Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study.

BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

Quantifying the supply-demand relationship of ecosystem services to identify ecological management zoning: A case study in mountainous areas of northwest Yunnan, China.

Establishing ecological management zones based on the supply-demand relationship of ecosystem services (ESs) is essential for fostering sustainable development within social-ecological systems and improving human well-being. In this study, the spatial pattern between supply and demand in five ESs (grain production (GP), carbon sequestration (CS), soil conservation (SC), water conservation (WC), and habitat quality (HQ)) is analyzed using the ESs supply-demand ratio (ESDR) method, the spatial autocorrelation method, and the coupled coordination degree model. Zoning is performed according to the differences in their spatial combinations, and differential zoning management policies are proposed. The following results were obtained: (1) In terms of the ESDR, except for a slight increase in GP surplus from 2010 to 2020, there is a decline in the surplus of the other four ESs. (2) CS, WC, and HQ are dominated by cluster types LH and HL. GP and SC are dominated by cluster types HH and LL. The average value of the coupling coordination degree (CCD) of comprehensive ESs supply and demand show five types: moderate disharmony, slight disharmony, near disharmony, basic coordination, and slight coordination. (3) Based on the multiple spatial heterogeneity of ESs supply and demand, differentiated ecological management strategies are proposed at the grid scale. Overall, this study discover the spatial pattern of mismatch between the supply and demand of ecosystem services (ESs) in mountainous urban areas. This contribution enhances the discourse surrounding sustainable development theory and advances research on the coupling of social-ecological systems. Furthermore, it offers valuable insights for the formulation of sustainable ecological management policies tailored to mountainous urban settings.

Direct and indirect effects of father-child attachment on academic burnout in college students.

The study aims to investigate the multiple mediating roles of core self-evaluation and sense of school belonging in the relationship between father-child attachment and academic burnout in college students. A sample of 418 college students completed the father-child attachment scale, the scale of sense of school belonging, core self-evaluation scale, and academic burnout scale. After controlling for variables such as mother-child attachment, gender, age, and grade, the results showed: (1) father-child attachment was significantly and negatively correlated with academic burnout, and positively correlated with core self-evaluation and sense of school belonging; both core self-evaluation and sense of school belonging were significantly and negatively correlated with academic burnout. (2) The multiple mediating model of father-child attachment influencing academic burnout in college students was established. Both core self-evaluation and sense of school belonging played a partial mediating role between father-child attachment and academic burnout. The direct effect of father-child attachment on academic burnout accounts for 33.3% of the total effect. The indirect effects of core self-evaluation and sense of school belonging between father-child attachment and academic burnout account for 50.0 and 16.7% of the total effect, respectively. These findings identify the internal mechanisms through which father-child attachment affects academic burnout in college students from personal traits and interpersonal perspectives.

The asymmetric effects of climate risk on higher-moment connectedness among carbon, energy and metals markets.

Climate change affects price fluctuations in the carbon, energy and metals markets through physical and transition risks. Climate physical risk is mainly caused by extreme weather, natural disasters and other events caused by climate change, whereas climate transition risk mainly results from the gradual switchover to a low-carbon economy. Given that the connectedness between financial markets may be affected by various factors such as extreme events and economic transformation, understanding the different roles of climate physical risk and transition risk on the higher-moment connectedness across markets has important implications for investors to construct portfolios and regulators to establish regulation system. Here, using the GJRSK model, time-frequency connectedness framework and quantile-on-quantile method, we show asymmetric effects of climate risk on connectedness among carbon, energy and metals markets, with higher impacts of climate physical risk on upward risk spillovers, and greater effects of climate transition risk on the downside risk of kurtosis connectedness.

Effects of adverse childhood health experiences on cognitive function in Chinese middle-aged and older adults: mediating role of depression.

BACKGROUND: Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied. METHODS: Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel's test and Baron and Kenny's causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach. RESULTS: In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (ß=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (ß=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (ß=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction. CONCLUSION: The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.

The effect of childhood social isolation on behavioral cognition in Chinese middle-aged and older adults: The moderating effect of family support.

