Achieving Low-Dose Rate X-Ray Imaging Based on 2D/3D-Mixed Perovskite Films.

X-ray detection and imaging are widely used in medical diagnosis, product inspection, security monitoring, etc. Large-scale polycrystalline perovskite thick films possess high potential for direct X-ray imaging. However, the notorious problems of baseline drift and high detection limit caused by ions migration are still remained. Here, ion migration is reduced by incorporating 2D perovskite into 3D perovskite, thereby increasing the ion activation energy. This approach hinders ion migration within the perovskite film, consequently suppressing baseline drift and reducing the lowest detection limit(LOD) of the device. As a result, the baseline drifting declines by 20 times and the LOD reduces to 21.1 nGy s-1, while the device maintains a satisfactory sensitivity of 5.6 × 103 µC Gy-1 cm-2. This work provides a new strategy to achieve low ion migration in large-scale X-ray detectors and may provide new thoughts for the application of mixed-dimension perovskite.

A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens.

The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin ß5) as the essential integrin α/ß pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the ß-propeller domain of ITGAV for integrin αVß5 dimerization. Combined with in silico compound docking, we developed a CRISPR-Tiling-Instructed Computer-Aided (CRISPR-TICA) pipeline for drug discovery and identified Cpd_AV2 as a lead inhibitor targeting the ß-propeller central pocket of ITGAV. Cpd_AV2 treatment led to rapid uncoupling of integrin αVß5 and cellular apoptosis, providing a unique class of therapeutic action that eliminates the integrin signaling via heterodimer dissociation. We also foresee the CRISPR-TICA approach to be an accessible method for future drug discovery studies.

Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery.

Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of the epigenetic reader Tudor domains in leukemia progression and therapy remain unexplored. Here, we conducted a Tudor domain-focused CRISPR screen and identified SGF29, a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis. To facilitate drug development, we integrated the CRISPR tiling scan with compound docking and molecular dynamics simulation, presenting a generally applicable strategy called CRISPR-Scan Assisted Drug Discovery (CRISPR-SADD). Using this approach, we identified a lead inhibitor that selectively targets SGF29's Tudor domain and demonstrates efficacy against leukemia. Furthermore, we propose that the structural genetics approach used in our study can be widely applied to diverse fields for de novo drug discovery.

Using N-I-N Photodiodes Made of Perovskite Single Crystals for Low Noise Gamma-Ray Spectroscopy.

Solution-processed lead halide perovskite single crystals (LHPSCs) are believed to have great potential in gamma-ray spectroscopy. However, obtaining low-defect LHPSCs from a solution at low temperatures is difficult compared to obtaining Bridgman single crystals such as CdTe and Si. Herein, noise from the intrinsic defects of LHPSCs is considered as the main problem hindering their gamma-ray detection performance. By isolating the defect-induced holes in LHPSCs via energy barriers, we show that NIN photodiodes based on three types of LHPSCs, i.e., MAPbBr3 (MA = CH3NH3), MAPbBr2.5Cl0.5, and cascade LHPSCs, have demonstrated good energy resolution in the range of 6.7-10.3% for 662 keV 137Cs gamma-ray photons. The noise for >10 mm3 devices is low, in the order of 340-860 electrons, and the electron collection efficiency reaches 23-43%. These results pave the way for obtaining low-cost, large, high energy-resolution gamma-ray detectors at room temperature (300 K).

Differential Mortality Among Heart Failure Patients Across Different COVID-19 Surges in New York City.

ABSTRACT: Learning from the healthcare system's response to the COVID-19 pandemic is essential to better prepare for potential future crises. We sought to assess mortality rates for patients admitted for acute decompensated heart failure (HF) and to analyze which factors demonstrated a statistically significant correlation with this primary endpoint. We performed a retrospective analysis of patients hospitalized with a primary diagnosis of acute decompensated HF within the New York City Health and Hospitals 11-hospital system across the different COVID surge periods. Mortality information was collected in 4,405 participants (mean [SD] age 70.54 [14.44] years, 1885 [42.87%] female).The highest mortality existed in the first surge (9.02%), then improved to near prepandemic levels (3.65%) in the second (3.91%) and third surges (5.94%, p < 0.0001). In-hospital mortality inversely correlated with receipt of a COVID-19 vaccination, but had no correlation with left ventricular ejection fraction or the number of vaccination doses. Mortality for acute decompensated HF patients improved after the first surge, suggesting that hospitals adequately adapted to provide quality care. As future infectious outbreaks may occur, emergency preparedness must ensure that adequate focus and resources remain for other clinical entities, such as HF, to ensure optimal care is delivered across all areas of illness.

