Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72 ± 93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

C-phycocyanin improves the developmental potential of cryopreserved human oocytes by minimizing ROS production and cell apoptosis.

PURPOSE: The cryopreservation process damages oocytes and impairs development potential. As a potent antioxidant, C-phycocyanin (PC) regulates reproductive performance. However, its beneficial effects on vitrified human oocytes remain unknown. METHODS: In this study, human GV-stage oocytes obtained from controlled ovarian hyperstimulation (COH) cycles were randomly allocated to three groups: fresh oocyte without freezing (F group), vitrification in medium supplemented with PC (P group), and vitrification in medium without PC as control group (C group). After warming, viable oocytes underwent in vitro maturation. RESULTS: Our results showed that 3 µg/mL PC treatment increased the oocyte maturation rate after cryopreservation. We also found that PC treatment maintains the regular morphological features of oocytes. After PC treatment, confocal fluorescence staining showed a significant increase in the mitochondrial membrane potential of the vitrified oocytes, along with a notable decrease in intracellular reactive oxygen species and the early apoptosis rate. Finally, after in vitro maturation and parthenogenetic activation, vitrified oocytes had a higher potential for cleavage and blastocyst formation after PC treatment. CONCLUSION: Our results suggest that PC improves the developmental potential of cryopreserved human GV-stage oocytes by attenuating oxidative stress and early apoptosis and increasing the mitochondrial membrane potential.

C-Phycocyanin improves the quality of goat oocytes after in vitro maturation and vitrification.

In vitro maturation (IVM) and cryopreservation of goat oocytes are important for establishing a valuable genetic bank for domesticated female animals and improving livestock reproductive efficiency. C-Phycocyanin (PC) is a Spirulina extract with antioxidant, antiinflammatory, and radical scavenging properties. However, whether PC has positive effect on goat oocytes IVM or developmental competence after vitrification is still unknown. In this study, we found that first polar body extrusion (n = 293), cumulus expansion index (n = 269), and parthenogenetic blastocyst formation (n = 281) were facilitated by adding 30 µg/mL PC to the oocyte maturation medium when compared with the control groups and that supplemented with 3, 10, 100 or 300 µg/mL PC (P < 0.05). Although PC supplementation did not affect spindle formation or chromosome alignment (n = 115), it facilitated or improved cortical granules migration (n = 46, P < 0.05), mitochondria distribution (n = 39, P < 0.05), and mitochondrial membrane potential (n = 46, P < 10-4). Meanwhile, supplementation with 30 µg/mL PC in the maturation medium could significantly inhibit the reactive oxygen species accumulation (n = 65, P < 10-4), and cell apoptosis (n = 42, P < 0.05). In addition, PC increased the oocyte mRNA levels of GPX4 (P < 0.01), and decreased the mRNA and protein levels of BAX (P < 0.01). Next, we investigated the effect of PC supplementation in the vitrification solution on oocyte cryopreservation. When compared with the those equilibrate in the vitrification solution without PC, recovered oocytes in the 30 µg/mL PC group showed higher ratios of normal morphology (n = 85, P < 0.05), survival (n = 85, P < 0.05), first polar body extrusion (n = 62, P < 0.05), and parthenogenetic blastocyst formation (n = 107, P < 0.05). Meanwhile, PC supplementation of the vitrification solution increased oocyte mitochondrial membrane potential (n = 53, P < 0.05), decreased the reactive oxygen species accumulation (n = 73, P < 0.05), promoted mitochondria distribution (n = 58, P < 0.05), and inhibited apoptosis (n = 46, P < 10-3). Collectively, our findings suggest that PC improves goat oocyte IVM and vitrification by reducing oxidative stress and early apoptosis, which providing a novel strategy for livestock gamete preservation and utilization.

Absolute Configuration of 12S-Deoxynortryptoquivaline from Ascidian-Derived Fungus Aspergillus clavatus Determined by Anisotropic NMR and Chiroptical Spectroscopy.

