Gradually Self-Strengthen DNA Supramolecular Hydrogels.

The dynamic mechanical strength of the extracellular matrix (ECM) has been demonstrated to play important role in determining the cell behavior. Growing evidences suggest that the gradual stiffening process of the matrix is particularly decisive during tissue development and wound healing. Herein, a novel strategy to prepare hydrogels with gradually enhanced mechanical strength is provided. Such hydrogels could maintain the dynamic properties at their initial states, such as self-healing and shear-thinning properties. With subsequent slow covalent crosslinking, the stability and mechanical properties would be gradually improved. This method is useful for sequence programmability and oxidation strategies, which has provided an alternated tool to study cell behavior during dynamic increase in mechanical strength of ECM.

Melittin induces autophagy to alleviate chronic renal failure in 5/6-nephrectomized rats and angiotensin II-induced damage in podocytes.

BACKGROUND/OBJECTIVES: Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear. MATERIALS/METHODS: A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. RESULTS: In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes. CONCLUSION: Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

Polyurethane with ß-Selenocarbonyl Structure Enabling the Combination of Plastic Degradation and Waste Upcycling.

Degradable polymers offer a promising solution to mitigate global plastic pollution, but the degraded products often suffer from diminished value. Upcycling is a more sustainable approach to upgrade polymer waste into value-added products. Herein, we report a ß-selenocarbonyl-containing polyurethane (SePU), which can be directly degraded under mild conditions into valuable selenium fertilizers for selenium-rich vegetable cultivation globally, enabling both plastic degradation and waste upcycling. Under oxidation condition, this polymer can be easily and selectively degraded via selenoxide elimination reaction from mixed plastic waste. The degraded product can serve as effective selenium fertilizers to increase selenium content in radish and pak choi. The SePU exhibits excellent mechanical properties. Additionally, we observed the formation of spherulites-like selenium particles within the materials during degradation for the first time. Our research offers a successful application of selenoxide elimination reaction in the field of plastic degradation for the first time, endowing plastics with both degradability and high reusable value. This strategy provides a promising solution to reduce pollution and improve economy and sustainability of plastics.

Selenium-Containing Nanocomplexes Achieve Dual Immune Checkpoint Blockade for NK Cell Reinvigoration.

The blockade of immune checkpoints has emerged as a promising strategy for cancer immunotherapy. However, most of the current approaches focus on T cells, leaving natural killer (NK) cell-mediated therapeutic strategies rarely explored. Here, a selenium-containing nanocomplex is developed that acts as a dual immune checkpoint inhibitor to reinvigorate NK cell-based cancer immunotherapy. The Se nanocomplex can deliver and release siRNA that targets programmed death ligand-1 (PD-L1) in tumor cells, thereby silencing the checkpoint receptor PD-L1. The intracellular reactive oxygen species generated by porphyrin derivatives in the nanocomplexes can oxidize the diselenide bond into seleninic acid, which blocks the expression of another checkpoint receptor, human leukocyte antigen E. The blockade of dual immune checkpoints shows synergistic effects on promoting NK cell-mediated antitumoral activity. This study provides a new strategy to reinvigorate NK cell immunity for the development of combined cancer immunotherapy.

Extreme long-lifetime self-assembled monolayer for air-stable molecular junctions.

The molecular electronic devices based on self-assembled monolayer (SAM) on metal surfaces demonstrate novel electronic functions for device minimization yet are unable to realize in practical applications, due to their instability against oxidation of the sulfur-metal bond. This paper describes an alternative to the thiolate anchoring group to form stable SAMs on gold by selenides anchoring group. Because of the formation of strong selenium-gold bonds, these stable SAMs allow us to incorporate them in molecular tunnel junctions to yield extremely stable junctions for over 200 days. A detailed structural characterization supported by spectroscopy and first-principles modeling shows that the oxidation process is much slower with the selenium-gold bond than the sulfur-gold bond, and the selenium-gold bond is strong enough to avoid bond breaking even when it is eventually oxidized. This proof of concept demonstrates that the extraordinarily stable SAMs derived from selenides are useful for long-lived molecular electronic devices and can possibly become important in many air-stable applications involving SAMs.

Visualizing Chain Growth of Polytelluoxane via Polymerization Induced Emission.

