Coumarin-Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis.

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

Effects of Porous Supports in Thin-Film Composite Membranes on CO2 Separation Performances.

Despite numerous publications on membrane materials and the fabrication of thin-film composite (TFC) membranes for CO2 separation in recent decades, the effects of porous supports on TFC membrane performance have rarely been reported, especially when humid conditions are concerned. In this work, six commonly used porous supports were investigated to study their effects on membrane morphology and the gas transport properties of TFC membranes. Two common membrane materials, Pebax and poly(vinyl alcohol) (PVA), were employed as selective layers to make sample membranes. The fabricated TFC membranes were tested under humid conditions, and the effect of water vapor on gas permeation in the supports was studied. The experiments showed that all membranes exhibited notably different performances under dry or humid conditions. For polyacrylonitrile (PAN) and poly(ether sulfones) (PESF) membranes, the water vapor easily condenses in the pores of these supports, thus sharply increasing the mass transfer resistance. The effect of water vapor is less in the case of polyvinylidene difluoride (PVDF) and polysulfone (PSF), showing better long-term stability. Porous supports significantly contribute to the overall mass transfer resistance. The presence of water vapor worsens the mass transfer in the porous support due to the pore condensation and support material swelling. The membrane fabrication condition must be optimized to avoid pore condensation and maintain good separation performance.

Curdione Relieved Isoproterenol-Induced Myocardial Damage through Inhibiting Oxidative Stress and Apoptosis.

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH. Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage.

Hg0 Conversion over Sulfureted HPMo/γ-Fe2O3 with HCl at Low Temperatures: Mechanism, Kinetics, and Application in Hg0 Removal from Coal-Fired Flue Gas.

Recently, sulfureted metal oxides have been developed for the catalytic oxidation of Hg0 to HgCl2 using HCl as an oxidant at low temperatures, and they exhibit excellent Hg0 removal performance. Owing to the lack of reaction mechanisms and kinetics, further improvement in their performance for Hg0 conversion is extremely restricted. In this study, the reaction mechanism of Hg0 conversion over sulfureted HPMo/γ-Fe2O3 with HCl at low temperatures was investigated using Hg balance analysis and transient reaction. The chemical adsorption of Hg0 as HgS and the catalytic oxidation of Hg0 to HgCl2 both contributed to Hg0 conversion over sulfureted HPMo/γ-Fe2O3. Meanwhile, the formed HgCl2 can adsorb onto sulfureted HPMo/γ-Fe2O3. Then, the kinetics of Hg0 conversion, Hgt adsorption, and HgCl2 desorption were developed, and the kinetic parameters were gained by fitting the Hg balance curves. Subsequently, the inhibition mechanism of H2O and SO2 on Hg0 conversion over sulfureted HPMo/γ-Fe2O3 was determined by comparing the kinetic parameters. The kinetic model suggested that both HgCl2 resulting from Hg0 oxidation and unoxidized Hg0 can be completely adsorbed on sulfureted HPMo/γ-Fe2O3 with a moderate mass hourly space velocity. Therefore, sulfureted HPMo/γ-Fe2O3 can be developed as a reproducible sorbent for recovering Hg0 emitted from coal-fired power plants.

Land Degradation Caused by Construction Activity: Investigation, Cause and Control Measures.

The rapid expansion of construction land has been a common phenomenon worldwide, which resulted in the loss of high-quality arable land and severe land degradation. Here, a statistical analysis, together with a field investigation, was carried out in China to address the challenges. This study has gathered data on the reduction of land amount and quality caused by construction activities and has collected the relevant policies to control land deterioration caused by those activities. The increasing amount of farmland and open space are occupied by construction use. The annual growth of construction land from 2001 to 2017 was 43.64 × 104 hm2, with an annual average of about 38 × 104 hm2 of cultivated land being converted to construction land in China. Construction activities usually cause a deterioration of the physico-chemical properties in and around construction site soils. The organic matter of post-construction soil was lower than the pre-construction by 257.4~879.8%. A lack of strong economic incentives for developers, limited effectiveness of measures to control land degradation, and weak requirements and enforcement of relevant laws and regulations allow land degradation from construction activities to remain at a significant level. For more efficiency and success, the study proposes effective measures to control the hazards that occur so widely in China.

Novel Nitric Oxide Donor Dinitroazetidine-Coumarin Hybrids as Potent Anti-Intrahepatic Cholangiocarcinoma Agents.

