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Once bone metastasis occurs in lung cancer, the efficiency of treatment can be greatly reduced. Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction. Microwave ablation (MWA) has been used to treat bone tumors. However, MWA may damage the surrounding normal tissues. Therefore, it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis. Herein, a microwave-responsive nanoplatform (MgFe2O4@ZOL) was constructed. MgFe2O4@ZOL NPs release the cargos of Fe3+, Mg2+and zoledronic acid (ZOL) in the acidic tumor microenvironment (TME). Fe3+can deplete intracellular glutathione (GSH) and catalyze H2O2to generate •OH, resulting in chemodynamic therapy (CDT). In addition, the microwave can significantly enhance the production of reactive oxygen species (ROS), thereby enabling the effective implementation of microwave dynamic therapy (MDT). Moreover, Mg2+and ZOL promote osteoblast differentiation. In addition, MgFe2O4@ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy (MTT). Both in vitro and in vivo experiments revealed that synergistic targeting, GSH depletion-enhanced CDT, MDT, and selective MTT exhibited significant antitumor efficacy and bone repair. This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.

Byline: Tao. Yang, Jin. Ke, Shi. Cheng, Yue. He, Wenhan. Huang, Mengyu. Yao, Jielong. Zhou, Guoqing. Zhong, Yongcheng. Hu, Yu. Zhang Spinal metastases are the most common source of morbidity [...]

Oxygen redox cathodes, such as Li1.2Ni0.13Co0.13Mn0.54O2, deliver higher energy densities than those based on transition metal redox alone. However, they commonly exhibit voltage fade, a gradually diminishing discharge voltage on extended cycling. Recent research has shown that, on the first charge, oxidation of O2−ions forms O2molecules trapped in nano-sized voids within the structure, which can be fully reduced to O2−on the subsequent discharge. Here we show that the loss of O-redox capacity on cycling and therefore voltage fade arises from a combination of a reduction in the reversibility of the O2−/O2redox process and O2loss. The closed voids that trap O2grow on cycling, rendering more of the trapped O2electrochemically inactive. The size and density of voids leads to cracking of the particles and open voids at the surfaces, releasing O2. Our findings implicate the thermodynamic driving force to form O2as the root cause of transition metal migration, void formation and consequently voltage fade in Li-rich cathodes.

Montmorillonite (Mt) is a ubiquitous swelling clay mineral and major component of soft rocks, sediments, and soils with an inherent capability to sorb metal cations. This unique feature renders Mt important for the enrichment and mobilization of environmentally important metal cations, retardation of heavy metals and radionuclide ions, the evolution of clay mineral itself, soils and sediments, and other geological processes. Understanding the interfacial interactions of Mt with metal cations at the molecular level is of fundamental importance in all these processes, but still remains elusive, due to the chemical and structural complexity of Mt surfaces and the diverse chemistries of metal cations. In this Review, we aim to provide the reader with a comprehensive overview of the adsorption modes of metal cations on basal and edge surfaces of Mt, local chemical environments of the cation binding sites, the driving forces for metal sorption, and factors influencing the dynamics of cation uptake onto Mt surfaces. Various surface complexation models [i.e., nonelectrostatic model (NEM), constant capacitance model (CCM), diffuse layer model (DLM), and triple-layer model (TLM)], advanced spectroscopic techniques (i.e., NEM, CCM, DLM, and TLM), and atomistic simulation methods (i.e., MD, DFT, and FPMD) have been used in conjunction with macroscopic adsorption experiments to gain detailed insights into the interfacial interactions of metal cations on Mt. Mt adsorbs metal cations via three independent pathways: (1) cation exchange; (2) surface complexation; and (3) nucleation and surface precipitation. The principal driving force for cation exchange is electrostatic interaction, while chemical bonding governs the two other mechanisms that depend on the basal and edge surface properties of Mt. The siloxane cavities on the tetrahedral basal plane exhibit the strongest adsorption sites for cation exchange and are greatly affected by the the degree of Al3+/Si4+tetrahedral substitutions. At the amphoteric edge surfaces bearing hydroxyl groups, metal cations could form mono/multidentate surface complexes on Mt [010] and [110] edges. Ionic strength, pH, the presence of competing cations, temperature, and layer charge have been shown to affect the adsorption mechanisms and quantity of adsorbed cations. The updated information on the interfacial interactions of metal cations with Mt basal and edge surfaces presented in this review provides an improved understanding of the enrichment of metals, formation of metal ores, and natural biogeochemical cycles, as well as may promote technological and engineering applications of this important clay mineral in environmental remediation, geological repository, petroleum exploration and extraction, and extraterrestrial research.

This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 μL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro–computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of chalcone analogues were designed and synthesized. In vitroanti-inflammatory activity of these compounds was evaluated by screening their inhibitory effects on NO production in RAW264.7 cell lines. The most promising compounds 3hand 3lwere selected for further investigation by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, and IL-6 and PGE2 release. The further study also indicated that 3hand 3lcould significantly suppress the expression of iNOS and COX-2 through the NF-κB/JNK signaling pathway. Furthermore, compounds 3hand 3lcould also remarkably inhibit the mRNA expression of inflammation-related genes. Meanwhile, 3hcould also down-regulate ROS production. Docking simulation was conducted to position compounds 3hand 3linto the iNOS binding site to predict the probable binding mode. In conclusion, this series of chalcone analogues with reasonable drug-likeness obtained via in silicorapid prediction can be used as promising lead candidates.

