Activation of NOTCH signaling impedes cell proliferation and survival in acute megakaryoblastic leukemia.

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines, and detected frequent genetic mutations in NOTCH pathway, besides previously reported alternations in GATA-1 and JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis and NOTCH activation holds a potential of therapeutic application for AMKL.

Immunogenicity after vaccination of COVID-19 vaccines in patients with cancer: a prospective, single center, observational study.

BACKGROUND: Patients with cancer, particularly those undergoing chemotherapy, are at risk from the low immunogenicity of Coronavirus Disease 19 (COVID-19) vaccines. METHODS: This prospective study assessed the seroconversion rate of COVID-19 vaccines among patients with cancer and hospital staff. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG (S-IgG) concentrations were evaluated before the first vaccination, and 1-3 and 4-6 months after the second vaccination. The primary endpoint was the seroconversion rate measured 1-3 months after the second vaccine. RESULTS: In total, 590 patients and 183 healthy hospital staff were analyzed. At 1-3 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/mL) in 96.1% (567/590) of the patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4-6 months after the second vaccination, the S-IgG antibody concentration exceeded the cut-off value (20 BAU/ml for S-IgG) in 93.1% (461/495) of the patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). Old age, being male, and low lymphocyte count were related to low SARS-CoV-2 S-IgG levels 1-3 months after the second vaccination among patients, while body mass index, smoking history, and serum albumin level were not. Patients undergoing platinum combination therapy and alkylating agent among cytotoxic drugs, and PARP inhibitor, mTOR inhibitor, and BCR-ABL inhibitor exhibited a low S-IgG antibody concentration compared to the no treatment group. CONCLUSIONS: COVID-19 vaccine immunogenicity was reduced among patients with cancer, especially under several treatment regimens.

Defect passivation in methylammonium/bromine free inverted perovskite solar cells using charge-modulated molecular bonding.

Molecular passivation is a prominent approach for improving the performance and operation stability of halide perovskite solar cells (HPSCs). Herein, we reveal discernible effects of diammonium molecules with either an aryl or alkyl core onto Methylammonium-free perovskites. Piperazine dihydriodide (PZDI), characterized by an alkyl core-electron cloud-rich-NH terminal, proves effective in mitigating surface and bulk defects and modifying surface chemistry or interfacial energy band, ultimately leading to improved carrier extraction. Benefiting from superior PZDI passivation, the device achieves an impressive efficiency of 23.17% (area ~1 cm2) (low open circuit voltage deficit ~0.327 V) along with superior operational stability. We achieve a certified efficiency of ~21.47% (area ~1.024 cm2) for inverted HPSC. PZDI strengthens adhesion to the perovskite via -NH2I and Mulliken charge distribution. Device analysis corroborates that stronger bonding interaction attenuates the defect densities and suppresses ion migration. This work underscores the crucial role of bifunctional molecules with stronger surface adsorption in defect mitigation, setting the stage for the design of charge-regulated molecular passivation to enhance the performance and stability of HPSC.

Real-world Data on the Incidence of Coronavirus Disease (COVID-19) in Patients With Advanced Thoracic Cancer During the Early Phase of the Pandemic in Japan.

BACKGROUND/AIM: The severity and associated mortality of coronavirus disease 2019 (COVID-19) are higher in patients with thoracic cancer than in healthy populations and those with other cancer types. Here, we investigated real-world data on the incidence of COVID-19 and false-negative cases using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing in patients with thoracic cancer. PATIENTS AND METHODS: We retrospectively reviewed patients with advanced thoracic cancer at the National Cancer Center Hospital between March 2020-May 2021. Blood samples were collected and evaluated for IgM and IgG antibodies specific for nucleocapsid (N) and spike (S) protein SARS-CoV-2 before and after rRT-PCR testing. False-negative cases were assessed based on anti-SARS-CoV-2 antibody levels before and after rRT-PCR testing. RESULTS: A total of 2,107 patients with thoracic cancer were identified between March 2020 and May 2021, 7 (0.3%) of whom developed COVID-19. Among the 218 patients who underwent at least one rRT-PCR test because of suspected COVID-19 symptoms or as a screening test at our institute, the most common diagnosis was non-COVID-19 pneumonia (34.4%), followed by tumor fever (30.7%). Furthermore, of the 218 patients, 120 paired serum samples before and after rRT-PCR testing were available. Seroconversion was identified in all three patients with positive SARS-CoV-2 rRT-PCR results but was only observed in 1 out of the 117 patients who tested negative; the rate of false-negative cases was low (0.9%). CONCLUSION: COVID-19 incidence among patients with advanced thoracic cancer was low during the early phase of the pandemic in Japan.

