Application of fluorocarbon nanoparticles of 131I-fulvestrant as a targeted radiation drug for endocrine therapy on human breast cancer.

BACKGROUND: Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant. METHOD: To address these challenges, we engineered tumor-targeting nanoparticles termed 131I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with 131I to create 131I-fulvestrant. Subsequently, we incorporated the 131I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach-endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer. RESULTS: Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The 131I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations. CONCLUSION: We've pioneered a nanoparticle system loaded with radioactive isotope 131I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.

Study on interface engineering and chemical bonding of the ReS2@ZnO heterointerface for efficient charge transfer and nonlinear optical conversion efficiency.

Rhenium sulfide (ReS2) has emerged as a promising two-dimensional material, demonstrating broad-spectrum visible absorption properties that make it highly relevant for diverse optoelectronic applications. Manipulating and optimizing the pathway of photogenerated carriers play a pivotal role in enhancing the efficiency of charge separation and transfer in novel semiconductor composites. This study focuses on the strategic construction of a semiconductor heterostructure by synthesizing ZnO on vacancy-containing ReS2 (VRe-ReS2) through chemical bonding processes. The ingeniously engineered built-in electric field within the heterostructure effectively suppresses the recombination of photogenerated electron-hole pairs. A direct and well-established interfacial connection between VRe-ReS2 and ZnO is achieved through a robust Zn-S bond. This distinctive bond configuration leads to enhanced nonlinear optical conversion efficiency, attributed to shortened carrier migration distances and accelerated charge transfer rates. Furthermore, theoretical calculations unveil the superior chemical interactions between Re vacancies and sulfide moieties, facilitating the formation of Zn-S bonds. The photoluminescence (PL) intensity is increased by the formation of VRe-ReS2 and ZnO heterostructure and the PL quantum yield of VRe-ReS2 is improved. The intricate impact of the Zn-S bond on the nonlinear absorption behavior of the VRe-ReS2@ZnO heterostructure is systematically investigated using femtosecond Z-scan techniques. The charge transfer from ZnO to ReS2 defect levels induces a transition from saturable absorption to reverse saturable absorption in the VRe-ReS2@ZnO heterostructure. Transient absorption measurements further confirm the presence of the Zn-S bond between the interfaces, as evidenced by the prolonged relaxation time (τ3) in the VRe-ReS2@ZnO heterostructure. This study offers valuable insights into the rational construction of heterojunctions through tailored interfacial bonding and surface/interface charge transfer pathways. These endeavors facilitate the modulation of electron transfer dynamics, ultimately yielding superior nonlinear optical conversion efficiency and effective charge regulation in optoelectronic functional materials.

[Impact of Accelerated Electrification Under the Low Carbon Path in Dongguan City on the Coordinated Emission Reduction of CO2 and Pollutants].

Cities are the center of energy consumption. Electrification integrates urban energy structure and achieves the efficient use of clean energy. Exploring the urban impact of accelerated electrification under the low-carbon path is crucial to reducing urban pollution and carbon. Based on the Long-range Energy Alternative Planning System(LEAP-DG), this study set up three scenarios, including the baseline, low-carbon, and accelerated electrification scenarios, to evaluate the emission reduction potential of electrification under different power structures, quantify the contribution of key sectors, and discuss the coordinated emission reduction effect of Dongguan, a typical manufacturing city in Guangdong. The results showed that accelerated electrification under the low-carbon path would reduce the emission intensity of power pollutants, and in 2050, Dongguan will further reduce CO2, NOx, VOC, and CO by 7.35×106, 1.28×104, 1.62×104, and 8.13×104 t; SO2 and PM2.5 emission reductions on the consumption side and increased emissions on the production side had been balanced. Accelerated electrification in the industrial and transportation sectors would reduce CO2 and air pollutant emissions at the same time, and the transportation sector would benefit from the high conversion efficiency of fuel vehicles and electric vehicles, reducing CO2, CO, VOC, and NOx by 5.42×106, 7.76×104, 1.43×104, and 1.06×104 t, respectively, in 2050. In the building sector with high electrification rates, coal power was higher in extra electricity, increasing CO2 and pollutant emissions. Under the optimization of power supply structure, cities can reasonably adjust the electrification of different departments to achieve targeted pollution prevention and control.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Multi-environment evaluations across ecological regions reveal climate and soil effects on amides contents in Chinese prickly ash peels (Zanthoxylum bungeanum Maxim.).

