Transcriptional regulation of FACT involves Coordination of chromatin accessibility and CTCF binding.

Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.

DNA Hypomethylation-Mediated Transcription Dysregulation Participates in Pathogenesis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggests that abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. Herein, a dehydroepiandrosterone-induced PCOS-like mouse model which has a similar metabolic and reproductive phenotype as human patients with PCOS was generated. It was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provide direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease.

Topological properties analysis and identification of mild cognitive impairment based on individual morphological brain network connectome.

Mild cognitive impairment is considered the prodromal stage of Alzheimer's disease. Accurate diagnosis and the exploration of the pathological mechanism of mild cognitive impairment are extremely valuable for targeted Alzheimer's disease prevention and early intervention. In all, 100 mild cognitive impairment patients and 86 normal controls were recruited in this study. We innovatively constructed the individual morphological brain networks and derived multiple brain connectome features based on 3D-T1 structural magnetic resonance imaging with the Jensen-Shannon divergence similarity estimation method. Our results showed that the most distinguishing morphological brain connectome features in mild cognitive impairment patients were consensus connections and nodal graph metrics, mainly located in the frontal, occipital, limbic lobes, and subcortical gray matter nuclei, corresponding to the default mode network. Topological properties analysis revealed that mild cognitive impairment patients exhibited compensatory changes in the frontal lobe, while abnormal cortical-subcortical circuits associated with cognition were present. Moreover, the combination of multidimensional brain connectome features using multiple kernel-support vector machine achieved the best classification performance in distinguishing mild cognitive impairment patients and normal controls, with an accuracy of 84.21%. Therefore, our findings are of significant importance for developing potential brain imaging biomarkers for early detection of Alzheimer's disease and understanding the neuroimaging mechanisms of the disease.

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. METHODS: The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models. RESULTS: Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway. CONCLUSION: High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.

The Value of Amide Proton Transfer MRI in the Diagnosis of Malignant and Benign Urinary Bladder Lesions: Comparison With Diffusion-Weighted Imaging.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has certain limitations in distinguishing between malignant and benign urinary bladder (UB) lesions. Amide proton transfer (APT) imaging may provide more diagnostic information than diffusion-weighted imaging (DWI) to distinguish between malignant and benign UB. PURPOSE: To investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and to compare its diagnostic efficacy with that of conventional DWI. STUDY TYPE: Prospective. SUBJECTS: Eighty patients with UB lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/turbo spin echo (TSE) T1-weighted and T2-weighted imaging, single-shot echo planar DWI, and three-dimensional TSE APT imaging. ASSESSMENT: Patients underwent radical cystectomy or transurethral resection of the bladder lesions within 2 weeks after CT urography and MRI examination. APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions. STATISTICAL TESTS: Kolmogorov-Smirnov test, Student's t test or Mann-Whitney U test, Spearman rank correlation coefficient, area under the receiver operating characteristic (ROC) curve (AUC), Delong test, and intraclass correlation coefficient (ICC). The significance threshold was set at P < 0.05. RESULTS: Thirty-two patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumor, and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma. Urothelial carcinomas showed significantly higher MTRasym values (1.53% [0.74%] vs. 0.85% [0.23%]) and significantly lower ADC values (1.24 ± 0.34 × 10-3 mm2/s vs. 1.43 ± 0.22 × 10-3 mm2/s) than benign UB lesions. The MTRasym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722). DATA CONCLUSION: APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Biomimetic Molybdenum Sulfide-Catalyzed Tumor Ferroptosis and Bioimaging.

