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The stability of protein folded states is crucial for its function, yet the relationship with the protein sequence remains poorly understood. Prior studies have focused on the amino acid composition and thermodynamic couplings within a single folded conformation, overlooking the potential contribution of protein dynamics. Here, we address this gap by systematically analyzing the impact of alanine mutations in the C-terminal β-strand (β5) of ubiquitin, a model protein exhibiting millisecond timescale interconversion between two conformational states differing in the β5 position. Our findings unveil a negative correlation between millisecond dynamics and thermal stability, with alanine substitutions at seemingly flexible C-terminal residues significantly enhancing thermostability. Integrating spectroscopic and computational approaches, we demonstrate that the thermally unfolded state retains a substantial secondary structure but lacks β5 engagement, recapitulating the transition state for millisecond dynamics. Thus, alanine mutations that modulate the stabilities of the folded states with respect to the partially unfolded state impact both the dynamics and stability. Our findings underscore the importance of conformational dynamics with implications for protein engineering and design.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV–vis–NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1exhibits strong binding affinities for fullerenes, leading to host–guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Diamond is considered the most promising next-generation semiconductor material due to its excellent physical characteristics. It has been more than three decades since the discovery of a special structure named n-diamond. However, despite extensive efforts, its crystallographic structure and properties are still unclear. Here, we show that subdisordered structures in diamond provide an explanation for the structural feature of n-diamond. Monocrystalline diamond with subdisordered structures is synthesized via the chemical vapor deposition method. Atomic-resolution scanning transmission electron microscopy characterizations combined with the picometer-precision peak finder technology and diffraction simulations reveal that picometer-scale shifts of atoms within cells of diamond govern the subdisordered structures. First-principles calculations indicate that the bandgap of diamond decreases rapidly with increasing shifting distance, in accordance with experimental results. These findings clarify the crystallographic structure and electronic properties of n-diamond and provide new insights into the bandgap adjustment in diamond.

The implementation of China's national carbon market trading policy forms a unique model of parallel national and pilot markets, and makes its risk spillover relationship with energy markets a new issue to be explored. The risk transmission network of China's carbon-energy system is constructed using the connectedness approach in this paper, which also investigates the size, structure, time-varying characteristics, and long- and short-term differences of risk contagion as well as the role of major events in causing risk spillovers. We find that, first, there exists a certain degree of risk contagion within the carbon-energy system that is affected by short-term risk spillovers and is most pronounced at the right-tailed extremes. Second, the national carbon market and coal market are the primary sources of risk contagion in the risk spillover network. The former holds a central place in the network and exhibits a strong interaction with mature carbon pilot markets. Third, fluctuations in the energy market and carbon policy events dominate the overall spillover changes, with the former significantly affecting the risk spillover from the energy market, while the latter drives the risk spillover from the national carbon market.

The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS3)) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS3, and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains. Therefore, the flat-bottom Lorentz-like potentials are recommended to represent cross-link restraints. It was also found that significant improvement of model quality upon the introduction of cross-link restraints is obtained when the sum of differences of indices of cross-linked residues exceeds 150.

As a popular complementary therapy, the safety of acupuncture must be considered. Acupuncture case reports of adverse events (ACR-AEs) significantly contribute to the assessment of acupuncture safety. However, the reporting quality of ACR-AEs remains unclear. We aimed to promote the application of the CARE (case report) guidelines and improve the reporting quality of ACR-AEs.

Piezoelectric polymer films are forthcoming choices for self-powered portable flexible electronics due to instant mechanoelectrical transduction, ease of fabrication, and assembly for device integration. However, the low piezoelectricity of polymers in comparison with piezoelectric ceramics precludes their practical applications significantly. Here, we report an interesting method to fabricate piezoelectric poly(vinylidene fluoride) (PVDF) fiber mats with excellent piezoelectricity by collecting electrospun fibers using low-temperature electrolytes. Specifically, fiber collection assisted by liquid electrolytes enables the formation of piezoelectric PVDF crystals with zigzag conformation induced by strong solvent–electrolyte and dipole–ion interactions, as well as the immobilization of aligned dipoles at low temperature. Consequently, compared with conventional PVDF fibers collected by aluminum foils, those fiber mats electrospun using liquid electrolytes can generate an open-circuit voltage of 2.3 V under a pressure of 20 N at 1 Hz for an effective area of 1 cm2, showing a nearly eight-times improvement. In addition, the as-prepared piezoelectric fiber mats enable the conversion of mechanical energy into electricity with an instantaneous output power density of ∼16.2 mW/m2, which allows for self-powered sensing or energy harvesting. Such an electrospinning technology enables simple fabrication of high-performance piezoelectric polymer fiber mats with diverse surface microstructure for self-powered flexible electronics.

