Enhanced Electron Transport and Mitigated Voltage Loss in Perovskite Photovoltaics Using Sb2O5@SnO2 Composite Electron Transport Layer.

The efficacy of electron transport layers (ETLs) is pivotal for optimizing the device performance of perovskite photovoltaic applications. However, colloidal dispersions of SnO2 are prone to aggregation and possess structural defects, such as terminal-hydroxyls (OHT) and oxygen vacancies (VOs), which can degrade the quality of ETLs, impede charge extraction and transport, and affect the nucleation and growth processes of the perovskite layer. In this study, the Sb(OH)4 - ions hydrolyzed from SbCl3 in colloidal dispersion can bind to defect sites and effectively stabilize the SnO2 nanocrystals are demonstrated. Upon oxidative annealing, a Sb2O5@SnO2 composite film is formed, in which the Sb2O5 not only mitigates the aforementioned defects but also broadens the energy range of unoccupied states through its dispersed conduction band. The increased electron affinity (EA) facilitates more efficient capture of photoexcited electrons from the perovskite layer, thus augmenting electron extraction and minimizing electron-hole recombination. As a result, a significant improvement in power conversion efficiency (PCE) from 22.60% to 24.54% is achieved, with an open circuit voltage (VOC) of up to 1.195 V, along with excellent stability of unsealed devices under various conditions. This study provides valuable insights for the understanding and design of ETLs in perovskite photovoltaic applications.

OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate.

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

Inhibition of Carbohydrate Metabolism Potentiated by the Therapeutic Effects of Oxidative Phosphorylation Inhibitors in Colon Cancer Cells.

Cancer cells undergo a significant level of "metabolic reprogramming" or "remodeling" to ensure an adequate supply of ATP and "building blocks" for cell survival and to facilitate accelerated proliferation. Cancer cells preferentially use glycolysis for ATP production (the Warburg effect); however, cancer cells, including colorectal cancer (CRC) cells, also depend on oxidative phosphorylation (OXPHOS) for ATP production, a finding that suggests that both glycolysis and OXPHOS play significant roles in facilitating cancer progression and proliferation. Our prior studies identified a semisynthetic isoflavonoid, DBI-1, that served as an AMPK activator targeting mitochondrial complex I. Furthermore, DBI-1 and a glucose transporter 1 (GLUT1) inhibitor, BAY-876, synergistically inhibited CRC cell growth in vitro and in vivo. We now report a study of the structure-activity relationships (SARs) in the isoflavonoid family in which we identified a new DBI-1 analog, namely, DBI-2, with promising properties. Here, we aimed to explore the antitumor mechanisms of DBIs and to develop new combination strategies by targeting both glycolysis and OXPHOS. We identified DBI-2 as a novel AMPK activator using an AMPK phosphorylation assay as a readout. DBI-2 inhibited mitochondrial complex I in the Seahorse assays. We performed proliferation and Western blotting assays and conducted studies of apoptosis, necrosis, and autophagy to corroborate the synergistic effects of DBI-2 and BAY-876 on CRC cells in vitro. We hypothesized that restricting the carbohydrate uptake with a KD would mimic the effects of GLUT1 inhibitors, and we found that a ketogenic diet significantly enhanced the therapeutic efficacy of DBI-2 in CRC xenograft mouse models, an outcome that suggested a potentially new approach for combination cancer therapy.

Genome-wide association studies identified OsTMF as a gene regulating rice seed germination under salt stress.

Introduction: Salt tolerance during seed germination is an important trait for direct seeding and low-cost rice production. Nevertheless, it is still not clear how seed germination under salt stress is regulated genetically. Methods: In this study, genome-wide association studies (GWAS) were performed to decipher the genetic basis of seed germination under salt stress using 541 rice varieties collected worldwide. Results and discussion: Three quantitative trait loci (QTLs) were identified including qGRG3-1 on chromosome 3, qGRG3-2 on chromosome 5, and qGRG4 on chromosome 4. Assessment of candidate genes in these loci for their responses to salt stress identified a TATA modulatory factor (OsTMF) in qGRG3-2. The expression of OsTMF was up-regulated in both roots and shoots after exposure to salt stress, and OsTMF knockout mutants exhibited delayed seed germination under salt stress. Haplotype analysis showed that rice varieties carrying OsTMF-Hap2 displayed elevated salt tolerance during seed germination. These results provide important knowledge and resources to improve rice seed germination under salt stress in the future.

