Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Objective To explore the application effect of team-based learning(TBL)teaching method combined with scenario simulation in the team-based cardiopulmonary resuscitation(CPR)training for standardized training of resident physicians in department of emergency.Methods A total of 86 standardized training resident physicians rotating in the department of emergency of Guangdong Provincial People's Hospital Southern Medical University from May 2022 to July 2023 were included as study subjects.These resident physicians were divided into a control group(n=42)and an observation group(n=44)according to different teaching methods.The control group was taught using the conventional teaching method,whereas the observation group was taught using a combination of TBL and scenario simulation-based method.The difference of theoretical assessment scores,practical skill competency and training satisfaction were compared before and after training between groups.Results The theoretical and practice skill assessment scores of both groups significantly improved after training(all P<0.05).However,there was no significant difference in the theoretical assessment scores or the score increase between the two groups before and after training.In the subcategory of theoretical assessment scores,the observation group had significantly higher points than the control group in the precautions category after training(21.09±2.07 vs.20.07±1.85,P<0.05).Compared with the control group,the observation group had significantly higher post-training practical skill scores and a significantly greater score increase(scores:86.77±3.89 vs.81.17±4.18,score increase:11±5.15 vs.8±4.60,both P<0.05).Among the subcategory practical skill scores,the observation group outperformed the control group in communication skills,emergency skills and teamwork+humanistic care(communication skills points:21.36±1.71 vs.20.07±1.54,emergency skills points:21.73±1.35 vs.20.21±1.79,teamwork+humanistic care points:22.27±1.76 vs.19.71±2.71,all P<0.05).The degree of satisfaction in overall training satisfaction,the novelty of the teaching method,teacher affinity,interests in learning,developing teamwork ability,class atmosphere,communication and expression ability,and confidence in skill mastery were significantly higher in the observation group than in the control group[overall training satisfaction:97.73%(43/44)vs.50.00%(21/42),the novelty of the teaching method:90.91%(40/44)vs.47.62%(20/42),teacher affinity:93.18%(41/44)vs.57.14%(24/42),interests in learning:97.73%(43/44)vs.59.52%(25/42),developing teamwork ability:95.45%(42/44)vs.52.38%(22/42),class atmosphere:93.18%(41/44)vs.57.14%(24/42),improve communication and expression ability:100.00%(44/44)vs.50.00%(21/42),and confidence in skill mastery:93.18%(41/44)vs.45.24%(19/42),all P<0.05].Conclusion The application of TBL teaching method combined with scenario simulation in CPR training for standardized training of resident physicians can effectively improve quality of clinical skill training.

To explore the feasibility of using UAV-LiDAR for measuring the leaf area index (LAI) of crop canopies, we employed UAV-LiDAR to scan sugarcane canopies during the tillering and elongation stages, acquiring canopy point cloud data. Subsequently, features such as average row height, projected row area, point cloud density at different canopy layers, and the ratios between these parameters were extracted. Three feature selection methods-partial least squares regression (PLSR), XGBoost feature importance (XGBoost-FI), and random forest-recursive feature elimination (RF-RFE)-were adopted to evaluate and identify the optimal input variables for modeling. With these selected variables, LAI inversion models were developed based on random forest (RF) and adaptive boosting (AdaBoost) algorithms, and their performance was assessed. Among the extracted features, the projected row area S_p and the total row point count C_total exhibited strong correlations with LAI, with correlation coefficients of 0.73 and 0.72, respectively. The AdaBoost-based LAI inversion model, using the projected row area S_p, average height H_avg, mid-layer point cloud density C_m, and total row point count C_total as input variables, achieved the best performance, with a coefficient of determination (R_v²) of 0.713 and a root mean square error (RMSE_v) of 0.25 on the validation set. This study provides an effective method for high-throughput acquisition of LAI in field crops, offering valuable scientific support for sugarcane field management and breeding efforts.
Plant Leaves/growth & development* ; Saccharum/growth & development* ; Algorithms ; Unmanned Aerial Devices ; Remote Sensing Technology/methods* ; Crops, Agricultural/growth & development*

