Tumor­associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review).

Hepatocellular carcinoma (HCC) tissue is rich in dendritic cells, T cells, B cells, macrophages, natural killer cells and cellular stroma. Together they form the tumor microenvironment (TME), which is also rich in numerous cytokines. Tumor­associated macrophages (TAMs) are involved in the regulation of tumor development. TAMs in HCC receive stimuli in different directions, polarize in different directions and release different cytokines to regulate the development of HCC. TAMs are mostly divided into two cell phenotypes: M1 and M2. M1 TAMs secrete pro­inflammatory mediators, and M2 TAMs secrete a variety of anti­inflammatory and pro­tumorigenic substances. The TAM polarization in HCC tumors is M2. Both direct and indirect methods for TAMs to regulate the development of HCC are discussed. TAMs indirectly support HCC development by promoting peripheral angiogenesis and regulating the immune microenvironment of the TME. In terms of the direct regulation between TAMs and HCC cells, the present review mainly focuses on the molecular mechanism. TAMs are involved in both the proliferation and apoptosis of HCC cells to regulate the quantitative changes of HCC, and stimulate the related invasive migratory ability and cell stemness of HCC cells. The present review aims to identify immunotherapeutic options based on the mechanisms of TAMs in the TME of HCC.

Associations between sleep-related disorders and cardiovascular disease risk in hypertensive patients: Insights from the National Health and Nutrition Examination Survey (NHANES): A cross-sectional study.

Both sleep-related disorders (SRD) and hypertension (HTN) are closely related to the occurrence of cardiovascular disease (CVD); however, few studies have explored their combined effect. Based on the National Health and Nutrition Examination Survey (NHANES) database, we comprehensively analyzed the combined effect of SRD and HTN on the occurrence of CVD. The weighted multivariate logistic regression analysis was adopted to explore how SRD and HTN can affect the occurrence of CVD. Specifically, the additive interaction was evaluated by the relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (SI), and the multiplicative interaction was evaluated by the odds ratio (OR) along with 95% confidence interval (CI) from the product term. All the 33,383 participants from the NHANES database were divided into 2 groups, i.e., the CVD (n = 3712) and non-CVD (n = 29,671) groups. The results indicated that SRD (Model 3: OR = 1.90, 95% CI: 1.60-2.25) and HTN (Model 3: OR = 2.28, 95% CI: 1.87-2.79) were both significantly associated with an increased risk of CVD. Additionally, we observed a significant additive interaction (RERI = 0.88, 95% CI: 0.03-0.65; AP = 0.22, 95% CI: 0.01-0.21; SI = 1.15, 95% CI: 1.07-1.33) and a significant multiplicative interaction (OR = 1.07, 95% CI: 1.03-1.10) between SRD and HTN on the occurrence of CVD. While both SRD and HTN are associated with CVD occurrence, their interaction can also contribute to the development of CVD.

Qili Qiangxin capsule attenuates myocardial fibrosis by modulating collagen homeostasis post-infarction in rats.

Myocardial fibrosis (MF) is a major cause of morbidity and mortality worldwide. Qili Qiangxin capsule (QLQX) is a traditional Chinese medicine (TCM) formula used for treating MF, QLQX can affect ventricular remodeling by regulating collagen deposition; however, the specific mechanism by which QLQX modulates collagen homeostasis remains unclear. Thus, this study aimed to explore the effect of QLQX on collagen fibers and its mechanism of action in rats after myocardial infarction (MI). Rats were subjected to left anterior descending artery ligation and then were divided equally into five groups: sham, model, low-dose QLQX, high-dose QLQX and empagliflozin groups. QLQX treatment for 28 days significantly improved cardiac function, as evidenced by decreases in heart mass index, cardiac volume, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, N-terminal B-type natriuretic peptide levels, and high-sensitivity cardiac troponin I levels and increases in left ventricular ejection fraction and left ventricular fraction shortening. Hematoxylin and eosin, Masson, and Picrosirius red staining under a light microscope indicated that QLQX treatment suppressed fibrosis and promoted angiogenesis by decreasing the protein expression levels of proteins related to cardiac remodeling including transforming growth factor-ß1, metalloproteinase-9 and α-smooth muscle actin and increasing the expression of tissue inhibitor of matrix metalloproteinase-1 concentration. Picrosirius red staining under the polarized light microscope and western blotting showed that MI increased the contents of collagen I and III, and reduced the contents of collagen II and IV. QLQX treatment improved cardiac function and attenuated MF by modulating collagen homeostasis and promoting angiogenesis. This study provides novel insights into the mechanism of action of QLQX in preventing MF after MI.

