HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 µM, more potent than the positive control indomethacin.

Dielectric modulation strategy of carbon nanotube field effect transistors based pressure sensor: towards precise monitoring of human pulse.

Continuous monitoring of arterial pulse has great significance for detecting the early onset of cardiovascular disease and assessing health status, while needs pressure sensors with high sensitivity and signal-to-noise ratio (SNR) to accurately capture more health information concealed in pulse waves. Field effect transistors (FETs) combined with the piezoelectric film is an ultrahigh sensitive pressure sensor category, especially when the FET works in the subthreshold regime, where the signal enhancement effect on the piezoelectric response is the most effective. However, controlling the work regime of FET needs extra external bias assistance which will interfere with the piezoelectric response signal and complicate the test system thus making the scheme difficult to implement. Here, we described a gate dielectric modulation strategy to match the subthreshold region of the FET with the piezoelectric output voltage without external gate bias, finally enhancing the sensitivity of the pressure sensor. A carbon nanotube field effect transistor and polyvinylidene fluoride (PVDF) together form the pressure sensor with a high sensitivity of 7 × 10-1kPa-1for a pressure range of 0.038-0.467 kPa and 6.86 × 10-2kPa-1for a pressure range of 0.467-15.5 kPa, SNR, and the ability to continuously monitor pulse in real-time. Additionally, the sensor enables high-resolution detection of weak pulse signals under large static pressure.

A novel enzyme synthesized by Acinetobacter sp. SM04 is responsible for zearalenone biodegradation.

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin produced by multiple Fusarium species, contaminates cereals and threatens the health of both humans and animals by inducing hepatotoxicity, immunotoxicity, and genotoxicity. A new alkali tolerant enzyme named Ase, capable of degrading ZEA without H2O2, was derived from Acinetobacter sp. SM04 in this study. The Ase gene shares 97% sequence identity with hypothetical proteins from Acinetobacter pittii strain WCHAP 100004 and YMC 2010/8/T346 and Acinetobacter calcoaceticus PHEA-2, respectively. Based on the Acinetobacter genus database, the gene encoding Ase was cloned and extracellularly expressed in Escherichia coli BL21. After degrading 88.4% of ZEA (20 µg/mL), it was confirmed through MCF-7 cell proliferation assays that Ase can transform ZEA into a nonestrogenic toxic metabolite. Recombinant Ase (molecular weight: 28 kDa), produced by E. coli BL21/pET32a(+)-His-Ase, was identified as an oxygen-utilizing and cytochrome-related enzyme with optimal activity at 60 °C and pH 9.0.

Furanaspermeroterpenes A and B, two unusual meroterpenoids with a unique 6/6/6/5/5 pentacyclic skeleton from the Marine-derived fungus Aspergillus terreus GZU-31-1.

Furanaspermeroterpenes A (1) and B (2), with a unique 6/6/6/5/5 pentacyclic skeleton, and five new congeners aspermeroterpenes D-H (3-7) were co-isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Among them, compounds 1 and 2 with rare five-membered D/E coupling rings were the first example of DMOA-derived meroterpenoids. Moreover, compound 3 was the first reported 6/6/6/6/5 pentacyclic meroterpenoid featuring an unusual cis-fused A/B ring. In the bioassays, all of the isolates were evaluated on the inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells, and compounds 3-7 exhibited significant anti-inflammatory activity with IC50 values ranging from 6.74 to 29.59 µM than positive control (Indomethacin, IC50 30.98 µM).

Butyrolactone and sesquiterpene derivatives as inhibitors of iNOS from the roots of Lindera glauca.

Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 µM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.

Furanasperterpenes A and B, two meroterpenoids with a novel 6/6/6/6/5 ring system from the marine-derived fungus Aspergillus terreus GZU-31-1.

Furanasperterpenes A (1) and B (2) with a novel 6/6/6/6/5 pentacyclic skeleton and a new 11-acetoxy-terretonin E (3), were isolated from the marine-derived Aspergillus terreus GZU-31-1. Their structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. A possible biogenetic pathway was proposed. These compounds were evaluated for their lipid-lowering effects in 3T3-L1 adipocytes. Furanasperterpene A (1) showed the equivalent activity in reducing TG levels to positive control (berberine) at the concentration of 5 µM.

