Salidroside protects pulmonary artery endothelial cells against hypoxia-induced apoptosis via the AhR/NF-κB and Nrf2/HO-1 pathways.

BACKGROUND: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive. PURPOSE: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms. STUDY DESIGN: Male Sprague-Dawley (SD) rats were subjected to hypoxia (10% O2) for 4 weeks to establish a model of PH. Rats were intraperitoneally injected daily with SAL (2, 8, and 32 mg/kg/d) or vehicle. To define the molecular mechanisms of SAL in PAECs, an in vitro model of hypoxic cell injury was also generated by exposed PAECs to 1% O2 for 48 h. METHODS: Various techniques including hematoxylin and eosin (HE) staining, immunofluorescence, flow cytometry, CCK-8, Western blot, qPCR, molecular docking, and surface plasmon resonance (SPR) were used to determine the role of SAL in rats and in PAECs in vitro. RESULTS: Hypoxia stimulation increases AhR nuclear translocation and activates the NF-κB signaling pathway, as evidenced by upregulated expression of CYP1A1, CYP1B1, IL-1ß, and IL-6, resulting in oxidative stress and inflammatory response and ultimately apoptosis of PAECs. SAL inhibited the activation of AhR and NF-κB, while promoted the nuclear translocation of Nrf2 and increased the expression of its downstream antioxidant proteins HO-1 and NQO1 in PAECs, ameliorating the hypoxia-induced oxidative stress in PAECs. Furthermore, SAL lowered right ventricular systolic pressure, and decreased pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-exposed rats. CONCLUSIONS: SAL may attenuate the apoptosis of PAECs by suppressing NF-κB and activating Nrf2/HO-1 pathways, thereby delaying the progressive pathology of PH.

Reduced generalization of reward among individuals with subthreshold depression: Behavioral and EEG evidence.

Altered stimulus generalization has been well-documented in anxiety disorders; however, there is a paucity of research investigating this phenomenon in the context of depression. Depression is characterized by impaired reward processing and heightened attention to negative stimuli. It is hypothesized that individuals with depression exhibit reduced generalization of reward stimuli and enhanced generalization of loss stimuli. Nevertheless, no study has examined this process and its underlying neural mechanisms. In the present study, we recruited 25 participants with subthreshold depression (SD group) and 24 age-matched healthy controls (HC group). Participants completed an acquisition task, in which they learned to associate three distinct pure tones (conditioned stimuli, CSs) with a reward, a loss, or no outcome. Subsequently, a generalization session was conducted, during which similar tones (generalization stimuli, GSs) were presented, and participants were required to classify them as a reward tone, a loss tone, or neither. The results revealed that the SD group exhibited reduced generalization errors in the early phase of generalization, suggesting a diminished ability to generalize reward-related stimuli. The event-related potential (ERP) results indicated that the SD group exhibited decreased generalization of positive valence to reward-related GSs and heightened generalization of negative valence to loss-related GSs, as reflected by the N1 and P2 components. However, the late positive potential (LPP) was not modulated by depression in reward generalization or loss generalization. These findings suggested that individuals with subthreshold depression may have a blunted or reduced ability to generalize reward stimuli, shedding light on potential treatment strategies targeting this particular process.

Sustainable development of environmental protection talents training: Research on the behavior decision of government, university and enterprise under the background of evolutionary game.

Environmental protection talents training (EPTT) is recognized as a key prerequisite for maintaining environmental sustainability, and in order to study the influence of each player on EPTT. This paper innovatively constructs a tripartite evolutionary game model of government, university and enterprise. The equilibrium points and evolutionary stabilization strategies of each participant are solved by replicating the dynamic equations, and the behaviors of each subject in EPTT are analyzed so as to clarify the behavioral characteristics and optimal strategies of the government's participation in EPTT. The results show that enterprises occupy a more important position in influencing government decisions. The government should reduce the financial incentives for enterprises and replace them with greater policy support. Meanwhile, the government should actively promote the cultivation mechanism that integrates universities and enterprises. The results of the study can provide a decision-making basis for the government to promote the sustainable development of EPTT.

Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner.

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

Nrf2/HO-1 signaling activation alleviates cigarette smoke-induced inflammation in chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis.