Sensitive Thermography via Sensing Visible Photons Detected from the Manipulation of the Trap State in MAPbX3.

Sensitive thermometry or thermography by responding to blackbody radiation is urgently desired in the intelligent information life, including scientific research, medical diagnosis, remote sensing, defense, etc. Even though thermography techniques based on infrared sensing have undergone unprecedented development, the poor compatibility with common optical components and the high diffraction limit impose an impediment to their integration into the established photonic integrated circuit or the realization of high-spatial-resolution and high-thermal-resolution imaging. In this work, we present a sensitive temperature-dependent visible photon detection in Bi-doped MAPbX3 (X = Cl, Br, and I) and employ it for uncooled thermography. Systematic measurements reveal that the Bi dopant introduces trap states in MAPbX3, thermal energy facilitates the carriers jumping from trap states to the conduction band, while the vacancies of trap states ensure the sequential absorption of visible photons with energy less than the band gap. Subsequently, the change of response toward the visible photon is applied to construct the thermograph, and it possesses a specific sensitivity of 2.11% K-1 along temperature variation. As a result, our thermograph presents a temperature resolution of 0.21 nA K-1, a high responsivity of 2.06 mA W-1, and a high detectivity of 2.08 × 109 Jones at room temperature. Furthermore, remote thermal imaging is successfully achieved with our thermograph.

Cascade perovskite single crystal for gamma-ray spectroscopy.

The halide lead perovskite single crystals (HLPSCs) have great potential in gamma-ray detection with high attenuation coefficient, strong defects tolerance, and large mobility-lifetime product. However, mobile halide ions would migrate under high external bias, which would both weaken the gamma-ray response and cause additional noise. Here, we report the gamma-ray PIN photodiodes made of cascade HLPSCs including both ion-formed and electron-hole-formed electrical junctions that could suppress the ions migration and improve the charges collection. Our photodiodes based on cascade HLPSCs (MAPbBr3/MAPbBr2.5Cl0.5/MAPbCl3) show a wide halide-ion-formed depletion layer of ∼52 µm. The built-in potential along the wide ionic-formed junction ensures a high mobility-lifetime product of 1.1 × 10-2 cm2V-1. As a result, our gamma-ray PIN photodiodes exhibit compelling response to 241Am, 137Cs, and 60Co; the energy resolution can reach 9.4%@59.5keV and 5.9%@662keV, respectively. This work provides a new path toward constructing high-performance gamma-ray detectors based on HLPSCs.

Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1-EEF1A1 Axis.

Epigenetic dysregulation is reported in multiple cancers including Ewing sarcoma (EwS). However, the epigenetic networks underlying the maintenance of oncogenic signaling and therapeutic response remain unclear. Using a series of epigenetics- and complex-focused CRISPR screens, RUVBL1, the ATPase component of NuA4 histone acetyltransferase complex, is identified to be essential for EwS tumor progression. Suppression of RUVBL1 leads to attenuated tumor growth, loss of histone H4 acetylation, and ablated MYC signaling. Mechanistically, RUVBL1 controls MYC chromatin binding and modulates the MYC-driven EEF1A1 expression and thus protein synthesis. High-density CRISPR gene body scan pinpoints the critical MYC interacting residue in RUVBL1. Finally, this study reveals the synergism between RUVBL1 suppression and pharmacological inhibition of MYC in EwS xenografts and patient-derived samples. These results indicate that the dynamic interplay between chromatin remodelers, oncogenic transcription factors, and protein translation machinery can provide novel opportunities for combination cancer therapy.

Compositional gradient engineering and applications in halide perovskites.

Organic-inorganic halide perovskites (HPs) have attracted respectable interests as active layers in solar cells, light-emitting diodes, photodetectors, etc. Besides the promising optoelectronic properties and solution-processed preparation, the soft lattice in HPs leads to flexible and versatile compositions and structures, providing an effective platform to regulate the bandgaps and optoelectronic properties. However, conventional solution-processed HPs are homogeneous in composition. Therefore, it often requires the cooperation of multiple devices in order to achieve multi-band detection or emission, which increases the complexity of the detection/emission system. In light of this, the construction of a multi-component compositional gradient in a single active layer has promising prospects. In this review, we summarize the gradient engineering methods for different forms of HPs. The advantages and limitations of these methods are compared. Moreover, the entropy-driven ion diffusion favors compositional homogeneity, thus the stability issue of the gradient is also discussed for long-term applications. Furthermore, applications based on these compositional gradient HPs will also be presented, where the gradient bandgap introduced therein can facilitate carrier extraction, and the multi-components on one device facilitate functional integration. It is expected that this review can provide guidance for the further development of gradient HPs and their applications.

