Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets.

PURPOSE: Venetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets. METHODS: An open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing. FINDINGS: The crushed and ground tablets met the bioequivalence criteria (0.80-1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUCinf) but exhibited a slightly lower maximum plasma concentration (Cmax). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity. IMPLICATIONS: Crushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding. GOV IDENTIFIERS: NCT05909553, registered June 12, 2023.

Anlotinib inhibits growth of human esophageal cancer TE-1 cells by negative regulating PI3K/Akt signaling pathway.

Anlotinib is effective in treatment of many kinds of malignant cancer, but its antineoplastic effects on esophageal cancer remains unclear. This study aims to investigate its impact on esophageal cancer and the underlying mechanisms. Anlotiniband 5-fluorouracil + cisplatin (5-FU + DDP) was administered separately to human esophageal cancer TE- 1 cells tumor xenograft mouse models every 3 days. Tumor size and body weight were measured before each treatment and at the end of the experiment. In vitro studies were conducted using TE- 1 cells to examine the effects of Anlotinib. Cell viability, migration, proliferation, apoptosis, cell cycle, their regulatory proteins and the transcriptomic changes were analyzed. Anlotinib reduced tumor size, tumor weight, and the ratio of tumor weight to body weight in vivo. It decreased the viability of TE- 1 cells, with a 50% growth-inhibitory concentration of 9.454 µM for 24 h, induced apoptosis, and arrested TE- 1 cell cycle in the S phase. It inhibited migration and proliferation while negatively regulating the PI3K/Akt signaling pathway. Enhanced expressions of P21, Bax, and lowered expressions of cyclin A1, cyclin B1, CDK1, PI3K, Akt, p-Akt, and Bcl-2 were observed after Anlotinib treatment. Anlotinib exhibits antineoplastic activity against human esophageal cancer TE- 1 cells by negatively regulating the PI3K/Akt signaling pathway, consequently altering the expressions of proteins related to proliferation, apoptosis, and the cell cycle.

Passivation of 2D Cs2PbI2Cl2 Nanosheets for Efficient and Stable CsPbI3 Quantum Dot Solar Cells.

Inorganic CsPbI3 perovskite quantum dots (PQDs) possess remarkable optical properties, making them highly promising for photovoltaic applications. However, the inadequate stability resulting from internal structural instability and the complex external surface chemical environment of CsPbI3 PQDs has hindered the development of CsPbI3 PQD solar cells (PQDSCs). In this work, the capping layer composed of inorganic two-dimensional (2D) Ruddlesden-Popper (RP) phase Cs2PbI2Cl2 nanosheets (NSs) is introduced, which may be effectively treated to improve the surface properties of the CsPbI3 PQD film. This modification serves to passivate defects by filling cesium and iodine vacancies while optimizing the energy band arrangement and preventing humidity intrusion, leading to the meliorative stability and photovoltaic performance. The optimized CsPbI3 PQDSCs achieve an enhanced power conversion efficiency (PCE) of 14.73%, with the superb stability of only a 16% efficiency loss after being exposed to ambient conditions (30 ± 5% RH) for 432 h.

TpPa-1 COFs-Enhanced Zwitterion Hydrogel for Efficient Harvesting of Atmospheric Water.

Zwitterionic hydrogel, serving as carriers for hygroscopic salts, holds significant potential in atmospheric water harvesting. However, their further application is limited by structural collapse in high-concentration salt solution and poor photothermal conversion performance. Herein, the graded pore structure of poly-3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate (PDMAPS) zwitterionic hydrogel/TpPa-1 covalent organic frameworks (COFs)/LiCl composite (named as PCL composite hydrogel) is proposed, which leads to the accelerated diffusion effect for water molecules. As a result, the vapor adsorption capacity of the optimal composite hydrogel (PCL-42) reaches 2.88 g g-1 within 12 hours under conditions of 25 °C and 90 % RH. Simultaneously, the maximum temperature of PCL-42 composite could reach 53.9 °C after 9 minutes under a simulated solar intensity of 1.0 kW m-2, releasing 91 % of the adsorbed water in 3 hours, providing a promising prospect for efficient solar-driven atmospheric water harvesting. One cycle could collect 7.55 g of fresh water under outdoor conditions, and the maximum daily water production may reach 2.71 kg kg-1. The reason lies in that TpPa-1 COFs lead hydrogel to form a gradient pore structure, which may accelerate the transport of water molecules, increase the loading capacity of LiCl and enhance the photothermal property.