[Characteristics of sperm donors and the eligibility rate of screening for sperm donation].

OBJECTIVE: To investigate the relationship of the characteristics of sperm donors with the results of screening and provide some reference for the screening of sperm donors. METHODS: We statistically analyzed the screening data about 12 362 sperm donors at the Guangdong Human Sperm Bank from January 2003 to June 2017 and the relationship of the eligibility rate of screening with the donors' age, education, occupation, marriage, and fatherhood. RESULTS: Of the 12 362 sperm donors, 3 968 (32.1%) met the standards of semen quality and 3 127 (25.3%) filled all the requirements of sperm donation. The eligibility rate of screening was 27.7% in the donors aged 20－24 years, 24.3% in those aged 25－29 years, 23.8% in those aged 30－34 years, and 17.5% in those aged =≥35 years (P < 0.01); 23.5% in the senior high school students, 24% in the junior college students, 25.9% in the undergraduates, and 30.3% in the postgraduates (P < 0.01); 29.3% in the students versus 22.9% in the others (P < 0.01), 41.5% in the married versus 20.7% in the unmarried (P < 0.01), and 45.6% in the fathers versus 20.9% in the childless husbands (P < 0.01). CONCLUSIONS: A higher eligibility rate of screening was found among the sperm donors aged <35 years or with a bachelor's or higher degree, particularly among students.

A novel glycosyltransferase from Bacillus subtilis achieves zearalenone detoxification by diglycosylation modification.

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin produced by Fusarium spp., contaminates cereals and threatens human and animal health by inducing hepatotoxicity, immunotoxicity, and genotoxicity. In this study, a new Bacillus subtilis strain, YQ-1, with a strong ability to detoxify ZEN, was isolated from soil samples and characterized. YQ-1 was confirmed to degrade more than 46.26% of 20 µg mL-1 ZEN in Luria-Bertani broth and 98.36% in fermentation broth within 16 h at 37 °C; one of the two resulting products was ZEN-diglucoside. Under optimal reaction conditions (50 °C and pH 5.0-9.0), the reaction mixture generated by YQ-1 catalyzing ZEN significantly reduced the promoting effect of ZEN on MCF-7 cell proliferation, effectively eliminating the estrogenic toxicity of ZEN. In addition, a new glycosyltransferase gene (yqgt) from B. subtilis YQ-1 was cloned with 98% similarity to Bs-YjiC from B. subtilis 168 and over-expressed in E. coli BL21 (DE3). ZEN glycosylation activity converted 25.63% of ZEN (20 µg mL-1) to ZEN-diG after 48 h of reaction at 37 °C. The characterization of ZEN degradation by B. subtilis YQ-1 and the expression of YQGT provide a theoretical basis for analyzing the mechanism by which Bacillus spp. degrades ZEN.

Monitoring and evaluation of vegetation restoration in the Ebinur Lake Wetland National Nature Reserve under lockdown protection.