The chemical generation of singlet oxygen (1 O2 ) by the MoO4 2- -catalyzed disproportionation of hydrogen peroxide (H2 O2 ) has been widely applied in numerous catalytic processes; however, such molybdate ions cannot be administered for redox-based cancer therapeutics. This work reports the albumin-mediated biomimetic synthesis of highly active molybdenum sulfide (denoted MoB) nanocatalysts that mediate the simultaneous generation of 1 O2 and superoxide anion (O2 •- ) from H2 O2 , which is relatively abundant in malignant tumors. The MoB-catalyzed reactive oxygen species (ROS) are able to activate the ferroptosis pathway and cause lipid peroxidation for efficient cancer therapy. Furthermore, for the first time, the catalytic activity of MoB is visualized in situ. Moreover, a catalytic imaging modality based on MoB is developed for specific imaging of inflammation diseases without background interference. Therefore, this study presents a biomimetic strategy toward Mo-based nanocatalysts for ROS-facilitated tumor ferroptosis and catalytic imaging.

Interactions between flue gas desulfurization gypsum and biochar on water infiltration characteristics and physicochemical properties of saline-alkaline soil.

The application of flue gas desulfurization gypsum (FGDG) improves the soil structure, reduces soil pH, and accelerates soil salt leaching. Biochar amendment to soil can affect the soil infiltration rate, increase soil porosity, decrease soil bulk density, and enhance the water retention capacity. This study investigated the interactive effect of FGDG and biochar on water infiltration characteristics and physicochemical properties as well as determined the optimal amendment rate as a saline-alkaline soil conditioner. Seven experimental schemes were designed, and the newly reclaimed cultivated soil from Pingtan Comprehensive Experimental Zone in Fujian Province, China, was used in an indoor soil column experiment to simulate soil infiltration. Five models were employed to describe the infiltration process. The power function was used to represent the dynamic process of the wetting front. The conclusions of this study are as follows: (1) there was a reduction in the infiltration capacity of saline-alkaline soil (sandy soil) in each treatment, and the application of FGDG alone had the highest inhibition effect compared to the control (CK). The Kostiakov model provides the best fit for the experimental data of soil cumulative infiltration. (2) All treatments increased the total porosity and water content of saline-alkali soil, with the combined application of FGDG and biochar found to be more effective. (3) The application of FGDG alone or in combination with biochar decreased the pH and increased the electrical conductivity of the saline-alkali soil significantly, with the combined application having the most significant effect. In contrast, soil amended with biochar alone had minimal effect on the pH and EC of the soil. (4) The best improvement ratio was achieved with the F1B2 combination (75 g/kg FGDG + 30 g/kg biochar).

Fluorine-Containing Passivation Layer via Surface Chelation for Inorganic Perovskite Solar Cells.

Minimizing surface defect is vital to further improve power conversion efficiency (PCE) and stability of inorganic perovskite solar cells (PSCs). Herein, we designed a passivator trifluoroacetamidine (TFA) to suppress CsPbI3-x Brx film defects. The amidine group of TFA can strongly chelate onto the perovskite surface to suppress the iodide vacancy, strengthened by additional hydrogen bonds. Moreover, three fluorine atoms allow strong intermolecular connection via intermolecular hydrogen bonds, thus constructing a robust shield against moisture. The TFA-treated PSCs exhibit remarkably suppressed recombination, yielding the record PCEs of 21.35 % and 17.21 % for 0.09 cm2 and 1.0 cm2 device areas, both of which are the highest for all-inorganic PSCs so far. The device also achieves a PCE of 39.78 % under indoor illumination, the highest for all-inorganic indoor photovoltaic devices. Furthermore, TFA greatly improves device ambient stability by preserving 93 % of the initial PCE after 960 h.

Excessive activation of HOXB13/PIMREG axis promotes hepatocellular carcinoma progression and drug resistance.

