Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

The Impact of Delirium after Radical Prostatectomy on Cognitive Function and Health Perception during the Recovery Period.

OBJECTIVE: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. METHODS: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients' mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. RESULTS: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). CONCLUSIONS: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception. A significant correlation exists between postoperative delirium and cognitive function as well as health perception.

Acesulfame and other artificial sweeteners in a wastewater treatment plant in Alberta, Canada: Occurrence, degradation, and emission.

Acesulfame (ACE), sucralose (SUC), cyclamate (CYC), and saccharin (SAC) are widely used artificial sweeteners that undergo negligible metabolism in the human body, and thus ubiquitously exist in wastewater treatment plants (WWTPs). Due to their persistence in WWTPs, ACE and SUC are found in natural waters globally. Wastewater samples were collected from the primary influent, primary effluent, secondary effluent, and final effluent of a WWTP in Alberta, Canada between August 2022 and February 2023, and the artificial sweeteners concentrations were measured by LC-MS/MS. Using wastewater-based epidemiology, the daily per capita consumption of ACE in the studied wastewater treatment plant catchment was estimated to be the highest in the world. Similar to other studies, the removal efficiency in WWTP was high for SAC and CYC, but low or even negative for SUC. However, ACE removal remained surprisingly high (>96%), even in the cold Canadian winter months. This result may indicate a further adaptation of microorganisms capable of biodegrading ACE in WWTP. The estimated per capita discharge into the environment of ACE, CYC, and SAC is low in Alberta due to the prevalent utilization of secondary treatment throughout the province, but is 17.4-18.8 times higher in Canada, since only 70.3% of total discharged wastewater in Canada undergoes secondary treatment.

The Impact of Delirium after Radical Prostatectomy on Cognitive Function and Health Perception during the Recovery Period

Objective: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. Methods: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients’ mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. Results: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). Conclusions: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception... (AU)

Serum amyloid A promotes glycolysis of neutrophils during PD-1 blockade resistance in hepatocellular carcinoma.

The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.

Self-Powered MAPbI3 Heterojunction Photodetector with Gradient-Level Electron Transport Layers and Dual Pyro-Phototronic Effects.

An electron transport layer (ETL) with a suitable gradient energy level can enhance electron transfer, suppress carrier recombination, and effectively improve the photoresponse of photodetectors (PDs). In this letter, a series of ITO/ZnO/CdS/MAPbI3/Spiro-OMeTAD heterojunction PDs were prepared by incorporating a ZnO layer at the CdS/ITO interface upon varying the thickness from 0 to 95 nm. The optimized band arrangement in the PD results in an excellent self-powering ability and improved photoresponse. Moreover, both the photovoltaic and pyroelectric responses strongly correlate with the thickness of the ZnO layer. The PD with an optimal ZnO thin film thickness of 50 nm achieves a huge responsivity (R) of 1.19 × 104 V/W and detectivity (D) of 2.22 × 109 Jones, primarily due to the strengthened pyro-phototronic effects enabled by the dual ETL layers. In addition, the enhanced pyroelectric effect broadens the spectral range of the PD to 360-1550 nm, largely surpassing the band gap of the heterojunction.

Broadband Self-Powered CdS ETL-Based MAPbI3 Heterojunction Photodetector Induced by a Photovoltaic-Pyroelectric-Thermoelectric Effect.

CdS, with a noncentrosymmetric structure, is thought as an important electron transport layer (ETL) in perovskite-based devices, but its pyroelectric effect, which can efficiently modulate the optoelectronic processes, is not well explored. In this work, a MAPbI3 heterojunction of CdS/MAPbI3/Spiro-OMeTAD with a c-axis preferred oxygen-doped CdS ETL is developed as a high-performance photodetector (PD). This PD exhibits a stable self-powered property in the spectral range of ∼360-780 nm due to its excellent photovoltaic effect. Moreover, the light-induced pyroelectric potential in the CdS ETL is demonstrated to be an efficient approach for improving the photoresponses, and different effects are observed for different laser irradiations, which can be well understood from their working mechanisms. Upon 450 nm laser irradiation, the photovoltage responsivity (R) is greatly improved from 596.9 to 6383.6 V/W with an increment of 1069.54%. In addition, the response spectrum is also extended outside the bandgap restriction of the MAPbI3 to 1550 nm due to both the pyroelectric and photothermoelectric effects, which is a big breakthrough for the perovskite heterojunction PD. Through turning the external bias voltage and ambient temperature, the coupling mechanisms of the pyroelectric and photovoltaic effects are further analyzed. This work provides an important understanding of designing the CdS ETL-based perovskite heterojunction for broadband high-performance photoelectric devices by introducing the pyroelectric effect.

