Unraveling multi-scale neuroimaging biomarkers and molecular foundations for schizophrenia: A combined multivariate pattern analysis and transcriptome-neuroimaging association study.

AIMS: Schizophrenia is characterized by alterations in resting-state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia. METHODS: A cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting-state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel-level (Scale 1) and regional-level (Scales 2-4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome-neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia. RESULTS: The ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome-neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity. CONCLUSIONS: This study highlights the potential of multi-scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia.

Exploring the anti-inflammatory ingredients and potential of golden buckwheat (Fagopyrum dibotrys) on the TLR4/NLRP3 pathway in acute lung injury.

Golden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS-induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC-Q-Exactive Orbitrap-HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry-to-wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL-1ß, TNFα, and IL-6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway.

Electroreductive Cross-Coupling between Aromatic Aldehydes and Chlorosilanes Enabling the Synthesis of α-Silyl Alcohols.

α-Silyl alcohols are powerful structural motifs for pharmaceutical chemistry, materials chemistry, and organic synthesis. The limitations of current synthetic techniques encompass a requirement for difficult-to-obtain silyl precursors, noble-metal catalysts, and narrow substrate scopes. Here, we developed a general synthetic method for α-silyl alcohols through electroreductive cross-coupling of aldehydes and chlorosilane. This method features easily available reagents, mild conditions, and a wide substrate scope. The establishment of this protocol will provide an alternative for access to α-silyl alcohols.

Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution.

The microgeometry of the cellular microenvironment profoundly impacts cellular behaviors, yet the link between it and the ubiquitously expressed mechanosensitive ion channel PIEZO1 remains unclear. Herein, we describe a fluorescent micropipette aspiration assay that allows for simultaneous visualization of intracellular calcium dynamics and cytoskeletal architecture in real-time, under varied micropipette geometries. By integrating elastic shell finite element analysis with fluorescent lifetime imaging microscopy and employing PIEZO1-specific transgenic red blood cells and HEK cell lines, we demonstrate a direct correlation between the microscale geometry of aspiration and PIEZO1-mediated calcium signaling. We reveal that increased micropipette tip angles and physical constrictions lead to a significant reorganization of F-actin, accumulation at the aspirated cell neck, and subsequently amplify the tension stress at the dome of the cell to induce more PIEZO1's activity. Disruption of the F-actin network or inhibition of its mobility leads to a notable decline in PIEZO1 mediated calcium influx, underscoring its critical role in cellular mechanosensing amidst geometrical constraints.

A qualitative study on the perioperative experiences and demands of haemophilic arthropathy patients undergoing total joint replacement.

INTRODUCTION: Total joint replacement is the optimal treatment option for patients with severe haemophilic arthritis. Current research emphasizes patient-reported outcomes as a vital measure for evaluating surgical outcomes and patient satisfaction. Nevertheless, very limited information about the subjective experience of perioperative haemophiliacs in the literature, highlighting the need for exploration in this area. AIM: To investigate the psychological experiences and health demands of haemophilic arthropathy patients during the perioperative period of total joint replacement. DESIGN: Qualitative descriptive research with semistructured individual interviews. METHODS: From June to September 2023, nine patients with severe haemophilic arthropathy who underwent total joint replacement at a Haemophilia Diagnosis and Treatment Centre in China were interviewed for average 37 min per person. Data were analysed using the traditional content analysis method and reported following the consolidated criteria for reporting qualitative research. The study is reported according to the COREQ checklist. RESULTS: Interviews described two main themes: (1) emotional decline which involves preoperative overoptimism, early postoperative anxiety and disease uncertainty during the early independent rehabilitation. (2) wellness aspiration which includes rehabilitation support and spiritual healing. CONCLUSION: This study reveals the patients' significant psychological changes and their well-being aspiration, particularly out-of-hospital rehabilitation needs. Strengthening communication between multidisciplinary teams and patients, enhancing the involvement of nurses, broadening the scope of functions at primary Haemophilia Treatment Centres, and developing telerehabilitation, these concerted efforts may improve the overall treatment experience for patients.

The Transcriptional Regulator TfmR Directly Regulates Two Pathogenic Pathways in Xanthomonas oryzae pv. oryzicola.