The conventional approach toward molecules with large two-photon absorption (TPA) involves donor–acceptor conjugation. Herein we show a new strategy involving the use of hexa-branched nanographenes. We synthesized two hexa-branched nanographenes, one with six benzoaceanthrylene arms fused to the coronene core and the other with six pyrenyl arms fused to the coronene core. Neither of these hexa-branched nanographenes has a donor–acceptor structure, yet they exhibited high TPA values of 3.6 × 103and 1.9 × 104GM, respectively, which are the highest values recorded for heteroatom-free hydrocarbon molecules. Theoretical analysis suggests that the fused branched structures are responsible for the large TPA cross-section. These findings illustrate the importance of the topology of the fused conjugated skeleton in TPA and provide an alternative structural design toward large TPA.

Organic trisradicals featuring threefold symmetry have attracted significant interest because of their unique magnetic properties associated with spin frustration. Herein, we describe the synthesis and characterization of a triangular prism-shaped organic cage for which we have coined the name PrismCage6+and its trisradical trication─TR3(•+). PrismCage6+is composed of three 4,4′-bipyridinium dications and two 1,3,5-phenylene units bridged by six methylene groups. In the solid state, PrismCage6+adopts a highly twisted conformation with close to C3symmetry as a result of encapsulating one PF6–anion as a guest. PrismCage6+undergoes stepwise reduction to its mono-, di-, and trisradical cations in MeCN on account of strong electronic communication between its 4,4′-bipyridinium units. TR3(•+), which is obtained by the reduction of PrismCage6+employing CoCp2, adopts a triangular prism-shaped conformation with close to C2vsymmetry in the solid state. Temperature-dependent continuous-wave and nutation-frequency-selective electron paramagnetic resonance spectra of TR3(•+)in frozen N,N-dimethylformamide indicate its doublet ground state. The doublet–quartet energy gap of TR3(•+)is estimated to be −0.08 kcal mol–1, and the critical temperature of spin-state conversion is found to be ca. 50 K, suggesting that it displays pronounced spin frustration at the molecular level. To the best of our knowledge, this example is the first organic radical cage to exhibit spin frustration. The trisradical trication of PrismCage6+opens up new possibilities for fundamental investigations and potential applications in the fields of both organic cages and spin chemistry.

Conjugated molecules play a critical role in the construction of single-molecule devices. However, most conventional conjugated molecules, such as hydrocarbons, involve only a pπ–pπ conjugation of light elements. While the metal d-orbitals can introduce abundant electronic effects to achieve novel electronic properties, it is very scarce for the charge transport study of dπ–pπ conjugated pathways with a metal involved. Here, we employed the single-molecule break junction technique to investigate the charge transport through dπ–pπ conjugated backbones with metal–carbon multiple bonds integrated into the alternative conjugated pathways. The involved dπ–pπ conjugation not only supports high conductivity comparable to that of conjugated hydrocarbons but also significantly enhances the tunable diversity in electronic properties through the metal-induced secondary interaction. Specifically, the introduction of the metal brings an unconventionally stereoelectronic effect triggered by metal–carbon dπ–pπ hyperconjugation, which can be tuned by protonation taking place on the metal–carbon multiple bonds, collectively modulating the single-molecule rectification feature and transmission mechanism. This work demonstrates the promise of utilizing the diverse electronic effect of metals to design molecular devices.

Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and COPD.

