Lactate is a prominent energy substrate for oxidative tumor cells. Interfering with the lactate‐fueled respiration of oxidative tumor cells would be a promising therapeutic strategy for cancer ...treatment. In this study, α‐cyano‐4‐hydroxycinnamate (CHC) is incorporated into a porous Zr (IV)‐based porphyrinic metal‐organic framework (PZM) nanoparticle, to reduce the lactate uptake by inhibiting the expression of lactate‐proton symporter, monocarboxylate transporter 1 (MCT1) in tumor cells, thus transform lactate‐fueled aerobic respiration to anaerobic glycolysis. The alteration in energy supply can also decrease the oxygen consumption in tumor cells, which would facilitate the photodynamic therapy (PDT) in cancer treatment. Moreover, hyaluronic acid (HA) is coated on the surface of PZM nanoparticles for CD44‐targeting and hyaluronidase‐induced intracellular drug releasing. Both in vitro and in vivo studies confirmed good biocompatibility and enhanced PDT efficacy of the HA‐coated PZM nanoparticles (CHC‐PZM@HA) in tumor cells. The CHC‐PZM@HA platform will provide a new perspective in cancer therapy.
Enhanced photodynamic therapy (PDT) by inhibiting lactate uptake. Hyaluronic acid modified porphyrinic metal‐organic framework nanoparticles delivered MCT1 inhibitor into cancer cells. With the releasing of loaded drugs by enzymatic degradation, the aerobic respiration of lactate is disturbed and intratumoral oxygen pressure is upregulated. The nanocarrier system significant enhances the anticancer effect of PDT.
Inorganic–organic hybrid molecular multiferroic and magnetoelectric materials, similar to multiferroic oxide compounds, have recently attracted increasing attention because they exhibit diverse ...architectures, a flexible framework, fascinating physics, and potential magnetoelectric functionalities in novel multifunctional devices such as energy transformation devices, sensors, and information storage systems. Herein, the classification of multiferroicity and magnetoelectricity is briefly outlined and then the recent advances in the multiferroicity and magnetoelectricity of inorganic–organic hybrid molecular materials, particularly magnetoelectricity and the relevant magnetoelectric mechanisms and their categories are summarized. In addition, a personal perspective and an outlook are provided.
Magnetoelectricity plays a huge role in the development of next‐generation devices. Since the discovery of multiferroic properties in inorganic–organic hybrid molecular materials, the related magnetoelectric behaviors have been gradually discovered and advanced at a vigorous pace. This brief development of multiferroicity/magnetoelectricity in inorganic–organic hybrid molecular materials shows their prospect for future development.
Magnetoelectric materials with a large magnetoelectric response, a low operating magnetic (or electric) field, and a room‐temperature (or higher) operating temperature are of key importance for ...practical applications. However, such materials are extremely rare because a large magnetoelectric response often requires strong coupling between spins and electric dipoles. Herein, an example of a magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic ferroelectric, tetramethylammonium tetrachlorogallate(III) (1). Investigation of the magnetoelectric effect of the magnetoelectric laminate composite indicates that its room‐temperature magnetoelectric voltage coefficient (αME) is as high as 186 mV cm−1 Oe−1 at HDC = 275 Oe and at the HAC frequency of ≈39 kHz, providing a valid approach for the preparation of magnetoelectric materials and adding a new member to the magnetoelectric material family.
A magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic tetramethylammonium tetrachlorogallate(III) ferroelectric. The room‐temperature magnetoelectric voltage coefficient is up to 186 mV cm−1 Oe−1 at HDC = 275 Oe and the HAC frequency is ≈39 kHz. This work demonstrates that multiaxial molecular–ionic ferroelectrics are new excellent candidates for the preparation of magnetoelectric composites.
Cataract, the leading cause of blindness worldwide, is caused by crystallin protein aggregation within the protected lens environment. Phase separation has been implicated as an important mechanism ...of protein aggregation diseases, such as neurodegeneration. Similarly, cataract has been proposed to be a protein condensation disease in the last century. However, whether crystallin proteins aggregate via a phase separation mechanism and which crystallin protein initiates the aggregation remain unclear. Here, we showed that all types of crystallin-GFP proteins remain soluble under physiological conditions, including protein concentrations, ion strength, and crowding environments. However, in age or disease-induced aberrant conditions, α-crystallin-GFP, including αA- and αB-crystallin-GFP, but not other crystallin-GFP proteins, undergo phase separation in vivo and in vitro. We found that aging-related changes, including higher crystallin concentrations, increased Na
, and decreased K
concentrations, induced the aggregation of α-crystallin-GFP. Furthermore, H
O
, glucose, and sorbitol, the well-known risk factors for cataract, significantly enhanced the aggregation of αB-crystallin-GFP. Taken together, our results revealed that α-crystallin-GFP forms aggregates via a phase transition process, which may play roles in cataract disease. Opposite to the previously reported function of enhancing the solubility of other crystallin, α-crystallin may be the major aggregated crystallin in the lens of cataract patients.
