Therapeutic effect of E-Lip-siRNA-sFlt1 on pre-eclampsia: targeted gene silencing and improved pregnancy outcomes.

Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE). Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured. Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats. Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia.

[Box: see text].

Microglia as a Game Changer in Epilepsy Comorbid Depression.

As one of the most common neurological diseases, epilepsy is often accompanied by psychiatric disorders. Depression is the most universal comorbidity of epilepsy, especially in temporal lobe epilepsy (TLE). Therefore, it is urgently needed to figure out potential mechanisms and the optimization of therapeutic strategies. Microglia play a pivotal role in the coexistent relationship between epilepsy and depression. Activated microglia released cytokines like IL-6 and IL-1ß, orchestrating neuroinflammation especially in the hippocampus, worsening both depression and epilepsy. The decrease of intracellular K+ is a common part in various molecular changes. The P2X7-NLRP3-IL-1ß is a major inflammatory pathway that disrupts brain network. Extra ATP and CX3CL1 also lead to neuronal excitotoxicity and blood-brain barrier (BBB) disruption. Regulating neuroinflammation aiming at microglia-related molecules is capable of suspending the vicious mutual aggravating circle of epilepsy and depression. Other overlaps between epilepsy and depression lie in transcriptomic, neuroimaging, diagnosis and treatment. Hippocampal sclerosis (HS) and amygdala enlargement (AE) may be the underlying macroscopic pathological changes according to current studies. Extant evidence shows that cognitive behavioral therapy (CBT) and antidepressants like selective serotonin-reuptake inhibitors (SSRIs) are safe, but the effect is limited. Improvement in depression is likely to reduce the frequency of seizure. More comprehensive experiments are warranted to better understand the relationship between them.

Liquid Nitrogen Sources Assisting Gram-Scale Production of Single-Atom Catalysts for Electrochemical Carbon Dioxide Reduction.

Developing metal-nitrogen-carbon (M-N-C)-based single-atom electrocatalysts for carbon dioxide reduction reaction (CO2 RR) have captured widespread interest because of their outstanding activity and selectivity. Yet, the loss of nitrogen sources during the synthetic process hinders their further development. Herein, an effective strategy using 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ]) as a liquid nitrogen source to construct a nickel single-atom electrocatalyst (Ni-SA) with well-defined Ni-N4 sites on a carbon support (denoted as Ni-SA-BB/C) is reported. This is shown to deliver a carbon monoxide faradaic efficiency of >95% over a potential of -0.7 to -1.1 V (vs reversible hydrogen electrode) with excellent durability. Furthermore, the obtained Ni-SA-BB/C catalyst possesses higher nitrogen content than the Ni-SA catalyst prepared by conventional nitrogen sources. Importantly, only thimbleful Ni nanoparticles (Ni-NP) are contained in the large-scale-prepared Ni-SA-BB/C catalyst without acid leaching, and with only a slight decrease in the catalytic activity. Density functional theory calculations indicate a salient difference between Ni-SA and Ni-NP in the catalytic performance toward CO2 RR. This work introduces a simple and amenable manufacturing strategy to large-scale fabrication of nickel single-atom electrocatalysts for CO2 -to-CO conversion.

Preparation of liposome coated hollow copper sulfide nano-enzyme and their combined laser irradiation to against melanoma B16-F10 cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：构建中空硫化铜纳米酶脂质复合载体CuS@LIP并探讨其联合激光照射杀伤黑色素瘤B6-F10细胞的效果与机制。方法：构建（2,3-二油酰基-丙基）-三甲胺-丙烷（氯盐）（DOTAP）阳离子脂质体包被硫化铜纳米载体CuS@LIP，研究不同质量浓度的CuS与CuS@LIP在1 064 nm激光照射下的光热性能和热稳定性，通过H2O2与3,3',5,5'-四甲基联苯胺（TMB）催化活性检测体系检测CuS@LIP的类过氧化物活性；用系列质量浓度梯度的CuS、CuS@LIP在有/无激光条件下分别处理B16-F10细胞，CCK-8法检测细胞的存活率，Calcein-AM/PI染色法、Annexin Ⅴ-FITC/PI染色法结合流式细胞仪分别检测20 μg/mL CuS或CuS@LIP在激光照射或非激光照射条件下对B16-F10细胞活力和凋亡的影响。结果：成功制备的CuS@LIP的平均粒径为（178.23±6.46）nm，平均Zeta电位为（20.47±0.93）mV；在激光照射下，80 μg/mL CuS@LIP最高温度可达65.4 ℃，比单纯CuS的63.4 ℃更高；经3个激光开关周期测试，CuS@LIP终点温度基本保持不变；此外，CuS@LIP与CuS具有相同的类过氧化物酶催化活性。低于20 μg/mL的CuS@LIP在体外对B16-F10细胞的增殖活性没有明显影响（P>0.05），但联合激光照射后细胞存活率明显降低（29.76±3.60）% vs （87.95±8.18）%，P<0.000 1，细胞凋亡率显著升高[（19.34±4.41）% vs （13.36±0.86）%，P<0.01]。结论：制备的CuS@LIP具有符合设计要求的理化性质、良好的光热性能和优异的类过氧化物酶催化活性，其与激光照射联合后显示出更优异的杀伤B16-F10细胞的效果。