Coronavirus Porcine Epidemic Diarrhea Virus Utilizes Chemokine Interleukin-8 to Facilitate Viral Replication by Regulating Ca2+ Flux.

Chemokine production by epithelial cells is crucial for neutrophil recruitment to sites of inflammation during viral infection. However, the effect of chemokine on epithelia and how chemokine is involved in coronavirus infection remains to be fully understood. Here, we identified an inducible chemokine interleukin-8 (CXCL8/IL-8), which could promote coronavirus porcine epidemic diarrhea virus (PEDV) infection in African green monkey kidney epithelial cells (Vero) and Lilly Laboratories cell-porcine kidney 1 epithelial cells (LLC-PK1). IL-8 deletion restrained cytosolic calcium (Ca2+), whereas IL-8 stimulation improved cytosolic Ca2+. The consumption of Ca2+ restricted PEDV infection. PEDV internalization and budding were obvious reductions when cytosolic Ca2+ was abolished in the presence of Ca2+ chelators. Further study revealed that the upregulated cytosolic Ca2+ redistributes intracellular Ca2+. Finally, we identified that G protein-coupled receptor (GPCR)-phospholipase C (PLC)-inositol trisphosphate receptor (IP3R)-store-operated Ca2+ (SOC) signaling was crucial for enhancive cytosolic Ca2+ and PEDV infection. To our knowledge, this study is the first to uncover the function of chemokine IL-8 during coronavirus PEDV infection in epithelia. PEDV induces IL-8 expression to elevate cytosolic Ca2+, promoting its infection. Our findings reveal a novel role of IL-8 in PEDV infection and suggest that targeting IL-8 could be a new approach to controlling PEDV infection. IMPORTANCE Coronavirus porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that caused severe economic losses worldwide, and more effort is needed to develop economical and efficient vaccines to control or eliminate this disease. The chemokine interleukin-8 (CXCL8/IL-8) is indispensable for the activation and trafficking of inflammatory mediators and tumor progression and metastasis. This study evaluated the effect of IL-8 on PEDV infection in epithelia. We found that IL-8 expression improved cytosolic Ca2+ in epithelia, facilitating PEDV rapid internalization and egress. G protein-coupled receptor (GPCR)-phospholipase C (PLC)-inositol trisphosphate receptor (IP3R)-SOC signaling was activated by IL-8, releasing the intracellular Ca2+ stores from endoplasmic reticulum (ER). These findings provide a better understanding of the role of IL-8 in PEDV-induced immune responses, which will help develop small-molecule drugs for coronavirus cure.

Self-Powered Bi2Se3/Si Position-Sensitive Detector and Its Performance Enhancement by Introducing a Si Nanopyramid Structure.

Bi2Se3, as a novel 3D topological insulator (TI), is expected to be a strong candidate for next-generation optoelectronic devices due to its intriguing optical and electrical properties. In this study, a series of Bi2Se3 films with different thicknesses of 5-40 nm were successfully prepared on planar-Si substrates and developed as self-powered light position-sensitive detectors (PSDs) by introducing lateral photovoltaic effect (LPE). It is demonstrated that the Bi2Se3/planar-Si heterojunction shows a broad-band response range of 450-1064 nm, and the LPE response is strongly dependent on the Bi2Se3 layer thickness, which can be mainly attributed to the thickness-modulated longitudinal carrier separation and transport. The 15 nm thick PSD shows the best performance with a position sensitivity of up to 89.7 mV/mm, a nonlinearity of lower than 7%, and response time as fast as 62.6/49.4 µs. Moreover, to further enhance the LPE response, a novel Bi2Se3/pyramid-Si heterojunction is built by constructing a nanopyramid structure for the Si substrate. Owing to the improvement of the light absorption capability in the heterojunction, the position sensitivity is largely boosted up to 178.9 mV/mm, which gets an increment of 199% as compared with that of the Bi2Se3/planar-Si heterojunction device. At the same time, the nonlinearity is still kept within 10% as well due to the excellent conduction property of the Bi2Se3 film. In addition, an ultrafast response speed of 173/97.4 µs is also achieved in the newly proposed PSD with excellent stability and reproducibility. This result not only demonstrates the great potential of TIs in PSD but also provides a promising approach for tuning its performance.

