Multidrug resistance (MDR) has been restricting the efficacy of chemotherapy, which mainly include pump resistance and non-pump resistance. In order to fight overall MDR, a novel targeted gene/drug ...co-deliver nano system is developed, which can suppress the drug efflux pumps and modulate autophagy to overcoming both pump and non-pump resistance. Here, small interfere RNA (siRNA) is incorporated into polymer-drug conjugates (PEI-PTX, PP) which are composed of polyethyleneimine (PEI) and paclitaxel (PTX) via covalent bonds, and hyaluronic acid (HA) is coated on the surface of PP/siRNA to achieve long blood cycle and CD44-targeted delivery. The RNA interference to mdr1 gene is combined with autophagy inhibition by PP, which efficiently facilitate apoptosis of Taxol-resistant lung cancer cells (A549/T). Further study indicates that PEI in PP may play a significant role to block the autophagosome-lysosome fusion process by means of alkalizing lysosomes. Both in vitro and in vivo studies confirm that the nanoassemblies can successfully deliver PTX and siRNA into tumor cells and significantly inhibited A549/T tumor growth. In summary, the polymeric nanoassemblies provide a potential strategy for combating both pump and non-pump resistance via the synergism of RNAi and autophagy modulation.
Temperature control of solar cells at high concentrations is a key issue. Short-term efficiency drop and long-term degradation should be avoided by effective cooling methods. Liquid immersion cooling ...eliminates the contact thermal resistance of back cooling and should improve cell performance. A 250X dish concentrator with two-axis tracking was utilized to evaluate a new CPV system using de-ionized water for immersion cooling. Time-dependent temperature distributions of the PV module of high power back point-contact cells were measured, as well as the
I–
V curves. The cooling capacities of the liquid immersion approach are very favorable. The module temperature can be cooled to 45
°C at a 940
W/m
2 direct normal irradiance, 17
°C ambient temperature and 30
°C water inlet temperature. The temperature distribution of the module is quite uniform, but the electrical performance of the cell module degrades after a fairly long time immersion in the de-ionized water.
Background/Aims: Circulating (serous or plasmic) long non-coding RNA (lncRNA) as biomarkers for predicting the diagnosis or prognosis of human disease have been well documented. Due to the ...sensibility or specificity limitation of Alpha Fetoprotein (AFP), a cluster lncRNAs were revealed as fingerprints for hepatocellular carcinoma (HCC). In this study, we enrolled all the reported circulating lncRNAs in HCC as candidate targets and examined in an independent cohort. Methods: The candidate lncRNAs were determined by qRT-PCR divided into training and validation sets. The risk score analysis was employed to evaluate the potential diagnosis ability of the lncRNAs independently or combining with AFP value. The receiver operating characteristic curve (ROC) was applied for presentation of sensibility or specificity. Results: Among the ten candidate circulating lncRNA, LINC00152, RP11-160H22.5, XLOC014172 and LOC149086 were screened with significant difference in training set. Further investigation in validation set indicated LINC00152, RP11-160H22.5 and XLOC014172 might be the fingerprints for HCC comparing with chronic hepatitis (CH) patients or healthy controls. The risk score analysis revealed the combination of three lncRNAs with AFP could distinguish the HCC from either CH or healthy control with the area under curve value (AUC) of 0.986 and 0.985, respectively. Conclusion: The three lncRNAs may act as novel biomarkers for acting as fingerprint in HCC combining with AFP.
The contents of cellulose and hemicellulose (C and H) in corn stover (CS) have an important influence on its biochemical transformation and utilization. To rapidly detect the C and H contents in CS ...by near-infrared spectroscopy (NIRS), the characteristic wavelength selection algorithms of backward partial least squares (BIPLS), competitive adaptive reweighted sampling (CARS), BIPLS combined with CARS, BIPLS combined with a genetic simulated annealing algorithm (GSA), and CARS combined with a GSA were used to select the wavelength variables (WVs) for C and H, and the corresponding regression correction models were established. The results showed that five wavelength selection algorithms could effectively eliminate irrelevant redundant WVs, and their modeling performance was significantly superior to that of the full spectrum. Through comparison and analysis, it was found that CARS combined with GSA had the best comprehensive performance; the predictive root mean squared errors of the C and H regression model were 0.786% and 0.893%, and the residual predictive deviations were 3.815 and 12.435, respectively. The wavelength selection algorithm could effectively improve the accuracy of the quantitative analysis of C and H contents in CS by NIRS, providing theoretical support for the research and development of related online detection equipment.
