Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Diabetic Retinopathy Prediction by Ensemble Learning Based on Biochemical and Physical Data.

(1) Background: Diabetic retinopathy, one of the most serious complications of diabetes, is the primary cause of blindness in developed countries. Therefore, the prediction of diabetic retinopathy has a positive impact on its early detection and treatment. The prediction of diabetic retinopathy based on high-dimensional and small-sample-structured datasets (such as biochemical data and physical data) was the problem to be solved in this study. (2) Methods: This study proposed the XGB-Stacking model with the foundation of XGBoost and stacking. First, a wrapped feature selection algorithm, XGBIBS (Improved Backward Search Based on XGBoost), was used to reduce data feature redundancy and improve the effect of a single ensemble learning classifier. Second, in view of the slight limitation of a single classifier, a stacking model fusion method, Sel-Stacking (Select-Stacking), which keeps Label-Proba as the input matrix of meta-classifier and determines the optimal combination of learners by a global search, was used in the XGB-Stacking model. (3) Results: XGBIBS greatly improved the prediction accuracy and the feature reduction rate of a single classifier. Compared to a single classifier, the accuracy of the Sel-Stacking model was improved to varying degrees. Experiments proved that the prediction model of XGB-Stacking based on the XGBIBS algorithm and the Sel-Stacking method made effective predictions on diabetes retinopathy. (4) Conclusion: The XGB-Stacking prediction model of diabetic retinopathy based on biochemical and physical data had outstanding performance. This is highly significant to improve the screening efficiency of diabetes retinopathy and reduce the cost of diagnosis.

Pharmacokinetics, Bioavailability, and Tissue Distribution of the Kirsten Rat Sarcoma Inhibitor Adagrasib in Rats Using UPLC-MS/MS.

Purpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined. Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ±15%. The matrix effect and recovery were within ±15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration. Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.

Buried interface modification and light outcoupling strategy for efficient blue perovskite light-emitting diodes.

Perovskite light-emitting diodes (PeLEDs) exhibit remarkable potential in the field of displays and solid-state lighting. However, blue PeLEDs, a key element for practical applications, still lag behind their green and red counterparts, due to a combination of strong nonradiative recombination losses and unoptimized device structures. In this report, we propose a buried interface modification strategy to address these challenges by focusing on the bottom-hole transport layer (HTL) of the PeLEDs. On the one hand, a multifunctional molecule, aminoacetic acid hydrochloride (AACl), is introduced to modify the HTL/perovskite interface to regulate the perovskite crystallization. Experimental investigations and theoretical calculations demonstrate that AACl can effectively reduce the nonradiative recombination losses in bulk perovskites by suppressing the growth of low-n perovskite phases and also the losses at the bottom interface by passivating interfacial defects. On the other hand, a self-assembly nanomesh structure is ingeniously developed within the HTLs. This nanomesh structure is meticulously crafted through the blending of poly-(9,9-dioctyl-fluorene-co-N-(4-butyl phenyl) diphenylamine) and poly (n-vinyl carbazole), significantly enhancing the light outcoupling efficiency in PeLEDs. As a result, our blue PeLEDs achieve remarkable external quantum efficiencies, 20.4% at 487 nm and 12.5% at 470 nm, which are among the highest reported values. Our results offer valuable insights and effective methods for achieving high-performance blue PeLEDs.

Intermediate Phase Suppression with Long Chain Diammonium Alkane for High Performance Wide-Bandgap and Tandem Perovskite Solar Cells.

Wide bandgap (WBG) perovskite can construct tandem cells with narrow bandgap solar cells by adjusting the band gap to overcome the Shockley-Queisser limitation of single junction perovskite solar cells (PSCs). However, WBG perovskites still suffer from severe nonradiative carrier recombination and large open-circuit voltage loss. Here, this work uses an in situ photoluminescence (PL) measurement to monitor the intermediate phase evolution and crystallization process via blade coating. This work reports a strategy to fabricate efficient and stable WBG perovskite solar cells through doping a long carbon chain molecule octane-1,8-diamine dihydroiodide (ODADI). It is found that ODADI doping not only suppresses intermediate phases but also promote the crystallization of perovskite and passivate defects in blade coated 1.67 eV WBG FA0.7Cs0.25MA0.05Pb(I0.8Br0.2)3 perovskite films. As a result, the champion single junction inverted PSCs deliver the efficiencies of 22.06% and 19.63% for the active area of 0.07 and 1.02 cm2, respectively, which are the highest power conversion efficiencies (PCEs) in WBG PSCs by blade coating. The unencapsulated device demonstrates excellent stability in air, which maintains its initial efficiency at the maximum power points under constant AM 1.5G illumination in open air for nearly 500 h. The resulting semitransparent WBG device delivers a high PCE of 20.06%, and the 4-terminal all-perovskite tandem device delivers a PCE of 28.35%.