The present study aims to plumb blockage of the deep-sea mining pump transporting large particles with different shapes. A numerical work was performed through combining the computational fluid dynamics (CFD) technique and the discrete element method (DEM). Six particle shapes with sphericity ranging from 0.67 to 1.0 were selected. A velocity triangle is built with the absolute, relative, and circumferential velocities of particles. Velocity triangles with absolute velocity angles ranging from 90° to 180° prevail in the first-stage impeller. With declining sphericity, more particles follow the velocity triangle with absolute velocity angles ranging from 0° to 90°, which weakens the ability of particles to pass through the flow passage. Furthermore, the forces acting on the particles traveling in the impeller passage are analyzed. Large particles, especially non-spherical ones, suffer from high centrifugal force and therefore move along the suction surface of the impeller blades. Non-spherical particles undergo great drag force as a result of large surface area. The distribution of drag force angles is featured by two peaks, and one vanishes due to blockage. As particle sphericity declines, both magnitude and angle of the pressure gradient force decrease. Variation of the drag force and the pressure gradient force causes clockwise deflection of the centripetal force, resulting in deflection and elongation of particle trajectory, which increases the possibility of blockage.

The newly discovered nickelate superconductors so far only exist in epitaxial thin films synthesized by a topotactic reaction with metal hydrides1. This method changes the nickelates from the perovskite to an infinite-layer structure by deintercalation of apical oxygens1–3. Such a chemical reaction may introduce hydrogen (H), influencing the physical properties of the end materials4–9. Unfortunately, H is insensitive to most characterization techniques and is difficult to detect because of its light weight. Here, in optimally Sr doped Nd0.8Sr0.2NiO2H epitaxial films, secondary-ion mass spectroscopy shows abundant H existing in the form of Nd0.8Sr0.2NiO2Hx(x≅ 0.2–0.5). Zero resistivity is found within a very narrow H-doping window of 0.22 ≤ x≤ 0.28, showing unequivocally the critical role of H in superconductivity. Resonant inelastic X-ray scattering demonstrates the existence of itinerant interstitial s(IIS) orbitals originating from apical oxygen deintercalation. Density functional theory calculations show that electronegative H–occupies the apical oxygen sites annihilating IIS orbitals, reducing the IIS–Ni 3dorbital hybridization. This leads the electronic structure of H-doped Nd0.8Sr0.2NiO2Hxto be more two-dimensional-like, which might be relevant for the observed superconductivity. We highlight that H is an important ingredient for superconductivity in epitaxial infinite-layer nickelates.

This study aimed to introduce the clinical application of the CAD/CAM-guided modified Dautrey’s procedure in recurrent anterior temporomandibular joint luxation and evaluate its clinical effects. Four selected patients were treated by the CAD/CAM-guided modified Dautrey’s procedure and were followed-up to access their curative effect. Joint pain and sound, recurrence rate, mandibular function, maximum mouth opening (MMO), symptoms of facial nerve injury, and changes in zygomatic facial appearance were observed in postoperative follow-up. The followed-up period ranged from 3 months to 1 year with an average time of 7.5 months. There was no recurrence in all 4 patients, and no symptoms of facial nerve injury and zygomaticofacial appearance changes were found. All patients showed improvement in MMO, with a mean preoperative and postoperative MMO of 4.74 and 3.74 cm, respectively. All of them showed relief of joint pain or sound 3 months or more after the operation and could exercise mandibular normally. This results showed that the CAD/CAM-guided modified Dautrey’s procedure was effective in the treatment of recurrent temporomandibular joint luxation and could be used as a good alternative treatment for it.

The concept of chirality is of great relevance in nature, from chiral molecules such as sugar to parity transformations in particle physics. In condensed matter physics, recent studies have demonstrated chiral fermions and their relevance in emergent phenomena closely related to topology1–3. The experimental verification of chiral phonons (bosons) remains challenging, however, despite their expected strong impact on fundamental physical properties4–6. Here we show experimental proof of chiral phonons using resonant inelastic X-ray scattering with circularly polarized X-rays. Using the prototypical chiral material quartz, we demonstrate that circularly polarized X-rays, which are intrinsically chiral, couple to chiral phonons at specific positions in reciprocal space, allowing us to determine the chiral dispersion of the lattice modes. Our experimental proof of chiral phonons demonstrates a new degree of freedom in condensed matter that is both of fundamental importance and opens the door to exploration of new emergent phenomena based on chiral bosons.

The nanostructure of Ag nanoparticles (NPs) plays a critical role in their surface-enhanced Raman scattering (SERS) activity. Despite many efforts to tune the nanostructure of Ag NPs, it remains a great challenge as Ag NPs tend to agglomerate and their nanostructure is difficult to control. Herein, newly-discovered clay-surfactant-Ag+materials and interfacial processes were developed and used to prepare uniform spherical Ag@synthetic hectorite (Ag@Hct) nanomaterials for ultrasensitive SERS assay. Sodium dodecyl sulfate (SDS), an anionic surfactant, acted as a bridge to conjugate the positively charged edge of Hct NPs and Ag+viaelectrostatic interaction to form the bridging nanostructure of Hct-SDS-Ag+, which promoted the uniform dispersion of Hct NPs. Following this, Ag+was reduced to Ag0by the reductant, and Ag0grew on the surface of disc-like Hct NPs to form spherical Ag@Hct nanomaterials with an average particle size of ∼24 nm. The prepared Ag@Hct nanomaterials showed an ultrasensitive SERS response to methylene blue (MB) with a detection limit of 10−12M. The detection limit of MB in sewage was 10−11M. The prepared Ag@Hct nanomaterials also exhibited great SERS enhancement for malachite green and crystal violet. This work provides a novel and simple approach to prepare Ag@Hct nanomaterials with uniform spheres and adjustable particle size, allowing more sensitive and reproducible detection of MB.