INTRODUCTION: This study aimed to analyze the association of childhood social isolation and behavioral cognition, and moderating effect of family support in middle-aged and older adults. METHODS: The study samples were from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. The dependent variable was behavioral cognitive ability, measured by episodic memory and mental state; The independent variable was childhood social isolation, and the moderating variable was family support. The baseline OLS regression model was used to explore the correlation among independent variables, dependent variables and moderating variables, the least square regression model was used to analyze the moderating effect of family support, and the replacement model and the method of replacing characteristic variables were used for the robustness test. Hierarchical regression heterogeneity analysis was performed to further verify the results of the moderating effect. RESULTS: In this study, 3459 samples were selected for analysis. OLS baseline regression results showed that the deepening of childhood social isolation was significantly correlated with the decline of behavioral cognitive ability in middle-aged and elderly people (ß=-0.9664, t = 0.0893). After adding all covariates, we found that childhood social isolation was significantly negatively correlated with behavioral cognitive ability in middle-aged and elderly people (ß=-0.4118, t = 0.0785). Among the moderating variables of family support, we found that there is a moderating effect on female guardians' efforts of caring in early parental support (ß=0.0948, t = 0.0320) and the frequency of children's visits in late children support (ß=0.0073, t = 0.0036). Finally, through the heterogeneity test, we found that there were differences in the relationship between childhood social isolation and behavioral cognitive ability among middle-aged and elderly people of different ages, genders and places of residence. Moreover, there are significant differences in the moderating effect of female guardian's effort of caring and the frequency of children's visits in heterogeneous groups. CONCLUSIONS: The greater the degree of childhood social isolation experienced by middle-aged and elderly people, the worse their behavioral cognitive ability. Female guardian's effort of caring and the frequency of children's visits have a moderating effect to suppress this negative effect.

How does the fiscal pressure of local governments affect China's PM2.5 emissions?

Affected by the epidemic and other factors, the global economy is in a downturn, and countries around the world are under unprecedented debt pressure. How will this affect environmental protection? Taking China as an example, this paper empirically studies the impact of changes in local government behavior on urban air quality under fiscal pressure. This paper uses the generalized method of moments (GMM) to find that fiscal pressure has significantly reduced PM2.5 emissions, with a unit increase in fiscal pressure will increase PM2.5 by about 2%. The mechanism verification shows that three channels affect PM2.5 emissions: (1) fiscal pressure has prompted local governments to relax the supervision of existing pollution-intensive enterprises. (2) Local governments reduce environmental regulations for attracting more pollution-intensive enterprises. (3) Local governments tend to reduce environmental protection investment to save fiscal expenses. The paper's conclusions provide new policy ideas for promoting environmental protection in China, as well as served as a case for analyzing current changes in environmental protection in other countries.

The correlation analysis of WeChat usage and depression among the middle-aged and elderly in China: the mediating role of social participation.

BACKGROUND: We aimed to explore the association between WeChat usage and depression in the Chinese middle-aged and elderly and the role of social participation. METHODS: Data were obtained from China Health and Retirement Longitudinal Study (CHARLS) of 2018. The dependent variable was depressive symptoms, measured with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). We used the propensity score matching (PSM) to match the WeChat users with the non-WeChat users. Correlations between WeChat usage and depressive symptoms were verified by using logistic regression and linear regression, and the mediating role of social participation was verified by using stepwise regression and KHB method. RESULTS: Four thousand five hundred forty-five samples were ultimately matched for analysis in this study. After including all control variables, results of logistic regression showed that WeChat usage was significantly associated with a lower prevalence of depression (aOR:0.701,95% CI: 0.605-0.812). And the results of linear regression showed that WeChat usage was associated with lower levels of depression which was significant (p < 0.001). The results of the stepwise regression and the KHB method showed a mediating role of social participation in WeChat usage and depressive symptoms. Among the four types of social participation, the mediating effect of recreational activities was significant, while the mediating effects of voluntary activities, cultural activities, and other activities were not significant. Meanwhile, the effect of WeChat usage on depression and the mediating effect of social participation were heterogeneous because of differences in age and gender. CONCLUSION: Social participation partly mediated the effect between WeChat usage and depression in middle-aged and older adults. Among the four types of social participation, only recreational activities had a mediating effect. Encouraging more active social participation and other types of social activities should be considered to improve the mental health of the middle-aged and older adults in China through social media usage.

Cerium-Doped Indium Oxide as a Top Electrode of Semitransparent Perovskite Solar Cells.

Semitransparent perovskite solar cells (ST-PSCs) play a very important role in high-efficiency tandem solar cells and building integrated photovoltaics (BIPV). One of the main challenges for high-performance ST-PSCs is to obtain suitable top-transparent electrodes by appropriate methods. Transparent conductive oxide (TCO) films, as the most widely used transparent electrodes, are also adopted in ST-PSCs. However, the possible ion bombardment damage during the TCO deposition and the relatively high postannealing temperature usually required for high-quality TCO films is not conducive to improving the performance of the perovskite solar cells with low ion bombardment and temperature tolerances. Herein, cerium-doped indium oxide (ICO) thin films are prepared by reactive plasma deposition (RPD) at substrate temperatures below 60 °C. A high carrier mobility of 50.26 cm2 V-1 s-1, a low resistivity of 7.18 × 10-4 Ω·cm, and an average transmittance of 86.53% in the wavelength range of 400-800 nm and 87.37% in the wavelength range of 800-1200 nm are achieved. The RPD-prepared ICO film is used as a transparent electrode on top of the ST-PSCs (band gap ∼1.68 eV), and photovoltaic conversion efficiency (PCE) of 18.96% is achieved on the champion device.

