Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Exceptional enhancement of mechanical properties in high-entropy alloys via thermodynamically guided local chemical ordering.

Understanding the local chemical ordering propensity in random solid solutions, and tailoring its strength, can guide the design and discovery of complex, paradigm-shifting multicomponent alloys. First, we present a simple thermodynamic framework, based solely on binary enthalpies of mixing, to select optimal alloying elements to control the nature and extent of chemical ordering in high-entropy alloys (HEAs). Next, we couple high-resolution electron microscopy, atom probe tomography, hybrid Monte-Carlo, special quasirandom structures, and density functional theory calculations to demonstrate how controlled additions of Al and Ti and subsequent annealing drive chemical ordering in nearly random equiatomic face-centered cubic CoFeNi solid solution. We establish that short-range ordered domains, the precursors of long-range ordered precipitates, inform mechanical properties. Specifically, a progressively increasing local order boosts the tensile yield strengths of the parent CoFeNi alloy by a factor of four while also substantially improving ductility, which breaks the so-called strength-ductility paradox. Finally, we validate the generality of our approach by predicting and demonstrating that controlled additions of Al, which has large negative enthalpies of mixing with the constituent elements of another nearly random body-centered cubic refractory NbTaTi HEA, also introduces chemical ordering and enhances mechanical properties.

Ferromagnetic ordering correlated strong metal-oxygen hybridization for superior oxygen reduction reaction activity.

The efficiency of transition-metal oxide materials toward oxygen-related electrochemical reactions is classically controlled by metal-oxygen hybridization. Recently, the unique magnetic exchange interactions in transition-metal oxides are proposed to facilitate charge transfer and reduce activation barrier in electrochemical reactions. Such spin/magnetism-related effects offer a new and rich playground to engineer oxide electrocatalysts, but their connection with the classical metal-oxygen hybridization theory remains an open question. Here, using the MnxVyOz family as a platform, we show that ferromagnetic (FM) ordering is intrinsically correlated with the strong manganese (Mn)-oxygen (O) hybridization of Mn oxides, thus significantly increasing the oxygen reduction reaction (ORR) activity. We demonstrate that this enhanced Mn-O hybridization in FM Mn oxides is closely associated with the generation of active Mn sites on the oxide surface and obtaining favorable reaction thermodynamics under operating conditions. As a result, FM-Mn2V2O7 with a high degree of Mn-O hybridization achieves a record high ORR activity. Our work highlights the potential applications of magnetic oxide materials with strong metal-oxygen hybridization in energy devices.

Unveiling the complexity of nanodiamond structures.

Understanding nanodiamond structures is of great scientific and practical interest. It has been a long-standing challenge to unravel the complexity underlying nanodiamond structures and to resolve the controversies surrounding their polymorphic forms. Here, we use transmission electron microscopy with high-resolution imaging, electron diffraction, multislice simulations, and other supplementary techniques to study the impacts of small sizes and defects on cubic diamond nanostructures. The experimental results show that common cubic diamond nanoparticles display the (200) forbidden reflections in their electron diffraction patterns, which makes them indistinguishable from new diamond (n-diamond). The multislice simulations demonstrate that cubic nanodiamonds smaller than 5 nm can present the d-spacing at 1.78 Å corresponding to the (200) forbidden reflections, and the relative intensity of these reflections increases as the particle size decreases. Our simulation results also reveal that defects, such as surface distortions, internal dislocations, and grain boundaries can also make the (200) forbidden reflections visible. These findings provide valuable insights into the diamond structural complexity at nanoscale, the impact of defects on nanodiamond structures, and the discovery of novel diamond structures.

Crystallization of heavy fermions via epitaxial strain in spinel LiV2O4 thin film.

The mixed-valent spinel LiV2O4 is known as the first oxide heavy-fermion system. There is a general consensus that a subtle interplay of charge, spin, and orbital degrees of freedom of correlated electrons plays a crucial role in the enhancement of quasi-particle mass, but the specific mechanism has remained yet elusive. A charge-ordering (CO) instability of V3+ and V4+ ions that is geometrically frustrated by the V pyrochlore sublattice from forming a long-range CO down to T = 0 K has been proposed as a prime candidate for the mechanism. Here, we uncover the hidden CO instability by applying epitaxial strain on single-crystalline LiV2O4 thin films. We find a crystallization of heavy fermions in a LiV2O4 film on MgO, where a charge-ordered insulator comprising of a stack of V3+ and V4+ layers along [001], the historical Verwey-type ordering, is stabilized by the in-plane tensile and out-of-plane compressive strains from the substrate. Our discovery of the [001] Verwey-type CO, together with previous realizations of a distinct [111] CO, evidence the close proximity of the heavy-fermion state to degenerate CO states mirroring the geometrical frustration of the V pyrochlore lattice, which supports the CO instability scenario for the mechanism behind the heavy-fermion formation.

