Chemical Control of Fluorescence Lifetime towards Multiplexing Imaging.

Fluorescence lifetime imaging has been a powerful tool for biomedical research. Recently, fluorescence lifetime-based multiplexing imaging has expanded imaging channels by using probes that harbor the same spectral channels and distinct excited state lifetime. While it is desirable to control the excited state lifetime of any given fluorescent probes, the rational control of fluorescence lifetimes remains a challenge. Herein, we chose boron dipyrromethene (BODIPY) as a model system and provided chemical strategies to regulate the fluorescence lifetime of its derivatives with varying spectral features. We find electronegativity of structural substituents at the 8' and 5' positions are important to control the lifetime for the green-emitting and red-emitting BODIPY scaffolds. Mechanistically, such influences are exerted via the photo-induced electron transfer and the intramolecular charge transfer processes for the 8' and 5' positions of BODIPY, respectively. Based on these principles, we have generated a group of BODIPY probes that enable imaging experiments to separate multiple targets using fluorescence lifetime as a signal. In addition to BODIPY, we envision modulation of electronegativity of chemical substituents could serve as a feasible strategy to achieve rational control of fluorescence lifetime for a variety of small molecule fluorophores.

Distinguishing the responsive mechanisms of fluorescent probes to hydrogen peroxide, proteins, and DNA/RNA.

The responsive mechanisms of cationic quinolinium-vinyl-N,N-dimethylaniline boronate (QVD-B) derivative probes to hydrogen peroxide (H2O2), proteins and DNA/RNA are theoretically investigated in this study. The potential energy curves of QVD-B scanned on a dihedral angle (N+-C-CC) in the first singlet (S1) state exhibit large torsional energy barriers. Additionally, the energy of the lowest unoccupied molecular orbital (LUMO) of an acceptor moiety (-3.14 eV) is lower than that of a donor moiety (-1.13 eV) in QVD-B. This demonstrates that photoinduced electron transfer (PET) quenches the fluorescence of QVD-B, as opposed to the previous report of intramolecular single-bond rotation. After reacting with H2O2, the reaction product of quinoline-vinyl-N,N-dimethylaniline (QVD) turns off the PET pathway and turns on the fluorescence at 550 nm, which is consistent with the experimental results (580 nm). Among the possible configurations of QVD-B that forms with proteins and DNA, the calculated fluorescence values of corresponding twisted QVD-B-P (638 nm) and QVD-B-D (686 nm) are consistent with the experimental results (632 and 688 nm). The frontier molecular orbital and electron-hole analysis show that the charge transfer distance follows the order of QVD (1.88 Å) < QVD-B-P (4.49 Å) < QVD-B-D (6.39 Å), which induces the fluorescence red-shifts of QVD-B-P and QVD-B-D compared to that of QVD. The multi-detection mechanism of the fluorescent probe QVD-B is attributed to PET progress and different degrees of local charge transfer after photoexcitation.

Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells.

Human myeloid leukemia cells (such as K562) could be used for the study of erythropoiesis, and mature erythroid markers and globins could be induced during leukemia cell differentiation; however, the pathways involved are different compared with those of hematopoietic stem cells (HSCs).We identified the differentially expressed genes (DEGs) of K562 cells and HSCs associated with stem cells and erythroid differentiation. Furthermore, we showed that hemin-induced differentiation of K562 cells could be induced by serum starvation or treatment with the tyrosine kinase inhibitor saracatinib. However, erythroid differentiation of HSCs was inhibited by the deprivation of the important serum component erythropoietin (EPO) or treatment with saracatinib. Finally, we found that the mRNA expression of K562 cells and HSCs was different during saracatinib-treated erythroid differentiation, and the DEGs of K562 cells and HSCs associated with tyrosine-protein kinase were identified.These findings elucidated the cellular phenomenon of saracatinib induction during erythroid differentiation of K562 cells and HSCs, and the potential mechanism is the different mRNA expression profile of tyrosine-protein kinase in K562 cells and HSCs.

Xie-Bai-San increases NSCLC cells sensitivity to gefitinib by inhibiting Beclin-1 mediated autophagosome formation.