BACKGROUND: This study examined the effect of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on chronic obstructive pulmonary disease (COPD) and the potential molecular mechanism. METHODS: A COPD mouse model was established by cigarette smoke exposure and administered with either ML385 or dimethyl fumarate (DMF). Airway resistance of mice was detected. IL-1ß and IL-6 levels in mice alveolar lavage fluid were examined by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining and immunohistochemical of lung tissues were utilized to detect lung injury and NLRP3 expression. DMF was used to treat COPD cell model constructed by exposing normal human bronchial epithelial (NHBE) cells to cigarette smoke extract. NHBE cells were transfected by NLRP3-expression vectors. Expression of proteins was detected by Western blot. RESULTS: COPD mice showed the enhanced airway resistance, the inactivated Nrf2/HO-1 pathway and the overexpressed NLRP3, Caspase-1 and GSDMD-N proteins in lung tissues, and the increased IL-1ß and IL-6 levels in alveolar lavage fluid. ML385 treatment augmented these indicators and lung injury in COPD mice. However, DMF intervention attenuated these indicators and lung injury in COPD mice. Nrf2/HO-1 pathway inactivation and overexpression of NLRP3, Caspase-1 and GSDMD-N proteins were observed in COPD cells. DMF intervention activated Nrf2/HO-1 pathway and down-regulated NLRP3, Caspase-1 and GSDMD-N proteins in COPD cells. However, NLRP3 overexpression abolished the effect of DMF on COPD cells. CONCLUSION: Nrf2/HO-1 pathway activation may alleviate inflammation in COPD by suppressing the NLRP3-related pyroptosis. Activating the Nrf2/HO-1 pathway may be an effective method to treat COPD.

Removal of Cr(VI) from aqueous solution using ball mill modified biochar: multivariate modeling, optimization and experimental study.

Chromium (Cr(VI)) pollution has attracted wide attention due to its high toxicity and carcinogenicity. Modified biochar has been widely used in the removal of Cr(VI) in water as an efficient and green adsorbent. However, the existing biochar prepared by chemical modification is usually complicated in process, high in cost, and has secondary pollution, which limits its application. It is urgent to explore modified biochar with simple process, low cost and environmental friendliness. Therefore, ball milling wheat straw biochar (BM-WB) was prepared by ball milling technology in this paper. The adsorption characteristics and mechanism of Cr(VI) removal by BM-WB were analyzed by functional group characterization, adsorption model and response surface method. The results showed that ball milling effectively reduced the particle size of biochar, increased the specific surface area, and more importantly, enhanced the content of oxygen-containing functional groups on the surface of biochar. After ball milling, the adsorption capacity of Cr(VI) increased by 3.5-9.1 times, and the adsorption capacity reached 52.21 mg/g. The adsorption behavior of Cr(VI) follows the pseudo-second-order kinetics and Langmuir isotherm adsorption model rate. Moreover, the Cr(VI) adsorption process of BM-WB is endothermic and spontaneous. Under the optimized conditions of pH 2, temperature 45 °C, and adsorbent dosage 0.1 g, the removal rate of Cr(VI) in the solution can reach 100%. The mechanism of Cr(VI) adsorption by BM-WB is mainly based on electrostatic attraction, redox and complexation. Therefore, ball milled biochar is a cheap, simple and efficient Cr(VI) removal material, which has a good application prospect in the field of remediation of Cr(VI) pollution in water.

Blood-brain barrier-crossing dendrimers for glioma theranostics.

Glioma, as a disease of the central nervous system, is difficult to be treated due to the presence of the blood-brain barrier (BBB) that can severely hamper the efficacy of most therapeutic agents. Hence, drug delivery to glioma in an efficient, safe, and specifically targeted manner is the key to effective treatment of glioma. With the advances in nanotechnology, targeted drug delivery systems have been extensively explored to deliver chemotherapeutic agents, nucleic acids, and contrast agents. Among these nanocarriers, dendrimers have played a significant role since they possess highly branched structures, and are easy to be decorated, thus offering numerous binding sites for various drugs and ligands. Dendrimers can be designed to cross the BBB for glioma targeting, therapy or theranostics. In this review, we provide a concise overview of dendrimer-based carrier designs including dendrimer surface modification with hydroxyl termini, peptides, and transferrin etc. for glioma imaging diagnostics, chemotherapy, gene therapy, or imaging-guided therapy. Finally, the future perspectives of dendrimer-based glioma theraputics are also briefly discussed.

Neurocognitive mechanisms of mental imagery-based disgust learning.

