Exceptional electronic transport and quantum oscillations in thin bismuth crystals grown inside van der Waals materials.

Confining materials to two-dimensional forms changes the behaviour of the electrons and enables the creation of new devices. However, most materials are challenging to produce as uniform, thin crystals. Here we present a synthesis approach where thin crystals are grown in a nanoscale mould defined by atomically flat van der Waals (vdW) materials. By heating and compressing bismuth in a vdW mould made of hexagonal boron nitride, we grow ultraflat bismuth crystals less than 10 nm thick. Due to quantum confinement, the bismuth bulk states are gapped, isolating intrinsic Rashba surface states for transport studies. The vdW-moulded bismuth shows exceptional electronic transport, enabling the observation of Shubnikov-de Haas quantum oscillations originating from the (111) surface state Landau levels. By measuring the gate-dependent magnetoresistance, we observe multi-carrier quantum oscillations and Landau level splitting, with features originating from both the top and bottom surfaces. Our vdW mould growth technique establishes a platform for electronic studies and control of bismuth's Rashba surface states and topological boundary modes1-3. Beyond bismuth, the vdW-moulding approach provides a low-cost way to synthesize ultrathin crystals and directly integrate them into a vdW heterostructure.

Interfacial Features Govern Nanoscale Jumping Droplets.

The solid surfaces with different profile levels impact the liquid-solid contact nature and hence wetting characteristics, showing a vital role in liquid droplets' mobility and dynamic behaviors. Therefore, engineering nanostructured features ultimately enables tuning and controlling the dynamic motion of droplets. In this study, we demonstrate an approach to manipulate nanodroplets' motion behaviors in contact with a surface through tailoring the surface morphological profile. By tracking the trajectories of water molecules at the interface, we find that the motions of a nanodroplet subjected to different levels of lateral force reveal various modes that are identified as creeping, rolling, and jumping motions. Interestingly, the elastic deformation of the droplet and sudden changes in the receding contact angle provide the mechanistic origin for droplet jumping. Guided by computational simulations, a regime map delineating the droplet motion modes with surface profile levels and applied forces is constructed, providing a design strategy for controlling droplet motions via surface engineering.

Potential energy landscape activations governing plastic flows in glass rheology.

While glasses are ubiquitous in natural and manufactured materials, the atomic-level mechanisms governing their deformation and how these mechanisms relate to rheological behavior are still open questions for fundamental understanding. Using atomistic simulations spanning nearly 10 orders of magnitude in the applied strain rate we probe the atomic rearrangements associated with 3 characteristic regimes of homogeneous and heterogeneous shear flow. In the low and high strain-rate limits, simulation results together with theoretical models reveal distinct scaling behavior in flow stress variation with strain rate, signifying a nonlinear coupling between thermally activated diffusion and stress-driven motion. Moreover, we find the emergence of flow heterogeneity is closely correlated with extreme values of local strain bursts that are not readily accommodated by immediate surroundings, acting as origins of shear localization. The atomistic mechanisms underlying the flow regimes are interpreted by analyzing a distance matrix of nonaffine particle displacements, yielding evidence of various barrier-hopping processes on a fractal potential energy landscape (PEL) in which shear transformations and liquid-like regions are triggered by the interplay of thermal and stress activations.

Intraoperative transit-time ultrasonography combined with FLOW800 predicts the occurrence of cerebral hyperperfusion syndrome after direct revascularization of Moyamoya disease: a preliminary study.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is a common complication after direct bypass surgery in patients with Moyamoya disease (MMD). Since preventive measures may be inadequate, we assessed whether the blood flow difference between the superficial temporal artery (STA) and recipient vessels (△BF) and the direct perfusion range (DPR) are related to CHS. METHODS: We measured blood flow in the STA and recipient blood vessels before bypass surgery by transit-time probe to calculate △BF. Perfusion changes around the anastomosis before and after bypass were analyzed with FLOW800 to obtain DPR. Multiple factors, such as △BF, DPR, and postoperative CHS, were analyzed using binary logistic regression. RESULTS: Forty-one patients with MMD who underwent direct bypass surgery were included in the study. Postoperative CHS symptoms occurred in 13/41 patients. △BF and DPR significantly differed between the CHS and non-CHS groups. The optimal receiver operating characteristic (ROC) curve cut-off value was 31.4 ml/min for ΔBF, and the area under the ROC curve (AUC) was 0.695 (sensitivity 0.846, specificity 0.500). The optimal cut-off value was 3.5 cm for DPR, and the AUC was 0.702 (sensitivity 0.615, specificity 0.750). CONCLUSION: Postoperative CHS is caused by multiple factors. △BF is a risk factor for CHS while DPR is a protective factor against CHS.