Customer knowledge management competence evaluation of agritourism enterprises by using the balanced scorecard and fuzzy-AHP: Evidence from Chengdu-Chongqing economic circle.

This paper provides an evaluation framework to explore the linking mechanisms between customer knowledge management competence (CKMC) and Balanced Scorecard (BSC). With a case study from Chengdu-Chongqing Economic Circle of China, this paper attempts to empirically justify the framework. An index system was established for evaluating CKMC based on BSC and knowledge management process, the weight design and consistency check of the indexes were implemented by using the analytic hierarchy process (AHP), and the overall evaluation value and concrete index scores at all levels were obtained via the fuzzy evaluation method. Empirical results show that CKMC performance measurement indicators were ranked in order of importance as Business process performance dimensions (0.465), System support dimensions (0.289), Customer communication dimensions (0.152) and Market performance dimension (0.094). It also shows that the overall score of CKMC was 3.404, reflecting that the CKMC was in a state of general satisfaction. This research also identifies key factors hindering implementation of CKMC, including Attention from senior leaders (2.871), customer knowledge sharing efficiency (2.928), and information technology level (3.133). This research could contribute to CKM theory by extending customer knowledge management competence research with BSC initiatively. For practitioners, this study may provide useful suggestions to identify key factors promoting business CKMC, and finally promotes sustainable development of Agritourism.

A generic lanthanum doping strategy enabling efficient lead halide perovskite luminescence for backlights.

Metal halide perovskites films have attracted great interest because of their solution-proceed fabrication and potential applications for next-generation displays. However, their non-ideal photoluminescence quantum efficiency (PLQE) and stability still does not meet the requirements of displays. Here, we adopt lanthanum ion (La3+) doping strategy to enhance its luminescence performance and the possibility of taking it to commercialization. In addition to the entry of lanthanum ions into the lattice to greatly improve the crystal quality, the excess La3+ gives rise to the formation of newly developed formamidinium cesium lanthanum bromine, (FA, Cs)2LaBr5, which provides additional energy transport pathways, therefore concentrating more energy onto the perovskite host. Consequently, a near-unity PLQE of 99.5% is realized in standardized green-emission cesium (Cs)/formamidinium (FA) mixed FA0.7Cs0.3PbBr3 perovskite films. The introduction of La3+ can also lead to markedly stability with nearly 1000 days' shelf storage half-lifetime and 400 hours' light-irradiation T90 lifetime as well as much-enhanced color purity. Moreover, the films with La3+ doping enable full-visible spectral enhancement and high-performance white light emission and trichromatic luminescence with 98.9% coverage of the color gamut area required for the Rec. 2020 standard, which suggest that perovskite films have great application potential for backlights in liquid crystal display technologies.

A Multifunctional Additive Strategy Enables Efficient Pure-Blue Perovskite Light-Emitting Diodes.

Lead halide perovskites have shown exceptional performance in light-emitting devices (PeLEDs), particularly in producing significant electroluminescence in sky-blue to near-infrared wavelengths. However, PeLEDs emitting pure-blue light at 465-475 nm are still not satisfactory. Herein, efficient and stable pure-blue PeLEDs are reported by controlling phase distribution, passivation of defects, as well as surface modifications using multifunctional phenylethylammonium trifluoroacetate (PEATFA) in reduced-dimensional p-F-PEA2 Csn-1 Pbn (Br0.55 Cl0.45 )3n+1 polycrystalline perovskite films. Compared with 4-fluorophenylethylammonium (p-F-PEA+ ) in the pristine films, phenylethylammonium (PEA+ ) has lower adsorption energy while interacting with perovskites, resulting in large-n low-dimensional perovskites, which can greatly facilitate charge transport within the low-dimensional perovskite films. The interaction between the CO group in trifluoroacetate (TFA- ) and perovskites significantly reduces defects in the perovskite films. Additionally, the electron-giving CF3 group in TFA- uplifts surface potential in the films, resulting in smooth electronic injection in devices. The multifunctional additive strategy leads to elevated radiative recombination and efficient carrier transport in the films and devices. As a result, the devices exhibit a maximum external quantum efficiency (EQE) of 11.87% at 468 nm with stable spectral output, the highest reported to date for pure-blue PeLEDs. Thus, this study extends the way for high-efficiency pure-blue LED with perovskite polycrystal films.

