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Background The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). Methods We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. Results Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. Discussion By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

Get in-depth understanding of each part of visual pathway yields insights to conquer the challenges that classic computer vision is facing. Here, we first report the bioinspired striate cortex with binocular and orientation selective receptive field based on the crossbar array of self-powered memristors which is solution-processed monolithic all-perovskite system with each cross-point containing one CsFAPbI3 solar cell directly stacking on the CsPbBr2I memristor. The plasticity of self-powered memristor can be modulated by optical stimuli following triplet-STDP rules. Furthermore, plasticity of 3 × 3 flexible crossbar array of self-powered memristors has been successfully modulated based on generalized BCM learning rule for optical-encoded pattern recognition. Finally, we implemented artificial striate cortex with binocularity and orientation selectivity based on two simulated 9 × 9 self-powered memristors networks. The emulation of striate cortex with binocular and orientation selectivity will facilitate the brisk edge and corner detection for machine vision in the future applications.

Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of nucleotide metabolism, our understanding of nucleotide metabolism in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness of nucleotide antimetabolites for enhancing immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies.

Catalytic hydrogenation is one of the backbones of the chemical industry. Controlling the reaction behaviour of the activated hydrogen species over oxide-supported metal catalysts is essential. Aside from the expected addition to substrates, the activated hydrogen species would also destroy the active structures. Here we show that, with the assistance of alkali cations, the atomically dispersed Ru(iii) on Al2O3 exhibits enhanced performance in the hydrogenation of a broad range of substrates. The alkali cations facilitate the hydrogenation mediated by heterolytic hydrogen species, which not only restrain the hydride species from migrating to interfacial oxygen, thus suppressing the reduction and aggregation of ruthenium, but also stabilize the negatively charged transition states and intermediates through enhanced Columbic attraction. Distinctively, an inverse H/D isotope effect related to H2 splitting as the rate-determining step over the atomically dispersed ruthenium-catalysed hydrogenation is predicted and confirmed. Alkali metals have been traditionally used to promote heterogeneous catalysts, albeit their mode of action remains controversial. Now, the authors demonstrate the multifaceted role of sodium ions in promoting atomically dispersed Ru(iii) on Al2O3, resulting in a superior hydrogenation catalyst.

Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a promising family of materials to investigate. Herein we developed a general host–guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M1/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir1/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$ whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10−3 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$). The activity of Ir1/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir1/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir1/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst. Single-atom catalysts maximize metal atom efficiency and exhibit properties that can be considerably different to their nanoparticle equivalent. Now a general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.

In this study we investigate the prediction and prognostic value of CXCL8–CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2− patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900–0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933–4.949; CXCR1/2++, HR 3.466, 95% CI 1.569–7.655, CXCR1/2− was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8–CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.

Controlled synthesis of transition metal dichalcogenide (TMD) monolayers with unusual crystal phases has attracted increasing attention due to their promising applications in electrocatalysis. However, the facile and large-scale preparation of TMD monolayers with high-concentration unusual crystal phase still remains a challenge. Herein, we report the synthesis of MoX2 (X = Se or S) monolayers with high-concentration semimetallic 1T′ phase by using the 4H/face-centered cubic (fcc)-Au nanorod as template to form the 4H/fcc-Au@MoX2 nanocomposite. The concentrations of 1T′ phase in the prepared MoSe2 and MoS2 monolayers are up to 86% and 81%, respectively. As a proof-of-concept application, the obtained Au@MoS2 nanocomposite is used for the electrocatalytic hydrogen evolution reaction (HER) in acid medium, exhibiting excellent performance with a low overpotential of 178 mV at the current density of 10 mA/cm2, a small Tafel slope of 43.3 mV/dec, and excellent HER stability. This work paves a way for direct synthesis of TMD monolayers with high-concentration of unusual crystal phase for the electrocatalytic application.