Hybrid double-spiral microfluidic chip for RBC-lysis-free enrichment of rare cells from whole blood.

Drug selection and treatment monitoring via minimally invasive liquid biopsy using circulating tumor cells (CTCs) are expected to be realized in the near future. For clinical applications of CTCs, simple, high-throughput, single-step CTC isolation from whole blood without red blood cell (RBC) lysis and centrifugation remains a crucial challenge. In this study, we developed a novel cancer cell separation chip, "hybrid double-spiral chip", that involves the serial combination of two different Dean flow fractionation (DFF) separation modes of half and full Dean cycles, which is the hybrid DFF separation mode for ultra-high-throughput blood processing at high precision and size-resolution separation. The chip allows fast processing of 5 mL whole blood within 30 min without RBC lysis and centrifugation. RBC and white blood cell (WBC) depletion rates of over 99.9% and 99%, respectively, were achieved. The average recovery rate of spiked A549 cancer cells was 87% with as low as 200 cells in 5 mL blood. The device can achieve serial reduction in the number of cells from approximately 1010 cells of whole blood to 108 cells, and subsequently to an order of 106 cells. The developed method can be combined with measurements of all recovered cells using imaging flow cytometry. As proof of concept, CTCs were successfully enriched and enumerated from the blood of metastatic breast cancer patients (N = 10, 1-69 CTCs per 5 mL) and metastatic prostate cancer patients (N = 10, 1-39 CTCs per 5 mL). We believe that the developed method will be beneficial for automated clinical analysis of rare CTCs from whole blood.

Highly sensitive and non-disruptive detection of residual undifferentiated cells by measuring miRNAs in culture supernatant.

The clinical usage of induced pluripotent stem cell (iPSC)-derived regenerative medicine products is limited by the possibility of residual undifferentiated cells forming tumours after transplantation. Most of the existing quality control tests involve crushing of cells. As a result, the cells to be transplanted cannot be directly tested, thereby increasing the cost of transplantation. Therefore, we tested a highly sensitive and non-disruptive quality-testing method that involves measuring microRNAs (miRNAs) in culture supernatants released by cells. By measuring miR-302b in the culture supernatant, residual iPSCs were detected with higher sensitivity than by measuring LIN28 (Lin-28 Homolog A) in the cells. To use this method, we also monitored the progression of differentiation. Our novel highly sensitive and non-disruptive method for detecting residual undifferentiated cells will contribute to reducing the manufacturing cost of iPSC-derived products and improving the safety of transplantation.

Surface Passivation of Sputtered NiO x Using a SAM Interface Layer to Enhance the Performance of Perovskite Solar Cells.

Sputtered NiO x (sp-NiO x ) is a preferred hole transporting material for perovskite solar cells because of its hole mobility, ease of manufacturability, good stability, and suitable Fermi level for hole extraction. However, uncontrolled defects in sp-NiO x can limit the efficiency of solar cells fabricated with this hole transporting layer. An interfacial layer has been proposed to modify the sp-NiO x /perovskite interface, which can contribute to improving the crystallinity of the perovskite film. Herein, a 2-(3,6-dimethoxy-9H-carbazol-9-yl)ethyl]phosphonic acid (MeO-2PACz) self-assembled monolayer was used to modify an sp-NiO x surface. We found that the MeO-2PACz interlayer improves the quality of the perovskite film due to an enlarged domain size, reduced charge recombination at the sp-NiO x /perovskite interface, and passivation of the defects in sp-NiO x surfaces. In addition, the band tail states are also reduced, as indicated by photothermal deflection spectroscopy, which thus indicates a reduction in defect levels. The overall outcome is an improvement in the device efficiency from 11.9% to 17.2% due to the modified sp-NiO x /perovskite interface, with an active area of 1 cm2 (certified efficiency of 16.25%). On the basis of these results, the interfacial engineering of the electronic properties of sp-NiO x /MeO-2PACz/perovskite is discussed in relation to the improved device performance.