Breaking the bottleneck of lead-free perovskite solar cells through dimensionality modulation.

The emerging perovskite solar cell (PSC) technology has attracted significant attention due to its superior power conversion efficiency (PCE) among the thin-film photovoltaic technologies. However, the toxicity of lead and poor stability of lead halide materials hinder their commercialization. In this case, after a decade of effort, various categories of lead-free perovskites and perovskite-like materials have been developed, including tin halide perovskites, double perovskites, defect-structured perovskites, and rudorffites. However, the performance of the corresponding devices still falls short of expectations, especially their PCE. The limitations mainly originate from either the unstable lattice structure of these materials, which causes the distortion of their octahedra, or their low dimensionality (e.g., structural and electronic dimensionality)-correlated poor carrier transport and self-trapping effect, accelerating nonradiative recombination. Therefore, understanding the relationship between the structures and performance in these emerging candidates and leveraging these insights to design or modify new lead-free perovskites is of great significance. Herein, we review the variety of dimensionalities in different categories of lead-free perovskites and perovskite-like materials and conclude that dimensionality is an important aspect among the crucial indexes that determine the performance of lead-free PSCs. In addition, we summarize the modulation of both structural and electronic dimensionality, and the corresponding enhanced optoelectronic properties in different categories. Finally, perspectives on the future development of lead-free perovskites and perovskite-like materials for photovoltaic applications are provided. We hope that this review will provide researchers with a concise overview of these emerging materials and help them leverage dimensionality to break the bottleneck in photovoltaic applications.

Heteroepitaxial Growth to Construct Hexagonal/Hexagonal ß-NaYF4:Yb,Tm/Cs4PbBr6 Multi-Code Emitting Core/Shell Nanocrystals.

Synthesis of upconversion nanoparticles (UCNPs)-metal halide perovskites (MHPs) heterostructure is garnered immense attentions due to their unparalleled photophysical properties. However, the obvious difference in their structural forms makes it a huge challenge. Herein, hexagonal ß-NaYF4 and hexagonal Cs4PbBr6 are filtrated to construct the UCNP/MHP heterostructural luminescent material. The similarity in their crystal structures facilitate the heteroepitaxial growth of Cs4PbBr6 on the surface of ß-NaYF4 NPs, leading to the formation of high-quality ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell nanocrystals (NCs). Interestingly, this heterostructure endows the core/shell NCs with typically narrow-band green emission centered at 524 nm under 980 nm excitation, which should be attributed to the Förster resonance energy transfer (FRET) from Tm3+ to Cs4PbBr6. It is noteworthy that the FRET efficiency of ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell NCs (58.33%) is much higher than that of the physically mixed sample (1.84%). In addition, the reduced defect density, lattice anchoring effect, as well as diluted ionic bonding proportion induced by the core/shell structure further increase the excellent water-resistance and thermal cycling stability of Cs4PbBr6. These findings open up a new way to construct UCNP/MHP heterostructure with better multi-code luminescence performance and stability and promote its wide optoelectronic applications.

IL-27-induced, MSC-derived Exosomes Promote MMP3 Expression Through the miR-206/L3MBTL4 Axis in Synovial Fibroblasts.

