Parkinson's disease （PD） is a neurodegenerative disorder primarily characterized by motor dysfunction. Traditionally， its main clinical features include resting tremor， muscular rigidity， bradykinesia， and postural balance disorders. However， an increasing number of studies have shown that its non-motor symptoms （NMS） exert an even greater impact on patients' quality of life than motor symptoms， severely affecting daily functioning and increasing the burden on families and society. Among these， depression is one of the most common and most debilitating NMS， with statistics indicating that the incidence of depression among PD patients reaches as high as 40%-50%. The pathological mechanisms are complex， involving the interplay between degenerative changes in dopaminergic neurons and disruptions in emotional regulatory circuits， which poses a substantial challenge to clinical treatment. Traditional Chinese medicine （TCM）， characterized by holistic regulation and multi-target intervention， has demonstrated significant advantages in the treatment of PD and depression， offering new insights for managing PD-depression comorbidity. This study integrates research extracted from multiple databases， including PubMed， Web of Science， Google Scholar， and China National Knowledge Infrastructure （CNKI）， that investigates the potential mechanisms of PD and depression as well as TCM-based treatments for these conditions. The aim is to elucidate the shared pathological mechanisms underlying PD and depression and to explore the therapeutic potential of TCM in effectively combating PD-depression comorbidity through these shared mechanisms， thereby providing valuable insights for the development of targeted therapies.

Objective: To explore the distribution and metabolic characteristics of bongkrekic acid in plasma, serum and urine, and to identify potential biomarkers for bongkrekic acid poisoning, so as to provide evidence for etiological identification and therapeutic effect evaluation. Methods: Blood samples were centrifuged to separate plasma or serum and then stored frozen, while urine samples were directly frozen for preservation. After thawing, the samples were treated with internal standard working solution and 0.5% formic acid acetonitrile solution, and detected after centrifugation and filtration. A C18 chromatographic column with gradient elution was adopted, and electrospray ionization in negative multiple reaction monitoring mode was used with optimized ion pair parameters for the determination of bongkrekic acid. The method was evaluated in terms of matrix effect, linear range, coefficient of determination (R2), limit of detection, limit of quantification, average spiked recovery rate, and relative standard deviation (RSD). Determination of the distribution and mass concentration of bongkrekic acid in three types of samples by liquid chromatography-tandem mass spectrometry, and analysis of its metabolic characteristics Results: The matrix effects of bongkrekic acid in plasma, serum and urine were 86.8%, 88.1% and 93.3%, respectively. The results of methodological validation demonstrated that bongkrekic acid exhibited good linearity within the concentration range of 0.2-100 ng/mL, with R2 of 0.999. The limit of detection and limit of quantification were determined to be 1.0 ng/mL and 2.0 ng/mL, respectively. No interfering peaks were observed in the chromatograms. The average spiked recovery rates ranged from 92.1% to 104.0%, with RSD ranging from 2.9% to 6.8%. Among the 12 patients with bongkrekic acid poisoning, the mass concentrations of bongkrekic acid in plasma and serum from 8 patients within 1-14 days of poisoning ranged from 168.0 to 967.0 ng/mL and from 163.0 to 1 017.0 ng/mL, respectively, with average mass concentration proportions of 50.3% and 49.7%, respectively. Among them, bongkrekic acid mass concentration decreased overall in 2 patients after plasma exchange treatment. Conclusion Bongkrekic acid in plasma or serum can serve as an effective biomarker for poisoning diagnosis and therapeutic effect evaluation of bongkrekic acid poisoning.

