Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

Homogeneous electrochemical ratiometric biosensor for MircoRNA detection based on UiO-66-NH2 signal probe and waste-free entropy-driven DNA machine.

The construction of efficient methods for highly sensitive and rapid detection of disease markers is essential for the early diagnosis of serious diseases. In this paper, taking advantage of the UiO-66-NH2 signal molecule in combination with a waste-free entropy-driven DNA machine, a novel homogeneous electrochemical ratiometric platform is developed to detect MircoRNA (miRNA). Metal-organic framework materials (UiO-66-NH2 MOF) and ferrocene were utilized as electrochemical signal tags and reference probes, respectively. The target-initiated waste-free three-dimensional (3D) entropy-driven DNA nanomachine is activated in the presence of miRNA, resulting in DNA-labeled-UiO-66-NH2 falling off from the electrode, leading to a decrease in the signal of UiO-66-NH2 at 0.83V. Our strategy can mitigate false positive responses induced by the DNA probes immobilized on electrodes in traditional distance-dependent signal adjustment ratiometric strategies. The proposed ratiometric platform demonstrates superior sensitivity (a detection limit of 9.8 fM), simplified operation, high selectivity, and high repeatability. The ratiometric biosensor is also applied to detect miRNA content in spiked serum samples.

Three-dimensional DNA biomimetic networks (B-3D Net)-based ratiometric fluorescence platform for cancer-related gene biosensing.

Efficient detection of cancer-related nucleic acids is pivotal for early cancer diagnosis. This study introduces a target induced three-dimensional DNA biomimetic networks (B-3D Net)-based ratiometric fluorescence platform using manganese dioxide nanosheets (MnO2 NS)/o-phenylenediamine in combination with hybridization chain reaction to detect cancer-related genes (p53 gene). The incorporation of multiple signals within the B-3D networks can significantly enhance catalytic activity and amplify the output signals, enabling a high sensitivity. Compared with traditional ratio fluorescence platforms, there is no demand to synthesize fluorescent nanoprobes due to the in-situ formation of fluorescence species, which is simple and cost-effective. The corresponding assay demonstrated exceptional sensitivity (with a detection limit as low as 2 fM), selectivity, reproducibility, and accuracy, which mitigates disturbances caused by instrument errors, an inaccurate probe count, and the microenvironment. Furthermore, the ease and straightforwardness of discerning changes in fluorescent brightness and colour by the naked eye are evident. Using the relevant software, a linear relationship between fluorescent images using a smartphone and target concentration was obtained. Hence, the novel ratiometric sensing system will demonstrate new opportunities on determination of target DNA samples in complex biological environments.

Fabrication and characterization of a bioactive composite scaffold based on polymeric collagen/gelatin/nano ß-TCP for alveolar bone regeneration.

One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (ß-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano ß-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP could be further studied for being used to treat alveolar bone defects in vivo.

Cu(II)-Catalyzed Enantioselective Aza-Friedel-Crafts Reaction of 1-Naphthols and Electron-Rich Phenols with Isatin-Derived Ketimines.

New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine-tuned by the use of different substituents. In the presence of Cu(II) catalyst bearing such chiral ligands, aza-Friedel-Crafts reaction of 1-naphthols and electron-rich phenols with isatin-derived ketimines provided the desired products with good to excellent yields and up to 99 % ee. The reactions showed good scalability, and excellent ee could still be obtained when the reaction was carried out in gram-scale.

Bioremediation of trichloroethylene-contaminated groundwater using green carbon-releasing substrate with pH control capability.