Tryptoquivalines are highly toxic metabolites initially isolated from the fungus Aspergillus clavatus. The relative and absolute configuration of tryptoquivaline derivates was primarily established by comparison of the chemical shifts, NOE data, and ECD calculations. A de novo determination of the complete relative configuration using NMR spectroscopy was challenging due to multiple spatially separated stereocenters, including one nonprotonated carbon. In this study, we isolated a new tryptoquivaline derivative, 12S-deoxynortryptoquivaline (1), from the marine ascidian-derived fungus Aspergillus clavatus AS-107. The correct assignment of the relative configuration of 1 was accomplished using anisotropic NMR spectroscopy, while the absolute configuration was determined by comparing calculated and experimental ECD spectra. This case study highlights the effectiveness of anisotropic NMR parameters over isotropic NMR parameters in determining the relative configuration of complex natural products without the need for crystallization.

[Research Progress on Distribution, Transportation, and Control of Per- and Polyfluoroalkyl Substances in Chinese Soils].

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that have attracted much attention in recent years, which has the characteristics of diverse species, refractory degradation, long-distance transportation, easy bioaccumulation, etc. The distribution, accumulation, and potential toxicity of PFAS in water and organisms have received extensive attention worldwide. However, studies on PFAS distribution and transportation in soil are still hovering at a preliminary stage. The PFAS pollution surveys in Chinese soils are mainly concentrated in the economically developed eastern regions. The types and concentrations of PFAS in soils are directly related to the industrial types, atmospheric deposition, and human activities in these surveyed areas, which are similar to foreign soil surveys. Traditional perfluoro carboxylic acid (PFCAs) and perfluoro octane sulfonate (PFSAs) are the most important types of PFAS in Chinese soils. This study reviewed the distribution characteristics, transportation pathways, and influencing factors of PFAS in Chinese soils, as well as domestic and foreign control policies on PFAS pollution. Meanwhile, this study further pointed out the shortcomings of the current research on the distribution and control of PFAS in soil in order to provide a reference for the investigation, research, and control of PFAS pollution in Chinese soils.

Bistability in Radiatively Heated Melt Ponds.

Melting and solidification processes, intertwined with convective flows, play a fundamental role in geophysical contexts. One of these processes is the formation of melt ponds on glaciers, ice shelves, and sea ice. It is driven by solar radiation and is of great significance for Earth's heat balance, as it significantly lowers the albedo. Through direct numerical simulations and theoretical analysis, we unveil a bistability phenomenon in the melt pond dynamics. As solar radiation intensity and the melt pond's initial depth vary, an abrupt transition occurs: this tipping point transforms the system from a stable fully frozen state to another stable equilibrium state, characterized by a distinct melt pond depth. The physics of this transition can be understood within a heat flux balance model, which exhibits excellent agreement with our numerical results. Together with the Grossmann-Lohse theory for internally heated convection, the model correctly predicts the bulk temperature and the flow strength within the melt ponds, offering insight into the coupling of phase transitions with adjacent turbulent flows and the interplay between convective melting and radiation-driven processes.

Efficient and Reversible Separation of Chloroform from Chlorinated Hydrocarbons and Water Utilizing a Two-Dimensional Coordination Network.

Chloroform is a volatile organic solvent and a contaminant that is slightly soluble in water, making the reversible separation of chloroform from water a critical and challenging task within the chemical and environmental industries. In this study, we present a newly developed coordination framework, [Zn(4-pmntd)(opa)] [4-pmntd, N,N'-bis(4-pyridylmethyl)naphthalene diimide; opa, o-phthalic acid], which demonstrates a high adsorption capacity for chloroform (2.5 mmol/g) and an excellent ability to separate chloroform from water. The effectiveness of chloroform extraction by Zn(4-pmntd)(opa) was confirmed through vapor sorption, grand canonical Monte Carlo simulation, and 1H nuclear magnetic resonance spectroscopy. The porous framework was also utilized to create a filtration film using natural rubber, which successfully separated chloroform from water with a minimum test concentration of approximately 1 × 10-6 mol/L and a chloroform purity of 99.2%. [Zn(4-pmntd)(opa)] therefore has significant potential for low-energy separation and recycling of chloroform from water under ambient conditions.

Design, synthesis and the evaluation of cholinesterase inhibition and blood-brain permeability of daidzein derivatives or analogs.