A defining signature of strongly correlated electronic systems is a rich phase diagram, which consists of multiple broken symmetries, such as magnetism, superconductivity and charge order1,2. In the recently discovered nickelate superconductors3–10, a large antiferromagnetic exchange energy has been reported, which implies the existence of strong electronic correlations11. However, signatures of a broken-symmetry state other than superconductivity have not yet been observed. Here we observe charge ordering in infinite-layer nickelates La1−xSrxNiO2using resonant X-ray scattering. The parent compound orders along the Ni–O bond direction with an incommensurate wavevector, distinct from the stripe order observed in other nickelates12–14that propagates along a direction 45° to the Ni–O bond. The resonance profile we measure indicates that ordering originates from the nickelate layers and induces a parasitic charge modulation of lanthanum electrons. Upon doping, the charge order diminishes and its wavevector shifts towards commensurate, hinting that strong electronic correlations are likely to be responsible for the ordered state. Our results suggest that the existence of charge order and its potential interplay with antiferromagnetic fluctuations and superconductivity are important themes in nickel-based superconductors.

ABSTRACTTo study the mechanism of gynostemma pentaphyllumsaponins (GpS) regulating mitochondrial autophagy and anti-inflammatory through Sirtuin 1 (Sirt1) pathway in systemic lupus erythematosus (SLE). JURKAT cells were cultured in vitro, RT-PCR and western blotting (WB) were utilized to identify the expression of related-proteins in Sirt1 pathway and global autophagy and mitochondrial autophagy markers in JURKAT before and after GpS treatment induced by ultraviolet B (UVB), and the related-mechanism of GpS regulation of autophagy was analyzed. The SLE model was established to analyze the alleviating effects of GpS on various symptoms of lupus mice. Sirt1/AMPK/mTOR pathway was activated in UVB induced JURKAT cells. After the addition of GpS, WB revealed that the phosphorylation of AMPK decreased, the phosphorylation of mTOR increased, the expression of Sirt1 protein decreased, and the activation of the pathway was inhibited. Moreover, autophagy of JURKAT cells wasinhibited. In order to further verify the role of Sirt1 pathway, we activated Sirt1 expression in cells by constructing lentiviral vectors, and the therapeutic effect of GpS was significantly reduced. These results indicate GpS can exert autophagy regulation by inhibiting the activity of Sirt1 pathway. To treat SLE. GpS can significantly reduce the level of autoantibodies, kidney inflammation, immune complex deposition and urinary protein excretion, improve kidney function in lupus-prone mice. GpS can regulate autophagy and mitochondrial autophagy through Sirt1 pathway, which may be a potential mechanism for GpS to reduce the level of autoantibodies, kidney inflammation, immune complex deposition and urinary protein excretion, improve kidney function in lupus-prone mice.

In materials science, much effort has been devoted to the reproduction of superconductivity in chemical compositions, analogous to cuprate superconductors since their discovery over 30 years ago. This approach was recently successful in realising superconductivity in infinite-layer nickelates1–6. Although differing from cuprates in electronic and magnetic properties, strong Coulomb interactions suggest that infinite-layer nickelates have a propensity towards various symmetry-breaking orders that populate cuprates7–10. Here we report the observation of charge density waves (CDWs) in infinite-layer NdNiO2films using Ni L3resonant X-ray scattering. Remarkably, CDWs form in Nd 5dand Ni 3dorbitals at the same commensurate wavevector (0.333, 0) reciprocal lattice units, with non-negligible out-of-plane dependence and an in-plane correlation length of up to ~60 Å. Spectroscopic studies reveal a strong connection between CDWs and Nd 5d–Ni 3dorbital hybridization. Upon entering the superconducting state at 20% Sr doping, the CDWs disappear. Our work demonstrates the existence of CDWs in infinite-layer nickelates with a multiorbital character distinct from cuprates, which establishes their low-energy physics.

ABSTRACTDrought is one of the most important abiotic stressors that affect crop yield. Therefore, the aim of the present study was to investigate correlations between germination-stage drought tolerance and the microscopic testa (i.e., seed coat) characteristics (color and papilla morphology) and imbibition abilities of 35 rapeseed (Brassica napusL.) accessions. After 2 h imbibition, seed water uptake (fresh weight increase) was significantly positively correlated with testa hue (HHSB), brightness (BHSB,), blue (BRGB), and lightness (L*), with correlation coefficients of 0.38, 0.34, 0.53, and 0.36, respectively, and significantly negatively correlated with saturation (SHSB), greenness-redness (a*), blueness-yellowness (b*), magenta (M), and yellow components (Y), with correlation coefficients of −0.53, −0.40, −0.53, −0.39, and −0.55, respectively. Furthermore, 5-h seed water uptake was significantly positively correlated with number of papillae (No.P), mean papillae area (APA), the papillae area ratio (PAR), gray value of red channel of papillae, with correlation coefficients of 33, 0.36, 0.43, and 0.43, respectively. Under drought conditions, genotypes with more rapid water absorption exhibited higher germination rates and stronger drought tolerance, and the germination rate and drought tolerance of black-seeded accessions were highest, followed by red-seeded accessions and then yellow-seeded accessions, which exhibited the lowest germination rate and drought tolerance. Germination rate was significantly negatively correlated with BRGB, HHSB, L*, Dg, and Dband significantly positively correlated with SHSBand Y, regardless of drought conditions. At the germination stage, DbTP was negatively correlated with drought tolerance.