Fused solar-blind UV/VIS Bi-spectral sensing and imaging with vertically stacking ZnGa2O4/MAPbI3structure.

Various spectral bands provide different types of information, and information enhancement could be achieved by selective fusion of different spectral bands. The fused solar-blind Ultraviolet (UV)/Visible (VIS) bi-spectral sensing and imaging can provide the precise location of UV targets in virtue of VIS background, which has been increasingly promoted. However, most reported UV/VIS bi-spectral photodetectors (PDs) only have one single channel towards a broadband spectrum of both UV and VIS light, which cannot distinguish two kinds of signals, hindering the image fusion of bi-spectral signals. This work demonstrates the solar-blind UV/VIS bi-spectral PD based on vertically stacking perovskite of MAPbI3and ternary oxide of ZnGa2O4with independent and distinct response toward solar-blind UV and VIS light in a single pixel. The PD exhibits excellent sensing properties with anIon/Ioffratio of >107and 102, detectivity of >1010and 108Jones, and response decay time of 90µs and 16 ms for VIS and UV channels, respectively. The successful fusion of VIS and UV images suggests that our bi-spectral PD can be applied in the accurate identification of corona discharge and fire detection.

ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner.

Epigenetic dysregulation of cell cycle is a hallmark of tumorigenesis in multiple cancers, including hepatocellular carcinoma (HCC). Nonetheless, the epigenetic mechanisms underlying the aberrant cell cycle signaling and therapeutic response remain unclear. Here, we used an epigenetics-focused CRISPR interference screen and identified ACTR5 (actin-related protein 5), a component of the INO80 chromatin remodeling complex, to be essential for HCC tumor progression. Suppression of ACTR5 activated CDKN2A expression, ablated CDK/E2F-driven cell cycle signaling, and attenuated HCC tumor growth. Furthermore, high-density CRISPR gene tiling scans revealed a distinct HCC-specific usage of ACTR5 and its interacting partner IES6 compared to the other INO80 complex members, suggesting an INO80-independent mechanism of ACTR5/IES6 in supporting the HCC proliferation. Last, our study revealed the synergism between ACTR5/IES6-targeting and pharmacological inhibition of CDK in treating HCC. These results indicate that the dynamic interplay between epigenetic regulators, tumor suppressors, and cell cycle machinery could provide novel opportunities for combinational HCC therapy.

Flexible Miniaturized Multispectral Detector Derived from Blade-Coated Organic Narrowband Response Unit Array.

Multispectral sensing is extremely desired in intelligent systems, e.g., autonomous vehicles, encrypted information communication, and health biometric monitoring, due to its highly sensitive spectral discrimination ability. Nevertheless, rigid bulky optics and delicate optical paths in devices significantly increase their complexity and size, which subsequently impede their integration in smart optoelectronic chips for universal applications. In this work, a filterless miniaturized multispectral photodetector is realized with an organic narrowband response unit array. With the manipulation of Frenkel exciton dissociation in active layers, a series of narrowband organic sensing units with full-width-at-half-maximum (fwhm) narrowing to ∼50 nm are achieved from 700 to 1050 nm with a laudable performance of responsivity of over 60 mA/W, -3 dB bandwidth over 10 kHz, linear dynamic range (LDR) reaching ∼120 dB, and a low noise current of less than 4 × 10-14 A·Hz-0.5. Furthermore, a 6 × 8 multispectral sensing array on a flexible substrate was fabricated with blade-coating. Assisted by a computational process, we successfully demonstrate the spectral recognition with a resolution of ∼50 nm and a mismatch of ∼10 nm. Finally, the function of matter identification is successfully achieved with our multispectral detector array.

Monolithic RGB-NIR Perovskite Photodetector for Fused Multispectral Sensing and Imaging.

The multispectral fusion of near-infrared (NIR) and visible red-green-blue (RGB) photons can enhance target identification under weak light conditions. Nevertheless, the crosstalk between NIR and RGB photons in a traditional pixelated sensor impedes their practical application, while using complex algorithms and optical filters would significantly increase the cost, form factor, and frame latency. In this work, a delicate monolithic RGBN (RGB-NIR) multispectral photodetector (PD) is proposed on the basis of perovskite materials without complicated algorithms or optical filters. The multispectral response toward selective RGBN signals in this monolithic PD pixels can be achieved by switching the polarity of the applied bias, affording the following benefits: Ion/Ioff ratio of >104, detectivity of >1010 Jones, crosstalk of -74 dB, and fast response with -3 dB > 103 Hz. Moreover, proof-of-concept imaging of the iris and periocular with successful recognition in multispectral fusion further confirms its potential for identity authentication.