Chemical and Electronic Investigation of Buried NiO1-δ, PCBM, and PTAA/MAPbI3-xClx Interfaces Using Hard X-ray Photoelectron Spectroscopy and Transmission Electron Microscopy.

Identification and profiling of molecular fragments generated over the lifespan of halide perovskite solar cells are needed to overcome the stability issues associated with these devices. Herein, we report the characterization of buried CH3NH3PbI3-xClx (HaP)-transport layer (TL) interfaces. By using hard X-ray photoelectron spectroscopy in conjunction with transmission electron microscopy, we reveal that the chemical decomposition of HaP is TL-dependent. With NiO1-δ, phenyl-C61-butyric acid methyl ester (PCBM), or poly(bis(4-phenyl) (2,4,6-trimethylphenyl)amine) (PTAA) as TLs, probing depth analysis shows that the degradation takes place at the interface (HaP/TL) rather than the HaP bulk area. From core-level data analysis, we identified iodine migration toward the PCBM- and PTAA-TLs. Unexpected diffusion of nitrogen inside NiO1-δ-TL was also found for the HaP/NiO1-δ sample. With a HaP/PCBM junction, HaP is dissociated to PbI2, whereas HaP/PTAA contact favored the formation of CH3I. The low stability of HaP solar cells in the PTAA-TL system is attributed to the formation of CH3I and iodide ion vacancies. Improved stability observed with NiO1-δ-TL is related to weak dissociation of stoichiometric HaP. Here, we provide a new insight to further distinguish different mechanisms of degradation to improve the long-term stability and performance of HaP solar cells.

Photoinduced ion-redistribution in CH3NH3PbI3 perovskite solar cells.

We use photoinduced absorption spectroscopy (PAS) to study the ionic motion in CH3NH3PbI3 perovskite solar cells, consisting of indium tin oxide (ITO)/NiOx/perovskite/phenyl-C61-butyric-acid-methyl ester (PCBM)/aluminum-doped zinc oxide (AZO)/ITO. We observed a slow (∼50 mHz) spectral blue shift (∼10-4 eV) under modulated 520 nm illumination, which we interpreted in terms of the modulation in the bulk ion density. Numerical simulation shows that the mobile ion moves in and out from the double layers at the perovskite/charge transport layer interfaces in order to recover the bulk charge neutrality tipped off-balance by the photocarriers. The diffusion coefficient of the ion is 10-10 to 10-11 cm2 s-1, when we assume that the characteristic time constant of the ion motion is governed by the diffusion.

Integrated system for detection and molecular characterization of circulating tumor cells.

Circulating tumor cells (CTCs) invade blood vessels in solid tumors and promote metastases by circulating in the blood. CTCs are thus recognized as targets for liquid biopsy and can provide useful information for design of treatments. This diagnostic approach must consider not only the number of CTCs but also their molecular and genetic characteristics. For this purpose, use of devices that enrich CTCs independent of these characteristics and detectors that recognize various CTC characteristics is essential. In the present study, we developed a CTC detection system comprising ClearCell FX and ImageStream Mark II. We clarified the analytical performance of this system by evaluating recovery rate, lower limits of detection, and linearity. These parameters are critical for detecting rare cells, such as CTCs. We tested these parameters using three cell lines with different expression levels of the epithelial marker-epithelial cell adhesion molecule (EpCAM) and spiked these cells into whole-blood samples from healthy donors. The average recovery rate and lower limit of detection were approximately 40% and five cells/7.5 mL of whole blood, respectively. High linearity was observed for all evaluated samples. We also evaluated the ability of the system to distinguish between normal and abnormal cells based on protein expression levels and gene amplification and found that the system can identify abnormal cells using these characteristics. The CTC detection system thus displays the ability to distinguish specific characteristics of CTC, thereby providing valuable information for cancer treatment.