Super-Hygroscopic Calcium Chloride/Graphene Oxide/Poly(N-isopropylacrylamide) Gels for Spontaneous Harvesting of Atmospheric Water and Solar-Driven Water Release.

Although atmospheric water harvesting is a promising approach for extracting clean water in water deficient areas, most atmospheric water collectors require additional energy for releasing the water absorbed. It is still challenging to improve both moisture absorption capacity and desorption efficiency of moisture water collectors. Inspired by clean solar energy and the large humidity difference between day and night, super-hygroscopic calcium chloride (CaCl2)/graphene oxide (GO)/poly(N-isopropylacrylamide) (PNIPAM) gels are designed for spontaneous collection of atmospheric water in a wide range of relative humidity (RH) followed by solar-driven release of the water absorbed. An optimal CaCl2/GO/PNIPAM hygroscopic gel possesses a hierarchical porous structure with directional water transport channels, facilitating water capture and release, thus exhibiting a high moisture absorption capacity of up to 3.6 g g-1 at an RH of 90%. Driven by simulated sunlight, the solar-thermal energy conversion effect of the GO component triggers a unique hydrophilic-hydrophobic conformational transition and shrinkage of the PNIPAM for efficient release of the water absorbed. The integration of the spontaneous harvesting of atmospheric water and the solar-driven water release makes the super-hygroscopic gels promising for efficiently utilizing atmospheric water for special applications where water is desperately necessary but unavailable.

DNA-Modified Liquid Crystal Droplets.

In this work, we have combined the advantages of sequence programmability of DNA nanotechnology and optical birefringence of liquid crystals (LCs). Herein, DNA amphiphiles were adsorbed onto LC droplets. A unique phenomenon of LC droplet aggregation was demonstrated, using DNA-modified LC droplets, through complementary DNA hybridization. Further functionalization of DNA-modified LC droplets with a desired DNA sequence was used to detect a wide range of chemicals and biomolecules, such as Hg2+, thrombin, and enzymes, through LC droplet aggregation and vice versa, which can be seen through the naked eye. These DNA-modified LC droplets can be printed onto a desired patterned surface with temperature-induced responsiveness and reversibility. Overall, our work is the first to report DNA-modified LC droplet, which provides a general detection platform based on the development of DNA aptamers. Additionally, this work inspires the exploration of surface information visualization combined with microcontact printing.

Insight into the Active Sites of N,P-Codoped Carbon Materials for Electrocatalytic CO2 Reduction.

Doping heteroatoms in carbon materials is a promising method to prepare the robust electrocatalysts for the carbon dioxide reduction reaction (CO2RR), which is beneficial for sustainable energy storage and environmental remediation. However, the obscure recognition of active sites is the obstacle for further development of high-efficiency electrocatalysts, especially for the N,P-codoped carbon materials. Herein, a series of N,P-codoped carbon materials (CNP) is prepared with different N and P contents to explore the relationship between the N/P configuration and the CO2RR activity. As compared with the N-doped carbon materials, the additional P doping is helpful to improve the activity. The optimum N,P-codoped carbon materials (CNP-900) achieve 80.8% CO Faradaic efficiency (FECO) at a mild overpotential of 0.44 V. On the basis of the X-ray photoelectron spectroscopy results, the suitable ratio between pyridinic N and graphitic N and the least P-N content are beneficial for CO2RR. The density functional theory calculations further illustrate that two elementary steps to form *COOH and *CO in CO2RR are determined by the graphitic N and pyridinic N configurations, respectively. The existence of the P-N configuration breaks the equilibrium between graphitic N and pyridinic N to suppress the activity.

Experimental Investigation of a Novel Nanocomposite Particle Gel for Water Shutoff Treatment in Mature Oilfields.

