Fufang Zhenshu Tiaozhi capsule enhances bone formation and safeguards against glucocorticoid-induced osteoporosis through innovative Mekk2-mediated ß-catenin deubiquitination.

INTRODUCTION: Bone homeostasis depends on the regulation of ß-catenin in osteoblasts. Glucocorticoids (GCs) are known to diminish ß-catenin activity via Wnt pathway signaling, leading to osteoporosis. Conversely, activating ß-catenin in osteoblasts through mitogen-activated protein kinase kinase kinase 2 (Mekk2) offers an innovative approach to combat GC-induced osteoporosis (GIOP). Fufang Zhenshu Tiaozhi (FTZ) capsules have shown effectiveness in treating GIOP, but the mechanisms behind this are still unclear. MATERIALS AND METHODS: In this study, Mekk2 knockout mice (Mekk2-/-) was generated by CRISPR/Cas9. These mice were then subjected to Alcian Blue-Alizarin Red staining and immunofluorescence to assess their bone and cartilage development. To establish models of GIOP, both Mekk2-/- and wild-type (WT) mice were treated with dexamethasone (DXMS) and subsequently given FTZ capsules. We analyzed the resulting phenotypic changes in these mice using Micro-CT scans and histomorphological studies. Primary osteoblasts, isolated from both Mekk2-/- and WT mice, underwent qRT-PCR to measure key osteogenesis markers, including Runx2, Sp7, Bgalp, Col1a1 and Alp. Cells were then exposed to treatments with either FTZ or Wnt3a and the phosphorylation levels of ß-catenin and Mekk2, along with the protein expression of Runx2, were evaluated using Western blotting and immunoprecipitation. Additionally, C3H10T1/2 cells transfected with TOPflash-luciferase and Renilla luciferase reporters were treated with FTZ and Wnt3a to measure ß-catenin activity. RESULTS: In our study, administering FTZ in vivo effectively prevented bone loss typically induced by GCs. However, it's important to note that this protective effect was substantially reduced in mice lacking Mekk2. Additionally, FTZ showed a significant ability to enhance osteogenic differentiation in primary osteoblasts, doing so by altering the expression of Mekk2. Intriguingly, the impact of FTZ on Mekk2 appears to function through a pathway separate from the traditional Wnt signaling route. Furthermore, our findings indicate that FTZ also promotes the deubiquitination of ß-catenin, contributing further to its positive effects on bone health. CONCLUSIONS: This study suggests that FTZ plays a significant role in protecting bone mass in cases of GIOP. The mechanism through which FTZ confers this benefit involves the activation of Mekk2/ß-catenin signaling pathways, which represents a promising alternative strategy to counteract the deleterious effects of GIOP by augmenting osteoblastogenesis.

In Situ Prelithiation by Direct Integration of Lithium Mesh into Battery Cells.

Silicon (Si)-based anodes are promising for next-generation lithium (Li)-ion batteries due to their high theoretical capacity (∼3600 mAh/g). However, they suffer quantities of capacity loss in the first cycle from initial solid electrolyte interphase (SEI) formation. Here, we present an in situ prelithiation method to directly integrate a Li metal mesh into the cell assembly. A series of Li meshes are designed as prelithiation reagents, which are applied to the Si anode in battery fabrication and spontaneously prelithiate Si with electrolyte addition. Various porosities of Li meshes tune prelithiation amounts to control the degree of prelithiation precisely. Besides, the patterned mesh design enhances the uniformity of prelithiation. With an optimized prelithiation amount, the in situ prelithiated Si-based full cell shows a constant >30% capacity improvement in 150 cycles. This work presents a facile prelithiation approach to improve battery performance.

A Class of Activatable NIR-II Photoacoustic Dyes for High-Contrast Bioimaging.