BACKGROUND: Environmental factors difference is the key factor for the difference in the production, transformation and accumulation of effective components in plants. UPLC-MS/MS and multivariate statistical methods were applied to describe the region difference of amides compounds in Chinese prickly ash peels from different regions and their correlation with climatic factors and soil factors. RESULTS: Amides compounds contents were significantly higher in high altitude areas, with obvious altitude change trend. Two ecotypes were classified based on the amides compounds contents, one was the high altitude-cool type from Qinghai, Gansu, Sichuan and western Shaanxi province, and the other one was low altitude-warm type from eastern Shaanxi, Shanxi, Henan, Hebei and Shandong province. Amides compounds content were negatively correlated with annual mean temperature, max temperature of warmest month, mean temperature of wettest quarter and mean temperature of warmest quarter (P < 0.01). Except for hydroxy-γ-sanshool and ZP-amide A, the residual amides contents were significantly positively correlated with organic carbon, available nitrogen, phosphorus and potassium in soil and negatively correlated with soil bulk density. Low temperature, low precipitation and high organic carbon in soil were conducive to amides accumulation. CONCLUSIONS: This study aided in site specific exploration of high amides contents yielding samples, enriched the environment factors effects on amides compounds, and provided scientific foundation for the improvement of Chinese prickly ash peels quality and the location of high-quality production areas.

Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Application of Tranexamic Acid in Shoulder Arthroscopic Surgery: A Randomised Controlled Trial / 中国医学科学杂志(英文版)

Objective To explore the optimal administration route of tranexamic acid (TXA) in shoulder arthroscopic surgery. Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups: control group (without TXA treatment), intravenous group (TXA was intravenously administered 10 minutes before surgery), irrigation group (TXA was added to the irrigation fluid during subacromial decompression and acromioplasty), and intravenous plus irrigation group (TXA was applied both intravenously and via intra-articular irrigation). The primary outcome was visual clarity assessed with visual analog scale (VAS) score, and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure. Results There were 134 patients enrolled in the study, including 33 in the control group, 35 in the intravenous group, 32 in the irrigation group, and 34 in the intravenous plus irrigation group. The median and interquartile range of VAS scores for the intravenous, irrigation, and intravenous plus irrigation groups were 2.70 (2.50, 2.86) (Z = -3.677, P = 0.002), 2.67 (2.50, 2.77) (Z = -3.058, P < 0.001), and 2.91 (2.75, 3.00) (Z = -6.634, P < 0.001), respectively, significantly higher than that of the control group [2.44 (2.37, 2.53)]. Moreover, the control group consumed more irrigation fluid than the intravenous group, irrigation group, and intravenous plus irrigation group (all P < 0.05). The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group (both P < 0.001). There was no difference in subacromial decompression and acromioplasty operative time among the four groups. Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity, and the combined application is more effective.

Heterologous production of bioactive xenoacremone analogs in Aspergillus nidulans / 中国天然药物

Tyrosine-decahydrofluorene derivatives are a class of hybrid compounds that integrate the properties of polyketides and nonribosomal peptides. These compounds feature a [6.5.6] tricarbocyclic core and a para-cyclophane ether moiety in their structures and exhibit anti-tumor and anti-microbial activities. In this study, we constructed the biosynthetic pathway of xenoacremones from Xenoacremonium sinensis ML-31 in the Aspergillus nidulans host, resulting in the identification of four novel tyrosine-decahydrofluorene analogs, xenoacremones I-L (1-4), along with two known analogs, xenoacremones A and B. Remarkably, compounds 3 and 4 contained a 12-membered para-cyclophane ring system, which is unprecedented among tyrosine-decahydrofluorene analogs in X. sinensis. The successful reconstruction of the biosynthetic pathway and the discovery of novel analogs demonstrate the utility of heterologous expression strategy for the generation of structurally diverse natural products with potential biological activities.

Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction / 中国中药杂志

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Roscovitine rescuing neuronal loss and neuroinflammation in brain regions associated with Parkinson’s disease mice / 解剖学报

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

Translocated HMGB3 is involved in papillary thyroid cancer progression by activating cytoplasmic TLR3 and transmembrane TREM1.

The family of high mobility group box (HMGB) proteins participates in various biological processes including immunity, inflammation, as well as cancer formation and progression. However, its role in thyroid cancer remains to be clarified. We performed quantitative RT-PCR (qRT-PCR), western blot, enzyme-linked immunosorbent, immunohistochemistry, and immunofluorescence assays to evaluate the expression level and subcellular location of HMGB3. The effects of HMGB3 knockdown on malignant biological behaviors of thyroid cancer were determined by cell proliferation assays, cell cycle and apoptosis assays, and transwell chamber migration and invasion assays. Differential expression genes (DEGs) altered by HMGB3 were analyzed using the Ingenuity Pathway Analysis (IPA) and TRRUST v2 database. HMGB3 correlated pathways predicted by bioinformatic analysis were then confirmed using western blot, co-immunoprecipitation, dual-luciferase reporter assay, and flow cytometry. We found that HMGB3 is overexpressed and its downregulation inhibits cell viability, promotes cell apoptosis and cell cycle arrest, and suppresses cell migration and invasion in thyroid cancer. In PTC, both tissue and serum levels of HMGB3 are elevated and are correlated with lymph node metastasis and advanced tumor stage. Mechanistically, we observed the translocation of HMGB3 in PTC, induced at least partially by hypoxia. Cytoplasmic HMGB3 activates nucleic-acid-mediated TLR3/NF-κB signaling and extracellular HMGB3 interacts with the transmembrane TREM1 receptor in PTC. This study demonstrates the oncogenic role of HMGB3 cytoplasmic and extracellular translocation in papillary thyroid cancers; we recommend its future use as a potential circulating biomarker and therapeutic target for PTC.

Evaluation of climate factors affecting the quality of red huajiao (Zanthoxylum bungeanum maxim.) based on UPLC-MS/MS and MaxEnt model.

Through field investigation, UPLC-MS/MS technology and MaxEnt model were performed to predict the suitable distribution area for red huajiao (Zanthoxylum bungeanum maxim.) in China from 2021 s to 2060 s, and evaluate the effects of climate factors on the quality of red huajiao. The results demonstrated that mean temperature of the coldest quarter and min temperature of the coldest month were the most important environmental variables influencing red huajiao distribution. Suitable habitats for red huajiao were located mainly in dry and hot valley zone in the Qinba Mountains and the semi-humid and semi-arid areas of the Loess Plateau. The amides contents were higher in high suitability areas, while it was decreased in medium and low suitability areas, and temperature, wind speed and precipitation played a key role in their accumulation. This investigation was of great significance for the planting area optimization, quality control, benefit improvement and industrial development of red huajiao.

Sequential treatment of severe pneumonia with respiratory failure and its influence on respiratory mechanical parameters and hemodynamics.