Enhanced Photosensitization by Carbon Dots Co-adsorbing with Dye on p-Type Semiconductor (Nickel Oxide) Solar Cells.

In this work, the effect of carbon dots (C-dots) on the performance of NiO-based dye-sensitized solar cells (DSSCs) was explored. NiO nanoparticles (NPs) with a rectangular shape (average size: 11.4 × 16.5 nm2) were mixed with C-dots, which were synthesized from citric acid (CA) and ethylenediamine (EDA). A photocathode consisting of a composite of C-dots with NiO NPs (NiO@C-dots) was then used to measure the photovoltaic performance of a DSSC. A power conversion efficiency (PCE) of 9.85% (430 nm LED@50 mW/cm2) was achieved by a DSSC fabricated via the adsorption of N719 sensitizer with a C-dot content of 12.5 wt % at a 1.5:1 EDA/CA molar ratio. This PCE value was far larger than the PCE value (2.44 or 0.152%) obtained for a NiO DSSC prepared without the addition of C-dots or N719, respectively, indicating the synergetic effect by the co-adsorption of C-dots and N719. This synergetically higher PCE of the NiO@C-dot-based DSSC was due to the larger amount of sensitizer adsorbed onto the composites with a larger specific surface area and the faster charge transfer in the NiO@C-dot working electrode. In addition, the C-dots bound to the NiO NPs shorten the band gap of the NiO NPs due to energy transfer and give rise to faster charge separation in the electrode. The most important fact is that C-dots are the main sensitizer, while N719 tightly adsorbs on C-dots and NiO behaves as an accelerator of a positive electron transfer and a restrainer of the electron-hole recombination. These results reveal that C-dots are a remarkable enhancer for NiO NPs in DSSCs and that NiO@C-dots are promising photovoltaic electrode materials for DSSCs.

Unraveling the Impacts Induced by Organic and Inorganic Hole Transport Layers in Inverted Halide Perovskite Solar Cells.

The carrier transport layers (CTLs) have exhibited the influence on performance and stability of halide perovskite solar cells (HaPSCs). The exploration of characteristic impacts on HaPSCs induced by the CTL unveils the key factors underlying the device physics. In this work, we investigate the impacts of the organic or inorganic hole transport layer (HTL) in HaPSCs by analyzing the elemental distribution, the current-voltage characteristics, and the capacitance spectroscopy. The organic HTL device shows the lower activation energy ( EA < Eg) indicating a dominant interface-mediated recombination. The defect analysis reveals that the device with the inorganic HTL induces rather deep antisite defects with slightly higher trap densities. This is attributed to the diffusion of metal cations into the halide perovskite (HaP) during crystallization of HaP layer grown on the inorganic HTLs. Our results suggest that the passivation of deep defect and suppression of trap densities in the HaP either using ideal CTLs or optimizing the fabrication route is crucial to improving the device parameters approaching the theoretical limit.

Raman spectroscopic study of ZnO/NiO nanocomposites based on spatial correlation model.

The effect of nickel concentration has been investigated in ZnO/NiO nanocomposites synthesized using the co-precipitation method. The X-ray diffraction and TEM measurements confirm the distinct phase of NiO in the ZnO/NiO samples. Furthermore, the Raman study shows the sharp modes at 99 cm-1 and 438 cm-1 corresponding to E(low) 2, E(high) 2 of hexagonal wurtzite ZnO structure and, 1080 cm-1 associated to the two-phonon (2P) mode of NiO, respectively. We also compared the effect of Ni concentration on the formation of ZnO/NiO by analyzing Ehigh 2 Raman mode of ZnO with the help of spatial correlation model. The correlation lengths, broadening and asymmetry ratio obtained from the fitting showed good agreement with the experimental results.

