Senescent cells promote breast cancer cells motility by secreting GM-CSF and bFGF that activate the JNK signaling pathway.

BACKGROUND: Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis. METHODS: In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility. RESULTS: Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models. CONCLUSIONS: These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.

Phenome-wide association study of population-differentiating genetic variants around gene ACSL1.

Background and objectives: Demographic dynamics and natural selection during human evolution shaped the present-day patterns of genetic variations, and geographically varying genetic factors contribute to different disease prevalences across human populations. This study aims to evaluate the presence of positive selection on the gene encoding long-chain fatty acyl-CoA synthetase 1 (ACSL1) and the phenotypic impacts of population-differentiating genetic variants around this gene. Methodology: Three types of statistical tests for positive selection, based on site frequency spectrum, extended haplotype homozygosity and population differentiation, were applied to the whole-genome sequencing data from the 1000 Genomes Project. A phenome-wide association study of ACSL1 was performed with published genome-wide association studies (GWAS) and transcriptome-wide association studies, including phenome-wide studies in biobanks. Results: Genetic variants associated with ACSL1 expression in various tissues exhibit geographically varying allele frequencies. Three types of statistical tests consistently supported the presence of positive selection on the coding and regulatory regions of ACSL1 in African, European, South Asian and East Asian populations. A phenome-wide association study of ACSL1 revealed associations with type 2 diabetes, blood glucose, age at menopause, mean platelet volume and mean reticulocyte volume. The top allele associated with lower diabetes risk has the highest frequency in European populations, whereas the top allele associated with later menopause has the highest frequency in African populations. Conclusions and implications: Positive selection on ACSL1 resulted in geographically varying genetic variants, which may contribute to differential phenotypes across human populations, including type 2 diabetes and age at menopause.

Concentration-Dependent Photoluminescence of Carbon Quantum Dots Useable in LED.

We synthesized carbon quantum dots (CQDs) using a solvothermal method with o-phenylenediamine as the carbon and nitrogen source. The sample was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. When we continued the optical characterization of the CQDs, we were surprised to discover that the colors of the synthesized CQDs changed with the dilution of the original solution. In addition, the photoluminescence (PL) of CQDs under 405 nm continuous wave laser excitation was also investigated. It was found that CQDs with different concentrations exhibited different PL spectra. In order to explain the mechanism of different PL spectra, chemical characterization of the CQDs at different concentrations was performed again, revealing that the color change is independent of particle size and surface functional groups. Systematic optical characterization and theoretical analysis indicate that this color change results from the interparticle distance. Furthermore, we investigated the PL lifetimes of CQDs using time-resolved PL measurements and found that the PL lifetime values change with the concentration of CQDs, which is attributed to nonradiative transitions. Finally, we fabricated warm white-light-emitting diodes with CQDs that are proportionally adjusted in concentrations. The investigation developed a simple and effective method to tune the color of CQDs by adjusting the concentration through dilution of the original solution, which provides a new approach for the preparation and regulation of multicolor CQDs.

A compact solid-state high repetition rate trigger based on a spiral generator.

The trigger generator made with a spiral generator (SG) has the advantages of light weight, compact structure, and low cost and has promising applications in the pulsed power field. This paper introduces a compact solid-state high-voltage pulse trigger system based on an improved SG, which has improved repetition rate and lowered the demands for semiconductor switches' maximum current and current rise rate when compared with previous studies. The improvement is achieved by winding outward an additional layer of the passive layer and low-voltage metal strip, which realizes a significant reduction of the peak current and current rise rate of the discharge switch. The final dimension of the trigger is 25 × 10 × 10 cm3, excluding the power supply. An experiment carried out in single shot mode shows that the peak value of the output pulse can reach 50 kV with a leading edge of 57 ns. Repetitive experiments were carried out up to 1 kHz, with the peak voltage of the output pulse being 30.5 kV, the leading edge being 48 ns, and the jitter being 0.84 ns. Finally, the generator is used to trigger a gas switch, and it works stably and reliably.

N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides.

Both the pyrroloindoline core and N-CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N-CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N-CF3 moiety with commercially available reagents N-halosuccinimide and Et3N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N-CF3-pyrroloindolines.

Lactic acid bacteria sequential fermentation improves viable counts and quality of fermented apple juice via generating two logarithmic phases.

