Syntheses and biological activities of calix[4]resorcinarene derivatives modified by sulfonic acid and sulfonamides.

Functionalization of C-propyl-resorcinolcalix[4]arene (1a) and C-iso-butyl-resorcinolcalix[4]arene (1b) with sodium sulfite and formaldehyde solution gave two corresponding sulfonatomethylated calix[4]resorcinarenes 2a/b. Further modification of 2a/b with different primary amines afforded three calix[4]resorcinarene sulfonamides 3a/b and 4c. Antibacterial and antitumor tests were performed on the starting calix[4]resorcinarenes and their sulfonic acid and sulfonamide derivatives. The results showed that in terms of antimicrobial activity calix[4]resorcinarenes and their derivatives showed bacteriostatic activity against both Escherichia coli and Staphylococcus aureus. Of which compound 1b was the most effective against Escherichia coli with a MIC value of 6.25 mg mL; compound 2b was the most effective against Staphylococcus aureus with a MIC value of 3.12 mg mL-1. In terms of antitumor activity, calix[4]resorcinarenes and their derivatives showed inhibitory effects on the three tumor cells selected for the experiment. Among them, the survival rate of A549 was 76.03% in the presence of 40 µM 1b, and the survival rates of HepG2 and MDA-MB-321 were 28.66% and 65.39% in the presence of 40 µM 2b, respectively.

Preparation and performance control of ultra-low near-infrared reflectivity coatings with super-hydrophobic and outstanding mechanical properties.

The development of ultra-low near-infrared reflectivity coatings with outstanding engineering properties remains a challenge in laser stealth materials research. Herein, we reported a laser stealth coating with outstanding mechanical properties, super-hydrophobicity, and an ultra-low near-infrared reflectivity for 1.06 µm wavelength. The effects of the mass ratio of graphene to nano-SiO2, the proportion of total filler, the addition of KH560, the mass ratio of Polydimethylsiloxane (PDMS) to acrylic-modified polyurethane (APU), and the addition of dioctyl phthalate (DOP) on the coating properties were thoroughly discussed. The coating can achieve a low reflectivity of 9.3% at 1.06 µm and a high water contact angle of 152° at a mass ratio of 7:3 for PDMS to APU and 6:4 for graphene to nano-SiO2 with a total filler amount of 40 wt%. KH560 can play a bridging role between the blended resin matrix and nano-SiO2, which can significantly improve the impact strength of the coating. The DOP, which contains a polar ester group and a non-polar carbon chain structure, can be inserted between the molecular chains of the resin to weaken the intermolecular force of the resin, so that the flexibility of the coating can be significantly improved. Adding KH560 at 4 wt% and DOP at 1 wt%, resulted in a coating with ultra-low near-infrared reflectivity of 1.06 µm (9.3%), super-hydrophobic properties, outstanding adhesion strength (grade 2), flexibility (2 mm), and impact strength (50 kg cm). The above super-hydrophobic ultra-low near-infrared reflectivity coating has significant potential for use in the field of laser stealth equipment, and it can serve as a useful reference for optimizing the mechanical properties of super-hydrophobic functional coatings.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy.

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S. After internalization of mB4S, EPI was acidic-responsively released to induce ICD, which was characterized by an increased level of calreticulin (CRT) exposure and enhanced ATP secretion. Meanwhile, diABZI effectively activated the STING pathway. Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells (DCs) and CD8+ T cells, promoting cytokines secretion, up-regulating M1-like tumor-associated macrophages (TAMs) and down-regulating immunosuppressive myeloid-derived suppressor cells (MDSCs). Therefore, this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+ T cells infiltration, creating an immuno-supportive microenvironment, thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

Progress of research on the bonding-strength improvement of two-layer adhesive-free flexible copper-clad laminates.