Photoacoustic (PA) imaging is emerging as one of the important non-invasive imaging techniques in biomedical research. Small molecule- second near-infrared window (NIR-II) PA dyes combined with imaging data can provide comprehensive and in-depth in vivo physiological and pathological information. However, the NIR-II PA dyes usually exhibit "always-on" properties due to the lack of a readily optically tunable group, which hinders the further applications in vivo. Herein, a novel class of dyes GX have been designed and synthesized as an activatable NIR-II PA platform, in which the absorption/emission wavelength of GX-5 extends up to 1082/1360 nm. Importantly, the GX dyes have a strong tissue penetration depth and high-resolution for the mouse vasculature structures in NIR-II PA 3D imaging and high signal-to-noise ratio in NIR-II fluorescence (FL) imaging. Furthermore, to demonstrate the applicability of GX dyes, the first NIR-II PA probe GX-5-CO activated by carbon monoxide (CO) was engineered and employed to reveal the enhancement of the CO levels in the hypertensive mice by high-contrast NIR-II PA and FL imaging. We expect that many derivatives of GX dyes will be developed to afford versatile NIR-II PA platforms for designing a wide variety activatable NIR-II PA probes as biomedical tools.

MoS2 Hollow Multishelled Nanospheres Doped Fe Single Atoms Capable of Fast Phase Transformation for Fast-charging Na-ion Batteries.

Low Na+ and electron diffusion kinetics severely restrain the rate capability of MoS2 as anode for sodium-ion batteries (SIBs). Slow phase transitions between 2H and 1T, and from NaxMoS2 to Mo and Na2S as well as the volume change during cycling, induce a poor cycling stability. Herein, an original Fe single atom doped MoS2 hollow multishelled structure (HoMS) is designed for the first time to address the above challenges. The Fe single atom in MoS2 promotes the electron transfer, companying with shortened charge diffusion path from unique HoMS, thereby achieving excellent rate capability. The strong adsorption with Na+ and self-catalysis of Fe single atom facilitates the reversible conversion between 2H and 1T, and from NaxMoS2 to Mo and Na2S. Moreover, the buffering effect of HoMS on volume change during cycling improves the cyclic stability. Consequently, the Fe single atom doped MoS2 quadruple-shelled sphere exhibits a high specific capacity of 213.3 mAh g-1 at an ultrahigh current density of 30 A g-1, which is superior to previously-reported results. Even at 5 A g-1, 259.4 mAh g-1 (83.68 %) was reserved after 500 cycles. Such elaborate catalytic site decorated HoMS is also promising to realize other "fast-charging" high-energy-density rechargeable batteries.

A Universal Formation Mechanism of Hollow Multi-Shelled Structures Dominated by Concentration Waves.

Hollow multi-shelled structures (HoMS), a new family of hierarchical nano/micro-structured materials, have evoked intensive studies to discover their unique temporal-spatial ordering features. The theoretical understanding of the general synthetic methods of HoMS, i.e. the sequential templating approach (STA), makes it possible to understand, predict, and control the shell formation process. Herein, a mathematical model is established based on the experiment results, which reveal the appearance of concentration waves in the STA. The numerical simulation results not only correspond well to the experimental observations but also explain the regulation methods. Whereby, the underlying physical essence of STA is elucidated, suggesting that HoMS is the concrete representation of the concentration waves. Thereafter the formation of HoMS is not limited to the solid-gas reactions through high-temperature calcination, but could be extended to solution systems under low-temperature conditions.

Hollow Multishelled Structured SrTiO3 with La/Rh Co-Doping for Enhanced Photocatalytic Water Splitting under Visible Light.

La- and Rh-co-doped SrTiO3 (STO:La/Rh) hollow multishelled structures (HoMSs) are fabricated by adding La3+ and Rh3+ ions during the hydrothermal process of converting TiO2 HoMSs to STO HoMSs. STO:La/Rh HoMSs have successfully expanded the light absorption edge to 520 nm. Accompanied with the benefits of the unique hierarchical structure and relatively thin shells, STO:La/Rh HoMSs exhibit elevated light-harvesting capacity and charge separation efficiency. Compared with STO:La/Rh nanoparticles (NPs), STO:La/Rh HoMSs demonstrate enhanced photocurrent response, photocatalytic hydrogen evolution activity, and the quantum efficiency. Moreover, overall water splitting is realized by a Z-scheme system combining STO:La/Rh HoMSs with BiVO4 (BVO) nanosheets with 1 wt% Pt as the co-catalyst. Steady evolution of hydrogen and oxygen is performed under both visible light and simulated sunlight irradiation. The solar-to-hydrogen efficiency of double-shelled STO:La/Rh HoMS-BVO photocatalysts reaches 0.08%, which is twofold higher than STO:La/Rh NP-BVO photocatalysts.

