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Background: Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated. Results: The hybrid (BS1453/11GF5135) wheat exhibited superiority in seed vigor and anti-aging capacity, compared to its male parent (11GF5135, MP) and female parent (BS1453, FP). We identified four miRNAs associated with seed vigor, all of which are novel miRNAs. The majority of targets of miRNAs were related to ubiquitin ligases, kinases, sucrose synthases and hydrolases, involving in starch and sucrose metabolism, hydrolysis, catalysis, plant hormone signal transduction, and other pathways, which played crucial roles in seed development. Additionally, we also found miR531 was differentially expressed in both male parent and hybrid, and its target gene was a component of the E1 subunit of α-ketoate dehydrogenase complex, which interacted with dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3). Finally, We established a presumptive interaction model to speculate the relationship of miR531 and seed vigor. Conclusions: This study analyzed the seed vigor of two-line hybrid wheat, and screened seed vigor-related miRNAs. Meanwhile speculated the genetic relationship of hybrid and parents, in terms of miRNAs. Consequently, the present study provides new insights into the miRNA-mediated gene and protein interaction network that regulates seed vigor. These findings hold significance for enhancing the yield and quality of two-line hybrid wheat, facilitating its future applications. [ABSTRACT FROM AUTHOR]

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket‐dependent small‐molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket‐independent STING‐activating agonists (piSTINGs), which act through multivalency‐driven oligomerization to activate STING. Additionally, a piSTING‐adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING‐based vaccine combination with aPD‐1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists. [ABSTRACT FROM AUTHOR]

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket‐dependent small‐molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket‐independent STING‐activating agonists (piSTINGs), which act through multivalency‐driven oligomerization to activate STING. Additionally, a piSTING‐adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING‐based vaccine combination with aPD‐1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists. [ABSTRACT FROM AUTHOR]

Lysine‐specific peptide and protein modification strategies are widely used to study charge‐related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge‐related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge‐related protein properties, such as liquid‐liquid phase separation behaviour of α‐synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine‐containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins. [ABSTRACT FROM AUTHOR]

Lysine‐specific peptide and protein modification strategies are widely used to study charge‐related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge‐related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge‐related protein properties, such as liquid‐liquid phase separation behaviour of α‐synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine‐containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins. [ABSTRACT FROM AUTHOR]

α-Synuclein forms amyloid fibrils that are critical in the progression of Parkinson's disease and serves as the pathological hallmark of this condition. Different posttranslational modifications have been identified at multiple sites of α-synuclein, influencing its conformation, aggregation and function. Here, we investigate how disease-related phosphorylation and O-GlcNAcylation at the same α-synuclein site (S87) affect fibril structure and neuropathology. Using semi-synthesis, we obtained homogenous α-synuclein monomer with site-specific phosphorylation (pS87) and O-GlcNAcylation (gS87) at S87, respectively. Cryo-EM revealed that pS87 and gS87 α-synuclein form two distinct fibril structures. The GlcNAc situated at S87 establishes interactions with K80 and E61, inducing a unique iron-like fold with the GlcNAc molecule on the iron handle. Phosphorylation at the same site prevents a lengthy C-terminal region including residues 73 to 140 from incorporating into the fibril core due to electrostatic repulsion. Instead, the N-terminal half of the fibril (1–72) takes on an arch-like fibril structure. We further show that both pS87 and gS87 α-synuclein fibrils display reduced neurotoxicity and propagation activity compared with unmodified α-synuclein fibrils. Our findings demonstrate that different posttranslational modifications at the same site can produce distinct fibril structures, which emphasizes link between posttranslational modifications and amyloid fibril formation and pathology. Here, the authors use cryo-EM to show that phosphorylating or O-GlcNAcylating α-synuclein on serine 87 leads to the formation of two distinct fibril structures. Both structures display reduced neurotoxicity and propagation activity. [ABSTRACT FROM AUTHOR]

