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Abstract Background The medial prefrontal cortex (mPFC) is involved in complex functions containing multiple types of neurons in distinct subregions with preferential roles. The pyramidal neurons had wide-range projections to cortical and subcortical regions with subregional preferences. Using a combination of viral tracing and fluorescence micro-optical sectioning tomography (fMOST) in transgenic mice, we systematically dissected the whole-brain connectomes of intratelencephalic (IT) and pyramidal tract (PT) neurons in four mPFC subregions. Results IT and PT neurons of the same subregion projected to different target areas while receiving inputs from similar upstream regions with quantitative differences. IT and PT neurons all project to the amygdala and basal forebrain, but their axons target different subregions. Compared to subregions in the prelimbic area (PL) which have more connections with sensorimotor-related regions, the infralimbic area (ILA) has stronger connections with limbic regions. The connection pattern of the mPFC subregions along the anterior–posterior axis showed a corresponding topological pattern with the isocortex and amygdala but an opposite orientation correspondence with the thalamus. Conclusions By using transgenic mice and fMOST imaging, we obtained the subregional preference whole-brain connectomes of IT and pyramidal tract PT neurons in the mPFC four subregions. These results provide a comprehensive resource for directing research into the complex functions of the mPFC by offering anatomical dissections of the different subregions.

ObjectiveTo investigate the effect of calcium channel blockers (CCBs) on tacrolimus blood concentrations in renal transplant recipients with different CYP3A5 genotypes.MethodsThis retrospective cohort study included renal transplant recipients receiving tacrolimus-based immunosuppressive therapy with or without CCBs in combination. Patients were divided into combination and control groups based on whether or not they were combined with CCBs, and then further analyzed according to the type of CCBs (nifedipine/amlodipine/felodipine). Propensity score matching was conducted for the combination and the control groups using SPSS 22.0 software to reduce the impact of confounding factors. The effect of different CCBs on tacrolimus blood concentrations was evaluated, and subgroup analysis was performed according to the patients’ CYP3A5 genotypes to explore the role of CYP3A5 genotypes in drug-drug interactions between tacrolimus and CCBs.ResultsA total of 164 patients combined with CCBs were included in the combination groups. After propensity score matching, 83 patients with nifedipine were matched 1:1 with the control group, 63 patients with felodipine were matched 1:2 with 126 controls, and 18 patients with amlodipine were matched 1:3 with 54 controls. Compared with the controls, the three CCBs increased the dose-adjusted trough concentration (C0/D) levels of tacrolimus by 41.61%–45.57% (P < 0.001). For both CYP3A5 expressers (CYP3A5*1*1 or CYP3A5*1*3) and non-expressers (CYP3A5*3*3), there were significant differences in tacrolimus C0/D between patients using felodipine/nifedipine and those without CCBs (P < 0.001). However, among CYP3A5 non-expressers, C0/D values of tacrolimus were significantly higher in patients combined with amlodipine compared to the controls (P = 0.001), while for CYP3A5 expressers, the difference in tacrolimus C0/D values between patients with amlodipine and without was not statistically significant (P = 0.065).ConclusionCCBs (felodipine/nifedipine/amlodipine) can affect tacrolimus blood concentration levels by inhibiting its metabolism. The CYP3A5 genotype may play a role in the drug interaction between tacrolimus and amlodipine. Therefore, genetic testing for tacrolimus and therapeutic drug monitoring are needed when renal transplant recipients are concurrently using CCBs.

Abstract Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159–520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.

Cytoarchitecture, the organization of cells within organs and tissues, serves as a crucial anatomical foundation for the delineation of various regions. It enables the segmentation of the cortex into distinct areas with unique structural and functional characteristics. While traditional 2D atlases have focused on cytoarchitectonic mapping of cortical regions through individual sections, the intricate cortical gyri and sulci demands a 3D perspective for unambiguous interpretation. In this study, we employed fluorescent micro-optical sectioning tomography to acquire architectural datasets of the entire macaque brain at a resolution of 0.65 μm × 0.65 μm × 3 μm. With these volumetric data, the cortical laminar textures were remarkably presented in appropriate view planes. Additionally, we established a stereo coordinate system to represent the cytoarchitectonic information as surface-based tomograms. Utilizing these cytoarchitectonic features, we were able to three-dimensionally parcel the macaque cortex into multiple regions exhibiting contrasting architectural patterns. The whole-brain analysis was also conducted on mice that clearly revealed the presence of barrel cortex and reflected biological reasonability of this method. Leveraging these high-resolution continuous datasets, our method offers a robust tool for exploring the organizational logic and pathological mechanisms of the brain’s 3D anatomical structure.