The widely distributed unconformity (T7) in Pearl River Mouth Basin, formed at ~ 30 Ma, is one of the most important unconformities of northern South China Sea related to the evolution of basin dynamics. Based on seismic data and logs, this study documents the distribution of the unconformity in Pearl River Mouth Basin (PRMB) and discusses the mechanism of the breakup unconformity in the evolution of the basin. The study verifies that the T7 boundary is a breakup unconformity: (1) most fault tips end at T7 unconformity or the offset diminishes markedly across the unconformity, and (2) these faults control the stratal thickness, reflected by the wedge shape formation. The T7 unconformity can be divided into three zones according to different structures and contact relationships: (1) the angular unconformity zone, (2) the local unconformity and onlap zone, and (3) the conformity zone, these three correspond to strong erosion zone, weak erosion zone, and non-erosion zone respectively. The distribution pattern of the breakup unconformity in this study area is controlled by the tectonic and geomorphology in the different zones of a basin: The angular erosion zone in the north is controlled by fault activity, but in local unconformity and onlap zone the erosion is mainly caused by diapir or local uplift. The conformity zone is located at the depression center in an underwater environment. This pattern indicates that the mechanism of the breakup unconformity is related to the erosion on shoulder uplift structure at the basin margin in rift stage.

The use of TiO2 as an anode in rechargeable sodium-ion batteries (NIBs) is hampered by intrinsic low electronic conductivity of TiO2 and inferior electrode kinetics. Here, a high-performance TiO2 electrode for NIBs is presented by designing a multichannel porous TiO2 nanofibers with well-dispersed Cu nanodots and Cu2+-doping derived oxygen vacancies (Cu-MPTO). The in-situ grown well-dispersed copper nanodots of about 3 nm on TiO2 surface could significantly enhance electronic conductivity of the TiO2 fibers. The one-dimensional multichannel porous structure could facilitate the electrolyte to soak in, leading to short transport path of Na+ through carbon toward the TiO2 nanoparticle. The Cu2+-doping induced oxygen vacancies could decrease the bandgap of TiO2, resulting in easy electron trapping. With this strategy, the Cu-MPTO electrodes render an outstanding rate performance for NIBs (120 mAh·g−1 at 20 C) and a superior cycling stability for ultralong cycle life (120 mAh·g−1 at 20 C and 96.5% retention over 2,000 cycles). Density functional theory (DFT) calculations also suggest that Cu2+ doping can enhance the conductivity and electron transfer of TiO2 and lower the sodiation energy barrier. This strategy is confirmed to be a general process and could be extended to improve the performance of other materials with low electronic conductivity applied in energy storage systems.

In the controlled synthesis of noble metal nanostructures using wet-chemical methods, normally, metal salts/complexes are used as precursors, and surfactants/ ligands are used to tune/stabilize the morphology of nanostructures. Here, we develop a facile electrochemical method to directly convert Pt wires to Pt concave icosahedra and nanocubes on carbon paper through the linear sweep voltammetry in a classic three-electrode electrochemical cell. The Pt wire, carbon paper and Ag/AgCl (3 mol L−1 KCl) are used as the counter, working and reference electrodes, respectively. Impressively, the formed Pt nanostructures exhibit better electrocatalytic activity towards the hydrogen evolution compared to the commercial Pt/C catalyst. This work provides a simple and effective way for direct conversion of Pt wires into well-defined Pt nanocrystals with clean surface. We believe it can also be used for preparation of other metal nanocrystals, such as Au and Pd, from their bulk materials, which could exhibit various promising applications. Ministry of Education (MOE) Nanyang Technological University This work was supported by the Ministry of Education under AcRF Tier 2 (ARC 19/15, No. MOE2014-T2-2-093; MOE2015-T2-2-057; MOE2016-T2-2-103; MOE2017-T2-1-162) and AcRF Tier 1 (2016-T1-001-147; 2016-T1-002-051; 2017-T1-001-150; 2017-T1-002-119), and Nanyang Technological University under Start- Up Grant (M4081296.070.500000) in Singapore. We would like to acknowledge the Facility for Analysis, Characterization, Testing and Simulation, Nanyang Technological University, Singapore, for use of their electron microscopy (and/or X-ray) facilities.