Active emulsions in living cell membranes driven by contractile stresses and transbilayer coupling.

The spatiotemporal organization of proteins and lipids on the cell surface has direct functional consequences for signaling, sorting, and endocytosis. Earlier studies have shown that multiple types of membrane proteins, including transmembrane proteins that have cytoplasmic actin binding capacity and lipid-tethered glycosylphosphatidylinositol-anchored proteins (GPI-APs), form nanoscale clusters driven by active contractile flows generated by the actin cortex. To gain insight into the role of lipids in organizing membrane domains in living cells, we study the molecular interactions that promote the actively generated nanoclusters of GPI-APs and transmembrane proteins. This motivates a theoretical description, wherein a combination of active contractile stresses and transbilayer coupling drives the creation of active emulsions, mesoscale liquid order (lo) domains of the GPI-APs and lipids, at temperatures greater than equilibrium lipid phase segregation. To test these ideas, we use spatial imaging of molecular clustering combined with local membrane order, and we demonstrate that mesoscopic domains enriched in nanoclusters of GPI-APs are maintained by cortical actin activity and transbilayer interactions and exhibit significant lipid order, consistent with predictions of the active composite model.

Metal-organic cycle-based multistage assemblies.

It is well known that chemical compositions and structural arrangements of materials have a great influence on their resultant properties. Diverse functional materials have been constructed by using either biomolecules (peptides, DNA, and RNA) in nature or artificially synthesized molecules (polymers and pillararenes). The relationships between traditional building blocks (such as peptides) have been widely investigated, for example how hydrogen bonds work in the peptide multistage assembly process. However, in contrast to traditional covalent bond-based building blocks-based assembly, suprastructures formed by noncovalent bonds are more influenced by specific bond features, but to date only a few results have been reported based on noncovalent bond-based building block multistage assembly. Here, three metal­organic cycles (MOCs) were used to show how coordination bonds influence the bimetallacycle conformation then lead to the topology differences of MOC multilevel ordered materials. It was found that the coordination linker (isophthalate-Pt-pyridine) is an important factor to tune the shape and size of the MOC-derived suprastructures.

Composition-dependent ordering transformations in Pt-Fe nanoalloys.

SignificanceDynamically understanding the microscopic processes governing ordering transformations has rarely been attained. The situation becomes even more challenging for nanoscale alloys, where the significantly increased surface-area-to-volume ratio not only opens up a variety of additional freedoms to initiate an ordering transformation but also allows for kinetic interplay between the surface and bulk due to their close proximity. We provide direct evidence of the microscopic processes controlling the ordering transformation through the surface-bulk interplay in Pt-Fe nanoalloys and new features rendered by variations in alloy composition and chemical stimuli. These results provide a mechanistic detail of ordering transformation phenomena which are widely relevant to nanoalloys as chemical ordering occurs in most multicomponent materials under suitable environmental bias.

Interlayer Coupling Controlled Ordering and Phases in Polar Vortex Superlattices.

The recent discovery of polar topological structures has opened the door for exciting physics and emergent properties. There is, however, little methodology to engineer stability and ordering in these systems, properties of interest for engineering emergent functionalities. Notably, when the surface area is extended to arbitrary thicknesses, the topological polar texture becomes unstable. Here we show that this instability of the phase is due to electrical coupling between successive layers. We demonstrate that this electrical coupling is indicative of an effective screening length in the dielectric, similar to the conductor-ferroelectric interface. Controlling the electrostatics of the superlattice interfaces, the system can be tuned between a pure topological vortex state and a mixed classical-topological phase. This coupling also enables engineering coherency among the vortices, not only tuning the bulk phase diagram but also enabling the emergence of a 3D lattice of polar textures.