BACKGROUND: Autophagy, a cellular process involving lysosomal self-digestion, plays a crucial role in recycling biomolecules and degrading dysfunctional proteins and damaged organelles. However, in non-small cell lung cancer (NSCLC), cancer cells can exploit autophagy to survive metabolic stress and develop resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which reduce treatment efficacies. Currently, most studies have found that late-stage autophagy inhibitors can hinder EGFR-TKIs resistance, while research on early-stage autophagy inhibitors is still limited. PURPOSE: This study investigates the mechanism via which the Xie-Bai-San (XBS) formula enhances NSCLC cell sensitivity to gefitinib, revealing the relationship between XBS-induced cell death and the inhibition of autophagosome formation. METHODS: Cell viability was assessed using CCK-8 and EdU assays, lentivirus transfection was utilized to generate PC9 cells harboring the PIK3CA E545K mutation (referred to as PC9-M), autophagic flux was monitored using mCherry-GFP-LC3 adenovirus. Protein expression and colocalization were observed through immunofluorescence staining. The interaction between Bcl-2 and Beclin-1 in PC9-GR and PC9-M cells was determined via co-immunoprecipitation (Co-IP) assay, cell apoptosis was assessed by flow cytometry and PI staining, and overall survival analysis of lung adenocarcinoma patients was conducted using the TCGA database. In vivo experiments included a patient-derived xenograft (PDX) model with EGFR and PIK3CA mutations and subcutaneous mice xenografts of NSCLC cell lines (PC9 and PC9-GR). In addition, autophagic vesicles in mouse tumor tissues were observed via transmission electron microscopy analysis. RESULTS: XBS effectively inhibits the proliferation of gefitinib-resistant NSCLC cells and induces apoptosis both in vitro and in vivo. Mechanistically, XBS suppresses gefitinib-induced autophagic flux by inhibiting autophagy through the upregulation of p-mTOR and Bcl-2 and downregulation of Beclin-1. Additionally, XBS enhances the interaction between Bcl-2 and Beclin-1, and the overexpression of Beclin-1 promotes NSCLC cell proliferation and counteracts XBS-induced cell death, while XBS demonstrates minimal impact on autophagosome-lysosome fusion or lysosome function. CONCLUSION: This study reveals a novel role for the XBS formula in impeding autophagy initiation and demonstrates its potential as a candidate drug to counteract autophagy-induced treatment resistance in NSCLC.

Molecular docking, 3D-QASR and molecular dynamics simulations of benzimidazole Pin1 inhibitors.

Pin1 (protein interacting with never-in-mitosis akinase-1) is a member of the family of peptidylprolyl cis-trans isomerases (PPIases) that specifically recognize and isomerize substrates containing phosphorylated Ser/Thr-Pro sequences. Pin1 is involved in many cellular processes and plays a key role in the cell cycle, transcriptional regulation, cell metabolism, proliferation and differentiation, and its abnormalities lead to degenerative and neoplastic diseases. Pin1 is highly expressed in human cancers and promotes the development of tumors by activating multiple oncogenes and inactivating multiple tumor suppressor genes, making it an attractive target for cancer therapy. In this study, we investigated the binding mechanism and conformational relationship between benzimidazole Pin1 inhibitors and Pin1 proteins by molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, binding free energy calculations and decomposition, and molecular dynamics simulations. Molecular docking and molecular dynamics simulations disclosed the most likely binding pose of benzimidazoles with the Pin1 protein. The results of 3D-QSAR modeling indicated that electrostatic fields, hydrophobic fields and hydrogen bonding play important roles in the binding process of inhibitors to proteins. The binding free energy calculations and energy decomposition indicated that Lys63, Arg69, Cys113, Leu122, Met130, and Ser154 may be key residues in the binding of benzimidazole-based inhibitors to the Pin1 protein. This study provides an important theoretical basis for the design and optimization of benzimidazole compounds.

Tumor Targeted Cuprous-Based Nanocomposite as Responsive Cascade Nanocatalyst for Efficient Tumor Synergistic Therapy.

