Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Mediating role of chiro-inositol metabolites on the effects of HLA-DR-expressing CD14 + monocytes in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD's genetic background. METHODS: Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated. RESULTS: We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%. CONCLUSION: Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.

Genetic analysis of a family affected by congenital myasthenic syndrome due to a Novel mutation in the SLC5A7 gene.

BACKGROUND: Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various genetic variations; however, exon deletion variants have yet to be reported in related cases. This study aims to explore the clinical phenotype and genetic traits of a patient with congenital myasthenic syndrome due to SLC5A7 gene variation and those of their family members. CASE PRESENTATION: We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1-9 in the SLC5A7 gene. QPCR confirmed a deletion in exon 9 of the SLC5A7 gene in the patient's mother and brother. Clinical symptoms of myasthenia improved following treatment with pyridostigmine. CONCLUSION: Exons 1, 5, and 9 of the SLC5A7 gene encode the choline transporter's transmembrane region. Mutations in these exons can impact the stability and plasma membrane levels of the choline transporter. Thus, a heterozygous deletion in exons 1-9 of the SLC5A7 gene could be the pathogenic cause for this patient. In patients exhibiting fluctuating weakness, positive RNS, and seronegativity for myasthenia gravis antibodies, a detailed family history should be considered, and enhanced genetic testing is recommended to determine the cause.

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients.

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.

BACKGROUND: Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). RESULTS: Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. CONCLUSIONS: Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma.

Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient's 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.

Melatonin promotes hair regeneration by modulating the Wnt/ß-catenin signalling pathway.

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/ß-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/ß-catenin signalling pathway revealed that MLT up-regulated the Wnt/ß-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/ß-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/ß-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans.

Profiling of long non-coding RNAs in hippocampal-entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer's disease.

Alzheimer's disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal-entorhinal system subfields of individuals with AD pathology and without AD pathology revealed distinctive lncRNA expression profiles. Through differential expression and coexpression analyses, we identified 16 pivotal lncRNAs. Notably, RN7SL1 knockdown significantly modulated microglial responses upon oligomeric amyloid-ß stimulation, resulting in a considerable decrease in proinflammatory cytokine production and subsequent neuronal damage. These findings highlight RN7SL1 as an essential neuroimmune-related lncRNA that could serve as a prospective target for AD diagnosis and treatment.

Individualized prediction of anxiety and depressive symptoms using gray matter volume in a non-clinical population.

Machine learning is an emerging tool in clinical psychology and neuroscience for the individualized prediction of psychiatric symptoms. However, its application in non-clinical populations is still in its infancy. Given the widespread morphological changes observed in psychiatric disorders, our study applies five supervised machine learning regression algorithms-ridge regression, support vector regression, partial least squares regression, least absolute shrinkage and selection operator regression, and Elastic-Net regression-to predict anxiety and depressive symptom scores. We base these predictions on the whole-brain gray matter volume in a large non-clinical sample (n = 425). Our results demonstrate that machine learning algorithms can effectively predict individual variability in anxiety and depressive symptoms, as measured by the Mood and Anxiety Symptoms Questionnaire. The most discriminative features contributing to the prediction models were primarily located in the prefrontal-parietal, temporal, visual, and sub-cortical regions (e.g. amygdala, hippocampus, and putamen). These regions showed distinct patterns for anxious arousal and high positive affect in three of the five models (partial least squares regression, support vector regression, and ridge regression). Importantly, these predictions were consistent across genders and robust to demographic variability (e.g. age, parental education, etc.). Our findings offer critical insights into the distinct brain morphological patterns underlying specific components of anxiety and depressive symptoms, supporting the existing tripartite theory from a neuroimaging perspective.

Heteroions Radii Matching Produced Intensely Luminescent Bismuth-Ag2S Nanocrystals for through-Skull NIR-II Imaging of Orthotopic Glioma.

Heteroions doped Ag2S nanocrystals (NCs) exhibiting enhanced near-infrared-II emission (NIR-II) hold great promise for glioma diagnosis. Nevertheless, current doped Ag2S NCs paradoxically improved properties via toxic dopants, and the blood-brain barrier (BBB) constitutes another challenge for orthotopic glioma imaging. Thus, it is urgent to develop biofriendly high-bright Ag2S NCs with active BBB-penetration for glioma-targeted imaging. Herein, bismuth (Bi) was screened to obtain Bi-Ag2S NCs with high absolute PLQY (∼13.3%) for its matched ionic-radius (1.03 Å) with Ag+. The Bi-Ag2S NCs exhibited a higher luminance and deeper penetration (5-6 mm) than clinical indocyanine green. Upon conjugation with lactoferrin, the NCs acquired BBB-crossing and glioma-targeting abilities. Time-dependent NIR-II-imaging demonstrated their effective accumulation in glioma with skull/scalp intact after intravenous injection. Moreover, the toxic-metal-free NCs exhibited negligible toxicity and great biocompatibility. The success of leveraging the ion-radii comparison may unlock the full potential of doped-Ag2S NCs in bioimaging and inspire the development of various doped NIR-II NCs.