VPA-induced autism impairs memory ability through disturbing neural oscillatory patterns in offspring rats.

Autism spectrum disorder (ASD) is a general neurodevelopmental disease characterized by unusual social communication and rigid, repetitive behavior patterns. The purpose of this study was to investigate the effects of ASD on the alteration of neural oscillatory patterns and synaptic plasticity, which commonly supported a wide range of basic and higher memory activities. Accordingly, a prenatal valproic acid (VPA) exposure rat model was established for studying autism. The behavioral experiments showed that the social orientation declined and the memory ability was significantly impaired in VPA rats, which was closely associated with the synaptic plasticity deficits. Neural oscillation is the rhythmic neuron-activity, and the pathological characteristics and neurological changes in autism may be peeped at the neural oscillatory analysis. Interestingly, neural oscillatory analysis showed that prenatal VPA exposure reduced the low-frequency power but increased high-frequency gamma (HG) power in the hippocampus CA1 area. Meanwhile, the coherence and synchronization between CA3 and CA1 were abnormally increased in the VPA group, especially in theta and HG rhythms. Furthermore, the cross-frequency coupling strength of theta-LG in the CA1 and CA3 → CA1 pathway was significantly attenuated, but the theta-HG coupling strength was increased. Additionally, prenatal VPA exposure inhibited the expression of SYP and NR2B but enhanced the expression of PSD-95 along with decreased synaptic plasticity. The neural oscillatory patterns in VPA-induced offspring were disturbed with the intensity and direction of neural information flow disordered, which are consistent with the changes in synaptic plasticity, suggesting that the decline in synaptic plasticity is the underlying mechanism.

Fabrication of PHFPO Surface-Modified Conductive AgNWs/PNAGA Hydrogels with Enhanced Water Retention Capacity toward Highly Sensitive Strain Sensors.

Conductive hydrogels, characterized by their unique features of flexibility, biocompatibility, electrical conductivity, and responsiveness to environmental stimuli, have emerged as promising materials for sensitive strain sensors. In this study, a facile strategy to prepare highly conductive hydrogels is reported. Through rational structural and synthetic design, silver nanowires (AgNWs) are incorporated into poly(N-acryloyl glycinamide) (PNAGA) hydrogels, achieving high electrical conductivity (up to 0.88 S m-1), significantly enhanced mechanical properties, and elevated deformative sensitivity. Furthermore, surface modification with polyhexafluoropropylene oxide (PHFPO) has substantially improved the water retention capacity and dressing comfort of this hydrogel material. Based on the above merits, these hydrogels are employed to fabricate highly sensitive wearable strain sensors which can detect and interpret subtle hand and finger movements and enable precise control of machine interfaces. The AgNWs/PNAGA based strain sensors can effectively sense finger motion, enabling the control of robotic fingers to replicate the human hand's gestures. In addition, the high deformative sensitivity and elevated water retention performance of the hydrogels makes them suitable for flow sensing. These conceptual applications demonstrate the potential of this conductive hydrogel in high-performance strain sensors in the future.

Study on the Tribological Properties of Multilayer Concentric Hexagonal Laser Texturing on Rubber Surfaces of Screw Pumps.

Given the friction and drag reduction effects observed in various biological hexagonal structures in nature, a new design was implemented on the rubber surface of the stator of a submersible screw pump. This design featured a multilayer concentric hexagonal groove structure. Furthermore, a composite multilayer hexagonal structure integrating grooves and pits was also developed and applied. This study investigated the influence of groove layer number, groove depth, pit depth, and multilayer hexagonal groove texture arrangement on the rubber surface flow characteristics. Additionally, the pressure field state, the degree of influence on the oil film-bearing capacity, and the biomimetic and hydrodynamic lubrication theories were tested using the finite element analysis method. Tribological experiments were conducted on nanosecond laser-processed rubber textures under simulated liquid lubrication conditions, reflecting actual shale oil well experiments. These experiments aimed to investigate the influence of multilayer hexagonal shape parameters on the tribological characteristics of the stator-rotor friction pair of a submersible screw pump. The results indicated that with a constant overall size, a multilayer hexagonal structure with ~0.1 mm groove depth enhanced the oil film-bearing capacity, providing significant friction and drag reduction. For composite textures, a deeper pit depth within the study area enhanced the oil film-bearing capacity. Furthermore, a gradient arrangement of groove textures featuring wider outer grooves and shallower depth exhibited superior performance in terms of bearing capacity.

