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Metal–organic frameworks (MOFs) take on highly ordered self-assembled structures and have gained much attention due to their intriguing structural features and enormous applications.

The major constituents of sand are silica and silicates. The facile and low-cost purification technology of silica from natural sand is of magnificent importance to the industrial applications of silicon-based materials. Herein, we report a green, low-cost, and universal method to purify silica from natural sand. Sand from deserts, rivers, and seas is selected as the representative of natural sand. The initial purity of silica is 52.1 wt% for desert sand, 39.3 wt% for river sand, and 35.8 wt% for sea sand. High-purity silica has been successfully separated and purified from natural sand via ball milling, reacting with 30 bar CO2 and hydrochloric acid. The purity of silica derived from natural sand reaches >96 wt%. In this work, the mechanism for the purification of silica from natural sand is discussed. This study provides a new method to separate high-purity silica from natural sand without the generation of toxic and harmful substances.

In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman’s correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.

As a typical class of crystalline porous materials, metal–organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented. Graphical Abstract

Covalent organic frameworks (COFs) have shown great potential in catalysis and the biomedical fields, but monodisperse COFs with tunable sizes are hard to obtain. Herein, we successfully developed a series of COFs based on electron donor-acceptor strategy in mild conditions. The synthetic COFs exhibit excellent colloidal stability with uniform spherical morphology. The sizes can be flexibly adjusted by the amount of catalyst, and the absorption spectra also vary with the sizes. By changing the electron-donating ability of the monomers, the corresponding COFs possess a wide range of absorption spectra, which can be even extended to the second near-infrared biowindow. The obtained COFs possess potent photothermal activity under laser irradiation, and could inhibit the growth of tumors effectively. This work provides a strategy for the synthesis of monodisperse COFs with variable absorption for their potential applications.

Electroless nickel composite coatings have the potential for high-temperature tribological applications, and a combination of high wear resistance and low friction factor is one of the desirable solutions but still a tricky problem. The addition of self-lubricating WS2 and hard Si3N4 nanoparticles to the Ni-P coatings is expected to obtain good high-temperature tribological performance. In this work, Ni-P-Si3N4-WS2 composite coatings with various contents of WS2 nanoparticles were prepared using electroless plating and subsequently annealed at 400 °C in an inert atmosphere. The tribological properties of the coatings were evaluated using a ball-on-disc wear instrument at operating temperatures from 25 to 600 °C. The microstructure, chemical composition, and surface morphology of the coatings were characterized by X-ray diffractometry (XRD), energy disperse spectroscopy (EDS), and scanning electron microscopy (SEM). Upon increasing the WS2 dosage in the bath, the WS2 content in the coating increased and the micro-hardness of the as-plated coating increased from 539 to 717 HV. After heat treatment, the coating underwent a crystallization process, and the hardness increased from 878 to 1094 HV. The main wear mechanism of the coating changed from adhesive wear in the as-plated state to abrasive wear in the annealed state. The annealed Ni-P-Si3N4-WS2 coating with a WS2 dosage of 2.5 g/L in the bath exhibited excellent mechanical properties, with a hardness of 10.9 GPa, a friction coefficient of ~0.51, and a wear rate of 8.4 × 10−15 m3N−1⋅m−1 at room temperature, and maintained optimal performance at high temperatures. At operating temperatures of 200, 400, and 600 °C, the form of wear was adhesive wear for coatings with a WS2 dosage

Advanced carbon materials have played an important function in the field of energy conversion and storage. The green and low-carbon synthesis of elemental carbon with controllable morphology and microstructure is the main problem for carbon materials. Herein, we develop a green and low-carbon method to synthesize porous carbon by reacting CO2 with LiAlH4 at low temperatures. The starting reaction temperatures are as low as 142, 121, and 104 °C for LiAlH4 reacting with 1, 30, and 60 bar CO2, respectively. For the elemental carbon, the porosity of elemental carbon gradually decreased, whereas its graphitization degree increased as the CO2 pressure increased from 1 bar to 60 bar. CO2 serves as one of the two reactants and the CO2 pressure can adjust the thermodynamic and kinetic properties of the formation reaction for synthesizing elemental carbon. The mechanism for CO2 pressure-dependent microstructure and morphology of carbon is discussed on the basis of the formation reaction of elemental carbon and gas blowing effect of H2 and CO2. The elemental carbon with different morphology and microstructure exhibits distinct electrochemical lithium storage performance including reversible capacity, rate capability, cycling stability, and Coulombic efficiency, owing to their different lithium storage mechanism. The elemental carbon synthesized at 30 bar CO2 delivers the highest reversible capacity of 506 mAh g−1 after 1000 cycles even at 1.0 A g−1. Advanced energy storage technology based on the green and low-carbon synthesis of carbon materials is a requisite for providing a stable and sustainable energy supply to meet the ever-growing demand for energy.