The arrival of the 5G era has placed high demands on the electronic products. Developing thin, light, and portable electronic products capable of simultaneously improving the transmission rate and reducing the signal delay and transmission loss is necessary to meet such demands. The traditional three-layer, adhesive, flexible copper-clad laminate (3L-FCCL) cannot satisfy these demands because of its adhesive component. The large thickness and poor heat resistance disadvantages of 3L-FCCL can be avoided with a two-layer, adhesive-free, flexible copper-clad laminate (2L-FCCL). However, 2L-FCCL has low bonding strength. This work introduces the selection of conductor materials and insulating base films for flexible copper-clad laminates. Modification studies aimed at increasing the bonding performance of 2L-FCCL are summarized based on three aspects. These modification techniques include the surface treatment of copper foils, modification and surface treatment of polyimide films, and surface treatment of liquid-crystal polymers. Prospects are further provided.

Injectable alginate hydrogel promotes antitumor immunity through glucose oxidase and Fe3+ amplified RSL3-induced ferroptosis.

Ferroptosis induced by RAS-selective lethal small molecule 3 (RSL3) can trigger anti-tumor immune responses by reversing the immunosuppressive tumor microenvironment (TME). However, it is challenging to achieve sufficient ferroptosis in the tumor via RSL3 alone. Because of the excellent reactive oxygen species (ROS) production capacity of glucose oxidase (GOx) and Fe3+, we hypothesized that GOx and Fe3+ could increase intracellular lipid peroxidation (LPO) accumulation, and strengthen RSL3-induced ferroptosis in tumor cells. Herein we designed an in-situ gelation strategy based on sodium alginate (SA) to realize localized transport and specific retention of GOx, RSL3, and Fe3+ in tumor tissues. We loaded hydrophobic RSL3 with the tannic acid (TA)/Fe3+ complexes to form nanoparticles (RTF NPs). GOx diluted in the SA solution was blended with RTF NPs to obtain a homogeneous solution. The solution could form hydrogels in the tumor site (RTFG@SA) upon injection. The retained GOx and Fe3+ amplified the induction of ferroptosis by RSL3, augmented immunogenic cell death (ICD) and promoted antitumor immunity. The RTFG@SA hydrogel presented a significant restraint of tumor growth and metastasis in the 4T1 tumor model. This hydrogel could offer an effective means of co-delivery of hydrophilic drugs, hydrophobic drugs, and metal ions.

Co-assembly of polymeric conjugates sensitizes neoadjuvant chemotherapy of triple-negative breast cancer with reduced systemic toxicity.

Rational design of polymeric conjugates could greatly potentiate the combination therapy of solid tumors. In this study, we designed and prepared two polymeric conjugates (HT-DTX and PEG-YC-1), whereas the drugs were attached to the PEG via a linker sensitive to cathepsin B, over-expressed in TNBC. Stable nanostructures were formed by these two polymer prodrug conjugates co-assembly (PPCC). The stimuli-responsiveness of PPCC was confirmed, and the size shrinkage under tumor microenvironment would facilitate the penetration of PPCC into tumor tissue. In vitro experiments revealed the molecular mechanism for the synergistic effect of the combination of DTX and YC-1. Moreover, the systemic side effects were significantly diminished since the biodistribution of PPCC was improved after i.v. administration in vivo. In this context, the co-assembled nano-structural approach could be employed for delivering therapeutic drugs with different mechanisms of action to exert a synergistic anti-tumor effect against solid tumors, including triple-negative breast cancer. STATEMENT OF SIGNIFICANCE.

User Pairing for Delay-Limited NOMA-Based Satellite Networks with Deep Reinforcement Learning.

In this paper, we investigate a user pairing problem in power domain non-orthogonal multiple access (NOMA) scheme-aided satellite networks. In the considered scenario, different satellite applications are assumed with various delay quality-of-service (QoS) requirements, and the concept of effective capacity is employed to characterize the effect of delay QoS limitations on achieved performance. Based on this, our objective was to select users to form a NOMA user pair and utilize resource efficiently. To this end, a power allocation coefficient was firstly obtained by ensuring that the achieved capacity of users with sensitive delay QoS requirements was not less than that achieved with an orthogonal multiple access (OMA) scheme. Then, considering that user selection in a delay-limited NOMA-based satellite network is intractable and non-convex, a deep reinforcement learning (DRL) algorithm was employed for dynamic user selection. Specifically, channel conditions and delay QoS requirements of users were carefully selected as state, and a DRL algorithm was used to search for the optimal user who could achieve the maximum performance with the power allocation factor, to pair with the delay QoS-sensitive user to form a NOMA user pair for each state. Simulation results are provided to demonstrate that the proposed DRL-based user selection scheme can output the optimal action in each time slot and, thus, provide superior performance than that achieved with a random selection strategy and OMA scheme.