Accurately obtaining the crop quantity and density is not only crucial for the demand-based input of water and fertilizer in the field but also vital for ensuring the yield and quality of crops. Aerial photography by unmanned aerial vehicles (UAVs) can quickly acquire the distribution image information of crops over a large area. However, the accurate recognition of a single type of dense targets is a huge challenge for most recognition algorithms. Taking banana seedlings as an example in this study, we captured the images of banana plantations by UAVs from high altitudes to explore an efficient recognition method for dense targets. We proposed a strategy of "cut-recognition-stitch" and constructed a counting method based on the improved Faster R-CNN algorithm. First, the images containing highly dense targets were cropped into a large number of image tiles according to different sizes (simulating different flight altitudes), and the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm was adopted to improve the image quality. A banana seedling dataset containing 36 000 image tiles was constructed. Then, the Faster R-CNN network with optimized parameters was used to train the banana seedling recognition model. Finally, the recognition results were reversely stitched together, and a boundary deduplication algorithm was designed to correct the final counting results to reduce the repeated recognition caused by image cropping. The results show that the recognition accuracy of the Faster R-CNN with optimized parameters for banana image datasets of different sizes can reach up to 0.99 at most. The deduplication algorithm can reduce the average counting error for the original aerial images from 1.60% to 0.60%, and the average counting accuracy of banana seedlings reaches 99.4%. The proposed method effectively addresses the challenge of recognizing dense small objects in high-resolution aerial images, providing an efficient and reliable technical solution for intelligent crop density monitoring in precision agriculture.
Musa/growth & development* ; Crops, Agricultural/growth & development* ; Algorithms ; Neural Networks, Computer ; Unmanned Aerial Devices ; Seedlings/growth & development* ; Image Processing, Computer-Assisted/methods* ; Photography ; Agriculture/methods*

Due to their unique physicochemical properties, nanomaterials can optimize drug delivery and reshape the tumor microenvironment. Manganese-based nanomaterials are primarily used in tumor immunotherapy for the following purpose, including targeted activating of the cyclic GMP-AMP synthase-stimulator of interferon gene pathway to enhance immunogenicity, utilizating of manganese′s redox properties to regulate the tumor microenvironment, and developing of manganese-based magnetic resonance imaging contrast agents to monitor immune responses in real time. In this review, synthesis methods of manganese-based nanomaterials such as thermal decomposition method, hydrothermal/solvothermal synthesis method, and chemical precipitation/mixing method as well as an in-depth analysis of their applications in tumor immunotherapy including immune regulation, regulation of tumor microenvironment and enhanced magnetic resonance imaging were reviewed.

AIM:To compare the degree of disease simulation between the two mouse models of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD)using intranasal instillation of lipopolysaccharide(LPS)and fine particulate matter(PM2.5)for 3 d based on exposure to cigarette smoke(CS)for 90 d.METHODS:Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group(n=8),CS group(n=8),CS+PM2.5 group(n=8)and CS+LPS group(n=8).The AECOPD models in CS+PM2.5 and CS+LPS groups were established by CS exposure combined with intranasal PM2.5 and LPS instillation.Lung function,lung pathology and airway goblet cell hyperplasia using histologi-cal staining were measured.To evaluate the degree of lung inflammation and mucus secretion in mice,the prorein levels of mucin 5AC(MUC5AC),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF)were detected by ELISA and total white blood cell(WBC)counts and the BALF differential cell counts(neutro-phils,macrophages,lymphocytes)were detected by Giemsa staining.RESULTS:In CS group,lung function decreased(P<0.05),and bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen de-position were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05),compared with control group.Compared with CS group,lung function decreased(P<0.05),the bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+PM2.5 and CS+LPS groups.Compared with CS+PM2.5 group,lung function decreased(P<0.05),the bronchial inflamma-tion index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+LPS group.CONCLUSION:Exposure to CS combined with both intrana-sal PM2.5 and LPS instillation allowed for establishing AECOPD models in mice,and CS exposure combined with intrana-sal LPS instillation better simulated AECOPD characteristics.

AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.

AIM:To compare the degree of disease simulation between the two mouse models of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD)using intranasal instillation of lipopolysaccharide(LPS)and fine particulate matter(PM2.5)for 3 d based on exposure to cigarette smoke(CS)for 90 d.METHODS:Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group(n=8),CS group(n=8),CS+PM2.5 group(n=8)and CS+LPS group(n=8).The AECOPD models in CS+PM2.5 and CS+LPS groups were established by CS exposure combined with intranasal PM2.5 and LPS instillation.Lung function,lung pathology and airway goblet cell hyperplasia using histologi-cal staining were measured.To evaluate the degree of lung inflammation and mucus secretion in mice,the prorein levels of mucin 5AC(MUC5AC),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF)were detected by ELISA and total white blood cell(WBC)counts and the BALF differential cell counts(neutro-phils,macrophages,lymphocytes)were detected by Giemsa staining.RESULTS:In CS group,lung function decreased(P<0.05),and bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen de-position were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05),compared with control group.Compared with CS group,lung function decreased(P<0.05),the bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+PM2.5 and CS+LPS groups.Compared with CS+PM2.5 group,lung function decreased(P<0.05),the bronchial inflamma-tion index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+LPS group.CONCLUSION:Exposure to CS combined with both intrana-sal PM2.5 and LPS instillation allowed for establishing AECOPD models in mice,and CS exposure combined with intrana-sal LPS instillation better simulated AECOPD characteristics.

AIM:To investigate the effects of nebulized sodium tanshinone ⅡA sulfonate(STS)in a mouse model of pulmonary hypertension associated with chronic obstructive pulmonary disease(COPD-PH).METHODS:A to-tal of 32 healthy SPF-grade male C57BL/6 mice were randomly divided into 4 groups:control(CTL,n=8)group,COPD-PH(CS+LPS,n=8)group,STS-treated COPD-PH(CS+LPS+STS,n=8)group,and STS(n=8)group.The COPD-PH model was established through whole-body exposure to cigarette smoke(CS)combined with lipopolysaccharide(LPS)in-halation.Mice were subjected to cigarette smoke exposure in a chamber(9 cigarettes/h,2 h/session,2 sessions/d,6 d/week)for 60 d,except on days of LPS inhalation.On days 1 and 14,COPD-PH model mice received LPS(7.5 μg/mouse in 50 μL saline)via intranasal inhalation,while the CTL and STS groups received an equivalent volume of saline.STS was administered via nebulized inhalation(5 mg/kg,30 min per session,twice daily)immediately before CS exposure.At the end of the modeling period,lung function and right heart pressure were assessed.Bronchoalveolar lavage fluid(BALF)was collected for inflammatory cell counting.Levels of interleukin-6(IL-6)in BALF supernatants and plasma were measured using ELISA.Pathological changes in the airway and lung tissues were evaluated.RESULTS:(1)Com-pared to CTL mice,those exposed to CS and LPS exhibited lesions characteristic of COPD-PH,including emphysema,lung inflammation,decreased lung function,and increased right ventricular systolic pressure(RVSP)and right ventricu-lar hypertrophy index(RVHI)(P<0.05);(2)COPD-PH mice showed significantly elevated IL-6 levels in both BALF and plasma(P<0.05);(3)STS treatment alleviated emphysema and lung inflammation,improved lung function,prevent-ed increases in RVSP and the RV/(LV+S)ratio,and reduced IL-6 levels in both BALF and plasma(P<0.05).CON-CLUSION:The results indicate that nebulized inhalation of STS significantly slows the progression of COPD-PH,likely due to its ability to inhibit lung inflammation and reduce IL-6 expression in the lungs.