The effect of Cu dopants on electron transfer to O2 and the connection with acetone photocatalytic oxidations over nano-TiO2.

Modifying TiO2 with the Cu element has been shown to be useful for photocatalysis. Although it had been known that Cu species could trap electrons from TiO2, whether they can affect the kinetics of electron transfer and how this can contribute to photocatalysis still remain unknown. In the current research, Cu-TiO2 samples were firstly prepared with a hydrothermal reaction and characterized in detail. It was shown that Cu elements were doped in the TiO2 lattice in +1/0 valence states and have a minor effect on the TiO2 structure. By means of photoconductances, it is shown that the Cu dopants could catalyze the electron transfer from TiO2 to O2 by reducing the apparent activation energy (Eapp) by about 2 times. The photocatalytic experiments conducted at different temperatures showed that the Eapp of the acetone photocatalytic oxidations could be decreased by ∼2 times; this implies that the Cu dopants change the photocatalytic pathway. First-principles computation showed that the surface Cu dopants, along with the compensated oxygen vacancies, can mediate both of the electron and hole transfer. By combining other studies, we proposed that the Cu sites could act as Lewis acid and base pairs that could combine with acetone and O2 molecules under UV light illumination; this allows electron transfer to O2via the Cu sites that then react with acetone. As compared to pure TiO2 surfaces, the different chemical environment of the Cu sites leads to the decrease in the Eapp of photocatalysis.

Electrolyte-Phobic Surface for the Next-Generation Nanostructured Battery Electrodes.

Nanostructured electrodes are among the most important candidates for high-capacity battery chemistry. However, the high surface area they possess causes serious issues. First, it would decrease the Coulombic efficiencies. Second, they have significant intakes of liquid electrolytes, which reduce the energy density and increase the battery cost. Third, solid-electrolyte interphase growth is accelerated, affecting the cycling stability. Therefore, the interphase chemistry regarding electrolyte contact is crucial, which was rarely studied. Here, we present a completely new strategy of limiting effective surface area by introducing an "electrolyte-phobic surface". Using this method, the electrolyte intake was limited. The initial Coulombic efficiencies were increased up to ∼88%, compared to ∼60% of the control. The electrolyte-phobic layer of Si particles is also compatible with the binder, stabilizing the electrode for long-term cycling. This study advances the understanding of interphase chemistry, and the introduction of the universal concept of electrolyte-phobicity benefits the next-generation battery designs.

Incorporating the Nanoscale Encapsulation Concept from Liquid Electrolytes into Solid-State Lithium-Sulfur Batteries.

Solid-state Li-S batteries are attractive due to their high energy density and safety. However, it is unclear whether the concepts from liquid electrolytes are applicable in the solid state to improve battery performance. Here, we demonstrate that the nanoscale encapsulation concept based on Li2S@TiS2 core-shell particles, originally developed in liquid electrolytes, is effective in solid polymer electrolytes. Using in situ optical cell and sulfur K-edge X-ray absorption, we find that polysulfides form and are well-trapped inside individual particles by the nanoscale TiS2 encapsulation. This TiS2 encapsulation layer also functions to catalyze the oxidation reaction of Li2S to sulfur, even in solid-state electrolytes, proven by both experiments and density functional theory calculations. A high cell-level specific energy of 427 W·h·kg-1 is achieved by integrating the Li2S@TiS2 cathode with a poly(ethylene oxide)-based electrolyte and a lithium metal anode. This study points to the fruitful direction of borrowing concepts from liquid electrolytes into solid-state batteries.

General Synthesis of Multiple-Cores@Multiple-Shells Hollow Composites and Their Application to Lithium-Ion Batteries.

Rational nanostructure design has proved fruitful in addressing the bottlenecks of diverse fields. Especially hollow multi-shelled structures (HoMS) have stood out due to their temporal-spatial ordering mass transfer and buffering effect. Localizing multiple cores in a HoMS is highly desired, which could endow it with more fascinating properties. However, such a structure has been barely reported due to the highly challenging fabrication. Here, we develop a controllable synthesis strategy to realize such a structure, which is applicable for diverse cores and shells. Additionally, cores and shells could be tuned to be homogeneous or heterogeneous, with the core and shell number well controlled. In situ TEM analysis verifies that the inner shell confines the expansion orientation of cores, while the outer shell maintains a stable interface. In addition to energy storage, such structure is also promising for multi-drug co-delivery and sequential responsive release as well as tandem catalysis applications.