The single-functionality of traditional chemodynamic therapy (CDT) reagents usually limits the therapeutic efficacy of cancer treatment. Synergistic nanocomposites that involve cascade reaction provide a promising strategy to achieve satisfactory anticancer effects. Herein, a cuprous-based nanocomposite (CCS@GOx@HA) is fabricated, which owns the tumor targeting ability and can undergo tumor microenvironment responsive cascade reaction to enhance the tumor therapeutic efficiency significantly. Surface modification of nanocomposite with hyaluronic acid enables the targeted delivery of the nanocomposite to cancer cells. Acid-triggered decomposition of nanocomposite in cancer cell results in the release of Cu+ , Se2- and GOx. The Cu+ improves the Fenton-like reaction with endogenous H2 O2 to generate highly toxic • OH for CDT. While GOx can not only catalyze the in situ generation of endogenous H2 O2 , but also accelerate the consumption of intratumoral glucose to reduce nutrient supply in tumor site. In addition, Se2- further improves the therapeutic effects of CDT by upregulating the reactive oxygen species (ROS) in tumor cells. Meanwhile, the surface modification endows the nanocomposite the good water dispersibility and biocompatibility. Moreover, in vitro and in vivo experiments demonstrate satisfactory anti-cancer therapeutic performance by the synergistic cascade function of CCS@GOx@HA than CDT alone.

Role of anthraquinones in combating insulin resistance.

Insulin resistance presents a formidable public health challenge that is intricately linked to the onset and progression of various chronic ailments, including diabetes, cardiovascular disease, hypertension, metabolic syndrome, nonalcoholic fatty liver disease, and cancer. Effectively addressing insulin resistance is paramount in preventing and managing these metabolic disorders. Natural herbal remedies show promise in combating insulin resistance, with anthraquinone extracts garnering attention for their role in enhancing insulin sensitivity and treating diabetes. Anthraquinones are believed to ameliorate insulin resistance through diverse pathways, encompassing activation of the AMP-activated protein kinase (AMPK) signaling pathway, restoration of insulin signal transduction, attenuation of inflammatory pathways, and modulation of gut microbiota. This comprehensive review aims to consolidate the potential anthraquinone compounds that exert beneficial effects on insulin resistance, elucidating the underlying mechanisms responsible for their therapeutic impact. The evidence discussed in this review points toward the potential utilization of anthraquinones as a promising therapeutic strategy to combat insulin resistance and its associated metabolic diseases.

Causal relationships between circulating inflammatory cytokines and diffuse large B cell lymphoma: a bidirectional Mendelian randomization study.

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Studies indicated that inflammatory cytokines involved in the occurrence and progression of DLBCL and it is challenging to discern causality from the effects due to the presence of feedback loops. We conducted a bidirectional Mendelian randomization (MR) study to investigate the potential causal relationship between DLBCL and inflammatory cytokines. The genetic variants associated with inflammatory cytokines were obtained from a genome-wide association study (GWAS) involving 8293 European participants, and the data on 1010 individuals with DLBCL were sourced from the FinnGen consortium. The primary method employed in this study was the inverse-variance weighted (IVW) method, with supplementary analyses conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. Based on the IVW method, genetically predicted that increasing level of Monokine induced by interferon gamma (MIG/CXC chemokine ligand 9, CXCL9) [OR: 1.31; 95% CI: 1.05-1.62; P = 0.01] and interferon gamma-induced protein 10(IP-10/CXC chemokine ligand 10, CXCL10) [OR: 1.30; 95% CI: 1.02-1.66; P = 0.03] showed suggestive associations with DLBCL risk. DLBCL may increase the level of macrophage colony-stimulating factor (M-CSF) [OR: 1.12; 95% CI: 1.01-1.2; P = 0.03], tumor necrosis factor beta (TNF-ß) [OR: 1.16; 95% CI: 1.02-1.31; P = 0.02] and TNF-related apoptosis-inducing ligand (TRAIL) [OR: 1.07; 95% CI: 1.01-1.13; P = 0.02]. This study presents evidence supporting a causal relationship between inflammation cytokines and DLBCL. Specifically, MIG/CXCL9 and IP-10/CXCL10 were identified as indicators of upstream causes of DLBCL; while, DLBCL itself was found to elevate the levels of M-CSF, TNF-ß, and TRAIL. These findings suggest that targeting specific inflammatory factors through regulation and intervention could serve as a potential approach for the treatment and prevention of DLBCL.