This paper adopted the 2D periodic boundary-condition (PBC) density functional theory (DFT) to examine the adsorption of CH3Br, CH3Cl, and CH3F halomethanes into not only bare boron phosphide (BP) nanosheets but also gallium- and aluminium-doped ones. Geometric optimisation was applied to all the structures at the B3LYP/6-311+G (d) level of theory. Moreover, the CAM-B3LYP/6-311+G(d), ωB97X-D3, and M06-2X levels of theory were implemented to calculate the single point energy. The quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis were carried out, evaluating the donor-acceptor interactions, partial natural charge, and Wiberg bond index (WBI). The adsorption energy values demonstrated that the gallium-doped BP had the highest adsorptive capability, while the lowest adsorption occurred in the bare BP. However, the adsorption of CH3Cl, with much smaller adsorption energy, was maximised in the aluminium-doped BP and minimised in the bare BP. Furthermore, CH3Br and CH3Cl showed the highest and lowest tendencies to be adsorbed onto the nanosheet surfaces, respectively. Gallium- and aluminium-doped BP structures appear to be efficient and effective in the development of new solid-state sensors of halomethanes. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) was known as the common endocrine disease in women, featured as hyperandrogenism, ovulation disorders, etc. Fat mass and obesity-associated protein (FTO), a m6A demethylase, is abnormal in the occurrence of ovarian diseases. However, the mechanism of FTO in the pathogenesis of PCOS is still unclear. The level of FTO in clinical samples, PCOS rat with hyperandrogenism and granulosa cells (GCs) lines effected by DHT were investigated by ELISA, qRT-PCR, WB, and IHC, while m6A RNA methylation level was studied by m6A Colorimetric and androgen level was tested through ELISA. Changes in steroid hormone synthetase and androgen receptor (AR)/prostate-specific antigen (PSA) levels in vitro were visualized by WB after transient transfection silenced FTO. The effect of DHT combined with FTO inhibitor meclofenamic acid (MA) on FTO, AR/PSA, and AKT phosphorylation were also demonstrated by WB. The co-localization of FTO and AR in KGN cells was analyzed by confocal microscopy, and the physiological interaction between FTO and AR was studied by Co-IP assay. The effect of FTO-specific inhibitor MA, AKT phosphorylation inhibitor LY294002, and the combined them on GCs proliferation and cell cycle were evaluated by drug combination index, EDU assay, and flow cytometry analysis. FTO expression was upregulated in follicular fluid and GCs in PCOS patients clinically. The high FTO expression in patients was negative with the level of m6A, but positive with the level of androgen. The upregulation of FTO was accompanied with a decrease in the level of m6A in PCOS rat with hyperandrogenism. Dihydrotestosterone (DHT) promoted the FTO expression and inhibited m6A content as a dose-dependent way in vitro. In contrast, suppression of FTO with siRNA attenuated the expression of steroid hormone synthetase such as CYP11A1, CYP17A1, HSD11B1, HSD3B2 except CYP19A1 synthetase, ultimately inducing the decrease of androgen level. Suppression of FTO also decreased the biological activity of androgen through downregulation AR/PSA. MA treatment as the specific FTO antagonist decreased cell survival in time- and dose-dependent way in GCs lines. Correspondingly, MA treatment decreased the expression of FTO, AR/PSA expression, and AKT phosphorylation in the presence of DHT stimulation. Additionally, we also speculate there is a potential relation between FTO and AR according to FTO was co-localized and interacted with AR in KGN cells. Compared with AKT phosphorylation inhibitor LY294002 or MA alone, LY294002 combined with MA synergistically inhibited cell survival and increased G2/M phase arrest in GC line. We first evaluated the correlation of FTO and m6A in PCOS clinically, and further explored the mechanism between FTO and hyperandrogenism in PCOS animal and cell models. These findings contributed the potential therapy by targeting the FTO for hyperandrogenism in PCOS. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation (LLPS) was recently discovered to be a ubiquitous method of substance organization in living organisms, which plays an important regulatory role in various life processes and can also be closely associated with the development of many diseases. Glycation is one of the most important non-enzymatic post-translational modifications (PTMs), which accumulates in vivo gradually with life processes and affects the properties and functions of proteins. Here, we investigated the effect of glycation on LLPS and explored the molecular mechanisms behind it. We found that glycation reduces electrostatic interactions and increases hydrophobic interactions, and consequently affects LLPS. [ABSTRACT FROM AUTHOR]