The clinically used androgen receptor (AR) antagonists for the treatment of prostate cancer (PCa) are all targeting the AR ligand binding pocket (LBP), resulting in various drug-resistant problems. Therefore, a new strategy to combat PCa is urgently needed. Enlightened by the gain-of-function mutations of androgen insensitivity syndrome, we discovered for the first time small-molecule antagonists toward a prospective pocket on the AR dimer interface named the dimer interface pocket (DIP) via molecular dynamics (MD) simulation, structure-based virtual screening, structure–activity relationship exploration, and bioassays. The first-in-class antagonist M17-B15 targeting the DIP is capable of effectively disrupting AR self-association, thereby suppressing AR signaling. Furthermore, M17-B15 exhibits extraordinary anti-PCa efficacy in vitro and also in mouse xenograft tumor models, demonstrating that AR dimerization disruption by small molecules targeting the DIP is a novel and valid strategy against PCa.

Strain and antiaromaticity in compounds are recognized as two substantial destabilizing features, and consequently, realization of dual destabilizing features in a single molecule is challenging and far more difficult in a single ring. Moreover, transformation of an antiaromatic framework to different antiaromatic or aromatic species is a significant subject in antiaromatic chemistry and has attracted increasing interest. In this work, we isolated a highly strained antiaromatic metallacycle in which a cyclic metal vinylidene unit is embedded. Computational studies revealed its ring strain energies and antiaromatic character and showed that the metal incorporation and the phosphonium substituents play a crucial role in its stabilization. The mechanism of its formation has been illustrated by density functional theory (DFT) calculations and the isolation of a key intermediate. We further discovered diverse reactivities and structural reshuffling of this unusual strained antiaromatic complex according to its two destabilizing characters. We obtained two isomers of metallaindenes fused with oxiranes from the direct oxidation of the metal vinylidene or by nucleophilic addition to an isolated metallacyclocumulene formed by the reaction of metal vinylidene with hydroxide ion, achieving a reconfiguration of the antiaromatic framework. Transformations of the antiaromatic metallacycle by electrophiles to various aromatic metallaindynes have been achieved, and that a condensed Fukui function was employed to confirm the regioselectivity of the electrophilic additions, and the acid/base-induced aromaticity switch along with tunable photophysical properties were investigated. These interesting transformations not only enrich the chemistry of metal vinylidenes and antiaromatics and could also perform potentially as switchable optical materials.

BackgroundVision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth.MethodsBaseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤−5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13–15 years and 16–18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted.ResultsAlmost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia.ConclusionIn highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Voltage-gated sodium channel 1.7 (Nav1.7) remains one of the most promising drug targets for pain relief. In the current study, we conducted a high-throughput screening of natural products in our in-house compound library to discover novel Nav1.7 inhibitors, then characterized their pharmacological properties. We identified 25 naphthylisoquinoline alkaloids (NIQs) from Ancistrocladus tectoriusto be a novel type of Nav1.7 channel inhibitors. Their stereostructures including the linkage modes of the naphthalene group at the isoquinoline core were revealed by a comprehensive analysis of HRESIMS, 1D, and 2D NMR spectra as well as ECD spectra and single-crystal X-ray diffraction analysis with Cu Kαradiation. All the NIQs showed inhibitory activities against the Nav1.7 channel stably expressed in HEK293 cells, and the naphthalene ring in the C-7 position displayed a more important role in the inhibitory activity than that in the C-5 site. Among the NIQs tested, compound 2was the most potent with an IC50of 0.73 ± 0.03 µM. We demonstrated that compound 2(3 µM) caused dramatical shift of steady-state slow inactivation toward the hyperpolarizing direction (V1/2values were changed from −39.54 ± 2.77 mV to −65.53 ± 4.39 mV, which might contribute to the inhibition of compound 2against the Nav1.7 channel. In acutely isolated dorsal root ganglion (DRG) neurons, compound 2(10 μM) dramatically suppressed native sodium currents and action potential firing. In the formalin-induced mouse inflammatory pain model, local intraplantar administration of compound 2(2, 20, 200 nmol) dose-dependently attenuated the nociceptive behaviors. In summary, NIQs represent a new type of Nav1.7 channel inhibitors and may act as structural templates for the following analgesic drug development.