Exploring the release mechanism of micro/nanoplastics from different layers of masks in water: towards reduction of plastic contamination in masks.

During the COVID-19 pandemic, a substantial quantity of disposable face masks was discarded, consisting of three layers of nonwoven fabric. However, their improper disposal led to the release of microplastics (MPs) and nanoplastics (NPs) when they ended up in aquatic environments. To analyze the release kinetics and size characteristics of these masks, release experiments were performed on commercially available disposable masks over a period of 7 days and micro- and nanoplastic releases were detected using fiber counting and nanoparticle tracking analysis. The study's findings revealed that there was no significant difference (p > 0.05) in the quantity of MPs released among the layers of the masks. However, the quantity of NPs released from the middle layer of the mask was 25.9 ± 1.3 × 108 to 81.3 ± 5.3 × 108 particles/piece, significantly higher than the inner and outer layers (p < 0.05). The release process of micro/nanoplastics (M/NPs) from each layer of the mask followed the Elovich equation and the power function equation, indicating that the release was divided into two stages. MPs in the range of 1-500 µm and NPs in the range of 100-300 nm dominated the release from each layer of the mask, accounting for an average of 93.81% and 67.52%, respectively. Based on these findings, recommendations are proposed to reduce the release of M/NPs from masks during subsequent use.

Surgery for longer duration supranuclear ophthalmoplegia secondary to brain stem cavernoma: A case report and literature review.

BACKGROUND: Previous reports revealed that patients with acquired paralytic strabismus caused by central nervous system diseases are primarily affected by the etiology and treatment of the condition. Strabismus correction for these acquired paralytic strabismus should be performed as soon as the primary disease has been stabilized for 6 months in order to archive a favorable surgical outcome. CASE: We followed an infrequent case of longer-lasting supranuclear ophthalmoplegia secondary to brain stem cavernoma. OBSERVATION: A 25-year-old Chinese Han female developed aberrant head posture and ipsilateral conjugate gaze palsies 8 years after the first brainstem hemorrhage caused by pontine cavernoma. The patient was diagnosed with supranuclear ophthalmic palsy and brain stem cavernoma after surgery. A resection-recession procedure along with a rectus muscle transposition was performed. The patient's abnormal head position disappeared, with a normal primary position. CONCLUSION: Resection-recession procedures combined with rectus muscle transposition works very well for longer duration large-angle strabismus caused by brain stem cavernoma.

Three-Point-Star Deoxyribonucleic Acid Tiles with the Core Arm Length at Three Half-Turns for Two-Dimensional Archimedean Tilings and Beyond.

2D Archimedean tiling and complex tessellation patterns assembled from soft materials including modular DNA tiles have attracted great interest because of their specific structures and potential applications in nanofabrication, nanoelectronics, nanophotonics, biomedical sensing, drug delivery, therapeutics, etc. Traditional three- and four-point-star DNA tiles with the core arm length at two half-turns (specified as three- and four-point-star-E previously and abbreviated as 3PSE and 4PSE tiles here) have been applied to assemble intricate tessellations through tuning the size of inserted nT (n = 1-7, T is thymine) loops on helper strands at the tile center. Following our recent findings using a new type of four-point-star tiles with the core arm length at three half-turns (specified as four-point-star-O previously and abbreviated as 4PSO tiles here) to assemble DNA tubes and flat 2D arrays, we report here the cross-hybridization weaving architectures at the tile center to construct three new 3PSO tiles with circular DNA oligonucleotides of 96-nt (nucleotides) serving as the scaffolds, further the monotonous and combinatory E- and O-tilings on one type of 3PSO tiles to create 2D Archimedean tiling patterns (6.6.6) and (4.8.8), and finally, the combination of 3PSO with 4PSO as well as 2PSO tiles to tile into complex tessellation patterns. The easy realization of regular and intricate DNA tessellations with 2-4PSO tiles not only richens the fundamental DNA modules and complex DNA nanostructures in types but also broadens the potential application scopes of DNA nanostructures in nanofabrication, DNA computing, biomedicine, etc.

