Selenium Nanomaterials Enhance Sheath Blight Resistance and Nutritional Quality of Rice: Mechanisms of Action and Human Health Benefit.

In the current work, the foliar application of selenium nanomaterials (Se0 NMs) suppressed sheath blight in rice (Oryza sativa). The beneficial effects were nanoscale specific and concentration dependent. Specifically, foliar amendment of 5 mg/L Se0 NMs decreased the disease severity by 68.8% in Rhizoctonia solani-infected rice; this level of control was 1.57- and 2.20-fold greater than that of the Se ions with equivalent Se mass and a commercially available pesticide (Thifluzamide). Mechanistically, (1) the controlled release ability of Se0 NMs enabled a wider safe concentration range and greater bioavailability to Se0 NMs, and (2) transcriptomic and metabolomic analyses demonstrated that Se0 NMs simultaneously promoted the salicylic acid- and jasmonic-acid-dependent acquired disease resistance pathways, antioxidative system, and flavonoid biosynthesis. Additionally, Se0 NMs improved rice yield by 31.1%, increased the nutritional quality by 6.4-7.2%, enhanced organic Se content by 44.8%, and decreased arsenic and cadmium contents by 38.7 and 42.1%, respectively, in grains as compared with infected controls. Human simulated gastrointestinal tract model results showed that the application of Se0 NMs enhanced the bioaccessibility of Se in grains by 22.0% and decreased the bioaccessibility of As and Cd in grains by 20.3 and 13.4%, respectively. These findings demonstrate that Se0 NMs can serve as an effective and sustainable strategy to increase food quality and security.

Lycopene Promotes Osteogenesis and Reduces Adipogenesis through Regulating FoxO1/PPARγ Signaling in Ovariectomized Rats and Bone Marrow Mesenchymal Stem Cells.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.

Stochastic process is main factor to affect plateau river fish community assembly.

Plateau river ecosystems are often highly vulnerable and responsive to environmental change. The driving mechanism of fish diversity and community assembly in plateau rivers under changing environments presents a significant complexity to the interdisciplinary study of ecology and environment. This study integrated molecular biological techniques and mathematical models to identify the mechanisms influencing spatial heterogeneity of freshwater fish diversity and driving fish community assembly in plateau rivers. By utilizing environmental-DNA metabarcoding and the null model, this study revealed the impact of the stochastic process on fish diversity variations and community assembly in the Huangshui Plateau River of the Yellow River Basin (YRB) in China. This research identified 30 operational taxonomic units (OTUs), which correspond to 20 different fish species. The findings of this study revealed that the fish α-diversity in the upstream region of Xining is significantly higher than in the middle-lower reach (Shannon index: P = 0.017 and Simpson: P = 0.035). This pattern was not found to be related to any other environmental factors besides altitude (P = 0.023) that we measured. Further, the study indicated that the assembly of fish communities in the Huangshui River primarily depends on stochastic ecological processes. These findings suggested that elevation was not the primary factor impacting the biodiversity patterns of fish in plateau rivers. In plateau rivers, spatial heterogeneity of fish community on elevation is mainly determined by stochastic processes under habitat fragmentation, rather than any other physicochemical environmental factors. The limitations of connectivity in the downstream channel of the river could be taken the mainly responsibility for stochastic processes of fish community in Huangshui River. Incorporating ecological processes in the eDNA approach holds great potential for future monitoring and evaluation of fish biodiversity and community assembly in plateau rivers.

The Glucose-Succinate Pathway: A Crucial Anaerobic Metabolic Pathway in the Scallop Chlamys farreri Experiencing Heat Stress.

