Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.

Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.

Autophagy Regulation Attenuates Neuroinflammation and Cognitive Decline in an Alzheimer's Disease Mouse Model with Chronic Cerebral Hypoperfusion.

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.

The association between ferroptosis-related patterns and tumor microenvironment in colorectal cancer.

Ferroptosis, a form of regulated cell death (RCD), exhibits distinct characteristics such as iron-dependence and lipid peroxidation accumulation (ROS), setting it apart from other types of cell death like apoptosis and necrosis. Its role in cancer biology is increasingly recognized, particularly its potential interaction with tumor microenvironment (TME) and CD8 T cells in cancer immunotherapy. However, the impact of ferroptosis on TME cell infiltration remains unclear. In this study, we conducted unsupervised clustering analysis on patient data from public databases, identifying three ferroptosis patterns with distinct TME cell infiltration characteristics: immune-inflamed, immune-excluded, and immune-desert phenotypes. We developed a ferroptosis score based on differentially expressed genes (DEGs) among these patterns, which correlated with various biological features including chemotherapy-resistance and immune cells infiltration. Despite patients with high ferroptosis scores exhibiting worse prognosis, they showed increased likelihood of benefiting from immunotherapy. Our findings highlight the importance of ferroptosis-related patterns in understanding TME cell infiltration and suggest novel strategies for drug combinations and immune-related therapies.

Frequency of HBsAg variants in occult hepatitis B virus infected patients and detection by ARCHITECT HBsAg quantitative.

Objective: To analyze the amino acid substitution caused by mutations in the major hydrophilic region (MHR) of the S-region genes in the serum samples of occult hepatitis B virus infection (OBI), and to explore the reasons for the missed detection of HBsAg. Method: The full-length gene of the S-region in hepatitis B virus(HBV) in the chronic hepatitis B virus(CHB)(10 samples) and OBI groups(42 samples) was amplified using a lab-developed, two-round PCR amplification technology. The PCR amplification products were sequenced/clone sequenced, and the nucleotide sequences of the S-region gene in HBV were compared to the respective genotype consensus sequence. Results: Only 20 of the 42 samples in the OBI group had the S-region genes successfully amplified, with the lowest HBV DNA load of 20.1IU/ml. As S-region genes in HBV, 68 cloned strains were sequenced. In the OBI and CHB groups MHR region, with a mutation rate of 3.21% (155/4828) and 0.70% (5/710). The genetic mutation rate was significantly higher in the OBI group than in the CHB group (P<0.05). The common mutation types in the MHR region were: I126T, L162R, K122E, C124R, and C147Y.Mutations at s122, s126, and s162 were associated with subgenotypes, most of which being C genotypes. The high-frequency mutation sites L162R and K122E found in this study have not been reported in previous literature. Conclusion: The results of this study confirmed that MHR mutations can cause the missed detection of HBsAg, giving rise to OBI.

EV-LFV: Synthesizing Light Field Event Streams from an Event Camera and Multiple RGB Cameras.

Light field videos captured in RGB frames (RGB-LFV) can provide users with a 6 degree-of-freedom immersive video experience by capturing dense multi-subview video. Despite its potential benefits, the processing of dense multi-subview video is extremely resource-intensive, which currently limits the frame rate of RGB-LFV (i.e., lower than 30 fps) and results in blurred frames when capturing fast motion. To address this issue, we propose leveraging event cameras, which provide high temporal resolution for capturing fast motion. However, the cost of current event camera models makes it prohibitive to use multiple event cameras for RGB-LFV platforms. Therefore, we propose EV-LFV, an event synthesis framework that generates full multi-subview event-based RGB-LFV with only one event camera and multiple traditional RGB cameras. EV-LFV utilizes spatial-angular convolution, ConvLSTM, and Transformer to model RGB-LFV's angular features, temporal features, and long-range dependency, respectively, to effectively synthesize event streams for RGB-LFV. To train EV-LFV, we construct the first event-to-LFV dataset consisting of 200 RGB-LFV sequences with ground-truth event streams. Experimental results demonstrate that EV-LFV outperforms state-of-the-art event synthesis methods for generating event-based RGB-LFV, effectively alleviating motion blur in the reconstructed RGB-LFV.

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment.

Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database. By LASSO regression, ABC-associated prognostic signature was constructed in breast cancer. Subsequently, immune microenvironment analysis was performed. Finally, cell experiments were performed to verify the function of ABCB7 in the breast cancer cell lines MDA-MB-231 and MCF-7. Using the ABC transporter-associated signature, we calculated a risk score for each breast cancer patient. Patients with breast cancer were subsequently categorized into high-risk and low-risk groups, utilizing the median risk score as the threshold. Notably, patients in the high-risk group exhibited significantly worse prognosis (P<0.05). Additionally, differences were observed in terms of immune cell infiltration levels, immune correlations, and gene expression of immune checkpoints between the two groups. Functional experiments conducted on breast cancer cell lines MDA-MB-231 and MCF-7 demonstrated that ABCB7 knockdown significantly diminished cell activity, proliferation, invasion, and migration. These findings emphasize the significance of understanding ABC transporter-mediated metabolic and transport characteristics in breast cancer, offering promising directions for further research and potential therapeutic interventions.

Automatic Diagnosis of Significant Liver Fibrosis From Ultrasound B-Mode Images Using a Handcrafted-Feature-Assisted Deep Convolutional Neural Network.

The accurate diagnosis of significant liver fibrosis ( ≥ F2) in patients with chronic liver disease (CLD) is critical, as ≥ F2 is a crucial factor that should be considered in selecting an antiviral therapy for these patients. This article proposes a handcrafted-feature-assisted deep convolutional neural network (HFA-DCNN) that helps radiologists automatically and accurately diagnose significant liver fibrosis from ultrasound (US) brightness (B)-mode images. The HFA-DCNN model has three main branches: one for automatic region of interest (ROI) segmentation in the US images, another for attention deep feature learning from the segmented ROI, and the third for handcrafted feature extraction. The attention deep learning features and handcrafted features are fused in the back end of the model to enable more accurate diagnosis of significant liver fibrosis. The usefulness and effectiveness of the proposed model were validated on a dataset built upon 321 CLD patients with liver fibrosis stages confirmed by pathological evaluations. In a fivefold cross validation (FFCV), the proposed model achieves accuracy, sensitivity, specificity, and area under the receiver-operating-characteristic (ROC) curve (AUC) values of 0.863 (95% confidence interval (CI) 0.820-0.899), 0.879 (95% CI 0.823-0.920), 0.872 (95% CI 0.800-0.925), and 0.925 (95% CI 0.891-0.952), which are significantly better than those obtained by the comparative methods. Given its excellent performance, the proposed HFA-DCNN model can serve as a promising tool for the noninvasive and accurate diagnosis of significant liver fibrosis in CLD patients.

Efficient utilization of free radicals in advanced oxidation processes under high-gravity environment for disposing pollutants in effluents and gases: A critical review.

Advanced oxidation processes (AOPs) using strongly oxidizing radicals are promising for wastewater treatment and gas purification. Nevertheless, the short half-life of radicals and the limited mass transfer in traditional reactors cause under-utilization of radicals and low pollutant removal efficiency. High-gravity technology (HiGee)-enhanced AOPs (HiGee-AOPs) have been demonstrated a promising way to enhance radical utilization in a rotating packed bed reactor (RPB). Here, we review the potential mechanisms of intensified radical utilization in HiGee-AOPs, structures and performance of RPB, and applications of HiGee in AOPs. The intensification mechanisms are described from three aspects: enhanced generation of radicals by efficient mass transfer, in-situ radical utilization under frequent liquid film renewal, and selective effect on radical utilization due to micromixing in RPB. Based on these mechanisms, we propose a novel High-gravity flow reaction with the essence of efficiency, in-situ, and selectivity in order to better explain the strengthening mechanisms in HiGee-AOPs. HiGee-AOPs possess great potential for treating effluent and gaseous pollutants due to characteristics of High-gravity flow reaction. We discuss the pros and cons of different RPBs and their applications to specific HiGee-AOPs. HiGee improve the following AOPs: (1) facilitate interfacial mass transfer in homogeneous AOPs, (2) enhance mass transfer to expose more catalytically active sites and mass-produce nanocatalysts for heterogeneous AOPs, (3) inhibit bubble accumulation on the electrode surface of electrochemical AOPs, (4) increase the mass transfer between liquid and catalysts in UV-assisted AOPs, (5) improve the micromixing efficiency of ultrasound-based AOPs. Strategies outlined in this paper should inspire further development of HiGee-AOPs.