Context: In rheumatoid arthritis (RA), hyperproliferative fibroblast-like synoviocytes (FLS) can secrete a variety of tissue hydrolases, such as matrix metalloproteinases (MMPs), causing the destruction of chondrocytes. Mesenchymal stem cells (MSCs) can directly affect FLS through extracellular vesicles (EVs). Interleukin-27 (IL-27) is a pleiotropic immune regulator frequently overexpressed in RA. Objective: The study intended to examine the effects of IL-27-induced exosomes from bone-marrow mesenchymal stem cells (BM-MSCs) and to determine if they promote the secretion of MMP3 in synovial cells. Design: The research team performed a genetic study. Setting: The study took place at the First Affiliated Hospital of Hainan Medical University in Haikou City, Hainan, China. Outcome Measures: The research team: (1) determined if IL-27 expression had occurred in the synovial fluid; (2) co-cultured IL-27-induced MSCs with FLS to detect the expression of MMP3 in the FLS; (3) Under IL-27 induction, MSC-derived exosomes with IL-27R knockdown were collected to detect the expression of microRNAs(miRNAs) associated with RA; (4) screened the miRNAs to determine the most significant differences in expression; (5) determined the miRNA target genes in arthritis, using Western blot (WB) and qRT-PCR; and (6) Dual luciferase and ChIP experiments confirm regulation of MMP3 by L3MBTL4. Results: IL-27 was highly expressed in RA, and the IL-27-induced, MSC-derived exosomes promoted the expression of MMP3 in FLS. The IL-27-induced MSC-derived exosomes significantly upregulated the expression of miR-206-3p, and the miR-206-3p target, miR-206/ lethal(3) malignant brain tumor-like protein 4 (L3MBTL4), regulated the MMP3 transcription. The IL-27-induced, MSC-derived exosomes promoted MMP3 expression in the FLS through the miR-206-3p/L3MBTL4 axis, thereby promoting chondrocyte degradation and aggravating RA. Conclusions: IL-27 can induce the expression of miR-206 in MSCs, and miR-206 can be transported into FLS through MSC-EVs to promote FLS migration and MMP3 expression and aggravate articular cartilage damage. Patients with RA who have a high IL-27 expression may not be suitable to receive treatment with MSCs, and clinicians can use MSCs that knock down or delete IL-27R to treat RA patients who have a high IL-27 expression.

Surface polarization-induced emission and stability enhancement of CsPbX3 nanocrystals.

Recently, the polarization effect has been receiving tremendous attention, as it can result in improved stability and charge transfer efficiency of metal-halide perovskites (MHPs). However, realizing the polarization effect on CsPbX3 NCs still remains a challenge. Here, metal ions with small radii (such as Mg2+, Li+, Ni2+, etc.) are introduced on the surface of CsPbX3 NCs, which facilitate the arising of electric dipole and surface polarization. The surface polarization effect promotes redistribution of the surface electron density, leading to reinforced surface ligand bonding, reduced surface defects, near unity photoluminescence quantum yields (PLQYs), and enhanced stability. Moreover, further introduction of hydroiodic acid results in the in situ formation of tert-butyl iodide (TBI), which facilitates the successful synthesis of pure iodine-based CsPbI3 NCs with high PLQY (95.3%) and stability under ambient conditions. The results of this work provide sufficient evidence to exhibit the crucial role of the surface polarization effect, which promotes the synthesis of high-quality MHPs and their applications in the fields of optoelectronic devices.

Modulation of the canonical Wnt activity by androgen signaling in prostate epithelial basal stem cells.

Both the canonical Wnt and androgen receptor (AR) signaling pathways are important for prostate organogenesis and homeostasis. How they crosstalk to regulate prostate stem cell behaviors remains unclear. Here, we show in lineage-tracing mouse models that although Wnt is essential for basal stem cell multipotency, ectopic Wnt activity promotes basal cell over-proliferation and squamous phenotypes, which are counteracted by elevated levels of androgen. In prostate basal cell organoids, dihydrotestosterone (DHT) antagonizes R-spondin-stimulated growth in a concentration-dependent manner. DHT down-regulates the expressions of a Wnt reporter and target genes, and RNA sequencing (RNA-seq) analyses identify Wnt signaling as a key altered pathway. Mechanistically, DHT enhances AR and ß-catenin protein binding, and CUT&RUN analyses reveal that ectopic AR sequesters ß-catenin away from its Wnt-related cistrome. Our results suggest that an intermediate level of Wnt activity in prostate basal stem cells, achieved via AR-ß-catenin interaction, is essential for normal prostate homeostasis.

Photocatalytic CO2 reduction using La-Ni bimetallic sites within a covalent organic framework.

The precise construction of photocatalysts with diatomic sites that simultaneously foster light absorption and catalytic activity is a formidable challenge, as both processes follow distinct pathways. Herein, an electrostatically driven self-assembly approach is used, where phenanthroline is used to synthesize bifunctional LaNi sites within covalent organic framework. The La and Ni site acts as optically and catalytically active center for photocarriers generation and highly selective CO2-to-CO reduction, respectively. Theory calculations and in-situ characterization reveal the directional charge transfer between La-Ni double-atomic sites, leading to decreased reaction energy barriers of *COOH intermediate and enhanced CO2-to-CO conversion. As a result, without any additional photosensitizers, a 15.2 times enhancement of the CO2 reduction rate (605.8 µmol·g-1·h-1) over that of a benchmark covalent organic framework colloid (39.9 µmol·g-1·h-1) and improved CO selectivity (98.2%) are achieved. This work presents a potential strategy for integrating optically and catalytically active centers to enhance photocatalytic CO2 reduction.