Intrahepatic cholangiocarcinoma (iCC) is a serious liver cancer threatening human health. However, there are a few chemotherapeutic drugs for the treatment of iCC in the clinic. It is extremely urgent to develop new drugs for iCC. In this study, twenty dinitroazetidine and coumarin hybrids were synthesized and evaluated anti-iCC bioactivity as a new type of nitric oxide (NO) donors. Among them, compounds 2-5 and 21 showed a higher antiproliferative activity against RBE cell lines (human intrahepatic cholangiocarcinoma cell lines) and low cytotoxicity in nontumor cells (HOSEpiC and T29). The preliminary study of pharmacology mechanism indicated that compounds 2-5 and 21 could release effective concentration of NO in RBE cell lines, which leaded to inhibit the proliferation of RBE cell lines. The research results revealed that compound 3 inhibited the proliferation of RBE cell lines by inducing apoptosis and arresting cell cycle at G2/M phase. Additionally, compound 3 had acceptable metabolic stability. Therefore, compound 3 was merited to further explore for developing a desirable NO donor lead with anti-iCC activity.

Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones, a traditional medicine, is used for various medicinal purposes worldwide. This species is popular for its gastro-protective properties and has been verified to exert antidiarrheal effects. Qiuxieling mixture, an oral liquid preparation used to treat diarrhea in children in clinical practice, was extracted from V. jatamansi Jones. AIM OF THE STUDY: Although Qiuxieling mixture has a good preventive effect on diarrhea children, the disgusting smell makes it intolerable. Therefore, we extracted odorless products from V. jatamansi Jones and Qiuxieling mixture. The present study is aimed to investigate the protective effects of two ethanolic extracts of V. jatamansi Jones and Qiuxieling mixture against castor oil-induced diarrhea and their possible mechanisms in mice. MATERIALS AND METHODS: The two extracts of V. jatamansi Jones and Qiuxieling mixture were detected by HPLC. A castor oil-induced diarrheal model was used to evaluate the antidiarrheal effects. The expression of Occludin in the small intestine was measured by IHC. Western blotting and immunofluorescence were used to detect the expression of proteins related to the oxidative stress and GSDMD-mediated pyroptosis signaling pathways. ELISA was used to detect the expression of IL-6 and IL-1ß in the small intestine of mice with diarrhea. RESULTS: The two extracts of V. jatamansi Jones and Qiuxieling mixture dose-dependently reduced the diarrhea index and the diarrhea rate, delayed the onset of diarrhea, and decreased the weight of the intestinal content. Meanwhile, they reversed the decreased expression of Occludin and restored the activity of Na+-K+-ATPase in the intestines of diarrheal mice. In addition, they reversed the depletion of GSH, attenuated the activation of the ERK/JNK pathway, promoted the Nrf2/SOD1 signaling pathways, and decreased the release of ROS in the intestines of diarrheal mice. Moreover, they suppressed GSDMD-mediated pyroptosis by downregulating the NLRP3/caspase-1/GSDMD signaling pathway. CONCLUSIONS: The two extracts of V. jatamansi Jones and Qiuxieling mixture exerted protective effects on castor oil-induced diarrhea in mice through a variety of mechanisms, including antioxidant stress, restoration of tight junctions between intestinal mucosal cells and regulation of the GSDMD-mediated pyroptosis pathway.

Simultaneous Adsorption of Gaseous Hg0 and Hg(II) by Regenerable Monolithic FeMoSx/TiO2: Mechanism and its Application in the Centralized Control of Hg Pollution in Coal-Fired Flue Gas.

FeMoSx/TiO2 was investigated as a regenerable sorbent to simultaneously adsorb Hg0 and Hg(II) from coal-fired flue gas for the centralized control of Hg pollution discharged from coal-fired power plants. The performance of FeMoSx/TiO2 for Hg(II) and/or Hg0 adsorption was evaluated on a fixed-bed reactor at 80 oC, and the mutual interference between Hg0 adsorption and Hg(II) adsorption was analyzed using individual adsorption, simultaneous adsorption, and two-stage adsorption. FeMoSx/TiO2 displayed an excellent capacity for individual Hg0 adsorption (41.8 mg g-1) and a moderate capacity for individual Hg(II) adsorption (0.48 mg g-1). Two types of adsorption sites were present on FeMoSx/TiO2 for gaseous Hg adsorption (S0 and FeS2/MoS3 sites). X-ray photoelectron spectroscope and kinetic analyses demonstrated that Hg0 and Hg(II) could adsorb onto S0 sites, whereas only Hg0 was adsorbed onto FeS2/MoS3 sites. As Hg0 competed with Hg(II) for the S0 sites, the amount of Hg(II) adsorbed slightly decreased by 16% in the presence of Hg0. However, Hg0 adsorption onto the FeS2/MoS3 sites predominated over the Hg0 adsorption onto FeMoSx/TiO2 and it was not inhibited in the presence of Hg(II). Therefore, the amount of Hg0 adsorbed on FeMoSx/TiO2 was only decreased by 2% in the presence of Hg(II).

Novel Hybrids of 3-Substituted Coumarin and Phenylsulfonylfuroxan as Potent Antitumor Agents with Collateral Sensitivity against MCF-7/ADR.