The Strongest Size in Gradient Nanograined Metals.

Conventional polycrystalline metals become stronger with decreasing grain size, yet softening starts to take over at the nanometer regime, giving rise to the strongest size at which the predominate strengthening mechanism switches to softening. We show that this critical size for the onset of softening can be tuned by tailoring grain size gradient, and raising in the gradient shifts the size toward the smaller value. The decrease in the strongest size is prompted by mitigation of grain boundary-mediated softening processes accompanying by enhanced intragranular plastic deformations. We found that the nanograins smaller than 6 nm, mainly involving intergranular sliding in homogeneous structures, reveal anomalous plastic deformation in gradient systems, which is mediated by partial dislocation nucleation, faulting and twinning activated in a gradient stress field. The results on extended dislocation slip and gradient plasticity, stemming from the structure heterogeneity, shed light on an emerging class of heterogeneous nanostructured materials of improved strength-ductility synergy.

High variance of intraoperative blood pressure predicts early cerebral infarction after revascularization surgery in patients with Moyamoya disease.

Few studies focused on the intraoperative blood pressure in Moyamoya disease (MMD) patients. We aimed to clarify whether or not it relates to early cerebral infarction after revascularization. We reviewed a retrospective cohort of Moyamoya disease from 2011 to 2018 in Beijing Tiantan Hospital, and patients with radiologically confirmed early postoperative infarction were included in the analysis. Controls were matched based on age, sex, and revascularization modality at a ratio of 1:5. Perioperative clinical factors and intraoperative blood pressure data were collected and analyzed. A total of 52 patients out of 1497 revascularization surgeries (3.5%) who experienced CT or MRI confirmed early postoperatively cerebral infarction, aged 38.46 ± 11.70; 26 were male (50.0%). Average real variability (ARV)-systolic blood pressure (SBP) (OR 3.29, p = 0.003), ARV-diastolic blood pressure (DBP) (OR 4.10, p = 0.005), ARV-mean arterial pressure (MAP) (OR 4.08, p = 0.004), and the maximum drops of DBP (OR 1.08, p = 0.003) and MAP (OR 1.06, p = 0.004) were associated with early postoperative infarction. In patients who experienced massive cerebral infarction, the maximum drops of DBP (OR 1.11, p = 0.004) and MAP (OR 1.11, p = 0.003) are independent risk factors, whereas ARVs of SBP (OR 3.90, p < 0.001), DBP (OR 4.69, p = 0.008), and MAP (OR 4.72, p = 0.003) are significantly associated with regional infarction. High variance of intraoperative blood pressure and drastic blood pressure decline are independent risk factors for postoperative infarction in MMD patients who underwent revascularization surgery. Maintaining stable intraoperative blood pressure is suggested to prevent early postoperative cerebral infarction in MMD patients.

Understanding the mechanisms of amorphous creep through molecular simulation.

Molecular processes of creep in metallic glass thin films are simulated at experimental timescales using a metadynamics-based atomistic method. Space-time evolutions of the atomic strains and nonaffine atom displacements are analyzed to reveal details of the atomic-level deformation and flow processes of amorphous creep in response to stress and thermal activations. From the simulation results, resolved spatially on the nanoscale and temporally over time increments of fractions of a second, we derive a mechanistic explanation of the well-known variation of creep rate with stress. We also construct a deformation map delineating the predominant regimes of diffusional creep at low stress and high temperature and deformational creep at high stress. Our findings validate the relevance of two original models of the mechanisms of amorphous plasticity: one focusing on atomic diffusion via free volume and the other focusing on stress-induced shear deformation. These processes are found to be nonlinearly coupled through dynamically heterogeneous fluctuations that characterize the slow dynamics of systems out of equilibrium.

Purine nucleotide biosynthetic gene GARS controls early chloroplast development in rice (Oryza sativa L.).