Probing non-equilibrium inner structure of polymeric nanoparticle via aggregation-induced emission of luminogen.

A molecular segregation inside a nanoparticle was crucial for its properties but usually hard to be determined, especially for organic particles. Herein, non-equilibrium polymeric nanoparticles loading a luminogen via an aggregation-induced emission (AIE) were prepared via an instant formation process, flash nanoprecipitation (FNP). Small organic molecules, polymeric excipients, and oily compounds were used as coprecipitants to reveal effects of conjugate moiety, glass transition temperature (Tg), and a condensed state of a coprecipitant on the fluorescence (FL) intensity of the suspension. The results indicated that the addition of a small molecule in a solid state without any conjugate moiety or a polymeric excipient with high Tg would facilitate enhancing the FL intensity, while a coprecipitant with a conjugate moiety or low Tg or in liquid would decrease the intensity. Moreover, this study revealed that the nanoparticle formed via FNP had a randomly packed inner structure where different compositions tended to evenly distribute inside rather than a micellar structure with a phase-separated core-shell one. These findings provided a guide to selecting a suitable coprecipitant for AIE-luminogen nanoparticles in applications. The developed probing method would also benefit for better understanding the particle formation kinetics in FNP.

Green, General and Low-cost Synthesis of Porous Organic Polymers in Sub-kilogram Scale for Catalysis and CO2 Capture.

Porous organic polymers (POPs) with high porosity and tunable functionalities have been widely studied for use in gas separation, catalysis, energy conversion and energy storage. However, the high cost of organic monomers, and the use of toxic solvents and high temperatures during synthesis pose obstacles for large-scale production. Herein, we report the synthesis of imine and aminal-linked POPs using inexpensive diamine and dialdehyde monomers in green solvents. Theoretical calculations and control experiments show that using meta-diamines is crucial for forming aminal linkages and branching porous networks from [2+2] polycondensation reactions. The method demonstrates good generality in that 6 POPs were successfully synthesized from different monomers. Additionally, we scaled up the synthesis in ethanol at room temperature, resulting in the production of POPs in sub-kilogram quantities at a relatively low cost. Proof-of-concept studies demonstrate that the POPs can be used as high-performance sorbents for CO2 separation and as porous substrates for efficient heterogeneous catalysis. This method provides an environmentally friendly and cost-effective approach for large-scale synthesis of various POPs.

Asymmetric ring-opening reactions of donor-acceptor cyclopropanes with 1,3-cyclodiones.

Asymmetric ring-opening reactions of donor-acceptor cyclopropanes with 1,3-cyclodiones have been established for the synthesis of enantioenriched γ-hydroxybutyric acid derivatives in the presence of Cu(ii)/trisoxazoline catalyst. These reactions offered the desired products in 70% to 93% yields with 79% to 99% enantiomeric excesses.

Modulating tumor-stromal crosstalk via a redox-responsive nanomedicine for combination tumor therapy.

Interaction between carcinoma-associated fibroblasts (CAFs) and tumor cells leads to the invasion and metastasis of breast cancer. Herein, we prepared a redox-responsive chondroitin sulfate (CS)-based nanomedicine, in which hydrophobic cabazitaxel (CTX) was conjugated to the backbone of CS via glutathione (GSH)-sensitive dithiomaleimide (DTM) to form an amphipathic CS-DTM-CTX (CDC) conjugate, and dasatinib (DAS) co-assembled with the CDC conjugate to obtain DAS@CDC. After CD44 receptor-mediated internalization by CAFs, the nanomedicine could reverse CAFs to normal fibroblasts, blocking their crosstalk with tumor cells and reducing synthesis of major tumor extracellular matrix proteins, including collagen and fibronectin. Meanwhile, the nanomedicine internalized by tumor cells could effectively inhibit tumor proliferation and metastasis, leading to shrinkage of the tumor volume and inhibition of lung metastasis in a subcutaneous 4T1 tumor model with low side effects. Collectively, the nanomedicine showed a remarkably synergistic therapy effect against breast cancer by modulating tumor-stromal crosstalk.