For a long time, human activities have been prohibited in ecologically protected areas in the Ebinur Lake Wetland National Nature Reserve (ELWNNR). The implementation of total closure is one of the main methods for ecological protection. For arid zones, there is a lack of in-depth research on whether this measure contributes to ecological restoration in the reserve. The Normalized Difference Vegetation Index (NDVI) is considered to be the best indicator for ecological monitoring and has a key role to play in assessing the ecological impacts of total closure. In this study, we used Sentinel-2, Landsat-8, and Moderate Resolution Imaging Spectroradiometer (MODIS) remote sensing data to select optimal data and utilized Sen slope estimation, Mann-Kendall statistical tests, and the geographical detector model to quantitatively analyze the normalized difference vegetation index (NDVI) dynamics and its driving factors. Results were as follows: (1) The vegetation distribution of the Ebinur Lake Wetland National Nature Reserve (ELWNNR) had obvious spatial heterogeneity, showing low distribution in the middle and high distribution in the surroundings. The correlation coefficients of Landsat-8 and MODIS, Sentinel-2 and MODIS, and Sentinel-2 and Landsat-8 were 0.952, 0.842, and 0.861, respectively. The NDVI calculated from MODIS remote sensing data was higher than the value calculated by Landsat-8 and Sentinel-2 remote sensing images, and Landsat-8 remote sensing data were the most suitable data. (2) NDVI indicated more degraded areas on the whole, but the ecological recovery was obvious in the localized areas where anthropogenic closure was implemented. The ecological environment change was the result of the joint action of man and nature. Man-made intervention will change the local ecological environment, but the overall ecological environment change was still dominated by natural environmental factors. (3) Factors affecting the distribution of NDVI in descending order were as follows: precipitation > evapotranspiration > land use type > elevation > vegetation type > soil type > soil erosion > slope > temperature > slope direction. Precipitation was the main driver of vegetation change in ELWNNR. The synergistic effect of the factors showed two-factor enhancement and nonlinear enhancement, and the combined effect of the driving factors would increase the influence on NDVI.

Meroterpenoids from the marine-derived fungus Aspergillus terreus GZU-31-1 exerts anti-liver fibrosis effects by targeting the Nrf2 signaling in vitro.

Six undescribed meroterpenoids aspertermeroterpenes A-F and four known analogues were isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Their structures were elucidated based on spectroscopic methods and electronic circular dichroism calculations. All meroterpenoids possessed the unique acetyl group at C-11, and also aspertermeroterpene A featured the rare C-14 decarboxylated in DMOA meroterpenoids. In the bioassays, aspermeroterpene B exhibited a potent inhibitory effect on the activation of hepatic stellate cells at the concentration of 5 µM via targeting the Nrf2 signaling. This is the first time reported that aspermeroterpene B as a previously undescribed carbon skeleton of meroterpenoid possessed anti-liver fibrosis effect.

Adverse effects of bisphenol A and its analogues on male fertility: An epigenetic perspective.

In recent years, there has been growing concern about the adverse effects of endocrine disrupting chemicals (EDCs) on male fertility. Epigenetic modification is critical for male germline development, and has been suggested as a potential mechanism for impaired fertility induced by EDCs. Bisphenol A (BPA) has been recognized as a typical EDC. BPA and its analogues, which are still widely used in various consumer products, have garnered increasing attention due to their reproductive toxicity and the potential to induce epigenetic alteration. This literature review provides an overview of studies investigating the adverse effects of bisphenol exposures on epigenetic modifications and male fertility. Existing studies provide evidence that exposure to bisphenols can lead to adverse effects on male fertility, including declined semen quality, altered reproductive hormone levels, and adverse reproductive outcomes. Epigenetic patterns, including DNA methylation, histone modification, and non-coding RNA expression, can be altered by bisphenol exposures. Transgenerational effects, which influence the fertility and epigenetic patterns of unexposed generations, have also been identified. However, the magnitude and direction of certain outcomes varied across different studies. Investigations into the dynamics of histopathological and epigenetic alterations associated with bisphenol exposures during developmental stages can enhance the understanding of the epigenetic effects of bisphenols, the implication of epigenetic alteration on male fertility, and the health of successive generation.

Two-Step Epimerization of Deoxynivalenol by Quinone-Dependent Dehydrogenase and Candida parapsilosis ACCC 20221.

Deoxynivalenol (DON), one of the main mycotoxins with enteric toxicity, genetic toxicity, and immunotoxicity, and is widely found in corn, barley, wheat, and rye. In order to achieve effective detoxification of DON, the least toxic 3-epi-DON (1/357th of the toxicity of DON) was chosen as the target for degradation. Quinone-dependent dehydrogenase (QDDH) reported from Devosia train D6-9 detoxifies DON by converting C3-OH to a ketone group with toxicity of less than 1/10 that of DON. In this study, the recombinant plasmid pPIC9K-QDDH was constructed and successfully expressed in Pichia pastoris GS115. Within 12 h, recombinant QDDH converted 78.46% of the 20 µg/mL DON to 3-keto-DON. Candida parapsilosis ACCC 20221 was screened for its activity in reducing 86.59% of 3-keto-DON within 48 h; its main products were identified as 3-epi-DON and DON. In addition, a two-step method was performed for epimerizing DON: 12 h catalysis by recombinant QDDH and 6 h transformation of the C. parapsilosis ACCC 20221 cell catalyst. The production rates of 3-keto-DON and 3-epi-DON were 51.59% and 32.57%, respectively, after manipulation. Through this study, effective detoxification of 84.16% of DON was achieved, with the products being mainly 3-keto-DON and 3-epi-DON.