Study of Intermolecular Reconfiguration of Flexible COF-5 Film and Its Ultra-high Chemiresistive Humidity Sensitivity.

Recently, abundant active materials are developed to achieve the wearable detection of human body humidity. However, the limited response signal and sensitivity restrict further application due to their moderate affinity to water. Herein, we propose a flexible COF-5 film synthesized by a brief vapor-assisted method at room temperature. Intermediates are calculated by DFT simulation to investigate the interaction between COF-5 and water. The adsorption and desorption of water molecule result in a reversible deformation of COF layers while creating new conductive path by π-π stacking. The as-prepared COF-5 films are applied to the flexible humidity sensors, exhibiting a resistance change in 4 orders of magnitude with remarkable linear relation between log function of resistance and relative humidity (RH) in 11 %-98 % RH range. Applications including respiratory monitoring and non-contact switch are tested, providing a promising prospect for the detection of human body humidity.

Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.

Androgen receptor (AR) is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology. Although low expression of stromal AR is clinically associated with advanced cancer stage and worse outcome, whether stromal AR inhibits or promotes prostate cancer progression remains controversial. Here, we specifically delete AR in smooth muscle cells of the adult mouse prostate under two tumorigenic conditions, namely, the Hi-Myc genetic model and the T + E2 hormonal carcinogenesis model. Histology analyses show that stromal AR deletion exacerbates tumor progression phenotypes in both models. Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal AR deletion, as they transition to a cellular state of potentiated PI3K-mTORC1 activities. Our results suggest that stromal AR normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy.

Density Functional Investigation on α-MoO3 (100): Amines Adsorption and Surface Chemistry.

The (100) surface of α-MoO3 should possess overwhelmingly more exposed Mo atoms than the (010), and the exposed Mo has been extensively considered as an active site for amine adsorption. However, α-MoO3 (100) has drawn little attention concerning the amine sensing mechanism. In this research, adsorption of ammonia (NH3), monomethylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) is systematically investigated by density functional theory (DFT). All four of these molecules have high affinity to α-MoO3 (100) through interaction between the N and the exposed Mo, and the affinity is mainly influenced by both the characteristics of the molecules and the geometric environment of the surface active site. Adsorption and dissociation of water and oxygen molecule on stoichiometric and defective α-MoO3 (100) surfaces are then simulated to fully understand the surface chemistry of α-MoO3 (100) in practical conditions. At low temperature, α-MoO3 (100) must be covered with a large number of water molecules; the water can desorb or dissociate into hydroxyl groups at high temperature. Oxygen vacancy (VO) can be generated through the annealing process during sensor device fabrication; VO must be filled with an O2 molecule, which can further interact with adsorbed water nearby to form hydroxyl groups. According to this research, α-MoO3 (100) must be the active surface for amine sensing and its surface chemistry is well understood. In the near future, further reaction and interaction will be simulated at α-MoO3 (100), and much more attention should be paid to α-MoO3 (100) not only theoretically but also experimentally.

A 3D-printed transfusion platform reveals beneficial effects of normoglycemic erythrocyte storage solutions and a novel rejuvenating solution.

A set of 3D-printed analytical devices were developed to investigate erythrocytes (ERYs) processed in conventional and modified storage solutions used in transfusion medicine. During storage, prior to transfusion into a patient recipient, ERYs undergo many chemical and physical changes that are not completely understood. However, these changes are thought to contribute to an increase in post-transfusion complications, and even an increase in mortality rates. Here, a reusable fluidic device (fabricated with additive manufacturing technologies) enabled the evaluation of ERYs prior to, and after, introduction into a stream of flowing fresh ERYs, thus representing components of an in vivo ERY transfusion on an in vitro platform. Specifically, ERYs stored in conventional and glucose-modified solutions were assayed by chemiluminescence for their ability to release flow-induced ATP. The ERY's deformability was also determined throughout the storage duration using a novel membrane transport approach housed in a 3D-printed scaffold. Results show that hyperglycemic conditions permanently alter ERY deformability, which may explain the reduced ATP release, as this phenomenon is related to cell deformability. Importantly, the reduced deformability and ATP release were reversible in an in vitro model of transfusion; specifically, when stored cells were introduced into a flowing stream of healthy cells, the ERY-derived release of ATP and cell deformability both returned to states similar to that of non-stored cells. However, after 1-2 weeks of storage, the deleterious effects of the storage were permanent. These results suggest that currently approved hyperglycemic storage solutions are having adverse effects on stored ERYs used in transfusion medicine and that normoglycemic storage may reduce the storage lesion, especially for cells stored for longer than 14 days.