The pulse light mode enhances the effect of photobiomodulation on B16F10 melanoma cells through autophagy pathway.

Photobiomodulation (PBM) is the use of low irradiance light of specific wavelengths to generate physiological changes and therapeutic effects. However, there are few studies on the effects of PBM of different LED light modes on cells. Here, we investigated the difference of influence between continuous wave (CW) and pulse-PBM on B16F10 melanoma cells. Our results suggested that the pulse mode had a more significant PBM than the CW mode on B16F10 melanoma cells. Our study confirmed that ROS and Ca2+ levels in B16F10 melanoma cells treated with pulse-PBM were significantly higher than those in the control and CW-PBM groups. One mechanism that causes the difference in CW and pulse-PBM action is that pulse-PBM activates autophagy of melanoma cells through the ROS/OPN3/Ca2+ signaling pathway, and excessive autophagy activation inhibits proliferation and apoptosis of melanoma cells. Autophagy may be one of the reasons for the difference between pulse- and CW-PBM on melanoma cells. More importantly, melanoma cells responded to brief PBM pulses by increasing intracellular Ca2+ levels.

CD142 promotes trophoblast cell migration by inhibiting BCL2-related autophagic degradation of IL-8.

The maintenance of migration of trophoblast cells is beneficial to pregnancy, and its weakening can lead to preeclampsia (PE). CD142 is considered as a classical motility-promoting factor. Our research aimed to explore the role of CD142 in trophoblast cell migration and potential mechanism. Through fluorescence-activated cell sorting (FACS) and gene transduction assays, CD142 expression levels of mouse trophoblast cell lines were upregulated and downregulated respectively. Then, the migratory level was detected through Transwell assays in different groups of trophoblast cells. The corresponding chemokines were screened by ELISA in different sorted trophoblast cells. Based on gene overexpression and knockdown assays, the production mode of identified valuable chemokine was analyzed by detecting gene and protein expression in trophoblast cells. Finally, the contribution of autophagy response to specific chemokine regulated by CD142 was explored by combining different groups of cells and autophagy regulators. Our results showed that both CD142 positive sorting and CD142 overexpression promoted the migratory ability of trophoblast cells, and trophoblast cells with the highest level of CD142 had the strongest migratory ability. In addition, CD142+ cells contained the highest level of IL-8. Consistently, CD142 overexpression promoted IL-8 protein expression in trophoblast cells while CD142 silencing was contrary. However, both CD142 overexpression and CD142 silencing did not affect IL-8 mRNA expression. Moreover, both CD142+ and CD142-overexpressed cells showed higher BCL2 protein expression and poorer autophagic activity. Importantly, autophagy activation with TAT-Beclin1 recovered the increased IL-8 protein expression in CD142+ cells. Obviously, the migratory ability of CD142+ cells inhibited by TAT-Beclin1 was recovered by the addition of IL-8 recombinant factor. In conclusion, CD142 inhibits the degradation of IL-8 through the inhibition of BCL2-Beclin1-autophagy signal transduction, thereby promoting the migration of trophoblast cells.

Metaverse-based virtual reality experience and endurance performance in sports economy: Mediating role of mental health and performance anxiety.

Metaverse sports arena is gaining popularity globally that empowers virtual reality sporting experience through digital avatars. The main objective of the current study is to explore the impact of the Metaverse-based virtual reality sporting experience on the endurance performance of young Chinese athletes, with the mediating role of their mental health condition and performance anxiety. The study's participants mainly included Chinese athletes, especially the sample group is an accurate depiction of young athletes using a convenience sampling approach. SEM-AMOS statistical software was used for the analysis and validation of the proposed relationships. The study findings statistically validate that mental health and performance anxiety fully mediate the direct associations between virtual reality sporting experiences and the endurance performance of young Chinese athletes. Interestingly, the mental health condition of the young Chinese athletes imposes a greater impact on their endurance performance, in contrast to the adverse effects of their performance anxiety. The outcomes of the present research guide young athletes on the opportunities to enhance their virtual reality sporting abilities and boost their endurance performance. Policymakers can also build systems to dissolve physical and geographical barriers, reduce performance anxiety, and sustain mental health in virtual reality sporting events through the metaverse.