Structural, electronic phase transitions and thermal spin transport properties in 2D NbSe2 and NbS2: a first-principles study.

How to effectively tune 2D electronic and magnetic properties is key to developing novel spintronic materials and devices. Although the strain induced metal-to-half-metal electronic phase transition (EPT) has been studied in 2H NbSe2 and NbS2 monolayers, the 1T phase, the Coulomb interaction and the transport properties have not been explored. Here, using first-principles calculations in junction with nonequilibrium Green's function, we present a comprehensive and comparative study on the strain tuned structural, electronic, magnetic and thermal spin transport properties for NbSe2 and NbS2 monolayers with and without Coulomb interaction. It is found that the Coulomb interaction makes the strain induced 2H-to-1T structural phase transition easier. Similar to the 2H phase, there is also a strain induced metal-to-half-metal EPT for the 1T phase without Coulomb interaction, and the Coulomb interaction makes the ETP easier. Remarkably, the 2H-NbSe2 monolayer with Coulomb interaction is a bipolar spin gapless semiconductor (SGS), and novel Dirac half-metal and usually SGS can be obtained by the tensile strain. In addition, we predict the excellent spin Seebeck effect and thermal spin diode effect in the bipolar SGS of the 2H-NbSe2 monolayer with Coulomb interaction, and expect the spin filtering effect and high magnetoresistance in the half-metals driven by the strain. We also discuss the strength of Coulomb interaction by comparing the theoretical and available experimental electronic states, indicating the indispensability of Coulomb interactions. These results suggest that 2D NbSe2 and NbS2 are promising candidates for phase-change spintronic materials and devices, and will stimulate extensive studies on this class of 2D systems.

Multifunctional high-performance position sensitive detector based on a Sb2Se3-nanorod/CdS core-shell heterojunction.

Sb2Se3 exhibits fascinating optical and electrical properties owing to its unique one-dimensional crystal structure. In this study, a Sb2Se3-nanorod/CdS core-shell heterostructure was successfully constructed, and the lateral photovoltaic effect (LPE), as well as the lateral photocurrent and photoresistance effects, were first studied. The measurements indicate that this heterojunction exhibits excellent lateral photoelectric performance in a broad range of 405-1064 nm with the best position sensitivities (PSs) of 525.9 mV/mm, 79.1 µA/mm, and 25.6 kΩ/mm for the lateral photovoltage, photocurrent, and photoresistance, respectively, while the nonlinearity is maintained below 7%, demonstrating its great potential in a novel high-performance multifunctional position sensitive detector (PSD). Moreover, this PSD could work well at different frequencies with good stability and repeatability, and the rise and fall times were deduced to be 48 and 180 µs, respectively. Besides, large linear working distances are achieved in this heterojunction PSD, and the PS can still reach 75.5 mV/mm even at an ultra-large working distance of 9 mm. These outstanding performances can be attributed to the high-quality Sb2Se3 nanorod arrays and the fast charge-carrier separation and transport properties of this core-shell heterojunction. This study provides important ideas for developing high-performance, broadband, large working distances, and ultrafast multifunctional PSDs based on the new core-shell heterostructure.

Application of CAD in Landscape Grid Space Design and Drawing.

CAD technology has brought great convenience and effect to the design. This paper proposes to update the comparative analysis of the basic classical landscape grid space structure by constructing a landscape grid space design. According to the actual situation of domestic landscape grid space design and drawing, this paper highlights the role of CAD technology in landscape grid space design and drawing and provides an important basis for the subsequent application of CAD software in landscape grid space design.

Greatly improved photoresponse in the MAPbBr3/Si heterojunction by introducing an ITO layer and optimizing MAPbBr3 layer thickness.