The global economic policy uncertainty spillover analysis: In the background of COVID-19 pandemic.

Combining the spillover index approach and LASSO-VAR method, we construct the spillover network of 19 specific countries' economic policy uncertainty (EPU). Then we deconstruct the constructed network into four blocks by the block models, the impacts of COVID-19 on EPU spillover effects between each country and blocks is analyzed gradually. The results reveal that: (1) The transnational contagion of EPU is significant, and the spillover network of policy uncertainty is time-varying. (2) EPU networks can be divided into four different blocks by block models. The role of blocks and the spatial spillover transmission path between blocks are different in different periods. (3) The new infection cases and deaths of COVID-19 have a significant effect on reception and transmission directional EPU spillovers, while there is no significant impact on net spillovers. The international movement restrictions during the period of COVID-19 significantly increase the directional and net EPU spillovers. Our findings have some implications for policy-makers and market regulators in the context of the COVID-19 pandemic.

Cellular Uptake and Transport Characteristics of FL118 Derivatives in Caco-2 Cell Monolayers.

In the evaluation of the druggability of candidate compounds, it was vital to predict the oral bioavailability of compounds from apparent permeability (Papp) across Caco-2 cell-culture model of intestinal epithelium cultured on commercial transwell plate inserts. The study was to investigate the transport characteristics and permeability of FL118 (10, 11-Methylenedioxy-20(S)-camptothecin) derivatives 7-Q6 (7-(4-Ethylphenyl)-10, 11-methylenedioxy-20(S)-camptothecin) and 7-Q20 (7-(4-Trifluoromethylphenyl)-10, 11-methylenedioxy-20(S)-camptothecin). Transport characteristics and permeability of the tested compounds to the small intestine were assessed at different concentrations (0.5, 1 µM) via Caco-2 cell monolayers model in vitro. Uptake studies based on Caco-2 cells, including temperatures, concentrations, and the influence of efflux transporters, were combined to confirm the transport characteristics of the tested compounds. Furthermore, cytotoxicity results showed that the concentrations used in the experiments were non-toxic and harmless to cells. In addition, The Papp of 7-Q6 was (3.69 ± 1.07) × 10-6 cm/s with efflux ratio (ER) 0.98, while the Papp of 7-Q20 was (7.78 ± 0.89) × 10-6 cm/s with ER 1.05 for apical-to-basolateral (AP→BL) at 0.5 µM, suggesting that 7-Q20 might possess higher oral bioavailability in vivo. Furthermore, P-glycoprotein (P-gp) was proved to slightly affect the accumulations of 7-Q20, while the absorption of 7-Q6 was irrelevant with P-gp and breast cancer resistant protein (BCRP) based on the cellular uptake assays. Accordingly, 7-Q6 was completely absorbed by passive diffusion, and 7-Q20 was mainly dependent on passive diffusion with being effluxed by P-gp slightly. Meanwhile, both 7-Q6 and 7-Q20 were potential antitumor drugs that might exhibit high oral bioavailability in the body.

The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus.

BACKGROUND: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. METHODS: Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. RESULTS: The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. CONCLUSION: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

Entrepreneurial Passion Psychology- Based Influencing Factors of New Venture Performance.

Small and medium-sized enterprises have been the driving force of social economy. As the social formation and the rise of many emerging economies, the domestic economic environment changes dramatically, which makes small and medium-sized enterprises face severe challenges. In the face of the fierce competition environment, how to improve the performance of entrepreneurship and gain competitive advantage is a very important topic in the practical management of entrepreneurs. This exploration is carried out with the entrepreneurial passion and risk taking as the antecedent variable, entrepreneurial performance as the outcome variable, and then work engagement as the mediator. With the entrepreneurs of small and medium-sized enterprises as the research object, questionnaire method is used to carry out empirical research. The empirical analysis results show that entrepreneurial passion has a significant positive impact on work engagement; risk taking has a significant positive impact on work engagement; work engagement has a significant positive impact on entrepreneurship performance; in addition, work participation plays a mediating role in the process of entrepreneurial passion and risk taking. The results provide academic and practical implications for entrepreneurs.