Molecular recognition, based on noncovalent bonding interactions, plays a central role in directing supramolecular phenomena in both chemical and biological environments. The identification and investigation of weakly associated recognition motifs, however, remains a major challenge, especially when the motifs are interlinked with and obscured by other robust binding modes in complicated systems. For example, although the host–guest recognition between the radical cations of both cyclobis(paraquat-p-phenylene) (CBPQT) and 4,4′-bipyridinium (BIPY) salts has been thoroughly investigated, the question of whether other binding modes exist between these two positively charged entities is the subject of some debate because of the complexity and dynamic nature of this supramolecular system. In order to address this conundrum, we have synthesized a [2]catenane─formed by mechanical interlocking between CBPQT and another BIPY-containing ring─which enhances the weak interactions between components and reduces significantly the complexity of the system for easier characterization. By employing this [2]catenane as a model compound, we have performed a full-spectrum investigation of radical interactions and revealed unambiguously a total of three possible binding modes between CBPQT and BIPY─to be specific, a bisradical tetracationic, a trisradical tricationic, and a bisradical dicationic association─as demonstrated by various methods of characterization including UV/vis/NIR, EPR, and NMR spectroscopies, electrochemical measurements and X-ray crystallography. The two newly discovered bisradical binding modes have potential applications in the construction of self-assembled materials and in mediating supramolecular catalysis. The mechanical bond-assisted approach used in this research is broadly applicable to investigating noncovalent bonding interactions.

We study the existence of solutions for the quasilinear Schrödinger equation with the critical exponent and steep potential well. By using a change of variables, the quasilinear equations are reduced to a semilinear one, whose associated functionals satisfy the geometric conditions of the Mountain Pass Theorem for suitable assumptions. The existence of a ground state solution is obtained, and its concentration behavior is also considered.

The high prevalence and mortality of cardiovascular diseases in China’s large population has increased the use of cardiovascular imaging for the assessment of conditions in recent years. In this study, we review the past 20 years of cardiovascular imaging in China, the increasingly important role played by cardiovascular computed tomography in coronary artery disease and pulmonary embolism assessment, magnetic resonance imaging’s use for cardiomyopathy assessment, the development and application of artificial intelligence in cardiovascular imaging, and the future of Chinese cardiovascular imaging.

In this paper, we study the existence of positive solutions for a class of Kirchhoff equation with critical growth -a+b∫Ω|∇u|2dxΔu+V(x)u=u5inΩ,u∈D01,2(Ω),where a>0, b>0, V∈L32(Ω)is a given nonnegative function and Ω⊆R3is an exterior domain, that is, an unbounded domain with smooth boundary ∂Ω≠∅such that R3\Ωnon-empty and bounded. By using barycentric functions and Brouwer degree theory to prove that there exists a positive solution u∈D01,2(Ω)if R3\Ωis contained in a small ball.

Vacancies generally reduce the number of chemical bonds and hence cause structural softening. It is puzzling, however, that substoichiometric Re0.5W0.5C0.4with 60% carbon vacancies was identified as a superhard material. Here, we report the underlying mechanism responsible for such anomalous vacancy-induced hardening in the Re0.5W0.5C1–xsystem via first-principles calculations. The shear stiffness and hardness increase consistently with rising carbon vacancy concentration in Re0.5W0.5C1–xand reach the maximum at about x= 40%. Such an unexpected hardening phenomenon originates from a gradual relief of the shear-unstable dd bonding and unfavorable pd antibonding interactions owing to the formation of C-vacancies. We further predict that the simultaneous ordered vacancies of W and C atoms can produce a cubic crystalline Re2/3W1/3C that is isomorphic with the NbO type. The calculations on vibrational, mechanical, and electronic properties reveal that this phase has considerable structural stability and is a hard metallic material. This work not only elucidates the intriguing mechanism responsible for the vacancy hardening in this class of systems but also provides a new principle for the structural stability of other transition-metal compounds.

In-memory computing provides an opportunity to meet the growing demands of large data-driven applications such as machine learning, by colocating logic operations and data storage. Despite being regarded as the ultimate solution for high-density integration and low-power manipulation, the use of spin or electric dipole at the single-molecule level to realize in-memory logic functions has yet to be realized at room temperature, due to their random orientation. Here, we demonstrate logic-in-memory operations, based on single electric dipole flipping in a two-terminal single-metallofullerene (Sc2C2@Cs(hept)-C88) device at room temperature. By applying a low voltage of ±0.8 V to the single-metallofullerene junction, we found that the digital information recorded among the different dipole states could be reversibly encoded in situ and stored. As a consequence, 14 types of Boolean logic operation were shown from a single-metallofullerene device. Density functional theory calculations reveal that the non-volatile memory behaviour comes from dipole reorientation of the [Sc2C2] group in the fullerene cage. This proof-of-concept represents a major step towards room-temperature electrically manipulated, low-power, two-terminal in-memory logic devices and a direction for in-memory computing using nanoelectronic devices.