In this paper, the consensus problem is considered for multi-agent systems with input constraint under directed graphs, including leaderless and leader-following cases. Different from existing related works, the distinct feature of this paper is that both the amplitude and rate of the agents' input are ensured in the given ranges. For the leaderless case, the saturation control strategy is designed and employed for multi-agent systems consensus with the aid of a novel saturation function. For the leader-following case, the saturation-function-based distributed observer as well as the observer-based saturation controller are proposed to achieve consensus. Finally, simulation results show the effectiveness of the designed methods. [ABSTRACT FROM AUTHOR]

Electrochemistry has been successfully applied in metal catalysis to avoid the usage of chemical redox agents. This strategy proved to be a powerful approach to construct carbon–carbon (C–C) and carbon–heteroatom (C–X) bonds. However, most of the developed methods are based on either anodic oxidation or cathodic reduction, in which a sacrificial reaction occurs at the counter electrode. Paired electrolysis merging with metal catalysis is underdeveloped, wherein both anodic and cathodic processes are taking place simultaneously. Herein, we demonstrated that by using esterification of carboxylic acids with aryl halides via paired electrolysis using nickel as the catalyst the respective aryl esters were obtained in good to excellent yields at room temperature in an undivided electrochemical cell.

Oral fast dissolving films (OFDFs) are popular dosage forms for enhanced oral absorption of active ingredients without experiencing gastrointestinal interference or first-pass metabolism. The primary challenge in OFDF design is balancing drug loading capacity with film properties, particularly for poorly soluble drugs. In the present work, an OFDF formulation containing co-amorphous mixture was successfully designed for co-administration of two natural products at a drug content of 14%. Breviscapine and matrine are commonly used for cardiovascular and cerebrovascular related diseases, but their clinical application was limited by low bioavailability, short biological half-life, and instability problems. Their co-administration as a compound remedy requires a novel product too enhance drug dissolution and patient compliance. A 33Box-Behnken design was used to generate OFDF preparations by solvent casting method. The optimized blank film formulation, comprising 57.40% HPMC E50, 14.01% PEG 400 and 5.35% L-HPC, demonstrated a rapid disintegration in 18 s. XRD and FTIR analysis on drug-loaded films revealed good compatibility of drugs and polymers, and amorphous state of films with co-precipitates. The films were evaluated for morphology, folding endurance, disintegration time and in vitroBRE dissolution. Drugs incorporation extended the disintegration time of blank films, yet remained under 30 s. The co-amorphous mixture of BRE and MAT in films exhibited a faster BRE dissolution rate compared to the physical mixture. In conclusion, a compound OFDF formulation featuring a co-amorphous mixture of BRE and MAT offers an efficient strategy for hydrophobic drug delivery at high dose.

• Sr was incorporated on 3D-printed porous Ta via dopamine self-polymerization. • Sr-loaded 3D-printed porous Ta showed enhanced angiogenic and osteogenic behavior in vitro. • Sr-loaded 3D-printed porous Ta showed improved osteointegration in vivo. Tantalum (Ta) is used in orthopedic implants because it has excellent biocompatibility. However, high elastic modulus, bio-inertness, and unsatisfactory osteointegration limits its wider use in clinical applications. Herein, a 3D porous Ta scaffold with low elastic modulus was fabricated using selective laser melting (SLM). Strontium (Sr) was incorporated on the surface of the scaffold with the aid of polydopamine (PDA) to further improve its osteointegration ability. The prepared scaffolds exhibited a stable Sr ion release in 14 d. Rat bone marrow stem cells (BMSCs) showed improved early adhesion and spreading after Sr was incorporated on the porous Ta surface. The osteogenic behavior, including extracellular matrix mineralization (ECM), alkaline phosphatase activity (ALP), and expression of bone-related RNA, were all enhanced. Furthermore, the Sr-incorporated porous Ta scaffolds exhibited better angiogenic behavior, such as promoting migration, tube formation, and angiogenesis-related RNA expression abilities of human vascular endothelial cells (HUVECs). Additionally, histological images (H&E, Masson and CD31 immunofluorescent staining) suggested that Sr-incorporated porous Ta scaffolds displayed enhanced osteointegration and angiogenesis after implantation in rat femur for 12 weeks. These findings prove that the PDA-based Sr-incorporated porous Ta scaffolds show promising use in orthopedic implants. [ABSTRACT FROM AUTHOR]

Copper oxide high-TCsuperconductors possess a number of exotic orders that coexist with or are proximal to superconductivity. Quantum fluctuations associated with these orders may account for the unusual characteristics of the normal state, and possibly affect the superconductivity1–4. Yet, spectroscopic evidence for such quantum fluctuations remains elusive. Here, we use resonant inelastic X-ray scattering to reveal spectroscopic evidence of fluctuations associated with a charge order5–14in nearly optimally doped Bi2Sr2CaCu2O8+d. In the superconducting state, while the quasielastic charge order signal decreases with temperature, the interplay between charge order fluctuations and bond-stretching phonons in the form of a Fano-like interference increases, an observation that is incompatible with expectations for competing orders. Invoking general principles, we argue that this behaviour reflects the properties of a dissipative system near an order–disorder quantum critical point, where the dissipation varies with the opening of the pseudogap and superconducting gap at low temperatures, leading to the proliferation of quantum critical fluctuations, which melt charge order.