Environmental filling materials based on phosphogypsum powder with municipal solid waste incineration ash.

A new building filling materials (NBFM) using phosphogypsum and municipal solid waste incineration (MSWI) fly ash is prepared in this paper. The effects of MSWI fly ash dosage and MSWI fly ash water washing pretreatment on mechanical properties, setting time, metal leaching, hydration products and microstructure of NBFM are analyzed by a range of experimental studies. The results indicate that the mechanical properties, setting time and the density of micro interface of NBFM are optimal when the MSWI fly ash dosage is 3%. The mechanical properties of NBFM rise and the condensation time and leaching concentration of heavy metals decline after washing the MSWI fly ash. With the increase of the curing age, the metal element leaching of NBFM decreases, and when the curing age is 7 days, the solidification effect of NBFM on most metal elements meets the standard of Chinese code (GB5085.3-2007). The feasibility of MSWI fly ash and phosphogypsum as filling materials for building engineering is verified, and the change of macroscopic properties of NBFM is explained as well.

Epigallocatechin-3-gallate (EGCG) attenuates inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced endometritis via silent information regulator transcript-1 (SIRT1)/nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) pathway.

The protective effects of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl-2, cleaved caspase-3, silent information regulator transcript-1 (SIRT1), nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase1 was detected by Western blot and real-time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS-induced uterine histopathological changes, MPO activity, pro-inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.

An Environmentally Friendly Inverse Microemulsion Method to Synthesize Polyacrylamide.

Polyacrylamide (PAM) was prepared by a new method of inverse microemulsion polymerization, with (NH4)2S2O8-Na2SO3 as initiator and liquid paraffin/Span80-Op10/AM-H2O-NaAc as polymerization system in this paper. The effects of initiator dosage, emulsifier dosage, monomer concentration, oil-water ratio, and temperature on molecular weight, electrical conductivity, particle size distribution, and monomer conversion were studied as well. The results indicate that that the more stable Polyacrylamide (PAM) polymer was prepared under the conditions of initiator dosage of 0.4~0.5%, emulsifier dosage of 55~60%, temperature of 40~45 °C, hydrophile-lipophile balance (HLB) value of 8.0~8.2, and NaAc concentration of 3%.

MYC inhibition reprograms tumor immune microenvironment by recruiting T lymphocytes and activating the CD40/CD40L system in osteosarcoma.

The efficacy of immune checkpoint blockade (ICB) therapy depends on sufficient infiltration and activation of primed tumor-specific cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. However, many tumor types, including osteosarcoma, mainly display immune-desert or immune-excluded phenotypes, which are characterized by a lack of tumor-infiltrating lymphocytes and a poor response to ICB monotherapy. Thus, novel therapeutic strategies are urgently needed to surmount these obstacles. In this study, we found that the expression of the c-Myc oncogene is negatively correlated with the T cell infiltration rate in osteosarcoma. Pharmacological inhibition of c-Myc with JQ-1 significantly reduced tumor burden and improved overall survival in an immunocompetent syngeneic murine model of osteosarcoma (K7M2). A mechanistic study revealed that JQ-1 administration dramatically reprogrammed the tumor immune microenvironment (TIME) within K7M2 tumors. On the one hand, JQ-1 can promote T cell trafficking into tumors by increasing the expression and secretion of T cell-recruiting chemokines. On the other hand, JQ-1 is capable of facilitating crosstalk between antigen-presenting dendritic cells and T cells through the CD40/CD40L costimulatory pathway, leading to activation of tumor-specific CTLs. Combined treatment with anti-PD-1 antibody and JQ-1 resulted in more pronounced tumor regression than either monotherapy, showing an obvious synergistic effect. These findings uncover for the first time that c-Myc inhibition can promote T cell infiltration and activation in osteosarcoma in multiple ways, delivering a one-two punch for modulating TIME. The present work also provides the basis for establishing c-Myc inhibitor and ICB coadministration as a novel therapeutic regimen for patients with osteosarcoma.

