Latest ArticlesRecently, the utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) to sensitize cisplatin (CDDP) has gained substantial traction in the treatment of ovarian cancer (OC). However, even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events, notably thrombosis. Furthermore, the diminished sensitivity to CDDP therapy in OC is multifactorial, rendering the application of NSAIDs only partially effective due to their cyclooxygenase-2 (COX-2) inhibiting mechanism. Hence, in this study, reactive oxygen species (ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(Ⅳ) prodrug (DTP@AP NPs) were prepared to achieve comprehensive chemosensitization. On one front, allicin achieved COX-2 blocking therapy, encompassing the inhibition of proliferation, angiogenesis and endothelial mesenchymal transition (EMT), thereby mitigating the adverse impacts of CDDP chemotherapy. Simultaneously, synergistic chemosensitization was achieved from multifaceted mechanisms by decreasing CDDP inactivation, damaging mitochondria and inhibiting DNA repair. In essence, these findings provided an optimized approach for synergizing CDDP with COX-2 inhibitors, offering a promising avenue for enhancing OC treatment outcomes.
Under the guidance of the approach which integrates molecular networking, MolNetEnhancer and Network Annotation Propagation (NAP), daphnaltaicanoids A and B (1 and 2) with unprecedented 9-oxa-tetracyclo[6.6.1.02,6.08,13]pentadecane and tetracyclo[5.3.0.12,5.24,11]tridecane central frameworks were isolated from Daphne altaica Pall., representing two types of unparalleled meroterpenoid cores. Their structures were elucidated by extensive spectroscopic analysis, nuclear magnetic resonance (NMR) calculations, DP4+ analysis and electronic circular dichroism (ECD) calculations. The plausible biosynthetic pathways for 1 and 2 were postulated. Biologically, 2 exerted potent neuroprotective activities which were superior to trolox at 12.5 and 25 µmol/L. Moreover, 1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with acetylcholinesterase. The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.
Traditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment, and more effective treatments are urgently required. Recent studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7 (CDK7) could effectively suppress prostate cancer progression. However, the toxicity of CDK7 inhibitors such as THZ1 is the main limitation of the clinical application. In this work, we synthesized Cys8E (C8E) nanoparticles (NPs) loaded with THZ1 (C8E@THZ1), a novel GSH-targeting and stimuli-responsive nano-delivery platform, and investigated its anti-tumor potential and biosafety properties. In vitro, C8E@THZ1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer cells. On tumor-bearing mice, C8E@THZ1 inhibited tumors by up to 85%, while the damage of THZ1 to liver function was effectively avoided. These results confirmed that inhibition of CDK7 can effectively block the progression of prostate cancer, and that Cys8E NPs is a highly prospective delivery platform to promote the clinical application of CDK7 inhibitors.
Recently, a novel 2-electron oxygen reduction reaction (ORR) based electro-oxidation (EO) system was developed, which utilizes a H2O2 generation cathode instead of H2 evolution cathode. A Ti-based Ni-Sb co-doped SnO2 (Ti/NATO) anode was selected for efficient degradation of refractory organics and O3 production. The synergistic reaction of O3/H2O2 further accelerated the generation of hydroxyl radicals (•OH) in the ORR-EO system. However, the catalytic activity and long-term effectiveness of the Ti/NATO anode limited the large-scale application of the ORR-EO process. In this study, a blue TiO2 nanotube array (blue-TiO2-NTA) inter-layer was introduced into the fabrication process between the Ti substrate and NATO catalyst layer. Compared to the Ti/NATO anode, the Ti/blue-TiO2-NTA/NATO anode achieved higher efficiency of organic removal and O3 generation. Additionally, the accelerated lifetime of the Ti/blue-TiO2-NTA/NATO anode was increased by 7 times compared to the Ti/NATO anode. When combined with CNTs-C/PTFE air cathode in ORR-EO system, all anodic oxidation and O3/H2O2 processes achieved higher •OH production. Over 92% of TOC in leachate bio-effluent was effectively eliminated with a relatively low energy cost of 45 kWh/t.
We report here the synthesis and characterization of two new members of the M2E12 family of endohedral Zintl clusters, [Fe2Sn4Bi8]3– and [Cr2Sb12]3–, both of which contain open-shell metal dimers encapsulated inside a triple-decker cluster of main-group atoms. The 75-electron [Fe2Sn4Bi8]3– cluster has a D4h-symmetric structure, while [Cr2Sb12]3–, despite having the same 75-electron count, is strongly distorted to a geometry that resembles a CrSb8 crown capped by a CrSb4 unit. The structural differences between the two are driven by the increasing availability of 3d electron density in the earlier transition metal, which leads, ultimately, to different electronic configurations in the two clusters. The trends precisely mirror those observed in the ME10 and ME12 families containing a single transition metal ion.
Bioprinting is emerging as an advanced tool in tissue engineering. However, there is still a lack of bioinks able to form hydrogels with desirable bioactivities that support positive cell behaviors. In this study, modified plasma proteins capable of forming hydrogels with multiple biological functions are developed as bioinks for digital light processing (DLP) printing. The Plasma-MA (BM) was synthesized via a one-pot method through the reaction between the fresh frozen plasma and methacrylic anhydride. The methacrylated levels were observed to influence the physical properties of BM hydrogels including mechanical properties, swelling, and degradation. The photo-crosslinked BM hydrogels can sustainedly release vascular endothelial growth factor (VEGF) and exhibit positive biological effects on cell adhesion and proliferation, and cell functionality such as tube formation of human umbilical vein endothelial cells (HUVECs), and neurite elongation of rat pheochromocytoma cells (PC12). Meanwhile, BM hydrogels can also induce cell infiltration, modulate immune response, and promote angiogenesis in vivo. Moreover, the plasma bioinks can be used to fabricate customized scaffolds with complex structures through a DLP printing process. These findings implicate that the modified plasma with growth factor release is a promising candidate for bioprinting in autologous and personalized tissue engineering.
