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When the drilling core method is used to determine the coalbed gas content, the cutting heat generated by the core bit cutting coal will increase the core tube temperature, and the excessively high core tube temperature will have an heating effect on the coal core, which will accelerate the coal core gas desorption rate and increase the gas loss amount. The generation of cutting heat of core bit and the measurement of core tube temperature are the basis for grasping the gas desorption law of coal core and projecting the amount of gas loss. Firstly, the self-developed core tube temperature measurement device was used to conduct on-site core temperature measurement experiments at different cutting speeds. Then, the cutting temperature of core bit was solved by establishing thermodynamic model for cutting coal and heat transfer model of cutting edge. Finally, based on the thermal conductivity characteristics of the core tube, the core tube temperature at different cutting speeds was simulated, and the simulated temperature was compared with the on-site measured temperature to verify the reliability of the model. The results show that when coring in primary structural coal, the temperature change trend of core tube wall temperature measurement point at different cutting speeds is basically consistent, the temperature measurement point at the front end of the core tube mainly goes through a relatively stable period in the drilling process, a sharp rising period in the cutting process, a slow rise and cooling period in the withdrawal process. However, the temperature measurement point at the back end of the core tube wall mainly goes through a relatively stable phase and a slowly increasing phase. The temperature rise of the core bit and the core tube wall are significantly positively correlated with the cutting speed. When coring in hard coal seam and the core depth is not large, the cutting heat generated by the core bit and the coal body is the dominant factor for the temperature rise of the core tube. The core tube wall temperature calculated using the model matches well with the field measured temperature, and the error is small, which fully shows that the coring thermodynamic model is feasible. This study provides a basis for further research on the dynamic distribution characteristic of coal core temperature during coring, which is of profound significance to calculate the gas loss and coalbed gas content.
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RATIONALE AND OBJECTIVES: The preoperative diagnosis of small prevascular mediastinal nodules (SPMNs) presents a challenge, often leading to unnecessary surgical interventions. Our objective was to develop a nomogram based on preoperative CT-radiomics features, serving as a non-invasive diagnostic tool for SPMNs. MATERIALS AND METHODS: Patients with surgically resected SPMNs from two medical centers between January 2018 and December 2022 were retrospectively reviewed. Radiomics features were extracted and screened from preoperative CT images. Logistic regression was employed to establish clinical, radiomics, and hybrid models for differentiating thymic epithelial tumors (TETs) from cysts. The performance of these models was validated in both internal and external test sets by area under the receiver operating characteristic curve (AUC), while also comparing their diagnostic capability with human experts. RESULTS: The study enrolled a total of 363 patients (median age, 53 years [IQR:45-59 years]; 175 [48.2%] males) for model development and validation, including 136 TETs and 227 cysts. Lesions' enhancement status, shape, calcification, and rad-score were identified as independent factors for distinction. The hybrid model demonstrated superior diagnostic performance compared to other models and human experts, with an AUC of 0.95 (95% CI:0.92-0.98), 0.94 (95% CI:0.89-0.99), and 0.93 (95% CI:0.83-1.00) in the training set, internal test set, and external test set respectively. The calibration curve of the model demonstrated excellent fit, while decision curve analysis underscored its clinical value. CONCLUSION: The radiomics-based nomogram effectively discriminates between the most prevalent types of SPMNs, namely TETs and cysts, thus presenting a promising tool for treatment guidance.
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Background: Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. Methods: E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. Conclusions: E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.
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Polymer-matrix composites have been widely used in the manufacture of seals, bearings, electrical insulators, and self-lubricating films as engineering applications move toward lighter weight, higher strength, and corrosion resistance. However, the high-speed shear effect of the friction pairs in relative motion leads to localized heating of the polymer surface, resulting in deformation or softening of the device. Herein, acer mono maple and canna leaves were used as templates to construct polymer-matrix sulfonated polyether-etherketone/polytetrafluoro-wax (SPEEK/PFW) composites with a surface-textured structure. As the bionic texture reduces the level of direct contact between the friction pairs, the frictional thermosoftening of SPEEK occurs in the localized areas of the bumps and leads to the release of PFW stored in textures, resulting in the formation of a soft polymer sliding layer in the worn area and greatly enhancing the frictional stability. By investigation of the tribological properties of textured SPEEK/PFW composites under different loads and sliding speeds, the mechanisms from surface wear to matrix softening and spontaneous construction of a slipping layer are summarized. The results of scanning electron microscopy and three-dimensional profilometer characterization of the wear scars show the surface state of SPEEK/PFW after friction, revealing the friction-thermotropic deformation of the surface texture. The results of this study not only improve our understanding of the frictional heat-induced surface self-lubrication mechanism of textured polymer composites but also provide a reference for the development of multiphase hybrid polymer-matrix composites with excellent self-lubrication properties.