Abstract
Stimulus‐responsive fragrance microcapsules gradually bring about the attention of the people by using the external environment as the “on/off” switch to achieve intelligent release of ...aromatic compounds. In this paper, the photothermal responsive fragrance microcapsules are successfully synthesized by in situ polymerization using methyl methacrylate (MMA) and trimethylolpropane triacrylate (TMPTA) as wall materials simultaneously doped with polyaniline (PANI). The results indicate that the synthesized fragrance microcapsules have good spherical shape and thermal stability, which can prevent the leakage of essential oil. Furthermore, the addition of PANI effectively promotes the release of fragrance under the stimulation of light source, achieving photothermal responsive release. Meanwhile, the prepared fragrance microcapsules are applied to fabricate fragrance silk fabrics through soaking‐rolling‐baking procedure. The obtained aromatic fabrics show interesting light stimulation release behavior and good washing fastness.
Photoassisted steam reforming and dry (CO2) reforming of methane (SRM and DRM) at room temperature with high syngas selectivity have been achieved in the gas‐phase catalysis for the first time. The ...catalysts used are bimetallic rhodium–vanadium oxide cluster anions of Rh2VO1–3−. Both the oxidation of methane and reduction of H2O/CO2 can take place efficiently in the dark while the pivotal step to govern syngas selectivity is photo‐excitation of the reaction intermediates Rh2VO2,3CH2− to specific electronically excited states that can selectively produce CO and H2. Electronic excitation over Rh2VO2,3CH2− to control the syngas selectivity is further confirmed from the comparison with the thermal excitation of Rh2VO2,3CH2−, which leads to diversity of products. The atomic‐level mechanism obtained from the well‐controlled cluster reactions provides insight into the process of selective syngas production from the photocatalytic SRM and DRM reactions over supported metal oxide catalysts.
Steam and dry reforming of methane catalyzed by gas‐phase rhodium–vanadium–oxygen cluster anions at room temperature with high syngas selectivity has been identified under photo‐irradiation conditions. The crucial step to govern syngas selectivity is the photo‐excitation of reaction intermediates such as Rh2VO3CH2− to electronically excited states that selectively produce H2 and CO.
Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional ...covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COFTTA-DHTA) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COFTTA-DHTA@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.
A covalent organic framework (COF)-based nanosystem PCPP was fabricated to enhance tumor photodynamic therapy (PDT). PCPP can trigger the depletion of tumor extracellular matrix (ECM), leading to improved oxygen supply as well as photosensitizer uptake in tumor to achieve enhanced tumor PDT. Display omitted
Hashimoto's thyroiditis (HT) is the most common autoimmune disease characterized by lymphocytic infiltration and thyrocyte destruction. Dissection of the interaction between the thyroidal stromal ...microenvironment and the infiltrating immune cells might lead to a better understanding of HT pathogenesis. Here we show, using single-cell RNA-sequencing, that three thyroidal stromal cell subsets, ACKR1
endothelial cells and CCL21
myofibroblasts and CCL21
fibroblasts, contribute to the thyroidal tissue microenvironment in HT. These cell types occupy distinct histological locations within the thyroid gland. Our experiments suggest that they might facilitate lymphocyte trafficking from the blood to thyroid tissues, and T cell zone CCL21
fibroblasts may also promote the formation of tertiary lymphoid organs characteristic to HT. Our study also demonstrates the presence of inflammatory macrophages and dendritic cells expressing high levels of IL-1β in the thyroid, which may contribute to thyrocyte destruction in HT patients. Our findings thus provide a deeper insight into the cellular interactions that might prompt the pathogenesis of HT.
Roles for SOX2 have been extensively studied in several types of cancer, including colorectal cancer, glioblastoma and breast cancer, with particular emphasis placed on the roles of SOX2 in cancer ...stem cell. Our previous study identified SOX2 as a marker in cervical cancer stem cells driven by a full promoter element of SOX2 EGFP reporter. Here, dual-luciferase reporter and mutagenesis analyses were employed, identifying key cis-elements in the SOX2 promoter, including binding sites for SOX2, OCT4 and NF-YA factors in SOX2 promoter. Mutagenesis analysis provided additional evidence to show that one high affinity-binding domain CCAAT box was precisely recognized and bound by the transcription factor NF-YA. Furthermore, overexpression of NF-YA in primitive cervical cancer cells SiHa and C33A significantly activated the transcription and the protein expression of SOX2. Collectively, our data identified NF-YA box CCAAT as a key cis-element in the SOX2 promoter, suggesting that NF-YA is a potent cellular regulator in the maintenance of SOX2-positive cervical cancer stem cell by specific transcriptional activation of SOX2.
Sepsis represents a life-threatening organ dysfunction due to an aberrant host response. Of note is that majority of patients have experienced a severe immune depression during and after sepsis, ...which is significantly correlated with the occurrence of nosocomial infection and higher risk of in-hospital death. Nevertheless, the clinical sign of sepsis-induced immune paralysis remains highly indetectable and ambiguous. Given that, specific yet robust biomarkers for monitoring the immune functional status of septic patients are of prominent significance in clinical practice. In turn, the stratification of a subgroup of septic patients with an immunosuppressive state will greatly contribute to the implementation of personalized adjuvant immunotherapy. In this review, we comprehensively summarize the mechanism of sepsis-associated immunosuppression at the cellular level and highlight the recent advances in immune monitoring approaches targeting the functional status of both innate and adaptive immune responses.
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