Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.

Conformational and static properties of tagged chains in solvents: effect of chain connectivity in solvent molecules.

Polymer chains immersed in different solvent molecules exhibit diverse properties due to multiple spatiotemporal scales and complex interactions. Using molecular dynamics simulations, we study the conformational and static properties of tagged chains in different solvent molecules. Two types of solvent molecules were examined: one type consisted of chain molecules connected by bonds, while the other type consisted of individual bead molecules without any bonds. The only difference between the two solvent molecules lies in the chain connectivity. Our results show a compression of the tagged chains with the addition of bead or chain molecules. Chain molecule confinement induces a stronger compression compared to bead molecule confinement. In chain solvent molecules, the tagged chain's radius of gyration reached a minimum at a monomer volume fraction of ∼0.3. Notably, the probability distributions of chain size remain unchanged at different solvent densities, irrespective of whether the solvent consists of beads or polymers. Furthermore, as solvent density increases, a crossover from a unimodal to a bimodal distribution of bond angles is observed, indicating the presence of both compressed and expanded regions within the chain. The effective monomer-solvent interaction is obtained by calculating the partial radial distribution function and the potential of the mean force. In chain solvents, the correlation hole effect results in a reduced number of nearest neighbors around tagged monomers compared to bead solvents. The calculation of pore size distribution reveals that the solvent nonhomogeneity induced by chain connectivity leads to a broader distribution of pore sizes and larger pore dimensions at low volume fractions. These findings provide a deeper understanding of the conformational behavior of polymer chains in different solvent environments.

Autophagy-mediated ferroptosis is involved in development of severe acute pancreatitis.

BACKGROUND: Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. METHODS: We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. RESULTS: Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. CONCLUSIONS: Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP.

Spatial interaction and risk zoning of compound pollutants in farmland soils: Insights from heavy metals and polycyclic aromatic hydrocarbons in Hezhang County, China.

The accurate identification and assessment of comprehensive risks associated with compound pollution in agricultural ecosystems remain significant challenges due to the complexity of pollution sources, soil heterogeneity, and spatial variability. In this study, bivariate local indicators of spatial association (LISA) were applied to analyze the spatial interaction between heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in farmland soils in Hezhang County. The results revealed distinct clusters with elevated concentrations of both HMs and PAHs, predominantly in areas affected by long-standing lead-zinc mining and smelting activities. Positive matrix factorization (PMF) was utilized to identify mining and smelting activities, and associated coal consumption as common sources of both pollutants, contributing 53 % and 28 %, respectively. Ecological health risk assessment results indicated that the combined pollution in this area has led to particularly severe ecological and cancer risks, with the pollution coefficient (Pc) exceeding 3.0, and risk values for both adults and children surpassing the threshold of 10-4. Through the integration of advanced bivariate LISA mapping and thorough risk assessment, this study precisely delineated ecological risk zones (33.1 %) and more refined health risk zones (40.1 %) associated with combined pollution. The southwest of Hezhang was identified as a critical hotspot for combined pollution risks, primarily due to intensive mining and smelting activities in the region. Overall, this study underscores the utility of bivariate LISA as a robust approach for delineating spatial clustering patterns caused by combined pollutants. It provides crucial insights for identifying regions with heightened human health and ecological risks in rural settings.

Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission.

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1, a molecular scaffold with a carbazole-pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant Ka =6.04×105  M-1 . Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π-π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.

Design, synthesis and mechanistic studies of a TICT based fluorogenic probe for lighting up protein HSA.

Human serum albumin (HSA) in blood serves as an important biomarker for clinical diagnosis, and fluorescence sensing method has attracted extensive attention. In this work, a small organic molecule probe, YS8, involving twisted intramolecular charge transfer (TICT) characteristic, was designed and investigated to detect HSA. YS8 kept silent state in fluorescence under physiological conditions, but the encapsulation of YS8 in the hydrophobic subdomain IB region of HSA inhibited the TICT state and produced a clear light-up fluorescent signal. Especially, YS8 was demonstrated to be an efficient fluorogenic probe to discriminate HSA from other proteins including the bovine serum albumin (BSA). Moreover, YS8/HSA complex could be applied in fluorescence imaging in living cells and is also useful in the study of artificial fluorescent protein (AFP).

