Jinshan Hospital of Fudan University

Endometriomsis (EMs) is a complex and chronic gynecological disease characterized by distressing symptoms. Its pathogenesis remains unknown, and there is no effective treatment. Therefore, establishing patient-derived models is crucial for elucidating disease mechanisms and identifying potential therapeutic agents. We developed a coculture system combining epithelial organoids and stromal cells, enabling the study of their dynamic interactions. Using this model, we assessed the therapeutic efficacy of dienogest, a drug clinically used for treating endometriomas. The epithelial gland-like organoids and stromal cells derived from patients with endometriomas were isolated and cultured, respectively. Both of them were cocultured in matrix for partially mimicking invivo pathological features. Immunohistochemical (IHC) assay was used to identify their biomarkers. Cell viability was quantitatively assessed using the CellTiter-Glo® assay following drug treatment. We successfully cultured patient-derived epithelial gland-like organoids and stromal cells derived from patients with endometriomas, a form of endometriosis characterized by ovarian cysts. Morphological and immunohistochemical analyses confirmed high consistency with native endometriotic lesions. These models exhibited comparable expression profiles for key biological markers, including estrogen receptors (ERs), progesterone receptors (PRs), E-cadherin, CD44, Intercellular Adhesion Molecule-1 (ICAM1), Integrin Beta 3 (ITGB3), Cytokeratin 7 (CK7), Matrix Metalloproteinase 2/9 (MMP2/9), Tissue Inhibitor of Metalloproteinases 1 (TIMP1), and TIMP2. Notably, drug responsiveness varied among the patient-derived models by coculturing two types of cells, indicating potential interpatient heterogeneity in treatment outcomes. We propose that this patient-specific endometriomas model serves as a valuable platform for investigating disease mechanisms and screening drug in endometriomas. We established a novel coculture system integrating epithelial organoids and stromal cells to recapitulate the intricate cellular interactions within the endometriotic microenvironment, providing a more relevant invitro representation of the disease. Upon evaluation with dienogest, a clinically used therapeutic agent for endometriomas, the patient-derived models exhibited heterogeneous drug responses.

We aimed to examine the psychometric properties of the second version of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD-V2.0) and its correspondence with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity scale (CGI-S) scores. This cross-sectional study was conducted at 18 institutes in Japan. We performed correlational analyses to test the convergent and divergent validity of the BE-PSD-V2.0. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). The equipercentile equating method was employed to examine the linking of the BE-PSD-V2.0 with the PANSS and the CGI-S. A total of 353 patients with schizophrenia spectrum disorders were included. Spearman's rank correlation coefficients between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores ranged from 0.64 to 0.86, indicating sufficient convergent validity. These specific correlation coefficients were consistently the highest among all item-to-factor comparisons, indicating sufficient divergent validity. In 34 patients, ICCs for the BE-PSD-V2.0 itemand total scores ranged from 0.60 to 0.94, showing sufficient inter-rater reliability. Conversion tables were established between the BE-PSD-V2.0 total score and the PANSS total score, between the BE-PSD-V2.0 total score and the CGI-S score, and between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores. A correspondence between symptomatic remission criteria using the PANSS and BE-PSD-V2.0 was confirmed. The BE-PSD-V2.0 possesses sufficient psychometric properties and corresponds to the PANSS and CGI-S. It is a sound and reliable brief rating scale for assessing symptoms in schizophrenia spectrum disorders, and its established conversion correspondences facilitate score interpretation within existing clinical paradigms for both clinical practice and research.

To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs. Forty-two-week-old guinea pigs were randomly divided into four groups to assess pupillary responses under varying light intensities (100, 250, 500 lx) and pharmacological interventions (1% atropine, 1% cyclopentolate, 1% tropicamide, or 2% pilocarpine). Baseline pupil size and eccentricity were recorded using a non-contact Python-based imaging system integrating edge detection and pixel-to-distance conversion. Direct illumination effects were measured at sequential time points, followed by drug administration and longitudinal tracking of pupillary changes. The protocol was repeated at 12wk of age for developmental comparisons. Post-experiment, enucleated eyes were analyzed to evaluate in vitro vs in vivo differences. Significant age-dependent differences in pupil dynamics were observed. Both 2- and 12-week-old guinea pigs exhibited marked pupil constriction under direct illumination (P<0.001), with decreased eccentricity post-constriction (P<0.001). Indirect illumination caused inconsistent pupil size changes (2-week: P=0.68; 12-week: P=0.49). Pharmacologically, atropine, cyclopentolate, and tropicamide induced pupil dilation (P<0.001), whereas pilocarpine caused constriction (P<0.001). All drug groups showed reduced eccentricity (P<0.001). In vivo/in vitro comparisons revealed significant structural differences. This study investigates pupillary responses in developing guinea pigs, revealing a direct pupillary light reflex (PLR) with light intensity-dependent responses, while indirect PLR was undetectable. The differential effects of muscarinic modulators on pupillary responses underscore the critical role of cholinergic signaling in ocular accommodation, with age-related variations in sensitivity. Additionally, a novel non-contact measurement methodology achieved a precision of 0.01 mm for pupillary quantification, enhancing accuracy in ocular studies.