Controlled Self-Assembly of Nanoscale Superstructures in Phase-Change Ge-Sb-Te Nanowires.

Controlled growth of semiconductor nanowires with atomic precision offers the potential to tune the material properties for integration into scalable functional devices. Despite significant progress in understanding the nanowire growth mechanism, definitive control over atomic positions of its constituents, structure, and morphology via self-assembly remains challenging. Here, we demonstrate an exquisite control over synthesis of cation-ordered nanoscale superstructures in Ge-Sb-Te nanowires with the ability to deterministically vary the nanowire growth direction, crystal facets, and periodicity of cation ordering by tuning the relative precursor flux during synthesis. Furthermore, the role of anisotropy on material properties in cation-ordered nanowire superstructures is illustrated by fabricating phase-change memory (PCM) devices, which show significantly different growth direction dependent amorphization current density. This level of control in synthesizing chemically ordered nanoscale superstructures holds potential to precisely modulate fundamental material properties such as the electronic and thermal transport, which may have implications for PCM, thermoelectrics, and other nanoelectronic devices.

Resolving Multielement Semiconductor Nanocrystals at the Atomic Level: Complete Deciphering of Domains and Order in Complex CuαZnßSnγSeδ (CZTSe) Tetrapods.

Semiconductor nanocrystals (NCs) with high elemental and structural complexity can be engineered to tailor for electronic, photovoltaic, thermoelectric, and battery applications etc. However, this greater complexity causes ambiguity in the atomic structure understanding. This in turn hinders the mechanistic studies of nucleation and growth, the theoretical calculations of functional properties, and the capability to extend functional design across complementary semiconductor nanocrystals. Herein, we successfully deciphered the atomic arrangements of 4 different nanocrystal domains in CuαZnßSnγSeδ (CZTSe) nanocrystals using crucial zone axis analysis on multiple crystals in different orientations. The results show that the essence of crystallographic progression from binary to multielemental semiconductors is actually the change of theoretical periodicity. This transition is caused by decreased symmetry in the crystal instead of previously assumed crystal deformation. We further reveal that these highly complex crystalline entities have highly ordered element arrangements as opposed to the previous understanding that their elemental orderings are random.

Don't ignore the middle: Distinct mnemonic functions of intermediate hippocampus.

The dorsal region of the hippocampus (dHC) mediates many of the mnemonic functions traditionally associated with the hippocampus proper, such as spatial and episodic memory, whereas ventral hippocampus (vHC) has been extensively implicated in emotional memory and motivational processes. By contrast, the functions of the intermediate hippocampus (iHC) are far less understood. In this study, we aimed to investigate the mnemonic functions of iHC by reversibly inactivating iHC prior to testing memory in behavioral tasks dependent on the integrity of dHC, iHC, or vHC, namely, rapid place water maze, inhibitory avoidance, spontaneous alternation, and temporal ordering of odors. Given our previous findings showing that dHC and vHC are involved in mnemonic control of ingestive behavior, we also assessed the effects of iHC inactivation on sucrose intake. The results showed that pharmacological inhibition of iHC impairs rapid place water maze memory, which has been previously shown to be dependent on iHC but not dHC or vHC. iHC inactivation does not impact memory dependent on dHC (spontaneous alternation), vHC (temporal odor memory), or either dHC or vHC (inhibitory avoidance), and only modestly affects sucrose intake. These findings provide support for the involvement of iHC in mnemonic functions that are distinct from dHC and vHC and highlight the need to further advance our understanding of the functions of this hippocampal region that has been relatively understudied.

Crystal structure and magnetism of actinide oxides: a review.

In actinide systems, the 5felectrons experience a uniquely delicate balance of effects and interactions having similar energy scales, which are often difficult to properly disentangle. This interplay of factors such as the dual nature of 5f-states, strong electronic correlations, and strong spin-orbit coupling results in electronically unusual and intriguing behavior such as multi-k antiferromagnetic ordering, multipolar ordering, Mott-physics, mixed valence configurations, and more. Despite the inherent allure of their exotic properties, the exploratory science of even the more basic, binary systems like the actinide oxides has been limited due to their toxicity, radioactivity, and reactivity. In this article, we provide an overview of the available synthesis techniques for selected binary actinide oxides, including the actinide dioxides, sesquioxides, and a selection of higher oxides. For these oxides, we also review and evaluate the current state of knowledge of their crystal structures and magnetic properties. In many aspects, substantial knowledge gaps exist in the current body of research on actinide oxides related to understanding their electronic ground states. Bridging these gaps is vital for improving not only a fundamental understanding of these systems but also of future nuclear technologies. To this end, we note the experimental techniques and necessary future investigations which may aid in better elucidating the nature of these fascinating systems.

Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

Jahn-Teller distortion, octahedra rotations and orbital ordering in perovskites: KScF 3 as a model system.

The KScF 3 perovskite has been used as a model for investigating the relative importance of the Jahn-Teller (JT) lift of degeneracy, the ScF 6 octahedra rotation (OR), and the quadrupole-quadrupole interaction linked to different occupancy of the Sc t 2 g subshell in various sites of the unit cell (orbital ordering, OO). The group-subgroup sequence P m 3 ¯ m , P 4 m m m , P 4 m b m , and P n m a , supplemented by C m m m and I 4 m c m , has been explored by using an all electron Gaussian type basis set, hybrid functionals, and the CRYSTAL17 code. The JT lift of degeneracy provides a stabilization about 5 times larger than the sum of the OO and OR effects. The energy gained in the transition from P 4 m m m to P 4 m b m , consisting in a rotation of the octahedra around the c axis, is 1077 µ E h . From P 4 m b m to P n m a , additional rotations around the a and b axes are possible, and the d Sc electron can occupy a different t 2 g orbital, with a total energy reduction of 2318 µ E h . The rotation of the octahedra reduces the strength of superexchange: in going from P 4 m m m to P n m a the G-AFM stabilization with respect to FM shrinks by a factor 4.

t 2 g d orbital ordering patterns in KBF 3 (B = Sc, Ti, Fe, Co) perovskites.

The orbital ordering (OO) resulting from the partial occupancy of the t 2 g d subshell of the transition metals in KBF 3 (B = Sc, Ti, Ffe, Co) perovskites, and the many possible patterns arising from the coupling between the B sites, have been investigated at the quantum mechanical level ( all electron Gaussian type basis set, B3LYP hybrid functional) in a 40 atoms supercell. The numerous patterns are distributed into 162 classes of equivalent configurations. For each fluoroperovskite, one representative per class has been calculated. The four compounds behave similarly: an identical dependence of the energy and volume (or cell parameters) on the OO pattern; the spanned energy interval is small (1 to 2 mE h per formula unit), suggesting that most of the configurations are occupied at room and even at low temperature. A linear model, taking into account the relative orbital order in contiguous sites, reproduces the energy order in the full set for each compound, suggesting that it could be used for studying OO in larger supercells.

Halide Ordering Enables Superior Charge Transport in 3D (NMPDA)Pb2 I4 Br2 Perovskitoid Single Crystal.

Halide composition engineering has been demonstrated as an effective strategy for optical and electronic properties modulation in 3D perovskites. While the impact of halide mixing on the structural and charge transport properties of 3D perovskitoids remains largely unexplored. Herein, it is demonstrated that bromine (Br) mixing in 3D (NMPDA)Pb2 I6 (NMPDA = N-methyl-1,3-propane diammonium) perovskitoid yields stabilized (NMPDA)Pb2 I4 Br2 with specific ordered halide sites, where Br ions locate at the edge-sharing sites. The halide ordered structure enables stronger H-bonds, shorter interlayer distance, and lower octahedra distortion in (NMPDA)Pb2 I4 Br2 with respect to the pristine (NMPDA)Pb2 I6 . These attributes further result in high ion migration activation energy, low defect states density, and enhanced carrier mobility-lifetime product (µτ), as underpinned by the electrical properties investigation and DFT calculations. Remarkably, the parallel configured photodetector based on (NMPDA)Pb2 I4 Br2 single crystal delivers a high on/off current ratio of 3.92 × 103 , a satisfying photoresponsivity and detectivity of 0.28 A W-1 and 3.05 × 1012 Jones under 10.94 µW cm-2 irradiation, superior to that of (NMPDA)Pb2 I6 and the reported 3D perovskitoids. This work sheds novel insight on exploring 3D mixed halide perovskitoids toward advanced and stable optoelectronic devices.

Harnessing Smectic Ordering for Electric-Field-Driven Guided-Growth of Surface Topography in a Liquid Crystal Polymer.