In the search for high energy density cathodes for next-generation lithium-ion batteries, the disordered rocksalt oxyfluorides are receiving significant attention due to their high capacity and lower voltage hysteresis compared with ordered Li-rich layered compounds. However, a deep understanding of these phenomena and their redox chemistry remains incomplete. Using the archetypal oxyfluoride, Li2MnO2F, we show that the oxygen redox process in such materials involves the formation of molecular O2trapped in the bulk structure of the charged cathode, which is reduced on discharge. The molecular O2is trapped rigidly within vacancy clusters and exhibits minimal mobility unlike free gaseous O2, making it more characteristic of a solid-like environment. The Mn redox process occurs between octahedral Mn3+and Mn4+with no evidence of tetrahedral Mn5+or Mn7+. We furthermore derive the relationship between local coordination environment and redox potential; this gives rise to the observed overlap in Mn and O redox couples and reveals that the onset potential of oxide ion oxidation is determined by the degree of ionicity around oxygen, which extends models based on linear Li–O–Li configurations. This study advances our fundamental understanding of redox mechanisms in disordered rocksalt oxyfluorides, highlighting their promise as high capacity cathodes.

The SnO2/Li4Ti5O12/C compound was gained via hydrothermal, sintering, and ball milling methods. Nano-grained SnO2/Li4Ti5O12are homogeneously wrapped in a sheet-like graphite. Li4Ti5O12possesses cyclic stability and superior rate capacity. Meanwhile, the SnO2/Li4Ti5O12hybrid can supply abundant active sites for absorption of Li+, mitigate chemical stress in cycling, and prevent the ultrathin graphite nanosheets from stacking. Besides, the sheet-like graphite could reduce volume variation in cycling and reduce transmission distance for the electron or Li+. Therefore, an outstanding electrochemical property of the SnO2/Li4Ti5O12/C composite can be obtained.

IMPORTANCE: The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. OBJECTIVE: To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol. INTERVENTIONS: Participants were randomized to receive PCb (paclitaxel 80 mg/m2 and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, and fluorouracil 500 mg/m2 every 3 weeks for 3 cycles followed by docetaxel 100 mg/m2 every 3 weeks for 3 cycles). MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)–related genes, and toxicity. RESULTS: A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs. CONCLUSIONS AND RELEVANCE: These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01216111

A new ternary Mo–SnO2–graphite composite has been constructed via hydrothermal and ball milling. The Mo/SnO2hybrids were homogeneously dispersed in graphite nanosheets. In the Mo–SnO2–graphite, Mo can inhibit the Sn nanoparticle aggregation, enhance the reversible conversion reaction in lithiation, and improve the electrochemical performance. Consequently, the Mo–SnO2–graphite composite contributes a high capacity of 1317.4 mAh g–1at 0.2 A g–1after 200 cycles, remarkable rate property of 514.0 mAh g–1at 5 A g–1, and long-term cyclic stabilization of 759.0 mAh g–1after 950 cycles at 1.0 A g–1. With outstanding electrochemical performance and facial synthesis, the ternary Mo–SnO2–graphite is a hopeful anode material for lithium-ion batteries (LIBs).

Asymmetric construction of α-carbolinones with easily available starting materials has recently attracted considerable attention from the synthesis community, and the development of effective catalysis for this target is in great demand. Here, a bifunctional Brønsted base catalyzed asymmetric [3 + 3] cyclization of indolin-2-imines and α,β-unsaturated N-acylated succinimides was developed by using the strategy of noncovalent bonding catalysis. With this organocatalytic protocol, a variety of tetrahydro-α-carbolinones bearing different substituents were synthesized with up to 99% yield and up to 96:4 er.

An exciton is the bosonic quasiparticle of electron–hole pairs bound by the Coulomb interaction1. Bose–Einstein condensation of this exciton state has long been the subject of speculation in various model systems2,3, and examples have been found more recently in optical lattices and two-dimensional materials4–9. Unlike these conventional excitons formed from extended Bloch states4–9, excitonic bound states from intrinsically many-body localized states are rare. Here we show that a spin–orbit-entangled exciton state appears below the Néel temperature of 150 kelvin in NiPS3, an antiferromagnetic van der Waals material. It arises intrinsically from the archetypal many-body states of the Zhang–Rice singlet10,11, and reaches a coherent state assisted by the antiferromagnetic order. Using configuration-interaction theory, we determine the origin of the coherent excitonic excitation to be a transition from a Zhang–Rice triplet to a Zhang–Rice singlet. We combine three spectroscopic tools—resonant inelastic X-ray scattering, photoluminescence and optical absorption—to characterize the exciton and to demonstrate an extremely narrow excitonic linewidth below 50 kelvin. The discovery of the spin–orbit-entangled exciton in antiferromagnetic NiPS3introduces van der Waals magnets as a platform to study coherent many-body excitons.