The transcription factor HOXB13 is bound up with the occurrence, progression and drug fast of many kinds of cancer. Nevertheless, the specific molecular mechanism of HOXB13 in hepatocellular carcinoma (HCC) is still unknown. This provides an obstacle to the exploration of HCC treatments targeting HOXB13. This study found that HOXB13 was up-regulated in HCC tissues. HOXB13 enhanced the multiplication and metastasis of HCC cells. It enhanced HCC cell drug and anoikis resistance. The analysis of HCC RNA seq data indicated that the expression of HOXB13 and PIMREG were positively correlated. Luciferase report assay showed that HOXB13 could activate PIMREG promoter transcription. The results of RT-qPCR and western blot showed that HOXB13 regulated the transcription of PIMREG. Western blot proved that high expression of PIMREG participated in DNA damage repair and cell cycle regulation by up-regulating RAD51, BRCA1, CDC25A, CDC25B and CDC25C and down-regulating HIPK2. This led to a significant increase in DNA repair capacity, accelerated cell cycle progression, and insensitive to DNA damage. Down-regulation of PIMREG in Hep3B cells overexpressing HOXB13 attenuated the phenotype induced by HOXB13. Therefore, HOXB13 functioned through PIMREG instead of directly regulating the transcription of RAD51, BRCA1, CDC25A, CDC25B and CDC25C. The same results were obtained in vivo. It was concluded that HOXB13 affected the expression of cell cycle and DNA repair related factors by up-regulating the transcription of PIMREG, thereby promoting the progression of HCC and enhancing the resistance of HCC to chemotherapeutics.

Molecular mechanism of circRNAs in drug resistance in renal cell carcinoma.

Renal cell carcinoma (RCC) is one of the most common malignant tumors with a poor response to radiotherapy and chemotherapy. The advent of molecular targeted drugs has initiated great breakthroughs in the treatment of RCC. However, drug resistance to targeted drugs has become an urgent problem. Various studies across the decades have confirmed the involvement of circular RNAs (circRNAs) in multiple pathophysiological processes and its abnormal expression in many malignant tumors. This review speculated that circRNAs can provide a new solution to drug resistance in RCC and perhaps be used as essential markers for the early diagnosis and prognosis of RCC. Through the analysis and discussion of relevant recent research, this review explored the relationship of circRNAs to and their regulatory mechanisms in drug resistance in RCC. The results indicate an association between the expression of circRNAs and the development of RCC, as well as the involvement of circRNAs in drug resistance in RCC.

Fe3O4 magnetic nanoparticle-enhanced radiotherapy for lung adenocarcinoma via delivery of siBIRC5 and AS-ODN.

BACKGROUND: Radiotherapy is the mainstay treatment for lung adenocarcinoma, yet remains highly susceptible to resistance. Fe3O4 magnetic nanoparticles (MNPs) possess the ability to induce biological therapeutic effects. Herein, the current study set out to explore the effects of Fe3O4 MNPs on radiosensitivity of lung adenocarcinoma cells. METHODS: Fe3O4 MNPs loaded with both negatively-charged small interfering RNA against baculoviral IAP repeat containing 5 (siBIRC5) and oligodeoxynucleotide antisense (AS-ODN) to generate co-delivery NPs, followed by evaluation. Gel retardation assay was further performed to determine the binding ability of Fe3O4 MNPs to AS-ODN/siBIRC5. The radiosensitizing effect of NPs on lung adenocarcinoma cells was determined in the absence or the presence of NPs or radiotherapy. A549 and H460 tumor-bearing mice were established, where tumor tissues were subjected to immunohistochemistry. RESULTS: NPs were successfully prepared and characterized. BIRC5 expression levels were augmented in tissues of lung cancer patients. Fe3O4 MNPs enhanced the uptake of siBIRC5 and AS-ODN by lung adenocarcinoma cells. The presence of NPs under magnetic field reduced the BIRC5 expression and elevated the DR5 expression in lung adenocarcinoma cells. Lung adenocarcinoma cells treated with NPs exhibited inhibited tumor cell migration and increased DNA damage. After magnetic field treatment, tumors were better suppressed in the tumor-bearing mice treated with NPs, followed by radiotherapy. CONCLUSION: Findings obtained in our study indicated that Fe3O4 MNPs-targeted delivery of siBIRC5 and AS-ODN enhances radiosensitivity, providing an innovative solution for the current clinically existing lung adenocarcinoma patients with radiotherapy resistance with a low risk of toxicity.