The information recovery of speckles is crucial in applications such as underwater exploration, satellite remote sensing, and biomedical imaging. The interplay of nonlinearity and scattering breaks the wavefronts and destroys the image formation. Previous studies have primarily focused on linear scattering models, leaving the reconstruction of images distorted by nonlinear perturbations largely unexplored. Here, we employ a convolutional neural network named the Attention U-Net to reconstruct images modulated by a chlorophyll solution, exhibiting self-defocusing nonlinearity. The proposed approach exhibits strong generalization capability for unseen object categories under nonlinear perturbation. Furthermore, by comparing the performance of models trained with single-power and multi-power mixed datasets, we reveal the relationship between reconstruction ability and nonlinear optical response. Our study establishes an effective connection between green-material-induced nonlinear modulation and deep learning-based optical decoding, offering promising potential for applications in optical information encryption and intelligent imaging systems.

Abstract Bears exhibit an unusual form of hibernation in which core body temperature remains relatively high despite profound suppression of whole-body metabolism. How such a warm yet hypometabolic state is achieved remains poorly understood. Here, through integrative analysis of 238 RNA-seq datasets spanning seven species, we identify transmembrane protein 41B (TMEM41B) as an evolutionarily conserved factor associated with thermogenic capacity. Loss of Tmem41b in mice and Drosophila results in severe cold intolerance, whereas its overexpression enhances thermogenic performance, supporting a conserved role in heat production. Comparative genomic analyses reveal a bear-specific 51 – amino acid N-terminal extension in TMEM41B, arising from a 5 ′ untranslated region mutation that converts a premature stop codon into coding sequence. Interactome profiling indicates that this bear-specific isoform differs from the canonical TMEM41B in its protein interaction landscape, including reduced association with components of mitochondria-associated endoplasmic reticulum membranes such as voltage-dependent anion-selective channel protein 1 (VDAC1). Consistent with this altered interaction profile, the extended isoform is associated with reduced mitochondrial oxidative activity. Functional analyses further suggest that the 51 – amino acid extension modulates multiple cellular programs, including suppression of oxidative phosphorylation and myogenic differentiation alongside activation of osteogenic pathways, collectively biasing cells toward a hypometabolic state. Notably, expression of the polar bear TMEM41B isoform in mice induces a torpor-like phenotype under fasting conditions. Together, these findings identify TMEM41B as a conserved regulator of thermogenic capacity and suggest that evolutionary modification of its N terminus may contribute to metabolic suppression and energy conservation during bear hibernation.

BackgroundMinimal hepatic encephalopathy (MHE) is a frequent neurocognitive complication in chronic hepatic schistosomiasis (CHS) patients. Conventional diagnostic tools are time-consuming and influenced by education level. Quantitative MRI mapping offers a potential non-invasive biomarker for MHE, but its role in CHS remains unclear.AimThis study aimed to evaluate the diagnostic value of quantitative T1 and T2 mapping for detecting MHE in CHS patients.MethodsThis prospective cross-sectional observational study was conducted from August 2023 to July 2024. A total of 88 CHS patients were enrolled and divided into MHE (n = 50) and non-MHE group (n = 38). MHE was assessed using the number connection test-A (NCT-A) and digit symbol test (DST). All participants underwent 3.0T MRI with T1 and T2 mapping. Group comparisons, correlation analyses, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed.ResultsMHE patients exhibited significantly lower T1 values across multiple brain regions, particularly the globus pallidus (all p < 0.001). T2 values showed no significant differences between groups. Multivariable regression confirmed that lower T1 values were independently associated with MHE (p = 0.009). ROC analysis demonstrated excellent diagnostic performance of globus pallidus T1 values (AUC = 0.92, 95% CI: 0.86–0.99), with sensitivity of 0.97 and specificity of 0.90. T1 values were also correlated with neuropsychological tests (NCT-A: r = −0.345, p < 0.001; DST: r = 0.232, p = 0.029). However, T2 values showed no significant group differences or diagnostic value.ConclusionQuantitative T1 mapping, rather than T2 mapping, could be used as a potential non-invasive biomarker for detecting MHE in CHS patients. This approach offers an objective complement to psychometric testing and may facilitate earlier diagnosis and monitoring of MHE progression.

Minimal hepatic encephalopathy (MHE) is a frequent neurocognitive complication in chronic hepatic schistosomiasis (CHS) patients. Conventional diagnostic tools are time-consuming and influenced by education level. Quantitative MRI mapping offers a potential non-invasive biomarker for MHE, but its role in CHS remains unclear. This study aimed to evaluate the diagnostic value of quantitative T1 and T2 mapping for detecting MHE in CHS patients. This prospective cross-sectional observational study was conducted from August 2023 to July 2024. A total of 88 CHS patients were enrolled and divided into MHE (n = 50) and non-MHE group (n = 38). MHE was assessed using the number connection test-A (NCT-A) and digit symbol test (DST). All participants underwent 3.0T MRI with T1 and T2 mapping. Group comparisons, correlation analyses, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. MHE patients exhibited significantly lower T1 values across multiple brain regions, particularly the globus pallidus (all p < 0.001). T2 values showed no significant differences between groups. Multivariable regression confirmed that lower T1 values were independently associated with MHE (p = 0.009). ROC analysis demonstrated excellent diagnostic performance of globus pallidus T1 values (AUC = 0.92, 95% CI: 0.86-0.99), with sensitivity of 0.97 and specificity of 0.90. T1 values were also correlated with neuropsychological tests (NCT-A: r = -0.345, p < 0.001; DST: r = 0.232, p = 0.029). However, T2 values showed no significant group differences or diagnostic value. Quantitative T1 mapping, rather than T2 mapping, could be used as a potential non-invasive biomarker for detecting MHE in CHS patients. This approach offers an objective complement to psychometric testing and may facilitate earlier diagnosis and monitoring of MHE progression.