In this article, we investigate the existence of least energy sign-changing solutions for the following Schrödinger-Poisson system −Δu+V(x)u+K(x)ϕu=f(u),x∈R3,−Δϕ=K(x)u2,x∈R3,\left\{\begin{array}{ll}-\Delta u+V\left(x)u+K\left(x)\phi u=f\left(u),\hspace{1.0em}& x\in {{\mathbb{R}}}^{3},\\ -\Delta \phi =K\left(x){u}^{2},\hspace{1.0em}& x\in {{\mathbb{R}}}^{3},\\ \hspace{1.0em}\end{array}\right.where the functions V(x),K(x)V\left(x),K\left(x)have finite limits as ∣x∣→∞| x| \to \infty satisfying some mild assumptions. By combining variational methods with the global compactness lemma, we obtain a least energy sign-changing solution with exactly two nodal domains, and its energy is strictly larger than twice that of least energy solutions.

The environmental condition is a critical regulation factor for protein behavior in solution. Several studies have shown that macromolecular crowders can modulate protein structures, interactions, and functions. Recent publications described the regulation of specific interaction by macromolecular crowders. However, the other category of protein–protein interaction, namely, the transient interaction, is rarely investigated, especially from the perspective of protein structure to study transient interactions between proteins. Here, we used nuclear magnetic resonance and small-angle X-ray/neutron scattering methods to structurally investigate the ensemble of the protein complex in dilute buffer and crowded environments. Histidine phosphocarrier protein (HPr) and the N-terminal domain of enzyme I (EIN) are the important components of the bacterial phosphotransfer system. Our results show that the addition of Ficoll-70 promotes HPr molecules to form the encounter complex with EIN maintained by long-range electrostatic interaction. However, when macromolecular crowder BSA is used, the soft interaction between BSA and HPr perturbs the active site of HPr, driving HPr to form an encounter complex with EIN at the weakly charged interface. Our results indicate that different macromolecular crowders could influence transient EIN-HPr interaction through different mechanisms and provide new insights into protein–protein interaction regulation in native environments.

This article is devoted to studying the existence of positive solutions to the following fractional Choquard equation: (−Δ)su+u=∫Ω∣u(y)∣p∣x−y∣N−αdy∣u∣p−2u+ε∫Ω∣u(y)∣2α,s*∣x−y∣N−αdy∣u∣2α,s*−2u,inΩ,u=0,onRN\Ω,\left\{\begin{array}{ll}{\left(-\Delta )}^{s}u+u=\left(\mathop{\displaystyle \int }\limits_{\Omega }\frac{{| u(y)| }^{p}}{{| x-y| }^{N-\alpha }}{\rm{d}}y\right){| u| }^{p-2}u+\varepsilon \left(\mathop{\displaystyle \int }\limits_{\Omega }\frac{{| u(y)| }^{{2}_{\alpha ,s}^{* }}}{{| x-y| }^{N-\alpha }}{\rm{d}}y\right){| u| }^{{2}_{\alpha ,s}^{* }-2}u,& \hspace{0.1em}\text{in}\hspace{0.1em}\hspace{0.33em}\Omega ,\\ u=0,& \hspace{0.1em}\text{on}\hspace{0.1em}\hspace{0.33em}{{\mathbb{R}}}^{N}\backslash \Omega \right,\end{array}\right.where Ω\Omega is an exterior domain with smooth boundary ∂Ω≠∅\partial \Omega \ne \varnothing such that RN\Ω{{\mathbb{R}}}^{N}\backslash \Omega is bounded, N>2s,20\varepsilon \gt 0is a parameter. We establish the limit profiles and uniqueness of positive radial ground-states for the limit equation without the critical exponent as α\alpha sufficiently close to NN. Then, combining variational method, barycentric functions, and Brouwer degree theory, we determine the existence of positive bound-state solutions provided that ε>0\varepsilon \gt 0is sufficiently small.