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience.

BACKGROUND: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. METHODS: We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6-56.8%) and 37.5% (95% CI, 24.0-52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. CONCLUSIONS: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

An intelligent responsive macrophage cell membrane-camouflaged mesoporous silicon nanorod drug delivery system for precise targeted therapy of tumors.

Macrophage cell membrane-camouflaged nanocarriers can effectively reduce immune cell clearance and actively target tumors. In this study, a macrophage cell membrane-camouflaged mesoporous silica nanorod (MSNR)-based antitumor drug carrier equipped with a cationic polymer layer was developed. As drug carriers, these MSNRs were loaded with the thermosensitive phase change material L-menthol (LM), the chemotherapy drug doxorubicin (DOX) and the fluorescent molecule indocyanine green (ICG). The rod-like shape of the MSNRs was shown to enhance the penetration of the drug carriers to tumors. In the weakly acidic tumor microenvironment, the cationic polymer exhibited a proton sponge effect to trigger macrophage cell membrane coating detachment, promoting tumor cell uptake. Following nanocarrier uptake, ICG is heated by near-infrared (NIR) irradiation to make LM undergo a phase transition to release DOX and generate a synergistic effect of thermochemotherapy which kills tumor cells and inhibits tumor growth together with reactive oxygen species (ROS) produced by ICG. Overall, this nanohybrid drug delivery system demonstrates an intelligent cascade response, leads to tissue-cell specific targeting and improves drug release accuracy, thus proving to be an effective cancer therapy.

TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis.

BACKGROUND: To investigate the roles of the transcription factors twist family bHLH transcription factor 1 (TWIST1), twist family bHLH transcription factor 2 (TWIST2), and peroxisome proliferator activated receptor gamma (PPARγ) in the progression of nonalcoholic steatohepatitis. METHODS: The protein levels of TWIST1, TWIST2 and PPARγ were determined in the serum of nonalcoholic fatty liver disease (NAFLD) patients and healthy controls by enzyme-linked immunosorbent assay (ELISA). An in vivo model for fatty liver was established by feeding C57BL/6 J mice a high-fat diet (HFD). An in vitro model of steatosis was established by treating LO-2 cells with oleic acid (OA). RNA sequencing was performed on untreated and OA-treated LO-2 cells followed by TWIST1, TWIST2 and PPARγ gene mRNA levels analysis, Gene Ontology (GO) enrichment and pathway analysis. RESULTS: The TWIST2 serum protein levels decreased significantly in all fatty liver groups (P < 0.05), while TWIST1 varied. TWIST2 tended to be lower in mice fed an HFD and was significantly lower at 3 months. Similarly, in the in vitro model, the TWIST2 protein level was downregulated significantly at 48 and 72 h after OA treatment. RNA sequencing of LO-2 cells showed an approximately 2.3-fold decrease in TWIST2, with no obvious change in TWIST1 and PPARγ. The PPAR signaling pathway was enriched, with 4 genes upregulated in OA-treated cells (P = 0.0018). The interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways were enriched in OA-treated cells. CONCLUSIONS: The results provide evidence that the TWIST2 and PPAR signaling pathways are important in NAFLD and shed light on a potential mechanism of steatosis.

CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer.

Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax.

OBJECTIVE: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUVmax), were used to evaluate the PET/CT scans before transplantation. RESULTS: In patients with Deauville 1-3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUVmax cut-off of 66% criterion, in patients with a ΔSUVmax of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUVmax, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. CONCLUSION: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUVmax in prognostic prediction.

Ultrastable Perovskite-Zeolite Composite Enabled by Encapsulation and In†Situ Passivation.