The Spartina alterniflora genome sequence provides insights into the salt-tolerance mechanisms of exo-recretohalophytes.

Spartina alterniflora is an exo-recretohalophyte Poaceae species that is able to grow well in seashore, but the genomic basis underlying its adaptation to salt tolerance remains unknown. Here, we report a high-quality, chromosome-level genome assembly of S. alterniflora constructed through PacBio HiFi sequencing, combined with high-throughput chromosome conformation capture (Hi-C) technology and Illumina-based transcriptomic analyses. The final 1.58 Gb genome assembly has a contig N50 size of 46.74 Mb. Phylogenetic analysis suggests that S. alterniflora diverged from Zoysia japonica approximately 21.72 million years ago (MYA). Moreover, whole-genome duplication (WGD) events in S. alterniflora appear to have expanded gene families and transcription factors relevant to salt tolerance and adaptation to saline environments. Comparative genomics analyses identified numerous species-specific genes, significantly expanded genes and positively selected genes that are enriched for 'ion transport' and 'response to salt stress'. RNA-seq analysis identified several ion transporter genes including the high-affinity K+ transporters (HKTs), SaHKT1;2, SaHKT1;3 and SaHKT1;8, and high copy number of Salt Overly Sensitive (SOS) up-regulated under high salt conditions, and the overexpression of SaHKT2;4 in Arabidopsis thaliana conferred salt tolerance to the plant, suggesting specialized roles for S. alterniflora to adapt to saline environments. Integrated metabolomics and transcriptomics analyses revealed that salt stress activate glutathione metabolism, with differential expressions of several genes such as γ-ECS, GSH-S, GPX, GST and PCS in the glutathione metabolism. This study suggests several adaptive mechanisms that could contribute our understanding of evolutional basis of the halophyte.

Fluorinated Polyimide Tunneling Layer for Efficient and Stable Perovskite Photovoltaics.

Despite the remarkable progress of perovskite solar cells (PSCs), challenges remain in terms of finding effective and viable strategies to enhance their long-term stability while maintaining high efficiency. In this study, a new insulating and hydrophobic fluorinated polyimide (FPI: 6FDA-6FAPB) was used as the interface layer between the perovskite layer and the hole transport layer (HTL) in PSCs. The functional groups of FPI play a pivotal role in passivating interface defects within the device. Due to its high work function, FPI demonstrates field-effect passivation (FEP) capabilities as an interface layer, effectively mitigating non-radiative recombination at the interface. Notably, the FPI insulating interface layer does not impede carrier transmission at the interface, which is attributed to the presence of hole tunneling effects. The optimized PSCs achieve an outstanding power conversion efficiency (PCE) of 24.61 % and demonstrate excellent stability, showcasing the efficacy of FPI in enhancing device performance and reliability.

Rapid screening and isolation of 5-lipoxygenase inhibitors in Inonotus obliquus and mechanism of action in the treatment of asthma.

Accurate screening and targeted preparative isolation of active substances in natural medicines have long been two technical challenges in natural medicine research. This study outlines a new approach to improve the efficiency of natural product preparation, focusing on rapidly and accurately screening potential active ingredients in Inonotus obliquus as well as efficiently preparing 5-lipoxidase (5-LOX) inhibitors, to provide new ideas for the treatment of asthma with Inonotus obliquus. First, we used ultrafiltration (UF) mass spectrometry to screen for three potential inhibitors of 5-LOX in Inonotus obliquus. Subsequently, the inhibitory effect of the active ingredients screened in the UF assay on 5-LOX was verified using the molecular docking technique, and the potential role of the active compounds in Inonotus obliquus for the treatment of asthma was analyzed by network pharmacology. Finally, based on the above activity screening guidelines, we used semi-preparative liquid chromatography and consecutive high-speed countercurrent chromatography to isolate three high-purity 5-LOX inhibitors such as betulin, lanosterol, and quercetin. Obviously, through the above approach, we have seamlessly combined rapid discovery, screening, and centralized preparation of the active ingredient with molecular-level interactions between the active ingredient and the protease.