Development of a Questionnaire to Assess Nursing Competencies for the Care of People with Psychiatric Disabilities in a Hospital Environment.

The recovery of people with psychiatric disabilities requires high-quality nursing care. However, the existing research on the nursing competencies needed for caring for people with psychiatric disabilities have been based on a narrow competency framework. By adopting a broader competency framework, this study aimed to find the competencies needed for the nursing care of people with psychiatric disabilities in a hospital environment. Accordingly, a questionnaire will be developed to measure these competences. First, a literature review and interviews with psychiatrists, psychiatric nurses, and people with psychiatric disabilities were conducted to develop the pool of competency items. Second, a pilot study was conducted to review the initial pool of items. Finally, a survey of 581 psychiatric nurses was used to conduct a series of principal component analyses to explore the structure of the questionnaire. The 17-item questionnaire included 5 factors, which accounted for 68.60% of the total variance: sense of responsibility, vocational identification, agreeableness, cooperation capacity, and carefulness; the Cronbach's alpha coefficients were 0.85, 0.85, 0.74, 0.80, and 0.77, respectively. Most of the competencies belonged to attitudes, values, and traits, which were overlooked in previous studies. The questionnaire has satisfactory internal reliability and structural validity, and could contribute some to the selection of the psychiatric workforce.

Dynamic chromatin changes associated with de novo centromere formation in maize euchromatin.

The inheritance and function of centromeres are not strictly dependent on any specific DNA sequence, but involve an epigenetic component in most species. CENH3, a centromere histone H3 variant, is one of the best-described epigenetic factors in centromere identity, but the chromatin features required during centromere formation have not yet been revealed. We previously identified two de novo centromeres on Zea mays (maize) minichromosomes derived from euchromatic sites with high-density gene distributions but low-density transposon distributions. The distribution of gene location and gene expression in these sites indicates that transcriptionally active regions can initiate de novo centromere formation, and CENH3 seeding shows a preference for gene-free regions or regions with no gene expression. The locations of the expressed genes detected were at relatively hypomethylated loci, and the altered gene expression resulted from de novo centromere formation, but not from the additional copy of the minichromosome. The initial overall DNA methylation level of the two de novo regions was at a low level, but increased substantially to that of native centromeres after centromere formation. These results illustrate the dynamic chromatin changes during euchromatin-originated de novo centromere formation, which provides insight into the mechanism of de novo centromere formation and regulation of subsequent consequences.

Association of habitual sleep duration with abnormal bowel symptoms: a cross-sectional study of the 2005-2010 national health and nutrition examination survey.

OBJECTIVES: Nowadays, few studies have examined the relationships between sleep duration and abnormal gut health. In this study, we used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the correlations between habitual sleep duration and abnormal bowel symptoms in adults. METHODS: This study included 11,533 participants aged ≥ 20 years from the NHANES conducted during 2005-2010. Chronic constipation and chronic diarrhea were defined based on the Bristol Stool Form Scale (BSFS) and frequency of bowel movements. Sleep duration was assessed based on the self-report questionnaire and classified into three groups: short sleep duration (< 7 h), normal sleep duration (7-9 h), and long sleep duration (> 9 h). Weighted data were calculated according to analytical guidelines. Logistic regression models and restricted cubic spline curves (RCS) were used to assess and describe the association between sleep duration and chronic diarrhea and constipation. Univariate and stratified analyses were also performed. RESULTS: There were 949 (7.27%) adults aged 20 years and older with chronic diarrhea and 1120 (8.94%) adults with constipation among the 11,533 individuals. A positive association was found between short sleep duration and chronic constipation, with a multivariate-adjusted OR of 1.32 (95% CI: 1.05-1.66). Additionally, long sleep duration was significantly associated with an increased risk of chronic diarrhea (OR: 1.75, 95% CI: 1.08-2.84, P = 0.026). The RCS models revealed a statistically significant nonlinear association (P for non-linearity < 0.05) between sleep duration and chronic diarrhea. Furthermore, obesity was found to modify the association between sleep duration and chronic diarrhea and constipation (p for interaction = 0.044). CONCLUSIONS: This study suggests that both long and short sleep durations are associated with a higher risk of chronic diarrhea and constipation in the general population. Furthermore, a non-linear association between sleep duration and these conditions persists even after adjusting for case complexities.

