Corrigendum: Melatonin mitigates cadmium phytotoxicity through modulation of phytochelatins biosynthesis, vacuolar sequestration, and antioxidant potential in Solanum lycopersicum L.

[This corrects the article DOI: 10.3389/fpls.2015.00601.].

Genome-wide characterization of cytochrome P450 genes reveals the potential roles in fruit ripening and response to cold stress in tomato.

Plant cytochrome P450 (CYP) superfamily, the largest enzyme metabolism family, has been identified in many species and plays a vital role in plant development and stress response via secondary metabolite biosynthesis. A comprehensive identification and functional investigation of CYPs in tomato plants would contribute to deeper understanding of their biological significance. In this study, 268 tomato CYP genes were identified and found to be unevenly located on 12 chromosomes. Based on the phylogenetic analysis, these 268 SlCYPs were classed into two distinct clades (A-type and non-A-type) and nine clans, including 48 families. Moreover, 67 tandem and 22 WGD (whole genome duplication)/segmental duplication events were detected, of which 12 SlCYP genes experienced both WGD/segmental and tandem duplication events, indicating that tandem duplication plays a major role in the expansion of the SlCYP family. Besides, 48 pairs containing 41 SlCYP and 44 AtCYP genes were orthologous, while 216 orthologous pairs were obtained between tomato and potato. The expression level of all SlCYP genes in tomato tissues at different development stages was analyzed, and most expressed SlCYPs showed a tissue-specific pattern. Meanwhile, 143 differentially expressed SlCYPs were identified under cold stress. Furthermore, the RT-qPCR results indicated that SlCYPs may be involved in fruit ripening and cold tolerance in tomato seedlings. These findings provide valuable insights into the evolutionary relationships and functional characteristics of SlCYPs, which can be utilized for further investigation of fruit metabolic pathways and cold tolerance in tomato.

Mitochondrial complex I subunit MT-ND1 mutations affect disease progression.

Mitochondrial respiratory chain complex I is an important component of the oxidative respiratory chain, with the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) being one of the core subunits. MT-ND1 plays a role in the assembly of complex I and its enzymatic function. MT-ND1 gene mutation affects pathophysiological processes, such as interfering with the early assembly of complex I, affecting the ubiquinone binding domain and proton channel of complex I, and affecting oxidative phosphorylation, thus leading to the occurrence of diseases. The relationship between MT-ND1 gene mutation and disease has been has received increasing research attention. Therefore, this article reviews the impact of MT-ND1 mutations on disease progression, focusing on the impact of such mutations on diseases and their possible mechanisms, as well as the application of targeting MT-ND1 gene mutations in disease diagnosis and treatment. We aim to provide a new perspective leading to a more comprehensive understanding of the relationship between MT-ND1 gene mutations and diseases.

Isorhamnetin: what is the in vitro evidence for its antitumor potential and beyond?

Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its "medicinal and food homologous" characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO's ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO's antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.

Fano resonance in molecular junctions of spin crossover complexes.

In this paper, we introduce a novel molecular switch paradigm that integrates spin crossover complexes with the Fano resonance effect. Specifically, by performing density-functional theory calculations, the feasibility of achieving Fano resonance using spin crossover complexes is demonstrated in our designed molecular junctions using the complex {Fe[H2B(pz)2]2[Bp(bipy)]} [pz = 1-pyrazolyl, Bp(bipy) = bis(phenylethynyl)(2,2'-bipyridine)]. It is further revealed that the Fano resonance, particularly the Fano dip, is most prominent in the junction with cobalt tips among all the schemes, together with the spin-filtering effect. Most importantly, this junction of cobalt tips is able to exhibit three distinct conductance states, which are controlled by the modulation of Fano resonance due to the spin-state transition of the complex and the applied gate voltage. Such a molecular switch paradigm holds potential for applications in logic gates, memory units, sensors, thermoelectrics, and beyond.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Zeaxanthin impairs angiogenesis and tumor growth of glioblastoma: An in vitro and in vivo study.