Boosting the Antioxidant Potential of Polymeric Proanthocyanidins in Litchi (Litchi chinensis Sonn.) Pericarp via Biotransformation of Utilizing Lactobacillus Plantarum.

In order to enhance the efficient utilization of polymeric proanthocyanidins from litchi pericarp, a process for transforming litchis' polymeric proanthocyanidins (LPPCs) by using Lactobacilli has been established for products with highly antioxidative properties. Lactobacillus plantarum was selected to enhance the transformation effect. The transformation rate of LPPCs reached 78.36%. The content of litchis' oligomeric proanthocyanidins (LOPCs) in the products achieved 302.84 µg grape seed proanthocyanidins (GPS)/mg DW, while that of total phenols was 1077.93 gallic acid equivalents (GAE) µg/mg DW. Seven kinds of substances have been identified in the products by using the HPLC-QTOF-MS/MS method, among which 4-hydroxycinnamic acid, 3,4-dihydroxy-cinnamic acid, and proanthocyanidin A2 were major components. The in vitro antioxidative activity of the products after transformation was significantly (p < 0.05) higher than those of LOPCs and LPPCs. The scavenging activity of the transformed products for DPPH free radicals was 1.71 times that of LOPCs. The rate of inhibiting conjugated diene hydroperoxides (CD-POV) was 2.0 times that of LPPCs. The scavenging activity of the products for ABTS free radicals was 11.5 times that of LPPCs. The ORAC value of the products was 4.13 times that of LPPCs. In general, this study realizes the transformation of polymeric proanthocyanidins into high-activity small-molecule substances.

Induced Expression of the Acinetobacter sp. Oxa Gene in Lactobacillus acidophilus and Its Increased ZEN Degradation Stability by Immobilization.

Zearalenone (ZEN, ZEA) contamination in various foods and feeds is a significant global problem. Similar to deoxynivalenol (DON) and other mycotoxins, ZEN in feed mainly enters the body of animals through absorption in the small intestine, resulting in estrogen-like toxicity. In this study, the gene encoding Oxa, a ZEN-degrading enzyme isolated from Acinetobacter SM04, was cloned into Lactobacillus acidophilus ATCC4356, a parthenogenic anaerobic gut probiotic, and the 38 kDa sized Oxa protein was expressed to detoxify ZEN intestinally. The transformed strain L. acidophilus pMG-Oxa acquired the capacity to degrade ZEN, with a degradation rate of 42.95% at 12 h (initial amount: 20 µg/mL). The probiotic properties of L. acidophilus pMG-Oxa (e.g., acid tolerance, bile salt tolerance, and adhesion properties) were not affected by the insertion and intracellular expression of Oxa. Considering the low amount of Oxa expressed by L. acidophilus pMG-Oxa and the damage to enzyme activity by digestive juices, Oxa was immobilized with 3.5% sodium alginate, 3.0% chitosan, and 0.2 M CaCl2 to improve the ZEN degradation efficiency (from 42.95% to 48.65%) and protect it from digestive juices. The activity of immobilized Oxa was 32-41% higher than that of the free crude enzyme at different temperatures (20-80 °C), pH values (2.0-12.0), storage conditions (4 °C and 25 °C), and gastrointestinal simulated digestion conditions. Accordingly, immobilized Oxa could be resistant to adverse environmental conditions. Owing to the colonization, efficient degradation performance, and probiotic functionality of L. acidophilus, it is an ideal host for detoxifying residual ZEN in vivo, demonstrating great potential for application in the feed industry.