GSDMD in regulated cell death: A novel therapeutic target for sepsis.

Sepsis is a life-threatening multi-organ dysfunction syndrome caused by an abnormal host response to infection. Regulated cell death is essential for maintaining tissue homeostasis and eliminating damaged, infected, or aging cells in multicellular organisms. Gasdermin D, as a member of the gasdermin family, plays a crucial role in the formation of cytoplasmic membrane pores. Research has found that GSDMD plays important roles in various forms of regulated cell death such as pyroptosis, NETosis, and necroptosis. Therefore, through mediating regulated cell death, GSDMD regulates different stages of disease pathophysiology. This article mainly summarizes the concept of GSDMD, its role in regulated cell death, its involvement in organ damage associated with sepsis-related injuries mediated by regulated cell death via GSDMD activation and introduces potential drugs targeting GSDMD that may provide more effective treatment options for sepsis patients through drug modification.

New insights into regulatory cell death and acute pancreatitis.

Acute pancreatitis (AP) may be associated with both local and systemic complications. Although it is usually self-limiting, up to 20% of patients develop severe acute pancreatitis (SAP), which leads to systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction and failure affecting the lung, kidney, liver and heart. Patients who survive the condition frequently develop devastating long-term consequences such as diabetes mellitus, exocrine pancreatic insufficiency, chronic pancreatitis (CP) and poor quality of life. A lack of specific targeted treatments is the main reason for high mortality and morbidity, indicating that more research on the pathogenesis of AP is needed. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of AP, including mechanisms of calcium-mediated acinar cell injury and death, the cytoprotective role of the unfolded protein response (UPR) and autophagy in preventing sustained endoplasmic reticulum stress (ERs); however, the mechanism of parenchymal cell death is relatively poorly understood. This paper reviews the research progress of the regulatory cell death (RCD) mode in the pathogenesis of AP, providing some new insights and regulatory targets for the pathogenesis and treatment of AP, facilitating better targeted drug development.

Serum Zonula Occludens-1 and Claudin-5 Levels in Patients with Insomnia Disorder: A Pilot Study.

Purpose: This research aimed to investigate serum Zonula occludens-1 (ZO-1) and Claudin-5 (CLDN5) levels to show whether or not their eventual changes in patients with insomnia disorder could have etiopathogenetic importance. There was no research investigating serum ZO-1 and CLDN5 concentrations in insomnia disorder. Patients and Methods: This study included 60 insomnia disorder patients and 45 normal controls. None of the patients received drugs for insomnia. The patients completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI), and Polysomnography (PSG) to score the insomnia disorder symptoms. Venous blood samples were collected, and serum ZO-1 and claudin-5 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Serum ZO-1 level was significantly higher without a significant difference between age, sex, and body mass index, whereas the difference in serum claudin-5 level between the two groups was not statistically significant. In addition, ZO-1 levels were positively correlated with ISI and PSQI and negatively with N1 and N1_perc. We also demonstrated a positive correlation between the levels of CLDN5 and HAMA, and a negative correlation with total sleep time (TST), N1 and N1_perc. Conclusion: Our findings suggest an association between these intestinal and brain endothelial permeability markers and insomnia disorders. However, these remain modest and preliminary and need more extensive studies, including long-term follow-up populations and involving gut microbes, to further validate and explore the mechanisms involved.

Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis.