Single noble metal atoms and ultrafine metal clusters catalysts tend to sinter into aggregated particles at elevated temperatures, driven by the decrease of metal surface free energy. Herein, we report an unexpected phenomenon that noble metal nanoparticles (Pd, Pt, Au-NPs) can be transformed to thermally stable single atoms (Pd, Pt, Au-SAs) above 900 °C in an inert atmosphere. The atomic dispersion of metal single atoms was confirmed by aberration-corrected scanning transmission electron microscopy and X-ray absorption fine structures. The dynamic process was recorded by in situ environmental transmission electron microscopy, which showed competing sintering and atomization processes during NP-to-SA conversion. Further, density functional theory calculations revealed that high-temperature NP-to-SA conversion was driven by the formation of the more thermodynamically stable Pd-N4 structure when mobile Pd atoms were captured on the defects of nitrogen-doped carbon. The thermally stable single atoms (Pd-SAs) exhibited even better activity and selectivity than nanoparticles (Pd-NPs) for semi-hydrogenation of acetylene.

The promoting effect of sulfur sources is an intriguing but poorly understood phenomenon. Herein, we studied the treatment of PdCu bimetallic nanoparticles (NPs) with different amounts of sulfur powder. Low-level sulfidation led to the generation of a Pd30Cu10S9 NP catalyst consisting of surface enriched Pd NPs, electron deficient Pd and Cu, as well as zero valence sulfur. The Pd30Cu10S9 NP catalyst showed pronouncedly enhanced activity and selectivity in the semihydrogenation of alkynes. Our study revealed for the first time a possible cause for the promoting effect of sulfur at the atomic level, suggesting a new strategy in catalyst design.

Controlled synthesis of structurally anisotropic rhenium diselenide (ReSe2) with macroscopically uniform and strictly monolayer thickness as well as tunable domain shape/size is of great interest for electronics-, optoelectronics-, and electrocatalysis-related applications. Herein, we describe the controlled synthesis of uniform monolayer ReSe2 flakes with variable morphology (sunflower- or truncated-triangle-shaped) on SiO2/Si substrates using different ambient-pressure chemical vapor deposition (CVD) setups. The prepared polycrystalline ReSe2 flakes were transferred intact onto Au foil electrodes and tested for activity in the hydrogen evolution reaction (HER). Interestingly, compared to the compact truncated-triangle-shaped ReSe2 flakes, their edge-abundant sunflower-shaped counterparts exhibited superior electrocatalytic HER activity, featuring a relatively low Tafel slope of ∼76 mV/dec and an exchange current density of 10.5 μA/cm2. Thus, our work demonstrates that CVD-grown ReSe2 is a promising two-dimensional anisotropic material for applications in the electrocatalytic HER.

Breeding for pollution-safe cultivars (PSCs) can reduce pollutant accumulation in crops. However, the PSC breeding would face the risk of nutritional quality reduction, which is usually ignored in conventional breeding programs targeting to increase crop yield or nutritional quality. Thus, the doubt whether the risk would exist has to be clarified for supporting the PSC breeding. In the present study, a newly bred Cd/Pb-PSC of water spinach (Ipomoea aquatic Forsk.) and its parents (QLQ with low-Cd/Pb accumulation ability and T308 with high yield) of water spinach were employed to clarify the above-mentioned issue. Yields, and concentrations of Cd, Pb, nitrite, and organic and inorganic nutrients in shoots of the three experimental lines were determined. There were no significant differences in Cd/Pb concentration between the new PSC and QLQ, in nitrite content between the new PSC and its two parents and in yield between the new PSC and T308. It is decisively significant that shoot concentrations of organic and inorganic nutrients in the Cd/Pb-PSC were as high as those in one of its parents. It is affirmed that the breeding operations (crossing and consequently continuous selfing) for lowering Cd/Pb accumulation capacity of water spinach would not lower the nutritional values of the obtained Cd/Pb-PSCs from the breeding, which should be a pillar that supports the feasibility to minimize Cd/Pb pollution in vegetables using PSC-breeding method.