Visualizing polymer chain growth is always a hot topic for tailoring structure-function properties in polymer chemistry. However, current characterization methods are limited in their ability to differentiate the degree of polymerization in real-time without isolating the samples from the reaction vessel, let alone to detect insoluble polymers. Herein, a reliable relationship is established between polymer chain growth and fluorescence properties through polymerization induced emission. (TPE-C2)2 -Te is used to realize in situ oxidative polymerization, leading to the aggregation of fluorophores. The relationship between polymerization degree of growing polytelluoxane (PTeO) and fluorescence intensity is constructed, enabling real-time monitoring of the polymerization reaction. More importantly, this novel method can be further applied to the observation of the polymerization process for growing insoluble polymer via surface polymerization. Therefore, the development of visualization technology will open a new avenue for visualizing polymer chain growth in real-time, regardless of polymer solubility.

Intracellular Hyperbranched Polymerization for Circumventing Cancer Drug Resistance.

Polymerization inside living cells provides chemists with a multitude of possibilities to modulate cell activities. Considering the advantages of hyperbranched polymers, such as a large surface area for target sites and multilevel branched structures for resistance to the efflux effect, we reported a hyperbranched polymerization in living cells based on the oxidative polymerization of organotellurides and intracellular redox environment. The intracellular hyperbranched polymerization was triggered by reactive oxygen species (ROS) in the intracellular redox microenvironment, effectively disrupting antioxidant systems in cells by an interaction between Te (+4) and selenoproteins, thus inducing selective apoptosis of cancer cells. Importantly, the obtained hyperbranched polymer aggregated into branched nanostructures in cells, which could effectively evade drug pumps and decrease drug efflux, ensuring the polymerization for persistent treatment. Finally, in vitro and in vivo studies confirmed that our strategy presented selective anticancer efficacy and well biosafety. This approach provides a way for intracellular polymerization with desirable biological applications to regulate cell activities.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

A Nanotherapeutic Strategy to Reverse NK Cell Exhaustion.

As a specialized immune effector cell, natural killer (NK) cells play a very important role in immunotherapy, but tumor immunosuppression caused by abnormal expression of cancer cells seriously weakens its therapeutic effect and leads to exhaustion. Here, self-assembled selenium-containing nanoparticles (NPs) composed of cetuximab, C5SeSeC5, and inhibitor LY345899 are developed to reverse NK cell exhaustion. The obtained NPs can target epidermal growth factor receptor on the surface of cancer cells and locate it in mitochondria. The released LY345899 can inhibit the activity of methylene tetrahydrofolate dehydrogenase 2 and produce excessive reactive oxygen species, leading to the formation of seleninic acid, further reducing the expression of human leukocyte antigen E , which is responsible for the NKG2A-related NK cell inhibition. As a result, the enhanced NK-cell-mediated immunotherapy in conjunction with the cetuximab-mediated antibody-dependent cell-mediated cytotoxicity effect can not only effectively inhibit the growth of xenograft tumors, but also significantly suppress the growth of untreated distant tumors via the abscopal effect. This work, the combination of seleninic acid, LY345899, and cetuximab, provides a new strategy for reversing NK cell exhaustion and has great potential for use in the treatment of metastatic tumors.

An efficient five-lncRNA signature for lung adenocarcinoma prognosis, with AL606489.1 showing sexual dimorphism.

Background: Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD. Methods: The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. OS-associated lncRNA with sex dimorphism was determined based on the analysis of expression between males and females. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures. Results: A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and <65-year and ≥65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity. Conclusion: Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.

Synthesis of dihydropyrroles from in situ-generated zwitterions via Rh2(adc)4/TBAI dual catalysis.

Triggered by formation of α-imino carbene, the regioselective synthesis of dihydropyrroles was achieved via a cascade 1,3-sulfinate migration/annulation. The sulfinate group was converted into sulfone during the group migration, and a stable anion bearing two electron-withdrawing groups was thus formed. The addition of a catalytic amount of iodide is believed to assist the cleavage of the C-O bond, and the formation of a more stable carbocation. Thermodynamic product dihydropyrroles were produced efficiently rather than kinetic product cyclopropanes. This dual catalysis system would afford chemists a new strategy to control the annulation selectivity of zwitterions bearing multiple reactive sites and may be employed in flexible and divergent synthesis of different ring systems.

Dynamic Fluorescent Patterning Based on Visible-Light-Responsive Diselenide Metathesis.

