Flow Channel with Wrinkles and Calcium Sites in a Ca-MOF for Direct One-Step Ethylene Purification from C2 Gases and MTO Products Separation.

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

Tuning Multiple Counter-Anions in Porous Coordination Polymers with lcy Topology for Acetylene/Ethylene Separation.

The efficient separation of acetylene (C2H2) and ethylene (C2H4) is an important and complex process in the industry. Herein, we report a new family of lcy-topologic coordination frameworks (termed NTU-90 to NTU-92) with Cu3MF6 (M = Si, Ti, and Zr) nodes. These charged frameworks are compensated by different counterbalanced ions (MF62-, BF4-, and Cl-), yielding changes in the size of the window apertures. Among these frameworks, NTU-92-a (activated NTU-92) shows good adsorption selectivity of C2H2/C2H4 and also significant ability in recovering both highly pure C2H4 (99.95%) and C2H2 (99.98%). Our work not only presents a potential alternative for energy-saving purification of C2 hydrocarbons but also provides a new approach for tuning the function of charged porous materials.

Flow Channel with Recognition Corners in a Stable La-MOF for One-Step Ethylene Production.

Single-step ethylene (C2H4) production from acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) mixtures was realized via the strategy of a flow channel with recognition corners in MOF NTUniv-64. Both the uptake amounts and the enthalpy of adsorption (Qst) showed the same order of C2H2 > C2H6 > C2H4. Breakthrough testing also verified the above data and the C2H4 purification ability. Grand Canonical Monte Carlo (GCMC) simulations indicated that uneven corners could precisely detain C2H2 and C2H6, in which the C-H···π interaction distance between C2H2 (2.84 Å) and C2H6 (3.03 Å) and the framework was shorter than that of C2H4 (3.85 Å).

Fine Tuning Metal-Organic Frameworks with Halogen Functional Groups for Ethylene Purification.

One-step C2H4 purification from a mixture of C2H2/C2H4/C2H6 could be achieved by metal-organic framework (MOF) NTUniv-70 with an F-functional group. The selectivities of C2H4/C2H6 and C2H4/C2H2 of NTUnvi-70 based on ideal adsorbed solution theory were at least twice that of the original MOF platform, which was in line with the enthalpy of adsorption (Qst) and breakthrough testing. Grand canonical Monte Carlo simulations indicated that the C-H···F interactions played an important role in enhanced C2H4/C2H6 and C2H4/C2H2 adsorption selectivities.

Expanding MOF with Unexpanded Channel via Ketone Decorated Ligand for Ethylene Purification and Stability Enhancement.

The concept of an expanding MOF with unexpanded channel size was realized in MOF NTUniv-61 by the utilization of a ketone-functional-group-decorated semirigid ligand and pillar-layer platform. After this unusual expansion, the preferential C2H6 adsorption was preserved via the unchanged pore size, and the functional group was inserted into the MOF. Interestingly, the C2H2 uptake ability, C2H4 selective adsorption ability, and structural stability were obviously enhanced due to the incorporation of the ketone functional group, which were further verified by isosteric heats of adsorption (Qst), GCMC modeling, and breakthrough experiments.

Creating an Ethane Trap in a Ketone-Decorated MOF for One-Step Ethylene Separation from C2 Hydrocarbons.

One-step C2H4 purification from a mixture of C2H2/C2H4/C2H6 by physical adsorption separation was realized via creating an ethane trap in MOF NTUniv-63 by the utilization of a ketone-decorated semirigid ligand, which has further been verified by the breakthrough experiment, isosteric heats of adsorption (Qst), and Grand Canonical Monte Carlo (GCMC) modeling.

Construction of a Biomimetic Receptor Based on Hydrophilic Multifunctional Monomer Covalent Organic Framework Molecularly Imprinted Polymers for Molecular Recognition of Cyanidin-3-O-Glucoside.

Anthocyanins (AOCs) are phenols that are readily soluble in water and are commonly present in plants. The chemical instability of AOC, however, causes it to be severely limited in terms of extraction and purification. Hence, in order to obtain efficient and stable extraction of AOC, we designed hydrophilic multifunctional monomer covalent organic framework molecularly imprinted polymers (HMCMIPs) as adsorbents. The functional reagent, p-aminobenzenesulfonic acid (ASA), was added to this material during synthesis to facilitate the sulfonation modification of covalent organic frameworks (COFs), which enhanced its affinity for hydrophilic guests (cyanidin-3-O-glucoside, the representative nutritional and functional ingredient in AOC). With ASA serving as a terminator, overextension of the material to form micron-level cross-linked structures is prevented, thereby increasing its surface area and mass transfer efficiency. The biomimetic receptors were then created by integrating MIPs into sulfonated COFs in order to create multiple binding sites specific for C3G recognition. HMCMIPs exhibited excellent adsorption capacity (1566 mg/g) and superior selectivity (selectivity coefficient >12) for C3G. It has been demonstrated that high purity (93.72%) C3G can be obtained rapidly and efficiently by utilizing HMCMIPs. There may be a potential benefit to the synthesis strategy of HMCMIPs for the extraction of specific active ingredients in the future.