Disgust imagery represents a potential pathological mechanism for disgust-related disorders. However, it remains controversial as to whether disgust can be conditioned with disgust-evoking mental imagery serving as the unconditioned stimulus (US). Therefore, we examined this using a conditioned learning paradigm in combination with event-related potential (ERP) analysis in 35 healthy college students. The results indicated that the initial neutral face (conditioned stimulus, CS+) became more disgust-evoking, unpleasant, and arousing after pairing with disgust-evoking imagery (disgust CS+), compared to pairing with neutral (neutral CS+) and no (CS-) imagery. Moreover, we observed that mental imagery-based disgust conditioning was resistant to extinction. While the disgust CS + evoked larger P3 and late positive potential amplitudes than CS- during acquisition, no significant differences were found between disgust CS+ and neutral CS+, indicating a dissociation between self-reported and neurophysiological responses. Future studies may additionally acquire facial EMG as an implicit index of conditioned disgust. This study provides the first neurobiological evidence that associative disgust learning can occur without aversive physical stimuli, with implications for understanding how disgust-related disorders may manifest or deteriorate without external perceptual aversive experiences, such as in obsessive-compulsive disorder (OCD).

Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates.

BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.

PPARß/δ-ANGPTL4 axis mediates the promotion of mono-2-ethylhexyl phthalic acid on MYCN-amplified neuroblastoma development.

Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) ß/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARß/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARß/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARß/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARß/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARß/δ and affect the progression of neuroblastoma by activating the PPARß/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma.

On the adsorption characteristics and mechanism of methylene blue by ball mill modified biochar.

In this study, modified biochar (BRB) was prepared from rice straw by ball milling technique and used for the adsorption of methylene blue (MB) in wastewater. The BRB was characterized by SEM, FTIR and XPS, and the adsorption model and Box-Behnken design were used to optimize the five influencing factors. The results showed that the ball milling technique could increase the content of functional groups (-OH, C=C and C-O, etc.) and aromatic structures on the surface of biochar, thus facilitating the removal of MB. The isotherm model was consistent with the Langmuir adsorption model (R2 = 0.947) and the maximum adsorption capacity was 50.27 mg/g. The adsorption kinetics was consistent with the pseudo-second-order kinetic model (R2 = 1) and the adsorption rate was mainly controlled by chemisorption. The thermodynamic model confirmed that the adsorption process was a spontaneous heat absorption reaction. The maximum adsorption efficiency was 99.78% under the optimal conditions (40℃, pH 8, reaction time = 90 min, dosing amount = 0.1 mg), and the adsorption efficiency could be improved by increasing the pH and BRB dosing amount. The surface functional groups and crystal structure properties of BRB were the main determinants of adsorption, and it was clarified that physical adsorption, electrostatic attraction and π-π interaction were the main mechanisms for the adsorption of MB by BRB. The main mechanisms were clarified. Therefore, BRB is an economic, efficient and green adsorption material with good potential for the removal of dye pollutants in the aqueous environment.

Modeling and analyzing an opinion network dynamics considering the environmental factor.

With the development of Internet technology, social media has gradually become an important platform where users can express opinions about hot events. Research on the mechanism of public opinion evolution is beneficial to guide the trend of opinions, making users' opinions change in a positive direction or reach a consensus among controversial crowds. To design effective strategies for public opinion management, we propose a dynamic opinion network susceptible-forwarding-immune model considering environmental factors (NET-OE-SFI), which divides the forwarding nodes into two types: support and opposition based on the real data of users. The NET-OE-SFI model introduces environmental factors from infectious diseases into the study of network information transmission, which aims to explore the evolution law of users' opinions affected by the environment. We attempt to combine the complex media environmental factors in social networks with users' opinion information to study the influence of environmental factors on the evolution of public opinion. Data fitting of real information transmission data fully demonstrates the validity of this model. We have also made a variety of sensitivity analysis experiments to study the influence of model parameters, contributing to the design of reasonable and effective strategies for public opinion guidance.

Fecal calprotectin as an intestinal inflammation marker is elevated in glaucoma.

Objective: The aim of this study was to investigate the potential association between glaucoma and fecal calprotectin. Methods: A total of 144 glaucomatous patients and 66 healthy controls were enlisted for this study. The fecal calprotectin was assessed using enzyme-linked immunosorbent assay. Results: The median fecal calprotectin levels were significantly elevated in glaucoma (73.67 vs 41.97 µg/g; p < 0.001), primary angle-closure glaucoma (76.85 µg/g; p < 0.001) and primary open-angle glaucoma (69.29 µg/g; p = 0.016) groups compared with controls. A notable proportion of the glaucoma (24%; p < 0.001), primary angle-closure glaucoma (21%; p < 0.001) and primary open-angle glaucoma (24%; p < 0.001) subgroups exhibited highly abnormal fecal calprotectin levels (≥250 µg/g). Conclusion: Elevated fecal calprotectin might indicate potential intestinal inflammation in glaucoma.