A diselenide bond, as a dynamic covalent bond, is a versatile tool to construct smart interfaces, which can respond to visible light. In this work, we used microcontact printing (µCP) to construct diselenide patterns on quartz substrates. Fluorescent patterns were obtained on the modified surfaces via the visible-light-induced diselenide metathesis reaction, which allowed the patterning process to be fast, dynamically erasable, and compatible with different fluorescent molecules including rhodamine B and boron-dipyrromethene (BODIPY) used in this work. A variety of analytical methods offered comprehensive evidence for the success of the printing of diselenides here. We further printed diselenide and disulfide intersecting stripes on one single quartz substrate layer by layer and introduced rhodamine B and BODIPY to obtain a multicolored pattern simultaneously. By taking advantage of their responsiveness to different wavelengths, the composite pattern of disulfides and diselenides could be erased by two stepwise stages. The fluorescent images of the modified substrate showed a good agreement with the pattern of the poly(dimethylsiloxane) (PDMS) stamp, indicating the methodology with a potential application for information storage.

Water-Enhanced and Remote Self-Healing Elastomers in Various Harsh Environments.

The development of underwater remote stimulus-responsive self-healing polymer materials for applications in inaccessible and urgent situations is very challenging because water can readily disturb traditional noncovalent bonds and absorb heat, UV light, IR light, and electromagnetic wave energy at the wave band of micrometers and millimeters. Herein, visible-light-responsive diselenide bonds are employed as the healing moieties to produce a water-enhanced and remote self-healing elastomer triggered by a blue laser, which possesses excellent underwater transmission capability. During healing, the strain at break reaches ∼200% in 5 min and its toughness almost fully recovers within 1 h, which is estimated to be the fastest reported to date for healing silicone elastomers with a healing efficiency above 90%. The remote underwater pipeline sealing is instantly accomplished with the diselenide-containing elastomers by a blue laser 3 m away, thereby providing a direction for future emergent healing applications.

Nanotechnology in the Olympic Winter Games and Beyond.

Modern Olympics have increasingly benefited from the advancement of materials science. From February 4 to March 13, 2022, the whole world has witnessed spectacular Olympic Winter Games and Winter Paralympic Games held in Beijing, during which nanotechnologies are extensively applied and play indispensable roles in many aspects. Although these nanotechnologies appear in a very small length scale, they have provided tremendous support to all athletes with the pursuit of "faster, higher, stronger". In this Article, we highlight several representative nanotechnologies applied in the Olympic and Paralympic Winter Games including nanoscience in ice skating, wearable monitoring devices, skiing sports equipment, winter protection, and Olympic printing and discuss their physicochemical principles, unique significance for athletes and sports.

Copper-Selenocysteine Quantum Dots for NIR-II Photothermally Enhanced Chemodynamic Therapy.

Chemodynamic therapy has been appealing for effective cancer treatment. Particularly, Fenton-like reactions catalyzed by Cu2+-based nanoparticles showed promising prospects. Herein, we fabricated copper-selenocysteine quantum dots (Cu-Sec QDs) with the majority of Cu+ by a facile and robust thermal titration process. No high temperature or pressure is needed for this synthetic route of QDs. The selenocysteine functioned as the reducing agent as well as the stabilizer, circumventing the poor water solubility and stability, leading to enhanced biocompatibility. The existence of Cu+ endowed the QDs the ability to catalyze the Fenton-like reaction without an extra reduction reaction of Cu2+ to Cu+. Moreover, the strong absorption in the near-infrared-II region (1000-1300 nm) of the final Cu-Sec QDs is in great favor of the chemodynamic therapy via the photothermally enhanced Fenton-like reaction. And the Cu-Sec QDs exhibited obvious cytotoxicity to various cancer cell lines. We believe that this facile and robust synthetic approach could open up another method for the fabrication of quantum dots toward the potential Fenton-like reaction-based applications in biological fields.

When Dynamic Diselenide Bonds Meet Dynamic Imine Bonds in Polymeric Materials.

In both natural and artificial functional systems, the cooperation between different dynamic interactions is of vital importance for realizing complicated functions. Dynamic covalent bonds are one kind of relatively stable dynamic interactions and have shown synergistic effect in natural systems such as functional proteins. However, synergistic interactions between different dynamic covalent bonds in polymeric materials are still unclear. Herein, polymeric materials containing diselenide and imine bonds are prepared, and then the synergistic effect between the two dynamic covalent bonds is quantitatively evaluated in typical processes of dynamic materials. The results reveal that dynamic covalent bonds show weak synergistic effect in the degradation process and have strong synergistic effect in stress relaxation process. Therefore, introducing multiple dynamic covalent bonds in polymeric materials can extensively enhance their dynamic properties.