OBJECTIVES: To investigate the therapeutic effects of Zeaxanthin (Zea), one of the oxidized xanthophyll carotenoids belonging to the isoprenoids, on inhibiting the angiogenesis and tumor growth of glioblastoma (GBM) via an in vitro and in vivo study. METHODS: The effects of Zea on the proliferation, adhesion, migration and invasion of human GBM cell lines were detected by cell proliferation assay, cell adhesion assay and Transwell assay. The effect of Zea on angiogenesis was detected by rat aortic ring assay and human umbilical vein endothelial cells (HUVEC) in vitro tube formation assay. The effects of Zea on PARP, Caspase 3 and VEGFR2 phosphorylation as well as VEGFR2's downstream signaling pathway were detected by Western blot. The in vivo human GBM xenograft mouse model was employed to study the therapeutic efficacy of Zea. RESULTS: Zea impaired the proliferation, adhesion, migration and invasion of U87 and U251 cells as well as HUVECs. Rat aortic ring experiments displayed Zea significantly inhibited angiogenesis during VEGF-induced microvascular germination. In vitro and in vivo vascular experiments verified that Zea inhibited VEGF-induced HUVEC proliferation and capillary-like tube formation. Additionally, Zea induced GBM cells apoptosis via increasing the expression of cleaved PARP and Caspase 3. In HUVECs and U251 GBM cells, Zea down-regulated VEGF-induced activation of the VEGFR2 kinase pathway. Meanwhile the expression of p-AKT, p-ERK, p-STAT3 and FAK were all attenuated in U251 cells. Moreover, the effects of Zea on GBM cells proliferation could be blocked by VEGFR2 kinase inhibitor SU5408. These results suggest that Zea may hinder GBM angiogenesis and tumor growth through down-regulating a cascade of oncogenic signaling pathways, both through the inhibition of angiogenesis and the anti-tumor mechanism of a direct cytotoxic effect. Besides, Zea inhibits GBM angiogenesis and tumor growth exemplified through a xenograft mouse model in vivo. CONCLUSION: Zea impairs angiogenesis and tumor growth of GBM both in vitro and in vivo. It can be declared that Zea is a potential valuable anticancer candidate for the future treatment strategy of GBM.

Phosphorylation of sugar transporter TST2 by protein kinase CPK27 enhances drought tolerance in tomato.

Drought is a major environmental stress threatening plant growth and productivity. Calcium-dependent protein kinases (CPKs) are plant-specific Ca2+ sensors with multifaceted roles in signaling drought responses. Nonetheless, the mechanisms underpinning how CPKs transmit downstream drought signaling remain unresolved. Through genetic investigations, our study unveiled that knocking out CPK27 reduced drought tolerance in tomato (Solanum lycopersicum) plants and impaired abscisic acid (ABA)-orchestrated plant response to drought stress. Proteomics and phosphoproteomics revealed that CPK27-dependent drought-induced proteins were highly associated with the sugar metabolism pathway, which was further verified by reduced soluble sugar content in the cpk27 mutant under drought conditions. Using protein-protein interaction assays and phosphorylation assessments, we demonstrated that CPK27 directly interacted with and phosphorylated tonoplast sugar transporter 2 (TST2), promoting intercellular soluble sugar accumulation during drought stress. Furthermore, Ca2+ and ABA enhanced CPK27-mediated interaction and phosphorylation of TST2, thus revealing a role of TST2 in tomato plant drought tolerance. These findings extend the toolbox of potential interventions for enhancing plant drought stress tolerance and provide a target to improve drought tolerance by manipulating CPK27-mediated soluble sugar accumulation for rendering drought tolerance in a changing climate.

Research progress in MCM family: Focus on the tumor treatment resistance.

Malignant tumors constitute a significant category of diseases posing a severe threat to human survival and health, thereby representing one of the most challenging and pressing issues in the field of biomedical research. Due to their malignant nature, which is characterized by a high potential for metastasis, rapid dissemination, and frequent recurrence, the prevailing approach in clinical oncology involves a comprehensive treatment strategy that combines surgery with radiotherapy, chemotherapy, targeted drug therapies, and other interventions. Treatment resistance remains a major obstacle in the comprehensive management of tumors, serving as a primary cause for the failure of integrated tumor therapies and a critical factor contributing to patient relapse and mortality. The Minichromosome Maintenance (MCM) protein family comprises functional proteins closely associated with the development of resistance in tumor therapy.The influence of MCMs manifests through various pathways, encompassing modulation of DNA replication, cell cycle regulation, and DNA damage repair mechanisms. Consequently, this leads to an enhanced tolerance of tumor cells to chemotherapy, targeted drugs, and radiation. Consequently, this review explores the specific roles of the MCM family in various cancer treatment strategies. Its objective is to enhance our comprehension of resistance mechanisms in tumor therapy, thereby presenting novel targets for clinical research aimed at overcoming resistance in cancer treatment. This bears substantial clinical relevance.