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia.

Increased endothelial cell (EC) proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). The underlying mechanism and disease relevance of this abnormal cell proliferative state of the ECs remain unknown. Here, we report the identification of a CDK6-driven mechanism of cell cycle progression deregulation directly involved in EC proliferation and HHT vascular pathology. Specifically, HHT mouse liver ECs exhibited defects in their cell cycle control characterized by a G1/S checkpoint bypass and acceleration of cell cycle speed. Phosphorylated retinoblastoma (p-RB1)-a marker of G1/S transition through the restriction point-significantly accumulated in ECs of HHT mouse retinal AVMs and HHT patient skin telangiectasias. Mechanistically, ALK1 loss of function increased the expression of key restriction point mediators, and treatment with palbociclib or ribociclib, two CDK4/6 inhibitors, blocked p-RB1 increase and retinal AVMs in HHT mice. Palbociclib also improved vascular pathology in the brain and slowed down endothelial cell cycle speed and EC proliferation. Specific deletion of Cdk6 in ECs was sufficient to protect HHT mice from AVM pathology. Thus, CDK6-mediated endothelial cell cycle acceleration controls EC proliferation in AVMs and is a central determinant of HHT pathogenesis. We propose that clinically approved CDK4/6 inhibitors have repurposing potential in HHT.

Structural analysis and attenuates hyperuricemic nephropathy of dextran from the Imperata cylindrica Beauv. var. major (Nees) C. E. Hubb.

ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.

Fine-Tuning MOFs with Amino Group for One-Step Ethylene Purification from the C2 Hydrocarbon Mixture.

Due to the similar kinetic diameters of C2H2, C2H4, and C2H6, one-step purification of C2H4 from a ternary C2H2/C2H4/C2H6 mixture by adsorption separation is still a challenge. Based on a C2H6-trapping platform and crystal engineering strategy, the N atom and amino group were introduced into NTUniv-58 and NTUniv-59, respectively. Gas adsorption testing of NTUniv-58 showed that both the C2H2 and C2H4 uptake capacities and the C2H2/C2H4 separation ability were boosted compared with the original platform. However, the C2H4 uptake value exceeds the C2H6 adsorption data. For NTUniv-59, the C2H2 uptake at low pressure increased and the C2H4 uptake decreased; thus, the C2H2/C2H4 selectivity was enhanced and the one-step purification of C2H4 from a ternary C2H2/C2H4/C2H6 mixture was realized, which was supported by the enthalpy of adsorption (Qst) and breakthrough testing. Grand canonical monte carlo (GCMC) simulation indicated that the preference for C2H2 over C2H4 originates from multiple hydrogen-bonding interactions between amino groups and C2H2 molecules.

Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT.

BACKGROUND: Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. METHODS: A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. RESULTS: It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H2O overexpressed at the tumor site. CONCLUSIONS: By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Combining Proteomics and Metabolomics to Analyze the Effects of Spaceflight on Rice Progeny.

Spaceflight is a special abiotic stress, the biological effect mechanism of which on contemporary rice has been clarified, However, its effect on offspring rice was still unclear. In order to understand the response mechanism of F2 generation plants to space flight, this study used SJ-10 recoverable satellite to carry DN423 rice seeds for 12.5 days in orbit flight. After returning to the ground, the plants were then planted to F2 generation to explore the biological effect mechanism. Our research showed that in the F2 generation of TLS, the rice plant height of the space flight group increased by 33.8%, the ear length and thousand-grain weight decreased by 9.7 and 4.6%, respectively, and the grain number per panicle increased by 6.5%. Moreover, related proteins that control changes in agronomic traits have been identified. The changes of MDA, H2O2, soluble sugar, electron leakage and antioxidant enzyme activity confirmed the stress response in F2 generation plants. ITRAQ and LC-MS technology were used to reveal the change pattern of protein levels and metabolite levels in F2 generation plants, 389 and 405 proteins were identified as differentially abundant proteins in TLS and TS, respectively. In addition, there were 124 and 125 metabolites that changed during these two periods. The proteome and metabolome result further confirmed that the F2 generation plants still retained the memory of space flight stress, and retained the memory of space flight stress through genome instability. Oxidative stress signals activated sugar signals to rebuild metabolic networks to adapt to space flight stress. The reconstruction of energy metabolism, amino acid metabolism, phenylalanine metabolism, and flavonoid metabolism played an important role in the process of adapting to space flight stress. The results of this study broaden the perspective of space biological effects and provide a basis for studying the effects of abiotic stress on plant progeny.