COF-5/CoAl-LDH Nanocomposite Heterojunction for Enhanced Visible-Light-Driven CO2 Reduction.

Photocatalytic conversion of CO2 into value-added chemical fuels is an attractive route to mitigate global warming and the energy crisis. Reasonable design of optical properties and electronic behavior of the photocatalyst are essential to improve their catalytic activity. Herein, the 1D/2D heterojunction by direct in-situ synthesis of the covalent organic framework (COF)-5 colloid on the surface of CoAl layered double hydroxide (LDH) was used as the prospective photocatalyst for CO2 reduction. COF-5/CoAl-LDH nanocomposite achieved 265.4 µmol g-1 of CO with 94.6 % selectivity over CH4 evolution in 5 h under visible light irradiation, which was 4.8 and 2.3 times higher than those of COF-5 colloid and CoAl-LDH, respectively. The enhanced catalytic activity was derived from the increased visible-light activity and the construction of type II-2 heterojunction, which greatly optimized visible light harvesting and accelerated the efficient separation of the photoinduced holes and electrons. This work paves the way for rational design of heterojunction catalysts in photocatalytic CO2 reduction.

Efficacy and safety of dapagliflozin in the treatment of chronic heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: As the last link in the chain of cardiovascular events, chronic heart failure (CHF) has high morbidity, high mortality, and poor prognosis. It is one of the main causes of death and disability worldwide. As a new drug for the treatment of chronic cardiovascular disease, dapagliflozin, the efficacy, and safety issues are still the focus of attention. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of dapagliflozin in the treatment of CHF. METHODS: According to the search strategy, regardless of publication date or language, randomized controlled trials (RCTs) of dapagliflozin for CHF will be retrieved from 8 databases. First of all, the literature was screened according to the eligibility criteria, and use the Cochrane Collaboration's tool to assess the quality of the included literature. Then, using Rev Man 5.3 and STATA 14.2 software for traditional meta-analysis. Finally, the evaluation of the quality of the evidence and the strength of the recommendations will adopt the Grading of Recommendations, Assessment, Development and Evaluation method. RESULTS: This study will evaluate the efficacy and safety of dapagliflozin for CHF, thereby providing more evidence support for clinical decision-making in CHF. CONCLUSION: Our research will provide more references for the clinical medication of patients with CHF. PROTOCOL REGISTRATION NUMBER: INPLASY202150046.

Doped Bilayer Tin(IV) Oxide Electron Transport Layer for High Open-Circuit Voltage Planar Perovskite Solar Cells with Reduced Hysteresis.

Tin oxide (SnO2 ) is an emerging electron transport layer (ETL) material in halide perovskite solar cells (PSCs). Among current limitations, open-circuit voltage (VOC ) loss is one of the major factors to be addressed for further improvement. Here a bilayer ETL consisting of two SnO2 nanoparticle layers doped with different amounts of ammonium chloride is proposed. As demonstrated by photoelectron spectroscopy and photophysical studies, the main effect of the novel ETL is to modify the energy level alignment at the SnO2 /perovskite interface, which leads to decreased carrier recombination, enhanced electron transfer, and reduced voltage loss. Moreover, X-ray diffraction reveals reduced strain in perovskite layers grown on bilayer ETLs with respect to single-layer ETLs, further contributing to a decrease of carrier recombination processes. Finally, the bilayer approach enables the more reproducible preparation of smooth and pinhole-free ETLs as compared to single-step deposition ETLs. PSCs with the doped bilayer SnO2 ETL demonstrate strongly increased VOC values of up to 1.21 V with a power conversion efficiency of 21.75% while showing negligible hysteresis and enhanced stability. Moreover, the SnO2 bilayer can be processed at low temperature (70 °C), and has therefore a high potential for use in tandem devices or flexible PSCs.