KEY MESSAGE: GARS encodes an enzyme catalyzing the second step of purine nucleotide biosynthesis and plays an important role to maintain the development of chloroplasts in juvenile plants by affecting the expression of plastid-encoded genes. A series of rice white striped mutants were previously described. In this research, we characterized a novel gars mutant with white striped leaves at the seedling stage. By positional cloning, we identified the mutated gene, which encodes a glycinamide ribonucleotide synthetase (GARS) that catalyzes the second step of purine nucleotide biosynthesis. Thylakoid membranes were less abundant in the albinic sectors of mutant seedling leaves compared to the wild type. The expression levels of genes involved in chlorophyll synthesis and photosynthesis were changed. Contents of ATP, ADP, AMP, GTP and GDP, which are crucial for plant growth and development, were decreased in the mutant seedlings. Complementation and CrispR tests confirmed the role of the GARS allele, which was expressed in all rice tissues, especially in the leaves. GARS protein displayed a typical chloroplast location pattern in rice protoplasts. Our results indicated that GARS was involved in chloroplast development at early leaf development by affecting the expression of plastid-encoded genes.

Atomistic Simulation of the Rate-Dependent Ductile-to-Brittle Failure Transition in Bicrystalline Metal Nanowires.

The mechanical properties and plastic deformation mechanisms of metal nanowires have been studied intensely for many years. One of the important yet unresolved challenges in this field is to bridge the gap in properties and deformation mechanisms reported for slow strain rate experiments (∼10-2 s-1), and high strain rate molecular dynamics (MD) simulations (∼108 s-1) such that a complete understanding of strain rate effects on mechanical deformation and plasticity can be obtained. In this work, we use long time scale atomistic modeling based on potential energy surface exploration to elucidate the atomistic mechanisms governing a strain-rate-dependent incipient plasticity and yielding transition for face centered cubic (FCC) copper and silver nanowires. The transition occurs for both metals with both pristine and rough surfaces for all computationally accessible diameters (<10 nm). We find that the yield transition is induced by a transition in the incipient plastic event from Shockley partials nucleated on primary slip systems at MD strain rates to the nucleation of planar defects on non-Schmid slip planes at experimental strain rates, where multiple twin boundaries and planar stacking faults appear in copper and silver, respectively. Finally, we demonstrate that, at experimental strain rates, a ductile-to-brittle transition in failure mode similar to previous experimental studies on bicrystalline silver nanowires is observed, which is driven by differences in dislocation activity and grain boundary mobility as compared to the high strain rate case.

WSL5, a pentatricopeptide repeat protein, is essential for chloroplast biogenesis in rice under cold stress.

Chloroplasts play an essential role in plant growth and development, and cold conditions affect chloroplast development. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, many other components affecting chloroplast biogenesis under cold conditions have not been characterized. Here, we report the functional characterization of a white stripe leaf 5 (wsl5) mutant in rice. The mutant develops white-striped leaves during early leaf development and is albinic when planted under cold stress. Genetic and molecular analysis revealed that WSL5 encodes a novel chloroplast-targeted pentatricopeptide repeat protein. RNA sequencing analysis showed that expression of nuclear-encoded photosynthetic genes in the mutant was significantly repressed, and expression of many chloroplast-encoded genes was also significantly changed. Notably, the wsl5 mutation causes defects in editing of rpl2 and atpA, and splicing of rpl2 and rps12. wsl5 was impaired in chloroplast ribosome biogenesis under cold stress. We propose that the WSL5 allele is required for normal chloroplast development in maintaining retrograde signaling from plastids to the nucleus under cold stress.

Anisotropic ion diffusion in α-Cr2O3: an atomistic simulation study.

Chromia (α-Cr2O3) is one of the most technologically important oxides, as it is the basis behind the passivation of many structural materials like stainless steel. It both resists oxygen ingress and slows the release of metals from its substrate by its high density and very low diffusivities. Were any further improvement to the protectiveness of chromia to be realized, no matter how small, it would have an enormous impact due to its ubiquitousness. Here we use molecular dynamics (MD) in conjunction with nudged elastic band (NEB) calculations to study the diffusion mechanisms of oxygen and chromium ions in α-Cr2O3. Significant anisotropic diffusion between the ab-plane and the c-axis is observed for both oxygen and chromium ions. We found that vacancy-mediated ion diffusion in the ab-plane is faster than diffusion along the c-axis, while interstitial-mediated diffusion along the c-axis is faster. Vacancy and interstitial defect migration paths unveil the atomistic mechanisms responsible for this anisotropic ion diffusion, as the most energetically favorable diffusion path accounts for the observed anisotropy. The results of this study have profound implications for the reduction and control of corrosion.