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Lightweight, flexible, efficient and easy-to-manufacture electromagnetic interference (EMI) shielding materials are in urgent demand in the communications industry, artificial intelligence and wearable electronics. Based on the large size difference between one-dimensional carboxymethyl cellulose nanofibers (CMC) and large-diameter silver nanowires (AgNWs), layered AgNWs/CMC nanocomposite films with large effective thickness, and high conductivity were first prepared by a simple one-step vacuum filtration self-assembly technique. The unique layered structure of the AgNWs/CMC nanocomposite film significantly enhances the conductive pathways within the film, endowing it excellent EMI shielding performance. The results show that the conductivity of the ultra-thin film with a thickness of 20 µm is 3.72 × 106 S/m, and the EMI SE in the X-band is 87.7 dB, which can effectively shield electromagnetic signals in mobile communications. Furthermore, the AgNWs/CMCs nanocomposite films exhibit excellent thermal management performance, which can be heated to 100-180 °C within 10 s at a low voltage of 1.5 V. In particular, this nanocomposite film with a new layered structure provides a noval preparation idea for future EMI shielding materials and wearable heating devices.
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Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.
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Carcinoma Hepatocelular , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Factor de Transcripción STAT1 , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/inmunología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/inmunología , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Factor de Transcripción STAT1/metabolismo , Animales , Ratones , Humanos , Proliferación Celular/efectos de los fármacos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Masculino , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunologíaRESUMEN
BACKGROUND: This study was aimed to establish a prediction model for spread through air spaces (STAS) in early-stage non-small cell lung cancer based on imaging and genomic features. METHODS: We retrospectively collected 204 patients (47 STAS+ and 157 STAS-) with non-small cell lung cancer who underwent surgical treatment in the Jinling Hospital from January 2021 to December 2021. Their preoperative CT images, genetic testing data (including next-generation sequencing data from other hospitals), and clinical data were collected. Patients were randomly divided into training and testing cohorts (7:3). RESULTS: The study included a total of 204 eligible patients. STAS were found in 47 (23.0%) patients, and no STAS were found in 157 (77.0%) patients. The receiver operating characteristic curve showed that radiomics model, clinical genomics model, and mixed model had good predictive performance (area under the curve [AUC] = 0.85; AUC = 0.70; AUC = 0.85). CONCLUSIONS: The prediction model based on radiomics and genomics features has a good prediction performance for STAS.
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As the depth of coal seam mining increases, coal and gas outburst prevention and control face unprecedented challenges. In recent years, freezing outburst prevention technology has received attention and been applied in industry; this method mainly improves the strength of the coal body while reducing its energy storage. Research has shown that due to the influence of moisture content, frost heaving occurs in coal bodies during the cooling process, weakening the coal bodies' strength. Therefore, it is necessary to explore the effect of the moisture content on the coal body frost heave. This paper uses a research method that combines laboratory experiments, theoretical analysis, and numerical simulation to study the critical moisture content of frost heaving in gas-containing coal. The results showed that the coal sample can be divided into three stages during the cooling process: the cold shrinkage stage, frost heave stage, and stabilization stage. When the moisture content is greater than 7%, as the moisture content increases, the amount of ice increases accordingly, which causes an increase in the frost heave deformation of the coal sample and produces an obvious frost heave effect. Utilizing COMSOL simulation software, the deformation of gas-containing coal samples at different moisture levels is simulated. By combining the results with laboratory measurements, the critical moisture content for the frost heave in gas-containing coal is determined to be 6.6%.
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OBJECTIVES: Sublobar resection has been shown to be feasible for non-small-cell lung cancers (NSCLC) <2 cm in size based on several prospective studies. However, the prognosis of clinical N0 patients who experience an N-stage upgrade after surgery [known as occult lymph node metastasis (OLM)] may be worse. The ability of predict OLM in patients eligible for sublobar resection remains a controversial issue. METHODS: Patients with NSCLC ≤2 cm in diameter and containing a solid component who underwent surgical treatment at the Affiliated Hospital of Qingdao University were retrospectively enrolled, and 1:1 case matching was performed. The risk factors were identified through logistic regression analyses and theoretical criteria, followed by the development of a nomogram that was evaluated using 200 iterations of 10-fold cross-validation. RESULTS: After case matching, 130 pairs of patients were selected for modelling. According to the multivariable logistic regression analysis, the carcinoembryonic antigen level, consolidation tumour ratio, mean computed tomography number and tumour margin were included in the nomogram. The cross-validated average area under the receiver operating characteristic curve was found to be 0.86. Furthermore, calibration curve and decision curve analyses demonstrated the excellent predictive accuracy and clinical utility of the nomogram respectively. CONCLUSIONS: By utilizing accessible characteristics, we developed a nomogram that predicts the probability of OLM in patients with NSCLC ≤2 cm with a solid component. Risk stratification with this nomogram could aid in surgical method decision-making. CLINICAL REGISTRATION NUMBER: Not applicable.