Do urban tourists prefer vegetarianism? An urban-rural comparison of vegetarian consumption in China.

The adoption of a vegetarian diet might have public health and environmental benefits. However, little is known about urban and rural Generation Z tourists' attitudes toward vegetarianism or vegetarian consumption within the Chinese urban and rural settings. Hence, to address this gap, the present study adopted a sequential and mixed research approach based on a survey (n = 212) and laddering interviews (n = 20) to validate post-millennial tourists' motives for adopting a vegetarian diet. The results identified the top four motives as environmental protection and resource conservation, ethical consideration, personal taste and choice, and personal healthcare issues. The top four barriers to vegetarianism were unavailability and limited choice, peer pressure, traditional prejudice/habit, and the inability to change. The results also demonstrated that both rural and urban tourists adopt vegetarianism mainly for environmental protection and ethical consideration, a subtle difference between them is that urban vegetarians emphasized ethical considerations more but rural ones emphasized food and variety. Urban consumers considered unavailability and limited choice as the topmost barriers to being vegetarian, while rural vegetarians found traditional prejudice to be restricting. Due to traditional dietary habits and peer influence, rural tourists face many more challenges when adopting a vegetarian diet. Understanding the perceived benefits and barriers to being vegetarian in different regions will not only enrich the theory of food nutrition but also expand Generation Z tourists' consumption behavior and practices.

Influence of Interpersonal and Institutional Trust on the Participation Willingness of Farmers in E-Commerce Poverty Alleviation.

To explore the influence of interpersonal trust and institutional trust on the participation willingness of farmers in e-commerce poverty alleviation in China, a questionnaire survey of 320 farmers in Chongqing Ecological Tourism District was adopted for data collection, and a binary logistic model was used for data analysis. The results showed that (1) both interpersonal trust and institutional trust had a positive influence on the participation behavior of farmers in e-commerce poverty alleviation, and the priority ranking from high to low was: trust in government, trust in relatives, trust in neighbors, and trust in village cadres. (2) Institutional trust had a greater impact on the participation behavior of farmers than interpersonal trust, especially in the poverty-stricken areas where economic development was relatively backward. (3) Individual attributes, household attributes, and rural resource attributes had a significant positive impact on the participation intention of farmers. Among these, the role of rural e-business service platform was particularly important. The role of institutional trust at the village level still did not perform well in promoting the participation willingness of farmers. Based on empirical analysis, the suggestions for promoting the active cooperation of farmers and participating in the cooperation of e-business were put forward, such as enhancing the interpersonal network of farmers, improving the rural e-commerce information service platform, and strengthening the construction of the rural business environment.

Environmental safety evaluation of geopark based on CPTED concept and fuzzy comprehensive analysis.

In recent years, with the increasingly popular and openness of Geoparks, Environmental safety has become a major concern for sustainable geo-tourism. It is therefore necessary to conduct an environmental safety performance evaluation for promoting geo-tourism development. In order to identify and figure out the factors influencing the tourists' environmental safety perception, an index system was established based on six principles of Crime Prevention Through environment design (CPTED) theory. A Questionnaire was adopted for data collection, and the overall evaluation value and concrete index scores at all levels were obtained via the fuzzy comprehensive analysis and Importance-Performance analysis. Empirical results show that: (1) tourists' perception of environmental safety performance in Shilin Park from high to low was: image and maintenance, Natural Surveillance, territoriality, Access control, Activity support and target hardening; (2) The sub-factors influencing tourists' safety perception mostly include electronic monitoring device, Lighting system, Public safety management, Road layout, environmental sanitation; While attention should be paid on the following aspects including park service center, inter-personal surveillance, surrounding environment, unobstructed view, parking lot, Signpost, for they are considered as high-importance items with relatively poor performance. Based on the analysis, three optimization measures were proposed, including optimizing the layout and design of each space, strengthening the deterrent force of the park and maintaining a good environmental image. This research provides useful suggestions for Geopark decision-makers on determining the priority of Geopark spatial planning and management, as well as achieving the optimal allocation of resources to promote the sustainable development of Geopark.