In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7-hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'-N,N-dimethylaminoethoxy-7-methoxyisoflavone) appeared the best inhibitory activity (IC50 : 2.14 ± 0.31 µmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC-MS/MS. The results show that CBrain/Serum of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors.

ANP32B suppresses B-cell acute lymphoblastic leukemia through activation of PU.1 in mice.

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, is critical for normal development because its constitutive knockout mice are perinatal lethal. It is also shown that ANP32B acts as a tumor-promoting gene in some kinds of cancer such as breast cancer and chronic myelogenous leukemia. Herein, we observe that ANP32B is lowly expressed in B-cell acute lymphoblastic leukemia (B-ALL) patients, which correlates with poor prognosis. Furthermore, we utilized the N-myc or BCR-ABLp190 -induced B-ALL mouse model to investigate the role of ANP32B in B-ALL development. Intriguingly, conditional deletion of Anp32b in hematopoietic cells significantly promotes leukemogenesis in two B-ALL mouse models. Mechanistically, ANP32B interacts with purine rich box-1 (PU.1) and enhances the transcriptional activity of PU.1 in B-ALL cells. Overexpression of PU.1 dramatically suppresses B-ALL progression, and highly expressed PU.1 significantly reverses the accelerated leukemogenesis in Anp32b-deficient mice. Collectively, our findings identify ANP32B as a suppressor gene and provide novel insight into B-ALL pathogenesis.

Expanding outpatient benefits package can reduce diabetes-related avoidable hospitalizations.

Objective: To evaluate the policy effect of replacing hospitalization service with outpatient service and reducing diabetes-related avoidable hospitalizations by improving outpatient benefits package. Methods: A database of hospital discharge from 2015 to 2017 in City Z was used. All diabetic inpatient cases enrolled in Urban Employee Basic Medical Insurance were selected as the intervention group, and diabetic inpatient cases enrolled in Urban and Rural Resident Basic Medical Insurance were selected as the control group. The Difference-in-Difference model was used to analyze the effect of improving outpatient benefits package level of diabetes from 1800 yuan (about $252.82) to 2400 yuan (about $337.09) per capita per year on avoidable hospitalization rate, average hospitalization cost and average length of stay. Results: The avoidable hospitalization rate of diabetes mellitus decreased by 0.21 percentage points (P < 0.01), the average total cost of hospitalization increased by 7.89% (P < 0.01), and the average length of stay per hospitalization increased by 5.63% (P < 0.01). Conclusions: Improving the outpatient benefits package of diabetes can play a role in replacing hospitalization service with outpatient service, reducing diabetes-related avoidable hospitalizations, and reducing the disease burden and financial burden.

FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia.

BACKGROUND: Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown. METHODS: We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22. RESULTS: FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22-deficient mice. CONCLUSIONS: FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis.

Cumulus Cells Accelerate Postovulatory Oocyte Aging through IL1-IL1R1 Interaction in Mice.

The oocytes of female mammals will undergo aging after ovulation, also known as postovulatory oocyte aging (POA). Until now, the mechanisms of POA have not been fully understood. Although studies have shown that cumulus cells accelerate POA over time, the exact relationship between the two is still unclear. In the study, by employing the methods of mouse cumulus cells and oocytes transcriptome sequencing and experimental verification, we revealed the unique characteristics of cumulus cells and oocytes through ligand-receptor interactions. The results indicate that cumulus cells activated NF-κB signaling in oocytes through the IL1-IL1R1 interaction. Furthermore, it promoted mitochondrial dysfunction, excessive ROS accumulation, and increased early apoptosis, ultimately leading to a decline in the oocyte quality and the appearance of POA. Our results indicate that cumulus cells have a role in accelerating POA, and this result lays a foundation for an in-depth understanding of the molecular mechanism of POA. Moreover, it provides clues for exploring the relationship between cumulus cells and oocytes.

A novel TcS allele conferring the high-theacrine and low-caffeine traits and having potential use in tea plant breeding.