Enhanced room-temperature terahertz detection and imaging derived from anti-reflection 2D perovskite layer on MAPbI3 single crystals.

Terahertz (THz) detection technology is getting increasing attention from scientists and industries alike due to its superiority in imaging, communication, and defense. Unfortunately, the detection of THz electromagnetic waves under room temperature requires a complicated device architecture design or additional cryogenic cooling units, which increase the cost and complexity of devices, subsequently imposing an impediment in its universal application. In this work, THz detectors operated under room temperature are designed based on the thermoelectric effect with MAPbI3 single crystals (SCs) as active layers. With solution-processed molecular growth engineering, the anti-reflection 2D perovskite layers were constructed on SCs' surfaces to suppress THz reflection loss. Simultaneously, by finely regulating the main carrier types and the direction of the applied bias across the inclined energy level, the thermoelectric effect is further promoted. As a result, THz-induced ΔT in MAPbI3 SCs reaches 4.6 °C, while the enhancement in the bolometric and photothermoelectric effects reach ∼4.8 times and ∼16.9 times, respectively. Finally, the devices achieve responsivity of 88.8 µA W-1 at 0.1 THz under 60 V cm-1, noise equivalent power (NEP) less than 2.16 × 10-9 W Hz-1/2, and specific detectivity (D*) of 1.5 × 108 Jones, which even surpasses the performance of state-of-the-art graphene-based room-temperature THz thermoelectric devices. More importantly, proof-of-concept imaging gives direct evidence of perovskite-based THz sensing in practical applications.

Further Advancement of Perovskite Single Crystals.

Halide perovskite (HP) single crystals (SCs) are garnering extensive attention as active materials to substitute polycrystalline counterparts in solar cells, photodiodes, and photodetectors, etc. Nevertheless, the large thickness and defect-rich surface results in severe carrier recombination and becomes the major bottleneck for augmented performance. In this perspective, we are looking forward to explaining in detail why the SCs hardly unleash their engrossing potential and introduce two parallel paths for further advancement. First is the modification of thick SCs by reducing the prepared thickness or surface passivation. Second is the large thickness that is conducive to the sufficient absorption of high-energy rays with strong penetrating ability and is beneficial to the thermoelectric effect due to the ultralow thermal conductivity of HPs. These applications provide a roundabout strategy to exploit freestanding SCs with a large thickness. Herein, direct modification and application of thick SCs are systematically introduced, expecting to give rise to the prosperity of HP SCs.

3-Ketodihydrosphingosine reductase maintains ER homeostasis and unfolded protein response in leukemia.

Sphingolipids and their metabolic pathways have been implicated in disease development and therapeutic response; however, the detailed mechanisms remain unclear. Using a sphingolipid network focused CRISPR/Cas9 library screen, we identified an endoplasmic reticulum (ER) enzyme, 3-Ketodihydrosphingosine reductase (KDSR), to be essential for leukemia cell maintenance. Loss of KDSR led to apoptosis, cell cycle arrest, and aberrant ER structure. Transcriptomic analysis revealed the indispensable role of KDSR in maintaining the unfolded protein response (UPR) in ER. High-density CRISPR tiling scan and sphingolipid mass spectrometry pinpointed the critical role of KDSR's catalytic function in leukemia. Mechanistically, depletion of KDSR resulted in accumulated 3-ketodihydrosphingosine (KDS) and dysregulated UPR checkpoint proteins PERK, ATF6, and ATF4. Finally, our study revealed the synergism between KDSR suppression and pharmacologically induced ER-stress, underscoring a therapeutic potential of combinatorial targeting sphingolipid metabolism and ER homeostasis in leukemia treatment.

Miniaturized Multispectral Detector Derived from Gradient Response Units on Single MAPbX3 Microwire.

