Carbon emissions have become a global challenge, and China, as the world's largest developing country, has a serious emissions problem. Developing green buildings is an important way of reducing carbon emissions. China's low-carbon city pilot policy may be an effective way of promoting green building development and reducing these emissions. This study uses the low carbon city pilot policy as a quasi-natural experiment and employs the staggered difference-in-differences method to investigate its impact on green building development. The results show that the low-carbon city pilot policy promotes green building development, and this policy promotes it by enhancing regional green innovation capacity, improving green total factor productivity at the firm and regional levels, and reducing the financing constraints of firms in the construction and real estate sectors. In addition, the promotion effect of the policy on green building development is stronger in western and non-resource-based regions and large-scale cities in China. This study contributes to the literature related to environmental policy, green building, and carbon emissions and supports the promotion of green building development and the reduction of carbon emissions.
Carbon , Environmental Policy , Sustainable Development , China , Cities , Humans , Construction Industry , Conservation of Natural Resources/methods
Soil organic carbon (SOC) is a crucial medium of the global carbon cycle and is profoundly affected by multiple factors, such as climate and management practices. However, interactions between different SOC fractions and land-use change have remained largely unexplored in karst ecosystems with widespread rock outcrops. Owing to the inherent heterogeneity and divergent response of SOC to land-use change, soil samples with close depth were collected from four typical land-use types (cropland, grassland, shrubland, and forestland) in the karst rocky desertification area of China. The aim of this study was to explore the responses of SOC dynamics to land-use types and underlying mechanism. The results showed that land-use type significantly affected SOC contents and its fractions. Compared with cropland, the other three land uses increased the total organic carbon (TOC), microbial biomass carbon (MBC), and non-labile organic carbon (NLOC) contents by 6.11-129.44%, 32.58-173.73%, and 90.98-347.00%, respectively; this demonstrated that a decrease in both labile and recalcitrant carbon resulted in SOC depletion under agricultural land use. Readily oxidized organic carbon (ROC) ranged from 42 to 69%, accounting for almost half of the TOC in the 0-40-cm soil layer. Cropland soil showed significantly higher ROC:TOC ratios than other land-use types. These results indicated that long-term vegetation restoration decreased SOC activity and improved SOC stability. Greater levels of soil exchangeable calcium (ECa) and clay contents were likely responsible for higher stabilization and then accumulation of SOC after vegetation restoration. The carbon pool index (CPI) rather than the carbon pool management index (CPMI) exhibited consistent variation trend with soil TOC contents among land-use types. Thus, further study is needed to validate the CPMI in evaluating land use effects on soil quality in karst ecosystems. Our findings suggest that land-use patterns characterized by grass or forest could be an effective approach for SOC-sequestration potential and ensure the sustainable use of soil resources in the karst area.
Intracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal reprogramming, and brain-computer interfaces. Despite the limited expansion of the drug armamentarium for ICH over the past few decades, the judicious selection of more efficacious therapeutic modalities and the exploration of multimodal combination therapies represent opportunities to improve patient prognoses after ICH.
The quantum denoising technology efficiently removes noise from images; however, the existing algorithms are only effective for additive noise and cannot remove multiplicative noise, such as speckle noise in synthetic aperture radar (SAR) images. In this paper, based on the grayscale morphology method, a quantum SAR image denoising algorithm is proposed, which performs morphological operations on all pixels simultaneously to remove the noise in the SAR image. In addition, we design a feasible quantum adder to perform cyclic shift operations. Then, quantum circuits for dilation and erosion are designed, and the complete quantum circuit is then constructed. For a 2n×2n quantum SAR image with q grayscale levels, the complexity of our algorithm is O (n+q). Compared with classical algorithms, it achieves exponential improvement and also has polynomial-level improvements than existing quantum algorithms. Finally, the feasibility of our algorithm is validated on IBM Q.
Background: In the double-blind phase III ADAURA randomized clinical trial, adjuvant osimertinib showed a substantial overall survival benefit in patients with stage IB to IIIA, EGFR-mutated, completely resected non-small cell lung cancer (NSCLC). We conduct a cost-effectiveness analysis comparing the use of adjuvant osimertinib to placebo in patients with stage IB to IIIA, EGFR-mutated, resected NSCLC. Methods: Based on the results obtained from the ADAURA trial, a Markov model with three-state was employed to simulate patients who were administered either osimertinib or placebo until disease recurrence or completion of the study period (3 years). Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model. Results: Osimertinib produced additional 1.59 QALYs with additional costs of $492,710 compared to placebo, giving rise to ICERs of $309,962.66/QALY. The results of the univariate sensitivity analysis indicated that the utility of disease-free survival (DFS), cost of osimertinib, and discount rate had the greatest impact on the outcomes. Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY. Conclusion: In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.