Molecular surface modification of silver chalcogenolate clusters.

This study presents a molecular surface modification approach to synthesizing a family of silver chalcogenolate clusters (SCCs) containing the same [Ag12S6] core and different surface-bonded organic ligands (DMAc or pyridines; DMAc = dimethylacetamide), with the aim of tuning the luminescence properties and increasing the structural stability of the SCCs. The SCCs displayed strong and tuneable luminescence emissions at 77 K (from green to orange to red) as influenced by the peripheral pyridine ligands. In addition, SCC 5 protected by pyridine molecules was stable in ambient air, humid air and even liquid water for a long time (up to 1 week), and it was more structurally stable than SCC 1 bonded with DMAc molecules under the same conditions. The high structural stability of SCC 5 can be explained by the ability of pyridine molecules to form strong coordination bonds with silver atoms. This study offers a new way of designing structurally stable metal nanoclusters with tuneable physicochemical properties.

Lewis acid-catalyzed [3 + 2] annulations of oxindole based spirocyclic donor-acceptor cyclopropanes with ynamides.

[3 + 2] annulations of oxindole based spirocyclic donor-acceptor cyclopropanes and ynamides catalyzed by copper triflate have been developed for the synthesis of biologically important spirocyclopenteneoxindoles. These reactions tolerated a wide scope of substrates and provided the desired products in good to high yields (up to 90%) with up to >40 : 1 diastereoselectivities under mild conditions.

Enhanced chemo-photodynamic therapy of an enzyme-responsive prodrug in bladder cancer patient-derived xenograft models.

Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)-PTX@Ce6 (NPs@Ce6) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the NPs@Ce6 had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-ß signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/ß-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.

Thermodynamic Properties Investigation of Process Volatile Organic Compounds (VOCs) and Its Transport Impact Factor in Oil Sands Management.

This paper presents a new approach for the determination of volatile organic compounds (VOCs) characteristics and their migration influencing factors in oil sands management processes and reveals the relationship between different asphaltene content and different solvents. Specifically, thermodynamic (i.e., partitioning coefficients, Kr, specific retention volume, Vg, the activity coefficients, γ and enthalpy of solution, ΔH0) and their impact factors are discussed. Gas-liquid chromatography (GLC) experimental measurements were used as the test data. A range of solvents (nC5, iC5, nC6, nC7, and Toluene) has been tested in different asphalt contents (0, 2.56, 9.93, 36.86, 53.67 wt%). There are temperatures in the range of 333.2-393.2 K (with 10 K increase) were conducted, respectively. The dynamics properties of asphalt mixture are calculated, and the relation between dynamics properties of asphalt mixture and absolute temperature, asphalt content and solvent type is discussed. The results show that within the acceptable error range, partitioning coefficients, Kr, specific retention volume, Vg, and enthalpy of solution, ΔH0 and other thermodynamic properties have a good tendency to predict, they decrease with the increase in asphaltene content and temperature and increase with the increase in solute carbon number.

Dendron-Functionalized Polyglutamate-Pyropheophorbide-a Conjugates as Nanomedicines for Breast Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) has shown its promise in the treatment of cancer. Herein, a dendron-functionalized polyglutamic acid (PGA) polymer (PG-L8G-Ppa-Dendron, PGPD) is synthesized and it is conjugated with pyropheophorbide-a (Ppa) for the first time to treat triple negative breast cancer (TNBC), whereas a linear polyglutamate-Ppa conjugate (PGP) is synthesized as a control. Compared to the linear counterpart, the glycosylated polymer-based PGPD with a dendritic structure has excellent solubility and it self-assembles to form uniform-sized nanoparticles. PGPD displays a highly effective PDT effect in the animal model, evidenced with effective induction of reactive oxygen species (ROS) production and cell apoptosis. This may be due to an enhanced efficiency in delivery and accumulation of Ppa by this glycosylated dendritic polymer at tumor sites. Therefore, PGPD can be a highly effective and biosafe nanoagent for PDT of TNBC.