Circulating Concentrations of advanced Glycation end Products, Carboxymethyl Lysine and Methylglyoxal are Associated With Renal Function in Individuals With Diabetes.

OBJECTIVE: Diabetic kidney disease (DKD) is one of the most severe chronic complications of diabetes and is associated with higher level of advanced glycation end products (AGEs). The aim of this study was to investigate the diagnostic potential of combined detection of multiple serum AGEs in diagnosing DKD. METHODS: Serum AGEs, Nε-(carboxymethyl) lysine (CML), Nε-(carboxyethyl) lysine, and methylglyoxal (MGO) levels were measured by enzyme-linked immunosorbent assay in 176 individuals with type 2 diabetes. Participants were classified into normoalbuminuria, microalbuminuria, and macroalbuminuria group according to their urinary albumin to creatinine ratio (UACR). RESULTS: Higher serum AGEs levels were found to be positively correlated with U-Alb, UACR, and blood urea nitrogen in the study of 176 individuals with type 2 diabetes. CML and MGO levels were positively correlated with U-Alb, UACR, blood urea nitrogen, Scr, and uric acid, and negatively correlated with estimated glomerular filtration rate (P < .05). Multivariate logistic regression analysis showed that elevated levels of AGEs, CML, and MGO were independent risk factors for the progression of DKD (odds ratio = 1.861, 1.016, 7.607, P < .01). The sensitivity, specificity, and area under receiver operating characteristic curve of combined detection of AGEs, MGO, and CML were higher than those of three individual detections (area under the curve = 0.952, 0.772, 0.868, 0905, respectively, P < .05). CONCLUSION: The combined detection of AGEs, CML, and MGO may improve the reliability of early diagnosis of DKD.

Safety of entecavir antiviral therapyduring an accidental pregnancy in patients with chronic hepatitis B.

The present study aimed to investigate the effects of accidental pregnancy CHB patients' reproductive age on their offspring during entecavir (ETV) antiviral therapy. A total of 112 couples were retrospectively enrolled, and they were divided into an observational and control group. A total of 53 couples who had accidental pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group. The control group consisted of 59 couples who became pregnant accidentally while receiving long-term tenofovir disoproxil fumarate (TDF) antiviral treatment. All mothers persisted in their pregnancies in the observational group, and ETV was promptly replaced with TDF. Every mother remained pregnant and continued to use TDF in the control group. The maternal and baby safety profiles, including the prevalence of congenital disabilities, were comparable across the observational and control groups at delivery. In addition, no unusual indications or symptoms of the newborns were noted during the follow-up intervals of 28, 48, and 96 weeks postpartum. Initiating ETV or TDF in early and middle pregnancy seems safe for mothers and infants. Important data from the present study support using ETV in early-mid gestational accidental pregnancies and the prompt substitution of TDF antiviral medication for ETV.

The complete chloroplast genome sequences of four Liparis species (Orchidaceae) and phylogenetic implications.

Liparis Richard (Malaxideae, Epidendroideae) is a large and diverse genus of the family Orchidaceae, the taxonomy of which is complicated and controversial. In this study, we sequenced, assembled and analyzed four complete chloroplast genomes of Liparis species including L. kumokiri, L. makinoana, L. pauliana, and L. viridiflora, and evaluated their phylogenetic relationships with related species for the first time. These four chloroplast genomes (size range 153,095 to 158,239 bp) possess typical quadripartite structures that consist of a large single copy (LSC, 83,533-86,752 bp), a small single copy (SSC, 17,938-18,156 bp) and a pair of inverted repeats (IRs, 26,421-26,933 bp). The genomes contain 133 genes, including 87 protein coding genes, 38 tRNAs and 8 rRNA genes. The genome arrangements, gene contents, gene order, long repeats and simple sequence repeats were similar with small differences observed among these four chloroplast genomes. Five highly variable regions including ycf1, ndhA, ndhF, trnQ and trnK were identified from the comparative analysis with other nine related Liparis species, which had the potential to be used as DNA markers for species identification and phylogenetic studies of Liparis species. Phylogenetic analysis based on the complete chloroplast genome sequences strongly supported the polyphyly of Liparis and its further division into three branches. These results provided valuable information to illustrate the complicated taxonomy, phylogeny and evolution process of the Liparis genus.