The adsorption process is regarded as a promising technology for removing organics and heavy metals. In this study, we used orange peels as biomass feedstock and used nickel-manganese ferrite (Ni1-x MnxFe2O4) as the precursor solution to prepare magnetic mesoporous biochar (MBC). Using a Box-Behnken design response, we investigated the adsorption of 2,4-difluoroaniline (2,4-DFA), as well as the influence of four preparation parameters (activation temperature, the molar mass of Mn in Ni1-x MnxFe2O4, activation time, and impregnation ratio). Based on the adsorption rate of 2,4-DFA, we obtained the following optimal preparation parameters of MBC: a temperature of 180 °C, a molar mass of Ni0.75 Mn0.25Fe2O4, an activation time of 8 h, and an impregnation ratio of 3. Then, we investigated the adsorption capacity of MBC and the mutual effect of 2,4-DFA and copper (II) [Cu(II)] through single and binary systems. The adsorption processes of 2,4-DFA and Cu(II) could be satisfactorily fitted to a pseudo-second-order kinetic model. The adsorption amount of 2,4-DFA was comparable in both single and binary systems. However, the adsorption of Cu(II) in the binary system was inhibited, with the adsorption capacity decreasing by 19.55%. The adsorption isotherms of 2,4-DFA and Cu(II) to MBC fitted the Freundlich model. The maximum adsorption capacity of 2,4-DFA and Cu(II) could reach 66.30 mg/g and 10.44 mg/g at 313 K, respectively. MBC exhibited good regeneration performance through the combination of 90% ethanol and 1 M NaOH solution. The adsorption mechanism mainly included electrostatic interactions, hydrogen bonds, ion exchange, and π-π interactions. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change = 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA. [ABSTRACT FROM AUTHOR]

Considering the fact that site‐selective late‐stage diversification of peptides and proteins remains a challenge for biochemistry, strategies targeting low‐abundance natural amino acids need to be further developed. As an extremely oxidation‐sensitive and low‐abundance amino acid, methionine emerges as a promising target for chemo‐ and site‐selective modification. Herein we report an efficient and highly selective modification on methionine residues by one‐pot O‐ and N‐transfer reaction, generating sulfoximine‐modified peptides with near‐perfect conversion within 10 min. Moreover, the great tolerance to other natural amino acids has been demonstrated in reactions with various peptide substrates. To demonstrate the generality of this protocol, we have modified natural peptides and obtained sulfoximination products with high conversion rates. This methodology provides a novel strategy as the expansion of the methionine‐based peptide functionalization toolbox. [ABSTRACT FROM AUTHOR]

Novel pocket‐independent STING‐activating agonists (piSTINGs), which act through multivalency‐driven oligomerization to activate downstream signalling pathways, were developed by Yan‐Mei Li et al. in their Research Article (e202407037). piSTINGs could serve as novel STING agonists for vaccines and combination therapies. STING oligomerization is a useful strategy for the development of a new generation of STING agonists...By Shao‐Hua Zhuo; Tian‐Yang Wang; Lang Zhao; Jing‐Yun Su; Jin‐Jian Hu; Yu‐Fen Zhao and Yan‐Mei LiReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Novel pocket‐independent STING‐activating agonists (piSTINGs), which act through multivalency‐driven oligomerization to activate downstream signalling pathways, were developed by Yan‐Mei Li et al. in their Research Article (e202407037). piSTINGs could serve as novel STING agonists for vaccines and combination therapies. STING oligomerization is a useful strategy for the development of a new generation of STING agonists...By Shao‐Hua Zhuo; Tian‐Yang Wang; Lang Zhao; Jing‐Yun Su; Jin‐Jian Hu; Yu‐Fen Zhao and Yan‐Mei LiReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

