Knockdown of LncRNA-HAGLR restrains the viability and motility of pancreatic cancer via miR-625-5p/TAF15 axis in vitro and in vivo.

Dysregulation of long non-coding RNAs (lncRNAs) has been strongly involved to the development of pancreatic cancer (PC). However, the potential mechanisms by which lncRNA regulate PC development still need to be further explored. We attempted to elucidate the functional role and regulatory mechanism of lncRNA HAGLR on PC progression in vitro and vivo. RT-qPCR, Western blot, RNA pull-down, luciferase reporter assay, RNA immunoprecipitation assay, CCK-8 assay, EdU assay, flow cytometry, transwell assay and xenograft tumor experiment were performed in this study. We found that the expressions of HAGLR and TAF15 were increased in PC tissues and cells. HAGLR silencing restrained the PC cell growth and invasion, but induced cell apoptosis. Moreover, HAGLR targeted miR-625-5p to modulate the expression of TAF15. HAGLR overexpression partially eliminated the suppressive effect of TAF15 depletion on PC cell growth and the stimulative effect on apoptosis. In vivo assays showed that HAGLR knockdown inhibited PC cell growth by regulating the TAF15 expression. These findings suggest HAGLR could facilitate PC cell malignant behaviors through regulating the TAF15 expression, demonstrating that HAGLR might be a valuable target for the PC treatment.

Differentiated thyroid cancer and adverse pregnancy outcomes: a propensity score-matched retrospective cohort study.

Background: Differentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC. Methods: We conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes. Results: After the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)]. Conclusions: DTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.

Nitrogen-to-functionalized carbon atom transmutation of pyridine.

The targeted and selective replacement of a single atom in an aromatic system represents a powerful strategy for the rapid interconversion of molecular scaffolds. Herein, we report a pyridine-to-benzene transformation via nitrogen-to-carbon skeletal editing. This approach proceeds via a sequence of pyridine ring-opening, imine hydrolysis, olefination, electrocyclization, and aromatization to achieve the desired transmutation. The most notable features of this transformation are the ability to directly install a wide variety of versatile functional groups in the benzene scaffolding, including ester, ketone, amide, nitrile, and phosphate ester fragments, as well as the inclusion of meta-substituted pyridines which have thus far been elusive for related strategies.

Molecular characterization, spatio-temporal expression patterns of crtc2 gene and its immune roles in yellow catfish (Pelteobagrus fulvidraco).

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning.

Hematoxylin and eosin (H&E) whole slide images provide valuable information for predicting prognostic outcomes in colorectal cancer (CRC) patients. However, extracting prognostic indicators from pathological images is challenging due to the subtle complexities of phenotypic information. We trained a weakly supervised deep learning model on data from 640 CRC patients in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial dataset and validated it using data from 522 CRC patients in the cancer genome atlas (TCGA) dataset. We created the colorectal cancer risk score (CRCRS) to assess patient prognosis, visualized the pathological phenotype of the risk score using Grad-CAM, and employed multiomics data from the TCGA CRC cohort to investigate the potential biological mechanisms underlying the risk score. The overall survival analysis revealed that the CRCRS served as an independent prognostic indicator for both the PLCO cohort (p < 0.001) and the TCGA cohort (p < 0.001), with its predictive efficacy remaining unaffected by the clinical staging system. Additionally, satisfactory chemotherapeutic benefits were observed in stage II/III CRC patients with high CRCRS but not in those with low CRCRS. A pathomics nomogram constructed by integrating the CRCRS with the tumor-node-metastasis (TNM) staging system enhanced prognostic prediction accuracy compared with using the TNM staging system alone. Noteworthy features of the risk score were identified, such as immature tumor mesenchyme, disorganized gland structures, small clusters of cancer cells associated with unfavorable prognosis, and infiltrating inflammatory cells associated with favorable prognosis. The TCGA multiomics data revealed potential correlations between the CRCRS and the activation of energy production and metabolic pathways, the tumor immune microenvironment, and genetic mutations in APC, SMAD2, EEF1AKMT4, EPG5, and TANC1. In summary, our deep learning algorithm identified the CRCRS as a prognostic indicator in CRC, providing a significant approach for prognostic risk stratification and tailoring precise treatment strategies for individual patients.

Safety evaluation of extracorporeal shockwave lithotripsy for pancreatic stones: Experience based on a large chronic pancreatitis cohort.