Interaction effects between sleep-related disorders and depression on hypertension among adults: a cross-sectional study.

BACKGROUND: Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. METHODS: This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. RESULTS: Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37-1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95-2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02-1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08-3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. CONCLUSIONS: Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.

[Material basis and mechanism of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" based on UHPLC-Q-Exactive Orbitrap HRMS coupled with network pharmacology and molecular docking].

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

Effect of Complex Well Conditions on the Swelling and Tribological Properties of High-Acrylonitrile Stator Rubber in Screw Pumps.

The effects of complex well conditions in shale oil wells on the swelling and tribological properties of high-acrylonitrile stator rubber used in screw pumps were investigated in this study. Tests were conducted considering the combined effects of immersion medium, temperature, and duration. The key parameters measured included mass change rate, volume change rate, hardness, elongation at break, tensile strength, surface micro-morphology of the rubber after thermal expansion and swelling, friction coefficient, and wear quantity. The results indicated that in the actual well fluids, the mass change rate of high-acrylonitrile rubber ranged from -1.08% to 1.29%, with a maximum volume change rate of 2.78%. In diesel oil, the greatest mass change rate of the rubber was 4.68%, and the volume change rate did not exceed ±1%, indicating superior swelling resistance. In both actual well fluids and diesel oil, the maximum decreases in hardness were 8.7% and 9.5%, respectively. Tensile strength and elongation at break decreased with increasing immersion temperature, with elongation at break in 80 °C diesel oil decreasing by over 50%, indicating a significant decline in the tensile properties of the rubber. The average friction coefficient of rubber specimens immersed in actual well fluids at three temperatures, as well as in diesel oil at 25 and 50 °C, decreased compared with the high-acrylonitrile rubber without thermal expansion and swelling. However, the average friction coefficient of rubber specimens immersed in diesel oil at 80 °C increased. The wear quantity of the rubber increased following immersion in both media. Additionally, the friction coefficient and wear quantity of the rubber increased with increasing immersion temperatures. The results of the study can offer valuable insights into assessing the durability of properties in high-acrylonitrile stator rubber under complex well conditions.

CRABP2 promotes cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways via upregulating LAMB3 in prostate cancer.

Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that cellular retinoic acid binding protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility and apoptosis in multiple cancers; however, the effect of CRABP2 on PCa is poorly reported. CRABP2 expression in different PCa cell lines and its effect on different cellular functions varied. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Additionally, CRABP2 had no influence on the cell cycle distribution of PCa cells. The RNA-seq assay showed that overexpressing CRABP2 upregulated laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in the phosphoinositide 3-kinase (PI3K)/activated protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signalling pathways. The following western blot experiments also confirmed the upregulated LAMB3 protein level and the activation of the PI3K/AKT and MAPK signalling pathways. Moreover, overexpressing CRABP2 significantly inhibited tumour growth in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways through upregulating LAMB3 in PCa.

New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

Research on the evolution of cross-platform online public opinion for public health emergencies considering stakeholders.

OBJECTIVE: To explore the different processes of the themes and emotional evolution of various stakeholders in the network public opinion of sudden public health emergencies at different stages of the public opinion evolution lifecycle. METHODS: This paper proposes a cross-platform analysis method for online public opinion during the public health emergencies based on stakeholders. Firstly, data from multiple platforms are collected and integrated. Secondly, stakeholders are categorized and the stages of public opinion evolution are determined based on stakeholder theory and lifecycle theory. Finally, the Latent Dirichlet Allocation (LDA)+Word2vec model and Convolutional Neural Network (CNN) model are used to analyze the themes and emotional evolution of stakeholders during different stages of public opinion evolution. RESULTS: There are differences in the evolution patterns of different types of stakeholders. The evolution process of stakeholders' focus points exhibits a two-stage transition from concentration to divergence. The focus points of stakeholders are closely associated with their respective social domains. The emotions of the public undergo a three-stage process of positive-negative-positive change. CONCLUSIONS: This study can provide a reference for the government to have a more comprehensive understanding of the development trend of public opinion and reduce the negative impact of public opinion.

The interaction between estimated glomerular filtration rate and dietary magnesium intake and its effect on stroke prevalence: a cross-sectional study spanning 2003-2018.