The effective co-delivery of antigens and immune potentiators (adjuvants) and the high degree of antigen presentation have been two major challenges in the development of subunit vaccines. Here, we address these issues by conjugating peptide antigens with cholicamide, a self-assembling small molecule adjuvant. Co-assemblies of the conjugates and cholicamide achieved high levels of both cytokine induction and MHC class II peptide presentation. [ABSTRACT FROM AUTHOR]

Immunotherapy is recognised as an attractive method for the treatment of cancer, and numerous treatment strategies have emerged over recent years. Investigations of the tumour microenvironment (TME) have led to the identification of many potential therapeutic targets and methods. However, many recently applied immunotherapies are based on previously identified strategies, such as boosting the immune response by combining commonly used stimulators, and the release of drugs through changes in pH. Although methodological improvements such as structural optimisation and combining strategies can be undertaken, applying those novel targets and methods in immunotherapy remains an important goal. In this review, we summarise the latest research on the TME, and discuss how small molecules, immune cells, and their interactions with tumour cells can be regulated in the TME. Additionally, the techniques currently employed for delivery of these agents to the TME are also mentioned. Strategies to modulate cell phenotypes and interactions between immune cells and tumours are mainly discussed. We consider both modulatory and targeting methods aiming to bridge the gap between the TME and chemical modulation thereof. [ABSTRACT FROM AUTHOR]

β-Thalassemia major (β-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with β-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-β (TGF-β) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of β-thalassemia (β-thal). To assess this hypothesis, we studied 23 pediatric patients with β-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-β, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with β-thal had higher IL-8, IL-13 and TGF-β concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with β-TM. Serum IL-4 level of β-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-β exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of β-TM in the future. Our study sheds new light on the pathogenesis of β-TM. [ABSTRACT FROM AUTHOR]

Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance. In addition, a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect. To address this problem, two or more agonist molecules are often used together to synergistically enhance immune efficacy. In this work, we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8 (TLR7/8) agonist 522 produced a broader cytokine response. Subsequently, we developed multicomponent nanovaccines (MCNVs) consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules. These MCNVs activate bone marrow-derived dendritic cells (BMDCs) to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor T-cell responses. In in vivo experiments, we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes, resulting in significant tumor regression and, notably, a 100% survival rate in mice through 25 days without other partnering therapies. These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency. [ABSTRACT FROM AUTHOR]