Twenty-three new coumarin-furoxan hybrids were synthesized, which exhibited nanomole antiproliferation activities in A2780, A2780/CDDP, MCF-7/ADR, and MDA-MB-231. Among them, compound 9 showed the strongest collateral sensitivity to MCF-7/ADR with 499-fold potency compared with MCF-7. Notably, the solubility of compound 9 increased 70-fold compared with the lead 2. And preliminary pharmacological studies displayed that compound 9 obviously increased Rh123 accumulation in MCF-7/ADR and released NO to produce ROS in lysosomes, which were able to damage lysosomal membrane and induce apoptosis. These results reasonably explained that the collateral sensitivity of compound 9 to MCF-7/ADR was closely related to P-gp-mediated lysosome damage and apoptosis. Additionally, compound 9 showed a very weak cytotoxicity both in MCF-10A and hERG potassium channels and had a desirable safety in ion cyclotron resonance (ICR) mice. Hence, compound 9 was merited to further study for developing a desirable candidate against MDR MCF-7/ADR via a potential mechanism of collateral sensitivity in MDR cancer cell lines.

Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response.

Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient. Here, we investigated whether IL-22 exerted nephroprotective effects to sodium oxalate-mediated kidney damage and its potential mechanism. Crystalline kidney injury models were developed in vitro and in vivo that was often observed in clinic. We provided evidence that IL-22 could effectively decrease the accumulation of ROS and mitochondrial damage in cell and animal models and reduce the death of TECs. Moreover, IL-22 decreased the expression of the NLRP3 inflammasome and mature IL-1ß in renal tissue induced by sodium oxalate. Further studies confirmed that IL-22 could play an anti-inflammatory role by reducing the levels of cytokines such as IL-1ß, IL-18, and TNF-α in serum. In conclusion, our study confirmed that IL-22 has protective effects on sodium oxalate-induced crystalline kidney injury by reducing the production of ROS, protecting mitochondrial membrane potential, and inhibiting the inflammatory response. Therefore, IL-22 may play a potential preventive role in sodium oxalate-induced acute renal injury. KEY POINTS: • IL-22 could reduce sodium oxalate-mediated cytotoxicity and ameliorate renal injury. • IL-22 could alleviate oxidative stress and mitochondrial dysfunction induced by sodium oxalate. • IL-22 could inhibit inflammatory response of renal injury caused by sodium oxalate.

Association of preoperative frailty with postoperative delirium after elective brain tumor resection: Retrospective analysis of a prospective cohort.

BACKGROUND: Preoperative frailty is associated with poor outcomes in major surgery. Postoperative delirium is common after neurosurgery. To date, the association of preoperative frailty with postoperative delirium after neurosurgery has not been established. We aimed to determine the association between preoperative frailty and postoperative delirium in patients undergoing elective brain tumor resection. METHODS: We retrospectively analyzed the data of a prospective cohort, consecutively enrolling adult patients admitted to the intensive care unit after elective craniotomy for brain tumor resection under general anesthesia in a tertiary hospital in China from March 1, 2017 to February 2, 2018. Preoperative frailty was evaluated using the modified frailty index. The primary outcome was postoperative delirium, assessed using the Confusion Assessment Method for the Intensive Care Unit. Univariate and multivariable regression analyses were performed to examine the association. RESULTS: 659 patients met inclusion criteria for our analysis. There were 398 (60.4%) non-frail (modified frailty index = 0), 237 (36.0%) pre-frail (modified frailty index = 1-2), and 24 (3.6%) frail (modified frailty index ≥ 3) patients. Of these, 124 (18.8%) developed postoperative delirium. In adjusted analyses, frailty was independently associated with postoperative delirium (odds ratio 1.7, 95% confidence interval 1.0-2.7, P = .032). Frail patients had longer length of hospital stay and higher total costs than non-frail patients. CONCLUSION: Preoperative frailty is associated with postoperative delirium, length of hospital stay, and total costs in patients undergoing elective brain tumor resection. Preoperative frailty assessment and appropriate management strategies should be involved in the perioperative management of postoperative delirium.

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound.

Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the real-time myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×ß showed significant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.

Ordered Large-Pore Mesoporous Cr2O3 with Ultrathin Framework for Formaldehyde Sensing.