Identifying serum metabolite biomarkers for autoimmune diseases: a two-sample mendelian randomization and meta-analysis.

Background: Extensive evidence suggests a link between alterations in serum metabolite composition and various autoimmune diseases (ADs). Nevertheless, the causal relationship underlying these correlations and their potential utility as dependable biomarkers for early AD detection remain uncertain. Objective: The objective of this study was to employ a two-sample Mendelian randomization (MR) approach to ascertain the causal relationship between serum metabolites and ADs. Additionally, a meta-analysis incorporating data from diverse samples was conducted to enhance the validation of this causal effect. Materials and methods: A two-sample MR analysis was performed to investigate the association between 486 human serum metabolites and six prevalent autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), dermatomyositis (DM), type 1 diabetes (T1D), and celiac disease (CeD). The inverse variance weighted (IVW) model was employed as the primary analytical technique for the two-sample MR analysis, aiming to identify blood metabolites linked with autoimmune diseases. Independent outcome samples were utilized for further validation of significant blood metabolites. Additional sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and retention rate analysis, were conducted. The results from these analyses were subsequently meta-integrated. Finally, metabolic pathway analysis was performed using the KEGG and Small Molecule Pathway Databases (SMPD). Results: Following the discovery and replication phases, eight metabolites were identified as causally associated with various autoimmune diseases, encompassing five lipid metabolism types: 1-oleoylglycerophosphoethanolamine, 1-arachidonoylglycerophosphoethanolamine, 1-myristoylglycerophosphocholine, arachidonate (20:4 n6), and glycerol. The meta-analysis indicated that three out of these eight metabolites exhibited a protective effect, while the remaining five were designated as pathogenic factors. The robustness of these associations was further confirmed through sensitivity analysis. Moreover, an investigation into metabolic pathways revealed a significant correlation between galactose metabolism and autoimmune diseases. Conclusion: This study revealed a causal relationship between lipid metabolites and ADs, providing novel insights into the mechanism of AD development mediated by serum metabolites and possible biomarkers for early diagnosis.

Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation.

Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results: We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion: We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted.

Comparative transcriptome analysis reveals the importance of phenylpropanoid biosynthesis for the induced resistance of 84K poplar to anthracnose.

BACKGROUND: Poplar anthracnose, which is one of the most important tree diseases, is primarily caused by Colletotrichum gloeosporioides, which has been detected in poplar plantations in China and is responsible for serious economic losses. The characteristics of 84K poplar that have made it one of the typical woody model plants used for investigating stress resistance include its rapid growth, simple reproduction, and adaptability. RESULTS: In this study, we found that the resistance of 84K poplar to anthracnose varied considerably depending on how the samples were inoculated of the two seedlings in each tissue culture bottle, one (84K-Cg) was inoculated for 6 days, whereas the 84K-DCg samples were another seedling inoculated at the 6th day and incubated for another 6 days under the same conditions. It was showed that the average anthracnose spot diameter on 84K-Cg and 84K-DCg leaves was 1.23 ± 0.0577 cm and 0.67 ± 0.1154 cm, respectively. Based on the transcriptome sequencing analysis, it was indicated that the upregulated phenylpropanoid biosynthesis-related genes in 84K poplar infected with C. gloeosporioides, including genes encoding PAL, C4H, 4CL, HCT, CCR, COMT, F5H, and CAD, are also involved in other KEGG pathways (i.e., flavonoid biosynthesis and phenylalanine metabolism). The expression levels of these genes were lowest in 84K-Cg and highest in 84K-DCg. CONCLUSIONS: It was found that PAL-related genes may be crucial for the induced resistance of 84K poplar to anthracnose, which enriched in the phenylpropanoid biosynthesis. These results will provide the basis for future research conducted to verify the contribution of phenylpropanoid biosynthesis to induced resistance and explore plant immune resistance-related signals that may regulate plant defense capabilities, which may provide valuable insights relevant to the development of effective and environmentally friendly methods for controlling poplar anthracnose.