A number of metallocalixnarenes, where n = 4, 6, or 8, of titanium and vanadium have been screened for their ability to act as catalysts for the co‐polymerization of propylene oxide and CO2 to form ...cyclic/polycarbonates. The vanadium‐containing catalysts, namely VO(L1Me) (1), (VO2)L2H6 (2), Na(NCMe)62(NaVO4L2)(Na(NCMe))32 (3), VO(μ‐OH)L3/H22∙6CH2Cl2 (4), {VO2(μ‐O)L4Na(NCMe)22} (5), {V(Np‐tolyl)2L4} (6) and V(Np‐RC6H4)Cl3 (R = Cl (7), OMe (8), CF3 (9)), where L1H3 = methylether‐p‐tert‐butylcalix4areneH3, L2H8 = p‐tert‐butylcalix8areneH8, L3H4 = p‐tert‐butylthiacalix4areneH4, L4H6 = p‐tert‐butyltetrahomodioxacalix6areneH6, performed poorly, affording, in the majority of cases, TONs less than 1 at 90°C over 6 h and low molecular weight oligomeric products (Mn ≤ 1665). In the case of the titanocalix8arenes, {(TiX)2TiX(NCMe)2(μ3‐O)2(L2)} (X = Cl (10), Br (11), I (12)), which all adopt a similar, ladder‐type structure, the activity under the same conditions is somewhat higher (TONs >6) and follows the trend Cl > Br > I; by comparison the non‐calixarene species TiCl4(THF)2 was virtually inactive. In the case of 10, it was observed that the use of PPNCl (bistriphenylphosphineiminium chloride) as co‐catalyst significantly improved both the polymer yield and molecular weight (Mn 3515). The molecular structures of the complexes HNEt32VO(μ‐O)L3H22∙3CH2Cl2 (4∙3CH2Cl2), VO(μ‐OH)L3/H22∙6CH2Cl2 (4/) (where L3/H2 is a partially oxidized form of L3H4) and {(TiCl)2TiCl(NCMe)2(μ3‐O)2(L2)}·6.5MeCN (10·6.5MeCN) are reported.
Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of ...the mismatch region between magnetic resonance transverse relaxation times (T2 and T2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T2 and T2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T2 and T2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T2 and T2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T2 and T2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T2 and T2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson’s disease patients. The length of the dorsal linear mismatch line based on the T2*-T2 mask was significantly shorter in the Parkinson’s disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of 18F FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T2 and T2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.
Limited precipitation restricts yield of winter wheat grown in the North China Plain (NCP). Irrigation experiments were conducted during different growing stages of winter wheat (
Triticum aestivum ...L.) at Luancheng agro-ecology systems station of the Chinese Academy of Sciences during 1999/2000, 2000/2001 and 2001/2002 to identify suitable irrigation schedules for winter wheat. The aim was also to develop relationships between seasonal amounts of irrigation and yield, water-use efficiency (WUE), irrigation water-use efficiency (WUEi), net water-use efficiency (WUEet) and evapotranspiration (ET). A comparison of irrigation schedules for wheat suggested that for maximum yield in the NCP, 300
mm is an optimal amount of irrigation, corresponding to an ET value of 426
mm. Results showed that with increasing ET, the irrigation requirements of winter wheat increase as do soil evaporation but excessive amounts of irrigation can decrease grain yield, WUE, and WUEi. These results indicate that excessive irrigation might not produce greater yield or optimal economic benefit, thus, suitable irrigation schedules must be established.
There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, ...benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM). Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens.
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•The Antifungal Combination Matrix reports 1,550 antifungal drug combinations•ACM combinations act against fungal pathogens including azole-resistant C. albicans•Clofazimine potentiates antifungals in diverse fungi by targeting membrane function•Clofazimine potentiates caspofungin in an invertebrate model of fungal pathogenesis
There is a dire need for new antifungal therapies. To address this necessity, Robbins et al. screened ∼86,000 unique chemical combinations for activity against fungi. The authors find that the antimycobacterial drug clofazimine increases the efficacy of antifungals by disrupting membrane integrity. This study unveils a rich dataset for antifungal development.
Knowledge of thermodynamics and phase equilibria of oxidic materials is crucial for advancement in the field of ceramics and glass. With the development of computational thermodynamics, predicting ...phase diagrams and chemical reactions of multicomponent systems has become possible. However, there are still plenty of oxides, the thermodynamic properties of which have not been identified due to the challenges in conducting experiments. Therefore, a key to the advancement in thermodynamic modeling would be to develop a universal model that can be used to estimate the thermodynamic properties of oxides with reliable extrapolation capacity. Atomistic (or molecular) scale models are still insufficient in predicting the thermodynamic properties of oxides at any scale. Alternatively, among group contribution–based methods, the polyhedron model has presented its potential in the estimation of the thermodynamic properties of ionic crystals. However, this model still demands improvements that increase the model's accuracy and extrapolation capacity. In this paper, the background and the state‐of‐the‐art of polyhedron model will be presented together with its strengths and shortcomings. Subsequently, it will be briefly discussed how the field of artificial intelligence could be exploited to devise the next generation of the polyhedron model, the modified polyhedron model.
Biofilm formation is one of the main obstacles in membrane treatment. The non-oxidizing biocide ethyl lauroyl arginate (LAE) is promising for mitigating biofilm development on membrane surfaces. ...However, the operating conditions of LAE and their impact on biofilm detachment are not comprehensively understood. In this study, a real-time in vitro flow cell system was utilized to observe biofilm dispersal caused by the shear rate, concentration, and treatment time of LAE. This confirmed that the biofilm was significantly reduced to 68.2% at a shear rate of 3.42 s−1 due to the increased physical lifting force. LAE exhibited two different mechanisms for bacterial inactivation and biofilm dispersal. Biofilms treated with LAE at sub-growth inhibitory concentrations for a longer time could effectively detach the biofilm formed on the surface of the glass slides, which can be attributed to the increased motility of microorganisms. However, a high concentration (i.e., bactericidal concentration) of LAE should be seriously considered because of the inactivated sessile bacteria and their residual debris remaining on the surface. This study sheds light on the effect of LAE on biofilm detachment and provides insights into biofouling mitigation during the membrane process.
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