BYL719 reverses gefitinib-resistance induced by PI3K/AKT activation in non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Oral administration of kynurenic acid delays the onset of type 2 diabetes in Goto-Kakizaki rats.

Kynurenic acid (KYNA) is an endogenous catabolite of tryptophan that has been found to demonstrate neuroprotective properties in psychiatric disorders. Recently, accumulating data have suggested that KYNA may also play a significant role in various metabolic diseases by stimulating energy metabolism in adipose tissue and muscle. However, whether KYNA can serves as an anti-diabetes agent has yet to be studied. In this study, we investigated the potential anti-diabetic effects of administering KYNA orally through drinking water in pre-diabetic Goto-Kakizaki rats and examined how this treatment may influence energy metabolism regulation within the liver. We found that hyperglycemic Goto-Kakizaki rats showed lower plasmatic KYNA levels compared to normal rats. Oral administration of KYNA significantly delayed the onset of diabetes in Goto-Kakizaki rats compared to untreated animals. Moreover, we found that KYNA treatment significantly increased respiration exchange ratio and promoted the energy expenditure by stimulating the expression of uncoupling protein (UCP). We confirmed that KYNA stimulated the UCP expression in HepG2 cells and mouse hepatocytes at mRNA and protein levels. Our study reveals that KYNA could potentially act as an anti-diabetic agent and KYNA-induced UCP upregulation is closely associated with the regulation of energy metabolism. These results provide further evidence for the therapeutic potential of KYNA in diabetes.

Catalyst-Controlled Direct Oxysulfonylation of Alkenes by Using Sulfonylazides as the Sulfonyl Radical.

A copper/cobalt-catalyzed difunctionalization of alkenes with sulfonylazides and tert-butyl hydroperoxide has been achieved. This protocol provides an efficient and direct oxysulfonylation approach to ß-ketosulfones and ß-sulfonyl peroxides in moderate to good yields under mild conditions. This methodology applies sulfonylazides as a new sulfonyl radical source and features a wide substrate scope and good functional group tolerance.

Treatment with imatinib was useful to delay the neointimal hyperplasia of aortocaval fistula in adenine-induced renal failure rats.

PURPOSE: The study was conducted to investigate the effect of the treatment with imatinib, a c-kit specific inhibitor, on the neointimal hyperplasia (NIH) of aortocaval fistula (ACF) in adenine-induced renal failure rats. MATERIALS AND METHODS: All rats were randomly assigned to 4 groups: rats were fed on a normal diet (normal group); rats were fed on a 0.75% adenine-rich diet (renal failure group). The remaining rats underwent ACF after receiving a 0.75% adenine-rich diet and received daily saline gavage (model group) or imatinib gavage (imatinib group) for 7 days after surgery. Immunohistochemical method was used to detect c-kit expression, and Elastomeric Verhoeff-Van Gieson (EVG) staining was used to observe morphological changes of the ACF. The Pearson correlation analysis was used to evaluate the correlations of c-kit expression with intimal thickness and the percentage of stenosis, respectively. RESULTS: The renal failure group showed positive c-kit expression on the intima of the inferior vena cava (IVC), whereas the normal group did not. Compared to the model group, intimal thickness (P = 0.001), the percentage of stenosis (P = 0.006) and c-kit expression (P = 0.04) were decreased in the imatinib group at 8 weeks postoperatively. C-kit expression was positively correlated with both intimal thickness and percentage of stenosis (intimal thickness: R = 0.650, P = 0.003; the percentage of stenosis: R = 0.581, P = 0.011) in both the model and imatinib groups. CONCLUSION: Treatment with imatinib, a c-kit specific inhibitor, was useful to delay the NIH of ACF in adenine-induced renal failure rats.

