study could benefit the further development and utilization of this plant.

Establishment and validation of an electron inelastic mean free path database for narrow bandgap inorganic compounds with a machine learning approach.

Narrow bandgap inorganic compounds are extremely important in many areas of physics. However, their basic parameter database for surface analysis is incomplete. Electron inelastic mean free paths (IMFPs) are important parameters in surface analysis methods, such as electron spectroscopy and electron microscopy. Our previous research has presented a machine learning (ML) method to describe and predict IMFPs from calculated IMFPs for 41 elemental solids. This paper extends the use of the same machine learning method to 42 inorganic compounds based on the experience in predicting elemental electron IMFPs. The in-depth discussion extends to including material dependence discussion and parameter value selections. After robust validation of the ML method, we have produced an extensive IMFP database for 12 039 narrow bandgap inorganic compounds. Our findings suggest that ML is very efficient and powerful for IMFP description and database completion for various materials and has many advantages, including stability and convenience, over traditional methods.

Exploring the absolute yield curve of secondary electrons using machine learning methods.

Knowledge of absolute secondary electron yield (δ) is important for various applications of electron emission materials. Besides, it is also crucial to know the dependence of δ on primary electron energy Ep and material properties like atomic number Z. The available experimental database of δ reveals a large discrepancy among the measurement data, while the oversimplified semi-empirical theories of secondary electron emission can only present the general shape of the yield curve but not the absolute yield value. This limits not only the validation of a Monte Carlo model for theoretical simulations but also presents large uncertainties in the applications of different materials for various purposes. In applications, it is highly desirable to have the knowledge of the absolute yield of a material. Therefore, it is highly desirable to establish the relationship of the absolute yield with material and electron energy based on the available experimental data. Recently, machine learning (ML) methods have been increasingly used for the prediction of material properties mainly based on the atomistic calculations with the first-principles theory. We propose here the application of ML models to a material property study, starting with experimental observations and unfolding the relationship of δ with basic material properties and primary electron energy. Our ML models are able to predict δ(Ep)-curve covering a wide energy range of 10 eV-30 keV for unknown elements within the uncertainty range of the experimental data and can suggest more reliable data among the scattered experimental data.

The transcription factor XBP1 in dendritic cells promotes the TH2 cell response in airway allergy.

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (TH2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box-binding protein-1 (XBP1) in the induction of the TH2 cell response through its role in generating TIM4+ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2-XBP1-TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant TH2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for TH2 cell responses by inducing the development of TIM4+ DCs, which depends on the IL-2-XBP1-SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of TH2 cell-dependent inflammation or allergic diseases.

Application of optical flow algorithm for drift correction in electron microscopy images.

Transmission electron microscopy (TEM) image drift correction has been effectively addressed using diverse approaches, including the cross correlation algorithm (CC) and other strategies. However, most of the strategies fall short of achieving sufficient accuracy or cannot strike a balance between time consumption and accuracy. The present study proposes a TEM image drift correction strategy that enhances accuracy without any additional time consumption. Unlike the CC algorithm that matches pixels one by one, our approach involves the extraction of multiple feature points from the first TEM image and then uses the Lucas-Kanade (LK) optical flow algorithm to calculate the optical field of these feature points in the subsequent TEM images. The LK algorithm is used to calculate the instantaneous velocity of these feature points, which can help track the movement of the TEM image series. In addition, a high-precision sub-pixel level correction strategy by the utilization of linear interpolation during the correction process is developed in this work. Experimental results confirm that this strategy offers superior accuracy in comparison with the CC algorithm and also is insensitive to the size of the image. Furthermore, we offer a semantic segmentation neural network for electron microscope image pre-processing, thereby expanding the applicability of our methodology.

Nitration of Pyrrolo[2,1-a]isoquinolines.

We have successfully modified a series of pyrrolo[2,1-a]isoquinolines via direct nitration under mild reaction conditions. Easily accessible nitrates including CAN, Cu(NO3)2·H2O, and Fe(NO3)3·9H2O all can serve as effective nitrating reagents for functionalizing pyrrolo[2,1-a]isoquinolines. Various nitro-bearing pyrrolo[2,1-a]isoquinolines have been efficiently prepared in acceptable to good yields.

Recent progress in the oxidative bromination of arenes and heteroarenes.

Oxidative bromination has been serving as a powerful tool for the synthesis of bromo-containing molecules, as this bromination strategy features environmental friendliness, high flexibility in reaction system design and wide abundance of bromide sources and oxidants. The past decade has witnessed a large number of efficient oxidative bromination reaction systems and novel brominated aromatics. This review summarizes recent developments in the field of oxidative preparation of bromoarenes and bromoheteroarenes covering from 2012 to 2022.

Two new diterpenoids from the rhizomes of Zingiber officinale.

