OBJECTIVE: This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy.
METHODS: This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded.
CONCLUSIONS: Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.

In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N+-O-) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/m). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.

Numerous small biomolecules exist in the human body and play roles in various biological and pathological processes. Small molecules are believed not to induce intrafibrillar mineralization alone. They are required to work in synergy with noncollagenous proteins (NCPs) and their analogs, e.g. polyelectrolytes, for inducing intrafibrillar mineralization, as the polymer-induced liquid-like precursor (PILP) process has been well-documented. In this study, we demonstrate that small charged molecules alone, such as sodium tripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane, could directly mediate fibrillar mineralization. We propose that small charged molecules might be immobilized in collagen fibrils to form the polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds. The PLCC could attract CaP precursors along with calcium and phosphate ions for inducing mineralization without any polyelectrolyte additives. The small charged molecule-mediated mineralization process was evidenced by Cryo-TEM, AFM, SEM, FTIR, ICP-OES, etc., as the PLCC exhibited both characteristic features of collagen fibrils and polyelectrolyte with increased charges, hydrophilicity, and density. This might hint at one mechanism of pathological biomineralization, especially for understanding the ectopic calcification process.

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10% A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.

In the current study, a tumor microenvironment responsive (TME-responsive) copper peroxide-mesoporous silica core-shell structure with H2O2 self-supplying ability was fabricated for targeted ferroptosis/chemotherapy against metastatic breast cancer. At the first stage, copper peroxide nanodot was synthesized and subsequently coated with mesoporous organosilica shell. After (3-Aminopropyl) triethoxysilane (APTMS) functionalization of the organosilica shell, doxorubicin (DOX) was loaded in the mesoporous structure of the nanoparticles and then, heterofunctional COOH-PEG-Maleimide was decorated on the surface through EDC/NHS chemistry. Afterward, thiol-functionalized AS1411 aptamer was conjugated to the maleimide groups of the PEGylated nanoparticles. In vitro study illustrated ROS generation of the system in the treated 4 T1 cell. Cellular uptake and cytotoxicity experiments showed enhanced internalization and cytotoxicity of the targeted system comparing to non-targeted one. The in vivo study on ectopic 4 T1 tumor induced in Female BALB/c mice showed ideal therapeutic effect of Apt-PEG-Silica-DOT@DOX with approximately 90 % tumor suppression in comparison with 50 % and 25 % tumor suppression for PEG-Silica-DOT@DOX and PEG-Silica-DOT. Moreover, Apt-PEG-Silica-DOT@DOX provide favorable characteristics for biosafety issues concerning the rate of survival and loss of body weight. The prepared platform could serve as a multifunctional system with smart behavior in drug release, tumor accumulation and capable for ferroptosis/chemotherapy against breast cancer.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.

Water treatment has turned out to be more important in most societies due to the expansion of most economies and to advancement of industrialization. Developing efficient materials and technologies for water treatment is of high interest. Thin film nanocomposite membranes are regarded as the most effective membranes available for salts, hydrocarbon, and environmental pollutants removal. These membranes improve productivity while using less energy than conventional asymmetric membranes. Here, the polyvinylidene fluoride (PVDF) membranes have been successfully modified via dip single-step coating by silica-aminopropyl triethoxysilane/trimesic acid/melamine nanocomposite (Si-APTES-TA-MM). The developed membranes were evaluated for separating the emulsified oil/water mixture, the surface wettability of the membrane materials is therefore essential. During the conditioning step, that is when the freshwater was introduced, the prepared membrane reached a flux of about 27.77 L m-2 h-1. However, when the contaminated water was introduced, the flux reached 18 L m-2 h-1, alongside an applied pressure of 400 kPa. Interestingly, during the first 8 h of the filtration test, the membrane showed 90 % rejection for ions including Mg2+, and SO42- and ≈100 % for organic pollutants including pentane, isooctane, toluene, and hexadecane. Also, the membrane showed 98 % rejection for heavy metals including strontium, lead, and cobalt ions. As per the results, the membrane could be recommended as a promising candidate to be used for a mixture of salt ions, hydrocarbons, and mixtures of heavy metals from wastewater.

The aging of paper seriously threatens the service life of cultural heritage documents. Bacterial cellulose (BC), which has a good fiber aspect ratio and is rich in hydroxyl groups, is suitable for strengthening aged paper. However, a single BC added was not ideal for paper restoration, since only strengthening was not able to resist the persistent acidification of ancient book. In this work, BC was functionalized by 3-aminopropyltriethoxysilane (APTES) to develop the interface bonding with aged paper. Fourier transform infrared (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and elemental analysis identified the successful amino-silanization of BC. The modification parameters were optimized as the concentration of APTES of 5 wt%, the reaction time of 4 h, and the reaction temperature of 80 °C based on a considerable improvement in the strength properties without obvious appearance impact on reinforced papers. Moreover, the pH value of the repaired paper was achieved at 8.03, ensuring the stability of the anti-aging effect. The results confirmed that APTES-BC had great potential applications in ancient books conservation.

A facial strategy of co-deposition is proposed to enhance the interfacial bonding in wood fiber (WF)/polylactic acid (PLA) composites. Dopamine or tannic acid (TA) was co-deposited with 3-aminopropyltriethoxysilane (APTES) onto the WF surface to create active coatings. These coatings were formed through Michael addition and Schiff base reactions and effectively attached to the WF through a combination of hydrogen and covalent bonding. Such active coatings facilitated the connection between WF and PLA through both covalent bonds and physical entanglements, thereby enhancing the interfacial interactions and compatibility between the two components. The co-deposition of TA with APTES was found to be more effective than with dopamine, leading to a dramatic improvement in the tensile strength and elongation at break of the composites by 33.4 % and 185.9 %, respectively. This work offers a facile method to prepare high performance plant fiber reinforced PLA composites, thereby broadening the potential applications of PLA.