Recently, the increase in marine temperatures has become an important global marine environmental issue. The ability of energy supply in marine animals plays a crucial role in avoiding the stress of elevated temperatures. The investigation into anaerobic metabolism, an essential mechanism for regulating energy provision under heat stress, is limited in mollusks. In this study, key enzymes of four anaerobic metabolic pathways were identified in the genome of scallop Chlamys farreri, respectively including five opine dehydrogenases (CfOpDHs), two aspartate aminotransferases (CfASTs) divided into cytoplasmic (CfAST1) and mitochondrial subtype (CfAST2), and two phosphoenolpyruvate carboxykinases (CfPEPCKs) divided into a primitive type (CfPEPCK2) and a cytoplasmic subtype (CfPEPCK1). It was surprising that lactate dehydrogenase (LDH), a key enzyme in the anaerobic metabolism of the glucose-lactate pathway in vertebrates, was absent in the genome of scallops. Phylogenetic analysis verified that CfOpDHs clustered according to the phylogenetic relationships of the organisms rather than substrate specificity. Furthermore, CfOpDHs, CfASTs, and CfPEPCKs displayed distinct expression patterns throughout the developmental process and showed a prominent expression in muscle, foot, kidney, male gonad, and ganglia tissues. Notably, CfASTs displayed the highest level of expression among these genes during the developmental process and in adult tissues. Under heat stress, the expression of CfASTs exhibited a general downregulation trend in the six tissues examined. The expression of CfOpDHs also displayed a downregulation trend in most tissues, except CfOpDH1/3 in striated muscle showing significant up-regulation at some time points. Remarkably, CfPEPCK1 was significantly upregulated in all six tested tissues at almost all time points. Therefore, we speculated that the glucose-succinate pathway, catalyzed by CfPEPCK1, serves as the primary anaerobic metabolic pathway in mollusks experiencing heat stress, with CfOpDH3 catalyzing the glucose-opine pathway in striated muscle as supplementary. Additionally, the high and stable expression level of CfASTs is crucial for the maintenance of the essential functions of aspartate aminotransferase (AST). This study provides a comprehensive and systematic analysis of the key enzymes involved in anaerobic metabolism pathways, which holds significant importance in understanding the mechanism of energy supply in mollusks.

A novel approach for melanoma detection utilizing GAN synthesis and vision transformer.

BACKGROUND AND OBJECTIVE: Melanoma, a malignant form of skin cancer, is a critical health concern worldwide. Early and accurate detection plays a pivotal role in improving patient's conditions. Current diagnosis of skin cancer largely relies on visual inspections such as dermoscopy examinations, clinical screening and histopathological examinations. However, these approaches are characterized by low efficiency, high costs, and a lack of guaranteed accuracy. Consequently, deep learning based techniques have emerged in the field of melanoma detection, successfully aiding in improving the accuracy of diagnosis. However, the high similarity between benign and malignant melanomas, combined with the class imbalance issue in skin lesion datasets, present a significant challenge in further improving the diagnosis accuracy. We propose a two-stage framework for melanoma detection to address these issues. METHODS: In the first stage, we use Style Generative Adversarial Networks with Adaptive discriminator augmentation synthesis to generate realistic and diverse melanoma images, which are then combined with the original dataset to create an augmented dataset. In the second stage, we utilize a vision Transformer of BatchFormer to extract features and detect melanoma or non-melanoma skin lesions on the augmented dataset obtained in the previous step, specifically, we employed a dual-branch training strategy in this process. RESULTS: Our experimental results on the ISIC2020 dataset demonstrate the effectiveness of the proposed approach, showing a significant improvement in melanoma detection. The method achieved an accuracy of 98.43%, an AUC value of 98.63%, and an F1 value of 99.01%, surpassing some existing methods. CONCLUSION: The method is feasible, efficient, and achieves early melanoma screening. It significantly enhances detection accuracy and can assist physicians in diagnosis to a great extent.

A dual-target SPR screening system for simultaneous ligand discovery of SARS-CoV-2 spike protein and its receptor ACE2 from Chinese herbs.

Traditional Chinese Medicine (TCM) is a supremely valuable resource for the development of drug discovery. Few methods are capable of hunting for potential molecule ligands from TCM towards more than one single protein target. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed to perform targeted compound screening of two key proteins involved in the cellular invasion process of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): the spike (S) protein receptor binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2). The screening and identification of active compounds from six Chinese herbs were conducted taking into consideration the multi-component and multi-target nature of Traditional Chinese Medicine (TCM). Puerarin from Radix Puerariae Lobatae was discovered to exhibit specific binding affinity to both S protein RBD and ACE2. The results highlight the efficiency of the dual-target SPR system in drug screening and provide a novel approach for exploring the targeted mechanisms of active components from Chinese herbs for disease treatment.