In order to enhance the wear property of TA2 alloy, ceramics reinforced composite coating was prepared on TA2 alloy by laser cladding with preplaced mixed WS2-TiC-Ti powders (mole ratio of 1:3:6). The micro-structure, phase compositions and micro-hardness of composite coating were analyzed in detail. The dry-sliding wear behaviors and corresponding wear mechanisms of TA2 alloy substrate and composite coating at different test temperatures (RT, 250 and 500°C) were also studied systematically. The results showed that α-Ti, TiS, Ti2SC, (Ti, W)C1−xand TiC were in-situ synthesized in laser processing. The micro-hardness of the coating was improved significantly due to the formation of carbide ceramics Ti2SC, (Ti, W)C1−xand TiC. The coating exhibited excellent wear property at 500°C, i.e. low friction coefficient (0.339) and wear rate (4.87×10−6mm3/Nm). The predominant wear mechanism of the composite coating was formation and peeling off of lubricating transfer films, with incidental effect of adhesive wear and oxidation wear.

Electrochemical synthesis of organic compounds has emerged as an attractive and environmentally benign alternative to conventional approaches for oxidation and reduction of organic compounds that utilizes electric current instead of chemical oxidants and reductants. As such, many useful transformations have been developed, including the Kolbe reaction, the Simons fluorination process, the Monsanto adiponitrile process, and the Shono oxidation, to name a few. Electrochemical C–H functionalization represents one of the most promising reaction types among many electrochemical transformations, since this process avoids prefunctionalization of substrates and provides novel retrosynthetic disconnections. However, site-selective anodic oxidation of C–H bonds is still a fundamental challenge due to the high oxidation potentials of C–H bonds compared to organic solvents and common functional groups. To overcome this issue, indirect electrolysis via the action of a mediator (a redox catalyst) is regularly employed, by which the selectivity can be controlled following reaction of said mediator with the substrate. Since the redox potentials of transition metal complexes can be easily tuned by modification of the ligand, the synergistic use of electrochemistry and transition metal catalysis to achieve site-selective C–H functionalization is an attractive strategy.

In conventional intercalation cathodes, alkali metal ions can move in and out of a layered material with the charge being compensated for by reversible reduction and oxidation of the transition metal ions. If the cathode material used in a lithium-ion or sodium-ion battery is alkali-rich, this can increase the battery’s energy density by storing charge on the oxide and the transition metal ions, rather than on the transition metal alone1–10. There is a high voltage associated with oxidation of O2−during the first charge, but this is not recovered on discharge, resulting in reduced energy density11. Displacement of transition metal ions into the alkali metal layers has been proposed to explain the first-cycle voltage loss (hysteresis)9,12–16. By comparing two closely related intercalation cathodes, Na0.75[Li0.25Mn0.75]O2and Na0.6[Li0.2Mn0.8]O2, here we show that the first-cycle voltage hysteresis is determined by the superstructure in the cathode, specifically the local ordering of lithium and transition metal ions in the transition metal layers. The honeycomb superstructure of Na0.75[Li0.25Mn0.75]O2, present in almost all oxygen-redox compounds, is lost on charging, driven in part by formation of molecular O2inside the solid. The O2molecules are cleaved on discharge, reforming O2−, but the manganese ions have migrated within the plane, changing the coordination around O2−and lowering the voltage on discharge. The ribbon superstructure in Na0.6[Li0.2Mn0.8]O2inhibits manganese disorder and hence O2formation, suppressing hysteresis and promoting stable electron holes on O2−that are revealed by X-ray absorption spectroscopy. The results show that voltage hysteresis can be avoided in oxygen-redox cathodes by forming materials with a ribbon superstructure in the transition metal layers that suppresses migration of the transition metal.

ObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres in China between 3 January 2016 and 17 July 2023.ParticipantsFemale patients aged 18-70 years with early triple negative breast cancer after definitive surgery.InterventionsAfter risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168).Main outcome measuresThe primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety.ResultsAmong the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred.ConclusionsThe multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity.Trial registrationClinicalTrials.gov NCT02641847.

Structural degradation of oxide electrodes during the electrocatalytic oxygen evolution reaction (OER) is a major challenge in water electrolysis. Although the OER is known to induce changes in the surface layer, little is known about its effect on the bulk of the electrocatalyst and its overall phase stability. Here, we show that under OER conditions, a highly active SrCoO3–xelectrocatalyst develops bulk lattice instability, which results in the formation of molecular O2dimers inside the bulk and nanoscale amorphization induced via chemo-mechanical coupling. Using high-resolution resonant inelastic X-ray scattering and first-principles calculations, we unveil the potential-dependent evolution of lattice oxygen inside the perovskite and demonstrate that O2dimers are stable in a densely packed crystal lattice, thus challenging the assumption that O2dimers require sufficient interatomic spacing. We also show that the energy cost of local atomic rearrangements in SrCoO3–xbecomes very low under the OER conditions, leading to an unusual amorphization under intercalation-induced stress. As a result, we propose that the amorphization energy can be calculated from the first principles and can be used to assess the stability of electrocatalysts. Our study demonstrates that extreme oxidation of electrocatalysts under OER can intrinsically destabilize the lattice and result in bulk anion redox and disorder, suggesting why some oxide materials are unstable and develop a thick amorphous layer under water electrolysis conditions.