Integrated analysis and separation of 5-lipoxygenase inhibitors from triterpenes of Poria cocos using bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking and target-based multiple complex networks.

Poria cocos (Schw.) Wolf (P. cocos) has been widely used as medical plant in East Asia with remarkable anti-Alzheimer's disease (anti-AD) activity. However, the underlying mechanisms are still confused. In this study, based on the ß-Amyloid deposition hypothesis of AD, an integrated analysis was conducted to screen and separation 5-lipoxygenase (5-LOX) inhibitors from triterpenoids of P. cocos and investigate the anti-AD mechanisms, containing bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking, and multiple complex networks. Five triterpenoids were identified as potential 5-LOX inhibitors, including Tumulosic acid, Polyporenic acid C, 3-Epi-dehydrotumulosic acid, Pachymic acid and Dehydrotrametenolic acid. Five potential 5-LOX inhibitors were screened by ultrafiltration affinity assay in P. cocos. The molecular docking simulation results are consistent with the ultrafiltration experimental results, which further verifies the accuracy of the experiment. The commercial 5-LOX inhibitor that Zileuton was used as a positive control to evaluate the inhibitory effect of active ingredients on 5-LOX. Subsequently, the established separation method allowed the five active ingredients (Pachymic acid, 3-Epi-dehydrotumulosic acid, Dehydrotrametenolic acid, Tumulosic acid and Polyporenic acid C) with high purity to be isolated. Targeting network pharmacology analysis showed that five active ingredients correspond to a total of 286 targets. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that target cells were mainly enriched in Pathways in cancer, Lipid and atherosclerosis. Our results indicate that P. cocos extract has the potential to be used in the prevention and treatment of neurodegenerative diseases. This will help elucidate the mechanisms of action of various medicinal plants at the molecular level and provide more opportunities for the discovery and development of new potential treatments from health food resources.

Efficient and fast screening and separation based on computer-aided screening and complex chromatography methods for lipoxygenase inhibitors from Ganoderma lucidum.

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.

In Operando Visualization of Elementary Turnovers in Photocatalytic Organic Synthesis.

We report the in operando visualization of the photocatalytic turnovers on single eosin Y (EY) through a redox-induced photoblinking phenomenon. The photocatalytic cyclization of thiobenzamide (TB) catalyzed by EY was investigated. The analysis of the intensity-versus-time trajectories of single EYs revealed the kinetics and dynamics of the elementary photocatalytic turnovers and the heterogeneity of the activity of individual EYs. The quenching turnover time showed a fast population and a slow population, which could be attributed to the singlet and triplet states of photoexcited EY. The slow quenching turnovers were more dominant at higher TB concentrations. The activity heterogeneity of EYs was studied over a series of reactant concentrations. Excess quenching reagent was found to decrease the percentage of active EYs. The method can be broadly applied to studying the elementary processes of photocatalytic organic reactions in operando.

Optical sequencing of single synthetic polymers.

Microscopic sequences of synthetic polymers play crucial roles in the polymer properties, but are generally unknown and inaccessible to traditional measurements. Here we report real-time optical sequencing of single synthetic copolymer chains under living polymerization conditions. We achieve this by carrying out multi-colour imaging of polymer growth by single catalysts at single-monomer resolution using CREATS (coupled reaction approach toward super-resolution imaging). CREATS makes a reaction effectively fluorogenic, enabling single-molecule localization microscopy of chemical reactions at higher reactant concentrations. Our data demonstrate that the chain propagation kinetics of surface-grafted polymerization contains temporal fluctuations with a defined memory time (which can be attributed to neighbouring monomer interactions) and chain-length dependence (due to surface electrostatic effects). Furthermore, the microscopic sequences of individual copolymers reveal their tendency to form block copolymers, and, more importantly, quantify the size distribution of individual blocks for comparison with theoretically random copolymers. Such sequencing capability paves the way for single-chain-level structure-function correlation studies of synthetic polymers.