Photocarrier dynamics in perovskite-based solar cells revealed by intensity-modulated photovoltage spectroscopy.

We studied perovskite photovoltaic devices with intensity-modulated photovoltage spectroscopy. Two coexisting relaxation times are found in accordance with the results of previous impedance spectroscopy (IS) measurements. The slower time constant is independent of the light power while the faster one is inversely proportional to the light power. We employed the surface polarization picture used in the IS analysis augmented by a plausible assumption that the surface polarization is proportional to the light intensity to explain the inverse power dependence of the fast time constant. Because the surface polarization results from the surface accumulated charges, its lateral (parallel to the electrode) distribution and dynamics should be known. We present evidence that the surface accumulated charges indeed form a two-dimensional layer, and have a finite binding energy and a diffusion length.

Tailoring the Open-Circuit Voltage Deficit of Wide-Band-Gap Perovskite Solar Cells Using Alkyl Chain-Substituted Fullerene Derivatives.

Wide-band-gap (WB) perovskite devices are promising as the top cell of silicon-perovskite tandem devices to boost the efficiency beyond the Shockley-Queisser limit. Here, we tailor the performance parameters of WB mixed-halide perovskite solar cell with long alkyl chain-substituted fullerene derivatives as an electron transport layer (ETL). The device with C60-fused N-methylpyrrolidine- meta-dodecyl phenyl (C60MC12) demonstrates an enhanced power conversion efficiency of 16.74% with the record open circuit voltage ( VOC) of 1.24 V, an increase by 70 mV with concomitant VOC deficit reduction to 0.47 V. This is achieved by mitigating the recombination loss through the use of highly crystalline C60MC12 film compared to amorphous [6,6]-phenyl-C61-butyric acid methyl ester layer. The device analysis reveals the soothing of the defect activities with shallower defect states and passivation of the interface recombination centers for the device with C60MC12. We ascribe this property to the crystallinity of fullerene derivatives as ETL, which is also important for the optimization of device parameters, besides the band alignment matching of WB perovskite devices.

Colloidal Synthesis of Air-Stable Alloyed CsSn1-xPbxI3 Perovskite Nanocrystals for Use in Solar Cells.

Organic-inorganic hybrid perovskite solar cells have demonstrated unprecedented high power conversion efficiencies in the past few years. Now, the universal instability of the perovskites has become the main barrier for this kind of solar cells to realize commercialization. This situation can be even worse for those tin-based perovskites, especially for CsSnI3, because upon exposure to ambient atmosphere the desired black orthorhombic phase CsSnI3 would promptly lose single crystallinity and degrade to the inactive yellow phase, followed by irreversible oxidation into metallic Cs2SnI6. By alloying CsSnI3 with CsPbI3, we herein report the synthesis of alloyed perovskite quantum dot (QD), CsSn1-xPbxI3, which not only can be phase-stable for months in purified colloidal solution but also remains intact even directly exposed to ambient air, far superior to both of its parent CsSnI3 and CsPbI3 QDs. Ultrafast transient absorption spectroscopy studies reveal that the photoexcited electrons in the alloyed QDs can be injected into TiO2 nanocrystals at a fast rate of 1.12 × 1011 s-1, which enables a high photocurrent generation in solar cells.

Direct Observation of Ultrafast Hole Injection from Lead Halide Perovskite by Differential Transient Transmission Spectroscopy.

Efficient charge separation at the interfaces of the perovskite with the carrier transport layers is crucial for perovskite solar cells to achieve high power conversion efficiency. We present a systematic experimental study on the hole injection dynamics from MAPbI3 perovskite to three typical hole transport materials (HTMs). We extract the carrier dynamics directly related to the hole injection by employing a pump light with short absorption depth and comparing the transient transmission signals excited on the two sides of the sample. The differential transmission signals reveal the hole injections to PTAA and PEDOT:PSS to be complete within 1 and 2 ps, respectively, and that to NiOx to exhibit an additional slow process on a 40 ps time scale. The obtained injection dynamics are discussed in comparison with the device performance of the solar cells containing the same MAPbI3/HTM interfaces.