In this research, a sustainable substrate, termed green and long-lasting substrate (GLS), featuring a blend of emulsified substrate (ES) and modified rice husk ash (m-RHA) was devised. The primary objective was to facilitate the bioremediation of groundwater contaminated with trichloroethylene (TCE) using innovative GLS for slow carbon release and pH control. The GLS was concocted by homogenizing a mixture of soybean oil, surfactants (Simple Green™ and soya lecithin), and m-RHA, ensuring a gradual release of carbon sources. The hydrothermal synthesis was applied for the production of m-RHA production. The analyses demonstrate that m-RHA were uniform sphere-shape granules with diameters in micro-scale ranges. Results from the microcosm study show that approximately 83% of TCE could be removed (initial TCE concentration = 7.6 mg/L) with GLS supplement after 60 days of operation. Compared to other substrates without RHA addition, higher TCE removal efficiency was obtained, and higher Dehalococcoides sp. (DHC) population and hydA gene (hydrogen-producing gene) copy number were also detected in microcosms with GLS addition. Higher hydrogen concentrations enhanced the DHC growth, which corresponded to the increased DHC populations. The addition of the GLS could provide alkalinity at the initial stage to neutralize the acidified groundwater caused by the produced organic acids after substrate biodegradation, which was advantageous to DHC growth and TCE dechlorination. The addition of m-RHA reached an increased TCE removal efficiency, which was due to the fact that the m-RHA had the zeolite-like structure with a higher surface area and lower granular diameter, and thus, it resulted in a more effective initial adsorption effect. Therefore, a significant amount of TCE could be adsorbed onto the surface of m-RHA, which caused a rapid TCE removal through adsorption. The carbon substrates released from m-RHA could then enhance the subsequent dechlorination. The developed GLS is an environmentally-friendly and green substrate.

Euphohelioscopin A enhances NK cell antitumor immunity through GSDME-triggered pyroptosis.

Immune evasion by cancer cells poses a significant challenge for natural killer (NK) cell-based immunotherapy. Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of NK cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting NK cell activity against cancer. In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increased the cleavage of GSDME, promoting GZMB-induced pyroptosis, which could be reversed by GSDME knockdown and IFN-γ blockade. Overall, the findings suggested that Eupho-A enhanced NK cell-mediated killing of cancer cells by triggering pyroptosis, making Eupho-A a promising pyroptosis activator with great potential for using in NK cell-based cancer immunotherapy.

Blood biomarkers to distinguish complicated and uncomplicated appendicitis in pediatric patients.

BACKGROUND: /Purpose: Acute appendicitis (AA) stands as the most prevalent cause of acute abdominal pain among children. The potential for morbidity escalates significantly when uncomplicated appendicitis (UA) progresses to complicated appendicitis (CA), which can encompass gangrenous, necrotic, or perforated appendicitis. Consequently, establishing an early and accurate diagnosis of AA, and effectively differentiating CA from UA, becomes paramount. This study explores the diagnostic utility of various blood biomarkers for distinguishing CA from UA in pediatric patients. METHODS: We conducted a retrospective review of medical records pertaining to pediatric patients who underwent surgery for AA. Patients were categorized as either having UA or CA based on histopathological examination of the appendix. The data collected and analyzed included demographic information, white blood cell (WBC) count, neutrophil proportion, lymphocyte proportion, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels upon admission. RESULTS: Among the 192 pediatric patients who underwent surgery for AA, 150 were diagnosed with UA, while 42 were diagnosed with CA. The CA group exhibited significantly higher neutrophil proportions, NLRs, PLRs, and CRP levels, alongside lower lymphocyte proportions (all p < 0.01) compared to the UA group. Receiver operating characteristic (ROC) curve analysis disclosed that CRP exhibited the highest specificity, sensitivity, and positive and negative predictive values for predicting CA. CONCLUSION: CRP emerges as a valuable biomarker for differentiating complicated appendicitis from uncomplicated appendicitis.

Upcycling discarded polyethylene terephthalate plastics into superior tensile strength and impact resistance materials with a facile one-pot process.