Theacrine (1,3,7,9-tetramethyluric acid) is a natural product with remarkable pharmacological activities such as antidepressant, sedative and hypnotic activities, while caffeine (1,3,7-trimethylxanthine) has certain side effects to special populations. Hence, breeding tea plants with high theacrine and low caffeine will increase tea health benefits and promote consumption. In this study, we construct an F1 population by crossing 'Zhongcha 302' (theacrine-free) and a tea germplasm 'Ruyuan Kucha' (RY, theacrine-rich) to identify the causal gene for accumulating theacrine. The results showed that the content of theacrine was highly negatively correlated with caffeine (R2 > 0.9). Bulked segregant RNA sequencing analysis, molecular markers and gene expression analysis indicated that the theacrine synthase (TcS) gene was the candidate gene. The TcS was located in the nucleus and cytoplasm, and the theacrine can be detected in stably genetic transformed tobacco by feeding the substrate 1,3,7-trimethyluric acid. Moreover, an in vitro enzyme activity experiment revealed that the 241st amino acid residue was the key residue. Besides, we amplified the promoter region in several tea accessions with varied theacrine levels, and found a 234-bp deletion and a 271-bp insertion in RY. Both GUS histochemical analysis and dual-luciferase assay showed that TcS promoter activity in RY was relatively high. Lastly, we developed a molecular marker that is co-segregate with high-theacrine individuals in RY's offspring. These results demonstrate that the novel TcS allele in RY results in the high-theacrine and low-caffeine traits and the developed functional marker will facilitate the breeding of characteristic tea plants.

Vacuoles in Bryophytes: Properties, Biogenesis, and Evolution.

Vacuoles are the most conspicuous organelles in plants for their indispensable functions in cell expansion, solute storage, water balance, etc. Extensive studies on angiosperms have revealed that a set of conserved core molecular machineries orchestrate the formation of vacuoles from multiple pathways. Usually, vacuoles in seed plants are classified into protein storage vacuoles and lytic vacuoles for their distinctive morphology and physiology function. Bryophytes represent early diverged non-vascular land plants, and are of great value for a better understanding of plant science. However, knowledge about vacuole morphology and biogenesis is far less characterized in bryophytes. In this review, first we summarize known knowledge about the morphological and metabolic constitution properties of bryophytes' vacuoles. Then based on known genome information of representative bryophytes, we compared the conserved molecular machinery for vacuole biogenesis among different species including yeast, mammals, Arabidopsis and bryophytes and listed out significant changes in terms of the presence/absence of key machinery genes which participate in vacuole biogenesis. Finally, we propose the possible conserved and diverged mechanism for the biogenesis of vacuoles in bryophytes compared with seed plants.

Pore-Structure Control in Metal-Organic Frameworks (MOFs) for Capture of the Greenhouse Gas SF6 with Record Separation.

In the electronics industry, the efficient recovery and capture of sulfur hexafluoride (SF6 ) from SF6 /N2 mixtures is of great importance. Herein, three metal-organic frameworks with fine-tuning pore structures, Cu(peba)2 , Ni(pba)2 , and Ni(ina)2 , were designed for SF6 capture. Among them, Ni(ina)2 has perfect pore sizes (6 Å) that are comparable to the kinetic diameter of sulfur hexafluoride (5.2 Å), affording the benchmark binding affinity for SF6 gas. Ni(ina)2 exhibits the highest SF6 /N2 selectivity (375.1 at 298 K and 1 bar) and ultra-high SF6 uptake capacity (53.5 cm3 g-1 at 298 K and 0.1 bar) at ambient conditions. The remarkable separation performance of Ni(ina)2 was verified by dynamic breakthrough experiments. Theoretical calculations and the SF6 -loaded single-crystal structure provided critical insight into the adsorption/separation mechanism. This porous coordination network has the potential to be used in industrial applications.

GRIM19 is involved in WT1 expression and epithelial-to-mesenchymal transition in adenomyotic lesions.