In stereoscopic 3D (S3D) color correction, visual inconsistency is a common problem that leads to perceptual quality degradations. In this paper, we propose an S3D image/video color correction strategy that resolves global, local, and temporal color discrepancies simultaneously. We achieve the image-based S3D color correction by three steps: a coarse-grain color correction for global color matching, a fine-grain color correction to further improve both global and local color consistencies, and a guided filtering process to guarantee the structural consistency before and after color correction. In addition, we extend the above strategy to S3D and multiview video color correction. To achieve temporal consistency between successive video frames, we develop an improved histogram matching within a sliding window on time axis. In our method, the mapping functions for each color channel change gradually following the video stream to avoid abrupt temporal changes in colors. The experimental results demonstrate that the proposed strategy outperforms the state-of-the-art color correction algorithms for images and videos.

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle. Prior research on healthy muscle suggests that enhanced postexercise ISGU depends on elevated γ3-AMPK activity leading to greater phosphorylation of Akt substrate of 160 kDa (pAS160) on an AMPK-phosphomotif (Ser704). Phosphorylation of AS160Ser704, in turn, may favor greater insulin-stimulated pAS160 on an Akt-phosphomotif (Thr642) that regulates ISGU. Accordingly, we tested if exercise-induced increases in γ3-AMPK activity and pAS160 on key regulatory sites accompany improved ISGU at 3 h postexercise (3hPEX) in insulin-resistant muscle. Rats fed a high-fat diet (HFD; 2-wk) that induces insulin resistance either performed acute swim-exercise (2 h) or were sedentary (SED). SED rats fed a low-fat diet (LFD; 2 wk) served as healthy controls. Isolated epitrochlearis muscles from 3hPEX and SED rats were analyzed for ISGU, pAS160, pAkt2 (Akt-isoform that phosphorylates pAS160Thr642), and γ1-AMPK and γ3-AMPK activity. ISGU was lower in HFD-SED muscles versus LFD-SED, but this decrement was eliminated in the HFD-3hPEX group. γ3-AMPK activity, but not γ1-AMPK activity, was elevated in HFD-3hPEX muscles versus both SED controls. Furthermore, insulin-stimulated pAS160Thr642, pAS160Ser704, and pAkt2Ser474 in HFD-3hPEX muscles were elevated above HFD-SED and equal to values in LFD-SED muscles, but insulin-independent pAS160Ser704 was unaltered at 3hPEX. These results demonstrated, for the first time in an insulin-resistant model, that the postexercise increase in ISGU was accompanied by sustained enhancement of γ3-AMPK activation and greater pAkt2Ser474. Our working hypothesis is that these changes along with enhanced insulin-stimulated pAS160 increase ISGU of insulin-resistant muscles to values equaling insulin-sensitive sedentary controls. NEW & NOTEWORTHY Earlier research focusing on signaling events linked to increased insulin sensitivity in muscle has rarely evaluated insulin resistant muscle after exercise. We assessed insulin resistant muscle after an exercise protocol that improved insulin-stimulated glucose uptake. Prior exercise also amplified several signaling steps expected to favor enhanced insulin-stimulated glucose uptake: increased γ3-AMP-activated protein kinase activity, greater insulin-stimulated Akt2 phosphorylation on Ser474, and elevated insulin-stimulated Akt substrate of 160 kDa phosphorylation on Ser588, Thr642, and Ser704.