Solution Processed Organic/Silicon Nanowires Hybrid Heterojunction Solar Cells Using Organosilane Incorporated Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) as Hole Transport Layers.

Hybrid heterojunction solar cells (HHSCs) using crystalline Si nanowires (SiNWs) as the absorber and conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the hole-selective transport layer (HTL) show great potential in both low-cost and high-power conversion efficiency (PCE). However, due to the poor wettability of the PEDOT:PSS solution on SiNWs, conformal coverage of PEDOT:PSS on SiNWs is not easy to achieve. Here, an effective method was developed to decrease the surface tension of the PEDOT:PSS and increase the wettability between PEDOT:PSS and SiNWs by incorporating organosilane into the PEDOT:PSS solution. Two kinds of organosilanes including tetramethoxysilane (TMOS) and vinyltrimethoxysilane (VTMO) were selected as the additives. The surface passivation quality of the SiNWs was dramatically enhanced. The HHSCs utilizing VTMO as the additive show a higher open circuit voltage and higher PCE compared with the TMOS adding ones. By spin-coating Ag nanowires onto the PEDOT:PSS HTL layer and using spin-coated phenyl-C61-butyric acid methyl ester as the electron-selective transport layer, a champion PCE up to 18.12% and a fill factor of 80.1% have been achieved on the full solution processed PEDOT:PSS/n-type SiNWs HHSCs. The findings provide a simple and promising method to achieve high-performance PEDOT:PSS/SiNWs HHSCs.

Liver injury in septic mice were suppressed by a camptothecin-bile acid conjugate via inhibiting NF-κB signaling pathway.

BACKGROUND AND OBJECTIVES: Sepsis is a life-threatening organ dysfunction syndrome arising from uncontrolled inflammatory responses. Liver injury is a crucial factor for the prognosis of sepsis. Camptothecins (CPTs) have been reported to suppress the inflammatory response induced by sepsis. G2, a CPT-bile acid conjugate, has been demonstrated the property of liver targeting in our previous research. This study aimed to research the effects of G2 on liver injury induced by cecal ligation and puncture (CLP). METHODS: C57BL/6 mice were subjected to CLP surgery, and effects of G2 on liver damage and survival rates of CLP-induced mice were evaluated. To detect the related markers of hepatic injury or neutrophil infiltration, inflammatory cytokines and protein levels, hematoxylin-eosin staining assay, corresponding Detection Kits assay, ELISA and Western blot analysis were performed. RESULTS: Intraperitoneal administration of G2 reduced liver injury and enhanced the survival rates in mice with sepsis. Treatment with G2 decreased the levels of hepatic injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of mice induced by CLP. The hepatic level of neutrophil infiltration marker myeloperoxidase (MPO) was reduced in G2 administration group. And the levels of serum inflammatory cytokines, including Tumor Necrosis Factor-α (TNFα), Interleukin-6 (IL-6) and IL-1ß, were decreased by G2. Furthermore, the results of Western blot analysis indicated that G2 suppressed the up-regulation of NF-κB p-P65 and p-IκBα. It suggested that G2 suppressed the activation of NF-κB signaling pathway. CONCLUSION: G2 alleviated sepsis-induced liver injury via inhibiting the NF-κB signaling pathway.

Transporter-Targeted Bile Acid-Camptothecin Conjugate for Improved Oral Absorption.

Camptothecin (CPT), a natural alkaloid, possesses potent anticancer activity. However, its application was terminated due to its low bioavailability and high toxicity. This work evaluated the potential of deoxycholic acid-CPT conjugate (G2) to improve the oral absorption of CPT. Deoxycholic acid significantly reduced cytotoxicity and inhibited the uptake of G2, in vitro. And G2 showed sodium-dependent uptake. In addition, in vivo study in rats indicated that the oral bioavailability of G2 was 2.06-fold higher than that of CPT. The present study suggested that using bile acid as the conjugated moiety is a hopeful strategy to improve the oral bioavailability of CPT.

Measles Virus Forms Inclusion Bodies with Properties of Liquid Organelles.

