Prognostic predictive value of Ki-67 in stage I-II triple-negative breast cancer.

Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I-II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan-Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer.

This study aimed to find the best value of Ki-67, which is a marker used in breast cancer. At last, according to the Ki-67 level over 45%, triple-negative breast cancer may be divided into two groups. Based on the level of Ki-67, treatment decisions may be better. However, we still need more studies to confirm this.

Triple-negative breast cancer may be further subcategorized according to the Ki-67 level >45%, which is associated with a poorer prognosis. Treatment decisions based on the level of Ki-67 may be more favorable to the prognosis of patients.

Construction of Fe(III) Active Sites on Phenanthroline-Grafted g-C3N4: Reduced Work Function and Enhanced Intramolecular Charge Transfer for Efficient N2 Photofixation.

Photocatalytic nitrogen fixation is one of the important pathways for green and sustainable ammonia synthesis, but the extremely high bonding energy of the N≡N triple bond makes it difficult for conventional nitrogen fixation photocatalysts to directly activate and hydrogenate. Given this, we covalently grafted the phenanthroline unit onto graphitic carbon nitride nanosheets (CN) by the simple thermal oxidation method and complexed it with transition metal Fe3+ ions to obtain stable dispersed Fe active sites, which can significantly improve the photocatalytic activity. The Fe(III)-4-P-CN photocatalyst morphology consists of porous lamellar structures internally connected by nanowires. The special morphology of the catalysts gives them excellent nitrogen fixation performance, with an average NH3 yield of 492.9 µmol g-1 h-1, which is 6.5 times higher than that of the pristine CN, as well as better photocatalytic cycling stability. Comprehensive experiments and density-functional theory results show that Fe(III)-4-P-CN is more favorable than pristine CN for *N2 activation, effectively lowering the reaction energy barrier. Moreover, other byproducts (such as nitrate and H2O2) are also produced during the photocatalytic nitrogen fixation process, which also provides a new way for nitrogen-fixing photocatalysts to achieve multifunctional applications.

g-C3N4@TiO2 photoanodes for high-efficiency QDSSCs: improved electron transfer and photochemical stability.

In QDSSCs, a photoanode is an important part of connecting the external circuit, providing support for the transmission of photogenerated carriers to the external circuit, and also providing an attachment site for QDs. In this study, we prepared a g-C3N4@TiO2 composite for the photoanode by a two-step process. The results show that the use of g-C3N4@TiO2 greatly increases the specific surface area of the material, effectively inhibits the "electron-hole" recombination, and optimizes the stability and catalytic performance of the photoanode. Among them, the cell equipped with the g-C3N4@TiO2 photoanode has improved performance: Jsc = 26.5 mA cm-2, PCE = 8.2%, Voc = 0.62 eV, and FF = 0.50. Based on the research in this paper, it can be seen that the g-C3N4@TiO2 composite applied to the photoanode can effectively improve the cell performance and provide a feasible idea for optimizing QDSSCs.

Simulating arsenic discharge flux at a relic smelting site in Guangxi Zhuang Autonomous Region, China.

Anthropogenic groundwater arsenic (As) pollution is common in many aquifers in Southwest China. It is concerned that long-term random disposal of As smelting slag could induce the transport of high-As groundwater into previously uncontaminated aquifers. Here, we used HELP-MODFLOW-MT3DMS model simulations to integrate the percolation, groundwater flow, and solute transport processes at an aquifer at site scale, constrained by weather, hydrogeology, and monitoring data. Our simulations provide a new method framework of the simulated percolation by HELP model and have induced As spatiotemporal distribution in the aquifer. According to the HELP model simulation results, percolation volume accounts for 24% of rainfall over 18 years. This work determined that the As discharge trend was fitted by double-constants kinetics based on the leaching experiment. And this work calculates total mass distribution of As in the aquifer over 18 years. We have found that the sustained As pollution relies on the rainfall that acts as the primary contributor of elevated As concentrations. Model simulation results suggest that 51.70% of the total As mass (1.96 × 104 kg) was fixed in low permeability solid media. The total As mass discharged into groundwater reached 9.3 × 103 kg, accounting for 24.68%. The accumulative outflow mass of arsenic was 8.0 × 103 kg, accounting for 21.62%.

Core-shell ZnO@TiO2 hexagonal prism heterogeneous structures as photoanodes for boosting the efficiency of quantum dot sensitized solar cells.