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Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC. A schematic diagram demonstrating the regulatory effect of GAS5 on immune cell infiltration by activating type I interferon signaling via MYBBP1A-p53/IRF1 axis in non-small cell lung cancer. IFN, interferon.
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Construction of complex molecular skeletons with ubiquitous chemical feedstocks in a single transformation is highly appealing in organic synthesis. We report a novel visible-light-induced three-component reaction for the construction of complex 2,4,5-trisubstituted oxazoles, which are valuable in medicinal chemistry, from simple and readily available iodonium-phosphonium hybrid ylides, carboxylic acids, and nitriles. This reaction features a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade, in which a photo-generated α-phosphonium carbene acts as a sequence trigger. This catalyst- and additive-free transformation exhibits high efficiency and broad substrate scope for synthesizing diverse oxazoles.
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The inherent linear dichroism (LD), high absorption, and solution processability of organic semiconductors hold immense potential to revolutionize polarized light detection. However, the disordered molecular packing inherent to polycrystalline thin films obscures their intrinsic diattenuation, resulting in diminished polarization sensitivity. In this study, we develop filter-free organic polarization-sensitive phototransistors (PSPs) with both a high linear dichroic ratio (LDR) and exceptional photosensitivity utilizing molecularly thin dithieno[3,2-b:2',3'-d]thiophene derivatives (DTT-8) two-dimensional molecular crystals (2DMCs) as the active layer. The orderly molecular packing in 2DMCs amplifies the inherent LD, and their molecular-scale thickness enables complete channel depletion, significantly reducing the dark current. As a result, PSPs with an impressive LDR of 3.15 and a photosensitivity reaching 3.02 × 106 are obtained. These findings present a practical demonstration of using the polarization angle as an encryption key in optical communication, showcasing the potential of 2DMCs as a viable and promising category of semiconductors for filter-free, polarization-sensitive photodetectors.
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Organic phototransistors (OPTs), as photosensitive organic field-effect transistors (OFETs), have gained significant attention due to their pivotal roles in imaging, optical communication, and night vision. However, their performance is fundamentally limited by the Boltzmann distribution of charge carriers, which constrains the average subthreshold swing (SSave) to a minimum of 60 mV/decade at room temperature. In this study, an innovative one-transistor-one-memristor (1T1R) architecture is proposed to overcome the Boltzmann limit in conventional OFETs. By replacing the source electrode in an OFET with a memristor, the 1T1R device exploits the memristor's sharp resistance state transitions to achieve an ultra-low SSave of 18 mV/decade. Consequently, the 1T1R devices demonstrate remarkable sensitivity to photo illumination, with a high specific detectivity of 3.9 × 109 cm W-1Hz1/2, outperforming conventional OPTs (4.9 × 104 cm W-1Hz1/2) by more than four orders of magnitude. The 1T1R architecture presents a potentially universal solution for overcoming the detrimental effects of "Boltzmann tyranny," setting the stage for the development of ultra-low SSave devices in various optoelectronic applications.