Conventional preformed particle gels suffer from insufficient salt tolerance and weak mechanical properties after water absorption, which reduce the water shutoff effect in mature oilfields. In this paper, a nanocomposite particle gel (NCPG) is synthesized by copolymerization of acrylamide (AM) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) using laponite RD (LPT) as a physical cross-linker and N,N-methylene-bisacrylamide (MBA) as a chemical cross-linker via in situ free radical polymerization. Compared with the NCPG without LPT, both the swelling rate and mechanical properties of NCPG added with LPT are found to be improved. In addition, the pore sizes of the network of the swollen NCPG are smaller than those of the sample without LPT, and the thermal stability is also slightly enhanced. The swelling rate of NCPG increases with increasing AMPS concentration. The water absorbency of NCPG first increases and then decreases with increasing MBA and APS concentrations. The NCPG is sensitive to alkaline medium due to the presence of sulfonic acid groups on the molecular chains of the NCPG. The synthesized NCPG exhibits good salt tolerance at 80 °C in formation water. The plugging rate of the NCPG to a sand-pack is above 90%, and the residual resistance factor reaches 19.2 under reservoir conditions. These results indicate that the NCPG may have potential application for water shutoff treatment in mature oilfields.

Effects of Macrothele raven venom on intrarenal invasion and metastasis of H22 liver cancer cells in mice.

BACKGROUND: Extrahepatic metastatic hepatocellular carcinoma (HCC) and its insensitivity to chemotherapy are the main causes of poor prognosis in patients with HCC. This study investigated the anti-cancer effect of Macrothele raveni venom on intrarenal metastatic HCC. MATERIALS AND METHODS: Subrenal capsule xenograft model of HCC was established by inoculation of H22 liver cancer cells. RESULTS: The general health, histology, and molecular changes were observed after administering 10 times of different dose of Macrothele raven venom injections. A volume of 0.8 µg/ml and 1.0 µg/ml of Macrothele raven venom significantly improved general health status in mice with subrenal capsule HCC tumors. Hematoxylin and eosin staining showed that Macrothele raven venom dose-dependently reduced invasion and metastasis of liver cancer cells in the kidney. Immunohistochemistry and real-time polymerase chain reaction showed that Macrothele raven venom injection dose-dependently decreased PI3K mRNA and protein, Akt protein, and mTOR mRNA expression, but increased Bad mRNA and protein expression in the kidney with H22 tumor cell invasion. 0.8 µg/ml is the most effective dose for the treatment of intrarenal metastatic HCC. CONCLUSIONS: Macrothele raven venom dose-dependently inhibits invasion and metastasis of intrarenal metastatic HCC through inhibition of PI3K-Akt-mTOR signaling and increase of Bad expression.

The Assembly of DNA Amphiphiles at Liquid Crystal-Aqueous Interface.

In this article, we synthesized a type of DNA amphiphiles (called DNA-lipids) and systematically studied its assembly behavior at the liquid crystal (LC)-aqueous interface. It turned out that the pure DNA-lipids at various concentrations cannot trigger the optical transition of liquid crystals from planar anchoring to homeotropic anchoring at the liquid crystal-aqueous interface. The co-assembly of DNA-lipid and l-dilauroyl phosphatidylcholine (l-DLPC) indicated that the DLPC assembled all over the LC-aqueous interface, and DNA-lipids prefer to couple with LC in certain areas, particularly in polarized and fluorescent image, forming micron sized net-like structures. The addition of DNA complementary to DNA-lipids forming double stranded DNA-lipids caused de-assembly of DNA-lipids from LC-aqueous interface, resulting in the disappearance of net-like structures, which can be visualized through polarized microscope. The optical changes combined with DNA unique designable property and specific interaction with wide range of target molecules, the DNA-lipids decorated LC-aqueous interface would provide a new platform for biological sensing and diagnosis.

Specific and nonspecific thalamocortical functional connectivity in normal and vegetative states.

Recent theoretical advances describing consciousness from information and integration have highlighted the unique role of the thalamocortical system in leading to integrated information and thus, consciousness. Here, we examined the differential distributions of specific and nonspecific thalamocortical functional connections using resting-state fMRI in a group of healthy subjects and vegetative-state patients. We found that both thalamic systems were widely distributed, but they exhibited different patterns. Nonspecific connections were preferentially associated with brain regions involved in higher-order cognitive processing, self-awareness and introspective mentalizing (e.g., the dorsal prefrontal and anterior cingulate cortices). In contrast, specific connections were prevalent in the ventral and posterior part of the prefrontal and precuneus, known involved in representing externally-directed attentions. Significant reductions of functional connectivity in both systems, especially the nonspecific system, were observed in VS. These data suggest that brain networks sustaining information and integration may be differentiated by the nature of their thalamic functional connectivity.