In quantum dot sensitized solar cells (QDSSCs), the photoanode provides a stable support for the quantum dots, and promotes the production of photogenerated electrons and the transfer to external circuit. Therefore, it is very important to search for excellent photoanodes for the commercial application of QDSSCs. In this paper, a core-shell ZnO@TiO2 hexagonal prism heterogeneous structure was prepared by a two-step hydrothermal method. The ZnO@TiO2 heterogeneous structure not only has a unique 1D hexagonal prism morphology, but also can effectively inhibit the electron-hole recombination and has a greater light response and higher collection efficiency while speeding up the electron transmission rate. By adjusting the concentration of the TiO2 source, the best photoanode material Zn@Ti-2 was explored, and it showed excellent cell performance: Jsc = 25.4 mA cm-2, Voc = 0.71 V, PCE = 8.5%, and FF = 0.49. Compared with a single ZnO photoanode, the PCE value is increased by 25%. EIS, Tafel polarization and transient photocurrent responses confirm that the Zn@Ti-2 photoanode has higher catalytic activity and stability. Therefore, Zn@Ti-2 may be a promising photoanode material for QDSSCs.

Fabrication of Ultrafine Cu2 O Nanoparticles on W18 O49 Ultra-Thin Nanowires by In-Situ Reduction for Highly Efficient Photocatalytic Nitrogen Fixation.

Photocatalytic ammonia synthesis technology is one of the important methods to achieve green ammonia synthesis. Herein, two samples of Cu ion-doped W18 O49 with different morphologies, ultra-thin nanowires (Cu-W18 O49 -x UTNW) and sea urchin-like microspheres (Cu-W18 O49 -x SUMS), are synthesized by a simple solvothermal method. Subsequently, Cu2 O-W18 O49 -x UTNW/SUMS is synthesized by in situ reduction, where the NH3 production rate of Cu2 O-W18 O49 -30 UTNW is 252.4 µmol g-1  h-1 without sacrificial reagents, which is 11.8 times higher than that of the pristine W18 O49 UTNW. The Cu2 O-W18 O49 -30 UTNW sample is rich in oxygen vacancies, which promotes the chemisorption and activation of N2 molecules and makes the N≡N bond easier to dissociate by proton coupling. In addition, the in situ reduction-generated Cu2 O nanoparticles exhibit ideal S-scheme heterojunctions with W18 O49 UTNW, which enhances the internal electric field strength and improves the separation and transfer efficiency of the photogenerated carriers. Therefore, this study provides a new idea for the design of efficient nitrogen fixation photocatalysis.

Treatments and Prognosis of the Breast Ductal Carcinoma In Situ.

INTRODUCTION: With progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS. PATIENTS AND METHODS: This retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan-Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates. RESULTS: Among the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis. CONCLUSION: In conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

Limitation of WO3 in Zn-Co3O4 Nanopolyhedra by the Pyrolysis of H3PW12O40@BMZIF: Synergistic Effect of Heterostructure and Oxygen Vacancies for Enhanced Nitrogen Fixation.

The photocatalytic nitrogen fixation process is a crucial step toward carbon neutrality and sustainable development. The combination of polyoxometalates and metal-organic frameworks is a viable method to achieve high-efficiency photocatalytic nitrogen fixation. In this work, we employed bimetallic ZIF (BMZIF) composed of Co2+ and Zn2+ encapsulated with H3PW12O40 (PW12) as the precursor to synthesize Zn-doped Co3O4 nanopolyhedra loaded with WO3 nanoparticles. The NH3 yield of WO3/Zn-Co3O4-2 with the best photocatalytic performance can reach 231.9 µmol g-1 h-1 under visible light, about 2.4 and 6.4 times those of pure Zn-Co3O4 and WO3, respectively. The rhombic dodecahedral geometry of BMZIF is still maintained in the synthesized WO3/Zn-Co3O4 nanopolyhedra, with the significant increase in the specific surface area after calcination showing better catalytic performance. At the same time, Zn doping and the formation of WO3 nanoparticles result in abundant oxygen vacancies in WO3/Zn-Co3O4 heterostructures. Oxygen vacancies can supply nitrogen with active sites for adsorption and activation and improve photocarriers' capacity for separation, which can greatly increase the effectiveness of the photocatalytic synthesis of ammonia. This work can easily synthesize the heterostructure based on n-type WO3 nanoparticles and p-type Zn-doped Co3O4 nanopolyhedra, and the beneficial combination of POMs and metal-organic framework provides new thinking for the synthesis of efficient nitrogen-fixing photocatalysts.

Linking health to geology-a new assessment and zoning model based on the frame of medical geology.