A series of ordered mesoporous chromium oxides (Cr2O3) were synthesized by first replicating bicontinuous cubic Ia3d mesoporous silica (KIT-6), then a controlled mesostructural transformation from Ia3d to I4132 symmetry during the replication from KIT-6 to Cr2O3 was achieved by reducing the pore size and interconnectivities of KIT-6, accompanied with an increase in pore size from 3 to 12 nm and a decrease in framework thickness from 8.6 to 5 nm of the resultant Cr2O3 replicas. The gas-sensing behavior of the Cr2O3 replicas toward formaldehyde (HCHO) was systematically investigated. Ordered mesoporous Cr2O3 with both large accessible pores (12 nm) and an ultrathin framework (5 nm) exhibits the best sensing performance, with a response (Rgas/Rair = 119) toward 9 ppm of HCHO 4.4 times higher than that (Rgas/Rair = 27) of its counterpart with small pores and a thick framework. Moreover, it possesses excellent selectivity for detecting HCHO over other interference gases such as CO, benzene, toluene, p-xylene, NH3, H2S, and moisture. The significantly enhanced sensing performance of ordered large-pore mesoporous Cr2O3 with ultrathin framework suggests its great potential for the selective detection of HCHO.

Laparoscopic Versus Open Radical Nephrectomy for Renal Cell Carcinoma: a Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with renal cell carcinoma (RCC) in a meta-analysis. METHODS: Data were collected by searching Pubmed, Embase, Web of Science, and ScienceDirect for reports published up to September 26, 2016. Studies that reported data on comparisons of therapeutic efficacy of LRN and ORN were included. The fixed-effects model was used in this meta-analysis if there was no evidence of heterogeneity; otherwise, the random-effects model was used. RESULTS: Thirty-seven articles were included in the meta-analysis. The meta-analysis showed that the overall mortality was significantly lower in the LRN group than that in the ORN group (odds ratio [OR] =0.77, 95% confidence interval [CI]: 0.62-0.95). However, there was no statistically significant difference in cancer-specific mortality (OR=0.77, 95% CI: 0.55-1.07), local tumor recurrence (OR=0.86, 95% CI: 0.65-1.14), and intraoperative complications (OR=1.27, 95% CI: 0.83-1.94). The risk of postoperative complications was significantly lower in the LRN group (OR=0.71, 95% CI: 0.65-0.78). In addition, LRN has been shown to offer superior perioperative results to ORN, including shorter hospital stay days, time to start oral intake, and convalescence time, and less estimated blood loss, blood transfusion rate, and anesthetic consumption. CONCLUSION: LRN was associated with better surgical outcomes as assessed by overall mortality and postoperative complications compared with ORN. LRN has also been shown to offer superior perioperative results to ORN.

Structural and functional changes in gap junctional intercellular communication in a rat model of overactive bladder syndrome induced by partial bladder outlet obstruction.

The aim of the present study was to investigate the association between connexin (Cx)43 levels and alterations in gap junctional mediation of intercellular communication in overactive bladder syndrome (OAB), and to examine the effects of connexin inhibitor on this condition. Adult female Wistar rats with OAB following partial bladder outlet obstruction (PBBO) (OAB group, n=37) and sham-operated rats (control group, n=17) were studied. The ultrastructure of the rat detrusor was observed by transmission electron microscopy and the protein expression levels of Cx43 were analyzed using western blot analysis. Furthermore, bladder detrusor cells in both groups were cultured and cells in the OAB group were randomly divided into ten groups. In nine of these groups, 18-ß glycyrrhetinic acid (18ß-GA) was administered at various doses and durations. All groups were compared using fluorescence redistribution after photobleaching and a laser scanning confocal microscope. Cystometry demonstrated that gap junctions were an abundant mechanism among adjacent cells, and Cx43 protein expression levels were increased in the OAB group following 6 weeks of obstruction, as compared with the control group. Mean fluorescence recovery rates in the OAB group were significantly increased, as compared with the control group (P<0.01). Mean fluorescence recovery rates were noted following 18ß-GA administration. These results suggested that upregulation of Cx43 induces structural and functional alterations in gap junctional intercellular communication following PBOO, and connexin inhibitors may be a novel therapeutic strategy for the clinical treatment of OAB.

[Relationships between typical vegetations, soil salinity, and groundwater depth in the Yellow River Delta of China].

Soil salinity and groundwater depth are the two important factors affecting the vegetation growth and distribution in the Yellow River Delta. Through field investigation and statistical analysis, this paper studied the relationships between the typical vegetations (Suaeda heteroptera-Tamarix chinensis, Robinia pseudoacacia, Phragmites australis, and cotton) , soil salinity, and groundwater depth in the Delta. In the study area, groundwater depth had significant effects on soil salinity, with the average influence coefficient being 0.327. When the groundwater depth was 0.5-1.5 m, soil salinization was most severe. The vegetation growth in the Delta was poorer, with the NDVI in 78% of the total area being less than 0.4. Groundwater depth and soil salinity had significant effects on the vegetation distribution. Soil salinity had significant effects on the NDVI of R. pseudoacacia, S. heteroptera-T. chinensis, P. australis, and cotton, while groundwater depth had significant effects on the NDVI of S. heteroptera - T. chinensis, but lesser effects on the NDVI of P. australis, cotton and R. pseudoacacia.