Objective To investigate the causes of the abnormally elevated gross α and gross β activity concentrations in the water of Nanbei Lake located near the Qinshan Nuclear Power Plant. Methods Water and sediment samples were measured according to GB/T 5750.13-2023 Standard Examination Methods for Drinking Water. Results The gross α activity concentration in Nanbei Lake water was (0.135 ± 0.0108) Bq/L, and the gross β activity concentration was 0.345 ± 0.036 Bq/L, which were several times higher than those recorded during the same period in previous years. The spike recovery rates for Nanbei Lake water (gross α: 85.7% ± 4.7%; gross β: 101.8% ± 4.1%) showed no significant differences from those for tap water (gross α: 83.2% ± 3.6%; gross β: 105.1% ± 5.2%). Gross α activity concentration exhibited a positive correlation with sediment addition (r = 0.996), as did gross β activity concentration (r = 0.998). The gross α and gross β activity concentrations in sediments from Nanbei Lake were significantly higher than those in sediments from surrounding water bodies. The gross α (529 ± 41)Bq/L and gross β (927 ± 83)Bq/L activity concentrations in the residue retained on a 0.45 μm filter after filtering Nanbei Lake water were similar to those in the sediments of Nanbei Lake (gross α: (516 ± 35) Bq/L; gross β: (965 ± 68) Bq/L). Conclusion The elevated gross α and gross β activity concentrations in Nanbei Lake water could be attributed to dredging activities, which resuspended sediments into the water column, combined with the inherently high activity concentrations in the sediments.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

Objective: To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method based on solid-phase extraction column purification for simultaneous determination of cyromazine and melamine in poultry eggs and meat. Methods: Eggs, quail eggs, and chicken were collected from markets. After homogenization, the sample was extracted with 0.5% formic acid in acetonitrile, subjected to solid-phase extraction using an MCX cartridge, and eluted with 5% ammonia in methanol. The eluate was collected, evaporated to near dryness under nitrogen, and reconstituted in a 10% aqueous methanol solution. Separated using TSK gel Amide-80 column (2.0 mm×150 mm, 5 μm), cyromazine and melamine were simultaneously detected in positive ion multiple reaction monitoring mode via tandem mass spectrometry, with quantification achieved by isotope dilution internal standard methods. Efficiency was enhanced and matrix interference minimized by optimizing conditions such as sample extraction, solid-phase extraction cartridge selection, and instrumental parameters. Calibration curves were constructed, and detection limits, quantification limits, spiked recoveries, and relative standard deviations for (RSD) of cyromazine and melamine were calculated. Results: After method optimization, matrix effects for cyromazine and melamine ranged from 0.97 to 1.04, indicating no significant matrix suppression or enhancement. Both cyromazine and melamine exhibited excellent linearity within the concentration range of 1.0-200.0 ng/mL, with correlation coefficients ≥0.999 5. The limits of detection were 0.3 μg/kg for cyromazine and 0.5 μg/kg for melamine, the quantification limits were 1.0 and 1.5 μg/kg, respectively. At spiked levels of 1.0, 20.0, and 150.0 μg/kg, the average recoveries ranged from 78.6% to 103.1%, with RSD between 3.5% and 6.3%. Among 95 samples tested, cyromazine was detected in 6 samples and melamine in 5 samples; neither cyromazine nor melamine was detected in chicken samples. Conclusion The UPLC-MS/MS method established in this study enables simultaneous detection and accurate quantification of cyromazine and melamine in poultry eggs and meat.

Background Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants widely distributed in the environment. Epidemiological studies have shown that PFAS exposure is closely associated with liver dysfunction and an increased risk of liver cancer. Some animal and cell experiments have also revealed its hepatotoxicity and potential carcinogenicity; however, the related carcinogenic mechanism has not yet been fully elucidated. Objective To explore the potential molecular mechanism of PFAS-induced liver cancer, identify the key causal genes, and specifically evaluate the causal association and expression changes of KMT2C in this process, as well as the binding stability between KMT2C and PFAS, and to provid a theoretical basis for mechanistic studies and molecular target discovery in PFAS-related liver cancer. Methods Toxicity prediction was performed on six representative PFAS. Potential target genes of PFAS were identified by integrating results from SwissTargetPrediction, STITCH, and TargetNet databases. Liver cancer-related genes were retrieved from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection of PFAS targets and liver cancer-related genes was used to obtain core genes. A compound-gene-disease regulatory network was constructed, and a protein–protein interaction network was established using STRING database. A core gene network was visualized based on node degree values. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore biological functions and enriched signaling pathways. Subsequently, two-sample Mendelian randomization was employed to assess potential causal relationships between candidate genes and hepatocellular carcinoma, enabling the identification of key genes. Molecular docking analysis using AutoDock was conducted to evaluate the binding stability between KMT2C and PFAS, and TCGA data were used to validate the differential expression of KMT2C between hepatocellular carcinoma and adjacent normal tissues. Results PFAS exhibited multisystem toxicity and posed significant risks of liver injury and carcinogenesis. A total of 266 PFAS target genes and 2923 liver cancer-related genes were identified, with 61 intersecting genes obtained. The enrichment analysis revealed that these intersecting genes were primarily involved in epigenetic regulation, nuclear receptor signaling pathways, and apoptosis-related pathways including TGF-β FoxO and Notch, suggesting their roles in diverse tumor-related biological processes. The two-sample Mendelian randomization results showed a significant negative causal association between KMT2C and hepatocellular carcinoma (OR=0.68, P <0.05). The molecular docking results demonstrated that all tested PFAS exhibited favorable binding to the KMT2C protein, with binding energies below –5.0 kcal·mol⁻¹. KMT2C was significantly upregulated in hepatocellular carcinoma tissues (unpaired P=0.025; paired P=8.38 × 10⁻⁴). Conclusion The KMT2C protein is found to stably bind with all six PFAS, exhibiting strong structural affinity. A causal relationship is identified between KMT2C and the development of hepatocellular carcinoma. TCGA data indicate that KMT2C is significantly upregulated in hepatocellular carcinoma tissues, and it may serve as a key regulatory target in PFAS-related liver cancer.

Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.

Objective:To conduct visualization analysis on the literature on dietary restriction(DR)regulating inflammation based on CiteSpace and VOSviewer visualization software,and to explore research hotspots and trends in this field.Methods:The literature on DR regulation inflammation in Web of Science core databases from January 1 2010 to September 29 2022 were searched.CiteSpace and VOSviewer visualization software was used to conduct quantitative and visual analysis of the annual publication volume,countries,institutions,authors,citation frequency and keywords of the retrieved literature.Results:A total of 1 344 papers related to the topic were included,and the annual number of papers was generally on the rise,with the highest citation frequency of 1 676 times.The United States(481 papers)is the country with the largest number of publications,followed by China(181 papers).The research hotspots in this field focused on calorie restriction(CR),ketogenic diet,aging,metabolic diseases,adipose tissue and gut microbiota.Conclusion:DR regulation of inflammation is increasingly favored by international and domestic researchers,and future research hotspots may be CR mimics(CRMs),intestinal microbiota,neurodegenerative diseases and cardiovascular diseases.The overall research trend is to further clarify the anti-inflammatory mechanism of DR,find new therapeutic targets,and conduct more rigorous clinical trials with more effective regimens that have been proven in vitro and animal models.