Dietary Chito-oligosaccharide attenuates LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathway.

To investigate the regulatory effects of Chito-oligosaccharide (COS) on the anti-oxidative, anti-inflammatory, and MAPK signaling pathways. A total of 40 28-day-old weaned piglets were randomly allotted to 4 equal groups [including the control group, lipopolysaccharide (LPS) group, COS group, and COS*LPS group]. On the morning of d 14 and 21, piglets were injected with saline or LPS. At 2 h post-injection, whole blood samples were collected on d 14 and 21, and small intestine and liver samples were collected and analyzed on d 21. The results showed that COS inhibited the LPS-induced increase of malondialdehyde (MDA) concentration and hepatic TNF-α cytokines. COS significantly increased the serum total antioxidant capability (T-AOC) value on d 14, and total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) activities in both serum and liver on d 21. Furthermore, it increased hepatic catalase (CAT) activity. COS also increased the LPS-induced decrease in serum IgG concentrations. Immunohistochemical analysis results showed that COS significantly increased the jejunal and ileal Caspase 3, and ileal CD4+ values challenged by LPS. Dietary COS decreased the LPS-induced jejunal and ileal BAX and CCL2 mRNA levels, markedly decreased ileal COX2 and SOD1 mRNA levels, while increasing ileal iNOS. Furthermore, COS significantly increased the LPS-induced jejunal and ileal p-P38 and MyD88, as well as jejunal P38, while it effectively suppressed jejunal JNK1, and jejunal and ileal JNK2, p-JNK1, and p-JNK2 protein expressions. These results demonstrated that COS could be beneficial by attenuating LPS-challenged intestinal inflammation via regulating mitochondrial apoptotic and MAPK signaling pathways.

Rapid screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Polyporus umbellatus and mechanism of action in the treatment of gout.

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.

Screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Poria Cum Radix Pini and mechanism of action in the treatment of gout disease.

Poria Cum Radix Pini is a rare medicinal fungus that contains several potential therapeutic ingredients. On this basis, a particle swarm mathematical model was used to optimize the extraction process of total triterpenes from P. Cum Radix Pini, and xanthine oxidase inhibitors were screened using affinity ultrafiltration mass spectrometry. Meanwhile, the accuracy of the ultrafiltration assay was verified by molecular docking experiments and molecular dynamics analysis, and the mechanism of action of the active compounds for the treatment of gout was analyzed by enzymatic reaction kinetics and network pharmacology. A high-speed countercurrent chromatography method combined with the consecutive injection and the economical two-phase solvent system preparation using functional activity coefficient of universal quasichemical model (UNIFAC) mathematical model was developed for increasing the yield of target compound. In addition, dehydropachymic acid and pachymic acid were used as competitive inhibitors, and 3-O-acetyl-16alpha-hydroxydehydrotrametenolic acid and dehydrotrametenolic acid were used as mixed inhibitors. Then, activity-oriented separation and purification were performed by high-speed countercurrent chromatography combined with semi-preparative high-performance liquid chromatography and the purity of the four compounds isolated was higher than 90%. It will help to provide more opportunities to discover and develop new potential therapeutic remedies from health care food resources.

Zebrafish drug screening identifies Erlotinib as an inhibitor of Wnt/ß-catenin signaling and self-renewal in T-cell acute lymphoblastic leukemia.