To impart self-healing polymers largely adjustable dynamicity and mechanical performance, here we develop libraries of catalyst-free reversible polythioureas directly from commodity 1,4-phenylene diisothiocyanate and amines via facile click chemistry based modular assembly. By using the amine modules with various steric hindrances and flexibilities, the reversible thiourea units acquire triggering temperatures from room temperature to 120 °C. Accordingly, the derived self-healable, recyclable and controlled degradable dynamically crosslinked polythioureas can take effect within wide temperature range. Moreover, mechanical properties of the materials can be tuned covering plastics, elastomers and fibers using (i) different assemble modules or (ii) solid-state stretching. Particularly, unidirectional stretching leads to the record-high tensile strength of 266 MPa, while bidirectional stretching provides the materials with biaxial strengths up to over 120 MPa. The molecular mechanism and technological innovations discussed in this work may benefit promotion and application of self-healing polymers towards greatly diverse demands and scenarios. Intrinsic self-healing polymers attract increasing attention but often suffer from a narrow self-healing temperature range and unsatisfactory mechanical performance. Here, the authors use click chemistry to develop a library of catalyst-free reversible polythioureas and demonstrate that the self-healing temperature and mechanical properties can be adjusted by controlling the flexibility and the steric environment. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation (LLPS), a type of phase transition that is important in organisms, is a unique means of forming biomolecular condensates. LLPS plays a significant role in transcription, genome organisation, immune response and cell signaling, and its dysregulation may cause neurodegenerative diseases and cancers. Exploring the regulatory mechanism of LLPS contributes to the understanding of the pathogenic mechanism of abnormal phase transition and enables potential therapeutic targets to be proposed. Many factors have been found to regulate LLPS, of which post-translational modification (PTM) is among the most important. PTMs can change the structure, charge, hydrophobicity and other properties of the proteins involved in phase separation and thereby affect the phase transition behaviour. In this review, we discuss LLPS and the regulatory effects of PTMs, RNA and molecular chaperones in a phase separation system. We introduce several common PTMs (including phosphorylation, arginine methylation, arginine citrullination, acetylation, ubiquitination and poly(ADP-ribosyl)ation), highlight recent advances regarding their roles in LLPS and describe the regulatory mechanisms behind these features. This review provides a detailed overview of the field that will help further the understanding of and interventions in LLPS. [ABSTRACT FROM AUTHOR]

RFWD2, an E3 ubiquitin ligase, is overexpressed in numerous human cancers, including leukemia, lung cancer, breast cancer, renal cell carcinoma, and colorectal cancer. The roles of RFWD2 in cancer are related to the targeting of its substrates for ubiquitination and degradation. This study aimed to investigate the role of TRIB2 in relation to the regulation of protein degradation through RFWD2. inBio Discover™ results demonstrated that TRIB2 can perform its functions by interacting with RFWD2 or other factors. TRIB2 can interact with and regulate RFWD2, which further attends the proteasome-mediated degradation of the RFWD2 substrate p-IκB-α. TRIB2 colocalizes with RFWD2-related IκB-α to form a ternary complex and further affects the IκB-α degradation by regulating its phosphorylation. Specific domain analysis showed that TRIB2 may bind to RFWD2 via its C-terminus, whereas it binds to IκB via its pseudokinase domain. TRIB2 acts as an oncogene and promotes cancer cell proliferation and migration, whereas RFWD2 knockdown reversed the role of TRIB2 in promoting cancer cell growth and colony formation in vitro and in vivo. In summary, this study reveals that TRIB2 promotes the progression of cancer by affecting the proteasome-mediated degradation of proteins through the interaction with RFWD2. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Eleven biogenetically related polyprenylated acylphloroglucinols (PPAPs), including four novel skeletons (1—4) and five new compounds (5—9), were isolated from the flowers of Hypericum monogynum. Hypermonones A—D (1—4) represented the first example of a unique dilactone structure containing carbonyl bonded single δ‐lactone and tricyclic γ‐lactone moieties. Their structures were elucidated by NMR analysis, X‐ray crystallography, and ECD calculations. Moreover, we revised the structure of hyperibrin B to hypermonone I (9) via NMR analysis, a quantum computational chemistry method, and hypothetic biosynthetic considerations. Three compounds (5, 6, and 9) with significant MDR reversal activity (RF ranging from 61 to 223) were superior to the positive control verapamil (MCF‐7/ADR, RF: 53; HepG2/ADR, RF: 124). Mechanism study for compound 5 indicated that this compound could inhibit the function of P‐gp transport rather than its expression, and the possible recognition mechanism between compound 5 and P‐gp was predicted by molecular docking. [ABSTRACT FROM AUTHOR]

