Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

ObjectiveTo investigate the application value of a multimodal model integrating radiomics features， deep learning features， and clinical structured data in predicting severe acute pancreatitis （SAP）， and to provide more accurate tools for the early identification of SAP in clinical practice. MethodsThe patients with acute pancreatitis （AP） who attended The First Affiliated Hospital of Soochow University， Jintan Hospital Affiliated to Jiangsu University， and Suzhou Yongding Hospital from January 1， 2017 to December 31， 2023 were included. Related data were collected， including demographic information， previous medical history， etiology， laboratory test data， and systemic inflammatory response syndrome （SIRS） within 24 hours after admission， as well as imaging data within 72 hours after admission， while related scores were calculated， including Ranson score， modified CT severity index （MCTSI）， bedside index for severity in acute pancreatitis （BISAP）， and systemic inflammatory response syndrome， albumin， blood urea nitrogen and pleural effusion （SABP） score. The model was constructed in the following process： （1） three-dimensional CT images were used to extract and identify radiomics features， and a radiomics classification model was established based on the extreme gradient Boost （XGBoost） algorithm； （2） U-Net is used to perform semantic segmentation of three-dimensional CT images， and then the results of segmentation were imported into 3D ResNet50 to construct a deep learning classification model； （3） the predicted values of the above two models were integrated with clinical structured data to establish a multimodal model based on the XGBoost algorithm. The variable importance plot and local interpretability plot were used to perform visual interpretation of the model. The independent samples t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or Fisher’s exact test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted for each model and existing scoring systems， and the area under the ROC curve （AUC） was calculated to assess their performance； the Delong test was used for comparison of AUC. ResultsA total of 609 patients who met the criteria were included， among whom 114 （18.7%） developed SAP. In this study， the data of 426 patients from The First Affiliated Hospital of Soochow University was used as the training set， and the data of 183 patients from Jintan Hospital Affiliated to Jiangsu University and Suzhou Yongding Hospital were used as the independent test set. The multimodal model had an AUC of 0.914 in the test set， which was significantly higher than the AUC of traditional scoring systems such as MCTSI （AUC=0.827）， Ranson score （AUC=0.675）， BISAP （AUC=0.791）， and SABP score （AUC=0.648）； in addition， the multimodal model showed a significant improvement in performance compared with the radiomics classification model （AUC=0.739） and the deep learning classification model （AUC=0.685） （the Delong test： Z=-3.23， -4.83， -3.48， -4.92， -4.31， and -4.59， all P <0.01）. The top 10 variables in terms of importance in the multimodal model were pleural effusion， predicted value of the deep learning model， predicted value of the radiomics model， triglycerides， calcium ions， SIRS， white blood cell count， age， platelets， and C-reactive protein， suggesting that the above variables had significant contributions to the performance of the model in predicting SAP. ConclusionBased on structured data， radiomic features， and deep learning features， this study constructs a multicenter prediction model for SAP based on the XGBoost algorithm， which has a better predictive performance than existing traditional scoring systems and unimodal models.

Objective:To validate the morphological changes of the parieto-occipital sulcus on the transcalvarial axial plane between 20 and 32 weeks of gestation, simplify grade for assessing fetal parieto-occipital sulcus development, and confirm its clinical feasibility.Methods:This was a cross-sectional study analysis that included 550 cases of normal singleton fetuses between 20 and 32 weeks of gestation, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The morphological changes of the bilateral parieto-occipital sulci on the transcalvarial axial plane were observed. The development of the parieto-occipital sulcus was classified into 6 grades based on the developmental features of angulation, progressive closure, and curvilinear growth: straight or shallow arcuate (Grade 0), shallow and wide V-shaped (Grade 1), deep and narrow V-shaped (Grade 2), Y-shaped (Grade 3), I-shaped (Grade 4), and curvilinear (Grade 5). The gestational age at examination and pregnancy outcomes were recorded. The distribution of gestational weeks for fetuses with different grades of parieto-occipital sulci on the left and right sides was analyzed. The symmetry between bilateral parieto-occipital sulcus gradings within individuals, as well as the inter-observer and intra-observer reliability were assessed using the Weighted Kappa coefficient. The gender differences in asymmetry of parieto-occipital sulci grades between the left and right sides was analyzed. Moreover, a model for predicting the grade of the parieto-occipital sulcus based on gestational week was established.Results:Grade for the left parieto-occipital sulcus was obtained for 549 fetuses, while grade for the right was obtained for 550 fetuses. From 20 to 32 weeks of gestation, the morphology of the fetal parieto-occipital sulcus was divided into Grade 0-5, progressing from low to high with gestational development. Grade 0 showed that the sulcus was not visible or only had a slight arcuate indentation, occurring at 20-22 weeks; Grade 1 presented as a shallow and wide "V" shape with an obtuse angle at the top, appearing from 20 to 27 weeks; Grade 2 was a deep and narrow "V" shape with an acute angle at the top, appearing from 24 to 29 weeks; Grade 3 appeared as a "Y" shape with the top part partially closed and the bottom still open, occurring between 26 to 30 weeks; Grade 4 was a fully closed "I" shape, appearing at 29-32 weeks; Grade 5 presented as a curved shape, indicating the parieto-occipital sulcus was approaching maturity, appearing from 31 to 32 weeks. There was no statistically significant difference in the distribution of gestational weeks for bilateral parieto-occipital sulcus developmental grade ( P>0.05). Bilateral parieto-occipital sulcus grade could be assessed in 549 fetuses, of which 43 cases (7.83%) exhibited grade asymmetry with a one-grade difference between sides; such asymmetry showed no significant difference between male and female genders ( P=0.647). The weighted kappa coefficient analysis results indicated a strong consistency in the development of the parieto-occipital sulci on both sides within individuals, generally demonstrating symmetrical development ( P<0.001). The intra-observer and inter-observer weighted kappa coefficients were 0.92 and 0.75, respectively, with good consistency. Conclusions:Prenatal ultrasound via the transcalvarial axial plane enables a preliminary and rapid assessment of the development of bilateral parieto-occipital sulci, facilitating early evaluation of fetal cortical maturation.