The Wnt/ß-catenin pathway's significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/ß-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The efficacy of the top hit, Erlotinib, extended to human cells, where it blocked Wnt/ß-catenin signaling downstream of the destruction complex. Notably, Erlotinib treatment reduced self-renewal in human T-cell Acute Lymphoblastic Leukemia cells, which rely on active ß-catenin signaling for maintenance of leukemia-initiating cells. Erlotinib also reduced leukemia-initiating cell frequency and delayed disease formation in zebrafish models. This study underscores zebrafish's translational potential in drug discovery and repurposing and highlights a new use for Erlotinib as a Wnt inhibitor for cancers driven by aberrant Wnt/ß-catenin signaling.

Comprehensive improvement of nutrients and volatile compounds of black/purple rice by extrusion-puffing technology.

Introduction: Black/purple rice is a pigmented rice variety that contains high levels of anthocyanins, flavonoids, and other valuable bioactive compounds. Owing to its robust anti-inflammatory and antioxidant properties, black/purple rice exerts a beneficial effect on human health. Extrusion puffing technology has emerged as a promising means of improving rice flavor with lesser effect on nutrient content. In this study, metabolomics approach was used to conduct comprehensive metabolomics analyses aimed at examining the impact of extrusion puffing on black/purple rice nutritional value and flavor. Methods: Firstly, the basic nutrient composition contents and extrudate characteristics of black/purple rice and Extrusion puffed black/purple rice were conducted. Then metabolomics profiling analyses of black/purple rice samples were performed to explore the impact of the extrusion puffing process on nutrient content and bioactive properties, in which we quantitatively determined the flavonoids and evaluated relative contents of volatile compounds. Results: These analyses revealed that following extrusion puffing, black/purple rice exhibited significant improvements in the content of nutrients including flavonoids, minerals, and proteins together. Extrusion puffing additionally increased the diversity of volatile compounds within black/purple rice. Discussion: These results suggest that extrusion puffing represents an effective means of substantially improving the functional and nutritional properties of black/purple rice, offering beneficial effects on consumer health. Overall, these data provide novel insights into the quality of extrusion puffed black/purple rice that will guide future efforts to establish how extrusion puffing can alter the nutrient content in a range of foods, thereby supporting the further development of a range of healthy food products.

TMT and PRM Based Quantitative Proteomics to Explore the Protective Role and Mechanism of Iristectorin B in Stroke.

Stroke is a serious disease caused by the rupture or blockage of the cerebrovascular system. Its pathogenesis is complex and involves multiple mechanisms. Iristectorin B is a natural isoflavone that has certain anti stroke effects. In this study, an in vitro stroke injury model of glyoxylate deprivation was established using PC12 cells, which was used to evaluate the anti-stroke activity of Iristectorin B in ejecta stem. The results showed that Iristectorin B, a natural isoflavone derived from Dried Shoot, significantly reduced the damage to PC12 cells caused by oxygen glucose deprivation/reoxygenation, decreased apoptosis, enhanced cell survival and reduced Ca2+, LDH and ROS levels. The results showed that Iristectorin B had a significant protective effect on Na2S2O4-injured PC12 cells, and the mechanism may be related to the protective effect of neurons in the brain. After protein extraction and various analyses were performed, a series of cutting-edge technologies were organically combined to study the quantitative proteome of each group. Differential proteins were then analyzed. According to the protein screening principle, ferroptosis-related proteins were most closely associated with stroke. The differential proteins associated with ferroptosis screened were SLC3A2, TFR1 and HMOX1, with HMOX1 being the most significantly elevated and reduced via dosing. Iristectorin B may act as a protective agent against stroke by regulating ferroptosis, and SLC3A2, TFR1 and HMOX1 may serve as potential diagnostic biomarkers for stroke, providing additional evidence to support the importance of ferroptosis in stroke.

The cytokinin receptor OHK4/OsHK4 regulates inflorescence architecture in rice via an IDEAL PLANT ARCHITECTURE1/WEALTHY FARMER'S PANICLE-mediated positive feedback circuit.