Variations of pollen concentration in urban alleys of park city and the transmission pattern during the period of high allergenic risk: Taking Qingyang District of Chengdu City as an example.

Pollen (spores and pollen) allergy caused by green areas is one of the most serious environmental epidemics endangering urban public health. The pollen allergy rate in China reached 17.8% in 2022, characterized by a wide age range of onset, severity and diversity of symptoms. The aims of this study were to verify the consistency of the prediction results of pollen concentration and the index of allergenicity of urban green zones (IUGZA) equation, and to clarify the dispersal pattern of tree pollen in the urban alleys of cities with high density of static wind. We selected representative high, medium and low allergenic areas based on the allergenic stress in urban alleys of Qingyang District, Chengdu calculated by IUGZA equation, and monitored the pollen concentrations by selecting points and indicator species within the three allergenic areas. There was a consistency in the variation of pollen concentration in urban alleys of the three areas, with the highest pollen concentration in March. Mean pollen concentration showed a pattern of spring > autumn > summer > winter. The main pollen sources belonged to Ginkgo, Platanus, Firmiana and Cedrus, accounting for 42.4%, 16.3%, 9.0% and 6.5% of the total pollen, respectively. Wind speed had the greatest effect on pollen concentration and its dispersal distance in the urban alley. The horizontal dispersal distance of pollen was up to 260 m, and the number of pollen showed a significant negative linear correlation with the distance away from the pollen sources. The concentration of exotic pollen collected at the high site (4.5 m above ground) was much lower than that at the near-ground site (1.5 m above ground), but without difference in the types of pollen. The results of allergenic risk predicted by the IUGZA equation were consistent with the actual measured pollen concentration, which could be used in high-density static wind city.

Enhancing Photoluminescence of CsPb(ClxBr1-x)3 Perovskite Nanocrystals by Fe2+ Doping.

The doping of impurity ions into perovskite lattices has been scrupulously developed as a promising method to stabilize the crystallographic structure and modulate the optoelectronic properties. However, the photoluminescence (PL) of Fe2+-doped mixed halide perovskite NCs is still relatively unexplored. In this work, the Fe2+-doped CsPb(ClxBr1-x)3 nanocrystals (NCs) are prepared by a hot injection method. In addition, their optical absorption, photoluminescence (PL), PL lifetimes, and photostabilities are compared with those of undoped CsPb(Br1-xClx)3 NCs. We find the Fe2+ doping results in the redshift of the absorption edge and PL. Moreover, the full width at half maximums (FWHMs) are decreased, PL quantum yields (QYs) are improved, and PL lifetimes are extended, suggesting the defect density is reduced by the Fe2+ doping. Moreover, the photostability is significantly improved after the Fe2+ doping. Therefore, this work reveals that Fe2+ doping is a very promising approach to modulate the optical properties of mixed halide perovskite NCs.

Diurnal switches in diazotrophic lifestyle increase nitrogen contribution to cereals.

Uncoupling of biological nitrogen fixation from ammonia assimilation is a prerequisite step for engineering ammonia excretion and improvement of plant-associative nitrogen fixation. In this study, we have identified an amino acid substitution in glutamine synthetase, which provides temperature sensitive biosynthesis of glutamine, the intracellular metabolic signal of the nitrogen status. As a consequence, negative feedback regulation of genes and enzymes subject to nitrogen regulation, including nitrogenase is thermally controlled, enabling ammonia excretion in engineered Escherichia coli and the plant-associated diazotroph Klebsiella oxytoca at 23 °C, but not at 30 °C. We demonstrate that this temperature profile can be exploited to provide diurnal oscillation of ammonia excretion when variant bacteria are used to inoculate cereal crops. We provide evidence that diurnal temperature variation improves nitrogen donation to the plant because the inoculant bacteria have the ability to recover and proliferate at higher temperatures during the daytime.