The epithelial-to-mesenchymal transition may play a role in adenomyosis. GRIM19 expression is downregulated in adenomyotic lesions, and the effects of this downregulation in adenomyosis remain relatively unclear. In this study, we aimed to explore whether aberrant GRIM19 expression is associated with the epithelial-to-mesenchymal transition in adenomyosis and found that the expression of both GRIM19 and WT1 was low, and epithelial-to-mesenchymal transition, which included significant changes in CDH1, CDH2 and KRT8 expression, occurred in adenomyotic lesions, as confirmed by Western blotting and quantitative real-time PCR. We provided novel insights into WT1 expression in adenomyosis, revealing that WT1 expression was increased in the endometrial glands of adenomyotic lesions by immunohistochemistry. In vitro, knockdown of GRIM19 expression by small interfering RNA (siRNA) promoted the proliferation, migration and invasion of Ishikawa cells, as measured by Cell Counting Kit-8, wound healing assay and Transwell assays. Western blotting and quantitative real-time PCR confirmed that WT1 expression increased and epithelial-to-mesenchymal transition was induced, including the upregulation of CDH2 and downregulation of CDH1 and KRT8after transfecting the GRIM19 siRNA to Ishikawa cells. Furthermore, WT1 expression was upregulated and epithelial-to-mesenchymal transition was observed, including downregulation of CDH1 and KRT8in GRIM19 gene-knockdown mice. Upregulation of Wt1 expression in the endometrial glands of Grim19 knockdown mice was also verified by immunohistochemistry. Taken together, these results reveal that low expression of GRIM19 in adenomyosis may upregulate WT1 expression and induce epithelial-to-mesenchymal transition in the endometria, providing new insights into the pathogenesis of adenomyosis.

Advances in production and structural derivatization of the promising molecule ursolic acid.

Ursolic acid (UA) is a ursane-type pentacyclic triterpenoid compound, naturally produced in plants via specialized metabolism and exhibits vast range of remarkable physiological activities and pharmacological manifestations. Owing to significant safety and efficacy in different medical conditions, UA may serve as a backbone to produce its derivatives with novel therapeutic functions. This review aims to provide ideas for exploring more diverse structures to improve UA pharmacological activity and increasing its biological yield to meet the industrial requirements by systematically reviewing the current research progress of UA. We first provides an overview of the pharmacological activities, acquisition methods and structural modifications of UA. Among them, we focused on the synthetic modifications of UA to yield valuable derivatives with enhanced therapeutic potential. Furthermore, harnessing the essential advances for green synthesis of UA and its derivatives by advent of metabolic engineering and synthetic biology are of great concern. In this regard, all pivotal advances for enhancing the production of UA have been discussed. In combination with the advantages of UA biosynthesis and transformation strategy, large-scale microbial production of UA is a promising platform for further exploration.

Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition.

In this study, a series of new flavones (2-phenyl-chromone), 2-naphthyl chromone, 2-anthryl-chromone, or 2-biphenyl-chromone derivatives containing 6 or 7-substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC50 = 1.29 ± 0.10 µmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed-type inhibitory effect against AChE.

Pyridine-Functionalized Fullerene Electron Transport Layer for Efficient Planar Perovskite Solar Cells.

In regular perovskite solar cells (PSCs), the commonly used electron transport layer (ETL) is titanium oxide (TiO2). Nevertheless, the preparation of a high-quality TiO2 ETL demands an elevated-temperature sintering procedure, unfavorable for fabrication of PSCs on flexible substrates. Besides, TiO2-based devices often suffer from notorious photocurrent hysteresis and serious light soaking instability, limiting their potential commercialization. Herein, a novel pyridine-functionalized fullerene derivative [6,6]-(4-pyridinyl)-C61-ethyl acid ethyl ester (PyCEE) was synthesized and applied as an ETL to replace TiO2 in n-i-p PSCs. PyCEE-based devices achieved a champion power conversion efficiency (PCE) of 18.27% with significantly suppressed hysteresis, superior to that of TiO2-based devices. PyCEE has suitable energy levels and high electron mobility, which facilitate electron extraction/transport. Besides, the pyridine moiety within PyCEE affords coordination interactions with the Pb2+ ion within CH3NH3PbI3, passivating the trap states of CH3NH3PbI3 and thus improving the device performance and suppressing hysteresis greatly. Moreover, PyCEE ETLs were applied in flexible PSCs, achieving a PCE of 15.25%. Our results demonstrated the applicability of PyCEE ETLs in flexible devices and provided new opportunity for the commercialization of PSCs.