Neurotoxicity and the potential molecular mechanisms of mono-2-ethylhexyl phthalic acid (MEHP) in zebrafish.

Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at environmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1ß and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds.

A pH-responsive ZC-QPP hydrogel for synergistic antibacterial and antioxidant treatment to enhance wound healing.

The problems of bacterial resistance and high oxidation level severely limit wound healing. Therefore, we constructed a multifunctional platform of chitosan quaternary ammonium salts (QCS)/polyvinyl alcohol (PVA)/polyethylene glycol (PEG) hydrogels (QPP) loaded with ZnO@CeO2 (ZC-QPP). Firstly, the hydrogel was co-cross-linked by hydrogen and borate ester bonds, which allows easy adherence to a tissue surface for offering a protective barrier and moist environment for wounds. The chitosan quaternary ammonium salts due to their amino groups have inherent antibacterial properties to induce bacterial death. In response to the acidic conditions of the bacterial infection microenvironment, the borate ester bonds in the QPP hydrogel break and the ZC NCs dispersed in the hydrogel are released. The gradual dissociation of Zn2+ under acidic conditions can directly damage bacterial membranes. The wound site of bacterial infection always causes overexpression of reactive oxygen species (ROS) levels, often leading to inflammation and preventing rapid wound repair. CeO2 can eliminate excess ROS to reduce the inflammatory response. From in vitro and in vivo results, the high biosafety of the ZC-QPP hydrogel has demonstrated excellent antibacterial and antioxidant performance to enhance wound healing. Therefore, the ZC-QPP hydrogel opens a method to develop multifunctional synergistic therapeutic platforms combining enzyme-like nanomaterials with hydrogels for synergistic antibacterial and antioxidant treatment to promote wound healing.

Gut-licensed ß7+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma.

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.

Intolerance of uncertainty enhances generalisation of cued conditioned threat: An event-related potential study.

Overgeneralisation is one of the aetiologies of anxiety disorders and is closely associated with elevated intolerance of uncertainty (IU) levels. However, the underlying mechanisms are unclear. Considering the inconsistency of previous results and the high sensitivity of IU to uncertainty, the present study investigated the effect of IU on threat generalisation in predictable and unpredictable conditions. We compared self-reported unconditioned stimuli (US) expectancy and event-related potentials (ERPs) during generalisation in high IU (n = 34) and low IU (n = 35) participants. The results indicated that high IU was associated with higher US expectancy for generalisation stimuli (GS) than with low IU. At the electrophysiological level, compared to low IU, high IU showed increased P1 to ambiguous GS as well as decreased early late positive potential (LPP) to GS in unpredictable conditions, and no differential response to GS in late LPP in predictable conditions. These findings suggest that IU enhances threat generalisation and may be related to increased early automatic attention to ambiguous stimulus and inadequate late elaborate processing in a high uncertainty context. These findings might contribute to the treatment of mood disorders characterized by high IU.

Tongluo Shenggu capsule promotes angiogenesis to ameliorate glucocorticoid-induced femoral head necrosis via upregulating VEGF signaling pathway.

BACKGROUND: Tongluo Shenggu Capsule (TLSGC) is a product of Traditional Chinese patent medicine that has been effective in glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) clinically for many years. It is made from water extracts of a well-used herbal and dietary supplement-pigeon pea leaves. Nevertheless, the material basis and pharmacological mechanisms of TLSGC ameliorating GIONFH needed to be better defined. PURPOSE: To investigate the material basis and pharmacological mechanisms of TLSGC to ameliorate GIONFH. METHODS: The chemical compositions in TLSGC were characterized using the LC-MS system. Based on integrating the relevant targets of TLSGC in MedChem Studio software and GIONFH-related genes in our previous work, a "drug targets-disease genes" interaction network was constructed. The candidate targets of TLSGC ameliorating GIONFH were filtrated by topological characteristic parameters and further experimental validated based on methylprednisolone-induced rat model and dexamethasone-inhibited human umbilical vein endothelial cells (HUVECs). RESULTS: A total of 33 chemical compositions were characterized in TLSGC. Based on these compositions and GIONFH-related genes, 122 hub genes were selected according to topological parameters calculation. Biological functions were mainly enriched in four over-expressed modules of vascular damage, inflammation and apoptosis, bone metabolism and energy metabolism. The hub genes had the maximum enrichment degree in the VEGF-VEGFR2-PKC-Raf1-MEK-ERK signaling axis of the VEGF pathway. Experimentally, the therapeutic effects of TLSGC against GIONFH in rats were proved by micro-CT and pathological examination. Then, the protective effects of TLSGC on vascular damage were determined using angiography, CD31 immunohistochemistry, vascular function indicators in vivo, aortic ring test ex vivo, and the HUVECs activities in vitro including migration, invasion and tube formation. Mechanically, TLSGC effectively suppressed the downregulation of VEGF and VEGFR2 and their downstream targets, including Raf-1, PKC, p-MEK, and p-ERK proteins both in vivo and in vitro. CONCLUSION: TLSGC could promote angiogenesis by upregulating the VEGF-VEGFR2-PKC-Raf-1-MEK-ERK signaling axis, thereby exerting an apparent curative effect on GIONFH.