[Allergenic risk analysis of street trees of urban alleys in Qingyang District, Chengdu, China]. / æˆéƒ½é’ç¾ŠåŒºèƒŒè¡—å°å··è¡Œé“æ ‘å­¢ç²‰è‡´æ•é£Žé™©åˆ†æž.

We examined the pollen allergy risk of street trees in urban alleys, with 410 urban alleys in Qingyang District, Chengdu as an example. On the basis of recording the characteristics of street trees, we calculated the index of allergenicity of urban green zones (IUGZA) values and overlay the regional population density map, and finally obtained the pollen allergy risk map of urban alleys in Qingyang District. The results showed that there were 32461 street trees in 410 urban alleys, belonging to 27 families, 41 genera, and 52 species. The distribution of tree species was extremely uneven, with excessive plantation of Ficus concinna (31.8%), Ginkgo biloba (12.9%) and Cinnamomum camphora (8.5%). The risk of pollen allergy in urban alleys was high, with an average IUGZA value of 2.61 and spring as the primary risk season. Among them, 175 alleys were at the most low allergy degree (IUGZA=0-1), 174 alleys at low degree of allergy (IUGZA=1-5), and 6 alleys at extremely high risk of allergy (IUGZA=15-20). Results of correlation analysis showed that mean tree height and canopy-to-street area ratio were the key factors affecting IUGZA of street trees in urban alleys. After superimposing the population density map, Shaocheng Street, Caoshi Street, Xiyuhe Street, Funan Street, and Supo Street had a high risk of pollen allergy.

The proteolysis targeting chimera GMB-475 combined with dasatinib for the treatment of chronic myeloid leukemia with BCR::ABL1 mutants.

Patients with chronic myeloid leukemia (CML) show resistance to tyrosine kinase inhibitors (TKIs) targeting ABL1 due to the emergence of BCR::ABL1 mutants, especially compound mutants during the treatment, which brings great challenges to clinical practice. Combination therapy is an effective strategy for drug resistance. GMB-475, a proteolysis targeting chimera (PROTAC) targeting the myristoyl pocket of ABL1 in an allosteric manner, degrades the BCR::ABL1 through the ubiquitin-proteasome pathway. In this study, we combined GMB-475 with orthosteric TKIs targeting ABL1 to overcome resistance. We constructed Ba/F3 cells carrying BCR::ABL1 mutants by gene cloning technology and compared the effects of combination therapy with those of monotherapy on the biological characteristics and signaling pathways in CML cells. We found that the effects of ABL1 inhibitors, including imatinib, dasatinib, ponatinib, and ABL001, on growth inhibition and promoting apoptosis of Ba/F3 cells with BCR::ABL1 mutants, especially compound mutants, were weakened. GMB-475 combined with TKIs, especially dasatinib, synergistically inhibited growth, promoted apoptosis, and blocked the cell cycle of Ba/F3 cells carrying BCR::ABL1 mutants and synergistically blocked multiple molecules in the JAK-STAT pathway. In conclusion, dasatinib enhanced the antitumor effect of GMB-475; that is, the combination of PROTAC targeting ABL1 in an allosteric manner and orthosteric TKIs, especially dasatinib, provides a novel idea for the treatment of CML patients with BCR::ABL1 mutants in clinical practice.

Injection-free multiwavelength electroluminescence devices based on monolayer semiconductors driven by an alternating field.

Two-dimensional (2D) semiconductors have emerged as promising candidates for various optoelectronic devices especially electroluminescent (EL) devices. However, progress has been hampered by many challenges including metal contacts and injection, transport, and confinement of carriers due to small sizes of materials and the lack of proper double heterostructures. Here, we propose and demonstrate an alternative approach to conventional current injection devices. We take advantage of large exciton binding energies in 2D materials using impact generation of excitons through an alternating electric field, without requiring metal contacts to 2D materials. The conversion efficiency, defined as the ratio of the emitted photons to the preexisting carriers, can reach 16% at room temperature. In addition, we demonstrate the first multiwavelength 2D EL device, simultaneously operating at three wavelengths from red to near-infrared. Our approach provides an alternative to conventional current-based devices and could unleash the great potential of 2D materials for EL devices.