Xanthomonas oryzae pv. oryzicola (Xoc) is a notorious plant pathogen. Like most bacterial pathogens, Xoc has evolved a complex regulatory network to modulate the expression of various genes related to pathogenicity. Here, we have identified TfmR, a transcriptional regulator belonging to the TetR family, as a key player in the virulence mechanisms of this phytopathogenic bacterium. We have demonstrated genetically that tfmR is involved in the hypersensitive response (HR), pathogenicity, motility and extracellular polysaccharide production of this phytopathogenic bacterium. Our investigations extended to exploring TfmR's interaction with RpfG and HrpX, two prominent virulence regulators in Xanthomonas species. We found that TfmR directly binds to the promoter region of RpfG, thereby positively regulating its expression. Notably, constitutive expression of RpfG partly reinstates the pathogenicity compromised by TfmR-deletion mutants. Furthermore, our studies revealed that TfmR also exerts direct positive regulation on the expression of the T3SS regulator HrpX. Similar to RpfG, sustained expression of HrpX partially restores the pathogenicity of TfmR-deletion mutants. These findings underscore TfmR's multifaceted role as a central regulator governing key virulence pathways in Xoc. Importantly, our research sheds light on the intricate molecular mechanisms underlying the regulation of pathogenicity in this plant pathogen.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

Untargeted lipidomics of bronchopulmonary dysplasia induced by hyperoxia exposure in rats.

Background: Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease. Methods: In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Conclusions: Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.

Nanoscale insights into hematology: super-resolved imaging on blood cell structure, function, and pathology.

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level.

PC (16:0/14:0) ameliorates hyperoxia-induced bronchopulmonary dysplasia by upregulating claudin-1 and promoting alveolar type II cell repair.

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care, the pathogenesis of which potentially involves altered lipid metabolism. Given the critical role of lipids in lung development and the injury response, we hypothesized that specific lipid species could serve as therapeutic agents in BPD. This study aimed to investigate the role of the lipid Phosphatidylcholine (PC) (16:0/14:0) in modulating BPD pathology and to elucidate its underlying mechanisms of action. Our approach integrated in vitro and in vivo methodologies to assess the effects of PC (16:0/14:0) on the histopathology, cellular proliferation, apoptosis, and molecular markers in lung tissue. In a hyperoxia-induced BPD rat model, we observed a reduction in alveolar number and an enlargement in alveolar size, which were ameliorated by PC (16:0/14:0) treatment. Correspondingly, in BPD cell models, PC (16:0/14:0) intervention led to increased cell viability, enhanced proliferation, reduced apoptosis, and elevated surfactant protein C (SPC) expression. RNA sequencing revealed significant gene expression differences between BPD and PC (16:0/14:0) treated groups, with a particular focus on Cldn1 (encoding claudin 1), which was significantly enriched in our analysis. Our findings suggest that PC (16:0/14:0) might protect against hyperoxia-induced alveolar type II cell damage by upregulating CLDN1 expression, potentially serving as a novel therapeutic target for BPD. This study not only advances our understanding of the role of lipids in BPD pathogenesis, but also highlights the significance of PC (16:0/14:0) in the prevention and treatment of BPD, offering new avenues for future research and therapeutic development.

A Review of the Effect of Defect Modulation on the Photocatalytic Reduction Performance of Carbon Dioxide.

Constructive defect engineering has emerged as a prominent method for enhancing the performance of photocatalysts. The mechanisms of the influence of defect types, concentrations, and distributions on the efficiency, selectivity, and stability of CO2 reduction were revealed for this paper by analyzing the effects of different types of defects (e.g., metallic defects, non-metallic defects, and composite defects) on the performance of photocatalysts. There are three fundamental steps in defect engineering techniques to promote photocatalysis, namely, light absorption, charge transfer and separation, and surface-catalyzed reactions. Defect engineering has demonstrated significant potential in recent studies, particularly in enhancing the light-harvesting, charge separation, and adsorption properties of semiconductor photocatalysts for reducing processes like carbon dioxide reduction. Furthermore, this paper discusses the optimization method used in defect modulation strategy to offer theoretical guidance and an experimental foundation for designing and preparing efficient and stable photocatalysts.

Electroreductive Arylcarboxylation of Styrenes with CO2 and Aryl Halides via a Radical-Polar Crossover Mechanism.

2,3-Diaryl propanoic acids are important structures as a result of their widespread presence in numerous bioactive compounds. However, the limitations of existing synthetic techniques include the requirement for costly catalysts and limited substrates. Here, we developed a novel electroreductive arylcarboxylation of alkenes with CO2 based on a radical-polar crossover pathway assisted by easily accessible dimethyl terephthalate as a reductive mediator. This method will provide an efficient strategy for the synthesis of 2,3-diarylpropanoic acids.

Urinary neonicotinoid concentrations and obesity: A cross-sectional study among Chinese adolescents.