Miniaturized multispectral detectors are urgently desired given the unprecedented prosperity of smart optoelectronic chips for integrated functions including communication, imaging, scientific analysis, etc. However, multispectral detectors require complicated prism optics or interference/interferometric filters for spectral recognition, which hampers the miniaturization and their subsequent integration in photonic integrated circuits. In this work, inspired by the advance of computational imaging, optical-component-free miniaturized multispectral detector on 4 mm gradient bandgap MAPbX3 microwire with a diameter of 30 µm, is reported. With accurate composition engineering, halide ions in MAPbX3 microwire vary from Cl to I giving in the gradual variation of optical bandgap from 2.96 to 1.68 eV along axis. The sensing units on MAPbX3 microwire offer the response edge ranging from 450 to 790 nm with the responsivity over 20 mA W-1 , -3dB width over 450 Hz, LDR of ≈60 dB, and a noise current less than ≈1.4 × 10-12 A Hz-0.5 . As a result, the derived miniaturized detector achieves the function of multispectral sensing and discrimination with spectral resolution of ≈25 nm and mismatch of ≈10 nm. Finally, the proof-of-concept colorful imaging is successfully conducted with the miniaturized multispectral detector to further confirm its application in spectral recognition.

Perovskite White Light Emitting Diodes: Progress, Challenges, and Opportunities.

As global warming, energy shortages, and environment pollution have intensified, low-carbon and energy-saving lighting technology has attracted great attention worldwide. Light emitting diodes (LEDs) have been around for decades and are considered to be the most ideal lighting technology currently due to their high luminescence efficiency (LE) and long lifespan. Besides, along with the development of modern technology, lighting technologies with higher performance and more functions are desired. Perovskite based LEDs (PeLEDs) have recently emerged as ideal candidates for lighting technology owing to the extraordinary photoelectric properties of perovskite, such as high photoluminescence quantum yields (PLQYs), easy wavelength tuning, and low-cost synthesis. Herein, we open this review by introducing the background of white LEDs (WLEDs), including their light-emitting mechanism, typical characteristics, and key indicators in applications. Then, four main approaches to fabricate WLEDs are discussed and compared. After that, in accordance with the four categories, we focus on the recent progress of white PeLEDs (Pe-WLEDs), followed by the challenges and opportunities for Pe-WLEDs in practical application. Meanwhile, some pertinent countermeasures to their challenges are put forward. Finally, the development promise of Pe-WLEDs is explored.

High-resolution characterization of gene function using single-cell CRISPR tiling screen.

Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via CRISPR tiling of gene-coding exons has been demonstrated to identify functional regions in genes. Furthermore, breakthroughs in combining CRISPR library screens with single-cell droplet RNA sequencing (sc-RNAseq) platforms have revealed the capacity to monitor gene expression changes upon genetic perturbations at single-cell resolution. Here, we present "sc-Tiling," which integrates a CRISPR gene-tiling screen with single-cell transcriptomic and protein structural analyses. Distinct from other reported single-cell CRISPR screens focused on observing gene function and gene-to-gene/enhancer-to-gene regulation, sc-Tiling enables the capacity to identify regulatory mechanisms within a gene-coding region that dictate gene activity and therapeutic response.

Oriented Perovskite Growth Regulation Enables Sensitive Broadband Detection and Imaging of Polarized Photons Covering 300-1050 nm.

Photodetectors selective to the polarization empower breakthroughs in sensing technology for target identification. However, the realization of polarization-sensitive photodetectors based on intrinsically anisotropic crystal structure or extrinsically anisotropic device pattern requires complicated epitaxy and etching processes, which limit scalable production and application. Here, solution-processed PEA2 MA4 (Sn0.5 Pb0.5 )5 I16 (PEA= phenylethylammonium, MA= methylammonium) polycrystalline film is probed as photoactive layer toward sensing polarized photon from 300 to 1050 nm. The growth of the PEA2 MA4 (Sn0.5 Pb0.5 )5 I16 crystal occurs in confined crystallographic orientation of the (202) facet upon the assistance of NH4 SCN and NH4 Cl, enhancing anisotropic photoelectric properties. Therefore, the photodetector achieves a polarization ratio of 0.41 and dichroism ratio (Imax /Imin ) of 2.4 at 900 nm. At 520 nm, the Imax /Imin even surpasses the one of the perovskite crystalline films, 1.8 and ≈1.2, respectively. It is worth noting that the superior figure-of-merits possess a response width of 900 kHz, Ion /Ioff ratio of ≈3 × 108 , linear dynamic range from 0.15 nW to 12 mW, noise current of 8.28 × 10-13 A × Hz-0.5 , and specific detectivity of 1.53 × 1012 Jones, which demonstrate high resolution and high speed for weak signal sensing and imaging. The proof of concept in polarized imaging confirms that the polarization-sensitive photodetector meets the requirements for practical application in target recognition.