BACKGROUND: The safety of extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and adverse events were not evaluated and classified within large sample population. This study aimed to evaluate the safety and classify the adverse events of P-ESWL based on a large sample cohort. METHODS: This is an observational study based on the large prospective chronic pancreatitis (CP) cohort. Patients with painful pancreatic stones over 5 mm who underwent P-ESWL between March 2011 and June 2018 at Shanghai Changhai Hospital were included. Adverse events after P-ESWL including complications and transient adverse events (TAEs) were recorded. Risk factors of adverse events were analyzed through univariable and multivariable logistics regression analysis. Sensitivity analysis was conducted to test the stability of the study. RESULTS: Totally 2,071 patients underwent 5,002 sessions of P-ESWL were included. The overall complication rate and TAEs rate after all P-ESWL procedures were 5.2% and 20.9%. The complications and TAEs rate decreased obviously within the first 6 sessions. Several independent risk factors for adverse events after P-ESWL were identified. Sensitivity analysis suggested the stability of the results. CONCLUSIONS: P-ESWL is a safe treatment for pancreatic stones. Multiple P-ESWL sessions did not increase the complications and TAEs rate. ClincialTrials.gov number, NCT05916547.

Remnant cholesterol is superior to other lipid-related parameters for the prediction of cardiometabolic disease risk in individuals with hypertension: The Kailuan study.

BACKGROUND: It is uncertain which lipid-related parameter is most suitable for predicting the risk of cardiometabolic disease (CMD) in individuals with hypertension. AIMS: To explore which lipid-related parameter is most suitable for predicting the risk of CMD. METHODS AND RESULTS: We studied 30,378 patients with hypertension who completed the 2006-2007 Kailuan health examination and followed up until December 31, 2021. In the constructed model, the utilities of lipid-related parameters for the prediction of CMD were compared using the C-index, NRI, and IDI. The best predictor (remnant cholesterol, RC) was identified and the participants were grouped according to RC quartile. Cox proportional hazard analysis was then used to evaluate the relationship between RC and the risk of CMD. During a median follow-up period of 14.7 years (IQR 5.3-15.1), 9502 (31.27 %) participants with hypertension developed CMD. The C-index, NRI, and IDI values for RC were higher than those for the other lipid parameters. After adjustment for multiple potential confounding factors, compared with the quartile (Q)1 RC group, the adjusted hazard ratios for CMD of the Q2-Q4 groups were 1.09 (1.03-1.16), 1.17 (1.11-1.24), and 1.25 (1.18-1.33) (P < 0.0001). Restrictive cubic spline analysis revealed dose-dependent relationships of lipid parameters with the risk of CMD. CONCLUSIONS: RC is superior to other lipid parameters for the prediction of the risk of CMD in individuals with hypertension. As the concentration of RC increases, the risk of CMD in such individuals also increases.

Rampant intraspecific variation of plastid genomes in Gentiana section Chondrophyllae.

Exploring the level of intraspecific diversity in taxa experienced radiation is helpful to understanding speciation and biodiversity assembly. Gentiana section Chondrophyllae sensu lato encompasses more than 180 species and occupies more a half of species in the genus. In this study, we collected samples across the range of three species (Gentiana aristata, G. crassuloides and G. haynaldii) in section Chondrophyllae s.l., and recovered the intra-species variation by comparing with closely related taxon. Using 25 newly sequenced plastid genomes together with previously published data, we compared structural differences, quantified the variations in plastome size, and measured nucleotide diversity in various regions. Our results showed that the plastome size variation in the three Chondrophyllae species ranged from 285 to 628 bp, and the size variation in LSC, IR and SSC ranged from 236 to 898 bp, 52 to 393 bp and 135 to 356 bp, respectively. Nucleotide diversity of plastome or any of the four regions was much higher than the control species. The average nucleotide diversity in plastomes of the three species ranged from 0.0010 to 0.0023 in protein coding genes, and from 0.0023 to 0.0061 in intergenic regions. More repeat sequence variations were detected within the three Chondrophyllae species than the control species. Various plastid sequence matrixes resulted in different backbone topology in two target species, showed uncertainty in phylogenetic relationship based inference. In conclusion, our results recovered that species of G. section Chondrophyllae s.l. has high intraspecific plastome variation, and provided insights into the radiation in this speciose lineage.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

Chromosome-level genome assemblies of vulnerable male and female elongate loach (Leptobotia elongata).