With the growing concerns about the Earth's environment and human health, there has been a surge in research focused on the intersection of health and geology. This study quantitatively assesses the relationship between human health and geological factors using a new framework. The framework considers four key geological environment indicators related to health: soil, water, geological landform, and atmosphere. Results indicate that the atmospheric and water resource indicators in the study area were generally favorable, while the scores of geological landforms varied based on topography. The study also found that the selenium content in the soil greatly exceeded the local background value. Our research underscores the importance of geological factors on human health, establishes a new health-geological assessment model, and provides a scientific foundation for local spatial planning, water resource development, and land resource management. However, due to varying geological conditions worldwide, the framework and indicators for health geology may need to be adjusted accordingly.

Construction of an Endogenously Activated Signal Amplification Assay for In Situ Imaging of MicroRNA and Guided Precise Photodynamic Therapy for Cancer Cells.

The construction of a sensitive strategy for in situ visualizing and dynamic tracing intracellular microRNA is of great importance. Via the toehold-mediated strand displacement process, the catalytic hairpin assembly (CHA) could offer several hundreds-fold signal amplifications. However, the CHA may produce certain background interferences since microRNA may exist in normal cells. In this work, we constructed an endogenously and sequentially activated signal amplification strategy to provide the amplified dual-color fluorescence imaging of microRNA in living cancer cells, which was comprised of two successive reaction processes: the activation of the preprotective catalytic probe by the endogenous glutathione (GSH) and the subsequent catalytic hairpin assembly on the surface of the upconversion nanoprobe triggered by the specific microRNA. Since the concentration of GSH in cancer cells was much higher than that in normal cells and the extracellular environment, the activation of the designed nanoprobe could be controlled at the desirable site. With the merits of the endogenous initiation and selective activation, the designed nanoprobe could achieve the bioimaging of microRNA in living cancer cells with high precision and reliability. Furthermore, via the introduction of a photosensitizer molecule into the DNA strand, the designed nanoplatform could achieve the precise photodynamic therapy (PDT) for cancer cells and malignant tumors under the irradiation of the NIR laser. This work provided a new avenue to achieve the accurate imaging of intracellular microRNA and guided precise PDT, which would offer powerful hints to the early diagnosis and therapy of malignant tumors.

Construction of Co3O4 nanopolyhedra with rich oxygen vacancies from ZIF-67 for efficient photocatalytic nitrogen fixation.

Photocatalytic nitrogen fixation has attracted much attention due to the fact that it is a way of using solar energy to achieve clean and sustainable conversion of nitrogen to ammonia under mild conditions. In this paper, different proportions of Zn-doped Co3O4 nanopolyhedrons were synthesized using bimetallic ZIFs containing Co2+ and Zn2+ as precursors for the construction of photocatalytic nitrogen fixation semiconductor materials for the first time. The synthesized Co3O4 nano-polyhedron still retains the rhombic dodecahedron shape of ZIF-67 and exhibits a large specific surface area. Moreover, Zn doping results in abundant oxygen vacancies on the surface of Co3O4 polyhedron. These oxygen vacancies not only provide active sites for nitrogen adsorption and activation, but also enhance the separation ability of photocarriers, which can significantly improve the efficiency of photocatalytic nitrogen fixation of the material. When Zn-Co3O4-30 is utilized as the catalyst for photocatalytic nitrogen fixation, the nitrogen fixation rate is 96.8 µmol g-1 h-1, which is much higher than that of pure-Co3O4. In this study, heteroatom-doped Co3O4 polyhedron with rich oxygen vacancy was synthesized by low-temperature oxidation method, which provides a new idea for the design and synthesis of skeleton-based photocatalytic nitrogen fixation materials.

Upconversion nanoparticle-based optogenetic nanosystem for photodynamic therapy and cascade gene therapy.

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.

Acoustic-Based Theranostic Probes Activated by Tumor Microenvironment for Accurate Tumor Diagnosis and Assisted Tumor Therapy.

