ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(β-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 μmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 μmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.
Humans ; Corydalis/chemistry* ; Alkaloids/chemistry* ; Inflammation ; Spectrum Analysis ; Isoquinolines/pharmacology*

Colorectal cancer (CRC) has become a major medical and public health threat to human life and health. At present, the clinical diagnosis and treatment of CRC mainly depends on the laboratory tests. With the increasing demand for treatment and prognosis, screening methods for CRC are emerging. In order to provide a reference for reasonable selection of laboratory diagnostic biomarkers, and further improve the accuracy and reliability of colorectal cancer screening, auxiliary diagnosis, efficacy monitoring, as well as prognostic evaluation, this article reviews the laboratory screening and diagnostic methods for CRC, and makes outlook for the future detection markers of CRC.
Humans ; Biomarkers, Tumor ; Reproducibility of Results ; Colorectal Neoplasms/diagnosis*