Endemic to the upper and middle reaches of the Yangtze River in China, elongate loach (Leptobotia elongata) has become a vulnerable species mainly due to overfishing and habitat destruction. Thus far, no genome data of this species are reported. As a result, lacking of such genomic information has restricted practical conservation and utilization of this economic fish. Here, we constructed chromosome-level genome assemblies for both male and female elongate loach by integration of MGI, PacBio HiFi and Hi-C sequencing technologies. Two primary genome assemblies (586-Mb and 589-Mb) were obtained for female and male fishes, respectively. Indeed, 98.22% and 98.61% of the contig sequences were anchored onto 25 chromosomes, with identification of 26.22% and 25.92% repeat contents in both assembled genomes. Meanwhile, a total of 25,215 and 25,253 protein-coding genes were annotated, of which 97.41% and 98.8% could be predicted with functions. Taken together, our genome data presented here provide a valuable genomic resource for in-depth evolutionary and functional research, as well as molecular breeding and conservation of this economic fish species.

Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study.

BACKGROUND: A high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure. METHODS: We performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006-2007, 2008-2009, and 2010-2011 and had no history of heart failure or cancer before the third wave survey (2010-2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006-2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups. RESULTS: From 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98-8.07), moderate low-stable (n = 29,435; range, 8.60-8.65), moderate high-stable (n = 11,262; range, 9.31-9.30), and elevated-stable (n = 1,898; range, 10.04-10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group. CONCLUSIONS: Higher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.

Association between the atherogenic index of plasma trajectory and risk of heart failure among hypertensive patients: a prospective cohort study.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular events. However, it remains unclear whether hypertensive patients with long-term high AIP levels are at greater risk of developing heart failure (HF). Therefore, the aim of this study was to investigate the association between AIP trajectory and the incidence of HF in hypertensive patients. METHODS: This prospective study included 22,201 hypertensive patients from the Kailuan Study who underwent three waves of surveys between 2006 and 2010. Participants were free of HF or cancer before or during 2010. The AIP was calculated as the logarithmic conversion ratio of triglycerides to high-density lipoprotein cholesterol. Latent mixed modeling was employed to identify different trajectory patterns for AIP during the exposure period (2006-2010). Cox proportional hazard models were then used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF among different trajectory groups. RESULTS: Four distinct trajectory patterns were identified through latent mixture modeling analysis: low-stable group (n = 3,373; range, -0.82 to -0.70), moderate-low stable group (n = 12,700; range, -0.12 to -0.09), moderate-high stable group (n = 5,313; range, 0.53 to 0.58), and elevated-increasing group (n = 815; range, 1.22 to 1.56). During a median follow-up period of 9.98 years, a total of 822 hypertensive participants experienced HF. After adjusting for potential confounding factors, compared with those in the low-stable group, the HR and corresponding CI for incident HF in the elevated-increasing group, moderate-high stable group, and moderate-low stable group were estimated to be 1.79 (1.21,2.66), 1.49 (1.17,1.91), and 1.27 (1.02,1.58), respectively. These findings remained consistent across subgroup analyses and sensitivity analyses. CONCLUSION: Prolonged elevation of AIP in hypertensive patients is significantly associated with an increased risk of HF. This finding suggests that regular monitoring of AIP could aid in identifying individuals at a heightened risk of HF within the hypertensive population.

Nonenzymatic Sequestering of Formaldehyde into the Antibiotic Methylene-Bridged Dimer Phaeochromycin F by Streptomyces sp. OUCMDZ-4982 as a Possible Multipronged Chemical Defense Mechanism.

Metabolites with high chemical reactivity serve important roles in chemical defenses of organisms. Formaldehyde, as a simple and highly reactive small molecule, can be produced by microorganisms, plants, and animals. Its toxicity is well known, but information about its other biological functions remains scarce. Here, we report that the natural product SEK34b produced by Streptomyces species can react nonenzymatically with formaldehyde in water to yield the methylene-bridged dimer phaeochromycin F. This process can eliminate the toxic substance formaldehyde produced by Staphylococcus aureus. Furthermore, there is a substantial inhibitory impact of phaeochromycin F on S. aureus. We hypothesize that these constitute an integrated system of defense and attack of Streptomyces species against competitors. Our study indicates that formaldehyde can react with vancomycin and tigecycline under mild conditions to generate the derivatives bearing an imidazolidin-4-one moiety, thereby reducing the antibacterial activity of these antibiotics. These data provide a possible chemical interaction mechanism of bacteria involving the nonenzymatic reactions of formaldehyde with highly reactive natural products.