Peroxynitrite-activated fluorescent probe with two reaction triggers for pathological diagnosis and therapeutic evaluation of inflammation.

Excessive peroxynitrite (ONOO-) is closely related to the occurrence and progression of inflammation. Therefore, the development of an efficacious ONOO- activatable probe holds great potential for the early diagnosis of pathological inflammation, and the direct evaluation of the therapeutic efficacy of active protectants. In this work, a new ONOO--activated fluorescent probe (SZP) which greatly improved the specificity and sensitivity (LOD = 8.03 nM) with large Stokes shift (150 nm) through introducing two reaction triggers (diphenyl phosphinate moiety, CC unsaturated bond) was rationally designed for rapid detecting ONOO- (within 2 min). The excellent properties of probe SZP enable it to realize the fluorescence-guided diagnosis of inflammation. More importantly, probe SZP has also been utilized to assess the anti-inflammatory efficacy of traditional Chinese medicines (TCMs) active ingredients for the remediation of inflammation by monitoring ONOO- fluctuation for the first time.

Wighteone, a prenylated flavonoid from licorice, inhibits growth of SW480 colorectal cancer cells by allosteric inhibition of Akt.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.

OsMADS6-OsMADS32 and REP1 control palea cellular heterogeneity and morphogenesis in rice.

Precise regulation of cell proliferation and differentiation is vital for organ morphology. Rice palea, serving as sepal, comprises two distinct regions: the marginal region (MRP) and body of palea (BOP), housing heterogeneous cell populations, which makes it an ideal system for studying organ morphogenesis. We report that the transcription factor (TF) REP1 promotes epidermal cell proliferation and differentiation in the BOP, resulting in hard silicified protrusion cells, by regulating the cyclin-dependent kinase gene, OsCDKB1;1. Conversely, TFs OsMADS6 and OsMADS32 are expressed exclusively in the MRP, where they limit cell division rates by inhibiting OsCDKB2;1 expression and promote endoreduplication, yielding elongated epidermal cells. Furthermore, reciprocal inhibition between the OsMADS6-OsMADS32 complex and REP1 fine-tunes the balance between cell division and differentiation during palea morphogenesis. We further show the functional conservation of these organ identity genes in heterogeneous cell growth in Arabidopsis, emphasizing a critical framework for controlling cellular heterogeneity in organ morphogenesis.

A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening.

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).

Multi-Functional Integration of Phosphor, Initiator, and Crosslinker for the Photo-Polymerization of Flexible Phosphorescent Polymer Gels.

A general approach to constructing room temperature phosphorescence (RTP) materials involves the incorporation of a phosphorescent emitter into a rigid host or polymers with high glass transition temperature. However, these materials often suffer from poor processability and suboptimal mechanical properties, limiting their practical applications. In this work, we developed benzothiadiazole-based dialkene (BTD-HEA), a multifunctional phosphorescent emitter with a remarkable yield of intersystem crossing (ΦISC, 99.83 %). Its high triplet exciton generation ability and dialkene structure enable BTD-HEA to act as a photoinitiator and crosslinker, efficiently initiating the polymerization of various monomers within 120 seconds. A range of flexible phosphorescence gels, including hydrogels, organogels, ionogels, and aerogels were fabricated, which exhibit outstanding stretchability and recoverability. Furthermore, the unique fluorescent-phosphorescent colorimetric properties of the gels provide a more sensitive method for the visual determination of the polymerization process. Notably, the phosphorescent emission intensity of the hydrogel can be increased by the formation of ice, allowing for the precise detection of hydrogel freezing. The versatility of this emitter paves the way for fabricating various flexible phosphorescence gels with diverse morphologies using microfluidics, film-shearing, roll coating process, and two/three-dimensional printing, showcasing its potential applications in the fields of bioimaging and bioengineering.