Zn2Ti3O8/g-C3N4 (0, 1, 3 and 8 wt%) composites were prepared via a simple solvothermal method, and their physical and electrochemical properties were systematically analyzed. SEM and HRTEM results show that the Zn2Ti3O8/g-C3N4 spherical structures with width sizes of about 500–700 nm are plump and uniform. Moreover, g-C3N4 with a large specific surface area can effectively buffer the deformation of Zn2Ti3O8 and reduce the resistance of Zn2Ti3O8 charge transfer and Li+ diffusion, thus improving the conductivity of Zn2Ti3O8. The results reveal that Zn2Ti3O8/g-C3N4 (3 wt%) had the most outstanding electrochemical performance of all samples. It can deliver discharge (charge) capacities of 444.6 (387.9), 284.5 (280.8), 197.5 (199.9), 149.9 (149.3), 119.2 (118.7) and 81.4 (81) mA h g−1 cycled at 50, 100, 300, 600, 900, and 1500 mA g−1, respectively. At the same current densities, pure Zn2Ti3O8 only provides discharge (charge) capacities of 325.4 (283.5), 223.7 (219.5), 142.9 (141.8), 95.4(94.8), 69.4 (69.4) and 38.3 (39.3) mA h g−1. The results verify that Zn2Ti3O8/g-C3N4 materials are expected to be remarkable anode materials for Li-ion batteries. [ABSTRACT FROM AUTHOR]

The realization of universal quantum logical gates on nonlocal nitrogen‐vacancy center ensembles (NVEs) is a basic task for universal quantum computing with NVEs. In contrast to previous works on the construction of gates, a one‐step all‐resonance scheme is proposed to construct a controlled‐phase gate on two nonlocal NVEs that are coupled to different superconducting transmission line resonators connected by a superconducting transmon qubit. The gate can be easily realized using only one step. Moreover, the all‐resonance operation allows the gate to be achieved within a short time. By considering the feasible parameters obtained in the experiments, this gate can be completed within 101 ns with a high fidelity of approximately 97.8%, which has reached the threshold of fault‐tolerance quantum computing. [ABSTRACT FROM AUTHOR]

Background: Formin, a highly conserved multi-domain protein, interacts with microfilaments and microtubules. Although specifically expressed formin genes in anthers are potentially significant in research on male sterility and hybrid wheat breeding, similar reports in wheat, especially in thermo-sensitive genic male sterile (TGMS) wheat, remain elusive. Results: Herein, we systematically characterized the formin genes in TGMS wheat line BS366 named TaFormins (TaFHs) and predicted their functions in inducing stress response. In total, 25 TaFH genes were uncovered, majorly localized in 2A, 2B, and 2D chromosomes. According to the neighbor-joining (NJ) method, all TaFH proteins from wheat and other plants clustered in 6 sub-groups (A-F). The modeled 3D structures of TaFH1-A/B, TaFH2-A/B, TaFH3-A/B and TaFH3-B/D were validated. And different numbers of stress and hormone-responsive regulatory elements in their 1500 base pair promoter regions were contained in the TaFH genes copies. TaFHs had specific temporal and spatial expression characteristics, whereby TaFH1, TaFH4, and TaFH5 were expressed highly in the stamen of BS366. Besides, the accumulation of TaFHs was remarkably lower in a low-temperature sterile condition (Nanyang) than fertile condition (Beijing), particularly at the early stamen development stage. The pollen cytoskeleton of BS366 was abnormal in the three stages under sterile and fertile environments. Furthermore, under different stress levels, TaFHs expression could be induced by drought, salt, abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), indole-3-acetic acid (IAA), polyethylene glycol (PEG), and low temperature. Some miRNAs, including miR167, miR1120, and miR172, interacts with TaFH genes; thus, we constructed an interaction network between microRNAs, TaFHs, phytohormone responses, and distribution of cytoskeleton to reveal the regulatory association between upstream genes of TaFH family members and sterile. Conclusions: Collectively, this comprehensive analysis provides novel insights into TaFHs and miRNA resources for wheat breeding. These findings are, therefore, valuable in understanding the mechanism of TGMS fertility conversion in wheat. [ABSTRACT FROM AUTHOR]