Hollow Multishelled Structures for Promising Applications: Understanding the Structure-Performance Correlation.

The unique structural features of hollow multishelled structures (HoMSs) endow them with abundant beneficial physicochemical properties including high surface-to-volume ratio, low density, short mass transport length, and high loading capacity. As a result, HoMSs have been considered as promising candidates for various application areas including energy storage, electromagnetic wave (EW) absorption, catalysis, sensors, drug delivery, etc. However, for a long time, the general and controllable synthesis of HoMSs has remained a great challenge using conventional soft-templating or hierarchical self-assembly methods, which severely limits the development of HoMSs. Fortunately, the sequential templating approach (STA), which was first reported by our group and further developed by others, has been proven to be a versatile method for HoMS fabrication. By using the STA and through accurate physical and chemical manipulation of the synthesis conditions, the diversity of the HoMS family has been enriched in both compositional and geometrical aspects. Benefiting from the flourishing of synthetic methodology, various HoMSs have been fabricated and showed application prospect in diverse areas. However, the structure-performance correlation remained obscure, which hinders the design of optimal HoMSs to achieve the best application performance. This Account aims to explore the correlation between HoMS structural characteristics and their application performance. We first briefly summarize the achievements in the compositional and geometrical manipulation of HoMSs by physically and chemically tuning the synthesis process. Then, we systematically discuss the effect of structural engineering on optimizing performance in various application areas, especially for energy storage, EW absorption, catalysis, sensors, and drug delivery. Specifically, HoMSs with multiple thin shells can provide numerous active sites for energy storage, leading to a higher volumetric energy density than their single-shelled counterparts. The high shell porosity permits electrolyte access to the interior of HoMSs, along with shortened mass transport path through the thin shells, resulting in a high power density. The adequate inner cavity effectively buffers the ion-insertion strain, leading to prolonged cycling stability. For EW absorption, HoMSs with high surface-to-volume ratio can provide many sites for EW-sensitive material loading. The multiple separated shells with small intershell space enable multiple EW reflection and scattering, thus improving EW absorption efficiency. For catalysis and sensors, the increased reaction sites along with the facilitated transport of reactants and products can enhance the activity and sensitivity. The selectivity can be improved by optimizing the pore structure and hydrophobic or hydrophilic properties of the shells. Also the stability is improved with inner shells being protected by exterior ones. For drug delivery, the increased exposed sites and the inner cavity improve the drug loading capacity. The adjustable pore structure along with accurately designed shell composition leads to well-targeted drug release responding to different stimuli at different targeting sites. The multiple separated shells endow HoMSs with sustained drug release step-by-step from inside to outside. These in-depth understandings on the structure-performance correlation can guide the design of ideal HoMSs to satisfy the specific requirements for different application areas, thus further improving the application performance and expanding the HoMSs family.

Dual-Defects Adjusted Crystal-Field Splitting of LaCo1-x Nix O3-δ Hollow Multishelled Structures for Efficient Oxygen Evolution.

To boost the performance for various applications, a rational bottom-up design on materials is necessary. The defect engineering on nanoparticle at the atomic level can efficiently tune the electronic behavior, which offers great opportunities in enhancing the catalytic performance. In this paper, we optimized the surface oxygen vacancy concentration and created the lattice distortion in rare-earth-based perovskite oxide through gradient replacement of the B site with valence alternated element. The dual defects make the electron spin state transit from low spin state to high spin state, thus decreasing the charge transport resistance. Furthermore, assembly the modified nanoparticle subunits into the micro-sized hollow multishelled structures can provide porous shells, abundant interior space and effective contact, which enables an enhanced mass transfer and a shorter charge transport path. As a result, the systemic design in the electronic and nano-micro structures for catalyst has brought an excellent oxygen evolution performance.

Shell-Protective Secondary Silicon Nanostructures as Pressure-Resistant High-Volumetric-Capacity Anodes for Lithium-Ion Batteries.