Acoustic-based imaging techniques, including ultrasonography and photoacoustic imaging, are powerful noninvasive approaches for tumor imaging owing to sound transmission facilitation, deep tissue penetration, and high spatiotemporal resolution. Usually, imaging modes were classified into "always-on" mode and "activatable" mode. Conventional "always-on" acoustic-based probes often have difficulty distinguishing lesion regions of interest from surrounding healthy tissues due to poor target-to-background signal ratios. As compared, activatable probes have attracted attention with improved sensitivity, which can boost or amplify imaging signals only in response to specific biomolecular recognition or interactions. The tumor microenvironment (TME) exhibits abnormal physiological conditions that can be used to identify tumor sections from normal tissues. Various types of organic dyes and biomaterials can react with TME, leading to obvious changes in their optical properties. The TME also affects the self-assembly or aggregation state of nanoparticles, which can be used to design activatable imaging probes. Moreover, acoustic-based imaging probes and therapeutic agents can be coencapsulated into one nanocarrier to develop nanotheranostic probes, achieving tumor imaging and cooperative therapy. Satisfactorily, ultrasound waves not only accelerate the release of encapsulated therapeutic agents but also activate therapeutic agents to exert or enhance their therapeutic performance. Meanwhile, various photoacoustic probes can convert photon energy into heat under irradiation, achieving photoacoustic imaging and cooperative photothermal therapy. In this review, we focus on the recently developed TME-triggered ultrasound and photoacoustic theranostic probes for precise tumor imaging and targeted tumor therapy.

Induced neural stem cells from Macaca fascicularis show potential of dopaminergic neuron specification and efficacy in a mouse Parkinson's disease model.

Induced neural stem cells (iNSCs) can be reprogrammed from somatic cells and have shown potentials in treatment of various neurological diseases/disorders. Obtaining iNSCs of nonhuman primates serves as an important bridge for clinical translation using iNSCs. In the current study, cynomolgus (Macaca fascicularis) bone marrow mesenchymal stromal cells (MSCs) were reprogrammed into iNSCs by transduction of non-integrative Sendai virus encoding transgenes OCT4, SOX2, KLF4 and C-MYC. The obtained iNSCs showed characteristics of normal neural stem cells (NSCs) and could differentiate into neurons, astrocytes and oligodendrocytes. Furthermore, iNSCs could give rise to dopaminergic neural cells in vitro, which showed safety and efficacy after transplantation into the striatum of an immunodeficient mouse Parkinson's disease (PD) model.

Leaching experiments and risk assessment to explore the migration and risk of potentially toxic elements in soil from black shale.

Black shale is rich in potentially toxic elements (PTEs) that migrate through rock weathering or rainfall, adversely affecting human health and the environment. In this study, simulated rainfall leaching experiments were used to investigate the migration patterns and leaching kinetics of PTEs in black shale from the Lower Cambrian Hetang Formation and to analyze the water quality index (WQI) of PTEs in the leachate. A comparison between the risk of PTEs in the leachate and those in the soil was also made to determine the risk sources, risk status, and distribution characteristics of PTEs in the study area. The WQI of the indoor column experimental leachate indicated the highest As contamination. The geo-accumulation index (Igeo) and potential ecological risk (Er) of soils in the entire region revealed that the risk of Cd was the highest. Furthermore, by mapping the distribution of Igeo and Er in soils, the risk level in the region where black shale is located was found to be significantly higher than that in other areas. Comparing the leaching rate of PTEs with the WQI from leaching experiments, the risk associated with As in soil can be inferred to originate mainly from the leaching of black shale. Previous studies on PTEs in black shale in the study area tended to focus on Cd; however, this study found that the risk of As was not negligible. The health risk assessment also showed that the risk at the location of black shale was beyond the accepted range. Overall, this study provided a new and important evaluation law for the level of pollution by PTEs and health risks in typical black shale regions.

Fabrication of nanocomposite MoC-Mo2C@C/Cd0.5Zn0.5S: promoted electron migration and improved photocatalytic hydrogen evolution.

In this work, we successfully prepared composites of carbon-modified in-phase MoC-Mo2C (MoC-Mo2C@C, MMC) nanosheets with Cd0.5Zn0.5S (ZCS) nanorods. The loading of MMC nanosheets significantly improved the hydrogen production rate of ZCS nanorods. The results showed that the photocatalytic hydrogen production rate of ZCS is the highest when MMC nanosheets are 1 wt% of ZCS nanorods (1-MMC/ZCS), reaching 68.8 mmol h-1 g-1, which is 7.7 times that of pure ZCS nanorods. The 1-MMC/ZCS photocatalyst was measured with Na2S/Na2SO3 as a hole sacrifice reagent under irradiation with 420 nm monochromatic light, and the quantum efficiency of 1-MMC/ZCS was 32.9%. The carbon layer can promote the rapid transfer of photogenerated electrons, and in-phase Mo2C-MoC as the active site can synergistically improve the photocatalytic hydrogen production rate of ZCS. Most Mo2C-based materials are still used in the field of electrocatalysis. This study provides a new idea for exploring new molybdenum-based co-catalyst materials in the field of visible light catalytic hydrogen production.