Objectives To provide scientific basis for the quality control of different species of Baishouwu by establishing the HPLC fingerprint of domestic of Baishouwu and determining the main active components of acetophenones. Methods HPLC-DAD method was used to determine the HPLC fingerprints of domestic of Baishouwu. Then, the content of 4 kinds of acetophenones in Baishouwu was determined. The column was Diamonsil C₁₈（250mm×4.6mm, 5μm）with the mobile phase of methanol and 0.1% phosphoric acid at a flow rate of 1.0 ml/min. The detection wavelength of p-Hydroxyl acetophenone, baishouwu benzophenone, 2',4'-Dihydroxy acetophenone was set at 260 nm and 2',5'-Dihydroxy acetophenone at 280 nm respectively. Results The similarity and cluster analysis in HPLC fingerprint showed that the constituents were significantly different among C. bungei, C. auriculatum and C. wilfordii. The content of total acetophenones in C. wilfordii was significantly higher than that in other localities of C. auriculatum and C. bungei. Conclusions Acetophenone could be used as the evaluation index to evaluate the quality of Baishouwu in different origins. The content of total acetophenone in C. wilfordii is the highest, which could be used as the best quality resource of Baishouwu.

Objective To investigate the long non-coding RNA(lncRNA) MRAK08838 regulates macrophage function to influence the development of asthmatic airway inflammation. Methods MRAK088388 gene knockout (MRAK088388^-/-) mouse model was prepared and allergic asthma was induced by dust mite protein Dermatophagoides farinae 1 (Der f1). The mice were sacrificed after 28 days of modeling, and serum was collected to measure IgE and IgG. The FinePointe RC system was used to measure airway hyperresponsiveness and evaluate lung function in mice. Lung tissue was taken for HE staining, and periodic acid-Schiff (PAS) staining was used to evaluate inflammatory infiltration and mucus secretion in mouse lungs. Fluorescence quantitative PCR was used to detect the expression level of lncRNA MRAK08838 in bronchoalveolar lavage fluid (BALF) cells and lung tissue of asthmatic mice. ELISA was used to detect the levels of inflammatory cytokines IFN-γ, IL-4, IL-5, IL-13, IL-10 and IL-17A. Flow cytometry was used to evaluate the phenotype of macrophages in BALF and lung tissue, as well as the proportion of neutrophils, eosinophils, and alveolar macrophages. The changes of the above indicators were detected in mice by adoptive transfer of bone marrow-derived macrophages (BMDM). Results Under the challengle of Der f1, MRAK088388^-/- mice showed reduced allergic airway inflammation, including reduced eosinophils in BALF and reduced production of IgE and IgG1. In addition, Der f1-treated MRAK088388^-/- mice had fewer M2 macrophages than wild-type asthmatic mice. Wild-type mouse BMDM (M0) and Der f1-treated MRAK088388^-/- mice also showed mild inflammatory response. Conclusion Knockout of MRAK088388 alleviates airway inflammation in asthmatic mice by inhibiting M2 polarization of airway macrophages.
Animals ; Mice ; Mice, Knockout ; RNA, Long Noncoding/genetics* ; Asthma/genetics* ; Macrophages ; Immunoglobulin E

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.