This study investigated the impact of lactic acid bacteria (LAB) sequential fermentation on viable counts and apple juice quality. The optimal fermentation conditions were obtained by a step-by-step optimization process, including pH 4.5, temperature 37 °C, the second inoculation time 16 h, total fermentation time 40 h and fermentation sequence (first 21,805 + 21,828, second 20,241). Under the optimal conditions, sequential fermentation allowed LAB to experience two logarithmic phases, increasing viable counts to 1.38 × 108 CFU/mL, exceeding simultaneous fermentation for 24 h and 40 h by 4.10 × 107 CFU/mL and 5.40 × 107 CFU/mL, respectively. This process enhanced sugar utilization, yielding more lactic acid and polyphenols. Furthermore, sequential fermentation improved DPPH (71.71 %) and ABTS (84.79 %) scavenging rates, and enriched volatile compounds, particularly beta-Damascenone, potentially contributing to floral and richer apple flavor. Sequential fermentation also achieved optimal sensory acceptability. This study proposes a novel strategy for high-density LAB fermentation to produce high-quality apple juice.

Oral responsive delivery systems for probiotics targeting the intestinal tract.

The increasing prevalence of health issues, driven by sedentary lifestyles and unhealthy diets in modern society, has led to a growing demand for natural dietary supplements to support overall health and well-being. Probiotic dietary supplements have garnered widespread recognition for their potential health benefits. However, their efficacy is often hindered by the hostile conditions of the gastrointestinal tract. To surmount this challenge, biomaterial-based microencapsulation techniques have been extensively employed to shield probiotics from the harsh environments of stomach acid and bile salts, facilitating their precise delivery to the colon for optimal nutritional effects. With consideration of the distinctive gastrointestinal tract milieu, probiotic delivery systems have been categorized into pH-responsive release, enzyme-responsive release, redox-responsive release and pressure-triggered release systems. These responsive delivery systems have not only demonstrated improved probiotic survival rates in the stomach, but also successful release in the intestines, facilitating enhanced adhesion and colonization of probiotics within the gut. Consequently, these responsive delivery systems contribute to the effectiveness of probiotic supplementation in intervening with gastrointestinal diseases. This review provides a comprehensive overview of the diverse oral responsive delivery systems tailored for probiotics targeting the intestinal tract. Furthermore, the review critically examines the limitations and future prospects of these approaches. This review offers valuable guidance for the effective delivery of probiotics to the intestinal tract, enhancing the potential of probiotics as dietary supplements to promote gastrointestinal health and well-being. © 2024 Society of Chemical Industry.

AAV9-mediated CIRP gene transfer protects against cardiac dysfunction and remodelling in a rat model of myocardial infarction.

Cold-inducible RNA-binding protein (CIRP) is a stress-response protein that has been shown to protect cardiomyocytes under a variety of stress conditions from apoptosis. Our recent study showed that the expression of CIRP protein in the heart was downregulated in patients with heart failure and an animal model of ischaemia heart failure, but its role in heart failure is still unknown. The present study aimed at evaluating the potential role of CIRP on the heart in an animal model of myocardial infarction (MI). MI model of rats was induced by the ligation of the left coronary artery. CIRP overexpression was mediated by direct intracardiac injection of adeno-associated virus serotype 9 (AAV9) vectors carrying a CIRP coding sequence with a cardiac-specific promoter before the induction of the MI model. The effects of CIRP elevation on MI-induced heart were analysed through echocardiographic, pathological and molecular analysis. Our results showed that the intracardiac injection of AAV9 successfully mediated CIRP upregulation in cardiomyocytes. Upregulation of cardiac CIRP prevented MI-induced cardiac dysfunction and adverse remodelling, coupled with the reduced inflammatory response in the heart. Collectively, these results demonstrated the beneficial role of intracellular CIRP on the heart and suggest that CIRP may be a therapeutic target in ischaemic heart disease.

The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer.

Zeb1, a key epithelial-mesenchymal transition (EMT) regulator, has recently been found to be involved in M2 macrophage polarization in the tumor immune microenvironment, thereby promoting tumor development. However, the underlying mechanism of Zeb1-induced M2 macrophage polarization remains largely unexplored. To identify the potential role of Zeb1 in remodeling the tumor immune microenvironment in breast cancer, we crossed the floxed Zeb1 allele homozygously into PyMT mice to generate PyMT;Zeb1cKO (MMTV-Cre;PyMT;Zeb1fl/fl ) mice. We found that the recruitment of M2-type tumor-associated macrophages (TAMs) was significantly reduced in tumors from PyMT;Zeb1cKO mice, and their tumor suppressive effects were weakened. Mechanistically, Zeb1 played a crucial role in transcriptionally promoting the production of Cxcl1 in tumor cells. In turn, Cxcl1 activated the Cxcr2-Jak-Stat3 pathway to induce M2 polarization of TAMs in a paracrine manner, which eventually led to T-cell inactivation and impaired the antitumor immune response in breast cancer. Our results collectively revealed an important role of Zeb1 in remodeling the tumor microenvironment, suggesting a novel therapeutic intervention for the treatment of advanced breast cancer.