Discarding PET plastic (dPET) causes serious environmental pollution and enormous fossil resources waste. Processing techniques have mainly focused on the conversion of dPET into monomers, with minimal reports highlighting their transformation into high-value materials. This work intends to transform dPET into a high-performance material with potential alternative value in harsh production environments. The soft and hard segments of the thermoplastic polyester elastomeric (TPEE) molecular structure are reacted and cross-linked with dPET using a facile one-pot process, and two main polymers, (C8H4O4)n and ((C16H18O4)0.76·(C4H8O)0.24)n are generated after the reaction. Through chemical reactions between TPEE and dPET, new characteristic products and chemical bond-crossing structures are formed, while the resulting product particles or multiple TPEE particles are anchored by the high viscosity of dPET, which endows the material with superior tensile strength (34.21 MPa) and impact resistance. The glass transition temperature (Tg) of the material implies that neither the molecular chain nor the chain segments can move, while only the atoms or groups composing the molecule vibrate at their equilibrium positions. The development of this new treatment method may contribute to the reduction of environmental pollution and the improvement of the high-value conversion and utilization of dPET.

The transcription factor ZEB2 drives the formation of age-associated B cells.

Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax. ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity.

Monolithic Catalysts Supported by Emulsion-Templated Porous Polydivinylbenzene for Continuous Reduction of 4-Nitrophenol.

A monolithic catalyst was fabricated through an emulsion-templating method, postpolymerization modification, and in situ loading of active constituents. To achieve a high specific surface area, divinylbenzene (DVB) was solely employed as the monomer, while the porous structure was adjusted with the porogen content and the types of initiators. Then, anchor points were introduced on the pore wall through nitration and amination of the polymeric scaffold. Using a controlled "silver mirror reaction", monolithic catalysts were obtained after loading of silver nanoparticles (Ag NPs), which was verified from morphological and crystallinity characteristics. The catalytic performance of the resultant monolithic catalyst was determined with the model reduction of 4-nitrophenol (4-NP). In static catalysis, the monolithic catalyst was proved to have a reactively high apparent rate constant and a good reusability. Furthermore, a flow reactor was fabricated with the monolithic catalyst, showing a high efficiency and long-term durability for the continuous reduction of 4-NP. This work broadened the adjustment of porous structures and the subsequent application for emulsion-templated monoliths.

Porphyromonas gingivalis as a promotor in the development of the alcoholic liver disease via ferroptosis.

Alcoholic liver disease (ALD) is a liver disease caused by heavy drinking. Porphyromonas gingivalis (P.g), a major cause of periodontitis, whose antibodies are elevated in severe ALD patients in the plasma. The purpose of this study is to further study the role and the molecular mechanism of P.g in the progress of ALD. In this study, saliva of patients with ALD was collected. Then, an animal model of ALD with oral P.g administration was established, pathology of liver and spleen, intestinal microorganisms and metabolites were analyzed. The molecular mechanism of P.g on ALD was analyzed in vitro. ALD and intestinal microflora and metabolite changes were observed more serious in the alcohol and P.g groups than the alcohol group. Moreover, ferroptosis was aggravated by P.g in the liver. Meanwhile, P.g promoted ferroptosis accomplication with alcohol in vitro, which can be reversed by ferroptosis inhibitors. In conclusion, P.g aggravates ALD through exacerbation gut microbial metabolic disorder in mice with alcohol, which maybe depend on ferroptosis activation in hepatocytes. The study provides a new strategy for prevention and treatment of ALD by improving the oral micro-environment.

Therapeutic effects of fenticonazole on bacterial vaginosis in mice.