Background: Despite the known associations of dietary magnesium intake and estimated glomerular filtration rate (eGFR) with cardiovascular diseases, their combined effects on stroke risk remain unclear. Therefore, this study aims to explore the associations of dietary magnesium intake and eGFR with stroke risk. Methods: The National Health and Nutrition Examination Survey (NHANES) data of 37,637 adult participants (≥18 years) from 2003 to 2018 was analyzed. Dietary magnesium intake was categorized as low (≤ 254 mg/day) and normal (> 254 mg/day) based on experimental data. Multiple logistic regression analyses and interaction tests were conducted to assess the associations of dietary magnesium intake and eGFR with stroke risk, with a focus on the interaction between different chronic kidney disease (CKD) stages based on eGFR levels and dietary magnesium intake. Additional analyses included multiplicative interaction analysis, restricted cubic spline analysis, and subgroup evaluations by age, sex, and ethnicity. Results: Dietary magnesium intake and eGFR were inversely correlated with the risk of stroke. Participants with low dietary magnesium intake had a higher stroke risk than those with normal magnesium intake (odds ratio [OR] 1.09, 95% confidence interval [CI]: 1.03-1.42). Likewise, low eGFR was associated with an elevated stroke risk compared with normal eGFR (OR 1.56, 95% CI: 1.15-2.13). Furthermore, the two factors showed a multiplicative interaction effect on stroke risk (OR 1.05, 95% CI: 1.01-1.09). We observed a significant interaction between stage G3 CKD and low dietary magnesium intake (OR 1.05, 95% CI: 1.01-1.09), suggesting a potential association with stroke risk. However, similar associations were not observed for stages G4 and G5, possibly due to the smaller number of participants with G4 and G5 CKD. The restricted cubic spline analysis revealed a non-linear relationship between dietary magnesium intake, eGFR, and stroke risk. The interaction between magnesium deficiency and low eGFR persisted in participants aged >60 years, as well as in females, non-Hispanic Black people, and people of other races. Conclusion: Dietary magnesium intake and eGFR correlate negatively with stroke prevalence. Moreover, there was an interaction between dietary magnesium intake and stroke prevalence across different CKD stages. Further large-scale prospective studies are needed to analyze the potential relationship between dietary magnesium intake, eGFR, and stroke.

In vivo tracing of cyromazine and three neonicotinoids in cowpea under field conditions by solid-phase microextraction combined with ultra-performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: Excessive pesticide residues in agricultural products could accumulate in organisms through the food chain, causing potential harm to human health. The investigation of dissipation kinetics and residues of pesticides in crops is crucial for the scientific application of pesticides and the mitigation of their adverse effects on human health. In vivo solid-phase microextraction (in vivo SPME) has unique advantages, but the research on field plants is still lacking and the quantitative correction methods need to be further developed. RESULTS: A method combining in vivo solid-phase microextraction with ultra-performance liquid chromatography-tandem mass spectrometry (in vivo SPME-UPLC-MS/MS) was developed to monitor the presence of acetamiprid, cyromazine, thiamethoxam and imidacloprid in cowpea fruits grown in the field. The sampling rates (Rs) were determined using both in vitro SPME in homogenized cowpea samples and in vivo SPME in intact cowpea fruit samples. The in vivo-Rs values were significantly higher than the in vitro-Rs for the same analyte, which were used for in vivo SPME correction. The accuracy of this method was confirmed by comparison with a QuEChERS-based approach and subsequently applied to trace pesticide residues in field-grown cowpea fruits. The residual concentrations of each pesticide positively correlated with application doses. After 7 days of application at two different doses, all of the pesticides had residual concentrations below China's maximum residue limits. Both experimental data and predictions indicated that a safe preharvest interval for these pesticides is 7 days; however, if the European Union standards are to be met, a safe preharvest interval for cyromazine should be at least 13 days. SIGNIFICANCE: This study highlights the advantages of in vivo SPME for simultaneous analysis and tracking of multiple pesticides in crops under field conditions. This technique is environmentally friendly, minimally invasive, highly sensitive, accurate, rapid, user-friendly, cost-effective, and capable of providing precise and timely data for long-term pesticide surveillance. Consequently, it furnishes valuable insights to guide the safe utilization of pesticides in agricultural production.

Heterogeneous Porous Synergistic Photocatalysts for Organic Transformations.