BACKGROUND: The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance, alveolar capillary injury, pulmonary edema, refractory hypoxemia, and reduced lung compliance. Prolonged hypoxia can cause acid-base balance disorder, peripheral circulatory failure, blood-pressure reduction, arrhythmia, and other adverse consequences. AIM: To investigate sequential mechanical ventilation's effect on severe pneumonia complicated by respiratory failure. METHODS: We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital's Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial, with each group comprising 54 patients. The sequential group received invasive and non-invasive sequential mechanical ventilation, whereas the regular group received invasive mechanical ventilation. Blood-gas parameters, hemodynamic parameters, respiratory mechanical parameters, inflammatory factors, and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment. RESULTS: The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24, 48, and 72 h of treatment were higher than those of the conventional group (P < 0.05). The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group (P < 0.05). The pH value of the sequential group at 24 and 72 h of treatment, the central venous pressure value of the treatment at 24 h, and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group (P < 0.05). The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group (P < 0.05), the measured values of interleukin-6 and tumor necrosis factor-α in the sequential group at 72 h of treatment were lower than those in the conventional group (P < 0.05), and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group, with a statistically significant difference (P < 0.05). CONCLUSION: Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance, reducing inflammatory response, maintaining hemodynamic stability, and improving patient blood-gas levels; however, from this study's perspective, it cannot reduce patient mortality.

Evaluating the Impacts of Climate Factors and Flavonoids Content on Chinese Prickly Ash Peel Color Based on HPLC-MS and Structural Equation Model.

Climate affects Chinese prickly ash peel color directly through temperature and illumination and indirectly influences it through its effect on flavonoid compounds. In this study, a comprehensive evaluation strategy based on high performance liquid chromatography-mass spectrometry (HPLC-MS) technology and a structural equation model was applied to evaluate the effects of climate factors and flavonoids on Chinese prickly ash peel color. There were obvious geographical variations of peel color and flavonoid compounds with an obvious east-west distribution trend which were divided into high-altitude type and low-altitude type. Through path analysis, the wind speed, temperature and annual sunshine duration were found to be the key environmental factors affecting the flavonoids content and peel color, and their direct effects were higher than their indirect effect. Based on HPLC-MS technology and a structural equation model, correlation models of climatic factors and flavonoids with peel color were established, and the factors that had greater weight on pericarp color were obtained. Our results provide experimental evidence that climate factors affect the peel color by affecting flavonoid biosynthesis and accumulation, reveal the geographical variation of peel color and flavonoid component contents in Chinese prickly ash peel, establish a quantization color method for rapid evaluation of peel quality, expand on the influence of climatic factors on flavonoids content and peel coloration and promote agricultural practice in areas with similar climatic conditions.

Regulation mechanisms of flavonoids biosynthesis of Hancheng Dahongpao peels (Zanthoxylum bungeanum Maxim) at different development stages by integrated metabolomics and transcriptomics analysis.

BACKGROUND: Flavonoids have strong free radical scavenging and antioxidant capacity. The high abundance of flavonoids in Chinese prickly ash peels have many benefits to human health. In this study, 'Hancheng Dahongpao', a main cultivar, was taken as materials to investigate the flavonoids biosynthesis mechanism of Zanthoxylum bungeanum Maxim at three key development stages by integration of metabolomics and transcriptomics analysis. RESULTS: A total of 19 differentially accumulated metabolites were identified, the key flavonoids compounds were kaempferol, quercetin and their glycoside derivatives, and two major anthocyanins (peonidin O-hexoside and peonidin 3-O-glucoside). 5 gene networks/modules including 15 important candidate genes were identified, which was highly correlated with flavonoids. Among these genes, ZM-163828 and ZM-184209 were strongly correlated with kaempferol and quercetin, and ZM-125833 and ZM-97481 were controlled the anthocyanins biosynthesis. Moreover, it was shown that MYB-ZM1, MYB-ZM3, MYB-ZM5, MYB-ZM6 and MYB-ZM7 coordinately controlled flavonoids accumulation through regulating the structural genes. CONCLUSIONS: Generally, this study systematically revealed the flavonoids metabolic pathways and candidate genes involved in flavonoids biosynthesis and laid a foundation for the potential targets for the breeding of new valuable Chinese prickly ash cultivars.

Two-step strategy, growth mechanism and optical properties of plasmonic Ag-modified ZnO nanomaterials.