In this article, we consider the following Kirchhoff equation involving fractional Laplacian a+b[u]s2(-Δ)su+u=|u|p-2uinΩ,u=0onR3\Ω,where a,b>0are constants, 34

We performed a post hocanalysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.

Androgen receptor (AR) has proved to be a vital drug target for treating prostate cancer. Here, we reported the discovery of a novel AR antagonist 92targeting the AR ligand-binding pocket, but distinct from the marketed drug enzalutamide (Enz), 92demonstrated inhibition on the AR ligand-binding domain (LBD) dimerization, which is a novel mechanism reported for the first time. First, a novel hit (26, IC50= 5.57 μM) was identified through virtual screening based on a theoretical AR LBD dimer bound with the Enz model. Then, guided by molecular modeling, 92was discovered with 32.7-fold improved AR antagonistic activity (IC50= 0.17 μM). Besides showing high bioactivity and safety, 92can inhibit AR nuclear translocation. Furthermore, 92inhibited the formation of the AR LBD dimer, possibly through attenuating the hydrogen-bonding network between the two monomers. This interesting finding would pave the way for the discovery of a new class of AR antagonists.

Gut microbiota community shift with coronary artery disease (CAD) has been reported in several limited cohorts during the past several years. However, whether the enriched or decreased microbiota taxa with CAD can be reproducible deserves further investigation and validation. In this study, 78 human subjects were recruited. Of these, 19 were diagnosed without stenosis in coronary artery (control group, referred to herein as Ctrl), 14 with stenosis less than 50% (LT50), and 45 with stenosis greater than 50% (GT50). Fecal samples were collected and DNA was extracted to perform 16S ribosomal RNA (rRNA) gene sequencing. The operational taxonomic units (OTUs) were analyzed to identify taxa specific to different groups; next, multivariate logistic regression was employed to test whether the defined taxa could independently predict CAD risk. We found that Deltaproteobacteria, Fusobacterium, Bilophila, Actinomyces, and Clostridium XIXwere enriched in Ctrl; Prevotellaceae, Parabacteriodes, and Butyricicoccuswere enriched in LT50; and Roseburiaand Butyricimonaswere enriched in GT50. Further analysis revealed that increased populations of Deltaproteobacteria, Fusobacterium, Bilophila, and Desulfovibrionaceae were associated with a 0.26-fold, 0.21-fold, 0.18-fold, and 0.26-fold decreased risk of CAD, respectively (p < 0.05), and an increased Prevotellaceae population was associated with a 5.63-fold increased risk of CAD (p < 0.01). A combination of the 20 microbial taxa achieved an area under the receiver operating characteristic (ROC) curve of higher than 0.88 for all discriminations between LT50 vs Ctrl, GT50 vs Ctrl, LT50 + GT50 vs Ctrl, and GT50 vs Ctrl + LT50. However, the microbial taxa previously reported as enriched in CAD patients or healthy controls could not be observed in our cohort except for Bacteroides. In conclusion, CAD patients showed a different microbial taxa signature than the healthy controls. However, the non-reproducibility of the microbiota taxa enriched in CAD across different cohorts limits the use of this signature in early diagnosis and prevention. Only decreased Bacteroidesabundance was found to be a reliable marker to indicate CAD progression.

In this paper, we investigate the following Schrödinger–Poisson system -Δu+u+ϕu=f(u),inR3,-Δϕ=u2,inR3,where f∈C(R,R), and fsatisfies that 13f(t)t≥F(t)>0with t∈R\{0}. We construct a Palais–Smale sequence that is relevant to Pohožaev identity to obtain infinitely many high energy radial solutions for this system.

The arrival time difference ratio, an analysis of pulmonary artery and bronchial artery contrast-enhanced US, can provide an accurate method to distinguish benign subpleural pulmonary lesions from malignant ones.

Molecular rectifier, as a basic function of molecular electronic devices, has attracted extensive attention for the opportunity in constructing sub-nanometer electronic devices. However, tunneling leakage current has a significant contribution as electronic devices shrink in size, which leads to a challenge in fabricating molecular rectifiers at the sub-nanometer scale. Here, we experimentally demonstrate a sub-nanometer molecular rectifier based on the supramolecular junction assembled between water and 1,4-diazabicyclo[2.2.2]octane (DABCO) molecule. The charge transport through DABCO and corresponding supramolecular junctions exhibits destructive σ-interference, ensuring a sharp conductance variation for transmission modulation. The supramolecular interaction between DABCO and water readily introduces the asymmetric electrode-molecule interaction, which combines with the destructive σ-interference to support the sub-nanometer rectification.