Objective: To establish a method for the determination of anisodamine, atropine, and scopolamine in infant complementary foods and formula milk powder by solid-phase extraction combined with liquid chromatography-tandem mass spectrometry. Methods: Commercially available infant complementary foods (biscuits, noodles, and rice flour) and formula milk powder were collected. The samples were homogenized, extracted ultrasonically with 0.5% formic acid-80% aqueous methanol solution, and purified using polymer-based mixed-mode cation-exchange solid-phase extraction cartridges. Gradient elution was performed with 0.02% formic acid-1 mmol/L ammonium formate aqueous solution and methanol as mobile phases. The target compounds were separated using an XBridgeTM BEH C18 column (150 mm×3 mm, 2.5 μm), detected by positive electrospray ionization multiple reaction monitoring mode, and quantified using the isotope internal standard method. Results: When 0.5% formic acid-80% aqueous methanol solution was used for extraction and the loading volume was 5 mL, the peak areas and average spiked recovery rates of the target compounds were relatively high. The matrix effects of infant food were evaluated using the optimized method. Noodles showed a matrix suppression effect, whereas biscuits, rice flour, and formula milk powder exhibited matrix effects close to 100%, which were corrected by isotope internal standard quantification. The three tropane alkaloids had good linear relationships in the range of 0.1-50 ng/mL, with all correlation coefficients greater than 0.999. The limits of detection and limit of quantification were 0.1 and 0.3 μg/kg, respectively. At spiked concentrations of 0.3, 8.0, and 40.0 μg/kg, the average spiked recovery rates of anisodamine, atropine, and scopolamine were 95.7%-102.6%, 93.2%-104.7%, and 95.5%-104.1%, respectively, with relative standard deviations of 1.4%-8.5%, 1.5%-8.4%, and 3.1%-8.5%, respectively. None of the three tropane alkaloids were detected in 100 infant complementary food samples. Among 60 infant formula milk powder samples, atropine and scopolamine were detected in one sample, while anisodamine was not detected. Conclusions The method is simple, accurate, and sensitive, and can effectively eliminate the interference of complex matrix effects. It can be applied to the quantitative determination of tropane alkaloids in infant foods.
liquid chromatography-tandem mass spectrometry ; solid-phase extraction ; anisodamine ; atropine ; scopolamine ; infant complementary food ; formula milk powder

According to the theory of "toxin accumulation damaging yin"， the accumulation of pathological products and the disruption of homeostasis in the pre-metastatic niche （PMN） of malignant tumors correspond to "toxin accumulation" and "yin damage" respectively. During the dynamic evolution of PMN， the main pathogenesis in the initial stage is healthy qi deficiency and phlegm congestion， obstruction in the ying （营） and wei （卫） level， for which the therapeutic approach is fortifying spleen and warming yang， reinforcing healthy qi， consolidating the root， and assissting in resolving phlegm. In the progression stage， the predominant mechanism is mutual binding of phlegm and stasis， with collateral damage and pathological transformation. Treatment should focus on resolving phlegm and eliminating stasis， using insect-derived medicinals to attack accumulation and block pathological transmission. In the terminal stage， the main pathogenesis involves phlegm-stasis transforming into fire， with depletion of qi and yin， for which it is suggested to replenish qi and nourish yin， combine clearing and tonifying methods to control fire-toxin. After the PMN has formed， pathogenic toxin may flow along the collaterals， tending to lodge in corresponding viscera with functional imbalance and deviation between deficiency and excess， eventually giving rise to malignant tumors. Understanding the pathogenesis of the PMN in the malignant tumors based on the "toxin accumulation damaging yin" theory may provide a valuable perspective for developing traditional Chinese medicine strategies for the prevention and treatment of tumor metastasis.

Postpartum lumbopelvic pain(PLPP)occurs in women during the period from pregnancy to the puerperium.Its root cause lies in the deficiency of qi and blood,and the key pathogenesis is the imbalance of qi and blood,leading to meridian blockage.When treating PLPP clinically,it is essential to focus on its pathogenesis and address both the root and the symptoms.Acupuncture points from the spleen meridian,stomach meridian,kidney meridian,conception vessel,and governor vessel are selected to tonify qi,nourish blood,replenish the kidneys,and fill essence to treat the root.Acupuncture points from the liver meridian,heart meridian,and bladder meridian are chosen to regulate qi,activate blood,calm the mind,and dispel cold and dampness to alleviate the symptoms.Ultimately,this approach aims to achieve a state of harmonious qi and blood and smooth meridians,providing a clinical acupuncture strategy for the treatment of PLPP.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Due to its high sensitivity and non-destructive nature, Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development. Despite of the computational demands, data requirements, or ethical considerations, artificial intelligence (AI) and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing, feature extraction, and model optimization, which not only improves the accuracy and efficiency of Raman spectroscopy detection, but also greatly expands its range of application. AI-guided Raman spectroscopy has numerous applications in biomedicine, including characterizing drug structures, analyzing drug forms, controlling drug quality, identifying components, and studying drug-biomolecule interactions. AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics, particularly in disease early diagnosis and treatment optimization. Therefore, AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics, offering new perspectives and tools for disease treatment and pharmaceutical process control. In summary, integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities, offering innovative approaches for research and clinical applications.