Utilizing the interactions between tryptophan, methyl viologen and cucurbit[8]uril, we found that the distance between the targeted peptides/protein and the reactive peptide was shortened, which facilitated the Michael addition reaction between cysteine and dehydroalanine. The highest acceleration was observed on cysteines with suitable pKa and spatial location to tryptophan, suggesting that our system can be used for regioselective cysteine modification. [ABSTRACT FROM AUTHOR]

We developed a new method for protein droplet visualization by means of a droplet probe (DroProbe) based on an aggregation-induced emission (AIE) fluorogen. A simple method for viscosity comparison of the protein condensed phase based on the lifetime of the DroProbe was also developed. [ABSTRACT FROM AUTHOR]

Precipitation behavior of carbide/carbonitride in high-strength low-carbon steel is significantly affected by the ferrite transformation modes, which may change from the negligible partitional local equilibrium mode to the partitional local equilibrium mode as holding temperature increases or holding time increases at a certain temperature for ferrite phase transformation. Herein, the isothermal precipitation behavior of V(C, N) under negligible partitional local equilibrium mode of ferrite transformation in V-, N-added low carbon steel has been investigated. Not only the complex precipitation coexisting phenomenon of random precipitation and fibrous precipitation but also that of random precipitation and interphase precipitation was observed and certificated by the selected area electron diffraction patterns. In addition to Baker–Nutting orientation relationship, the Kurdjumov–Sachs OR [111]α//[110]P, 1 1 ¯ 0 α / / 1 1 ¯ 1 ¯ P between ferrite and interphase precipitation were found. Due to big variation in the movement velocity of austenite/ferrite interface, non-uniform distribution of precipitates occurred, resulting in hardness of ferrite grains changing from 185 to 215 HV. [ABSTRACT FROM AUTHOR]

A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time. [ABSTRACT FROM AUTHOR]

Chemical protein modifications facilitate the investigation of natural posttranslational protein modifications and allow the design of proteins with new functions. Proteins can be modified at a late stage on amino acid side chains by chemical methods. The indole moiety of tryptophan residues is an emerging target of such chemical modification strategies because of its unique reactivity and low abundance. This review provides an overview of the recently developed methods of tryptophan modification at the peptide and protein levels. [ABSTRACT FROM AUTHOR]

The pollen fertility of photoperiod/temperature sensitive genic male sterile (P/TGMS) wheat is controlled by light and/or temperature. Circular RNA (circRNA) and long non-coding RNA (lncRNA) are known to participate in the development of anthers in plants, but their impact on male sterility in the P/TGMS line is not well understood. In this study, we carried out high-throughput sequencing to investigate the differential expression of lncRNAs and circRNAs and their biological functions in anthers of photo-thermosensitive genic male sterile (PTGMS) wheat line BS366-42L during the transition phase of male fertility under four different photoperiod and temperature treatments. Eight lncRNAs, 40 mRNAs and three circRNAs were screened out and thought as essential candidates that closely related to male sterility. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential functions of differentially expressed RNAs. The results indicated that carbohydrate-related metabolism was important for male sterility in the wheat PTGMS line BS366-42L. lncRNA/circRNA-mRNA-miRNA (ceRNA) integrate networks were constructed to reflect their complex inner association with male sterility. Our study provides a systematic perspective on the potential function of RNAs in male fertility in PTGMS lines of wheat. [ABSTRACT FROM AUTHOR]

We developed a late-stage modification strategy by a phospha-Michael addition reaction between various functional phosphines and unprotected dehydroalanine (Dha) peptides and proteins under mild conditions. This strategy was applied to generate a staple peptide to enhance its cell membrane penetrability, and it was also able to regulate α-synuclein aggregation properties and morphological characteristics with the addition of different charges. [ABSTRACT FROM AUTHOR]

