Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

Climate change is altering the Earth's water cycle system. The resulting three extreme weather events—heatwaves, droughts, and extreme precipitation—impacts urban and rural water security through multi-layered mechanisms. A primary structural disparity exists between urban and rural systems: while urban areas benefit from comprehensive and standardized pipe networks that ensure terminal water quality, rural areas often suffer from "last mile" vulnerability due to inadequate infrastructure and outdated purification facilities. Extreme weather can directly alter the microbial community structure, concentrations of chemical pollutants and physicochemical properties of source water. These alterations interfere with the efficiency of water treatment processes and ultimately compromise the integrity of distribution systems. Because distribution networks often lack real-time monitoring and adaptive response capabilities, they have emerged as the most vulnerable link in the "water source-water treatment-distribution system" chain. Based on a systematic analysis of these chain-wide impacts, this paper proposed a series of control strategies, including security frameworks based on multi-model coupling and water source protection measures, improvement of water treatment technologies, optimization of distribution systems, and development of new water quality monitoring methods. These strategies aim to enhance the climate adaptability of urban and rural drinking water systems through multi-dimensional intervention, providing a theoretical basis for constructing climate-resilient water infrastructure.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

OBJECTIVES: To investigate the role of sphingosine-1-phosphate receptor 5 (S1PR5) in modulating barrier function of mouse brain microvascular endothelial cells with oxygen-glucose deprivation and reoxygenation (OGD/R). METHODS: Mouse brain microvascular endothelial cells (bEnd.3) were exposed to OGD/R to induce barrier dysfunction following treatment with S1PR5-specific agonist A971432 or lentivirus-mediated transfection with a S1PR5-specific siRNA, a S1PR5-overexpressing plasmid, or their respective negative control sequences. The changes in viability and endothelial barrier permeability of the treated cells were evaluated with CCK-8 assay and FITC-dextran permeability assay; the levels of intracellular reactive oxygen species (ROS) and localization and expression levels of the proteins related with barrier function and oxidative stress were detected using immunofluorescence staining, DCFH-DA probe and Western blotting. RESULTS: S1PR5 activation obviously enhanced viability of bEnd.3 cells exposed to OGD/R (P<0.0001). Both activation and overexpression of S1PR5 reduced FITC-dextran leakage, while S1PR5 knockdown significantly increased FITC-dextran leakage in the exposed bEnd.3 cells. Activation and overexpression of S1PR5 both increased the cellular expressions of the barrier proteins ZO-1 and occludin, while S1PR5 knockdown produced the opposite effect. In cells exposed to OGD/R, ROS production was significantly reduced by S1PR5 activation and overexpression but increased following S1PR5 knockdown. Overexpression of S1PR5 obviously increased the expressions of the antioxidant proteins Nrf2, HO-1 and SOD2 in the exposed cells. CONCLUSIONS S1PR5 activation and overexpression significantly improve cell viability and reduce permeability of a mouse brain microvascular endothelial cell model of OGD/R, the mechanism of which may involve the reduction in ROS production and upregulation of the antioxidant proteins.
Animals ; Mice ; Oxidative Stress ; Endothelial Cells/cytology* ; Brain/blood supply* ; Reactive Oxygen Species/metabolism* ; Receptors, Lysosphingolipid/metabolism* ; Sphingosine-1-Phosphate Receptors ; Blood-Brain Barrier/metabolism* ; Glucose ; Cell Line ; Oxygen/metabolism* ; NF-E2-Related Factor 2/metabolism*

Background The Qingcaosha Reservoir is facing issues of algal blooms and eutrophication, and the resulting increase in the level of chlorination disinfection by-products in the water has been a major concern. Objective To evaluate the impact of "Algae Monitoring and Control Program in Qingcaosha Reservoir" (hereinafter referred to as the program) on the control of trihalomethanes (THMs) in conventional finished water. Methods From 2011 to 2019, water samples were collected from the Lujiazui Water Plant once per season, one sample each time, and the concentrations of four THMs (trichloromethane, dichlorobromomethane, monochlorodibromomethane, and tribromomethane) were measured in the samples. Using 2014 when the program was implemented as a cut-off point, the entire study period was divided into two phases: pre-implementation (2011–2013) and post-implementation(2014–2019). Segmented linear regression with interrupted time series analysis was applied to assess the concentrations and trends of THMs in the finished water before and after the program launch. Results The concentration of total THMs in finished water increased by 1.561 µg·L⁻¹ (P=0.010) for each season of time extension before launching the program. The change in the concentration of total THMs in finished water was not statistically significant after the program launch, but the THMs concentration showed a decreasing trend as the slope was −0.626 (P=0.001). From 2017 until the end of 2019, the average concentration of THMs in finished water of Lujiazui Water Plant dropped to 10 μg·L⁻¹ or less. Conclusions The algae and eutrophication control measures in Qingcaosha Reservoir have achieved good results, controlling THMs in finished water at a low level, and the trend of THMs has changed from a yearly increase pattern before the program to a yearly decrease pattern after the program.

Objective:To analyze the clinicopathological features of giant ovarian masses(mean diameter≥10 cm)and analyze the clinical characteristics of patients in different age groups.Methods:The clinicopathological characteristics of 311 patients diagnosed with giant ovarian masses by surgery at Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2014 to December 2022 were retrospectively analyzed.Patients were further stratified by age and mass size to compare the differences of clinical and patho-logical features among different age groups and different mass diameter groups.Results:①The median age of thepatients were 44(24,60)years old.The first symptoms were as follows:ovarian mass discovered during physi-cal examination,abdominal pain,bloating,conscious abdominal distension,and symptoms of compression.②The surgical methods were as follows:unilateral oophorectomy(30.5％,95/311),ovarian cystectomy(28.9％,90/311),tumor staging or cytoreductive surgery(28.0％,87/311),total hysterectomy with bilateral adnexectomy(12.5％,39/311).③The pathological types were benign(49.5％,154/311),malignant(31.8％,99/311)and borderline(18.7％,58/311).④ Patients complained abdominal distension in＜20 years old group were signifi-cantly higher than the other two groups(P＜0.05).The ovarian resection rate in the＞50-year-old group was higher than that of the other two groups(P＜0.05),and the rate of unilateral ovarian resection in the＜20-year-old group was still as high as 30.1％(15/49).⑤ The size of the mass correlated with the duration of the disease.When the disease course was between 1 to 6 months,the mass diameter line＞30 cm was the most common(P＜0.05).The incidence of borderline tumors in the＞30 cm group was significantly higher than that in the other two groups,and the difference was statistically significant(P＜0.05).Conclusions:Ovarian mucinous and mucinous borderline tumors are the most common types of giant adnexal masses.The size of the mass tends to increase with the prolongation of the disease course.The incidence of borderline tumors increases with the in-crease of mass.Health education for young people should be strengthened.When abdominal pain,abdominal bloating,especially lower abdominal distension occurs,they should seek medical treatment in time to avoid adnex-ectomy due to borderline tumors.