Molybdenum ditelluride (MoTe2), which is an important transition-metal dichalcogenide, has attracted considerable interest owing to its unique properties, such as its small bandgap and large Seebeck coefficient. However, the batch production of monolayer MoTe2 has been rarely reported. In this study, we demonstrate the synthesis of large-domain (edge length exceeding 30 μm), monolayer MoTe2 from chemical vapor deposition-grown monolayer MoS2 using a chalcogen atom-exchange synthesis route. An in-depth investigation of the tellurization process reveals that the substitution of S atoms by Te is prevalently initiated at the edges and grain boundaries of the monolayer MoS2, which differs from the homogeneous selenization of MoS2 flakes with the formation of alloyed Mo−S−Se hybrids. Moreover, we detect a large compressive strain (approximately −10%) in the transformed MoTe2 lattice, which possibly drives the phase transition from 2H to 1T’ at the reaction temperature of 500 °C. This phase change is substantiated by experimental facts and first-principles calculations. This work introduces a novel route for the templated synthesis of two-dimensional layered materials through atom substitutional chemistry and provides a new pathway for engineering the strain and thus the intriguing physics and chemistry.

An experimental investigation into microscale transformation characteristics of polycrystalline NiTi wires of 500 µm diameter during shape memory cycling is discussed, with emphasis on the characterization of a pronounced heterogeneity in the strain distribution evident during detwinning of the martensite phase upon application of load and its persistence throughout the actuation cycle. Using scanning electron microscopy-digital image correlation, full-field strain maps at the microscale were obtained during shape memory cycling. It was found that the strains induced by detwinning were quite heterogeneous at the microscale, and could display a large degree of similarity with thermo-mechanical cycling that tended to increase as cycling progressed. Residual strain concentrated at locations where strain accumulation from detwinning and plasticity were significant, indicating that martensitic detwinning and the associated plasticity that occurs with it is spatially correlated to the subsequent accumulation of residual strain at the microscale.

The prevalence of non-communicable chronic diseases (NCDs) worldwide poses an alarming threat to public health. Recent literature has embraced the opinion that incorporating the social factors should advance the understanding of NCDs prevalence. In this context, examining the NCDs prevalence in association with area social deprivation should provide critical implications for coping with public health risks. However, few empirical studies have examined this specific issue, especially in the developing countries. Using the principal component analysis, an area social deprivation index (ASDI) is established for the Shenzhen city (China) by integrating ten indicators from four dimensions: education, housing, socially disadvantaged population, and economically disadvantaged population. The geographically weighted regression (GWR) is employed to analyze the associations between ASDI and the incidence rate of three prevalent NCDs at district scale. Spatial non-stationary relationships are identified for the three diseases. More specifically, prevalence of the three diseases is all positively correlated with the ASDI. Strength of the associations presents the geography that it generally decreases from the central city to the suburb. These findings suggest that greater possibility of NCDs prevalence would be expected in districts with higher social deprivation. Besides, the impact of social deprivation on NCDs prevalence is much stronger in the central city. The spatial stationarity can facilitate the formulation of location-specific preventive measurements. This paper is believed to provide an innovative insight for social indicators research.

Most technologically important electrode materials for lithium-ion batteries are essentially lithium ions plus a transition-metal oxide framework. However, their atomic and electronic structure evolution during electrochemical cycling remains poorly understood. Here we report the in situ observation of the three-dimensional structural evolution of the transition-metal oxide framework in an all-solid-state battery. The in situ studies LiNi0.5Mn1.5O4 from various zone axes reveal the evolution of both atomic and electronic structures during delithiation, which is found due to the migration of oxygen and transition-metal ions. Ordered to disordered structural transition proceeds along the , , directions and inhomogeneous structural evolution along the direction. Uneven extraction of lithium ions leads to localized migration of transition-metal ions and formation of antiphase boundaries. Dislocations facilitate transition-metal ions migration as well. Theoretical calculations suggest that doping of lower valence-state cations effectively stabilize the structure during delithiation and inhibit the formation of boundaries., Here, with the state-of-the-state electron microscope, the authors report three-dimensional atomic-scale observation of LiNi0.5Mn1.5O4 from various directions, revealing unprecedented insight into the evolution of both atomic and electronic structures during delithiation.