Mechanistic insight into the intensification of arsenic toxicity to rice (Oryza sativa L.) by nanoplastic: Phytohormone and glutathione metabolism modulation.

In this study, nanoplastic (NPs) at environmentally relevant concentration (0.001% w/w) had no effect on the growth of rice, while significantly elevated the phytotoxicity of As (III) by 9.4-22.8% based on the endpoints of biomass and photosynthesis. Mechanistically, NPs at 0.001% w/w enhanced As accumulation in the rice shoots and roots by 70.9% and 24.5%, respectively. Reasons of this finding can was that (1) the co-exposure with As and NPs significantly decreased abscisic acid content by 16.0% in rice, with subsequent increasing the expression of aquaporin related genes by 2.1- to 2.7-folds as compared with As alone treatment; (2) the presence of NPs significantly inhibited iron plaque formation on rice root surface by 22.5%. We firstly demonstrated that "Trojan horse effect" had no contribution to the enhancement of As accumulation by NPs exposure. Additionally, NPs disrupted the salicylic acid, jasmonic acid, and glutathione metabolism, which subsequently enhancing the oxidation (7.0%) and translocation (37.0%) of in planta As, and reducing arsenic detoxification pathways (e.g., antioxidative system (28.6-37.1%), As vacuolar sequestration (36.1%), and As efflux (18.7%)). Our findings reveal that the combined toxicity of NPs and traditional contaminations should be considered for realistic evaluations of NPs.

High-throughput BCRP inhibitors screening system based on styrene maleic acid polymer membrane protein stabilization strategy and surface plasmon resonance biosensor.

Multidrug resistance (MDR) is a dominant challenge in cancer chemotherapy failure. The over-expression of breast cancer resistance protein (BCRP) in tumorous cells, along with its extensive substrate profile, is a leading cause of tumor MDR. Herein, on the basis of styrene maleic acid (SMA) polymer membrane protein stabilization strategy and surface plasmon resonance (SPR) biosensor, a novel high-throughput screening (HTS) system for BCRP inhibitors has been established. Firstly, LLC-PK1 and LLC-PK1/BCRP cell membranes were co-incubated with SMA polymers to construct SMA lipid particles (SMALPs). PK1-SMALPs were thus immobilized in channel 1 of the L1 chip as the reference channel, and BCRP-SMALPs were immobilized in channel 2 as the detection channel to establish the BCRP-SMALPs-SPR screening system. The methodological investigation demonstrated that the screening system was highly specific and stable. Three active compounds were screened out from 26 natural products and their affinity constants with BCRP were determined. The KD of xanthotoxin, bergapten, and naringenin were 5.14 µM, 4.57 µM, and 3.72 µM, respectively. The in vitro cell verification experiments demonstrated that xanthotoxin, bergapten, and naringenin all significantly increased the sensitivity of LLC-PK1/BCRP cells to mitoxantrone with possessing reversal BCRP-mediated MDR activity. Collectively, the developed BCRP-SMALPs-SPR screening system in this study has the advantages of rapidity, efficiency, and specificity, providing a novel strategy for the in-depth screening of BCRP inhibitors with less side effects and higher efficacy.

7Li NMR Spectroscopy: A Tool for Determining Dimerization Constants and Averaged Dimerization Constants of the Monomer/Dimer Equilibrium of Hierarchical Helicates.

7Li nuclear magnetic resonance (NMR) spectroscopy is an ideal tool to study hierarchically assembled helicates of the form Li[Li3L6Ti2]. Internally bound and external lithium ions can be well distinguished by solution- or solid-state NMR spectroscopy and dimerization constants of the monomer/dimer equilibrium can be easily determined in solution. Averaged dimerization constants can be estimated in case of statistical mixtures of helicates formed from mixtures of ligands.

Multi-omics landscape to decrypt the distinct flavonoid biosynthesis of Scutellaria baicalensis across multiple tissues.

Scutellaria baicalensis Georgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensis genome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensis in the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensis through a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.