Covalent organic frameworks (COFs) represent a promising class of crystalline porous materials in various fields, but their applications as biomaterials are usually limited by the large sizes and low colloid stability in aqueous solution. Inspired by the biomimetic mineralization strategies for preparing nanoparticles, herein a homogeneous and stable porphyrin-based COF material (COF-B) has been developed with the assistance of bovine serum albumin (BSA), which exhibits both photothermal and photodynamic activity under the excitation of a laser at a single wavelength. COF-B possesses not only good water dispersibility, but also robust photostability and biocompatibility. Moreover, COF-B shows excellent phototherapy efficiency with effective inhibition or even complete elimination of tumors upon irradiation. This protein-assisted synthesis of COF materials propels the preparation of stable nanoscale COFs and the application of COFs as highly efficient biomedical materials.

BODIPYs are highly potential photoactive agents for cancer theragnostics. The rational design of BODIPY-based photoactive nanodrugs with high efficiency and near-infrared (NIR) absorption is imperative. Herein, we developed a donor-acceptor-donor (D-A-D) organic photosensitizer (PS) (BODIPY, named NBB), which possessed strong absorption in the NIR region due to the multi-intersection of intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and heavy atom effects. Through a nanoprecipitation method, NBB nanoparticles (NPs) were facilely prepared. The as-prepared NBB NPs exhibited favorable water-stability and photostability. In particular, the outstanding photon absorption capacity endows the NPs with high photothermal conversion efficiency (η = 53.8%) and active singlet oxygen (1O2) generation ability upon 808 nm laser irradiation, and promotes their tumour inhibition efficiency via the combination of photothermal/photodynamic therapy (half-maximal inhibitory concentration IC50 = 8.11 and 7.77 μM for HeLa and HepG2 cells, respectively). Together with the favorable synthetic yield and excellent antitumour effect, we envision that this exploration can provide beneficial guidance for the clinical translation of BODIPY-based PSs for phototherapy.

Scholars have long debated how effective public participation is in urban planning. While most research was designed to assess the effect of public participation, the knowledge gap concerns whether urban planning would receive negative reception without public participation due to failure in managing people’s emotions. One of the underlying reasons is that public participation is crucial to public emotion management. In this paper, we evaluate the impact of a case of public planning, and more specifically, the effects on public art reception when the planning project is developed by elites, without the involvement and participation of residents. Public art planning involves substantial symbolic and emotional components, and therefore constitutes a suitable case study. This research examines urban sculpture planning in Shanghai. The primary research method is a questionnaire survey, completed by 244 respondents. We argue that public participation is not the sole determinant of public art reception; other factors, particularly locality, also matter: an authoritarian-style urban sculpture planning creates a unanimous reverence and appreciation for flagship art projects on prominent public venues in central cities. However, people’s feelings towards sculptures vary in neighborhoods; people are more likely to resist imposed artworks in the environment of their everyday life. Finally, we conclude that a lack of public participation does not always result in a negative reception to cultural projects on the part of the public; however, this lack of public participation is, nevertheless, culturally unsustainable.

Objective: polypoid endometriosis (PEM) is a rare type of endometriosis (EMs), which is easy to be misdiagnosed. The purpose of this paper is to investigate the clinical features and diagnostic methods of PEM. Methods:The clinical data of 7 patients with PEM who were treated at Fujian Provincial Maternity and Children’s Hospital in China within July 2017 to December 2020 period were retrospectively analyzed, and their clinical characteristics, diagnosis, treatment and prognosis were summarized. Results: The age of onset was 31-41 (38.00 ± 1.72) years. There were 5 cases with adenomyosis, 4 cases with endometrial polyps and infertility. The clinical manifestations were diverse. Most of them were pelvic mass, compression symptoms and signs, dysmenorrhea and abnormal uterine bleeding, and three of them were similar to malignant tumors. The gross pathological features were cysts, endogenous or exogenous polypoid masses, which were all composed of endometrioid glands and stromal components, but more diverse than ordinary em. All the 7 patients were confirmed by operation and pathology. Conclusion: PEM is often complicated with adenomyosis, endometrial polyps and infertility. Pathological examination is the gold standard for diagnosis. Imaging examination is easy to be misdiagnosed. Abnormal increase of CA125 can assist in diagnosis.