To evaluate the anesthetic effect of ultrasound-guided (USG) ilioinguinal/iliohypogastric nerve (II/IHN) block combined with genital branch of genitofemoral nerve (GFN) block in the elderly undergoing inguinal hernia repair, 54 old patients (aged 60–96years, ASA I–III) with indirect hernia were enrolled and scheduled for unilateral tension-free herniorrhaphy. Patients were grouped randomly to receive either USG II/IHN plus GFN block (Group G) or USG II/IHN block alone (Group I). The intraoperative visual analogue scale (VAS) scores were recorded at skin incision, at spermatic cord/round ligament traction and at sac ligation. The resting and dynamic VAS scores were recorded postoperatively. The requirements of extra sedatives and analgesics for intra- and postoperative analgesia were assessed. Occurrence of complications of the block, postoperative nausea and vomiting and femoral nerve palsy was also reported. Both groups showed similar sensory block. When stretching spermatic cord/round ligament, the patients in group G had significantly lower VAS scores than in group I. And group G used much fewer adjuvant sedatives and analgesics to achieve adequate anaesthesia. In addition, group G was presented with better intraoperative anaesthesia and lower postoperative dynamic VAS scores at all time points tested. No significant difference was found in the postoperative requirement of rescue medication. Both groups showed no complications related to the block and group G reported no femoral nerve palsy. The addition of GFN block to II/IHN block improves the quality of perioperative anesthesia and analgesia in the elderly and reduces the consumption of extra sedatives and analgesics during the surgery.

The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution; it leads to femoral head collapse and severe arthritis when left untreated. The application of a pedicled bone flap graft is an effective treatment for femoral head necrosis. A pure Mg screw is a kind of degradable screw that can fix the grafted bone flap and prevent long-term stress occlusion and secondary dissection.

Objectives: Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhibits Toll-like receptor 4 (TLR4), on experimental inflammatory TMJOA pathology. Methods: An intra-articular injection of complete Freund’s adjuvant (CFA) was used to induce an experimental inflammatory mouse TMJOA model, and TLR4 expression was identified by immunofluorescent labeling. Intraperitoneal injections of Resatorvid were administered to CFA-induced TMJOA mice, and the pathology of TMJOA animals with and without Resatorvid treatment was examined by H&E, Safranin-O/Fast Green, and TRAP staining, as well as micro-CT, immunohistochemistry, and immunofluorescence. The impact of Resatorvid on chondrocyte pyroptosis and macrophage inflammation was further investigated using ATDC5 chondrocytes and RAW264.7 macrophages pretreated with relevant antagonists. Results: CFA-induced TMJOA mice revealed remarkable synovial inflammation, together with a time course of cartilage degradation and bone destruction, with TLR4 elevated in the synovium and condylar cartilage. Prophylactic treatment with Resatorvid mitigated synovial inflammation, cartilage degeneration, and bone destruction in CFA-induced TMJOA mice and downregulated MyD88/NF-κB expression. Ex vivo studies demonstrated that Resatorvid treatment alleviated NOD-like receptor protein 3 (NLRP3)-mediated chondrocyte pyroptosis and degeneration and relieved macrophage inflammation by preventing reactive oxygen species (ROS) production through NLRP3 signaling. Conclusion: Prophylactic treatment with Resatorvid alleviates TMJOA pathology by inhibiting chondrocyte pyroptosis and degeneration, as well as ROS-induced macrophage inflammation, through TLR4/MyD88/NF-κB/NLRP3.

Previous studies have implicated urotensin-II in the nociception of sensory neurons. However, to date the relevant mechanisms remain unknown. In the current study we determined the role of urotensin-II in the regulation of transient outward A-type potassium currents (IA) and neuronal excitability in trigeminal ganglion (TG) neurons. We found that application of urotensin-II to small-diameter TG neurons decreased IA in a dose-dependent manner, whereas the delayed rectifier potassium current was unaffected. The IA decrease induced by urotensin-II depended on the urotensin-II receptor (UT-R) and was associated with a hyperpolarizing shift in the steady-state inactivation curve. Exposure of TG cells to urotensin-II markedly increased protein kinase C (PKC) activity, and PKC inhibition eliminated the UT-R-mediated IA decrease. Antagonism of PKCα, either pharmacologically or genetically, but not of PKCβ prevented the decrease in IA induced by urotensin-II. Analysis of phospho-extracellular signal-regulated kinase (p-ERK) revealed that urotensin-II significantly increased the expression level of p-ERK, whereas p-p38 and p-c-Jun N-terminal kinase remained unchanged. Inhibition of mitogen-activated protein kinase/ERK signaling by the kinase antagonist U0126 and PD98059 completely abolished the UT-R-mediated IA decrease. Moreover, urotensin-II significantly increased the action potential firing rate of small TG neurons; pretreatment with 4-aminopyridine prevented this effect. In summary, our findings suggest that urotensin-II selectively attenuated IA through stimulation of the PKCα-dependent ERK1/2 signaling pathway. This UT-R-dependent mechanism might contribute to neuronal hyperexcitability in TG neurons.

Mechanical allodynia (MA) represents one prevalent symptom of chronic pain. Previously we and others have identified spinal and brain circuits that transmit or modulate the initial establishment of MA. However, brain-derived descending pathways that control the laterality and duration of MA are still poorly understood. Here we report that the contralateral brain-to-spinal circuits, from Oprm1 neurons in the lateral parabrachial nucleus (lPBNOprm1), via Pdyn neurons in the dorsal medial regions of hypothalamus (dmHPdyn), to the spinal dorsal horn (SDH), act to prevent nerve injury from inducing contralateral MA and reduce the duration of bilateral MA induced by capsaicin. Ablating/silencing dmH-projecting lPBNOprm1neurons or SDH-projecting dmHPdynneurons, deleting Dyn peptide from dmH, or blocking spinal κ-opioid receptors all led to long-lasting bilateral MA. Conversely, activation of dmHPdynneurons or their axonal terminals in SDH can suppress sustained bilateral MA induced by lPBN lesion.