[Corrigendum] BMP­6 inhibits the metastasis of MDA­MB­231 breast cancer cells by regulating MMP­1 expression.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the pair of data panels shown for the invasion experiments in Fig. 2D on p. 1826 were strikingly similar to the 'Control' data panels shown for the Transwell assay experiments in Fig. 5C on p. 1829. After having re­examined their original data files, the authors realized that Fig. 5C had been inadvertently assembled incorrectly. The revised version of Fig. 5, now featuring the correct data for the '231­control/Control' and '231­BMP­6/Control' experiments in Fig. 5C, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 35: 1823­1830, 2016; DOI: 10.3892/or.2015.4540].

NEU4-mediated desialylation enhances the activation of the oncogenic receptors for the dissemination of ovarian carcinoma.

Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveal a functionally important glycosite on EGFR for its abnormal activation in cancer.

Responses of birds to observers holding popguns: Hunting history influences escape behavior of urban birds.

Human activities affect bird behavior both directly and indirectly. Birds constantly regulate their behavior in response to human disturbance. Gun hunting, a major directional disturbance, puts enormous selection pressure on birds. In China, gun bans have been in place for nearly 30 years, and little hunting using guns occurs in modern cities. However, little attention has been paid to whether a history of hunting still affects the behavioral adaptations of urban birds. In this study, we compared the flight initiation distance (FID) of the Eurasian tree sparrow Passer montanus, Azure-winged magpie Cyanopica cyanus, Common hoopoe Upupa epops and Eurasian magpie Pica pica in the presence of observers with or without popguns. The Eurasian tree sparrow, Azure-winged magpie, and Eurasian magpie effectively recognized the difference between the observers, and perceived the armed observer as a greater threat, exhibiting earlier escape behavior, but this phenomenon was not found in the Common hoopoe. The different expressions in FID of experimental bird species in China cities may be affected by the different levels of recognition of hunting pressure due to different hunting histories.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality.

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols under different reaction conditions. Using this strategy, two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities (up to 99% yield, 95:5 er, >95:5 dr). Moreover, theoretical calculations were performed on the key transition states leading to different stereoisomers, which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions. More importantly, these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity, which demonstrated their potential applications. This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles, but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality.

Inhibition of ferroptosis attenuate lipopolysaccharide-induced early pregnancy loss by protecting against decidual damage of stromal cells.

Endometrial decidualization is critical for successful embryo implantation. Dysregulation of the immune microenvironment can disrupt normal decidualization processes, potentially resulting in early pregnancy loss. Ferroptosis, a form of cell death dependent on iron and lipid hydroperoxides, is closely associated with inflammation. In this study, we developed an inflammatory early pregnancy loss model to elucidate the mechanisms of decidual damage induced by lipopolysaccharide (LPS) and to assess whether ferroptosis contributes to LPS-induced early pregnancy loss. Through in vivo experiments, we observed that embryo implantation was significantly inhibited and endometrial decidualization was impaired during LPS-induced early pregnancy loss. LPS exposure resulted in abnormal mitochondrial morphology, reduced antioxidant capacity, accumulation of reactive oxygen species (ROS) and disruptions in iron metabolism during decidualization in mouse endometrial stromal cells (mESCs). The administration of ferroptosis inhibitors, specifically ferrostatin-1 (Fer-1) and deferoxamine (DFO), effectively reversed embryo loss and mitigated the decidual damage associated with LPS-induced early pregnancy loss. Fer-1 and DFO exhibited resistance to ferroptosis during decidualization by modulating the antioxidant system and iron metabolism in mESCs, respectively. Our findings indicate that the inhibition of ferroptosis can confer protective effects against decidual damage during LPS-induced early pregnancy loss in mice.

Bioorthogonal Chemistry: Enzyme Immune and Protein Capture for Enhanced LC-MS Bioanalysis.

Immunocapture liquid chromatography-mass spectrometry (IC-LC-MS) bioanalysis has become an indispensable technique across various scientific disciplines, ranging from drug discovery to clinical diagnostics. While traditional immunocapture techniques have proven to be effective, they often encounter limitations in sensitivity, specificity, and compatibility with MS analysis. Chemoenzymatic immunocapture and protein capture (IPC) offers a promising solution, combining the high specificity of antibodies or proteins with the versatility of enzymatic and chemical modifications. This Review explores the foundational principles of chemoenzymatic IPC and examines various modification strategies including bioorthogonal click-chemistry, enzymatic-tagging, and HaloTag/CLIP-tag. Recent advancements in chemoenzymatic IPC techniques have significantly expanded their applicability to a diverse range of biomolecules including small molecules, peptides, RNAs, and proteins. This Review focuses on improvements in analytical performance achieved through these innovative approaches. Moreover, we discuss the broad applications of chemoenzymatic immunocapture in drug discovery, clinical diagnostics, and environmental analysis and explore its potential for future advancements in bioanalysis. We propose a novel solid-phase chemoenzymatic IPC assay (SCEIA) that effectively utilizes bioorthogonal click chemistry and chemoenzymatic approaches for efficient IPC and target analyte release. In summary, chemoenzymatic IPC represents a transformative paradigm shift in IC-LC-MS bioanalysis. By overcoming the limitations of traditional IPC techniques, this approach paves the way for more robust, sensitive, and versatile analytical workflows.