Epidemiological and toxicological studies on neonicotinoids and obesity have been relevant to adults and young children, but data are limited in adolescents. This study aimed to examine the association between urinary neonicotinoid concentrations and obesity measures among Chinese adolescent. A total of 524 urine samples from 300 boys (11.3-16.1 years) and 224 girls (12.1-15.8 years) were collected to detect the concentrations of eleven neonicotinoids. Generalized linear regression, weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR) were used to estimate covariate-adjusted associations between detectable neonicotinoids and ten indicators of obesity. Nitenpyram concentration was associated with increased body mass index z-score (ß = 0.170, 95% CI: 0.041, 0.299) and greater odds of being general obesity (OR = 2.46, 95% CI: 1.11, 5.46). N-desmethyl- acetamiprid concentration was associated with an increase in waist-to-height ratio (ß = 0.102, 95% CI: 0.029, 0.176) and waist-to-hip ratio (ß = 0.083, 95% CI: 0.011, 0.155). The concentrations of clothianidin (OR = 2.06, 95% CI: 1.10, 3.88) and flonicamid (OR = 2.39, 95% CI: 1.07, 5.32) were associated with greater odds of being abdominal obesity. In contrast, the concentrations of imidacloprid (OR = 0.35, 95% CI: 0.14, 0.88) and thiacloprid (OR = 0.28, 95% CI: 0.08, 0.99) were associated with lower odds of being general obesity. The estimates of general obesity and abdominal obesity increased significantly when concentrations of neonicotinoids mixture were at or above the 55th and 65th percentiles, respectively, compared to the 50th percentile concentration. Sex modified the association between nitenpyram and clothianidin and the risk of obesity with a positive association among boys, and a nonsignificant inverse association among girls. The findings suggest that these associations may be mixed and sex-specific.

Full-Scale Experimental and Field Investigations into Expansion Mechanism of Foamed Polyurethane and its Lifting Behaviors for Repair and Maintenance of Railway Slab Track Systems.

Excessive settlement of the subgrade seriously reduces the service quality of slab tracks and threatens trains' running safety. While the utilization of foamed polyurethane is recognized as an effective solution, previous research on its expansion mechanism and its impact on track lifting requires further refinement. Accordingly, a series of full-scale tests, including expansion force tests on foamed polyurethane with diverse qualities and lifting tests of polyurethane grouting with varied qualities on the track structure, have been conducted. The expansion development process of foamed polyurethane is meticulously elucidated, and key expansion parameters are analyzed. Simultaneously, this research explores the lifting behavior of foamed polyurethane grouting under the slab tracks, yielding new insights into essential lifting parameters for track formation repair and maintenance. Based on the experimental data, this study proposes new empirical formulas to comprehensively describe both the expansion mechanism of foam polyurethane and its lifting behavior under the slab tracks. The outcomes of this research offer a new breakthrough for the design of lifting mechanism for maintaining slab track structures through the utilization of foam polyurethane slurry grouting, such as determining the optimal grouting quantity. In addition, these results are instrumental to the evaluation of lifting effects and service life, enhancing the circular economy of railway track systems.

Rich Club Reorganization in Nurses Before and After the Onset of Occupational Burnout: A Longitudinal MRI Study.

BACKGROUND: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross-sectional design. PURPOSE: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. STUDY TYPE: Prospective, longitudinal. POPULATION: Thirty-nine hospital nurses ( 23.67 ± 1.03 $$ 23.67\pm 1.03 $$ years old at baseline, 24.67 ± 1.03 $$ 24.67\pm 1.03 $$ years old at a follow-up within 1.5 years, 38 female). FIELD STRENGTH/SEQUENCE: Magnetization-prepared rapid gradient-echo and gradient-echo echo-planar imaging sequences at 3.0 T. ASSESSMENT: The Maslach Burnout Inventory and Symptom Check-List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow-up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short-, mid-, and long range). STATISTICAL TESTS: Chi-square, paired-samples t, two-sample t, Mann-Whitney U tests, network-based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni-corrected P < 0.05 $$ P<0.05 $$ . RESULTS: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short-, mid-, and long-range connectivities were significantly decreased at follow-up compared with baseline. 2) At follow-up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from -0.57 to -0.73) and anxiety scores (r = -0.56), respectively. 3) Longitudinal change (follow-up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. DATA CONCLUSION: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Applying the multiple object juggling task to measure the attention of athletes: Evidence from female soccer.

The purpose of this study is to investigate whether the presentation of targets can affect the performance of multiple object tracking and whether the difference between female soccer players and female college students is regulated by the presentation of targets. We enlisted a group of 20 Chinese female soccer players and another group of 20 non-players to complete a multiple object juggling (MOJ) task. The mean age was 20.24 ±â€…1.61 years in the athletes group and 21.35 ±â€…1.93 years in the non-athletes group. Accuracy was analyzed to examine the disparity between soccer players and non-players, as well as the disparity between 3 presentation conditions for targets (fixed, added, and dynamic). Regarding the MOJ task, female soccer players did not outperform non-players (F = 1.84, 95% CI [-1.14 to 6.02], P = .27). The performance of tracking in fixed conditions was superior to that in added and dynamic conditions (MD = 10.33%, 95% CI [4.93 to 15.71], P < .001; MD = 9.82%, 95% CI [4.43 to 15.21], P < .001). The tracking accuracy of female soccer players was significantly higher than non-players in dynamic condition (F = 7.26, 95% CI [2.19 to 14.59], P = .01). According to the findings, experts who specialize in team sports tend to exhibit a greater attention advantage in areas that are pertinent to their field of expertise. For future studies, it will be necessary to employ MOT conditions that are more representative of sport-specific characteristics to strengthen the task ecological validity.

Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

Arsenic and polystyrene-nano plastics co-exposure induced testicular toxicity: Triggers oxidative stress and promotes apoptosis and inflammation in mice.

Co-existing of polystyrene-nano plastics (PSNPs) and arsenic (As) in the environment caused a horrendous risk to human health. However, the potential mechanism of PSNPs and As combination induced testicular toxicity in mammals has not been elucidated. Therefore, we first explore the testicular toxicity and the potential mechanism in male Kunming mice exposed to As or/and PSNPs. Results revealed that compared to the As or PSNPs group, the combined group showed more significant testicular toxicity. Specifically, As and PSNPs combination induced irregular spermatozoa array and blood-testis barrier disruption. Simultaneously, As and PSNPs co-exposure also exacerbated oxidative stress, including increasing the MDA content, and down-regulating expression of Nrf-2, HO-1, SOD-1, and Trx. PSNPs and As combination also triggered testicular apoptosis, containing changes in apoptotic factors (P53, Bax, Bcl-2, Cytc, Caspase-8, Caspase-9, and Caspase-3). Furthermore, co-exposed to As and PSNPs aggravated inflammatory damage characterized by targeted phosphorylation of NF-κB and degradation of I-κB. In summary, our results strongly confirmed As + PSNPs co-exposure induced the synergistic toxicity of testis through excessive oxidative stress, apoptosis, and inflammation, which could offer a new sight into the mechanism of environmental pollutants co-exposure induced male reproductive toxicity.

Optical Nonlinearity Enabled Super-Resolved Multiplexing Microscopy.

Optical multiplexing for nanoscale object recognition is of great significance within the intricate domains of biology, medicine, anti-counterfeiting, and microscopic imaging. Traditionally, the multiplexing dimensions of nanoscopy are limited to emission intensity, color, lifetime, and polarization. Here, a novel dimension, optical nonlinearity, is proposed for super-resolved multiplexing microscopy. This optical nonlinearity is attributable to the energy transitions between multiple energy levels of the doped lanthanide ions in upconversion nanoparticles (UCNPs), resulting in unique optical fingerprints for UCNPs with different compositions. A vortex beam is applied to transport the optical nonlinearity onto the imaging point-spread function (PSF), creating a robust super-resolved multiplexing imaging strategy for differentiating UCNPs with distinctive optical nonlinearities. The composition information of the nanoparticles can be retrieved with variations of the corresponding PSF in the obtained image. Four channels multiplexing super-resolved imaging with a single scanning, applying emission color and nonlinearity of two orthogonal imaging dimensions with a spatial resolution higher than 150 nm (1/6.5λ), are demonstrated. This work provides a new and orthogonal dimension - optical nonlinearity - to existing multiplexing dimensions, which shows great potential in bioimaging, anti-counterfeiting, microarray assays, deep tissue multiplexing detection, and high-density data storage.

Arsenic-Induced Ferroptosis in Chicken Hepatocytes via the Mitochondrial ROS Pathway.

Arsenic has been shown to be highly toxic and can cause liver damage. Previous studies have shown that arsenic causes severe liver damage and induces accumulation of reactive oxygen species (ROS). This study aimed to investigate the effects of ferroptosis on the liver in arsenic trioxide (ATO) and to explore the underlying mechanisms. We confirmed the hepatotoxic effects of arsenic by in vivo and in vitro experiments. After 28 days of administration of arsenic trioxide (4-mg/kg, 8-mg/kg) by gavage, chickens exhibited body weight loss and liver damage in a dose-dependent manner. In addition, in vivo and in vitro western blot and real-time fluorescence quantitative PCR analyses simultaneously indicated that ferroptosis might be the main pathway of arsenic-induced liver injury. Finally, Mito-TEMPO effectively eliminated the ROS accumulation in mitochondria, significantly attenuating the process of cellular ferroptosis. In summary, the hepatotoxic effects of arsenic are related to ferroptosis, and the hepatic ferroptosis process of arsenic is regulated by mitochondrial ROS (MtROS). Our study reveals new mechanisms of arsenic toxicity to the liver, which may deepen our understanding of arsenic toxicology.