Electrically Induced Crystal Field Distortion in a Ferroelectric Perovskite Revealed by Electron Paramagnetic Resonance.

The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.

Orthogonal magnetic orbitals in high spin Cu-VO units: structure, magnetism and EPR study of anisotropic heterometallic complexes.

Molecular-based magnetic materials are expected to serve as building blocks for quantum bits. To realize high-dimensional Hilbert space and addressability, we constructed anisotropic multi-level systems based on CuII and VIV with orthogonal magnetic orbitals. The crystal structures and intramolecular magnetic couplings of four CuIIVOII complexes [{CuVO(appen)2}2], [{CuVO(fhma)2EDA}2], [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n are characterized. Due to the orthogonal magnetic orbitals of CuII and VIV, the Cu-V pairs in the four complexes have strong ferromagnetic couplings, and the coupling strength is linearly related to the dihedral angle between the two equatorial planes of the two coordination polyhedra. Because of the triplet ground state, the system can be described by an effective Hamiltonian model consisting of two S = 1 spins coupled together. The anisotropy parameters of [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n were obtained by the simulation of X-band continuous wave electron paramagnetic resonance (cw-EPR) spectra, confirming that both complexes have zero-field splitting addressable on the relative energy scale. The results indicate that constructing multi-centre complexes based on orthogonal magnetic orbitals is a promising strategy for designing multidimensional quantum bits.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

Enhancing corannulene chemiluminescence, electrochemiluminescence and photoluminescence by means of an azabora-helicene to slow down its bowl inversion.

Aromatic system extension of corannulene (Cor) is a synthetic challenge to access non-planar polyaromatic hydrocarbons (PAHs). Herein, we report the design and synthesis of azaborahelicene corannulene 1 through hybridization of an azabora[5] helical structure and subsequent luminescence studies. Significant enhancement in chemiluminescence (CL), electroluminescence (ECL) and photoluminescence (PL) is achieved compared to those of pristine Cor. Specifically, hybrid 1 shows a notable augmentation in absolute luminescence quantum efficiencies: 25-fold for CL, up to 23-fold for ECL with BPO as a coreactant, and 30-fold for PL, respectively, compared to those of pristine Cor. Intriguingly, the blue light emission observed in all three luminescence types suggests the presence of a single excited state. As revealed by variable-temperature (VT) 1H NMR experiments, the bowl inversion frequency apparently decelerates by the steric effect of the helix motif in 1, which could contribute to the enhanced luminescent properties by reducing excited energy losses non-radiatively through fewer molecular motions; these enhanced luminescence observations could be categorized alongside the aggregation induced emission (AIE) and crystallization-induced emission (CIE) phenomena. This work not only provides fundamental insights into improved luminescence quantum efficiencies via strategic modulation of the molecular structure and geometry, but the work also reveals Cor's inherent potential to build efficient blue-light emitting materials and devices.

Neratinib stimulates senescence of mammary cancer cells by reducing the levels of SIRT1.

Neratinib, a typical small-molecule, pan-human tyrosine kinase inhibitor (TKI), has been licensed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the underlying pharmacological mechanism is still unknown. In the current study, we report a novel function of Neratinib by showing that its treatment stimulates senescence of the mammary cancer AU565 cells. Our results demonstrate that Neratinib induces mitochondrial injury by increasing mitochondrial reactive oxygen species (ROS) and reducing intracellular adenosine triphosphate (ATP). Also, we found that Neratinib induced DNA damage by increasing the levels of 8-Hydroxy-desoxyguanosine (8-OHdG) and γH2AX in AU565 cells. Additionally, Neratinib reduced the levels of telomerase activity after 7 and 14 days incubation. Importantly, the senescence-associated-ß-galactosidase (SA-ß-Gal) assay revealed that Neratinib stimulated senescence of AU565 cells. Neratinib decreased the gene levels of human telomerase reverse transcriptase (hTERT) but increased those of telomeric repeat-binding factor 2 (TERF2) in AU565 cells. Further study displayed that Neratinib upregulated the expression of K382 acetylation of p53 (ac-K382) and p21 but reduced the levels of sirtuin-1 (SIRT1). However, overexpression of SIRT1 abolished the effects of Neratinib in cellular senescence. These findings provide strong preclinical evidence of Neratinib's treatment of breast cancer.