In this paper, a CH3NH3(MA)PbBr3/Si heterojunction photodetector (PD) is prepared, and a simple method is proposed to improve the performance by introducing an ITO conductive layer and modulating thickness of the MAPbBr3 layer. The results indicate that the MAPbBr3/Si heterojunction PD exhibits an ultra-broadband photoresponse ranging from 405 to 1064 nm, and excellent performances with the responsivity (R) of 0.394 mA/W, detectivity (D) of 0.11×1010 Jones, and response times of ∼2176/∼257 ms. When adding the ITO layer, the R and D are greatly improved to 0.426 A/W and 5.17×1010 Jones, which gets an increment of 1.08×105% and 4.7×103%, respectively. Meanwhile, the response times are reduced to ∼130/∼125 ms, and a good environmental stability is obtained. Moreover, it is found that the photoresponse is strongly dependent on the thickness of the MAPbBr3 layer. By modulating the MAPbBr3 layer thickness from ∼85 to ∼590 nm, the performances are further improved with the best R of ∼0.87 A/W, D of ∼1.92×1011 Jones, and response times of ∼129/∼130 ms achieved in the ∼215 nm-thick PD.

Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy.

BACKGROUND: Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial enzyme that catalyzes the metabolic conversion between isocitrate and alpha-ketoglutarate (α-KG) in the TCA cycle. IDH2 mutation is an oncogenic event in acute myeloid leukemia (AML) due to the generation of 2-hydroxyglutarate. However, the role of wild-type IDH2 in AML remains unknown, despite patients with it suffer worse clinical outcome than those harboring mutant type. METHODS: IDH2 expression in AML cell lines and patient samples was evaluated by RT-qPCR, western blotting and database analyses. The role of wild-type IDH2 in AML cell survival and proliferation was tested using genetic knockdown and pharmacological inhibition in AML cells and animal models. LC-MS, GC-MS, isotope metabolic tracing, and molecular analyses were performed to reveal the underlying mechanisms. RESULTS: We found that wild-type IDH2 was overexpressed in AML and played a major role in promoting leukemia cell survival and proliferation in vitro and in vivo. Metabolomic analyses revealed an active IDH2-mediated reductive TCA cycle that promoted the conversion of α-KG to isocitrate/citrate to facilitate glutamine utilization for lipid synthesis in AML cells. Suppression of wild-type IDH2 by shRNA resulted in elevated α-KG and decreased isocitrate/citrate, leading to reduced lipid synthesis, a significant decrease in c-Myc downregulated by α-KG, and an inhibition of AML viability and proliferation. Importantly, pharmacological inhibition of IDH2 showed significant therapeutic effect in mice inoculated with AML cells with wt-IDH2 and induced a downregulation of C-MYC in vivo. CONCLUSIONS: Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of α-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.

High-performance broadband position-sensitive detector based on lateral photovoltaic effect of PbSe heterostructure.

PbSe has attracted considerable attention due to its promising applications in optoelectronics and energy harvesting. In this work, we explore the lateral photovoltaic effect (LPE) of PbSe films with a simple PbSe/Si heterostructure under nonuniform light illumination and zero-bias conditions. The LPE response is strongly dependent on the thickness of the PbSe film, but always shows a linear dependence on the laser spot position in an ultra-large working size of 5 mm and exhibits a wide photoresponse ranging from visible to near-infrared. The maximum position sensitivity can reach up to 190 mV/mm for the 15-nm-thick PbSe device at 1064 nm and nonlinearity is less than 4%, demonstrating its new potential application in novel position sensitive detectors (PSDs). Besides, the device also shows an ultrafast response speed, with the rise and fall time of ∼40 µs and ∼105 µs, respectively, and excellent reproducibility. These results bring great inspirations for developing high-performance broadband and self-powered PSDs based on the PbSe/Si heterostructure.

Charge Transfer Gap Tuning via Structural Distortion in Monolayer 1T-NbSe2.

The Mott state in 1T-TaS2 is predicted to host quantum spin liquids (QSLs). However, its insulating mechanism is controversial due to complications from interlayer coupling. Here, we study the charge transfer state in monolayer 1T-NbSe2, an electronic analogue to TaS2 exempt from interlayer coupling, using spectroscopic imaging scanning tunneling microscopy and first-principles calculations. Monolayer NbSe2 surprisingly displays two types of star of David (SD) motifs with different charge transfer gap sizes, which are interconvertible via temperature variation. In addition, bilayer 1T-NbSe2 shows a Mott collapse by interlayer coupling. Our calculation unveils that the two types of SDs possess distinct structural distortions, altering the effective Coulomb energies of the central Nb orbital. Our calculation suggests that the charge transfer gap, the same parameter for determining the QSL regime, is tunable with strain. This finding offers a general strategy for manipulating the charge transfer state in related systems, which may be tuned into the potential QSL regime.

Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer.