Two undescribed labdane diterpenoids (5S,8S,9R,10S,11E)-8,17-epoxy-13,14-dinorlabd-11-en-13-one (1) and (5S,9R,10S,12E)-17-hydroxy-labd-7,12-dien-15(16)-olide (2), together with seven known sesquiterpenoids (3-9) and two known monoterpenoids (10-11) were isolated from the dried rhizome of Zingiber officinale. Their structures were elucidated by detailed spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), X-ray crystallographic and ECD analysis. Moreover, all the 11 compounds were tested for α-glucosidase inhibitory effects and 9 was found to exhibit stronger inhibitory effects at IC50 = 4.8 µM against a positive control acarbose with IC50 = 414.6 µM.

Understanding Complex Electron Radiolysis in Saline Solution by Big Data Analysis.

In this article, we developed a new method to analyze the complex chemical reactions induced by electron beam radiolysis based on big data analysis. At first, we built an element transport network to show the chemical reactions. Furthermore, the linearity between the species was quantified by Pearson correlation coefficient analysis. Based on the analysis, the mechanism of the high linearity between the special species pairs was interpreted by the element transport roadmap and chemical equations. The time variation of the pH of the solution and bubble formation in the solution were analyzed by simulation and data analysis. The simulation indicates that O2 and H2 can easily oversaturate and form bubbles. Finally, the radiolysis of high-energy electrons in pure water was analyzed as a reference for the radiolysis of high-energy electrons in saline solution. This work provides a new method for investigating a high-energy electron radiolysis process and for simplifying a complex chemical reaction based on quantitative analysis of the species variation in the reaction.

First Report of Black Spot Needle Blight of Pinus sylvestris var. mongolica Litv. Caused by Heterotruncatella spartii in China.

Pinus sylvestris var. mongolica Litv. (Pinales: Pinaceae) is an excellent tree for soil and water conservation in Northeast China. The Honghua'erji area in Inner Mongolia is the "hometown of P. sylvestris var. mongolica", however, in recent years, coniferous diseases of P. sylvestris var. mongolica have frequently occurred here. During the investigation, it was found that some black spot needle blight had been observed in addition to the common blight caused by Sphaeropsis sapinea. From May to September 2020, black spot needle blight was found on hundreds of P. sylvestris var. mongolica trees in four forest farms, and the infection rate among the forests was 24.58 % (n=240). This disease first appeared on the upper part of the needles, and the needles then became withered and gradually showed light black spots, although they remained green. As the disease progressed, the needles eventually died and turned gray with many dark black spots. Fungal isolate named YJ-1 was obtained from infected needles of symptomatic pine trees, and a voucher specimen was deposited in Heilongjiang Province Key Laboratory of Forest Protection. Microscopic observation showed the conidia were 3-septate (4 cells) clavate spindles that measured 23.9 µm (20.8-25.9) × 5.9 µm (4.5-8.2) (n=50). The middle two cells were dark brown, and the septa were darker than the cells. Both apical and basal cells were hyaline. The apical cell had 2-4 appendages (mostly 3), and the basal cell had a truncate base (n=50). The cultural characteristics on potato dextrose agar medium were flat off-white and dense in 3-5 d. At approximately 5-7 d, the reverse side of the colony turned pale to slightly luteous. Superficial black acervuli were distributed in the center of the mature colonies after 10 d. Morphological, cultural and microscopic characteristics observed were similar of Heterotruncatella spartii (basionym: Truncatella spartii) reported by Hlaiem et al (2019). To further identify, total DNA was extracted and the internal transcribed spacer region (ITS-rDNA) was amplified by PCR using the primers ITS1/ITS4 and sequenced for BLASTn analysis and phylogenetic tree construction. The resulting 564 bp sequence (GenBank Accession No. OL662864) had 99.24% (521/525) to H. spartii MFLUCC 15-0537, with bootstrap support of at least 94% using the Neighbor-Joining algorithm by MEGA-X (Felsenstein, 1985). The fungus was identified as H. spartii based on morphology and molecular methods. A pathogenicity test was conducted by preparing a conidial suspension of 2.0 × 107 conidia/mL. The suspension was sprayed onto the needles of 20 pots of annual P. sylvestris ar. mongolica seedlings, and the control was sprayed with sterile water. Then the seedlings were placed in a constant temperature room at 25 °C. After 30 d, typical symptoms appeared on 11 inoculated needles, while the control needles remained symptomless. After 50 d, the re-isolation infection rate reached 66.7 %. The fungus present on the inoculated seedlings was morphologically identical to that originally observed on diseased pines, fulfilling Koch's postulates. The fungus was isolated from Spartium junceum for the first time and designated Truncatella spartii (Senanayake et al, 2015). It was then renamed H. spartii (Liu et al, 2019) and has been reported to infect P. pinea in Tunisia (Hlaiem et al, 2019). To our knowledge, this is the first report of H. spartii causing black spot needle blight on P. sylvestris var. mongolica in China and worldwide.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Glutaminolysis is required in maintaining immune regulatory functions in B cells.

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.

Charging effect induced by electron beam irradiation: a review.

