The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA_A receptor (GABA_AR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Although microplastics have been detected in human blood, placenta and other tissues. In this study, for the first time, we characterized the presence and variation of microplastic deposition patterns in three human skeletal tissues, namely the bone, cartilage, and intervertebral discs. Forty microplastic fragments were observed in 24 samples from the bone, cartilage, and intervertebral disc, ranging from 25.44 to 407.39 μm in diameter. The deposition abundance of microplastics in the human intervertebral disc (61.1 ± 44.2 particles/g) was higher than those in the bone (22.9 ± 15.7 particles/g) and cartilage tissue (26.4 ± 17.6 particles/g). The average sizes of microplastics in intervertebral discs (159.5 ± 103.8 μm) and bone (138.86 ± 105.67 μm) were larger than that in the cartilage tissue (87.5 ± 30.7 μm). The most frequently identified polymers were polypropylene (35 %), ethylene vinyl acetate copolymer (30 %), and polystyrene (20 %). The in vivo experiment suggested that microplastics invaded the bone, cartilage, and intervertebral discs through blood circulation after 4 weeks of exposure. Serum levels of tumor necrosis factor-α (TNF-α), Type Ⅰ procollagen amino-terminal peptide (PINP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were elevated compared with those in the control group (p < 0.05). Our study suggests that microplastics invade the bone, cartilage, and intervertebral discs through the blood supply, causing distinct patterns of microplastic accumulation in these regions. Microplastic invasion can affect skeletal health by influencing the expression of inflammatory and bone morphogenetic cytokines. These findings provide insights into investigating the impact of microplastics on human skeletal health.

Diabetic polyneuropathy (DPN) presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies) and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies) in the dorsal root ganglion (DRG) and spinal cord of streptozotocin (STZ)-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB) to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

Meniscal injury represents a common type of knee injury, accounting for over 50% of all knee injuries. The clinical diagnosis and treatment of meniscal injury heavily rely on magnetic resonance imaging (MRI). However, accurately diagnosing the meniscus from a comprehensive knee MRI is challenging due to its limited and weak signal, significantly impeding the precise grading of meniscal injuries. In this study, a visual interpretable fine grading (VIFG) diagnosis model has been developed to facilitate intelligent and quantified grading of meniscal injuries. Leveraging a multilevel transfer learning framework, it extracts comprehensive features and incorporates an attributional attention module to precisely locate the injured positions. Moreover, the attention-enhancing feedback module effectively concentrates on and distinguishes regions with similar grades of injury. The proposed method underwent validation on FastMRI_Knee and Xijing_Knee dataset, achieving mean grading accuracies of 0.8631 and 0.8502, surpassing the state-of-the-art grading methods notably in error-prone Grade 1 and Grade 2 cases. Additionally, the visually interpretable heatmaps generated by VIFG provide accurate depictions of actual or potential meniscus injury areas beyond human visual capability. Building upon this, a novel fine grading criterion was introduced for subtypes of meniscal injury, further classifying Grade 2 into 2a, 2b, and 2c, aligning with the anatomical knowledge of meniscal blood supply. It can provide enhanced injury-specific details, facilitating the development of more precise surgical strategies. The efficacy of this subtype classification was evidenced in 20 arthroscopic cases, underscoring the potential enhancement brought by intelligent-assisted diagnosis and treatment for meniscal injuries.

Microplastics (MPs), pervasive environmental pollutants, have infiltrated human tissues, raising global health concerns. This study investigated the distribution and characteristics of MPs across seven major human organs (lungs, heart, liver, spleen, brain, kidneys, and small intestine) using Raman imaging and machine learning. Tissue samples from eight donors were analyzed for MP presence and characteristics. A deep learning-enhanced U-Net model segmented MPs in Raman images, while a random forest classifier was employed to identify organ-specific MP attribution using 120 imaging features. Animal models supported the systemic distribution of MPs. MPs were ubiquitous across all organs examined. The highest MP abundance was observed in the liver (65.28 ± 23.94 particles/g), small intestine (61.06 ± 25.25 particles/g), and kidneys (58.63 ± 16.50 particles/g). Organ-specific variations in MP characteristics were identified: larger particles dominated the lungs (56.80 ± 57.70 μm), while smaller particles (<10 μm) prevailed in the liver and spleen. Distinct polymer compositions and shape profiles were observed for each organ. The random forest classifier achieved 72.73% accuracy in organ-specific MP attribution. MP abundance was linked to organ vascularity. The findings highlight organ-specific risks of MPs and provide a framework for assessing health impacts, thus guiding targeted interventions to mitigate exposure.