NiO x Hole Transport Layer for Perovskite Solar Cells with Improved Stability and Reproducibility.

In this study, highly stable, low-temperature-processed planar lead halide perovskite (MAPbI3-x Cl x ) solar cells with NiO x interfaces have been developed. Our solar cells maintain over 85% of the initial efficiency for more than 670 h, at the maximum power point tracking (MPPT) under 1 sun illumination (no UV-light filtering) at 30 °C, and over 73% of the initial efficiency for more than 1000 h, at the accelerating aging test (85 °C) under the same MPPT condition. Storing the encapsulated devices at 85 °C in dark over 1000 h revealed no performance degradation. The key factor for the prolonged lifetime of the devices was the sputter-deposited polycrystalline NiO x hole transport layer (HTL). We observed that the properties of NiO x are dependent on its composition. At a higher Ni3+/Ni2+ ratio, the conductivity of NiO x is higher, but at the expense of optical transmittance. We obtained the highest power conversion efficiency of 15.2% at the optimized NiO x condition. The sputtered NiO x films were used to fabricate solar cells without annealing or any other treatments. The device stability enhanced significantly compared to that of the devices with PEDOT:PSS HTL. We clearly demonstrated that the illumination-induced degradation depends heavily on the nature of the HTL in the inverted perovskite solar cells (PVSCs). The sputtered NiO x HTL can be a good candidate to solve stability problems in the lead halide PVSCs.

Hysteresis, Stability, and Ion Migration in Lead Halide Perovskite Photovoltaics.

Ion migration has been suspected as the origin of various irreproducible and unstable properties, most notably the hysteresis, of lead halide perovskite photovoltaic (PV) cells since the early stage of the research. Although many evidence of ionic movement have been presented both numerically and experimentally, a coherent and quantitative picture that accounts for the observed irreproducible phenomena is still lacking. At the same time, however, it has been noticed that in certain types of PV cells, the hysteresis is absent or at least within the measurement reproducibility. We have previously shown that the electronic properties of hysteresis-free cells are well represented in terms of the conventional inorganic semiconductors. The reproducibility of these measurements was confirmed typically within tens of minutes under the biasing field of -1 V to +1.5 V. In order to probe the effect of ionic motion in the hysteresis-free cells, we extended the time scale and the biasing rage in the electronic measurements, from which we conclude the following: (1) From various evidence, it appears that ion migration is inevitable. However, it does not cause detrimental effects to the PV operation. (2) We propose, based on the quantitative characterization, that the degradation is more likely due to the chemical change at the interfaces between the carrier selective layers and perovskite rather than the compositional change of the lead iodide perovskite bulk. Together, they give much hope in the use of the lead iodide perovskite in the use of actual application.

Novel Surface Passivation Technique for Low-Temperature Solution-Processed Perovskite PV Cells.

Low-temperature solution-processed perovskite solar cells are attracting immense interest due to their ease of fabrication and potential for mass production on flexible substrates. However, the unfavorable surface properties of planar substrates often lead to large variations in perovskite crystal size and weak charge extractions at interfaces, resulting in inferior performance. Here, we report the improved performance, reproducibility, and high stability of "p-i-n" planar heterojunction perovskite solar cells. The key fabrication process is the addition of the amine-polymer poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN-P1) to a simple spin-coating process. The PFN-P1 works as a surfactant and helps promote uniform crystallization. As a result, perovskite films with PFN-P1 have a uniform distribution of grain sizes and improved open circuit voltage. Devices with PFN-P1 showed the best efficiency (13.2%), with a small standard deviation (0.40), out of 60 cells. Moreover, ∼90% of the initial efficiency was retained over more than 6 months. Additionally, devices fabricated from PFN-P1 mixed perovskite films showed higher stability under continuous operation at maximum power point over 150 h. Our results show that this approach is simple and effective for improving device performance, reproducibility, and stability by modifying perovskite properties with PFN-P1. Because of the simplicity of the fabrication process and reliable performance increase, this approach marks important progress in low-temperature solution-processed perovskite solar cells.