Photodynamic therapy (PDT) has emerged as a significant cancer therapy option. Currently, cation-based organic small molecule aggregation-induced emission (AIE) photosensitizers (PSs) attract the wide attention of many scientists, due to improved reactive oxygen species (ROS) production after cationization. However, such PSs tend to localize only the mitochondria, limiting the death way of tumor cells (usually apoptosis) during PDT process, which may affect the therapeutic effect under some circumstances. Herein, we designed a novel water-soluble three positive charge PS, TPAN-18F, which could be distributed uniformly in cell cytoplasm and had distribution in different sub-organelles (mitochondria, endoplasmic reticulum, lysosome). The experimental results showed that TPAN-18F-based PDT process can not only disrupt mitochondrial functions (reducing ATP production and destroying mitochondrial membrane potential), but also elevate the intracellular lipid peroxides (LPOs) level, which evoke the non-apoptotic death manner of tumor cells. Further, in vivo studies showed that TPAN-18F-based PDT could effectively inhibit tumor growth. Accordingly, we believe that the construction of TPAN-18F is suggestive for tumor non-apoptotic therapy.
Fe(II) is an essential trace element for anaerobic ammonium oxidation bacteria (AAOB) metabolism, and can improve the nitrogen removal efficiency of anaerobic ammonia oxidation (Anammox). Here we operated two identical expanded granular sludge bed (EGSB) reactors at low temperature (15 ± 3 ℃) for 154 days. Reactor 1 (R1) received additional Fe(II) (0.12 mmol/L) during the late startup phase, while reactor 0 (R0) served as the control and did not receive extra Fe(II). Nitrogen removal in R1 became stable at 55 d of operation, ten days earlier than R0. The nitrogen removal rate (NRR) of R1 was 1.64 kg N m−3 d−1 and its TN removal rate was as high as 89%, while R0 only reached 75%. The addition of Fe(II) was further beneficial to aggregation and stability of the granular sludge, and the used sludge of both reactors showed enrichment for AAOB populations compared to the inoculum, for instance, increased abundance of Candidatus-Kuenenia and in particular of Candidatus-Brocadia (from 0.17% to 10.10% in R0 and 7.79% in R1). Diverse microbial species and complex microbial network structure in R1 compared to R0 promoted the coupled denitrogenation by Anammox, dissimilatory nitrate reduction to ammonium (DNRA), nitrate-dependent Fe oxidation (NDFO), and ferric ammonium oxidation (Feammox). In addition, the microbial community in R1 was more resistant to short-term low temperature (2–7 ℃) starvation, illustrating a further positive effect of adding Fe(II) during the startup phase of an Anammox reactor.
Small molecule inhibitors have dominated the pharmaceutical landscape for a long time as the primary therapeutic paradigm targeting pathogenic proteins. However, their efficacy heavily relies on the amino acid composition and spatial constitution of proteins, rendering them susceptible to drug resistance and failing to target undruggable proteins. In recent years, the advent of targeted protein degradation (TPD) technology has captured substantial attention from both industry and academia. Employing an event-driven mode, TPD offers a novel approach to eliminate pathogenic proteins by promoting their degradation, thus circumventing the limitations associated with traditional small molecule inhibitors. Hydrophobic tag tethering degrader (HyTTD) technology represents one such TPD approach that is currently in the burgeoning stage. HyTTDs employ endogenous protein degradation systems to induce the degradation of target proteins through the proteasome pathway, which displays significant potential for medical value. In this review, we provide a comprehensive overview of the development history and the reported mechanism of action of HyTTDs. Additionally, we delve into the physiological roles, structure-activity relationships, and medical implications of HyTTDs targeting various disease-associated proteins. Moreover, we propose insights into the challenges that necessitate resolution for the successful development of HyTTDs, with the ultimate goal of initiating a new age of clinical treatment leveraging the immense potential of HyTTDs.
For treatment of sulfion-containing wastewater, coupling the electrochemical sulfion oxidation reaction (SOR) with hydrogen evolution reaction (HER) can be an ideal way for sulfur and H2 resources recovery. Herein, we synthesize a metal-modified carbon nanotube arrays electrode (Co@NCNTs/CC) for SOR and HER. This electrode has excellent performance for SOR and HER attributed to the unique array structure. It can achieve 99.36 mA/cm2 at 0.6 V for SOR, and 10 mA/cm2 at 0.067 V for HER. Density functional theory calculations verify that metal modification is able to regulate the electronic structure of carbon nanotube, which is able to optimize the adsorption of intermediates. Employed Co@NCNTs/CC as bifunctional electrodes to establish a hybrid electrolytic cell can reduce about 67% of energy consumption compared with the traditional water splitting electrolytic cell. Finally, the hybrid electrolytic cell is used to treat actual sulfion-containing wastewater, achieving the sulfur yield of 30 mg h−1 cm−2 and the hydrogen production of 0.64 mL/min.
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