Boosted Electrocatalytic Degradation of Levofloxacin by Chloride Ions: Performances Evaluation and Mechanism Insight with Different Anodes.

As chloride (Cl-) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl- improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl- affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl- participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

Drought stress reduces the photosynthetic source of subtending leaves and the transit sink function of podshells, leading to reduced seed weight in soybean plants.

Drought stress is the key factor limiting soybean yield potential. Soybean seed formation involves a coordinated "subtending leaf-podshell-seed" process, but little is known about the assimilation and transport of photoassimilates in subtending leaves, podshells and seeds or their relationships with soybean seed formation under drought stress. To address these research gaps, two-year experiments with two soybean cultivars, Wandou 37 (drought tolerant) and Zhonghuang 13 (drought sensitive), were conducted under three soil water content (SWC) conditions in 2020 and 2021 based on the responses of their yield to drought. We analyzed the photosynthetic assimilation and translocation of photoassimilates in subtending leaves, podshells and seeds by stable isotope labeling. Compared with those under 75% SWC, 60% SWC and 45% SWC significantly decreased the Wandou 37 seed weight by 19.4% and 37.5%, respectively, and that of Zhonghuang 13 by 26.9% and 48.6%, respectively. Compared with those under 75% SWC, drought stress decreased the net photosynthetic rate and the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SuSy), which in turn decreased the photosynthetic capacity of the subtending leaves. The podshells ensure the input of photoassimilates by increasing the SuSy activity, but the weakened source-sink relationship between podshells and seeds under drought stress leads to a decrease in the translocation of assimilates from podshells to seeds. The lack of assimilates under drought stress is an important factor restricting the development of soybean seeds. We conclude that the decrease in seed weight was caused by the decrease in the photosynthetic capacity of the subtending leaves and the decrease in the overall availability of photoassimilates; moreover, by a decrease in the translocation of assimilates from podshells to seeds.

Benzoylaconitine: A promising ACE2-targeted agonist for enhancing cardiac function in heart failure.

Benzoylaconitine is a natural product in the treatment of cardiovascular disease. However, its pharmacological effect, direct target protein, and molecular mechanisms for the treatment of heart failure are unclear. In this study, benzoylaconitine inhibited Ang II-induced cell hypertrophy and fibrosis in rat primary cardiomyocytes and rat fibroblasts, while attenuating cardiac function and cardiac remodeling in TAC mice. Using the limited proteolysis-mass spectrometry (LiP-MS) method, the angiotensin-converting enzyme 2 (ACE2) was confirmed as a direct binding target of benzoylaconitine for the treatment of heart failure. In ACE2-knockdown cells and ACE2-/- mice, benzoylaconitine failed to ameliorate cardiomyocyte hypertrophy, fibrosis, and heart failure. Online RNA-sequence analysis indicated p38/ERK-mediated mitochondrial reactive oxygen species (ROS) and nuclear factor kappa B (NF-κB) activation are the possible downstream molecular mechanisms for the effect of BAC-ACE2 interaction. Further studies in ACE2-knockdown cells and ACE2-/- mice suggested that benzoylaconitine targeted ACE2 to suppress p38/ERK-mediated mitochondrial ROS and NF-κB pathway activation. Our findings suggest that benzoylaconitine is a promising ACE2 agonist in regulating mitochondrial ROS release and inflammation activation to improve cardiac function in the treatment of heart failure.

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer.

Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation of iron metabolism and the accumulation of lipid peroxides. This nonapoptotic mode of cell death is implicated in various physiological and pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. This article focuses on ferroptosis-based therapeutic strategies for precision cancer treatment, covering the molecular mechanisms of ferroptosis, four major types of ferroptosis inducers and their inhibitory effects on diverse carcinomas, the detection of ferroptosis by fluorescent probes, and their implementation in image-guided therapy. These state-of-the-art tactics have manifested enhanced selectivity and efficacy against malignant carcinomas. Given that the administration of ferroptosis in cancer therapy is still at a burgeoning stage, some major challenges and future perspectives are discussed for the clinical translation of ferroptosis into precision cancer treatment.