The nanostructure design of a prereserved hollow space to accommodate 300% volume change of silicon anodes has created exciting promises for high-energy batteries. However, challenges with weak mechanical stability during the calendering process of electrode fabrication and poor volumetric energy density remain to be solved. Here we fabricated a pressure-resistant silicon structure by designing a dense silicon shell coating on secondary micrometer particles, each consisting of many silicon nanoparticles. The silicon skin layer significantly improves mechanical stability, while the inner porous structure efficiently accommodates the volume expansion. Such a structure can resist a high pressure of over 100 MPa and is well-maintained after the calendering process, demonstrating a high volumetric capacity of 2041 mAh cm-3. In addition, the dense silicon shell decreases the surface area and thus increases the initial Coulombic efficiency. With further encapsulation with a graphene cage, which allows the silicon core to expand within the cage while retaining electrical contact, the silicon hollow structure exhibits a high initial Coulombic efficiency and fast rise of later Coulombic efficiencies to >99.5% and superior stability in a full-cell battery.

Constructing SrTiO3 -TiO2 Heterogeneous Hollow Multi-shelled Structures for Enhanced Solar Water Splitting.

Constructing hollow multi-shelled structures (HoMSs) has a significant effect on promoting light absorption property of catalysts and enhancing their performance in solar energy conversion applications. A facile hydrothermal method is used to design the SrTiO3 -TiO2 heterogeneous HoMSs by hydrothermal crystallization of SrTiO3 on the surface of the TiO2 HoMSs, which will realize a full coverage of SrTiO3 on the TiO2 surface and construct the SrTiO3 /TiO2 junctions. The broccoli-like SrTiO3 -TiO2 heterogeneous HoMSs exhibited a fourfold higher overall water splitting performance of 10.6 µmol h-1 for H2 production and 5.1 µmol h-1 for O2 evolution than that of SrTiO3 nanoparticles and the apparent quantum efficiency (AQE) of 8.6 % at 365 nm, which can be mainly attributed to 1) HoMS increased the light absorption ability of the constructed photocatalysts and 2) the SrTiO3 -TiO2 junctions boosted the separation efficiency of the photogenerated charge carriers.

Temperature-Dependent Nucleation and Growth of Dendrite-Free Lithium Metal Anodes.

It is essential to develop a facile and effective method to enhance the electrochemical performance of lithium metal anodes for building high-energy-density Li-metal based batteries. Herein, we explored the temperature-dependent Li nucleation and growth behavior and constructed a dendrite-free Li metal anode by elevating temperature from room temperature (20 °C) to 60 °C. A series of ex situ and in situ microscopy investigations demonstrate that increasing Li deposition temperature results in large nuclei size, low nucleation density, and compact growth of Li metal. We reveal that the enhanced lithiophilicity and the increased Li-ion diffusion coefficient in aprotic electrolytes at high temperature are essential factors contributing to the dendrite-free Li growth behavior. As anodes in both half cells and full cells, the compact deposited Li with minimized specific surface area delivered high Coulombic efficiencies and long cycling stability at 60 °C.

Hollow Multi-Shelled Structural TiO2-x with Multiple Spatial Confinement for Long-Life Lithium-Sulfur Batteries.

TiO2-x with well-controlled hollow multi-shelled structures (HoMSs) were designed and synthesized, via a sequential templating approach (STA), to act as sulfur carrier materials. They were explored as physico-chemical encapsulation materials. Particularly, the sulfur cathode based on triple-shelled TiO2-x HoMSs delivered a specific capacity of 903 mAh g-1 with a capacity retention of 79 % at 0.5 C and a Coulombic efficiency of 97.5 % over 1000 cycles. The outstanding electrochemical performance is attributed to better spatial confinement and integrated conductivity of the intact triple-shell that combine the features of physico-chemical adsorption, short charge transfer path along with mechanical strength.

Hollow Multi-Shelled Structure with Metal-Organic-Framework-Derived Coatings for Enhanced Lithium Storage.

Herein, we present heterogeneous hollow multi-shelled structures (HoMSs) prepared by exploiting the properties of the metal-organic framework (MOFs) casing. Through accurately controlling the transformation of MOF layer into different heterogeneous casings, we can precisely design HoMSs of SnO2 @Fe2 O3 (MOF) and SnO2 @FeOx -C(MOF), which not only retain properties of the original SnO2 -HoMSs, but also structural information from the MOFs. Tested as anode materials in LIBs, SnO2 @Fe2 O3 (MOF)-HoMSs demonstrate superior lithium-storage capacity and cycling stability to the original SnO2 -HoMSs, which can be attributed to the topological features from the MOF casing. Making a sharp contrast to the electrodes of SnO2 @Fe2 O3 (particle)-HoMSs fabricated by hydrothermal method, the capacity retention after 100 cycles for the SnO2 @Fe2 O3 (MOF)-HoMSs is about eight times higher than that of the SnO2 @Fe2 O3 (particle)-HoMS.

