DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

Preparation and Performance of Resin-Gel-Rubber Expandable Lost Circulation Material Blend.

Aiming at the complex strata, lost circulation often occurs. and lost circulation control becomes a difficult issue. A drilling fluid loss accident delays the drilling progress and even causes major economic losses. If we take a self-made sodium polyacrylate grafting and modify a starch water absorbent resin, using an amphiphilic compatibilizer as raw material through mechanical blending and chemical compatibilization, we can synthesize a resin-rubber blend swelling lost circulation material. This material presents a good resistance to anti-high-temperature performance, but the quality declines while the temperature is higher than 363 °C, and with the increasing temperature, the water-swelling expansion ratio becomes higher. The range of the water-swelling expansion ratio is 8 to 25 times and the water swelling rate becomes larger along with the reduced diameter of the lost circulation materials and decreases with the increasing salinity. The resin-rubber blend swelling lost circulation material after water swelling has excellent toughness and high elastic deformation capacity, thus, forming a 7 Mpa to 2 mm fracture via expansion, extrusion, deformation, and filling, which presents a good performance for fracture plugging and realizes the purpose of lost circulation control.

Fuzheng Xiaoai Decoction 1 ameliorated cancer cachexia-induced muscle atrophy via Akt-mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Xiaoai Decoction 1 (FZXAD1) is a clinical experience prescription for the treatment of cancer patients at an advanced stage. FZXAD1 has been used for more than 10 years in the clinic and can effectively improve the deficiency syndrome of cancer patients. However, its mechanisms need further clarification. AIM OF THE STUDY: To check the effects of FZXAD1 in colon 26 (C26) cancer cachexia mice and try to clarify the mechanisms of FZXAD1 in ameliorating cancer cachexia symptoms. MATERIALS AND METHODS: An animal model of cancer cachexia was constructed with male BALB/c mice bearing C26 tumor cells. Food intake, body weight and tumor size were measured daily during the animal experiment. Tissue samples in different groups including tumor and gastrocnemius muscle, were dissected and weighed at the end of the assay. Serum biochemical indicators such as total protein (TP), glucose (GLU) and alkaline phosphatase (ALP) were also detected. Network pharmacology-based analysis predicted the possible targets and signaling pathways involved in the effects of FZXAD1 on cancer cachexia therapy. Western blotting assays of the gastrocnemius muscle tissues from C26 tumor-bearing mice were then used to confirm the predicted possible targets of FZXAD1. RESULTS: The results of animal experiments showed that FZXAD1 could ameliorate cancer cachexia by alleviating the muscle wasting as well as kidney atrophy and increasing the body weight of cancer cachexia mice. AKT1, MTOR, MAPK3, HIF1A and MAPK1 were predicted as the core targets of FZXAD1. Western blotting confirmed the prediction that FZXAD1 increased the expression levels of phosphorylated Akt and mTOR in the muscle tissues. In addition, FZXAD1 treatment obviously ameliorated the increased levels of HIF-1α and phosphorylated Erk1/2 in C26 tumor-bearing mice. CONCLUSION: FZXAD1 effectively ameliorated cancer cachexia in an animal model of mice, which is consistent with its efficacy in the treatment of cancer patients. The mechanisms of FZXAD1 might be mainly based on its alleviating effects on muscle atrophy by activating the Akt-mTOR pathway and thus helping to maintain body weight.

Simulation Analysis and Experimental Study of Piezoelectric Power Generation Device Based on Shape Memory Alloy Drive.

In order to solve the problem of waste heat collection from energy consumption, a thermal energy generation device combining shape memory alloy and piezoelectric materials has been designed. The shape memory alloy is heated and deformed to drive the drive wheel continuously, and the impact wheel is deformed against the piezoelectric cantilever beam during the rotation of the drive wheel to generate electricity. In this paper, the impact force generated by the impact wheel and the output voltage of the piezoelectric cantilever beam during the rotation process are given. Finally, the experimental test shows that the larger the radius of the drive wheel, the lower the impact force of the wheel and the lower the output voltage of the piezoelectric cantilever beam; the larger the diameter of the shape memory alloy wire, the higher the impact force of the wheel and the higher the output voltage of the piezoelectric cantilever beam; the more teeth of the drive wheel, the higher the impact frequency of the piezoelectric cantilever beam and the higher the output voltage. The maximum output voltage of the thermoelectric converter is 14.2 V, when the drive wheel radius is 13 mm, the shape memory alloy wire diameter is 1 mm and the number of impact wheel teeth is 6. The new structural design provides a new structural model for waste heat recovery and thermal energy generation technology. The new structural design provides a new approach and idea for waste heat recovery and thermal energy generation technology.

Design and Experiment Using Flexible Bumps for Piezoelectric-Driven Hydraulically Amplified Braille Dot Display.

This paper describes the design of a piezoelectric-driven hydraulically amplified Braille-flexible bump device that enables the flexible formation of Braille characters. A piezoelectric vibrator is used to excite fluid resonance in a cavity, and displacement is realized by compressing the fluid, allowing Braille character dots to be formed. First, the structural design and working principle of the device, as well as the method used to drive the fluid, are explained. Expressions for the output displacement and amplification ratio of the flexible film and piezoelectric vibrator are then obtained through kinetic analysis of the system unit. Subsequently, the structural parameters that affect the output displacement and the liquid amplification are described. Finally, experimental tests of the system are explained. The results indicate that the output displacement of the contact formed by the flexible film reaches 0.214 mm, satisfying the requirements of the touch sensitivity standard for the blind, when the fluid cavity diameter measures 31 mm and the resonance frequency is 375.4 Hz. The corresponding water discharge is 8.8 mL. This study proves that constructing a Braille bump device in this way is both feasible and effective.

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.