Improvement in the Anticancer Activity of 6-Mercaptopurine via Combination with Bismuth(III).

6-Mercaptopurine (6-MP) is a clinically important antitumor drug and its commercially available form is provided as monohydrate, belonging to biopharmaceuticals classification system (BCS) class II category. The combination of bismuth(III) (Bi(III)) with 6-MP was proved to significantly improve the anticancer activity of 6-MP, leading to the discovery of a new amorphous complex ([Bi(MP)3(NO3)2]NO3). The prepared [Bi(MP)3(NO3)2]NO3 was characterized by the matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF)-MS, etc. Noticeably, according to the in vitro evaluations of cytotoxicity, cellular apoptotic, colony formation as well as cell migration, the anticancer activity of amorphous [Bi(MP)3(NO3)2]NO3 was found to be of high therapeutic effect over 6-MP.

ß-sheet-like formation during the mechanical unfolding of prion protein.

Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrP(C), whose misfolded form PrP(Sc) can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded ß-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the ß-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

Neural network kinetics for exploring diffusion multiplicity and chemical ordering in compositionally complex materials.

Diffusion involving atom transport from one location to another governs many important processes and behaviors such as precipitation and phase nucleation. The inherent chemical complexity in compositionally complex materials poses challenges for modeling atomic diffusion and the resulting formation of chemically ordered structures. Here, we introduce a neural network kinetics (NNK) scheme that predicts and simulates diffusion-induced chemical and structural evolution in complex concentrated chemical environments. The framework is grounded on efficient on-lattice structure and chemistry representation combined with artificial neural networks, enabling precise prediction of all path-dependent migration barriers and individual atom jumps. To demonstrate the method, we study the temperature-dependent local chemical ordering in a refractory NbMoTa alloy and reveal a critical temperature at which the B2 order reaches a maximum. The atomic jump randomness map exhibits the highest diffusion heterogeneity (multiplicity) in the vicinity of this characteristic temperature, which is closely related to chemical ordering and B2 structure formation. The scalable NNK framework provides a promising new avenue to exploring diffusion-related properties in the vast compositional space within which extraordinary properties are hidden.

Frontal Theta Asymmetry may be a new target for reducing the severity of depression and improving cognitive function in depressed patients.

BACKGROUND: The prevalence of depressive disorder is increasing due to a variety of factors, which brings a huge strain on individuals, families and society. This study aims to investigate whether there is Frontal Theta Asymmetry (FTA) in depressed patients, and whether FTAs are related to depression severity and cognitive function changes in depressed patients. METHODS: Participants who met the inclusion criteria were enrolled in this study. Socio-demographic data of each participant were recorded. Zung's self-rating Depression Scale was used to assess the depression status of participants. P300 was used to evaluate the cognitive function of participants. EEG data from participants were collected by the NeuroScan SynAmps RT EEG system. t-test, Wilcoxon rank-sum test and Chi-square test were used to detect the differences of different variables between the two groups. Multiple linear regression analysis and multiple logistic regression analysis were used to analyze relationships between FTAs in different regions and participants' depression status and cognitive function. RESULTS: A total of 66 depressed participants and 47 healthy control participants were included in this study. The theta spectral power of the left frontal lobe was slightly stronger than that of the right frontal lobe in the depression group, while the opposite was true in the healthy control group. The FTA in F3/F4 had certain effects on the emergence of depression in participants, the emergence of depression in participants and Changes in cognitive function. CONCLUSIONS: FTAs are helpful to assess the severity of depression and early identify cognitive impairment in patients with depression.

Standardized Treatment and Shortened Depression Course can Reduce Cognitive Impairment in Adolescents With Depression.