Predicting the total PAHs concentrations in sediments from selected congeners using a multiple linear relationship.

In this study, we observed that four congeners, including naphthalene (Nap), acenaphthylene (Acy), phenanthrene (Phe), and benz(a)anthracene (BaA), are the characteristic congeners for predicting the emission and the sediment concentrations of polycyclic aromatic hydrocarbons (PAHs). A novel multiple relationship of the total PAHs concentrations (C∑PAHs) in sediments with the concentrations of four congeners was established (p < 0.01, R2 = 0.95) using published data over the past 30 years. Moreover, the multiple linear relationship of the total PAHs emission factors with the emission factors of four congeners was also established (p < 0.01, R2 = 0.99). Interestingly, the ratio of multicomponents coefficient from the multiple linear relationship in sediments to that from the multiple linear relationship in emission sources correlated positively with octanol-water partition coefficient (logKow) (p < 0.01, R2 = 0.88) of the four PAHs congeners. Therefore, a novel model was established to predict CΣPAHs in sediments using the emissions and logKow of the four characteristic PAHs congeners. The percent sample deviation between calculated C∑PAHs and their observed values was 54%, suggesting the established model can accurately predict CΣPAHs in sediments.

Selenium-containing nanoparticles synergistically enhance Pemetrexed&NK cell-based chemoimmunotherapy.

NK cell-based immunotherapy and pemetrexed (Pem)-based chemotherapy have broad application prospects in cancer treatment. However, the over-expressed NK cell inhibitory receptor on the surface of cancer cells and the low cell internalization efficiency of Pem greatly limit their clinical application. Herein, we construct a series of selenium-containing nanoparticles to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The nanoparticles could deliver Pem to tumor sites and strengthen the chemotherapy efficiency of Pem by seleninic acid, which is produced by the oxidation of ß-seleno ester. Moreover, seleninic acid can block the expression of inhibitory receptors against NK cells, thereby activating the immunocompetence of NK cells. The in vitro and in vivo experiments reveal the potential chemo-enhancing and immune-activating mechanism of seleninic acid, emphasizing the promising prospects of this strategy in effective chemoimmunotherapy.

Quantitative analysis of effects of salvianic acid a combined with hydroxy safflower yellow a on rat endothelial cells after hypoxic injury using the combination index method

Abstract Cerebrovascular disease is the second most serious disease in the world. It has the features of high morbidity, high mortality and recurrence rate. Numerous research on the compatibility of Chinese medicine with effective ingredients of cerebral ischemia has been made during the past decades. The purpose of this study is to quantitatively analyze the combined pharmacological effect of effective ingredients in Danshen and Honghua (Dan Hong) on rat microvascular endothelial cells after gradually oxygen-glucose deprivation. The experimental concentration range for the compatibility of two effective ingredients were determined in the preliminary experiments by Cell Counting kit-8 (CCK-8) method. Drugs were added to rat brain microvascular endothelial cells at a non-toxic dose level. After that, the cells were cultured for 12 h, and placed in a hypoxic environment. Finally, the cell survival rate was used as a measure of drug effect. In order to determine synergism or antagonism, the combination index (CI)-isobologram method was performed to analyze the data from the experiments. Based on this theory, the potencies of each drug and the shapes of their does-effect curves are both taken into account. The results show that the synergism or the antagonism between two effective ingredients compatibility change with different proportion and dosage. Furthermore, it can be seen from the results of these experiments that when these drugs are used in combination, the dosage required to achieve the same therapeutic effects is greatly reduced compared with the case of single one. It is worth mentioning that our experiments also prove that the median-effect equation and the CI method can be applied in the field of traditional Chinese medicine.

Laser-Induced Remote Healing of Stretchable Diselenide-Containing Conductive Composites.

Remotely controlled on-demand functional healing is vital to components that are difficult to access and repair in distance such as satellites and unmanned cruising aircrafts. Compared with other stimuli, a blue laser is a better choice to input energy to the damaged area in distance because of its high energy density and low dissipation through the air. Herein, diselenide-containing polyurethane (PUSe) is first employed to fabricate visible light-responsive stretchable conductive composites with multiwalled carbon nanotubes (MWCNTs). Then, laser-induced remote healing was realized based on the characteristics of long-distance propagation of lasers and the dynamic properties of diselenide bonds. Moreover, the PUSe/MWCNT composite film can be used to transfer an electrical signal in the circuit containing a signal generator. This laser-induced remote healing of conductivity paves the way for developing healing conductors which are difficult to access and repair.