ObjectiveThis study aims to explore the neurotoxicity mechanism of Dictamni Cortex by integrating network toxicology and metabolomics techniques. MethodsThe neurotoxicity targets induced by Dictamni Cortex were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCM-ID）， and Comparative Toxicogenomics Database （CTD）. The target predictions of the components were performed by the Swiss Target Prediction tool. Neurotoxicity-related targets were collected from the Pharmacophore Mapping and Potential Target Identification Platform （PharmMapper）， GeneCards Human Gene Database （GeneCards）， DisGeNET Disease Gene Network （DisGeNET）， and Online Mendelian Inheritance in Man （OMIM）， and the intersection targets were identified. Protein-protein interaction （PPI） analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and Gene Ontology （GO） enrichment analysis were conducted. A "drug-compound-toxicity target-pathway" network was constructed via Cytoscape software to display the core regulatory network. Based on the prediction results， the neurotoxicity mechanism of Dictamni Cortex in mice was verified by using hematoxylin-eosin （HE） staining， Nissl staining， enzyme-linked immunosorbent assay （ELISA）， quantitative real-time fluorescence polymerase chain reaction （Real-time PCR）， and Western blot. The effects of Dictamni Cortex on the metabolic profile of mouse brain tissue were further explored by non-targeted metabolomics. ResultsNetwork toxicology screening identified 13 compounds and 175 targets in Dictamni Cortex that were related to neurotoxicity. PPI network analysis revealed that serine/threonine-protein kinase （Akt1） and tumor protein 53 （TP53） were the core targets. Additionally， GO/KEGG enrichment analysis indicated that Dictamni Cortex may regulate the phosphatidylinositol 3-kinase （PI3K）/Akt pathway and affect oxidative stress and cell apoptosis， thereby inducing neural damage. The "Dictamni Cortex-compound-toxicity target-pathway-neural damage" network showed that dictamnine， phellodendrine， and fraxinellone may be the toxic compounds. Animal experiments showed that compared with those in the blank group， the hippocampal neurons in the brain tissue of mice treated with Dictamni Cortex were damaged. The level of superoxide dismutase （SOD） and acetylcholine （ACh） in the brain tissue was significantly reduced， while the content of malondialdehyde （MDA） was significantly increased. The level of Akt1 and p-Akt1 mRNAs and proteins in the brain tissue was significantly decreased， while the level of TP53 was significantly increased. Non-targeted metabolomics results showed that Dictamni Cortex could disrupt the level of 40 metabolites in mouse brain tissue， thereby regulating the homeostasis of 13 metabolism pathways， including phenylalanine， glycerophospholipid， and retinol. Combined analysis revealed that Akt1， p-Akt1， and TP53 were significantly correlated with phenylalanine， glycerophospholipid， and retinol metabolites. This suggested that Dictamni Cortex induced neurotoxicity in mice by regulating Akt1， p-Akt1， and TP53 and further modulating the phenylalanine， glycerophospholipid， and retinol metabolism pathways. ConclusionDictamni Cortex can induce neurotoxicity in mice， and its potential mechanism may be closely related to the activation of oxidative stress， inhibition of the PI3K/Akt signaling pathway， and regulation of phenylalanine， glycerophospholipid， and retinol metabolism pathways.