In this paper, plasma silver (Ag) modified zinc oxide (ZnO) (AZO) was used to form AZO nanomaterials (including AZO nanofilms (NFm), AZO nanowires (NWs) and AZO nanoflowers (NFw)) in a two-step-controlled manner to investigate the effect of compounding different contents of Ag on the linear optical aspects of ZnO materials. The growth mechanism of the AZO nanomaterials with different strategies is discussed. If Ag nanoparticles (NPs) grow on the ZnO NFm surface, they first grow with ZnO as the core and then self-core into islands, which are undoubtedly influenced by factors such as the growth mechanism of ZnO as well as Ag. If Ag is grown on the surface of the ZnO NWs and ZnO NFw, it is more likely to self-core owing to factors such as the roughness of the ZnO NWs and ZnO NFw surfaces. The AZO nanomaterials have excellent optical properties based on the surface plasmon resonance, local electromagnetic field and charge transfer mechanism between Ag and ZnO. With the increase in Ag content, the absorption edges of AZO NFm are red-shifted, and the absorption edges of AZO NWs and AZO NFw are first blue-shifted and then red-shifted. The results show that AZO nanomaterials prepared using different methods not only have different growth morphologies, but also have different optical properties with potential for the preparation of optical devices.

[Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway].

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway / 中国中药杂志

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.

Persistent acinar to ductal metaplasia (ADM) is a recently recognized precursor of pancreatic ductal adenocarcinoma (PDAC). Here we show that the ADM area of human pancreas tissue adjacent to PDAC expresses significantly higher levels of regenerating protein 3A (REG3A). Exogenous REG3A and its mouse homolog REG3B induce ADM in the 3D culture of primary human and murine acinar cells, respectively. Both Reg3b transgenic mice and REG3B-treated mice with caerulein-induced pancreatitis develop and sustain ADM. Two out of five Reg3b transgenic mice with caerulein-induced pancreatitis show progression from ADM to pancreatic intraepithelial neoplasia (PanIN). Both in vitro and in vivo ADM models demonstrate activation of the RAS-RAF-MEK-ERK signaling pathway. Exostosin-like glycosyltransferase 3 (EXTL3) functions as the receptor for REG3B and mediates the activation of downstream signaling proteins. Our data indicates that REG3A/REG3B promotes persistent ADM through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Targeting REG3A/REG3B, its receptor EXTL3, or other downstream molecules could interrupt the ADM process and prevent early PDAC carcinogenesis.

The association between subclinical hypothyroidism and metabolic syndrome: an update meta-analysis of observational studies.

The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) has been widely discussed. This study aimed to conduct an update and comprehensive meta-analysis to reveal the risk of MetS and its components in SCH. PubMed, Embase and ISI Web of Knowledge were searched to identify relevant studies through February 20th, 2020. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Both fixed-effects and random-effects models were used. In total, 18 articles (19 studies) incorporating 79,727 participants were included. The pooled OR for MetS comparing subjects with SCH with euthyroid subjects was 1.28 (95% CI: 1.19 to 1.39, p = 0.04, I2 = 40%). Subgroup analysis results showed significant associations of SCH and MetS in the adult subgroup (OR = 1.28, 95% CI: 1.18-1.40), Asian population subgroup (OR = 1.30, 95% CI: 1.19-1.42) and cross-sectional study design subgroup (OR = 1.31, 95% CI: 1.16-1.47). Significant associations of SCH and MetS also existed in all MetS definition criteria subgroups except the Chinese Diabetes Society (CDS) subgroup. SCH was correlated with MetS and was not affected by the subgroup analysis stratified by the proportion of females in the total population, the TSH cutoff value in SCH diagnostic criteria, or the adjustment for confounding factors. SCH was identified to be associated with an increased risk of obesity, hypertension, high triglyceride (TG) levels and low high-density lipoprotein cholesterol (HDL-C) levels. In conclusion, SCH is significantly associated with an increased risk of MetS and four out of five components of MetS.