Core–shell nanocatalysts have demonstrated potential as highly active low-Pt fuel cell cathodes for the oxygen reduction reaction (ORR); however, challenges remain in optimizing their surface and interfacial structures, which often exhibit undesirable structural degradation and poor durability. Here, we construct an unsupported nanoporous catalyst with a Pt–Pd shell of sub-nanometre thickness on Au, which demonstrates an initial ORR activity of 1.140 A mgPt−1 at 0.9 V. The activity increases to 1.471 A mgPt−1 after 30,000 potential cycles and is stable over a further 70,000 cycles. Using aberration-corrected scanning transmission electron microscopy and atomically resolved elemental mapping, the origin of the activity change is revealed to be an atomic-scale evolution of the shell from an initial Pt–Pd alloy into a bilayer structure with a Pt-rich trimetallic surface, and finally into a uniform and stable Pt–Pd–Au alloy. This Pt–Pd–Au alloy possesses a suitable configuration for ORR, giving a relatively low free energy change for the final water formation from adsorbed OH intermediate during the reaction. Metal alloys possessing core–shell structures have potential as low-Pt catalysts for the oxygen reduction reaction in fuel cells, but can suffer from poor stability. Using high-resolution microscopy, Li et al. find that a Pt–Pd–Au catalyst undergoes surface atomic rearrangement and becomes more active on electrochemical cycling.

To overcome the disadvantages of the positioning technologies by fuzzy theory in Wireless Sensor Networks (WSNs), positioning algorithms based on information fusion are presented in this article. The fuzzy theory is used to deal with the randomness and fuzziness in the WSNs. And the information fusion is introduced to improve the location accuracy. If the collinearity of the anchor nodes is larger, the misjudged reference nodes may be caused. They are removed by using clustering method. The algorithms in this paper can enhance the location accuracies compared with using the fuzzy theory and alleviate the effect of the RSSI (Received Signal Strength Indication) measure errors. Moreover, the algorithms avoid the high complexity of computation and the requirement of more anchor nodes. Simulation results indicate that the algorithms are more precise, robust as well as with good suitability.

We investigated the role of neutrophilic cells (neutrophils) in inflammatory angiogenesis and explored the possible mechanisms involved. Corneal angiogenesis was induced in vivo with a 75% silver nitrate applicator. Depletion of neutrophils was accomplished by the intraperitoneal administration of RB6-8C5, a neutrophil-depleting antibody. Angiogenesis, neutrophil infiltration, and the localization of vascular endothelial growth factor (VEGF) were evaluated by biomicroscopic observations, histology, and immunohistochemistry in control and RB6-8C5 treatment groups. Protein levels of VEGF, macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha in the cornea were determined by enzyme-linked immunosorbent assay. An in vitro model of neutrophil activation was also used to examine the ability of neutrophils to produce and release VEGF, MIP-1alpha, and MIP-2. At day 1 after injury, neutrophil infiltration in the cornea was highest, and VEGF was expressed in the infiltrating neutrophils. The enhanced protein levels of VEGF, MIP-1alpha, and MIP-2 correlated with the degree of neutrophil infiltration. Neutrophil depletion significantly inhibited corneal angiogenesis and reduced the protein levels of VEGF, MIP-1alpha, and MIP-2 in the cornea. Upon stimulation, isolated neutrophils released VEGF from preformed stores and MIP-1alpha and MIP-2 by de novo synthesis. Neutrophil depletion thus significantly impaired inflammatory angiogenesis, identifying neutrophils as an important player in inflammatory angiogenesis. Neutrophils may exercise their angiogenic function by releasing proangiogenic factors such as VEGF. Intervention measures targeting neutrophils may therefore help to deal with abnormal angiogenesis involved in chronic inflammatory diseases.