Individuals have different rumination patterns after experiencing traumatic events in different cultural backgrounds and situations. This study aimed to explore the experience of Chinese young and middle-aged patients with acute coronary syndrome (ACS) to understand the content and nature of their rumination. Sixteen participants were selected using the purposive sampling method in the First Affiliated Hospital of Soochow University from May 2023 to December 2023. Data were collected using semi-structured interviews and analyzed using Colaizzi’s seven-step phenomenological method. The participants went through two successive stages: non-adaptive rumination and adaptive rumination. During the initial admission phase, all the participants experienced varying degrees of non-adaptive rumination. Non-adaptive rumination included four sub-themes: worry or anxiety of daily activities and medical therapy (37.50%), fear of unpredictable outcomes and death (37.50%), sadness of maladjustment (25.00%), and remorse of carelessness (12.50%). During the period of stable condition and pre-discharge, the participants received health education and gradually all transitioned to adaptive rumination. Adaptive rumination included four sub-themes: tracing of disease processes (100%), enhancement of disease cognition (81.25%), improvement of health awareness (62.50%), and adjustment of lifestyle cognition (100%). In conclusion, although the Chinese young and middle-aged patients with ACS experienced negative emotions after a traumatic cardiac event, they gradually made positive changes, and optimism and information support played important roles in this transition. The results of this study provide a fundamental understanding of rumination experiences in Chinese young and middle-aged patients with ACS and provide new data for healthcare providers when designing intervention programs to enhance post-traumatic growth in these patients.

Efficient storage and sharing of massive biomedical data would open up their wide accessibility to different institutions and disciplines. However, compressors tailored for natural photos/videos are rapidly limited for biomedical data, while emerging deep learning-based methods demand huge training data and are difficult to generalize. Here, we propose to conduct Biomedical data compRession with Implicit nEural Function (BRIEF) by representing the target data with compact neural networks, which are data specific and thus have no generalization issues. Benefiting from the strong representation capability of implicit neural function, BRIEF achieves 2-3 orders of magnitude compression on diverse biomedical data at significantly higher fidelity than existing techniques. Besides, BRIEF is of consistent performance across the whole data volume, and supports customized spatially varying fidelity. BRIEF's multifold advantageous features also serve reliable downstream tasks at low bandwidth. Our approach will facilitate low-bandwidth data sharing and promote collaboration and progress in the biomedical field. [ABSTRACT FROM AUTHOR]

The main olfactory bulb is the key element of the olfactory pathway of rodents. To precisely dissect the neural pathway in the main olfactory bulb (MOB), it is necessary to construct the three-dimensional morphologies of the anatomical structures within it with micro-level resolution. However, the construction remains challenging due to the complicated shape of the anatomical structures in the main olfactory bulb and the high resolution of micro-optical images. To address these issues, we propose an interactive volume image segmentation method with micro-level resolution in the horizontal and axial direction. Firstly, we obtain the initial location of the anatomical structures by manual annotation and design a patch-based neural network to learn the complex texture feature of the anatomical structures. Then we randomly sample some patches to predict by the trained network and perform an annotation reconstruction based on intensity calculation to get the final location results of the anatomical structures. Our experiments were conducted using Nissl-stained brain images acquired by the Micro-optical sectioning tomography (MOST) system. Our method achieved a mean dice similarity coefficient (DSC) of 81.8% and obtain the best segmentation performance. At the same time, the experiment shows the three-dimensional morphology reconstruction results of the anatomical structures in the main olfactory bulb are smooth and consistent with their natural shapes, which addresses the possibility of constructing three-dimensional morphologies of the anatomical structures in the whole brain. [ABSTRACT FROM AUTHOR]

Antibiotics play a vital role in safeguarding people's health since most bacterial infection can be efficiently controlled and cured by treating with suitable antibiotics. However, excessive use of antibiotics in husbandry and aquaculture leaded to the pollution of eco-environment. Thus, it is important to develop simple facile methods and effective functional materials for quick on-site analysis of antibiotics. Covalent organic frameworks (COFs), as a kind of porous crystalline covalent bond linked polymers, have demonstrated its power in multiple fields. Herein, we will discuss COFs-based materials utilized as antibiotics sensors with fluorescence method. For each sensor, we will mainly discuss the mechanism for antibiotics recognition, the preparation, characterization and fluorescence sensing performance of specific antibiotics. The mechanism to illustrate the interaction between sensors and antibiotics analytes would also be stressed.