Recent interest has surged in using heterogeneous carriers to boost synergistic photocatalysis for organic transformations. Heterogeneous catalysts not only facilitate synergistic enhancement of distinct catalytic centers compared to their homogeneous counterparts, but also allow for the easy recovery and reuse of catalysts. This mini-review summarizes recent advancements in developing heterogeneous carriers, including metal-organic frameworks, covalent-organic frameworks, porous organic polymers, and others, for synergistic catalytic reactions. The advantages of porous materials in heterogeneous catalysis originate from their ability to provide a high surface area, facilitate enhanced mass transport, offer a tunable chemical structure, ensure the stability of active species, and enable easy recovery and reuse of catalysts. Both photosensitizers and catalysts can be intricately incorporated into suitable porous carriers to create heterogeneous dual photocatalysts for organic transformations. Notably, experimental evidence from reported cases has shown that the catalytic efficacy of heterogeneous catalysts often surpasses that of their homogeneous analogues. This enhanced performance is attributed to the proximity and confinement effects provided by the porous nature of the carriers. It is expected that porous carriers will provide a versatile platform for integrating diverse catalysts, thus exhibiting superior performance across a range of organic transformations and appealing prospect for industrial applications.

Identification of cuproptosis-related long non-coding RNA and construction of a novel prognostic signature for bladder cancer: An observational study.

Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan-Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA.

Alien emergent aquatic plants develop better ciprofloxacin tolerance and metabolic capacity than one native submerged species.

Antibiotic pollution and biological invasion pose significant risks to freshwater biodiversity and ecosystem health. However, few studies have compared the ecological adaptability and ciprofloxacin (CIPR) degradation potential between alien and native macrophytes. We examined growth, physiological response, and CIPR accumulation, translocation and metabolic abilities of two alien plants (Eichhornia crassipes and Myriophyllum aquaticum) and one native submerged species (Vallisneria natans) exposed to CIPR at 0, 1 and 10 mg/L. We found that E. crassipes and M. aquaticum's growth were unaffected by CIPR while V. natans was significantly hindered under the 10 mg/L treatment. CIPR significantly decreased the maximal quantum yield of PSII, actual quantum yield of PSII and relative electron transfer rate in E. crassipes and V. natans but didn't impact these photosynthetic characteristics in M. aquaticum. All the plants can accumulate, translocate and metabolize CIPR. M. aquaticum and E. crassipes in the 10 mg/L treatment group showed greater CIPR accumulation potential than V. natans indicated by higher CIPR contents in their roots. The oxidative cleavage of the piperazine ring acts as a key pathway for these aquatic plants to metabolize CIPR and the metabolites mainly distributed in plant roots. M. aquaticum and E. crassipes showed a higher production of CIPR metabolites compared to V. natans, with M. aquaticum exhibiting the strongest CIPR metabolic ability, as indicated by the most extensive structural breakdown of CIPR and the largest number of potential metabolic pathways. Taken together, alien species outperformed the native species in ecological adaptability, CIPR accumulation and metabolic capacity. These findings may shed light on the successful invasion mechanisms of alien aquatic species under antibiotic pressure and highlight the potential ecological impacts of alien species, particularly M. aquaticum. Additionally, the interaction of antibiotic contamination and invasion might further challenge the native submerged macrophytes and pose greater risks to freshwater ecosystems.

Low-frequency repetitive transcranial magnetic stimulation alleviates abnormal behavior in valproic acid rat model of autism through rescuing synaptic plasticity and inhibiting neuroinflammation.

Autism is a complex neurodevelopmental disorder with no effective treatment available currently. Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising neuromodulation technique to treat autism. However, the mechanism how rTMS works remains unclear, which restrict the clinical application of magnetic stimulation in the autism treatment. In this study, we investigated the effect of low-frequency rTMS on the autistic-like symptoms and explored if this neuroprotective effect was associated with synaptic plasticity and neuroinflammation in the hippocampus. A rat model of autism was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats and male offspring were treated with 1 Hz rTMS daily for two weeks continuously. Behavior tests were performed to identify behavioral abnormality. Synaptic plasticity was measured by in vivo electrophysiological recording and Golgi-Cox staining. Synapse and inflammation associated proteins were detected by immunofluorescence and Western blot analyses. Results showed prenatal VPA-exposed rats exhibited autistic-like and anxiety-like behaviors, and cognitive impairment. Synaptic plasticity deficits and the abnormality expression of synapse-associated proteins were found in the hippocampus of prenatal VPA-exposed rats. Prenatal VPA exposure increased the level of inflammation cytokines and promoted the excessive activation of microglia. rTMS significantly alleviated the prenatal VPA-induced abnormalities including behavioral and synaptic plasticity deficits, and excessive neuroinflammation. TMS maybe a potential strategy for autism therapy via rescuing synaptic plasticity and inhibiting neuroinflammation.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat's model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

[Discrimination of anti-tumor and cardioprotective effect quality markers from Aidi Injection based on "spider web" mode].

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.