Nanosensor-Based Flexible Electronic Assisted with Light Fidelity Communicating Technology for Volatolomics-Based Telemedicine.

Telemedicine provides an attractive vision for tele-monitoring human health conditions and, thus, offers the opportunity for timely preventing chronic disease. A key limitation of promoting telemedicine in clinic application is the lack of a noninvasive med-tech and effective monitoring platform, which should be wearable and capable of high-performance tele-monitoring of health risk. Here we proposed a volatolomics-based telemedicine for continuously and noninvasively assessing human health status through continuously tracking the variation of volatile markers derived from human breath or skin. Particularly, a nanosensor-based flexible electronic was specifically designed to serve as a powerful platform for implementing the proposed cost-effective healthcare. An all-flexible and highly packed makeup (all functional units were integrated in a 2*2*0.19 cm3 plate) enables an electronic, compact configuration and the capability of resisting negative impact derived from customers' daily movement. Notably, the nanosensor-based electronic demonstrates high specificity, quick response rate (t90% = 4.5 s), and desirable low detection limit (down to 0.117 ppm) in continuous tele-monitoring chronic-disease-related volatile marker (e.g., acetone). Assisted by the power saved light fidelity (Li-Fi) communicating technology, a clinic proof on the specifically designed electronic for noninvasively and uninterrupted assessing potential health risk (e.g., diabetics) is successfully implemented, with the accuracy of around 81%. A further increase in the accuracy of prewarning is predicted by excluding the impact of individual differences such as the gender, age, and smoking status of the customer. These promising pilot results indicate a bright future for the tailor-made nanosensing-device-supported volatolomics-based telemedicine in preventing chronic diseases and increasing patients' survival rate.

High Efficiency Mesoscopic Solar Cells Using CsPbI3 Perovskite Quantum Dots Enabled by Chemical Interface Engineering.

All-inorganic α-CsPbI3 perovskite quantum dots (QDs) are attracting great interest as solar cell absorbers due to their appealing light harvesting properties and enhanced stability due to the absence of volatile organic constituents. Moreover, ex situ synthesized QDs significantly reduce the variability of the perovskite layer deposition process. However, the incorporation of α-CsPbI3 QDs into mesoporous TiO2 (m-TiO2) is highly challenging, but these constitute the best performing electron transport materials in state-of-the-art perovskite solar cells. Herein, the m-TiO2 surface is engineered using an electron-rich cesium-ion containing methyl acetate solution. As one effect of this treatment, the solid-liquid interfacial tension at the TiO2 surface is reduced and the wettability is improved, facilitating the migration of the QDs into m-TiO2. As a second effect, Cs+ ions passivate the QD surface and promote the charge transfer at the m-TiO2/QD interface, leading to an enhancement of the electron injection rate by a factor of 3. In combination with an ethanol-environment smoothing route that significantly reduces the surface roughness of the m-TiO2/QD layer, optimized devices exhibit highly reproducible power conversion efficiencies exceeding 13%. The best cell with an efficiency of 14.32% (reverse scan) reaches a short-circuit current density of 17.77 mA cm-2, which is an outstanding value for QD-based perovskite solar cells.

Luminal-contact-inhibition of epithelial basal stem cell multipotency in prostate organogenesis and homeostasis.

Prostate epithelial basal cells are highly plastic in their luminal differentiation capability. Basal stem cells actively produce luminal cells during organogenesis, but become restricted in the adult prostate unless receiving oncogenic or inflammatory stimuli. Given that the number of luminal cells increases relative to basal cells through development and that equilibrium is reached in the adulthood, we hypothesize that a negative-feedback mechanism exists to inhibit basal-to-luminal differentiation. We provide evidence supporting this hypothesis by comparing murine prostatic growth in a tissue reconstitution assay with cell recombinants of different basal-to-luminal ratios. Additionally, in organoid culture, hybrid organoids derived from adjacent basal and luminal cells showed reduced basal stem cell activities, suggesting contact inhibition. Importantly, removal of adult luminal cells in vivo via either an inducible Cre/loxP-Dre/rox dual-lineage-tracing system or orthotopic trypsin injection led to robust reactivation of basal stem cell activities, which acts independent of androgen. These data illustrate the prostate organ as a distinctive paradigm where cell contact from differentiated daughter cells restricts adult stem cell multipotency to maintain the steady-state epithelial architecture.