High voltage, high rate, and cycling-stable cathodes are urgently needed for development of commercially viable sodium ion batteries (SIBs). Herein, we report a facial ball-milling to synthesize a carbon-coated Na3V2(PO4)2F3 composite (C-NVPF). Benefiting from the highly conductive carbon layer, the C-NVPF material exhibits a high reversible capacity (110.6 mA h g-1 at 0.1C), long-term cycle life (54% of capacity retention up to 2000 cycles at 5C), and excellent rate performance (35.1 mA h g-1 at 30C). The present results suggest promising applications of the C-NVPF material as a high-performance cathode for sodium ion batteries.
High-power-density electronic devices under vibrations call for soft and damping thermal interface materials (TIMs) for efficient heat dissipation. However, integrating low hardness, high damping, and superior heat transfer capability into one TIM is highly challenging. Herein, soft, damping, and thermally conductive TIMs are designed and prepared by constructing a honeycomb-board-mimetic boron nitride nanosheet (BNNS) network in a dynamic polyimine via one-step horizontal centrifugal casting. The unique filler network makes the TIMs perform a high through-plane thermal conductivity (> 7.69 W m-1 K-1) and a uniform heat transfer process. Meanwhile, the hierarchical dynamic bonding of the polyimine endows the TIMs with low compressive strength (2.16 MPa at 20% strain) and excellent damping performance (tan δ > ≈0.3 at 10-2-102 Hz). The resulting TIMs also exhibit electrical insulation and remarkable recycling ability. Compared with the commercial ones, the TIMs provide better heat dissipation (4.1 °C) for a high-power 5G base station and less temperature fluctuation (1.8 °C) for an automotive insulated gate bipolar transistor (IGBT) under vibrations. This rational design offers a viable approach to prepare soft and damping TIMs for effective heat dissipation of high-power-density electronic devices under vibrations.
A modified biodegradable plastic (PLA/PBAT) was developed by through covalent bonding with proteinase K, porcine pancreatic lipase, or amylase, and was then investigated in anaerobic co-digestion mixed with food waste. Fluorescence microscope validated that enzymes could remain stable in modified the plastic, even after co-digestion. The results of thermophilic anaerobic co-digestion showed that, degradation of the plastic modified with Proteinase K increased from 5.21 ± 0.63 % to 29.70 ± 1.86 % within 30 days compare to blank. Additionally, it was observed that the cumulative methane production increased from 240.9 ± 0.5 to 265.4 ± 1.8 mL/gVS, and the methane production cycle was shortened from 24 to 20 days. Interestingly, the kinetic model suggested that the modified the plastic promoted the overall hydrolysis progression of anaerobic co-digestion, possibly as a result of the enhanced activities of Bacteroidota and Thermotogota. In conclusion, under anaerobic co-digestion, the modified the plastic not only achieved effective degradation but also facilitated the co-digestion process.
Metastasis is responsible for about 90% of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.
Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis, and the cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here, we investigated the involvement of the female genital tract Peptostreptococcus species in gynecological cancer via indoleacrylic acid (IAA). IAA production from Peptostreptococcus species and the effect of bacterial culture on tumor growth in vivo were examined. The impact of IAA on cytokine production and indoleamine-2,3-dioxygenase 1 (IDO1) expression in an endometrial cancer (EC) cell line, as well as their effect on Treg and Teff cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, Peptostreptococcus species abundance, IAA, and IDO1 expression were verified in EC patients. The results showed that IAA production was induced in the uteri of BALB/c nude mice by Peptostreptococcus species transplantation, and the intratumoral injection of a conditioned medium from Peptostreptococcus cultures into tumor-grafted mice promoted tumor growth. IL-10 expression was upregulated by IAA; IFN-γ expression was increased by IL-10. IFN-γ induced IDO1 expression in the EC cell line. The co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the Treg proportion and decreased the M1/M2 ratio. Clinically, P. anaerobius was more abundant amongst the uterine microbiota of EC patients than the control. The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.
Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C19 norditerpenoids and intact cephalotane-type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between ß-oxo esters and ß-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.
With the rapid development of quantum computing, a variety of quantum convolutional neural networks (QCNNs) are proposed. However, only 1/2n2 features of an n-qubits input are transferred to the next layer in a quantum pooling layer, which results in the accuracy reduction. To solve this problem, a QCNN with a degressive circuit is proposed. In order to enhance the ability of extracting global features, we remove the parameters sharing strategy in the quantum convolutional layer and design a quantum convolutional kernel with global eyesight. In addition, to prevent a sharp feature reduction, a degressive parameterized quantum circuit is adopted to construct the pooling layer. Then the Z-basis measurement is only performed on the first qubit to control the operations on other qubits. Compared with the state-of-the-art QCNN, i.e., hybrid quantum-classical convolutional neural network, the accuracy of our model increased by 0.9%, 1%, and 3%, respectively, in three tasks: quantum state classification, binary code recognition, and quaternary code recognition.
