Berberine, an isoquinoline alkaloid isolated from the Chinese herb Coptis chinensis and other Berberis plants, has a wide range of pharmacological properties. Berberine can be used to treat many ...diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. Berberine has protective capacities in digestive diseases. It can inhibit toxins and bacteria, including Helicobacter pylori, protect the intestinal epithelial barrier from injury, and ameliorate liver injury. Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis. Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies. In addition, berberine regulates glycometabolism and lipid metabolism, improves energy expenditure, reduces body weight, and alleviates nonalcoholic fatty liver disease. Berberine also improves cardiovascular hemodynamics, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects, including antioxidative, antiapoptotic, and anti-ischemic. Furthermore, berberine exerts protective effects against other diseases. The mechanisms of its functions have been extensively explored, but much remains to be clarified. This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive, metabolic, cardiovascular, and neurological diseases.
•Spiral coil reactor is proposed based on combination of pneumatic transmission and secondary flow.•Flow behavior, energy charging and discharging is investigated by experimental methods.•CaCO3 ...conversion is around 2–5% during energy charging experiments.•CaO conversion is approximately 60–68% during energy discharging experiments.•The flow rate and reaction temperature have large effects on the CaO conversion.
Simultaneously offering sufficient heat and mass transfer is a significant challenge for the reactor design in the field of thermochemical energy storage owing to either a low thermal conductivity or a low permeability of the solid reactants. This paper proposes a spiral coil reactor based on combination of pneumatic transmission and secondary flow for thermochemical energy storage. The CaCO3/CaO is selected as reaction medium. The gas-solid flow behavior, energy charging and discharging are investigated by the experimental methods. The results show that CaCO3 conversion is around 2–5% during the energy charging experiments and CaO conversion is around 60–68% during the energy discharging experiments. The CaO conversion is a little higher than that in the fluidized bed under the same condition. Both the unstable gas velocity and the fluctuation of pressure drop in the spiral coil reactor due to particles agglomeration and sintering at high charging reaction temperature account for the low CaCO3 conversion. In addition, the energy discharging experiments also indicate that the flow rate and reaction temperature have large effects on the CaO conversion. An increase in the gas velocity relieves CaO sintering, consequently resulting in a higher CaO conversion. Moreover, the reaction rate can be improved at higher energy discharging temperature which leads to enough residence time and higher CaO conversion. Overall, this paper provides a novel insight for gas-solid reactor design in the field of thermochemical energy storage.
In China, the utilization of high-temperature flue gas waste heat recovery has been widely studied and developed, while the large number of low-temperature flue gas waste heat recovery has not been ...fully developed. Therefore, research has been conducted on the heat transfer characteristics of plate heat exchangers for low-temperature oil fume. The heat exchanger were 28–44 ℃ at the hot end and − 10 to 5 ℃ at the cold end. The outlet temperature, wind speed, etcetera were measured and recorded by changing indoor and outdoor temperature, variable flow rate and variable fin size. The impact of different working conditions on heat transfer and heat transfer efficiency of the heat exchanger was analyzed. The result showed that within the range of effective experimental test temperature, the variation trend of Nu and h was the same for heat exchangers with different finned fins and heat pipes with a different liquid-filled working medium The Nu value increased linearly with the increase of the Reynolds coefficient (Re), and the heat transfer coefficient presented a quadratic curve and increased with the increase of Re. Smaller fins had a higher efficiency and higher heat transfer. The heat exchange efficiency was stable between 0.75 and 0.97, which was higher than the value required by the national standard. At the same time, the heat exchanger also met the demand for high-efficiency heat recovery at low outdoor temperature, which has a wide application prospect.
