Bilateral Embedded Anchoring via Tailored Polymer Brush for Large-Area Air-processed Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

Myocardial Bridging Increases the Risk of Adverse Cardiovascular Events in Patients without Coronary Atherosclerosis.

Background: Myocardial bridging (MB) is a congenital coronary anomaly and an important cause of chest pain. The long-term effects of MB on cardiovascular events remain elusive. Methods: We used the National Health Insurance Research Database of Taiwan to conduct an analysis. All patients who had undergone coronary angiography were considered for inclusion. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. Results: We identified 10,749 patients from 2008 to 2018 and matched them with an equal number of controls by propensity-score matching. The mean follow-up period was 5.78 years. In patients without coronary artery disease, MB increased the risk of the composite endpoint (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.44-1.72, p < 0.001), which was driven by increased risks of nonfatal myocardial infarction and cardiovascular death. In patients with significant coronary artery disease, MB did not increase the risk of major adverse cardiovascular events. MB was identical to insignificant coronary artery disease from the viewpoint of clinical outcomes. Conclusions: The presence of MB significantly increases cardiovascular risks in patients with normal coronary vessels. Atherosclerotic coronary artery disease mitigates the effect of MB on cardiovascular outcomes. MB can be considered an insignificant coronary artery disease equivalent.

Development of a "Signal-On" Fluorescent Aptasensor for Highly Selective and Sensitive Detection of ZEN in Cereal Products Using Nitrogen-Doped Carbon Dots Based on the Inner Filter Effect.

This study aimed to develop a novel fluorescent aptasensor for the quantitative detection of zearalenone (ZEN), addressing the limitations of conventional detection techniques in terms of speed, sensitivity, and ease of use. Nitrogen-doped carbon dots (N-CDs) were synthesized via the hydrothermal method, resulting in spherical particles with a diameter of 3.25 nm. These N-CDs demonstrated high water solubility and emitted a bright blue light at 440 nm when excited at 355 nm. The fluorescence of N-CDs was quenched by dispersed gold nanoparticles (AuNPs) through the inner filter effect, while aggregated AuNPs induced by NaCl did not affect the fluorescence of N-CDs. The aptamer could protect AuNPs from NaCl-induced aggregation, but the presence of ZEN weakened this protective effect. Based on this principle, optimal conditions for ZEN detection included 57 mM NaCl, 12.5 nM aptamer concentration, incubation of AuNPs with NaCl for 15 min in Tris-EDTA(TE) buffer, and incubation of aptamer with ZEN and NaCl for 30 min. Under these optimized conditions, the "signal-on" fluorescent aptasensor for ZEN detection showed a linear range of 0.25 to 200 ng/mL with a low detection limit of 0.0875 ng/mL. Furthermore, the developed aptasensor exhibited excellent specificity and could rapidly detect ZEN in corn flour samples or corn oil, achieving satisfactory recovery rates ranging from 84.7% to 108.6%. Therefore, this study presents an economical, convenient, sensitive, and rapid method for accurately quantifying ZEN in cereal products.

PBI derivatives/surfactant-based fluorescent ensembles: Sensing of multiple aminoglycoside antibiotics and interaction mechanism studies.

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

[Damage and changes in expression of autophagy related factors LC3 and p62 of condylar cartilage in fluorosis mouse].

PURPOSE: To study the damage and the expression of LC3 and p62 of condylar cartilage in fluorosis mouse. METHODS: Thirty 4-week-old male C57BL/6 mice were randomly divided into control group and the experimental group with 15 animals in each group. The control group received regular drinking water and the experimental group received a fluoride concentration of 75 mg/L drinking water for 8 weeks. The structure of condylar cartilage was observed through modified safranine O-fast green FCF cartilage stain kit. Immunohistochemistry was used to detect the expression of MMP-13, type Ⅱ collagen and LC3 and p62. Two-way analysis of variance test was conducted for analysis of semi-quantitative results of immunohistochemistry using SPSS 22.0 software package. RESULTS: Compared with the control group, the fibrocartilage layer of the experimental group became thinner, the condrocytes were smaller, and the staining became deeper.Immunohistochemistry results showed that the expression of MMP-13 and LC3 increased; the expression of type Ⅱ collagen and p62 decreased in the experimental group. CONCLUSIONS: There was degeneration of the condylar cartilage and autophagy in mice with drinking water containing 75 mg/L fluoride.