Fabrication of molecular devices will meet the demands of the miniaturization of traditional electronic devices. Although microfabrication based on the complementary metal-oxide–semiconductor process can fabricate high-quality single-molecule devices, the cost is high, leading to a challenge to provide a hands-on experiment in the teaching practice of charge transport through single-molecule devices. Here, we demonstrate the low cost and simple procedures associated with a mechanically controllable break junction (MCBJ) technique to fabricate single-molecule devices. On the basis of the MCBJ technique, the conductance of gold–gold atomic contacts and single-molecule junctions can be readily characterized. The teaching practice helps students understand charge transport at the single-molecule level, that is, the quantum tunneling mechanisms. Moreover, the MCBJ technique study provides students the opportunity to develop interdisciplinary thinking, which is vital for understanding, designing, and developing single-molecule electronics.

In the present paper, a class of Schrödinger equations is investigated, which can be stated as −Δu+V(x)u=f(u),x∈ℝN.- \Delta u + V(x)u = f(u),\;\;\;\;x \in {{\rm{\mathbb R}}^N}.If the external potential Vis radial and coercive, then we give the local Ambrosetti-Rabinowitz super-linear condition on the nonlinearity term f∈ C(ℝ, ℝ) which assures the problem has not only infinitely many radial sign-changing solutions, but also infinitely many non-radial sign-changing solutions.

Reports reveal that the piezoresistance coefficients of silicon carbide (SiC) nanowires (NWs) are 2 to 4 times smaller than those of their corresponding bulk counterparts. It is a challenge to eliminate contamination in adhering NWs onto substrates. In this study, a new setup was developed, in which NWs were manipulated and fixed by a goat hair and conductive silver epoxy in air, respectively, in the absence of any depositions. The goat hair was not consumed during manipulation of the NWs. The process took advantage of the stiffness and tapered tip of the goat hair, which is unlike the loss issue of beam sources in depositions. With the new fixing method, in situ transmission electron microscopy (TEM) electromechanical coupling measurements were performed on pristine SiC NWs. The piezoresistance coefficient and carrier mobility of SiC NW are −94.78 × 10–11Pa–1and 30.05 cm2V–1s–1, respectively, which are 82 and 527 times respectively greater than those of SiC NWs reported previously. We, for the first time, report that the piezoresistance coefficient of SiC NW is 17 times those of its bulk counterparts. These findings provide new insights to develop high performance SiC devices and to help avoid catastrophic failure when working in harsh environments.

In the context of the development of the Low-Carbon Economy, the Carbon Market is an important way to guide enterprises to actively participate in environmental governance and promote enterprises to achieve green transformation. In this study, the first group of electric power industry companies participating in the carbon market on July 16, 2021, was selected as the treatment group. And the difference-in-differences (DID) model was used to investigate the influence of the Carbon Market on corporate financing behavior. This study finds that Carbon Market can significantly promote the level of corporate financing. This is achieved through enhancing credit financing and long-term financing. The heterogeneity analysis shows that the promotion impact is more obvious in state-owned enterprises, start-ups, and smaller enterprises. Additionally, we discuss the above impacts in terms of constraints and demands. In terms of constraints, the increase of external financing difficulty and the squeeze of own financing space will inhibit the promotion of the Carbon Market on the financing level. In terms of demand, corporate investment demand and investors’ attention will enhance the positive impact of the Carbon Market on the financing level. This paper expands the relevant research on the Carbon Market. It reveals the mechanism and effective path of corporate financing behavior in the Low-Carbon Economy. In addition, the paper provides new evidence for the improvement and development of the Carbon Market policies.

Frozen shoulder (FS) is characterized by restricted active and passive shoulder mobility and pain.