Nonsegmented negative-strand RNA viruses, including measles virus (MeV), a member of the Paramyxoviridae family, are assumed to replicate in cytoplasmic inclusion bodies. These cytoplasmic viral factories are not membrane bound, and they serve to concentrate the viral RNA replication machinery. Although inclusion bodies are a prominent feature in MeV-infected cells, their biogenesis and regulation are not well understood. Here, we show that infection with MeV triggers inclusion body formation via liquid-liquid phase separation (LLPS), a process underlying the formation of membraneless organelles. We find that the viral nucleoprotein (N) and phosphoprotein (P) are sufficient to trigger MeV phase separation, with the C-terminal domains of the viral N and P proteins playing a critical role in the phase transition. We provide evidence suggesting that the phosphorylation of P and dynein-mediated transport facilitate the growth of these organelles, implying that they may have key regulatory roles in the biophysical assembly process. In addition, our findings support the notion that these inclusions change from liquid to gel-like structures as a function of time after infection, leaving open the intriguing possibility that the dynamics of these organelles can be tuned during infection to optimally suit the changing needs during the viral replication cycle. Our study provides novel insight into the process of formation of viral inclusion factories, and taken together with earlier studies, suggests that Mononegavirales have broadly evolved to utilize LLPS as a common strategy to assemble cytoplasmic replication factories in infected cells.IMPORTANCE Measles virus remains a pathogen of significant global concern. Despite an effective vaccine, outbreaks continue to occur, and globally ∼100,000 measles-related deaths are seen annually. Understanding the molecular basis of virus-host interactions that impact the efficiency of virus replication is essential for the further development of prophylactic and therapeutic strategies. Measles virus replication occurs in the cytoplasm in association with discrete bodies, though little is known of the nature of the inclusion body structures. We recently established that the cellular protein WD repeat-containing protein 5 (WDR5) enhances MeV growth and is enriched in cytoplasmic viral inclusion bodies that include viral proteins responsible for RNA replication. Here, we show that MeV N and P proteins are sufficient to trigger the formation of WDR5-containing inclusion bodies, that these structures display properties characteristic of phase-separated liquid organelles, and that P phosphorylation together with the host dynein motor affect the efficiency of the liquid-liquid phase separation process.

Uptake and efflux of FL118 and two FL118 derivatives in 3D cell model.

Drug uptake and efflux are two of the critical factors required in order to be able to define drug efficacy. This study aims to investigate cytotoxicity and uptake mechanisms of two FL118 analogues (7-Q20 and val-FL118) in parallel with FL118 in three-dimensional multi-cellular spheroids model. The influence of compound concentration, time, temperature, cell lines, and the inhibitors of P-gp, BCRP and LAT1 on drug uptake and efflux were investigated. In vitro cytotoxicity studies revealed that FL118, 7-Q20 and val-FL118 exhibited sensitive cytotoxicity to the HCT-116 cell line and the water-soluble compound 7-Q20 showed the lowest IC50. Cellular uptake and efflux of FL118 was independent of efflux pump proteins. Uptake and efflux of 7-Q20 were affected by P-gp, which was one of reasons that caused a lower uptake at 37 °C than at 4 °C. The carrier protein LAT1 played a role in the cellular intakes of val-FL118. These findings provided basic information for FL118 and the two novel FL118 derivatives for further development.

A divergent strategy to synthesize gabosines featuring a switchable two-way aldol cyclization.

Gabosines and their natural analogues, belonging to C7 carbasugars, have attracted great attention in synthesis due to their rich structural variety and promising biological activities. A new diversity-oriented approach for the gabosine-type carbasugars based on a tunable regioselective aldol cyclization of flexible precursor 2 is explored. Two cyclization modes (A and B) of the precursor can be well controlled by switching promoters to selectively produce two resulting cyclohexa(e)nones 3 and 10, both of which are versatile intermediates for various C7 carbasugars. After the conversion of 3 to eight natural carbasugars, the utility of intermediate 10 is illustrated by the first synthesis of (-)-gabosine L, as well as the new synthesis of (-)-gabosine A, (-)-gabosine B, (-)-gabosine N and (-)-gabosine O. The chemical structure and the absolute configuration of (-)-gabosine L are confirmed by its total synthesis.

Solvent-controlled growth of inorganic perovskite films in dry environment for efficient and stable solar cells.

Inorganic halide perovskites such as cesium lead halide are promising due to their excellent thermal stability. Cesium lead iodide (CsPbI3) has a bandgap of 1.73 eV and is very suitable for making efficient tandem solar cells, either with low-bandgap perovskite or silicon. However, the phase instability of CsPbI3 is hindering the further optimization of device performance. Here, we show that high quality and stable α-phase CsPbI3 film is obtained via solvent-controlled growth of the precursor film in a dry environment. A 15.7% power conversion efficiency of CsPbI3 solar cells is achieved, which is the highest efficiency reported for inorganic perovskite solar cells up to now. And more importantly, the devices can tolerate continuous light soaking for more than 500 h without efficiency drop.