The Memory of Rice Response to Spaceflight Stress: From the Perspective of Metabolomics and Proteomics.

The stress response of plants to spaceflight has been confirmed in contemporary plants, and plants retained the memory of spaceflight through methylation reaction. However, how the progeny plants adapt to this cross-generational stress memory was rarely reported. Here, we used the ShiJian-10 retractable satellite carrying Dongnong416 rice seeds for a 12.5-day on-orbit flight and planted the F2 generation after returning to the ground. We evaluated the agronomic traits of the F2 generation plants and found that the F2 generation plants had no significant differences in plant height and number of tillers. Next, the redox state in F2 plants was evaluated, and it was found that the spaceflight broke the redox state of the F2 generation rice. In order to further illustrate the stress response caused by this redox state imbalance, we conducted proteomics and metabolomics analysis. Proteomics results showed that the redox process in F2 rice interacts with signal transduction, stress response, and other pathways, causing genome instability in the plant, leading to transcription, post-transcriptional modification, protein synthesis, protein modification, and degradation processes were suppressed. The metabolomics results showed that the metabolism of the F2 generation plants was reshaped. These metabolic pathways mainly included amino acid metabolism, sugar metabolism, cofactor and vitamin metabolism, purine metabolism, phenylpropane biosynthesis, and flavonoid metabolism. These metabolic pathways constituted a new metabolic network. This study confirmed that spaceflight affected the metabolic changes in offspring rice, which would help better understand the adaptation mechanism of plants to the space environment.

Portulaca oleracea L. Extract Alleviated Type 2 Diabetes Via Modulating the Gut Microbiota and Serum Branched-Chain Amino Acid Metabolism.

SCOPE: Portulaca oleracea L. extracts (PE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of PE with the gut microbiota modulation and BCAAs metabolism. METHODS AND RESULTS: The Orbitrap LC-MS to Orbitrap Fusion Lumos Tribrid mass spectrometer is employed to analyze the major compounds in PE. The components of the intestinal microflora in diet-induced/STZ-treated diabetic mice are analyzed by high-throughput 16S rRNA genes sequencing. The results show that PE improves blood glucose and insulin level, increases anti-inflammatory cytokine level, lowers serum branched-chain amino acids (BCAAs), and increases serum glutamine level. PE also protects the mucosal epithelium of the colon and cecum from damage. On the impact of gut microbial composition, PE reduces the Firmicutes to Bacteroidetes ratio and the abundance of the Lachnospiraceae_NK4A136_group, Blautia, Ruminiclostridium_9, Dubosiella, and increases the abundance of the Bacteroides, Akkermansia, and Mucisprillum genera. Bacterial functionality prediction indicates PE potentially inhibits bacterial BCAAs biosynthesis, and promotes the tissue-specific expression of BCAAs catabolic enzyme for reducing BCAAs supplementation. CONCLUSION: These results reveal that PE improving T2D-related biochemical abnormalities is associated not only with gut microbiota modification but also with the tissue-specific expression of BCAAs catabolic enzyme.

Protective effect of hydrogen sulfide on the kidney (Review).

Hydrogen sulfide (H2S) is a physiologically important gas transmitter that serves various biological functions in the body, in a manner similar to that of carbon monoxide and nitric oxide. Cystathionine­ß­synthase, cystathionine­Î³­lyase and cysteine transaminase/3­mercaptopyruvate sulphotransferase are important enzymes involved H2S production in vivo, and the mitochondria are the primary sites of metabolism. It has been reported that H2S serves an important physiological role in the kidney. Under disease conditions, such as ischemia­reperfusion injury, drug nephrotoxicity and diabetic nephropathy, H2S serves an important role in both the occurrence and development of the disease. The present review aimed to summarize the production, metabolism and physiological functions of H2S, and the progress in research with regards to its role in renal injury and renal fibrosis in recent years.

Exploring the self-assembly mechanism and effective synergistic antitumor chemophototherapy of a biodegradable and glutathione responsive ursolic acid prodrug mediated photosensitive nanodrug.

