Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy

Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70  eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg·bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg−1) were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), electrolyte levels, and the urinary protein (UP) content in 12 hr urine were measured. Interleukin-4 (IL-4) and interferon (INF-γ) were measured by enzyme-like immunosorbent assay (ELISA). The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2-associated protein (CD2AP) in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN) by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions

TIPE2 regulates periodontal inflammation by inhibiting NF-κB p65 phosphorylation

The roles and molecular mechanisms of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) in periodontitis remain largely unknown. Objective: This study aimed to determine the expression of TIPE2 and NF-κB p65 in rat Porphyromonas gingivalis-induced periodontics in vivo. Methodology: Periodontal inflammation and alveolar bone resorption were analyzed using western blotting, micro-computed tomography, TRAP staining, immunohistochemistry, and immunofluorescence. THP-1 monocytes were stimulated using 1 μg/ml Pg. lipopolysaccharide (Pg.LPS) to determine the expression of TIPE2 in vitro. TIPE2 mRNA was suppressed by siRNA transfection, and the transfection efficiency was proven using western blotting and real-time PCR. The NF-κB pathway was activated by treating the cells with 1 μg/ml Pg.LPS to explore related mechanisms. Results: The expression of both TIPE2 and NF-κB p65 was increased in the gingival tissues of rat periodontitis compared with normal tissues. Positive expression of TIPE2 was distributed in inflammatory infiltrating cells and osteoclasts in the marginal lacunae of the alveolar bone. However, strong positive expression of TIPE2 in THP-1 was downregulated after Pg.LPS stimulation. TIPE2 levels negatively correlated with TNF-α and IL-1β. Decreased TIPE2 in THP-1 further promoted NF-κB p65 phosphorylation. Mechanistically, TIPE2 knockdown upregulated NF-κB signaling pathway activity. Conclusions: Taken together, these findings demonstrate that TIPE2 knockdown aggravates periodontal inflammatory infiltration via NF-κB pathway. Interventions aimed at increasing TIPE2 may help in the therapeutic applications for periodontitis

Modelling long-term deformation of granular soils incorporating the concept of fractional calculus

Many constitutive models exist to characterise the cyclic behaviour of granular soils but can only simulate deformations for very limited cycles. Fractional derivatives have been regarded as one potential instrument for modelling memory-dependent phenomena. In this paper, the physical connection between the fractional derivative order and the fractal dimension of granular soils is investigated in detail. Then a modified elasto-plastic constitutive model is proposed for evaluating the long-term deformation of granular soils under cyclic loading by incorporating the concept of factional calculus. To describe the flow direction of granular soils under cyclic loading, a cyclic flow potential considering particle breakage is used. Test results of several types of granular soils are used to validate the model performance

Microstructure, Mechanical Properties and Wear Behavior of the Rheoformed 2024 Aluminum Matrix Composite Component Reinforced by Al2O3 Nanoparticles

The 2024 nanocomposite reinforced with Al2O3 nanoparticles was fabricated by the ultrasonic assisted semisolid stirring (UASS) method and rheoformed into a cylinder component. Microstructure, mechanical properties, and wear behavior of the rheoformed composite components were investigated. The results showed that the composite components with complete filling status and a good surface were rheoformed successfully. The deformation of semisolid slurries was mainly dominated by flow of liquid incorporating solid grains (FLS), sliding between solid grains (SSG), and plastic deformation of solid grains (PDS). Mechanical properties of the rheoformed composite components were influenced by stirring temperature, stirring time, and volume fraction of Al2O3 nanoparticles. The optimal ultimate tensile strength (UTS) of 358 MPa and YS of 245 MPa were obtained at the bottom of the rheoformed composite components after a 25-min stirring of composite semisolid slurry with 5% Al2O3 nanoparticles at 620 °C. Enhancement of mechanical properties was attributed to high density dislocations and dislocation tangles and uniform dispersed Al2O3 nanoparticles in the aluminum matrix. Natural ageing led to the occurrence of needle-like Al2CuMg phase and short-rod-like Al2Cu phase. UTS of 417 MPa and YS of 328 MPa of the rheoformed composite components were achieved after T6 heat treatment. Improvement of mechanical properties is due to the more precipitated needle-like Al2CuMg phase and short-rod-like Al2Cu phase. Wear resistance of the rheoformed composite components was higher than that of the rheoformed matrix component. Wear resistance of the rheoformed composite component increased with an increase in Al2O3 nanoparticles from 1% to 7%. A slight decrease in wear rate resulted from 10% Al2O3 nanoparticles due to greater agglomeration of Al2O3 nanoparticles. A combination mechanism of adhesion and delamination was determined according to worn surface morphology

Impacts of Human Activities on Hydrodynamic Structures during the Dry Season in the Modaomen Estuary

Over the past few decades, the topography and river-tide-salt dynamic characteristics of the Pearl River Delta (PRD) have undergone a myriad of changes due to the unnatural evolution process induced by diverse human activities, such as dam construction, land reclamation, sand excavation, and dredging for navigation. To investigate the impact of human activities on hydrodynamic structures in the PRD of the Modaomen Estuary (ME) during the dry season, a three-dimensional river-tide-salt dynamic model was used to simulate the hydrodynamic characteristics of the ME for different historical periods. The model results indicate that large-scale land reclamation weakened the tidal dynamics and mixing effects in the ME, promoting gravity circulation with opposite velocity directions at the surface and bottom within 15 km downstream of the estuary. Additionally, riverbed downcutting enhanced the tidal dynamics, which intensified saltwater intrusion, leading to the spatial scale-of-gravity circulation expanding 1–2 times. The enhancement of riverbed downcutting on the tidal dynamics in the ME was significantly greater than the weakening effect of land reclamation. Hence, due to the comprehensive influence of human activities between the 1970s and 2010, the hydrodynamic structures in the ME changed from a state of atypical gravity circulation, with nonobvious stratification, to a state of highly stratified and large-scale gravity circulation. The pollutant diffusion in the ME under different scenarios is also discussed in this paper. The results show that reclamation results in weakening of tidal dynamics, which is not conducive to the mixing and diffusion of pollutants in the estuary. However, the narrowed estuary due to land reclamation is conducive to the rapid entry of pollutants into the open sea

Construction and Thoughts of Intelligent “Three-Prevention” System in Shenzhen

Modern science and technology is a weapon against natural disasters. Shenzhen is a city of technology and innovation and we should endeavor to address flood control, drought relief and wind mitigation (named “three-prevention” in this context). In particular, we should vigorously promote the improvement of technology, and make use of modern information technologies such as big data, internet of things, cloud computing and artificial intelligence to create intelligent three-prevention system. This paper described in detail the characteristics and the construction status of the intelligent three-prevention system as well as the future development direction, in order to achieve the construction goals of the overall situation probing of the three-prevention, real-time decision-making assistance, flat command and control and urban resilience development. Since the intelligent three-prevention system’s launch in April 2020, it has started more than 20 times of emergency response against typhoon and flood. The whole process functions of front-end intelligent perception, fine dynamic simulation, real-time forecast and early warning, emergency command and post-disaster assessment have been preliminarily realized

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target