The MYC2-PUB22-JAZ4 module plays a crucial role in jasmonate signaling in tomato.

Jasmonates (JAs), a class of lipid-derived stress hormones, play a crucial role across an array of plant physiological processes and stress responses. Although JA signaling is thought to rely predominantly on the degradation of specific JAZ proteins by SCFCOI1, it remains unclear whether other pathways are involved in the regulation of JAZ protein stability. Here, we report that PUB22, a plant U-box type E3 ubiquitin ligase, plays a critical role in the regulation of plant resistance against Helicoverpa armigera and other JA responses in tomato. Whereas COI1 physically interacts with JAZ1/2/5/7, PUB22 physically interacts with JAZ1/3/4/6. PUB22 ubiquitinates JAZ4 to promote its degradation via the 26S proteasome pathway. Importantly, we observed that pub22 mutants showreduced resistance to H. armigera, whereas jaz4 single mutants and jaz1 jaz3 jaz4 jaz6 quadruple mutants have enhanced resistance. The hypersensitivity of pub22 mutants to herbivores could be partially rescued by JAZ4 mutation. Moreover, we found that expression of PUB22 can be transcriptionally activated by MYC2, thus forming a positive feedback circuit in JA signaling. We noticed that the PUB22-JAZ4 module also regulates other JA responses, including defense against B. cinerea, inhibition of root elongation, and anthocyanin accumulation. Taken together, these results indicate that PUB22 plays a crucial role in plant growth and defense responses, together with COI1-regulated JA signaling, by targeting specific JAZs.

Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study.

BACKGROUND: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ceprop) required to suppress response to cervical dilation in patients undergoing hysteroscopy. METHODS: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg-1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 µg⋅kg-1, and a target-controlled propofol infusion. The initial target Ceprop was 3.5 µg·mL-1 and was increased or decreased in subsequent patients by steps of 0.5 µg·mL-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ceprop that suppressed response to cervical dilation in 50% of patients (EC50). RESULTS: The EC50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg-1 (2.08 [95% confidence interval, CI, 1.88-2.28] µg·mL-1), 0.15 mg⋅kg-1 (1.83 [1.56-2.10] µg·mL-1), and 0.2 mg⋅kg-1 (1.43 [1.27-1.58] µg·mL-1) remimazolam than those given 0 mg⋅kg-1 (3.67 [3.49-3.86] µg·mL-1) or 0.05 mg⋅kg-1 (3.47 [3.28-3.67] µg·mL-1) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg-1 decreased EC50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg-1). Propofol consumption was lower in patients given 0.1 mg⋅kg-1 (4.15 [3.51-5.44] mg·kg-1), 0.15 mg⋅kg-1 (3.54 [3.16-4.46] mg·kg-1), and 0.2 mg⋅kg-1 (2.74 [1.73-4.01] mg·kg-1) remimazolam than those given 0 mg⋅kg-1 (6.09 [4.99-7.35] mg·kg-1) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. CONCLUSIONS: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg-1 reduced the EC50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.

High tunneling electroresistance in ferroelectric tunnel junctions based on two-dimensional α-In2Se3/MoTe2 van der Waals heterostructures.

Ferroelectric polarization-controlled band alignment can be realized in van der Waals heterostructures (vdWHs), which can be used to create new types of ferroelectric tunnel junctions (FTJs). In this work, we design six probable configurations of two-dimensional vdWHs based on a two-dimensional α-In2Se3 ferroelectric material which has two opposite polarization states P↑ and P↓, and the semiconductor MoTe2. First-principles calculations show robust ferroelectric polarization-controlled switching behavior between the high conductance state in configuration AA-P↓ and the low conductance state in configuration AA-P↑ in the most stable AA stacked vdWHs. Based on this vdWH, a two-dimensional transverse FTJ with AA-P↓ or AA-P↑ as the tunneling barrier and (In0.5Sn0.5)2Se3 monolayers (n-type doped) as electrodes is designed. The tunneling electroresistance ratio of the FTJs at the Fermi level reaches 1.22 × 104% when the tunneling barrier contains two repeating units N = 2 and can be greatly increased by increasing the thickness of the ferroelectric layer. Analysis of the work function, charge redistribution, and local density of states is performed to interpret the above phenomena. The findings suggest the great potential of the AA stacked α-In2Se3/MoTe2 vdWH in the design of high-performance FTJs and application in high-density non-volatile memory devices.