Suggestions on Relieving Physical Anxiety of Medical Workers and Improving Physical and Mental Health Under the COVID-19 Epidemic-A Case Study of Meizhou City.

The study examined the effects of swimming pools on healthcare professionals' willingness to engage in recreational activities, physical anxiety, and physical and mental well-being in the context of COVID-19. The research adopted the mixed research method, used SPSS 26.0 statistical software to test the reliability of the questionnaire, and then collected 840 valid questionnaires; first analyzed the data with basic statistics, t-test, ANOVA, and PPMCC test methods, and then used the interview method to collect expert opinions. A multi-check approach assembled all data and discussions. The study found that the use of personnel dynamic tracking systems or measures, combined with sodium hypochlorite and repeated filtration to stabilize water quality, could maintain the confidence of most medical workers in the swimming pool sports environment for epidemic prevention and avoid violations. The government could formulate safety prevention and control mechanisms in traffic and establish appropriate traffic routes. Next, formulated a prescription for swimming or other physical activity mechanisms for men aged 31-50 and redesigned measures for medical staff over 51 years old to have tense head issues and physical fatigue, promote blood circulation and improve sleep quality. This will promote the purpose of relieving stress and regulating the physical and mental health of medical staff after engaging in swimming.

MiR-129-5p/DLX1 signalling axis mediates functions of prostate cancer during malignant progression.

We mainly corroborated the potential mechanism of DLX1 and miR-129-5p in prostate cancer cells. DLX1 was upregulated in cancer cells according to qRT-PCR assay. We evaluated the functional changes of the transfected cells via Transwell assay, CCK-8 assay and wound healing assay. DLX1 was confirmed as a cancer promoter. In addition, qRT-PCR showed down-regulated miR-129-5p expression in prostate cancer. We further used dual-luciferase reporter detection to elucidate the targeting between these two genes. The inhibition of miR-129-5p on tumour was verified. Besides, co-transfection of oe-DLX1 and miR-129-5p mimics attenuated this inhibition. These data demonstrated functions of DLX1/miR-129-5p axis in prostate cancer: miR-129-5p hindered the biological functions of cancer cells via inhibiting DLX1 expression. We provide a novel biomarker for prostate cancer.

Metformin mitigates PLCε gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.

The present study aimed to establish a mouse model of patient-derived castration-resistant prostate cancer (CRPC) xenograft tumors, and to evaluate the effects of various doses of metformin on phospholipase Cε (PLCε) expression and the neurogenic locus notch homolog protein 1 (Notch1)/hairy and enhancer of split 1 and androgen receptor (AR) signaling pathways via western blotting and reverse transcription-quantitative PCR. Additionally, phorbol 12-myristate 13-acetate was used to activate PLC, and Jagged1 was used as a Notch activator to verify whether metformin could suppress CRPC development via the PLCε/Notch1/AR pathways. The results confirmed that metformin may serve critical roles in CRPC by significantly inhibiting the occurrence, growth and proliferation of CRPC tumors by decreasing PLCε/Notch1 expression and AR nucleation.

Exploring the effects of large-area dorsal skin irradiation on locomotor activity and plasm melatonin level in C3H/He mice.

As the largest organ exposed to the outside of mammals, skin has direct photosensitivity. Recent studies have even shown that cutaneous irradiation played a role in local circadian systems. However, whether it can further affect the central clock system is controversial. Here, plasm melatonin rhythm of melatonin-proficient C3H/He mice was assessed, and on this basis, a well-designed segmented lighting method was used to investigate the effects of dorsal skin irradiation on locomotor activity and plasm melatonin content in male C3H/He mice. In brief, mice were separately exposed to cutaneous irradiation, intraocular irradiation or darkness for 60 min at specific moments. The results showed that neither blue nor red cutaneous exposure had obvious effect on central rhythm oscillation while intraocular irradiation could significantly change the central clock of mice, and the effect of blue light was more forceful than red light. It suggests that intraocular nonvisual channels still play a dominant role in rhythmic regulation, which has not been challenged by the discovery of local light entrainment in exposed peripheral tissues.

Comparative transcriptome analysis of gene expression patterns on B16F10 melanoma cells under Photobiomodulation of different light modes.