Bacterial vaginitis (BV) is a syndrome of increased vaginal discharge, fishy smelling leucorrhea, and itching and burning vulva caused by the microecological imbalance in the vagina induced by mixture of Gardnerella vaginalis (GV) and some anaerobic bacteria. Fenticonazole, an imidazole derivative and antimicrobial compound, has been demonstrated to exert effective therapeutic effects in mixed vaginitis. Accordingly, our study was designed to explore the potential role of fenticonazole in GV-infected BV mouse models. Female C57/BL6 mice were injected intraperitoneally with ß-estradiol 3 days before and on the day of GV infection to maintain a pseudoestrus state. On the day of infection, mice were intravaginally inoculated with 20 µl of a suspension of GV (6 × 106 CFU/ml). Fenticonazole was administered as 2% vaginal cream (0.2 mg each mouse) by intravaginal application once a day for 3 days beginning the day of infection. At day 3 postinfection, the mice were sacrificed and vaginal washes were harvested. GV proliferation and Lactobacillus content were calculated in the vaginal lavage. Neutrophil counts in the vaginal lavage were observed through Pap staining. Myeloperoxidase (MPO) activity and proinflammatory cytokine (TNF-α, IL-1ß, IL-6, iNOS, COX2, and NF-κB) levels in vaginal tissues were measured by ELISA and western blotting. Vaginal tissues were stained by hematoxylin and eosin (H&E) to examine the exfoliation of vaginal epithelial cells. GV infection increased GV proliferation and neutrophil counts but reduced Lactobacillus content in the vaginal lavage, as well as enhanced MPO activity, proinflammatory cytokine levels, and the exfoliation of vaginal epithelial cells in vaginal tissues of BV mouse models. However, administration of fenticonazole significantly ameliorated the above phenomena. Fenticonazole greatly improves the symptoms of GV-induced BV in mouse models.

New Binaphthyl-Proline-Based Chiral Ligands Bearing Imidazoline Groups: Design, Synthesis, and Their Application in Enantioselective Conjugate Addition of 4-Hydroxycoumarin and Related Nucleophiles to ß,γ-Unsaturated α-Ketoesters.

This paper describes the design and application of new binaphthyl-proline-based chiral ligands bearing imidazoline functional groups. These chiral ligands incorporate the advantages of both the binaphthyl and proline skeletons, they are featured with regulatable electronic and steric properties for the imidazoline functional groups, and form chiral complexes with different metal salts such as cuprous acetate. In the presence of an appropriate amount of a chiral catalyst, enantioselective conjugate addition of 4-hydroxycoumarin or related nucleophiles to different ß,γ-unsaturated α-ketoesters proceeded readily, giving the desired products in high yield (up to 99%) and excellent enantiomeric excess (up to 99%).

Copper(II)-Catalyzed Enantioselective Aza-Friedel-Crafts Reaction of Indoles with Isatin-Derived N-Boc-Ketimines.

The copper(II)-catalyzed enantioselective aza-Friedel-Crafts reaction of indoles with isatin-derived N-Boc-ketimines was developed by using tunable chiral O-N-N tridentate ligands derived from BINOL and proline. In general, the reaction afforded chiral 3-indolyl-3-aminooxindoles under mild conditions in high yields (83-97%) with excellent ee (69-99%).

Remarkably Selective Binding, Behavior Modification, and Switchable Release of (Bipyridine)3Ru(II) vis-à-vis (Phenanthroline)3Ru(II) by Trimeric Cyclophanes in Water.

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, the more valuable the dream becomes. We now present multianionic trimeric cyclophane receptors with a remarkable ability to bind the iconic (bipyridine)3Ru(II) (with its huge range of applications) while rejecting the nearly equally iconic (phenanthroline)3Ru(II). These receptors not only selectively capture (bipyridine)3Ru(II) but also can be redox-switched to release the guest. 1D- and 2D(ROESY)-NMR spectroscopy, luminescence spectroscopy, and molecular modeling enabled this discovery. This outcome allows the control of these applications, e.g., as a photocatalyst or as a luminescent sensor, by selectively hiding or exposing (bipyridine)3Ru(II). Overall, a 3D nanometric object is selected, picked-up, and dropped-off by a discrete molecular host. The multianionic receptors protect excited states of these metal complexes from phenolate quenchers so that the initial step in photocatalytic phenolate oxidation is retarded by nearly 2 orders of magnitude. This work opens the way for (bipyridine)3Ru(II) to be manipulated in the presence of other functional nano-objects so that many of its applications can be commanded and controlled. We have a cyclophane-based toolkit that can emulate some aspects of proteins that selectively participate in cell signaling and metabolic pathways by changing shape upon environmental commands being received at a location remote from the active site.