Supermolecularly assembled photochemotherapeutic nanocomposites composed of pure drug small molecules are promising for synergistically improved tumor therapy, yet potential multiple challenges remain to be addressed. Herein, we rationally designed a novel multifunctional small molecule disulfide modified natural pentacyclic triterpene of ursolic acid (UASS) that simultaneously possesses self-assembly ability, glutathione (GSH) responsivity, anticancer activity, biocompatibility and biodegradability and further constructed carrier-free GSH-sensitive photosensitive nanocomposite UASS-Ce6 NPs for safe and synergistically improved chemophototherapy. Specifically, UASS-Ce6 NPs exhibit improved 1O2 generation by reducing the energy gap (ΔEST) of Ce6 as determined by density functional theory. Meanwhile, molecular dynamics simulation revealed the possible reasons why free UASS self-assembles and UASS-Ce6 NPs with different assembled morphologies may be primarily attributed to the coplanar arrangement of UASS dimer units. Importantly, via noncovalent π-stacking and hydrophobic interactions, the resulting co-assemblies showed improved water solubility, increased intercellular ROS generation, desirable GSH sensibility, excellent biocompatibility, and enhanced tumor accumulation accompanied by rapid biodegradation, thus leading to significant in vitro and in vivo synergistic antitumor efficacy with favorable biosafety. This study provides a promising insight into the development of a self-assembled active single component platform with desirable stimuli responsiveness and biosafety toward synergistic antitumor therapy based on terpenoid natural small molecules.

Investigation on the role of the free radicals and the controlled degradation of chitosan under solution plasma process based on radical scavengers.

This study investigated the role of various active species (OH, O, and H2O2) under solution plasma process (SPP) degradation based on the influence of different radical scavengers on the degradation effect and ESR spectra. The structures of oligochitosan with different radical scavengers were characterized by FT-IR, 1H NMR, and XRD analysis. The results indicated that OH, O, and H2O2 played important roles in SPP degradation. The degradation effect of the O was even higher than that of the OH. The physical effects (e.g. UV light and shockwaves) of SPP method or Fenton's reaction might contribute to the degradation treatment. Furthermore, the different scavengers could adjust the degradation effect of the corresponding free radicals. FT-IR, 1H NMR, and XRD analysis revealed that the primary chemical structure of chitosan was not changed by the scavengers. This study found that the controlled degradation by addition of a radical scavenger is feasible. Therefore, this study provided a straightforward analysis of the role of the free radicals and the controlled degradation of chitosan under SPP treatment, which will be beneficial to further develop SPP techniques for chitosan degradation.

Synthesis of magnetic covalent organic framework molecularly imprinted polymers at room temperature: A novel imprinted strategy for thermo-sensitive substance.

Molecularly imprinted polymers (MIPs) with specific selective recognition have shown excellent performance in the rapid and efficient separation and enrichment of targets in complex systems. Unfortunately, it is not suitable for thermosensitive substances with biological functions. To this end, an imine-linked MIPs with covalent organic frameworks and magnetic nanoparticles was developed by using a room temperature synthesis strategy for the purification of Cyaninin-3-O-glucoside (C3G) from black chokeberry. The prepared material recognized C3G through π-π interaction, assisted by hydrogen bond, and will not be disturbed by water environment. The adsorption capacity and equilibrium binding constant were 86.92 mg g-1 and 1.46 L mg-1, respectively. Based on this special structure, it can also act as a "protective umbrella" and improve the stability of C3G. Furthermore, it exhibited high selectivity compared with dummy template imprinting technique. After purification, the purity of C3G was obviously improved (from 11.96% to 84.72%). This work provided a new strategy for the selective separation of anthocyanin and a method to develop MIPs for thermosensitive substances.

A directed co-assembly of herbal small molecules into carrier-free nanodrugs for enhanced synergistic antitumor efficacy.

Carrier-free nanomedicines without structural modification are attractive for the development of natural small molecules (NSMs) and biomedical applications. Moreover, the combination of NSMs is expected to obtain nanomedicines with high efficacy and low side effects due to their inherent pharmacological activities and health benefits. However, poor water solubility and low bioavailability of NSMs limit their wider biomedical and clinical applications. In this study, we revealed the co-assembly properties of pentacyclic triterpenoids and constructed a series of carrier-free nanodrugs, which are co-assembled nanoparticles (NPs) formed by the combination of two NSMs via a supramolecular assembly strategy. Experimental work and simulation studies were combined to reveal the co-assembly mechanism of non-covalent interactions between NSMs. Not only do co-assembled NPs have rapid cellular uptake ability and passive targeting tumor ability based on the EPR effect, but also their constituent units could arrest the cell cycle at different stages of tumor cells and induce apoptosis, showing synergistic anti-tumor effects (CI < 0.7). Compared with self-assembled NPs and positive control, co-assembled NPs show the strongest therapeutic effect in vivo. Importantly, the co-assembled NPs highlight the unique advantages of NSMs in terms of biosafety and health benefits, and systemic toxicity and histological examination confirm that co-assembled NPs have reliable biosafety, and no side effects and nano toxicity risks were observed.