Quantum gate control of polar molecules with machine learning.

We propose a scheme for achieving basic quantum gates using ultracold polar molecules in pendular states. The qubits are encoded in the YbF molecules trapped in an electric field with a certain gradient and coupled by the dipole-dipole interaction. The time-dependent control sequences consisting of multiple pulses are considered to interact with the pendular qubits. To achieve high-fidelity quantum gates, we map the control problem for the coupled molecular system into a Markov decision process and deal with it using the techniques of deep reinforcement learning (DRL). By training the agents over multiple episodes, the optimal control pulse sequences for the two-qubit gates of NOT, controlled NOT, and Hadamard are discovered with high fidelities. Moreover, the population dynamics of YbF molecules driven by the discovered gate sequences are analyzed in detail. Furthermore, by combining the optimal gate sequences, we successfully simulate the quantum circuit for entanglement. Our findings could offer new insights into efficiently controlling molecular systems for practical molecule-based quantum computing using DRL.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.

Evaluating local plant species for effective fall armyworm management strategies in Taiwan.

BACKGROUND: The emergence of Spodoptera frugiperda (fall armyworm; FAW) in the world has raised concerns regarding its impact on crop production, particularly on corn and sorghum. While chemical control and Bt crops have been effective in managing FAW damage, the development of pesticide-resistant and Bt-resistant strains necessitates alternative control methods. The push-pull farming system has gained attention, but direct utilization of African plant species in Taiwan faces challenges due to invasive potential and climatic disparities. Therefore, identifying and evaluating suitable local plant species, such as Napier grass (Pennisetum purpureum), Desmodium species, and signal grass (Brachiaria brizantha), is crucial for implementing effective FAW management strategies in Taiwan. RESULTS: In screening fifty Napier grass germplasms, all demonstrated an antibiotic effect, reducing leaf consumption compared to corn. Notably, thirty-five germplasms exhibited robust antibiotic traits, decreasing FAW consumption and increasing mortality rates. Three Napier grass germplasms also attracted more female moths for oviposition. Further evaluation of selected Napier grass germplasms and signal grass demonstrated efficacy in reducing FAW larval weight and survival duration. Additionally, Desmodium species, particularly D. uncinatum, showed promising toxicity against FAW larvae. CONCLUSION: Our findings support the effectiveness of selected Napier grass germplasms and signal grass as pull plants, and highlight the potential of D. uncinatum as a push plant in FAW management strategies in Taiwan.

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia.

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

The Quantitative Evaluation of Automatic Segmentation in Lumbar Magnetic Resonance Images.

OBJECTIVE: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. METHODS: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net's segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. RESULTS: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. CONCLUSION: Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

Current status and needs of in-service training for psychiatric nurses in 24 provinces of China: a cross-sectional survey.

Aim: To investigate the current situation and need for post-competence training for psychiatric nurses in China and provide a reference for the development of training programs for psychiatric nurses. Design: A cross-sectional design. Methods: A cross-sectional study was conducted from August to October 2023 with 435 psychiatric nurses from 34 hospitals in 24 provinces of mainland China. A self-administered questionnaire was used for data collection. Descriptive statistics, non-parametric tests, and chi-square tests were used for data analysis. Results: The training content for psychiatric nurses is extensive, and the training load is large. Psychiatric nurses have high training demands for first aid knowledge, emergency handling ability, and anti-riot skills. Nurses with different years of experience have different training needs. The training needs of psychiatric nurses in specialized and general hospitals also different. Conclusion: The training status of psychiatric nurses is not consistent with the demand. Managers should combine this with psychiatric nurses' own work needs to develop practical and effective training programs.

Determinants of parental demand of human papillomavirus vaccination for adolescent daughters in China: Contingent valuation survey.