The study aimed to address the challenges related to insufficient dissolution and maintenance of supersaturation in binary solid dispersions. Lacidipine, categorized as a BCS class II drug, was employed as the model drug. A systematic screening of excipients was conducted to determine the most effective carriers for the formulations of the ternary solid dispersions, utilizing the solvent transfer method and equilibrium solubility measurements. Both binary and ternary solid dispersions were prepared via spray drying, and comprehensive physicochemical characterization confirmed the successful preparation of amorphous solid dispersions. In vitro dissolution tests, the ternary solid dispersion exhibited marked superiority over the binary solid dispersion in dissolution and maintenance of supersaturation. Furthermore, an exploration into the factors influencing the stability of ternary solid dispersions revealed their robust resistance under light-protected, room-temperature, and desiccated conditions. The formation of intermolecular hydrogen bonding within the molecules of the ternary solid dispersions significantly enhanced drug solubility and system stability. Strategic formulation optimization, coupled with judicious selection of suitable carrier types and ratios, may serve as a promising approach for designing supersaturated drug delivery systems.
Dihydropyridines , Drug Delivery Systems , Pharmaceutical Preparations , Excipients , Solubility
Background: The ALTA-1 L trial and EXP-3B arm of NCT01970865 trial found that both brigatinib and lorlatinib showed durable and robust responses in treating ALK-positive non-small cell lung cancer (NSCLC) patients. However, brigatinib and lorlatinib treatments are costly and need indefinite administration until the disease progression. Thus, it remains uncertain whether using brigatinib followed by lorlatinib before chemotherapy is cost-effective compared to reserving these two drugs until progression after chemotherapy. Methods: We used a Markov model to assess clinical outcomes and healthcare costs of treating ALK-positive NSCLC individuals with brigatinib followed by lorlatinib before chemotherapy versus a strategy of reserving these drugs until progression after chemotherapy. Transition probabilities were estimated using parametric survival modeling based on multiple clinical trials. The drug acquisition costs, adverse events costs, administration costs were extracted from published studies before and publicly available data. We calculated lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from the perspective of a United States payer. Results: Our base-case analysis indicated that the incremental cost-effectiveness ratios of using first-line brigatinib followed by lorlatinib compared with second-line brigatinib followed by lorlatinib is $-400,722.09/QALY which meant that second-line brigatinib followed by lorlatinib had less costs and better outcomes. Univariate sensitivity analysis indicated the results were most sensitive to the cost of brigatinib. Probability sensitivity analysis revealed that using brigatinib followed by lorlatinib before chemotherapy had a 0% probability of cost-effectiveness versus delaying these two drugs until progression after chemotherapy at a willingness-to-pay threshold of $150,000 per QALY. Sensitivity analyses conducted revealed the robustness of this result, as incremental cost-effectiveness ratios never exceeded the willingness-to-pay threshold. Conclusion: Using brigatinib as first-line treatment followed by lorlatinib for ALK-positive NSCLC may not be cost-effective given current pricing from the perspective of a United States payer. Delaying brigatinib followed by lorlatinib until subsequent lines of treatment may be a reasonable strategy that could limit healthcare costs without affecting clinical outcomes. More mature data are needed to better estimate cost-effectiveness in this setting.
Aminopyridines , Carcinoma, Non-Small-Cell Lung , Lactams , Lung Neoplasms , Organophosphorus Compounds , Pyrazoles , Pyrimidines , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Cost-Benefit Analysis , Lung Neoplasms/drug therapy , Lactams, Macrocyclic , Receptor Protein-Tyrosine Kinases
A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.
BACKGROUND: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown. OBJECTIVE: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups. METHODS: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure. RESULTS: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003). CONCLUSION: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men.
Excessive consumption of dietary sodium is a significant contributor to non-communicable diseases, including hypertension and cardiovascular disease. There is now a global consensus that regulating salt intake is among the most cost-effective measures for enhancing public health. More than half of the countries worldwide have implemented multiple strategies to decrease salt consumption. Nevertheless, a report on sodium intake reduction published by the World Health Organization revealed that the world is off-track to meet its targeted reduction of 30% by 2025. The global situation regarding salt reduction remains concerning. This review will center on domestic and international salt reduction policies, as well as diverse strategies, given the detrimental effects of excessive dietary salt intake and the existing global salt intake scenario. Besides, we used visualization software to analyze the literature related to salt reduction research in the last five years to explore the research hotspots in this field. Our objective is to enhance public awareness regarding the imperative of reducing salt intake and promoting the active implementation of diverse salt reduction policies.
Cardiovascular Diseases , Hypertension , Sodium, Dietary , Humans , Sodium Chloride, Dietary , Hypertension/prevention & control , Policy
OBJECTIVE: To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective. METHODS: A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase II, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature. RESULTS: Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of 839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective. CONCLUSION: Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness.