The compressive properties of metal–organic framework (MOF) crystals are not only crucial for their densification process but also key in determining their performance in many applications. We herein investigated the mechanical responses of a classic crystalline MOF, HKUST-1, using in situcompression tests. A serrated flow accompanied by the unique strain avalanches was found in individual and contacting crystals before their final flattening or fracture with splitting cracks. The plastic flow with serrations is ascribed to the dynamic phase mixing due to the progressive and irreversible local phase transition in HKUST-1 crystals, as revealed by molecular dynamics and finite element simulations. Such pressure-induced phase coexistence in HKUST-1 crystals also induces a significant loading-history dependence of their Young’s modulus. The observation of plastic avalanches in HKUST-1 crystals here not only expands our current understanding of the plasticity of MOF crystals but also unveils a novel mechanism for the avalanches and plastic flow in crystal plasticity.

This paper mainly studies the single distribution center in the circumstances, transport path selection and vehicle allocation problem of small batch of goods. Using the theory of minimum spanning tree theory to the entire logistics network path selection research, while determining the nodes need to configure the transport vehicle for shunt transport, further establish the logistic distribution routing out several cars choice model, but also provides a direction for future research on this type of problem.

We present a robust single-photon quantum secret sharing (QSS) scheme with phase encoding in three-party implementations and a design way of more parties over a 50 km single-mode fiber network using a single QSS protocol. This scheme automatically provides perfect compensation for birefringence. A high visibility of 99.4% is obtained over three hours in visibility and stability measurements without any system adjustments, showing good potential for practical systems. Furthermore, polarization-insensitive phase modulators are realized using this system.

3D Geological modeling technique can apply the existing data comprehensively, representing geological structure intuitively, so further the research has significant meaning on this basis. This article constructs the 3D layered model and ore grade model of the sulfide deposit based on exploration data and geological knowledge. In order to estimate precisely the amount of mineral resources depending on the ore grade model, which has been built by the constraint layer, this method can improve the calculation.

Reactive powder concrete (RPC) is an ultra-high performance concrete (UHPC). Cement and silica fume content of RPC are generally rather high compared to the conventional concrete. The aim of this paper is to decrease the cement content of RPC by using phosphorous slag powder. Firstly the effect of grinding time on the activity index of phosphorous slag was investigated. And then, the mix proportion design of this UHPC containing phosphorous slag powder and silica fume was done through orthogonal design. The results indicate that the utilization of phosphorous slag powder in RPC is feasible when the dosage of phosphorous slag powder is about 35% (by weight of the binder) and the water-binder ratio is less than 0.18. By substituting phosphorous slag powder for a part of cement and keeping the water-binder ratio at about 0.14, UHPC specimens whose content of mineral admixtures, including phosphorous slag powder and silica fume, was about 40%~50% (by weight of the binder) were obtained after they had been cured in 80 °C water for 72 hours. The compressive and flexural strength of those specimens was more than 150 MPa and 20 MPa respectively.

We use S-Parameter Methodto extract device parameter of InAlN/GaN HEMT in this paper. We find thatparasitic capacitance and parasitic inductance can be extracted in traditionaltest structure method, but do nothing about parasitic resistor. Cold parameter methodcan extract parasitic resistor efficiently, but there is greater error inparasitic capacitance and parasitic inductance extraction. We propose a methodwhich combines test structure method and cold parameter method to extract parasitic parameteraccurately. We can acquire intrinsic parameters through getting rid ofparasitism parameters, and can fitting test outcome satisfactorily. It canreflect accurately the physical characteristics of GaN HEMT devices, and givesfeedback and guidance to device technology at the same time.

Ka-band radio-frequency(RF) performance of a InAlN/GaN/AlGaN HFET on SiC was reported. Based on a detailed delay analysis,a maximum drain current density of 1.12 A/mm was obtained. Power measurements were performed, the maximum output power density is 2.1 W/mm and a power-added efficiency (PAE) is 22.3% at 29 GHz. The current gain cut-off frequency (fT) is 60 GHz, and the power gain cut-off frequency (fMAX) is 105 GHz.

La0.7Ca0.2Sr0.1MnO3/xIrO2 (LCSMO/xIrO2) compounds were fabricated by solid state reaction method. X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and Dc four probed method were used to investigate the structure, magnetic and magnetotransport properties. The results show that at low doping level (x≤0.15) IrO2 goes into the perovskite lattice substituting Mn in LCSMO, but at high doping level (x≥0.20) some part of the IrO2 substituted for Mn4+ in LCSMO lattice and the remainder resided in the grain boundaries in the form of IrO2. LCSMO/xIrO2 composites are influenced remarkabled by the IrO2 doping. With increasing IrO2 addition, the magnetic moment (s) decreases and Curie temperature (TC) decreases first, and then rises slowly of the compounds; In the doping range of 0~0.35, the resistivity rises first, and then decreases slowly, furthermore, the resistivity versus appears double peaks with increasing IrO2 addition. At room temperature, the magnetoresistance (MR) of the composites have been improved remarkably.