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Purpose: To investigate the effects of various intervention approaches on cancer-related fatigue (CRF) in patients with breast cancer. Method: Computer searches were conducted on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases from their establishment to June 2023. Selection was made using inclusion and exclusion criteria, and 77 articles were included to compare the effects of 12 interventions on patients with breast cancer. Results: Seventy-seven studies with 12 various interventions were examined. The network findings indicated that cognitive behavioral therapy (CBT) (SMD, -1.56; 95%CI, -3.08~-0.04), Chinese traditional exercises (CTE) (SMD, -0.85; 95%CI, -1.34~-0.36), aerobic exercise (AE) (SMD, -0.77; 95%CI, -1.09~-0.45), multimodal exercise (ME) (SMD, -0.75; 95%CI, -1.26~-0.25), music interventions (MI) (SMD, -0.74; 95%CI, -1.45~-0.03), and yoga (YG) (SMD, -0.44; 95%CI, -0.83 to -0.06) can reduce CRF more than the control group (CG). For relaxation exercises (RE) (MD, -6.69; 95%CI, -9.81~-3.57), MI (MD, -5.45; 95%CI, -7.98~-2.92), AE (MD, -4.34; 95%CI, -5.90~-2.78), ME (MD, -3.47; 95%CI, -4.95~-1.99), YG (MD, -2.07; 95%CI, -3.56~-0.57), and mindfulness training (MD, -1.68; 95%CI, -2.91~-0.46), PSQI improvement was superior to CG. In addition, for CTE (MD, 11.39; 95%CI, 4.11-18.66), YG (MD, 11.28; 95%CI, 1.63-20.93), and AE (MD, 9.34; 95%CI, 0.26~18.42), Functional Assessment of Cancer Therapy-Breast improvement was superior to CG. Conclusion: Cognitive behavioral therapy (CBT) is the most effective measure for alleviating CRF in patients with breast cancer and Relaxation exercises (RE) is the most effective measure for improving sleep quality. In addition, Chinese traditional exercises (CTE) is the best measure for enhancing quality of life. Additional randomized controlled trials (RCTs) are expected to further investigate the efficacy and mechanisms of these interventions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023471574.
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The relationship between plant diversity and the ecosystem carbon pool is important for understanding the role of biodiversity in regulating ecosystem functions. However, it is not clear how the relationship between plant diversity and soil carbon content changes under different grassland use patterns. In a 3-year study from 2013 to 2015, we investigated plant diversity and soil total carbon (TC) content of grasslands in northern China under different grassland utilization methods (grazing, mowing, and enclosure) and climatic conditions. Shannon-Wiener and Species richness index of grassland were significantly decreased by grazing and mowing. Plant diversity was positively correlated with annual precipitation (AP) and negatively correlated with annual mean temperature (AMT). AP was the primary regulator of plant diversity. Grazing and mowing decreased TC levels in grasslands compared with enclosures, especially in topsoil (0-20 cm). The average TC content was decreased by 58 % and 36 % in the 0-10 cm soil layer, while it was decreased by 68 % and 39 % in 10-20 cm soil layer. TC was positively correlated with AP and negatively correlated with AMT. Principal component analysis (PCA) showed that plant diversity was positively correlated with soil TC, and the correlation decreased with an increase in the soil depth. Overall, this study provides a theoretical basis for predicting soil carbon storage in grasslands under human disturbances and climate change impacts.
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Ecosistema , Pradera , Humanos , Biomasa , Suelo , China , Plantas , Carbono/análisisRESUMEN
Pore space is the main desorption space for methane in coal; to study the effect of changes in pore structure on the desorption hysteresis effect of methane in coal under high-temperature and high-pressure conditions, the coking coal from Pingdingshan Twelve Mine was taken as the research object, and the isothermal adsorption and desorption curves were obtained and quantitatively analyzed at different temperatures and pressures by the help of isothermal adsorption and desorption experiments, combined with the pressed mercury experiments and the low-temperature liquid nitrogen adsorption experiments to test the pore structure of the coal samples before and after the adsorption and desorption tests. The pore structure of coal samples before and after the adsorption and desorption tests was tested by combining the mercury pressure test and the low-temperature liquid nitrogen adsorption test, and the influence of the change in the pore structure of coal samples after the high-temperature and high-pressure adsorption and desorption tests on the hysteresis effect of methane desorption was studied. The results showed that under the same pressure, the pore volume of coal samples increased with the increase in temperature, the pore-specific surface area showed a tendency to decrease, and the fractal dimension could well characterize the relationship between the pore structure and the pore surface of coal, in which the fractal dimension of the pores in the large pore size section gradually increased with the increase of temperature, and the fractal dimension in the small pore size section gradually decreased; there was a good correlation between the pore structure of the coal samples after the high-temperature and high-pressure adsorption and desorption tests and the hysteresis coefficient of desorption. The structural characteristics of the coal samples after adsorption and desorption hysteresis coefficient at high temperature and high pressure showed good correlation, i.e., the pore volume, the fractal dimension of the large pore size section, and the desorption hysteresis effect were negatively correlated, while the specific surface area, the fractal dimension of the small pore size section, and the desorption hysteresis effect were positively correlated.