The inflammatory response is one of the host's mechanisms to combat pathogens. Normal and controlled inflammation can accelerate the clearance of pathogens. However, in sepsis, the host often exhibits an excessive inflammatory response to infection, leading to tissue and organ damage. Therefore, studying the mechanisms underlying the occurrence and development of sepsis is of significant importance. Pyroptosis is a form of programmed cell death (PCD) executed by the gasdermins (GSDMs) family, and its pro-inflammatory characteristics are considered a crucial component of the sepsis mechanism. Previous research on pyroptosis in sepsis has mainly focused on the caspase-1/4/5/11-GSDMD pathway, which has made significant progress. However, there is a lack of research on the roles of other GSDMs family members in sepsis. New research has revealed that the caspase-3/GSDME pathway can also mediate pyroptosis, playing important roles in cancer, other inflammatory diseases, and even some sepsis-related conditions. This discovery suggests the potential value of investigating caspase-3/GSDME in sepsis research. This review provides an overview of the role of the GSDMs family in infectious diseases, summarizes current research on the caspase-1/4/5/11-GSDMD pathway, describes the role of caspase-3 in sepsis, and discusses the research findings related to pyroptosis mediated by the caspase-3/GSDME pathway in cancer, inflammatory diseases, and sepsis-related conditions. The aim of this article is to propose the concept of caspase-3/GSDME as a potential target in sepsis research. Considering the role of this pathway in other diseases, including inflammatory conditions, and given the unique nature of sepsis as an inflammatory disease, the article suggests that this pathway may also play a role in sepsis. This hypothesis provides new insights and options for future sepsis research, although direct experiments are needed to validate this hypothesis.

Impairment of GABA inhibition in insomnia disorders: Evidence from the peripheral blood system.

Aim: To explore the change characteristics and related factors of various indexes of GABAergic system in peripheral blood of patients with insomnia disorder. Methods: In this study, a total of 30 patients who met the DSM-5 diagnostic criteria for insomnia disorder and 30 normal controls were included. All subjects had a structured clinical interview with the Brief International Neuropsychiatric Disorder Interview, and PSQI was used to evaluate the sleep status of the subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum γ-aminobutyric acid (GABA), and RT-PCR was used to detect GABAA receptor α1 and α2 subunit mRNA. All data were statistically analyzed using SPSS 23.0. Results: Compared with the normal control group, the mRNA levels of GABAA receptor α1 and α2 subunits in the insomnia disorder group were significantly lower, but there was no significant difference in the serum GABA levels between the two groups. And in the insomnia disorder group, there was no significant correlation between the GABA levels and the mRNA expression levels of α1 and α2 subunits of GABAA receptors. Although no significant correlation was found between PSQI and serum levels of these two subunit mRNAs, its component factors sleep quality and sleep time were negatively correlated with GABAA receptor α1 subunit mRNA levels, and daytime function was inversely correlated with GABAA receptor α2 subunit mRNA levels. Conclusion: The inhibitory function of serum GABA in patients with insomnia may be impaired, and the decreased expression levels of GABAA receptor α1 and α2 subunit mRNA may become a reliable indicator of insomnia disorder.

An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies.

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a "fluorescence-off" state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems.

Efficacy and Safety of Pulse Magnetic Therapy System in Insomnia Disorder: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study's objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. METHODS: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. RESULTS: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%-79.0%), 75.0% (95% CI: 64.1%-83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. CONCLUSION: PMTS is safe and effective in improving insomnia disorders.

Ferroptosis and its emerging roles in acute pancreatitis.

ABSTRACT: Acute pancreatitis (AP) is a common and potentially life-threatening pancreatic inflammatory disease. Although it is usually self-limiting, up to 20% of patients will develop into severe AP. It may lead to systemic inflammatory response syndrome and multiple organ dysfunction, affecting the lungs, kidneys, liver, heart, etc. Surviving patients usually have sequelae of varying degrees, such as chronic hyperglycemia after AP (CHAP), pancreatic exocrine insufficiency, and chronic pancreatitis. Lacking specific target treatments is the main reason for high mortality and morbidity, which means that more research on the pathogenesis of AP is needed. Ferroptosis is a newly discovered regulated cell death (RCD), originally described in cancer cells, involving the accumulation of iron and the depletion of plasma membrane polyunsaturated fatty acids, and a caspase-independent RCD. It is closely related to neurological diseases, myocardial infarction, ischemia/reperfusion injury, cancer, etc. Research in the past years has also found the effects of ferroptosis in AP, pancreatic cancer, and AP complications, such as acute lung injury and acute kidney injury. This article reviews the research progress of ferroptosis and its association with the pathophysiological mechanisms of AP, trying to provide new insight into the pathogenesis and treatment of AP, facilitating the development of better-targeted drugs.