Inflorescence architecture is important for rice (Oryza sativa) grain yield. The phytohormone cytokinin (CK) has been shown to regulate rice inflorescence development; however, the underlying mechanism mediated by CK perception is still unclear. Employing a forward genetic approach, we isolated an inactive variant of the CK receptor OHK4/OsHK4 gene named panicle length1, which shows decreased panicle size due to reduced inflorescence meristem (IM) activity. A 2-amino acid deletion in the long α-helix stalk of the sensory module of OHK4 impairs the homodimerization and ligand-binding capacity of the receptor, even though the residues do not touch the ligand-binding domain or the dimerization interface. This deletion impairs CK signaling that occurs through the type-B response regulator OsRR21, which acts downstream of OHK4 in controlling inflorescence size. Meanwhile, we found that IDEAL PLANT ARCHITECTURE1(IPA1)/WEALTHY FARMER'S PANICLE (WFP), encoding a positive regulator of IM development, acts downstream of CK signaling and is directly activated by OsRR21. Additionally, we revealed that IPA1/WFP directly binds to the OHK4 promoter and upregulates its expression through interactions with 2 TCP transcription factors, forming a positive feedback circuit. Altogether, we identified the OHK4-OsRR21-IPA1 regulatory module, providing important insights into the role of CK signaling in regulating rice inflorescence architecture.

Zebrafish Drug Screening Identifies Erlotinib as an Inhibitor of Wnt/ß-Catenin Signaling and Self-Renewal in T-cell Acute Lymphoblastic Leukemia.

The Wnt/ß-catenin pathway's significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential, yet clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex crosstalk with other pathways. In this study, we leveraged the zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/ß-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The efficacy of the top hit, Erlotinib, extended to human cells, where it blocked Wnt/ß-catenin signaling downstream of the destruction complex. Notably, Erlotinib treatment reduced self-renewal in human T-cell Acute Lymphoblastic Leukemia cells, which are known to rely on active ß-catenin signaling for maintenance of leukemia-initiating cells. Erlotinib also reduced leukemia-initiating cell frequency and delayed disease formation in zebrafish models. This study underscores zebrafish's translational potential in drug discovery and repurposing, and highlights a new use for Erlotinib as a Wnt inhibitor for cancers driven by aberrant Wnt/ß-catenin signaling. Highlights: Zebrafish-based drug screening offers an inexpensive and robust platform for identifying compounds with high efficacy and low toxicity in vivo . Erlotinib, an Epidermal Growth Factor Receptor (EGFR) inhibitor, emerged as a potent and promising Wnt inhibitor with effects in both zebrafish and human cell-based Wnt reporter assays.The identification of Erlotinib as a Wnt inhibitor underscores the value of repurposed drugs in developing targeted therapies to disrupt cancer stemness and improve clinical outcomes.

In-depth analysis of the xanthine oxidase inhibitors of Cicer arietinum L.-based receptor-ligand affinity coupled with complex chromatography.

INTRODUCTION: Cicer arietinum L. is the choice of health food for people with diabetes, hypertension, and hyperlipidemia. As an essential source of high-nutrition legumes, it is also an important source of dietary isoflavones. OBJECTIVES: In order to improve the preparation efficiency of natural plants, a rapid biological activity screening and preparation of xanthine oxidase inhibitors from C. arietinum L. was established. METHODS: Xanthine oxidase (XOD) inhibitors were rapidly screened using ultrafiltration liquid chromatography-mass spectrometry (UF-LC-MS) based on receptor-ligand affinity. The change in XOD activity was evaluated by enzymatic reaction kinetics measurement. The potential bioactive compounds were verified through molecular docking. In addition, the biological activity of ligands screened was separated and purified by complex chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS: Three active ingredients, namely daidzin, daidzein, calycosin with XOD binding affinities were identified and isolated from the raw plant materials via semi-preparative high-performance liquid chromatography (HPLC), 0-60 min, 5-50% B and countercurrent chromatography (CCC) (ethyl acetate/acetic acid/water [5:0.8:10, v/v/v]). CONCLUSION: This study will help to elucidate the mechanisms of action of natural plants of interest at the molecular level and could also provide more opportunities for the discovery and development of new nutritional value from other natural resources.