Cutaneous melanoma is one of the aggressive cancers. Recent studies have shown that Photobiomodulation (PBM) can inhibit the proliferation of melanoma cells. However, it is not clear that the effect of PBM light mode on the inhibition of melanoma cells. Herein, we investigated the difference of influence between continuous wave (CW) and Pulse PBM on B16F10 melanoma cells. Our results suggested that Pulse mode had a more significant inhibition on the viability of B16F10 melanoma cells than CW mode under the PBM light parameter of wavelength, dose, and average irradiance at 457 nm, 1.14 J/cm2, and 0.19 mW/cm2. Besides, we revealed the differentially expressed genes of B16F10 melanoma cells under the various treatments of PBM light mode (not PBM treatment, CW mode, and Pulse mode) by RNA sequencing. Together, our data suggested that Pulse-PBM can improve the effect of PBM on cells significantly and there may be different molecular mechanisms between Pulse and CW mode including anti-proliferative and cell necrosis. The study shed new light on investigating the molecular mechanisms of various PBM light modes on B16F10 melanoma cells.

Novel Porphyrin Zr Metal-Organic Framework (PCN-224)-Based Ultrastable Electrochemiluminescence System for PEDV Sensing.

The sensitive detection of coronavirus is of vital importance for the prevention of its rapid spread. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets. In this work, a novel PCN-224-based electrochemiluminescence (ECL) system was constructed for PEDV detection with high sensitivity. We found that PCN-224 can be employed as an ECL reporter with a strong signal because of its zirconium-based organic porous frame nanomaterial with a large specific surface area and stable structure. TiO2 nanoparticles were used as an accelerator for the first time to promote the reduction of coreactant potassium peroxydisulfate on the cathode; thus, the initial ECL signal of PCN-224 was significantly amplified. In the presence of PEDV, the ECL signal decreased due to the block effect to electron transfer. As a result, the novel "signal off" biosensor achieved a sensitive detection of PEDV ranging from 1 pg/mL to 10 ng/mL, with a detection limit of 0.4 pg/mL (S/N = 3). Importantly, the PCN-224 nanomaterial enriched the ECL system in biological analysis, and the proposed strategy provided a new route for coronavirus detection.

Bacteria Inspired Internal Standard SERS Substrate for Quantitative Detection.

Metal-respiring bacteria are frequently used to recycle metal resources by biosynthesizing nanoparticles on its surface in environment treatment. However, further utilization of biogenetic nanoparticles through combining the advantages of both bacteria and nanoparticles is still limited. Herein, biogenetic Au@Ag nanoislands are utilized as the surface-enhanced Raman spectroscopy (SERS) substrate for quantitative detection. Specifically, Au@Ag nanoislands enhance the Raman signal via surface plasmon resonance, while biomolecules (phospholipid, tyrosine, and phenylalanine, etc.) on bacterium serve as an internal standard to eliminate the discrepancy of the target SERS intensity in different hot spots. Gene-controlled biomolecules in bacteria guarantee the reproducibility of this SERS substrate. The generality of this analytical method is demonstrated by determining rhodamine 6G, malachite green, and uric acid. This discovery solves a pervasive problem in SERS analysis through a simple biogenetic nanosystem, which opens up an avenue to address scientific challenges by using versatile organisms from nature.

Kanamycin Adsorption on Gold Nanoparticles Dominates Its Label-Free Colorimetric Sensing with Its Aptamer.

A short kanamycin-binding aptamer has been widely used for detecting kanamycin. One of the popular signaling methods is based on the color change of gold nanoparticles (AuNPs) to develop label-free colorimetric biosensors. The general perception was that aptamer binding to its target would inhibit aptamer adsorption by the AuNPs. This inhibited adsorption results in the aggregation of the AuNPs and a color change upon addition of salt. However, the potential adsorption of kanamycin was ignored. Herein, we carefully studied the adsorption of kanamycin on AuNPs and performed a comprehensive analysis using two mutated aptamers and a randomly sequenced DNA which were not supposed to bind kanamycin. In addition, a total of six antibiotics were studied over a wide concentration range. As low as 90 nM kanamycin can induce the aggregation of 3 nM citrate-capped AuNPs, indicating very strong adsorption of kanamycin. The color change was independent of DNA sequence, and all the tested sequences showed a similar color response, regardless of aptamer. Among the different antibiotics, kanamycin and streptomycin induced a color change but not the other four. Our results support an alternative mechanism that kanamycin and streptomycin adsorption by the AuNPs was the main reason for the color change instead of aptamer binding.