Energy-constraint output formation for swarm systems with dynamic output feedback control protocols.

This paper studies the energy-constraint output formation control for swarm systems with leaderless and leader-following topology structures. Most existing results on output formation with the dynamic output feedback protocols focus on the swarm systems without the energy constraint, but it is well known that the energy constraint is critically important for practical applications. In order to analyze the impacts of the energy constraint, a new energy-constraint output formation protocol is proposed. First, by the observable decomposition approach, a dynamic output formation protocol is presented, which contains an energy-constraint term to restrict the whole consumption. Then, sufficient conditions for leaderless energy-constraint output formation are presented via establishing the relationship of the energy constraint and the matrix variables, where it is found that the designed gain matrices of the output formation protocol can ensure that the actual energy consumption is lower than the total energy supply. Especially, a partition checking algorithm is proposed to check those conditions, which can ensure the scalability and solvability of a swarm system. Moreover, the output formation center function is derived to depict the whole macroscopic movement of a swarm system. A nonsingular transformation approach is presented to unify leaderless energy-constraint output formation and energy-constraint output formation tracking into the same framework, which are usually discussed in different theoretical frameworks. Finally, two simulation examples are illustrated to show that the theoretical results about leaderless energy-constraint output formation and energy-constraint output formation tracking are correct.

Selective c-MYC G4 DNA recognition based on a fluorescent light-up probe with disaggregation-induced emission characteristics.

The c-MYC promoter is well-known as an important oncogene, the overexpression of which leads to ∼80% of all solid tumors. The four-stranded G4 present in the c-MYC promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Accordingly, strategies employed for c-MYC G4 DNA sensing have implications for the detection of many human pathologies. However, achieving specificity toward c-MYC G4 over other structurally similar G4s is a challenging task. Here, a supramolecular strategy that relies on the recognition-driven disaggregation of a novel BODIPY probe is outlined. The synthesized probe remained almost non-fluorescent in aqueous media in the aggregation state. Of all the tested G4 and non-G4 DNAs, only c-MYC triggered probe disaggregation and induced a significant increase in fluorescence intensity. The binding details discussed here suggest the basis for the recognition of a particular G4 structure, thus opening up a new way for the design and development of sequence-selective supramolecular G4 probes with desired properties.

Genome-wide identification and expression analysis of SBP-box gene family reveal their involvement in hormone response and abiotic stresses in Chrysanthemum nankingense.

SQUAMOSA promoter-binding-protein (SBP)-box family proteins are a class of plant-specific transcription factors, and widely regulate the development of floral and leaf morphology in plant growth and involve in environment and hormone signal response. In this study, we isolated and identified 21 non-redundant SBP-box genes in Chrysanthemum nankingense with bioinformatics analysis. Sequence alignments of 21 CnSBP proteins discovered a highly conserved SBP domain including two zinc finger-like structures and a nuclear localization signal region. According to the amino acid sequence alignments, 67 SBP-box genes from Arabidopsis thaliana, rice, Artemisia annua and C. nankingense were clustered into eight groups, and the motif and gene structure analysis also sustained this classification. The gene evolution analysis indicated the CnSBP genes experienced a duplication event about 10 million years ago (Mya), and the CnSBP and AtSPL genes occurred a divergence at 24 Mya. Transcriptome data provided valuable information for tissue-specific expression profiles of the CnSBPs, which highly expressed in floral tissues and differentially expressed in leaf, root and stem organs. Quantitative Real-time Polymerase Chain Reaction data showed expression patterns of the CnSBPs under exogenous hormone and abiotic stress treatments, separately abscisic acid, salicylic acid, gibberellin A3, methyl jasmonate and ethylene spraying as well as salt and drought stresses, indicating that the candidate CnSBP genes showed differentiated spatiotemporal expression patterns in response to hormone and abiotic stresses. Our study provides a systematic genome-wide analysis of the SBP-box gene family in C. nankingense. In general, it provides a fundamental theoretical basis that SBP-box genes may regulate the resistance of stress physiology in chrysanthemum via exogenous hormone pathways.