The regulatory relationship between transcription factor STAT3 and noncoding RNA.

Signal transducer and activator of transcription 3 (STAT3), as a key node in numerous carcinogenic signaling pathways, is activated in various tumor tissues and plays important roles in tumor formation, metastasis, and drug resistance. STAT3 is considered a potential subtarget for tumor therapy. Noncoding RNA (ncRNA) is a special type of RNA transcript. Transforming from "junk" transcripts into key molecules involved in cell apoptosis, growth, and functional regulation, ncRNA has been proven to be closely related to various epithelial-mesenchymal transition and drug resistance processes in tumor cells over the past few decades. Research on the relationship between transcription factor STAT3 and ncRNAs has attracted increased attention. To date, existing reviews have mainly focused on the regulation by ncRNAs on the transcription factor STAT3; there has been no review of the regulation by STAT3 on ncRNAs. However, understanding the regulation of ncRNAs by STAT3 and its mechanism is important to comprehensively understand the mutual regulatory relationship between STAT3 and ncRNAs. Therefore, in this review, we summarize the regulation by transcription factor STAT3 on long noncoding RNA, microRNA, and circular RNA and its possible mechanisms. In addition, we provide an update on research progress on the regulation of STAT3 by ncRNAs. This will provide a new perspective to comprehensively understand the regulatory relationship between transcription factor STAT3 and ncRNAs, as well as targeting STAT3 or ncRNAs to treat diseases such as tumors.

Far-red light inhibits lateral bud growth mainly through enhancing apical dominance independently of strigolactone synthesis in tomato.

The ratio of red light to far-red light (R:FR) is perceived by light receptors and consequently regulates plant architecture. Regulation of shoot branching by R:FR ratio involves plant hormones. However, the roles of strigolactone (SL), the key shoot branching hormone and the interplay of different hormones in the light regulation of shoot branching in tomato (Solanum lycopersicum) are elusive. Here, we found that defects in SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and CCD8 in tomato resulted in more lateral bud growth but failed to reverse the FR inhibition of lateral bud growth, which was associated with increased auxin synthesis and decreased synthesis of cytokinin (CK) and brassinosteroid (BR). Treatment of auxin also inhibited shoot branching in ccd mutants. However, CK released the FR inhibition of lateral bud growth in ccd mutants, concomitant with the upregulation of BR synthesis genes. Furthermore, plants that overexpressed BR synthesis gene showed more lateral bud growth and the shoot branching was less sensitive to the low R:FR ratio. The results indicate that SL synthesis is dispensable for light regulation of shoot branching in tomato. Auxin mediates the response to R:FR ratio to regulate shoot branching by suppressing CK and BR synthesis.

Prohibitin 2: A key regulator of cell function.

The PHB2 gene is located on chromosome 12p13 and encodes prohibitin 2, a highly conserved protein of 37 kDa. PHB2 is a dimer with antiparallel coils, possessing a unique negatively charged region crucial for its mitochondrial molecular chaperone functions. Thus, PHB2 plays a significant role in cell life activities such as mitosis, mitochondrial autophagy, signal transduction, and cell death. This review discusses how PHB2 inhibits transcription factors or nuclear receptors to maintain normal cell functions; how PHB2 in the cytoplasm or membrane ensures normal cell mitosis and regulates cell differentiation; how PHB2 affects mitochondrial structure, function, and cell apoptosis through mitochondrial intimal integrity and mitochondrial autophagy; how PHB2 affects mitochondrial stress and inhibits cell apoptosis by regulating cytochrome c migration and other pathways; how PHB2 affects cell growth, proliferation, and metastasis through a mitochondrial independent mechanism; and how PHB2 could be applied in disease treatment. We provide a theoretical basis and an innovative perspective for a comprehensive understanding of the role and mechanism of PHB2 in cell function regulation.

Red light induces salicylic acid accumulation by activating CaHY5 to enhance pepper resistance against Phytophthora capsici.