Although the role of isocitrate dehydrogenase (IDH) mutation in promoting cancer development has been well-characterized, the impact of wild-type IDH on cancer cells remains unclear. Here we show that the wild-type isocitrate dehydrogenase 2 (IDH2) is highly expressed in colorectal cancer (CRC) cells, and plays an unexpected role in protecting the cancer cells from oxidative damage. Genetic abrogation of IDH2 in CRC cells leads to reactive oxygen species (ROS)-mediated DNA damage and an accumulation of 8-oxoguanine with DNA strand breaks, which activates DNA damage response (DDR) with elevated γH2AX and phosphorylation of ataxia telangiectasia-mutated (ATM) protein, leading to a partial cell cycle arrest and eventually cell senescence. Mechanistically, the suppression of IDH2 results in a reduction of the tricarboxylic acid (TCA) cycle activity due to a decrease in the conversion of isocitrate to α-ketoglutarate (α-KG) with a concurrent decrease in NADPH production, leading to ROS accumulation and oxidative DNA damage. Importantly, abrogation of IDH2 inhibits CRC cell growth in vitro and in vivo, and renders CRC cells more vulnerable to DNA-damaging drugs. Screening of an FDA-approved drug library has identified oxaliplatin as a compound highly effective against CRC cells when IDH2 was suppressed. Our study has uncovered an important role of the wild-type IDH2 in protecting DNA from oxidative damage, and provides a novel biochemical basis for developing metabolic intervention strategy for cancer treatment.

A Self-Powered Photodetector Based on MAPbI3 Single-Crystal Film/n-Si Heterojunction with Broadband Response Enhanced by Pyro-Phototronic and Piezo-Phototronic Effects.

Pyro-phototronic and piezo-phototronic effect have shown their important roles for high performance heterojunction-based photodetectors (PDs). Here, a coupling effect of pyro-phototronic and piezo-phototronic effect is utilized to fabricate a self-powered and broadband PD based on the MAPbI3 single-crystal film/n-Si heterojunction. First, by using the pyro-phototronic effect derived from MAPbI3 , the maximum photoresponsivity of the self-powered PD is 1.5 mA W-1 for 780 nm illumination, which is enhanced by more than 20 times in consideration of the relative peak-to-peak output current. Light-induced temperature change in MAPbI3 film will create pyro-charges distributed at heterojunction interface, resulting in a downward bending of the energy band, facilitating the transport of photon-generated electrons and holes, and generating spike-like output currents. Second, piezo-phototronic effect is further introduced by applying vertical pressures onto the PD. With a vertical pressure of 155 kPa, the responsivity can be improved by more than 120% compared to the condition with no pressure. The overall enhancement is due to the piezo-phototronic and pyro-phototronic coupling effects which utilize the polarization charges to modulate the band structure of heterojunction. These results provide a promising approach to develop high-performance self-powered and broadband perovskite-based PDs by coupling pyro-phototronic and piezo-phototronic effect.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma.

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

High-Responsivity, Fast, and Self-Powered Narrowband Perovskite Heterojunction Photodetectors with a Tunable Response Range in the Visible and Near-Infrared Region.

In recent years, narrowband photodetectors (PDs) have been widely used in color imaging, spectral detection or discrimination, defense, and scientific research due to their special spectral selective responses. In this work, by combining organic-inorganic hybrid perovskite layers of different band gaps and thicknesses, a series of narrowband perovskite heterojunction PDs with a continuously adjustable spectral range in the visible and near-infrared range are designed and prepared. The PDs can achieve a narrowband photoresponse with a full width at half-maximum (FWHM) of less than 50 nm and a light rejection ratio (between 780 and 532 nm) of over 1100 and exhibit excellent photoresponse performances with an external quantum efficiency (EQE), responsivity (R), and detectivity (D*) as high as 50.3%, 0.331 A/W, and 4.27 × 1010 Jones, respectively. More importantly, the photoresponses of the PDs at zero bias are as good as those at the reverse bias voltages, indicating the outstanding self-powered property. In addition, a fast response time of ∼180/∼200 µs is obtained in the narrowband perovskite heterojunction, and the response speed nearly remains constant for different PDs in the whole tunable wavelength range, demonstrating the suitable and stable structure of the heterojunction, as well as the high crystalline quality of the perovskite layers. This work definitely provides a simple strategy for designing low-cost, high-photoresponsivity, fast speed, and self-powered narrowband PDs with a tunable spectral range.