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Improving urban carbon emission efficiency (CEE) is vital to achieving the goal of urban carbon neutrality. However, the synergistic configurational effect of multiple influencing factors on CEE is not clear. Taking the Yangtze River Economic Belt (YREB) as an example, this paper adopts the standard deviation ellipse and Dagum Gini coefficient method to investigate the spatiotemporal differences in urban CEE in the YREB, and using the fuzzy-set qualitative comparative analysis (fsQCA) method, it explores the configurational effect of CEE influencing factors from the system perspective. The main conclusions are as follows: first, the overall level of urban CEE in the YREB is low, with a certain polarization phenomenon. Second, the relative differences in urban CEE in the YREB show a fluctuating upward trend, and the regional differences mainly originate from the overlapping part between regions. Finally, the main CEE influencing factors do not act in isolation, they constitute a complex process of synergistic interaction, with complementary substitution and causal asymmetry.
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Carbono , Ríos , Carbono/análisis , Desarrollo Económico , Eficiencia , China , CiudadesRESUMEN
Objectives: Several randomized controlled trials (RCTs) indicated that first-line programmed cell death protein-1/death-ligand 1 inhibitors plus chemotherapy (PD-1/PD-L1 + chemo) led to survival benefits in extensive-stage small-cell lung cancer (ES-SCLC) compared with platinum-based chemotherapy. This study aims to identify the optimal PD-1/PD-L1 + chemo combination strategy. Methods: We included RCTs comparing PD-1/ PD-L1 + chemo versus chemo alone in ES-SCLC. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ⩾3 treatment-related adverse events were considered. Odds ratios (ORs), hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Results: Six RCTs with 2600 patients were analyzed in this Bayesian network meta-analysis. Results showed that adding PD-1/PD-L1 inhibitors to chemotherapy led to significant benefits in OS (HR = 0.72, 95% CI: 0.66-0.79), PFS (HR = 0.69, 95% CI: 0.63-0.75), and ORR (OR = 1.32, 95% CI: 1.12-1.56), and no differences in toxicity were found (OR = 1.09, 95% CI: 0.92-1.30). Serplulimab plus chemotherapy was found to provide the best OS (HR = 0.63, 95% CI: 0.49-0.82), the best PFS (HR = 0.47, 95% CI: 0.38-0.59), and the best ORR (OR = 1.7, 95% CI: 1.15-2.53). Moreover, although there were no difference between PD-L1 + chemo and PD-1 + chemo regarding OS (HR = 0.99, 95% CI: 0.91-1.08) and ORR (OR = 1.27, 95% CI: 0.91-1.78), PD-1 + chemo showed a significant benefit in PFS (HR = 0.82, 95% CI: 0.68-0.98) compared with PD-L1 + chemo. Conclusions: Serplulimab plus chemotherapy seems to be superior first-line immunotherapy combination for patients with ES-SCLC. PD-1 + chemo seems to outperform PD-L1 + chemo in PFS.
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Grazing and climate change both contribute to diversity loss and productivity fluctuations. Sensitive climate conditions and long-term grazing activities have a profound influence on community change, particularly in high-altitude mountain grassland ecosystems. However, knowledge about the role of long-term continuous grazing management on diversity, productivity and the regulation mechanisms in fragile grassland ecosystems is still rudimentary. We conducted a long-term grazing experiment on an alpine typical steppe in the Qilian Mountains to assess effects of grazing intensity on soil, diversity, productivity and the regulation mechanisms. Plants and soil were sampled along grazing gradients at different distances from the pasture entrance (0, 0.3, 0.6, 0.9, 1.2 and 1.5 km) under the non-growing (WP) and the growing season grazing pasture (SAP). The results revealed that community diversity and biomass did not change significantly on a time scale, while the concentration of soil organic carbon and total phosphorus increased significantly. Heavy grazing (0-0.3 km) decreased community diversity and biomass. Grazing increased soil chemical properties in heavy grazed areas of WP, while the opposite was recorded in SAP. Soil chemical properties explained the largest variances in community diversity and community biomass. The prediction model indicates that grazing in WP mainly affects community diversity through soil chemical properties, and promotes a positive correlation between community diversity and community biomass; in SAP, the direct effect of grazing gradients on community diversity and biomass is the main pathway, but not eliminating the single positive relationship between diversity and biomass, which means that diversity can still be used as a potential resource to promote productivity improvement. Therefore, we should focus on the regulation of soil chemical properties in WP, such as the health and quality of soil, strengthening its ability to store water, sequester carbon and increase nutrients; focus on the management of livestock in SAP, including providing fertilizer and sowing to increase diversity and production in heavily grazed regions and reducing grazing pressure through regional rotational grazing. Ultimately, we call for strengthening the stability and sustainability of ecosystems through targeted and active human intervention in ecologically sensitive areas to cope with future grazing pressures and climate disturbances.