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

In this paper, we study the following Chern–Simons–Schrödinger equation -?u+?u+?(h2(|x|)|x|2+?|x|+8h(s)su2(s)ds)u=g(u)inR2,u?Hr1(R2),where ?,?>0and h(s)=12?0sru2(r)dr. Since the nonlinearity gis asymptotically 5-linear at infinity, there would be a competition between gand the nonlocal term. By constrained minimization arguments and the quantitative deformation lemma, we prove the existence of least energy sign-changing radial solution, which changes sign exactly once. Further, we study the concentration of the least energy sign-changing radial solutions as ??0.

The single-molecule break junction technique provides a high-throughput method to explore the charge transport phenomena through a molecular junction at the ultimate scale of a single molecule. The most probable conductance of a molecular junction is normally extracted from histogram generated from repeated and massive break junction data. However, this conventional data analysis method only exhibits general charge transport properties of molecular junctions, and insightful information hidden in those recorded data remains unexplored. Among them, some of the conductance variations corresponding to different molecular junction conformations that occur during the break junction process might easily be overlooked. To accurately extract those hidden events, here we demonstrated a customized spectral clustering method with the evaluation of the Calinski–Harabasz index, which could be employed to analyze a large amount of data and to automatically extract different molecular junction conformations without subjective bias. Our approach was first validated through simulated data sets and was confirmed to be suitable for the product analysis during a chemical reaction. Moreover, using this method, an easily overlooked but unignorable junction conformation was found during the carborane molecular junction measurement, suggesting that spectral clustering with the Calinski–Harabasz index as a criterion offers a promising algorithm for junction conformation analysis in massive break junction data.

Nonaqueous organic redox flow batteries (NAORFBs) show great promise for grid energy storage but are currently facing key challenges such as high electroactive material cost and low energy density. Herein, we report the electrochemical properties and the potential application of a series of cost-effective electroactive nitrobenzene molecules in NAORFBs. Pairing the low-cost miscible liquid nitrobenzene (NB) with 2,5-di-tert-butyl-1-methoxy-4-(20-methoxyethoxy)-benzene (DBMMB) resulted in a flow battery that provides a high theoretical cell voltage of 2.2 V and a calculated energy density of 192 Wh L–1. In the charge–discharge testing, this battery delivers a stable cycling capacity retention of 99.5% per cycle over 100 cycles and a 70% energy efficiency at 40 mA cm–2operation current density, verifying that liquid nitrobenzene is a promising low-cost electroactive anode molecule for NAORFBs.

In this paper, we investigate the non-autonomous Choquard equation

Transient receptor potential channel TRPV4 and nicotinamide adenine dinucleotide phosphate oxidase (Nox2) are involved in oxidative stress that increases endothelial permeability. It has been shown that obesity enhances the physical association of TRPV4 and Nox2, but the role of TRPV4–Nox2 association in obesity has not been clarified. In this study we investigated the function of TRPV4–Nox2 complex in reducing oxidative stress and regulating abnormal vascular permeability in obesity. Obesity was induced in mice by feeding a high-fat diet (HFD) for 14 weeks. The physical interaction between TRPV4 and Nox2 was measured using FRET, co-immunoprecipitation and GST pull-down assays. The functional interaction was measured by rhodamine phalloidin, CM-H2DCFDA in vitro, the fluorescent dye dihydroethidium (DHE) staining assay, and the Evans blue permeability assay in vivo. We demonstrated that TRPV4 physically and functionally associated with Nox2, and this physical association was enhanced in aorta of obese mice. Furthermore, we showed that interrupting TRPV4–Nox2 coupling by TRPV4 knockout, or by treatment with a specific Nox2 inhibitor Nox2 dstat or a specific TRPV4 inhibitor HC067046 significantly attenuated obesity-induced ROS overproduction in aortic endothelial cells, and reversed the abnormal endothelial cytoskeletal structure. In order to discover small molecules disrupting the over-coupling of TPRV4 and Nox2 in obesity, we performed molecular docking analysis and found that compound M12 modulated TRPV4–Nox2 association, reduced ROS production, and finally reversed disruption of the vascular barrier in obesity. Together, this study, for the first time, provides evidence for the TRPV4 physically interacting with Nox2. TRPV4–Nox2 complex is a potential drug target in improving oxidative stress and disruption of the vascular barrier in obesity. Compound M12 targeting TRPV4–Nox2 complex can improve vascular barrier function in obesity.