JNMR: Joint Non-Linear Motion Regression for Video Frame Interpolation.

Video frame interpolation (VFI) aims to generate predictive frames by motion-warping from bidirectional references. Most examples of VFI utilize spatiotemporal semantic information to realize motion estimation and interpolation. However, due to variable acceleration, irregular movement trajectories, and camera movement in real-world cases, they can not be sufficient to deal with non-linear middle frame estimation. In this paper, we present a reformulation of the VFI as a joint non-linear motion regression (JNMR) strategy to model the complicated inter-frame motions. Specifically, the motion trajectory between the target frame and multiple reference frames is regressed by a temporal concatenation of multi-stage quadratic models. Then, a comprehensive joint distribution is constructed to connect all temporal motions. Moreover, to reserve more contextual details for joint regression, the feature learning network is devised to explore clarified feature expressions with dense skip-connection. Later, a coarse-to-fine synthesis enhancement module is utilized to learn visual dynamics at different resolutions with multi-scale textures. The experimental VFI results show the effectiveness and significant improvement of joint motion regression over the state-of-the-art methods. The code is available at https://github.com/ruhig6/JNMR.

Carbonized Syndiotactic Polystyrene/Carbon Nanotube/MXene Hybrid Aerogels with Egg-Box Structure: A Platform for Electromagnetic Interference Shielding and Solar Thermal Energy Management.

Functional materials for electromagnetic interference (EMI) shielding are a consistently hot topic in the booming communication engineering, proceeding the development that tends to the multifunctional EMI shielding materials. Herein, a series of carbonized syndiotactic polystyrene/carbon nanotube/MXene (CsPS/CNT/MXene) hybrid aerogels were fabricated for EMI shielding and solar thermal energy conversion purposes. To fabricate the hybrid aerogels, a porous CNT/MXene framework was initially prepared using freeze-casting. Subsequently, sPS was infused into the porous structure, followed by hyper-cross-linking and carbonization of sPS under an inert atmosphere. The resulting aerogels exhibited a distinctive egg-box structure, comprising numerous nanofibrous carbon microspheres embedded within the lamellar framework. The mass ratio between CNT and MXene was regulated to identify an optimum aerogel, that is, the CCM-4-6, which exhibited impressive properties including Young's compression modulus of 0.67 MPa, a water contact angle of 137.6 ± 4.1°, a specific surface area of 110 m2 g-1, an electrical conductivity of 43.0 S m-1, and an EMI SE value of 40 dB. Meanwhile, phase-change composites were fabricated through encapsulating paraffin wax within the hybrid aerogels. For the CCM-4-6 aerogel, a noteworthy encapsulation ratio was achieved at about 76.7%, along with remarkable latent heat, good thermal reliability, and commendable solar thermal energy conversion capacity. This study presents a facile route to prepare multifunctional EMI shielding materials.

Janus Hemispheres through Controlled Polymerization-Induced Phase Separations within Wax Droplets.

A series of Janus hemispheres with a patchy hemispherical surface and a flat undersurface were synthesized through controlled polymerization-induced phase separation within emulsified wax droplets. The hemispherical shape was generated through the polymerization of styrene within wax droplets, followed by the grafting of hydrophilic polymers on the exposed surface. Then, the patchy hemispherical surface was achieved after introducing the hydrophobic acrylate monomers within wax droplets and controlling the polymerization-induced phase separation. The morphological evolution of patches was recorded via the reaction time, followed by their morphological regulation through the type, feeding amount, and cross-linking degree of acrylate monomers. A functional monomer, vinyl benzyl chloride (VBC), was also used to copolymerize the patches for grafting a zwitterionic polymer via surface-initiated atom transfer radical polymerization (SI-ATRP). The as-obtained Janus hemispheres were employed to fabricate robust coatings with wettability tuned from superhydrophobicity to underwater superoleophobicity by the grafted zwitterionic polymers.