Pepper (Capsicum annuum L.) is frequently challenged by various pathogens, among which Phytophthora capsici is the most devastating to pepper production. Red light signal acts as a positive induction of plant resistance against multiple pathogens. However, little is known about how the red light signal affects pepper resistance to P. capsici infection (PCI). Here, we report that red light regulates salicylic acid (SA) accumulation by activating elongated hypocotyl5 (CaHY5), a basic leucine zipper (bZIP) transcription factor, thereby decreasing pepper susceptibility to PCI. Exogenous SA treatment reduced pepper susceptibility to PCI, while silencing of CaPHYB (a red light photoreceptor) increased its susceptibility. PCI significantly induced CaHY5 expression, and silencing of CaHY5 reduced SA accumulation, accompanied by decreases in the expression levels of phenylalanine ammonia-lyase 3 (CaPAL3), CaPAL7, pathogenesis-related 1 (CaPR1), and CaPR1L, which finally resulted in higher susceptibility of pepper to PCI. Moreover, CaHY5 was found to activate the expression of CaPAL3 and CaPAL7, which are essential for SA biosynthesis, by directly binding to their promoters. Further analysis revealed that exogenous SA treatment could restore the resistance of CaHY5-silenced pepper plants to PCI. Collectively, this study reveals a critical mechanism through which red light induces SA accumulation by regulating CaHY5-mediated CaPAL3 and CaPAL7 expression, leading to enhanced resistance to PCI. Moreover, red light-induced CaHY5 regulates pepper resistance to PCI, which may have implications for PCI control in protected vegetable production.

Endophytic fungus Falciphora oryzae enhances salt tolerance by modulating ion homeostasis and antioxidant defense systems in pepper.

Endophytic fungi play an important role in the induction of plant tolerance to abiotic and biotic stresses. However, the role of endophytic fungi in the response of horticultural plants to plant stress remains largely unknown. Here, we addressed the role of the endophytic fungus Falciphora oryzae in enhancing salt tolerance in pepper (Capsicum annuum L.) by inoculation with the endophyte in the rhizosphere. F. oryzae could indeed colonize the roots of pepper and significantly improved the tolerance of pepper to salt stress. This resulted in increased plant growth and photosynthetic performance compared with control plants, which was accompanied by increases in indole acetic acid and abscisic acid biosynthesis and signaling. Furthermore, inoculation with F. oryzae significantly upregulated a subset of transcripts involved in Na+ homeostasis (NHX3, NHX6, NHX8, HKT2-1, and SOS1) and the high-affinity K+ transporter protein-related gene HAK1 in the leaves to maintain Na+ /K+ homeostasis. Moreover, the activity of antioxidant enzymes (catalase, peroxidase, glutathione, and ascorbate peroxidase), the content of glutathione, the transcript level of genes related to antioxidants (catalase, ascorbate peroxidase, glutathione reductase, peroxidase, glutamate-cysteine ligase, and glutamine synthetase) in the leaves were significantly upregulated after inoculation with F. oryzae, which led to decreased levels of lipid peroxidation (malondialdehyde) and reactive oxygen species. These results indicate that inoculation with F. oryzae can enhance the salt tolerance of pepper by promoting ion homeostasis and upregulating antioxidant defense systems.

Light-induced pure spin current in carbon hexagonal-connected zigzag graphene nanoribbons via magnetic field modulation.

Pure spin current, exhibiting no Joule heat and self-powered characteristics, has recently attracted intensive attention. Here, through first-principles calculations and symmetry analysis, we propose a new method to generate photoelectric pure spin current in carbon hexagonal connected three zigzag graphene nanoribbons (ZGNRs) via magnetic field modulation. Specifically, a device with centro-symmetry is designed, which consists of three ZGNRs using two carbon hexagons as connectors ('2-C6'). When the edge spin states of the three ZGNRs from left to right are modulated to AFM-AFM-AFM or FM-AFM-FM by magnetic fields, excellent pure spin currents are obtained which are independent of the photon energy and the angle of the linearly polarized light. However, when the edge spin states are FM-FM-FM orderly, the photocurrent is nearly zero and can be neglected. Analysis show that the first two spin magnetic structures own the spatial inversion antisymmetric spin density which is the origin of stable pure spin currents, while the FM-FM-FM structure owns Cs symmetric spin density, leading to the nearly zero photocurrent. Our findings provide a scheme for obtaining pure spin currents by changing the spin states of the graphene nanoribbons via magnetic field modulation, which is of great importance for the design of spintronic devices.