BACKGROUND: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees. OBJECTIVE: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China. METHODS: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay. RESULTS: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels. CONCLUSIONS: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups.

Closed-Loop Recyclable Poly(ester-disulfide)s for Potential Alternatives to Engineering Plastic.

Facile fabrication, low material complexity and closed-loop recycling are essential for polymer plastics to alter their linear product economy towards a cradle-to-cradle one. Covalent adaptable networks (CANs) are one way to achieve that, which intrinsically exhibit decent mechanical properties of the thermosets but could also be easily recycled like the thermoplastics. In this work, we introduce rigid ester structural motifs into dynamic poly(disulfide)s to form a series of dual polymer networks. Owning to the coherence of soft/rigid segments and the reversible sacrificial crosslinking, they exhibit tailorable properties and good resistance towards different chemicals. Their closed-loop recycling is achieved via mild solvolysis, maintaining materials' mechanical integrities. It offers a solution as a sustainable replacement for engineering plastics which are massively under production but hard to be recycled.

GLP-1 receptor agonists' impact on cardio-renal outcomes and mortality in T2D with acute kidney disease.

Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.

[Benefit-risk assessment of three oral Chinese patent medicines for activating blood and eliminating mass in treating primary liver cancer based on network Meta-analysis and multi-criteria decision analysis].

Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.

An Air-Stable Carbon-Centered Triradical with a Well-Addressable Quartet Ground State.

Organic polyradicals with a high-spin ground state and quantum magnetic properties suitable for spin manipulation are valuable materials for diverse innovative technologies, including quantum devices. However, the typically high reactivity and low stability of conventional polyradicals present a major obstacle to such applications. In this study, a highly stable carbon-centered triradical TR with a quartet ground state and excellent stability (τ1/2 of ∼90 days in air-saturated toluene at room temperature) is achieved, which shows apposite magnetic anisotropy and Zeeman splitting partition with favorable addressability. By virtue of the optimal stability, thorough structural and magnetic characterizations are realized. With X-ray crystallography unambiguously proving the molecular structure, the quartet ground state (ΔED-Q = 0.78 kcal/mol) is confirmed by the SQUID measurements, while the cw- and pulsed EPR techniques offer additional supportive evidence for the high-spin nature. Remarkably, owing to the easily attained magnetic anisotropy, selective excitations between different Zeeman splitting levels are successfully demonstrated with TR in its frozen toluene solution without the requirement for special alignment, which is unprecedented for organic polyradicals. Along with the millisecond spin-lattice relaxation and microsecond coherence time manifested by TR, this triradical is promising for potential coherent spin manipulation applications as a multienergy-level quantum information carrier.

Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.

BACKGROUND: Neuroendocrine prostate cancer (NEPC), a lethal subset of prostate cancer (PCa), is characterized by loss of AR signaling and resistance to AR-targeted therapy. While it is well reported that second-generation AR blockers induce neuroendocrine (NE) trans-differentiation of castration-resistant prostate cancer (CRPC) to promote the occurrence of NEPC, and pluripotent transcription factors might be potential regulators, the underlying molecular mechanisms remain unclear. METHODS: We analyzed the data from public databsets to screen candidate genes and then focused on SOX4, a regulator of NE trans-differentiation. The expression changes of SOX4 and its relationship with tumor progression were validated in clinical tumor tissues. We evaluated malignant characteristics related to NEPC in prostate cancer cell lines with stable overexpression or knockdown of SOX4 in vitro. Tumor xenografts were analyzed after inoculating the relevant cell lines into nude mice. RNA-seq, ATAC-seq, non-targeted metabolomics analysis, as well as molecular and biochemical assays were carried out to determine the mechanism. RESULTS: We screened public datasets and identified that expression of SOX4 was significantly elevated in NEPC. Overexpressing SOX4 in C4-2B cells increased cell proliferation and migration, upregulated the expression of NE marker genes, and inhibited AR expression. Consistently, inhibition of SOX4 expression in DU-145 and PC-3 cells reduced the above malignant phenotypes and repressed the expression of NE marker genes. For the in vivo assay, we found that knockdown of SOX4 inhibited tumor growth of subcutaneous xenografts in castrated nude mice which were concomitantly treated with enzalutamide (ENZ). Mechanically, we identified that one of the key enzymes in gluconeogenesis, PCK2, was a novel target of SOX4. The activation of carbohydrate metabolism reprogramming by SOX4 could promote NE trans-differentiation via the SOX4/PCK2 pathway. CONCLUSIONS: Our findings reveal that SOX4 promotes NE trans-differentiation both in vitro and in vivo via directly enhancing PCK2 activity to activate carbohydrate metabolism reprogramming. The SOX4/PCK2 pathway and its downstream changes might be novel targets for blocking NE trans-differentiation.