Objectives: This study aimed to explore the influence of depression severity, disease course, treatment status, and other factors on cognitive function in adolescents with depressive disorders. Methods: Participants who met the inclusion criteria were enrolled in the study. Sociodemographic data of each participant were recorded, including age, sex, and family history of mental disorders. Zung's Self-Rating Depression Scale was used to assess depression status in adolescents. Moreover, P300 and mismatch negativity (MMN) were used to objectively evaluate the participants' cognitive function. Results: Only 26.8% of the adolescents with depression received standard antidepressant treatment. The latencies of N2 (267.80±23.34 ms), P3 (357.71±32.09 ms), and MMN (212.10±15.61 ms) in the adolescent depression group were longer than those in the healthy control group (p<0.01). Further analysis revealed that the latency of MMN was extended with increased levels of depression in adolescents. The MMN latency was short in participants with depression receiving standardized treatment. Furthermore, the latency of MMN was positively correlated with the severity and duration of depression (correlation coefficients were 0.465 and 0.479, respectively) (p<0.01). Conclusion: Receiving standardized treatment and shortening the course of depression can reduce cognitive impairment in adolescents with depression.

Regioselective synthesis of 3,4-diarylpyrimido[1,2-b]indazole derivatives enabled by iron-catalyzed ring-opening of styrene oxides.

The first synthesis of 3,4-diarylpyrimido[1,2-b]indazole derivatives from 3-aminoindazoles has been realized. The FeCl3-catalyzed intermolecular epoxide ring-opening reaction altered the order of annulation, with the free primary NH2 groups in 3-aminoindazoles preferentially reacting with styrene oxides instead of aromatic aldehydes. This protocol is further highlighted by its broad substrate compatibility, high chemo- and regioselectivities, and the late-stage modifications of bioactive molecules. Without aromatic aldehydes, the synthesis of 3-aryl-4-acylpyrimido[1,2-b]indazole derivatives can also be accomplished using alternative reaction conditions.

High-pressure phase transition in 3-D printed nanolamellar high-entropy alloy by imaging and simulation insights.

We report on the high-resolution imaging and molecular dynamics simulations of a 3D-printed eutectic high-entropy alloy (EHEA) Ni40Co20Fe10Cr10Al18W2 consisting of nanolamellar BCC and FCC phases. The direct lattice imaging of 3D-printed samples shows the Kurdjumov-Sachs (K-S) orientation relation {111} FCC parallel to {110} BCC planes in the dual-phase lamellae. Unlike traditional iron and steels, this alloy shows an irreversible BCC-to-FCC phase transformation under high pressures. The nanolamellar morphology is maintained after pressure cycling to 30 GPa, and nano-diffraction studies show both layers to be in the FCC phase. The chemical compositions of the dual-phase lamellae after pressure recovery remain unchanged, suggesting a diffusion-less BCC-FCC transformation in this EHEA. The lattice imaging of the pressure-recovered sample does not show any specific orientation relation between the two resulting FCC phases, indicating that many grain orientations are produced during the BCC-FCC phase transformation. Molecular dynamics simulations on phase transformation in a nanolamellar BCC/FCC in K-S orientation show that phase transformation from BCC to FCC is completed under high pressures, and the FCC phase is retained on decompression aided by the stable interfaces. Our work elucidates the irreversible phase transformation under static compression, providing an understanding of the orientation relationships in 3-D printed EHEA under high pressures.

Ubiquitous short-range order in multi-principal element alloys.

Recent research in multi-principal element alloys (MPEAs) has increasingly focused on the role of short-range order (SRO) on material performance. However, the mechanisms of SRO formation and its precise control remain elusive, limiting the progress of SRO engineering. Here, leveraging advanced additive manufacturing techniques that produce samples with a wide range of cooling rates (up to 107 K s-1) and an enhanced semi-quantitative electron microscopy method, we characterize SRO in three CoCrNi-based face-centered-cubic (FCC) MPEAs. Surprisingly, irrespective of the processing and thermal treatment history, all samples exhibit similar levels of SRO. Atomistic simulations reveal that during solidification, prevalent local chemical order arises in the liquid-solid interface (solidification front) even under the extreme cooling rate of 1011 K s-1. This phenomenon stems from the swift atomic diffusion in the supercooled liquid, which matches or even surpasses the rate of solidification. Therefore, SRO is an inherent characteristic of most FCC MPEAs, insensitive to variations in cooling rates and even annealing treatments typically available in experiments.

Multi-omics and pharmacological characterization of patient-derived glioma cell lines.

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.