Exploring the unique association between high-density lipoprotein cholesterol and vitamin D deficiency in adults aged 20-59: findings based on the NHANES database.

BACKGROUND: Serum lipids are highly heritable and play an important role in cardiovascular and metabolic health. However, the relationship between high-density lipoprotein cholesterol (HDL-C) and serum 25-hydroxyvitamin D [25(OH)D] levels is unclear. This study aims to explore the association between serum 25(OH)D levels and HDL-C in adults aged 20-59. METHODS: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression was used to assess the relationship between HDL-C and serum 25(OH)D, with further analysis using smooth spline fitting and generalized additive models. RESULTS: A total of 28,084 adults were included in the study. After adjusting for multiple variables, we found a significant positive correlation between HDL-C and serum 25(OH)D levels (ß = 8.3, 95% CI: 7.24-9.35, p < 0.001). Stratified subgroup analysis by gender showed that females consistently exhibited a positive correlation (ß = 10.12, 95% CI: 9.07-11.18, p < 0.001), while males demonstrated an inverted U-shaped relationship between HDL-C and serum 25(OH)D. CONCLUSION: In the population aged 20-59, HDL-C levels are significantly associated with serum 25(OH)D levels. Clinically, simultaneous monitoring of HDL-C and vitamin D is recommended to better assess and manage cardiovascular health. Increasing vitamin D intake should be considered, especially for males with low HDL-C levels, to prevent related health issues.

Effect of Flammulina velutipes Soluble Dietary Fiber on Dough Processing Characteristics and Micro-Fermented Dried Noodles Quality Properties.

Our research focused on the integration of Flammulina velutipes soluble dietary fiber (Fv-SDF) into wheat flour during the production of dried noodles, delving into the impact of different addition ratios of Fv-SDF on both dough processing characteristics and the quality of the micro-fermented dried noodles. The viscometric and thermodynamic analyses revealed that Fv-SDF notably improved the thermal stability of the mix powder, reduced viscosity, and delayed starch aging. Additionally, Fv-SDF elevated the gelatinization temperature and enthalpy value of the blend. Farinograph Properties and dynamic rheology properties further indicated that Fv-SDF improved dough formation time, stability time, powder quality index, and viscoelasticity. Notably, at a 10% Fv-SDF addition, the noodles achieved the highest sensory score (92) and water absorption rate (148%), while maintaining a lower dry matter loss rate (5.2%) and optimal cooking time (142 s). Gas chromatography-ion mobility spectrometry (GC-IMS) analysis showed that 67 volatile substances were detected, and the contents of furfural, 1-hydroxy-2-acetone, propionic acid, and 3-methylbutyraldehyde were higher in the Fv-SDF 10% group. These 10% Fv-SDF micro-fermented noodles were not only nutritionally enhanced, but also had a unique flavor. This study provides a valuable theoretical basis for the industrial application of F. velutipes and the development of high-quality dried noodles rich in Fv-SDF.

A review of intact glycopeptide enrichment and glycan separation through hydrophilic interaction liquid chromatography stationary phase materials.

Protein glycosylation, one of the most important biologically relevant post-translational modifications for biomarker discovery, faces analytical challenges due to heterogeneous glycosite, diverse glycans, and mass spectrometry limitations. Glycopeptide enrichment by removing abundant hydrophobic peptides helps overcome some of these obstacles. Hydrophilic interaction liquid chromatography (HILIC), known for its selectivity, glycan separations, intact glycopeptide enrichment, and compatibility with mass spectrometry, has seen recent advancements in stationary phases like Amide-80, glycoHILIC, amino acids or peptides for improved HILIC-based glycopeptide analysis. Utilization of these materials can improve glycopeptide enrichment through solid-phase extraction and separation via high-performance liquid chromatography. Additionally, using glycopeptides themselves to modify HILIC stationary phases holds promise for improving selectivity and sensitivity in glycosylation analysis. Additionally, HILIC has capability to assess the information about glycosites and structural information of glycans. This review summarizes recent breakthroughs in HILIC stationary materials, highlighting their impact on glycopeptide analysis. Ongoing research on advanced materials continues to refine HILIC's performance, solidifying its value as a tool for exploring protein glycosylation.