Diazo probe-based chemical isotope labeling assisted liquid chromatography-tandem mass spectrometry analysis for sensitive determination of amino acids in biofluids.

Amino acids are important biomolecules and contribute to essential biological processes. Liquid chromatography tandem mass spectrometry (LC-MS) now is a powerful tool for the analysis of amino acid metabolites; however, the structural similarity and polarity of amino acids can lead to the poor chromatographic retention and low detection sensitivities. In this study, we used a pair of light and heavy isotopomers of diazo probes, d0/d5-2-(diazomethyl)-N-methyl-N-phenyl-benzamide (2-DMBA/d5 -2-DMBA) to label amino acids. The paired MS probes of 2-DMBA and d5 -2-DMBA carry diazo groups that can efficiently and specifically react with the carboxyl group on free amino acid metabolites under mild conditions. Benefiting from the transfer of the 2-DMBA/d5 -2-DMBA to carboxyl group on amino acids, the ionization efficiencies of amino acids presented great enhancement during LC-MS analysis. The results suggested that the detection sensitivities of 17 amino acids increased by 9-133-fold upon 2-DMBA labeling, and the obtained limits of detection (LODs) of amino acids on-column ranged from 0.011 fmol-0.057 fmol. With the application of the developed method, we successfully achieved the sensitive and accurate detection of the 17 amino acids in microliter level of serum sample. Moreover, the contents of most amino acids were different in the serum from normal and B16F10-tumour mice, demonstrating that endogenous amino acids may play important roles in the regulation of tumors development. This developed method of chemical labeling of amino acids with diazo probes assisted LC-MS analysis provides a potentially valuable tool to investigate the relationships between amino acids metabolism and diseases.

The Associations between Meeting 24-Hour Movement Guidelines (24-HMG) and Mental Health in Adolescents-Cross Sectional Evidence from China.

(1) Background: This study determined the prevalence of adolescents that meet 24-HMGs alone and in combination, and their association with the risk of developing adolescent anxiety and depression. (2) Methods: Participants were drawn from 9420 K8 grade adolescents (age 14.53 ± 0.69 years; 54.78% boys) from the China Education Tracking Survey (CEPS) 2014-2015 tracking data. Data on depression and anxiety were collected from the results of the questionnaire in the CEPS for the adolescent mental health test. Compliance with the 24-HMG was defined as: physical activity time (PA) ≥ 60 min/day was defined as meeting the PA. Screen time (ST) ≤ 120 min/day was defined as meeting the ST. Adolescents aged 13 years achieved 9-11 h of sleep per night and adolescents aged 14-17 years achieved 8-10 h of sleep per night, defined as meeting sleep. Logistic regression models were used to examine the association between meeting and not meeting the recommendations and the risk of depression and anxiety in adolescents. (3) Results: Of the sample studied, 0.71% of adolescents met all three recommendations, 13.54% met two recommendations and 57.05% met one recommendation. Meeting sleep, meeting PA+ sleep, meeting ST + sleep, and meeting PA + ST + sleep were associated with a significantly lower risk of anxiety and depression in adolescents. Logistic regression results showed that differences in the effects of gender on the odds ratio (ORs) for depression and anxiety in adolescents were not significant. (4) Conclusions: This study determined the risk of developing depression and anxiety in adolescents who met the recommendations for 24-HMG alone and in combination. Overall, meeting more of the recommendations in the 24-HMGs was associated with lower anxiety and depression risk outcomes in adolescents. For boys, reducing the risk of depression and anxiety can be prioritised by meeting PA + ST + sleep, meeting ST + sleep and meeting sleep in the 24-HMGs. For girls, reducing the risk of depression and anxiety may be preferred by meeting PA + ST + sleep or meeting PA+ sleep and meeting sleep in 24-HMGs. However, only a small proportion of adolescents met all recommendations, highlighting the need to promote and support adherence to these behaviours.