Metal halide perovskites have been widely applied in optoelectronic fields, but their poor stability hinders their actual applications. A perovskite-zeolite composite was synthesized via in situ growth in air from aluminophosphate AlPO-5 zeolite crystals and perovskite nanocrystals. The zeolite matrix provides quantum confinement for perovskite nanocrystals, achieving efficient green emission, and it passivates the defects of perovskite by H-bonding interaction, which leads to a longer lifetime compared to bulk perovskite film. Furthermore, the AlPO-5 zeolite also acts as a protection shield and enables ultrahigh stability of perovskite nanocrystals under 150 °C heat stress, under a 15-month long-term ambient exposure, and even in water for more than 2 weeks, respectively. The strategy of in situ passivation and encapsulation for the perovskite@AlPO-5 composite was amenable to a range of perovskites, from MA- to Cs-based perovskites. Benefiting from high stability and photoluminescence performance, the composite exhibits great potential to be virtually applied in light-emitting diodes (LEDs) and backlight displays.

Dynamical Transformation of Two-Dimensional Perovskites with Alternating Cations in the Interlayer Space for High-Performance Photovoltaics.

The two-dimensional (2D) perovskites stabilized by alternating cations in the interlayer space (ACI) define a new type of structure with different physical properties than the more common Ruddlesden-Popper counterparts. However, there is a lack of understanding of material crystallization in films and its influence on the morphological/optoelectronic properties and the final photovoltaic devices. Herein, we undertake in situ studies of the solidification process for ACI 2D perovskite (GA)(MA) nPb nI3 n+1 (⟨ n⟩ = 3) from ink to solid-state semiconductor, using solvent mixture of DMSO:DMF (1:10 v/v) as the solvent and link this behavior to solar cell devices. The in situ grazing-incidence X-ray scattering (GIWAXS) analysis reveals a complex journey through disordered sol-gel precursors, intermediate phases, and ultimately to ACI perovskites. The intermediate phases, including a crystalline solvate compound and the 2D GA2PbI4 perovskite, provide a scaffold for the growth of the ACI perovskites during thermal annealing. We identify 2D GA2PbI4 to be the key intermediate phase, which is strongly influenced by the deposition technique and determines the formation of the 1D GAPbI3 byproducts and the distribution of various n phases of ACI perovskites in the final films. We also confirm the presence of internal charge transfer between different n phases through transient absorption spectroscopy. The high quality ACI perovskite films deposited from solvent mixture of DMSO:DMF (1:10 v/v) deliver a record power conversion efficiency of 14.7% in planar solar cells and significantly enhanced long-term stability of devices in contrast to the 3D MAPbI3 counterpart.

Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism.

BACKGROUND: Hematopoietic abnormality is a common cause of cirrhotic hypersplenism (CH) complications and death; it causes serious adverse effects and is associated with bleeding, anemia, infection in CH patients. However, the underlying mechanism is unclear. AIMS: We aimed to investigate the effects of the spleen on hematopoiesis and hematopoietic stem/progenitor cells (HSPCs) in CH patients. METHODS: Eleven CH patients were enrolled to assess the effects of the spleen on HSPC functions. Hematopoietic changes were examined by flow cytometry analysis. HSPC functions were detected with colony-forming assays and in vitro cell cultures. Enzyme-linked immunosorbent assay (ELISA) was used to test the concentration of epithelial growth factor (EGF). RESULTS: The number of HSPCs was decreased in CH patients and was rescued after splenectomy. Serum from CH patients dysregulated HSPCs function, and serum from splenectomy patients restored the dysregulated HSPC function in vitro. The concentration of EGF was decreased in CH patients and was restored to normal level after splenectomy. EGF rescued the dysregulated HSPCs function in vitro. CONCLUSIONS: The spleen can regulate the functions of HSPCs in CH patients by regulating EGF signaling. EGF may be a therapeutic target for CH treatment.

Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.

Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.