Letrozole induced a polycystic ovary syndrome model in zebrafish by interfering with the hypothalamic-pituitary-gonadal axis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women of childbearing age, with an incidence of 5-10%. This study compared the traits of zebrafish with three diagnostic criteria for human PCOS, and the diagnostic criteria for zebrafish PCOS were proposed: decreased fecundity, elevated testosterone (T) or 11-ketotestosterone (11-KT) levels and increased cortical-alveolar oocyte (CO) ratio, enhancing the zebrafish PCOS model's accuracy. According to the mammalian PCOS classification, the type of zebrafsh PCOS is divided into four phenotypes (A, B, C and D), but the four phenotypes of zebrafish PCOS are not fully covered in the existing studies (A and D). In this study, we successfully induced phenotype B zebrafish PCOS model using the aromatase inhibitor, letrozole (LET). That is, wild-type female zebrafish were exposed to 1000 µg/L LET for 30 days. Reproductive tests showed decreased fecundity in female zebrafish exposed to LET (Control: 132.63, 146.00, 173.00; LET: 29.20, 90.00, 82.71). Hormone analysis showed that female zebrafish exposed to LET had significantly lower 17ß-estradiol/testosterone (E2/T) ratios, indicating elevated T levels. Meanwhile, levels of 11-KT in the ovaries exposed to LET were significantly up-regulated (Control: 0.0076 pg/µg; LET: 0.0138 pg/µg). Pathological sections of the ovary showed fewer CO in the LET-exposed group (Control: 16.27%; LET: 8.38%). In summary, the zebrafish PCOS model summarized and studied in this study provide a reliable and economical tool for the screening of therapeutic drugs, as well as for the etiology research and treatment strategies of PCOS.

Mechanisms of imbalanced testicular homeostasis in infancy due to aberrant histone acetylation in undifferentiated spermatogonia under different concentrations of Di(2-ethylhexyl) phthalate (DEHP) exposure.

Di (2-ethylhexyl) phthalate (DEHP), identified as an endocrine-disrupting chemical, is associated with reproductive toxicity. This association is particularly noteworthy in newborns with incompletely developed metabolic functions, as exposure to DEHP can induce enduring damage to the reproductive system, potentially influencing adult reproductive health. In this study, we continuously administered 40 µg/kg and 80 µg/kg DEHP to postnatal day 5 (PD5) mice for ten days to simulate low and high doses of DEHP exposure during infancy. Utilizing single-cell RNA sequencing (scRNA-seq), our analysis revealed that varying concentrations of DEHP exposure during infancy induced distinct DNA damage response characteristics in testicular Undifferentiated spermatogonia (Undiff SPG). Specifically, DNA damage triggered mitochondrial dysfunction, leading to acetyl-CoA content alterations. Subsequently, this disruption caused aberrations in histone acetylation patterns, ultimately resulting in apoptosis of Undiff SPG in the 40 µg/kg DEHP group and autophagy in the 80 µg/kg DEHP group. Furthermore, we found that DEHP exposure impacts the development and functionality of Sertoli and Leydig cells through the focal adhesion and PPAR signaling pathways, respectively. We also revealed that Leydig cells regulate the metabolic environment of Undiff SPG via Ptn-Sdc4 and Mdk-Sdc4 after DEHP exposure. Finally, our study provided pioneering evidence that disruptions in testicular homeostasis induced by DEHP exposure during infancy endure into adulthood. In summary, this study elucidates the molecular mechanisms through which DEHP exposure during infancy influences the development of testicular cell populations.

Single Fluorescent Probe for Multiple Tasks: Illuminating Lipid Droplets and Lysosomes in Dual Channels and Distinguishing Autophagy and Apoptosis.

Lipid droplets (LDs) and lysosomes play key roles in autophagy and cell apoptosis, and the discriminative visualization of the two organelles and simultaneously of autophagy and apoptosis is very helpful to understand their internal relationships. However, fluorescent probes that can concurrently achieve these tasks are not available currently. Herein, we delicately fabricate a robust probe CAQ2 for multiple tasks: illumination of LDs and lysosomes in dual emission colors as well as discriminative visualization of cell apoptosis and autophagy. The probe exhibited both lipophilic and basic properties and displayed different emission colors in neutral and protonated forms; thus, LDs and lysosomes emitted blue and red fluorescence colors, respectively. Because of the lysosomal acidification during autophagy, CAQ2 detected autophagy with evidently enhanced red emission. Because of the lysosomal alkalization during apoptosis, CAQ2 imaged apoptosis with a drastically decreased red fluorescence intensity. With the robust probe, the autophagy under starvation and lipidless conditions was visualized, and the apoptosis induced by H2O2, ultraviolet (UV) irradiation, and rotenone treatment was successfully observed. The efficient detoxification of Na2S against rotenone treatment was successfully revealed.