Herein, the isothermal precipitation behaviors of V(C,N) in ferrite are studied. At 700 °C, the dominant precipitation behavior of V(C,N) is interphase precipitation (IP), whereas at 660 and 620 °C, random precipitation (RP) is dominant. Both IP and RP show the Nishiyama–Wassermann orientation relationship (OR) with ferrite, unlike the common OR between precipitation and ferrite. The size of most precipitated particles varies in the ranges of 5–8 nm at 660 °C and 3–5 nm at 620 °C. The average values of hardness of ferrite grain formed at 700, 660, and 620 °C are 195.1, 237.6, and 278.6 HV, respectively. [ABSTRACT FROM AUTHOR]

In this work, the spherical NiO-NiMoO4 composite was synthesized by solvothermal route followed by calcination, and then spherical NiO-NiMoO4/PPy composite was synthesized by in situ polymerization of pyrrole monomer. The NiO-NiMoO4 and NiO-NiMoO4/PPy microspheres with a particle size of around 1–2 μm consist of nanorods and nanosheets. Hence, NiO-NiMoO4/PPy anode shows a higher delithiation and lithiation capacities than NiO-NiMoO4 at each rate. At 0.2 A g−1, NiO-NiMoO4 only shows an initial delithiation capacity of ∼775 mAh g−1, and the capacity only keeps 207 mAh g−1 after 160 cycles. Nonetheless, NiO/NiMoO4/PPy shows an initial delithiation capacity of ~ 884 mAh g−1, and the capacity also maintains ~ 846 mAh g−1 even after 160 cycles. The corresponding capacity retention of NiO/NiMoO4/PPy and NiO/NiMoO4 are 95.7% and 26.7%, respectively. The PPy modification is a direct and effective strategy to improve the reversible capacity and cycling performance of NiO-NiMoO4 composite. [ABSTRACT FROM AUTHOR]

We developed a host–guest ATP responsive strategy for efficient intracellular delivery of phosphopeptides, employing a pegylated arginine clustered calix[5]arene nanocarrier system that has great capability of recognizing the phosphate moieties on peptides and penetrating the cell membrane. [ABSTRACT FROM AUTHOR]

Herein, we have successfully semi-synthesized a TDP-43 prion-like domain with Ser404 phosphorylation. We have demonstrated that Ser404 phosphorylation could accelerate the amyloid aggregation of the TDP-43 prion-like domain and aggravate its cytotoxicity. [ABSTRACT FROM AUTHOR]

A series of novel parthenolide–thiazolidinedione hybrids have been synthesized via a click chemistry-mediated coupling between parthenolide and thiazolidinedione, and evaluated for their cytotoxic activities. The results indicated that all the hybrids showed moderate cytotoxic effects on human cancer cell lines, including human erythroleukemia cell line (HEL), prostate (PC3), and breast (MDA-MB-231) by MTT assay. In particular, compound VI-6 exhibited the best cytotoxic activities against the MDA-MB-231 cells with IC50 value of 2.07 µM, which was about eight times more active than that of the original compound (PTL). These interesting results might be used to develop novel lead scaffolds for potential anticancer agents. [ABSTRACT FROM AUTHOR]

Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors' advances from two aspects, covalent, and noncovalent inhibitors. [ABSTRACT FROM AUTHOR]

It has been reported that many molecules could inhibit the aggregation of Aβ (amyloid‐β) through suppressing either primary nucleation, secondary nucleation, or elongation processes. In order to suppress multiple pathways of Aβ aggregation, we screened 23 small molecules and found two types of inhibitors with different inhibiting mechanisms based on chemical kinetics analysis. Trp‐glucose conjugates (AS2) could bind with fibril ends while natural products (D3 and D4) could associate with monomers. A cocktail of these two kinds of molecules achieved co‐inhibition of various fibrillar species and avoid unwanted interference. [ABSTRACT FROM AUTHOR]