In this study, calcium phosphate (CP)/calcium sulfate biphasic bone repair materials were modified with bioactive-glass (BG) to construct a self-curing bone repair material. Tetracalcium phosphate, ...calcium hydrogen phosphate dihydrate, and calcium sulfate hemihydrate (CSH) with different BG ratios and phosphate solution were reacted to prepare a porous self-curing bone repair material (CP/CSH/BG). The solidification time was about 12 min, and the material was morphologically stable in 24 h. The porosity was about 50%, with a pore size around 200 μm. The strength of CP/CSH/BG was approaching trabecular bone, and could be gradually degraded in Tris-HCl solution. MC3T3-E1 cells were cultured in the leaching solution of the materials. Cytotoxicity was detected using Cell Counting Kit 8 assays, and the expression of osteogenesis-related biomarkers was detected using quantitative real-time reverse transcription PCR (qRT-PCR). The results showed that all BG groups had increased ALP and ARS staining, implying that the BG groups could promote osteoblast mineralization in vitro. qRT-PCR showed significant upregulation of bone-related gene expression (Osx, Ocn, Runx2, and Col1) in the 20% BG group (p < 0.05). Therefore, the CP/CSH/BG self-curing bone repair materials can promote osteogenesis, and might be applied for bone regeneration, especially for polymorphic bone defect repair.
In the traditional shearer-positioning method, an odometer is used to assist the forward velocity correction of the inertial navigation system, but it cannot restrain the system’s error divergence. ...For this reason, this paper proposes a shearer positioning method based on non-holonomic constraints. In this method, an inertial measurement unit and odometer are installed in the middle of the shearer body and on the traction gear, respectively, the shearer attitude, speed, and position information are calculated through the inertial measurement-unit mechanization, and the shearer’s instantaneous velocity is calculated through the output of the odometer. The mechanization and error transfer process of the inertial navigation system are used to establish a Kalman filtering-state equation. The Kalman filtering observation equation is established through the difference between the projected velocity of the inertial navigation system at the joint and the output velocity of the odometer as the observation vector, and the non-holonomic constraint is introduced. Finally, the error feedback is derived from the results processed by the Kalman filtering algorithm, and the output of the inertial navigation system is corrected to obtain the optimal estimation of the shearer’s attitude, speed and position. The experiment shows that compared with the traditional inertial navigation and odometer combined positioning method, the degree of divergence in the positioning results over time is significantly reduced after adding the non-holonomic constraint. The positioning method has good tracking ability for the trajectory of the shearer. The error of the positioning results in the forward direction is reduced by 66%, the lateral direction is reduced by 62%, and the vertical direction is reduced by 67%.
Objective
In this study, we investigated the potential and mechanism of odontogenic ameloblast‐associated protein (ODAM) in the promoting junctional epithelium‐related gene expression in an ...ameloblast‐like cell line ALC.
Background
ODAM is expressed in ameloblasts and JE and acts as a component of the inner basal lamina (IBL) and intercellular matrix of JE. ODAM KO mice showed destruction of the integrity of the JE, which detaches from teeth. ODAM was confirmed to regulate the cytoskeleton through the ODAM‐ARHGEF5‐RhoA signaling pathway of the JE. Whether ODAM contributes to the regulation of ameloblast differentiation in JE remains unclear. After the formation of enamel, the ameloblast undergoes a series of morphological changes. Whether ODAM will affect the biological behavior of ameloblasts making them have the characteristics of JE is unclear.
Methods
A murine ameloblast‐like cell line, ALC, was used to investigate the effects of ODAM on the JE‐like changes of ALC cells in an epithelium‐induced environment by generating ODAM overexpression and ODAM knockdown cells through a lentivirus transduction approach. The biomarkers of junctional epithelium CK19, SLPI, and ODAM and the potential regulatory gene WNT1 were investigated by real‐time PCR, western blot, immunocytochemistry, immunostaining, luciferase reporter, and rescue assays.
Results
ODAM, CK19, and SLPI were significantly upregulated after epithelial induction. Overexpression of ODAM in ALC cells markedly increased CK19 and SLPI expression, while knockdown of ODAM in ALC cells clearly decreased CK19 and SLPI expression. A reporter luciferase assay showed that ODAM activated the WNT signaling pathway, especially through WNT1. Exogenous overexpression of ODAM upregulated WNT1 expression, while knockdown of ODAM reversed this effect. The WNT1 inhibition assay further confirmed the above results and showed that the WNT1 pathway was positively correlated with biomarkers of junctional epithelium CK19 and SLPI expression. Rescue studies showed that knocking down WNT1 in the ODAM‐overexpressing ALC cells decreased the expression of CK19 and SLPI. Immunocytochemistry showed that ODAM colocalized with CK19, SLPI, and WNT1 in the cells.
Conclusion
In conclusion, the research work showed that ODAM promotes junctional epithelium‐related gene expression in ALC via the ODAM‐WNT1 axis, which may provide new insight into the function of ODAM and JE formation.
Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and ...antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness.
The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection.
The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 NFATc1). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose.
D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.
Chemoresistance blunts the efficacy of temozolomide (TMZ) in the treatment of glioblastoma (GBM). Elevated levels of O6-methylguanine-DNA methyltransferase (MGMT) and activation of signal transducer ...and of transcription 3 (STAT3) have been reported to correlate with GBM resistance to alkylator chemotherapy. Resveratrol (Res) inhibits tumor growth and improves drug chemosensitivity by targeting STAT3 signaling. Whether the combined therapy of TMZ and Res could enhance chemosensitivity against GBM cells and the underlying molecular mechanism remains to be determined. In this study, Res was found to effectively improve chemosensitivities of different GBM cells to TMZ, which was evaluated by CCK-8, flow cytometry, and cell migration assay. The combined use of Res and TMZ downregulated STAT3 activity and STAT3-regulated gene products, thus inhibited cell proliferation and migration, as well as induced apoptosis, accompanied by increased levels of its negative regulators: PIAS3, SHP1, SHP2, and SOCS3. More importantly, a combination therapy of Res and TMZ reversed TMZ resistance of LN428 cells, which could be related to decreased MGMT and STAT3 levels. Furthermore, the JAK2-specific inhibitor AG490 was used to demonstrate that a reduced MGMT level was mediated by STAT3 inactivation. Taken together, Res inhibited STAT3 signaling through modulation of PIAS3, SHP1, SHP2, and SOCS3, thereby attenuating tumor growth and increasing sensitivity to TMZ. Therefore, Res is an ideal candidate to be used in TMZ combined chemotherapy for GBM.
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According to environmental and energy issues, renewable energy has been vigorously promoted. Now solar power is widely used in many areas but it is limited by the weather conditions ...and cannot work continuously. Heat storage is a considerable solution for this problem and thermochemical energy storage is the most promising way because of its great energy density and stability. However, this technology is not mature enough to be applied to the industry. The reactor is an important component in the thermochemical energy storage system where the charging and discharging process happens. In this paper, a spiral coil is proposed and used as a reactor in the thermochemical energy storage system. The advantages of the spiral coil include simple structure, small volume, and so on. To investigate the flow characteristics, the simulation was carried out based on energy-minimization multi-scale model (EMMS) and Eulerian two-phase model. CaCO3 particles were chosen as the reactants. Particle distribution was shown in the results. The gas initial velocity was set to 2 m·s−1, 3 m·s−1, and 4 m·s−1. When the particles flowed in the coil, gravity, centrifugal force and drag force influenced their flow. With the Reynold numbers increasing, centrifugal and drag force got larger. Accumulation phenomenon existed in the coil and results showed with the gas velocity increasing, accumulation moved from the bottom to the outer wall of the coil. Besides, the accumulation phenomenon was stabilized when φ > 720°. Also due to the centrifugal force, a secondary flow formed, which means solid particles moved from the inside wall to the outside wall. This secondary flow could promote turbulence and mixing of particles and gas. In addition, when the particle volume fraction is reduced from 0.2 to 0.1, the accumulation at the bottom of the coil decreases, and the unevenness of the velocity distribution becomes larger.
STAT3 is the most ubiquitous member of the STAT family and involved in many biological processes, such as cell proliferation, differentiation, and apoptosis. Mounting evidence has revealed that STAT3 ...is aberrantly activated in many malignant tumors and plays a critical role in cancer progression. STAT3 is usually regarded as an effective molecular target for cancer treatment, and abolishing the STAT3 activity may diminish tumor growth and metastasis. Recent studies have shown that negative regulators of STAT3 signaling such as PIAS, SOCS, and PTP, can effectively retard tumor progression. However, PIAS, SOCS, and PTP have also been reported to correlate with tumor malignancy, and their biological function in tumorigenesis and antitumor therapy are somewhat controversial. In this review, we summarize actual knowledge on the negative regulators of STAT3 in tumors, and focus on the potential role of PIAS, SOCS, and PTP in cancer treatment. Furthermore, we also outline the STAT3 inhibitors that have entered clinical trials. Targeting STAT3 seems to be a promising strategy in cancer therapy.
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