Construction of Multishelled Binary Metal Oxides via Coabsorption of Positive and Negative Ions as a Superior Cathode for Sodium-Ion Batteries.

Multishelled binary metal oxide, which can exert a synergetic effect of different oxides, is a promising electrochemical electrode material. However, it is challenging to synthesize this kind of binary metal oxide due to the severe hydrolysis and/or precipitation reactions of the precursors between cations and anions of different metals. Herein, by using citric acid as a chelating agent to inhibit hydrolysis and precipitation, a series of multishelled binary metal oxide hollow spheres (Fe2(MoO4)3, NiMoO4, MnMoO4, CoWO4, MnWO4, etc.) were obtained via coabsorption of negative and positive metal ions. In addition, the chelation between a metal ion and citric acid is systematically validated by NMR, MS, Raman, and UV-vis. In particular, multishelled Fe2(MoO4)3 hollow spheres show excellent electrochemical performance as cathode material for sodium-ion batteries benefited from their structural superiorities. Especially, the quintuple-shelled Fe2(MoO4)3 hollow sphere shows the highest specific capacity (99.03 mAh g-1) among all Fe2(MoO4)3 hollow spheres, excellent stability (85.6 mAh g-1 was retained after 100 cycles at a current density of 2.2 C), and outstanding rate capability (67.4 mAh g-1 can be obtained at a current density of 10 C). This general approach can be extended to the synthesis of other multishelled multielement metal oxides and greatly enrich the diversity of hollow multishelled structures.

Electrocatalytic N-Doped Graphitic Nanofiber - Metal/Metal Oxide Nanoparticle Composites.

Carbon-based nanocomposites have shown promising results in replacing commercial Pt/C as high-performance, low cost, nonprecious metal-based oxygen reduction reaction (ORR) catalysts. Developing unique nanostructures of active components (e.g., metal oxides) and carbon materials is essential for their application in next generation electrode materials for fuel cells and metal-air batteries. Herein, a general approach for the production of 1D porous nitrogen-doped graphitic carbon fibers embedded with active ORR components, (M/MOx , i.e., metal or metal oxide nanoparticles) using a facile two-step electrospinning and annealing process is reported. Metal nanoparticles/nanoclusters nucleate within the polymer nanofibers and subsequently catalyze graphitization of the surrounding polymer matrix and following oxidation, create an interconnected graphite-metal oxide framework with large pore channels, considerable active sites, and high specific surface area. The metal/metal oxide@N-doped graphitic carbon fibers, especially Co3 O4 , exhibit comparable ORR catalytic activity but superior stability and methanol tolerance versus Pt in alkaline solutions, which can be ascribed to the synergistic chemical coupling effects between Co3 O4 and robust 1D porous structures composed of interconnected N-doped graphitic nanocarbon rings. This finding provides a novel insight into the design of functional electrocatalysts using electrospun carbon nanomaterials for their application in energy storage and conversion fields.

Thermal Management in Nanofiber-Based Face Mask.

Face masks are widely used to filter airborne pollutants, especially when particulate matter (PM) pollution has become a serious concern to public health. Here, the concept of thermal management is introduced into face masks for the first time to enhance the thermal comfort of the user. A system of nanofiber on nanoporous polyethylene (fiber/nanoPE) is developed where the nanofibers with strong PM adhesion ensure high PM capture efficiency (99.6% for PM2.5) with low pressure drop and the nanoPE substrate with high-infrared (IR) transparency (92.1%, weighted based on human body radiation) results in effective radiative cooling. We further demonstrate that by coating nanoPE with a layer of Ag, the fiber/Ag/nanoPE mask shows a high IR reflectance (87.0%) and can be used for warming purposes. These multifunctional face mask designs can be explored for both outdoor and indoor applications to protect people from PM pollutants and simultaneously achieve personal thermal comfort.