Charging effect frequently occurs when characterizing nonconductive materials using electrons as probes and/or signals and can impede the acquisition of useful information about the material under investigation. It is not adequate to investigate it merely by experiments, but theoretical investigations, for which the Monte Carlo method is a suitable tool, are also necessary. In this paper we review Monte Carlo simulations and selected experiments, intending to provide general insight into the charging effects induced by electron beam irradiation. We will introduce categories of the charging effect, the theoretical framework that is adopted in Monte Carlo modeling of the charging effect and present some typical simulation results. At last, with the knowledge on charging effect imparted by the above contents, we will discuss the measures that can be used for minimizing it.

Particle Size Effect of Oyster Shell on Mortar: Experimental Investigation and Modeling.

In order to solve the problem of lack of natural river sand, crushed waste oyster shells (WOS) were used to replace river sand. By replacing 20% river sand, WOS mortar with different particle sizes of WOS were made for the experiment. Through experimental observation, the initial slump and slump flow loss rate were studied. The effects of different particle sizes and curing times on the compressive strength, flexural strength, static elastic modulus, and dry shrinkage of WOS mortar were analyzed. The relationship formulas between the compressive strength, flexural strength, particle size, and curing age were proposed. The results showed that the setting time and slump flow decreased with a decrease in the particle size of WOS. It was also found that the mortar with fine crushed WOS had high compressive strength, flexural strength, and static elastic modulus at both early and long-term curing age. A formula was proposed to describe the development of the compressive strength with the particle size of WOS and curing time, and the relations among these mechanical properties were discussed. Furthermore, drying shrinkage increased when WOS was used and could not satisfy the standard requirement of 0.075%. In contrast, the addition of fine WOS and double-dose sulfonated naphthalene-formaldehyde superplasticizer (SNF SP) reduced the shrinkage rate of the mortar by 8.35% and provided better workability and mechanical properties for mortar.

Discovery of pentapeptide-inhibitor hits targeting FKBP51 by combining computational modeling and X-ray crystallography.

FKBP51 is well-known as a cochaperone of Hsp90 machinery and implicated in many human diseases including stress-related diseases, tau-mediated neurodegeneration and cancers, which makes FKBP51 an attractive drug target for the therapy of FKBP51-associated diseases. However, it has been reported that only nature product rapamycin, cyclosporine A, FK506 and its derivatives exhibit good binding affinities when bound to FKBP51 by now. Given the advantages of peptide-inhibitors, we designed and obtained 20 peptide-inhibitor hits through structure-based drug design. We further characterized the interaction modes of the peptide-inhibitor hits on the FK1 domain of FKBP51 by biochemical and structural biology methods. Structural analysis revealed that peptide-inhibitor hits form U-shaped conformations and occupy the FK506 binding pocket and share similar interaction modes with FK506. Using molecular dynamics simulations, we delved into the interaction dynamics and found that hits are anchored to the FK506 binding pocket in a quite stable conformation. Meanwhile, it was shown that interactions between FK1 and peptide-inhibitor hits are mainly attributed to the hydrogen bond networks comprising I87 and Y113 and FPF cores of peptide-inhibitors involved extensive hydrophobic interactions. We presumed that the peptide design strategy based on the small molecule structure probably shed new lights on the peptide-inhibitor discovery of other targets. The findings presented here could also serve as a structural basis and starting point facilitating the optimization and generation of FKBP51 peptide-inhibitors with better bio-activities.

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress.

Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.

Interaction between Ras and Bcl2L12 in B cells suppresses IL-10 expression.

The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.

Livin in synergy with Ras induces and sustains corticosteroid resistance in the airway mucosa.

Rationale: Corticosteroid resistance (CR) seriously affects the therapeutic effects of steroids on many chronic inflammatory disorders, including airway allergy. The mechanism of CR development is unclear. Recent research indicates that livin, an apoptosis inhibitor, is associated with the regulation in cell activities. This study investigates the role of livin in the inducing and sustaining CR in the airway mucosa. Methods: Nasal epithelial cells (NECs) were isolated from surgically removed nasal mucosal tissues of patients with allergic rhinitis (AR) and nasal polyps with or without CR. Differentially expressed genes in NECs were analyzed by the RNA sequencing. A CR mouse model was developed to test the role of livin in CR development. Results: The results showed that NECs of AR patients with CR expressed high levels of livin, that was positively correlated with the thymic stromal lymphopoietin (TSLP) expression and the high Ras activation status in NECs. Livin and Ras activation mutually potentiating each other in the inducing and sustaining the TSLP expression in NECs. TSLP induced eosinophils and neutrophils to express glucocorticoid receptor-ß (GRß). Eosinophils and neutrophils with high CRß expression were resistant to corticosteroids. Depletion of livin or inhibition of TSLP markedly attenuated CR and airway allergy. Conclusions: Livin facilitates CR development in the airways by promoting TSLP expression in epithelial cells and the GRß expression in eosinophils and neutrophils. Depletion of livin or inhibiting TSLP attenuates CR development and inhibits airway allergy, this has the translational potential to be used in the treatment of airway allergy.