Prevalence and genotype distribution of human papillomavirus infections in Beijing, China between 2016 and 2020.

BACKGROUND: Certain types of human papillomavirus (HPV) induce long-lasting infections that cause cervical cancer. This study evaluated the prevalence of HPV infections and the distribution of their genotypes among clinic patients and healthy women in Beijing, China. METHODS: Cervical specimens were collected from 12,100 patients and 1176 subjects who underwent physical examinations at Dongzhimen Hospital, Beijing University of Chinese Medicine, between March 2016 and September 2020. HPV genotyping was performed using commercial kits designed to detect 15 high-risk and 2 low-risk HPV genotypes. RESULTS: There was a higher overall prevalence of HPV among the clinic patients (21.0%) than among the healthy women (11.9%). The most common HPV genotypes among the patients were: HPV-52 (5.4%), HPV-16 (3.4%), HPV-58 (3.2%), HPV-51 (2.6%), HPV-39 (2.0%), HPV-56 (2.0%), and HPV-66 (2.0%). Among the healthy women: HPV-52 (3.0%), HPV-51 (1.8%), HPV-58 (1.6%), HPV-66 (1.5%), HPV-16 (1.2%), HPV-56 (1.2%), and HPV-18 (1.1%). Multiple HPVs were detected in 29.1% of the gynecological outpatients and in 23.6% of the women receiving physical examinations. The most common pairs of HPV types detected were HPV-52 and HPV-16 in the clinic patients, and HPV-52 and HPV-56 in the healthy women. Age-specific HPV positivity and peak prevalence were observed among the individuals in both groups for women aged less than 25 years and those between 61 and 65 years of age. CONCLUSIONS: Our results provide current estimates of HPV prevalence and genotypes in the Beijing region. The epidemiological characteristics observed also provide a reference for the development of cervical cancer screening strategies and selection of HPV vaccine antigen targets for this region. A comparison of these HPV prevalence data with those from other regions suggests that regional vaccines may be an important direction for future research.

Deep Transfer Learning-Based Multi-Modal Digital Twins for Enhancement and Diagnostic Analysis of Brain MRI Image.

OBJECTIVE: it aims to adopt deep transfer learning combined with Digital Twins (DTs) in Magnetic Resonance Imaging (MRI) medical image enhancement. METHODS: MRI image enhancement method based on metamaterial composite technology is proposed by analyzing the application status of DTs in medical direction and the principle of MRI imaging. On the basis of deep transfer learning, MRI super-resolution deep neural network structure is established. To address the problem that different medical imaging methods have advantages and disadvantages, a multi-mode medical image fusion algorithm based on adaptive decomposition is proposed and verified by experiments. RESULTS: the optimal Peak Signal to Noise Ratio (PSNR) of 34.11dB can be obtained by introducing modified linear element and loss function of deep transfer learning neural network structure. The Structural Similarity Coefficient (SSIM) is 85.24%. It indicates that the MRI truthfulness and sharpness obtained by adding composite metasurface are improved greatly. The proposed medical image fusion algorithm has the highest overall score in the subjective evaluation of the six groups of fusion image results. Group III had the highest score in Magnetic Resonance Imaging- Positron Emission Computed Tomography (MRI-PET) image fusion, with a score of 4.67, close to the full score of 5. As for the objective evaluation in group I of Magnetic Resonance Imaging- Single Photon Emission Computed Tomography (MRI-SPECT) images, the Root Mean Square Error (RMSE), Relative Average Spectral Error (RASE) and Spectral Angle Mapper (SAM) are the highest, which are 39.2075, 116.688, and 0.594, respectively. Mutual Information (MI) is 5.8822. CONCLUSION: the proposed algorithm has better performance than other algorithms in preserving spatial details of MRI images and color information direction of SPECT images, and the other five groups have achieved similar results.