An Ultrathin Nonporous Polymer Separator Regulates Na Transfer Toward Dendrite-Free Sodium Storage Batteries.

Sodium storage batteries are one of the ever-increasing next-generation large-scale energy storage systems owing to the abundant resources and low cost. However, their viability is severely hampered by dendrite-related hazards on anodes. Herein, a novel ultrathin (8 µm) exterior-nonporous separator composed of honeycomb-structured fibers is prepared for homogeneous Na deposition and suppressed dendrite penetration. The unhindered ion transmission greatly benefits from honeycomb-structured fibers with huge electrolyte uptake (376.7%) and the polymer's inherent transport ability. Additionally, polar polymer chains consisting of polyethersulfone and polyvinylidene customize the highly aggregated solvation structure of electrolytes via substantial solvent immobilization, facilitating ion-conductivity-enhanced inorganic-rich solid-electrolyte interphase with remarkable interface endurance. With the reliable mechanical strength of the separator, the assembled sodium-ion full cell delivers significantly improved energy density and high safety, enabling stable operation under cutting and rolling. The as-prepared separator can further be generalized to lithium-based batteries for which apparent dendrite inhibition and cyclability are accessible and demonstrates its potential for practical application.

Natural borneol serves as an adjuvant agent to promote the cellular uptake of piperlongumine for improving its antiglioma efficacy.

Piperlongumine (PL) can selectively inhibit the proliferation of various cancer cells by increasing reactive oxygen species (ROS) level to cause a redox imbalance in cancer cells rather than in normal cells. However, the clinical application of PL is limited by its poor cellular uptake. Natural borneol (NB) is extracted from the fresh branches and leaves of Cinnamomum camphora (L.) Presl. with the purity of (+)-borneol no less than 96.0%. NB has been often used as an adjuvant agent to promote the cellular uptake of other drugs. This study aims to investigate the effect of NB on the cellular uptake of PL for improving its antiglioma efficacy and underlying mechanism. NB obviously promoted the cellular uptake of PL with a 1.3-fold increase in the maximum peak concentration and an earlier peak time of 30 min in C6 glioma cells. The cellular uptake of PL was enhanced by NB through down-regulating the expression levels of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). The combination of NB and PL significantly induced higher levels of ROS, which increased apoptosis and enhanced G2/M cycle arrest of C6 glioma cells, compared to PL alone administration. NB-enhanced antiglioma efficacy of PL without side effects was confirmed in tumor-bearing mice, which was attributed to the improved cellular uptake of PL. The distribution of PL in the tumor tissue of combined group increased 2.39 times than that of PL-treated group. We firstly report NB as an adjuvant agent to improve the antiglioma efficacy of PL in a ROS-dependent manner, which is due to the enhanced cellular uptake of PL by NB though down-regulating the expression levels of ABCB1 and ABCG2. This work provides a new strategy to promote the cellular uptake of PL with great potential for the treatment of glioma.

Plant Disease Resistance-Related Signaling Pathways: Recent Progress and Future Prospects.

Plant-pathogen interactions induce a signal transmission series that stimulates the plant's host defense system against pathogens and this, in turn, leads to disease resistance responses. Plant innate immunity mainly includes two lines of the defense system, called pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). There is extensive signal exchange and recognition in the process of triggering the plant immune signaling network. Plant messenger signaling molecules, such as calcium ions, reactive oxygen species, and nitric oxide, and plant hormone signaling molecules, such as salicylic acid, jasmonic acid, and ethylene, play key roles in inducing plant defense responses. In addition, heterotrimeric G proteins, the mitogen-activated protein kinase cascade, and non-coding RNAs (ncRNAs) play important roles in regulating disease resistance and the defense signal transduction network. This paper summarizes the status and progress in plant disease resistance and disease resistance signal transduction pathway research in recent years; discusses the complexities of, and interactions among, defense signal pathways; and forecasts future research prospects to provide new ideas for the prevention and control of plant diseases.