The guided-growth strategy has been widely explored and proved its efficacy in fabricating surface micro/nanostructures in a variety of systems. However, soft materials like polymers are much less investigated partly due to the lack of strong internal driving mechanisms. Herein, the possibility of utilizing liquid crystal (LC) ordering of smectic liquid crystal polymers (LCPs) to induce guided growth of surface topography during the formation of electrohydrodynamic (EHD) patterns is demonstrated. In a two-stage growth, regular stripes are first found to selectively emerge from the homogeneously aligned region of an initially flat LCP film, and then extend neatly along the normal direction of the boundary line between homogeneous and homeotropic alignments. The stripes can maintain their directions for quite a distance before deviating. Coupled with the advanced tools for controlling LC alignment, intricate surface topographies can be produced in LCP films starting from relatively simple designs. The regularity of grown pattern is determined by the LC ordering of the polymer material, and influenced by conditions of EHD growth. The proposed approach provides new opportunities to employ LCPs in optical and electrical applications.

Multiple Topological Phases with Electronic Correlation in Intrinsic Ferromagnetic Semimetal VI3 Monolayer.

2D topological materials with magnetic ordering have become hot topics due to their nontrivial band topology and quantum states. In this work, the second-order topological states and evolution of linear band crossing are successfully predicted utilizing the effective k· p and tight binding models in the intrinsic ferromagnetic VI3 monolayer under various effective Hubble interaction Ueff. Upon inclusion of spin orbit coupling, a small bandgap (Eg-1) of 12.7 meV is opened with a Chern invariant C = -1 at Ueff = 0 eV. The Eg-1 undergoes a transition from the non-trivial state to trivial state at Ueff = 0.80 eV, accompanied by the appearance of Dirac cone. Remarkably, the increase of Ueff causes the band inversion and adjustment of crystal symmetry, resulting in two unreported coexisting topological bandgaps (Eg-2 and Eg-3). Furthermore, a gapless node-loop appears at Ueff = 1.06 eV and disappears at Ueff = 1.09 eV around Γ point. Moreover, for the first time, the existence of second-order topological states with quantized corner fractional charges (e/3) is also observed in the VI3 monolayer at Ueff ≥0.96 eV. These results make the VI3 monolayer a compelling candidate for exploring topological devices.

A retrospective observational study of mNGS test utilization to examine the role of diagnostic stewardship at two academic medical centers.

Given the cost and unclear clinical impact of metagenomic next-generation sequencing (mNGS), laboratory stewardship may improve utilization. This retrospective observational study examines mNGS results from two academic medical centers employing different stewardship approaches. Eighty mNGS orders [54 cerebrospinal fluid (CSF) and 26 plasma] were identified from 2019 to 2021 at the University of Washington (UW), which requires director-level approval for mNGS orders, and the University of Utah (Utah), which does not restrict ordering. The impact of mNGS results and the relationship to traditional microbiology orders were evaluated. Nineteen percent (10/54) of CSF and 65% (17/26) of plasma studies detected at least one organism. Compared to CSF results, plasma results more frequently identified clinically significant organisms (31% vs 7%) and pathogens not detected by traditional methods (12% vs 0%). Antibiotic management was more frequently impacted by plasma versus CSF results (31% vs 4%). These outcome measures were not statistically different between study sites. The number and cumulative cost of traditional microbiology tests at UW were greater than Utah for CSF mNGS testing (UW: 46 tests, $6,237; Utah: 26 tests, $2,812; P < 0.05) but similar for plasma mNGS (UW: 31 tests, $3,975; Utah: 21 tests, $2,715; P = 0.14). mNGS testing accounted for 30%-50% of the total microbiology costs. Improving the diagnostic performance of mNGS by stewardship remains challenging due to low positivity rates and difficulties assessing clinical impact. From a fiscal perspective, stewardship efforts should focus on reducing testing in low-yield populations given the high costs of mNGS relative to overall microbiology testing expenditures. IMPORTANCE: Metagenomic next-generation sequencing (mNGS) stewardship practices remain poorly standardized. This study aims to provide actionable insights for institutions that seek to reduce the unnecessary usage of mNGS. Importantly, we highlight that clinical impact remains challenging to measure without standardized guidelines, and we provide an actual cost estimate of microbiology expenditures on individuals undergoing mNGS.