Unveiling the Structural and Dynamic Characteristics of Concentrated LiNO3 Aqueous Solutions through Ultrafast Infrared Spectroscopy and Molecular Dynamics Simulations.

Highly concentrated aqueous electrolytes have attracted a significant amount of attention for their potential applications in lithium-ion batteries. Nevertheless, a comprehensive understanding of the Li+ solvation structure and its migration within electrolyte solutions remains elusive. This study employs linear vibrational spectroscopy, ultrafast infrared spectroscopy, and molecular dynamics (MD) simulations to elucidate the structural dynamics in LiNO3 solutions by using intrinsic and extrinsic vibrational probes. The N-O stretching vibrations of NO3- exhibit a distinct spectral splitting, attributed to its asymmetric interaction with the surrounding solvation structure. Analysis of the vibrational relaxation dynamics of intrinsic and extrinsic probes, in combination with MD simulations, reveals cage-like networks formed through electrostatic interactions between Li+ and NO3-. This microscopic heterogeneity is reflected in the intertwined arrangement of ions and water molecules. Furthermore, both vehicular transport and structural diffusion assisted by solvent rearrangement for Li+ were analyzed, which are closely linked with the bulk concentration.

The anti-angiogenic and anti-vasculogenic mimicry effects of GN25 in endothelial and glioma cells.

BACKGROUND AND PURPOSE: Scientists have been exploring anti-angiogenic strategies to inhibit angiogenesis and prevent tumor growth. Vasculogenic mimicry (VM) in glioblastoma multiforme (GBM) poses a challenge, complicating anti-angiogenesis therapy. A novel drug, GN25 (3-[{1,4-dihydro-5,8-dimethoxy-1,4-dioxo-2-naphthalenyl}thio]-propanoic acid), can inhibit tumor formation. This study aims to investigate the microenvironmental effects and molecular mechanisms of GN25 in anti-angiogenesis and anti-VM. EXPERIMENTAL APPROACH: MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the cell viability of different concentrations of GN25 in human umbilical vein endothelial cells (HUVEC) and Uppsala 87 malignant glioma (U87MG) cells. Functional assays were used to investigate the effects of GN25 on angiogenesis-related processes, whereas gelatin zymography, enzyme-linked immunosorbent assays, and Western blotting were utilized to assess the influence on matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) secretion and related signaling pathways. KEY RESULTS: GN25 suppressed migration, wound healing, and tube formation in HUVECs and disrupted angiogenesis in a rat aorta ring and zebrafish embryo model. GN25 dose-dependently reduced phosphatidylinositol 3-kinase/AKT and inhibited MMP-2/VEGF secretion in HUVECs. In U87MG cells, GN25 inhibited migration, wound healing, and VM, accompanied by a decrease in MMP-2 and VEGF secretion. The results indicate that GN25 effectively inhibits angiogenesis and VM formation in HUVECs and U87MG cells without affecting preexisting vascular structures. CONCLUSION AND IMPLICATIONS: This study elaborated GN25's potential as an anti-angiogenic agent by elucidating its inhibitory effects on classical angiogenesis. VM provides valuable insights for developing novel therapeutic strategies against tumor progression and angiogenesis-related diseases. These results indicate the potential of GN25 as a promising candidate for angiogenesis-related diseases.

Macrolide-Resistant Mycoplasma pneumoniae Infections among Children before and during COVID-19 Pandemic, Taiwan, 2017-2023.

Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.