Polycystic ovary syndrome (PCOS) is a major cause of anovulatory sterility in women, and most PCOS patients exhibit hyperandrogenism (HA). Liver kinase b1 (LKB1) is a tumor suppressor that has recently been reported to be involved in PCOS. However, the mechanism by which LKB1 affects HA has not previously been elucidated. We report here that ovarian LKB1 levels are significantly decreased in a female mouse model of HA. Moreover, we report that LKB1 expression is inhibited by elevated androgens via activation of androgen receptors. In addition, LKB1 treatment was observed to suppress androgen synthesis in theca cells and promote estrogen production in granulosa cells by regulating steroidogenic enzyme expression. As expected, LKB1 knockdown inhibited estrogen levels and enhanced androgen levels, and LKB1‐transgenic mice were protected against HA. The effect of LKB1 appears to be mediated via IGF‐1 signaling. In summary, we describe here a key role for LKB1 in controlling sex hormone levels.

Three nanostructured photosensitizers with aggregation-induced emission (AIE) characteristics based on 2,3-bis(4ʹ-(diphenylamino)-[1,1ʹ-biphenyl]-4-yl) fumaronitrile (BDBF) were prepared for image-guided photodynamic therapy (PDT). BDBF was encapsulated with Pluronic F-127 (F127) to form usual spherical nanoparticles (F127@BDBF NPs) with a red fluorescence emission and 9.8% fluorescence quantum yield (FQY). Moreover, BDBF self-assembled into nanorods (BDBF NRs) in water. Compared with F127@BDBF NPs, BDBF NRs exhibited stronger orange fluorescence with a higher FQY of 23.3% and similar singlet oxygen (1O2) generation capability. BDBF NRs were further modified with F127 to form BDBF@F127 NRs with the same 1O2 generation ability as BDBF NRs. The three nanostructures exhibited a higher 1O2 production capacity than BDBF molecule in dissolved state and favorable stability in an aqueous solution as well as under physiological condition. In vitro photocytotoxicity experiments indicated that the three nanostructures inhibited tumor cell proliferation effectively. Therefore, to construct eligible nanostructures with a high FQY and 1O2 generation ability, simple self-assembly can serve as a valuable method to prepare photosensitizers with enhanced PDT.

Drug molecules assembling nanomedicines possess several advantages, including precise molecular structure, various combinations of therapeutic agents and high content of drugs. In this work, paclitaxel dimer and two-photo photosensitizer were devised and synthesized, which could coassemble into nanoparticles (Co-NPs) in aqueous medium through nanoprecipitation method. As-synthesized Co-NPs possess the uniform size of about 80 nm and great stability in physiological condition, and could produce the singlet oxygen upon near-infrared light irradiation. The Co-NPs indicate enhanced cellular uptake and endosomal escape upon irradiation, which result in the synergistic enhancement of cytotoxicity towards cancer cells and growth inhibition of human cervical cancer tumors. We believed this combination therapy based on organic nanoparticles represent a new and important development in the cancer therapy.

Inspired by the clinically approved albumin based PTX formulation (Abraxane) and high-drug-loading dimeric prodrug tactics, herein we report a theranostic “Abraxane-like” prodrug formulation, which is comprised of human serum albumin (HSA), a paclitaxel (PTX) dimer bridged with thioether liner (PTX2-S), and photosensitizer IR780 iodide. Nanoparticles (NPs) with PTX2-S and IR780 as the core and HSA as the stealth shell are formed. Compared with HSA-based PTX clinical formulation (Abraxane), the dimeric molecules not only constitute the bulk structure of the particles, but also act as crossing agent, thus realizing drug loading content increasing from 6.6 wt.% to 48.7 wt.% with high loading efficiency (> 90%) and excellent stability in biological conditions. Importantly, the thioether linkage dually responds to the tumor redox heterogeneity and the NPs gradually releases the parent drug PTX for chemotherapy. Meanwhile, PTX2-S facilitates the encapsulation of IR780 iodide due to their π-π stacking interaction and IR780 iodide generates spatio-temporal hyperthermia under light irradiation to kill cancer cells for photothermal therapy. The described craft integrates the biomimetic trait of HSA, high drug loading, tumor redox heterogeneity-initiated on-demand drug release, and combination therapy into one formulation and the developed nanoparticles are promising for cancer treatment.

The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. To address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature. In this work, a new kind of organic nanoparticles (tripolyphosphate (TPP)-NN NPs) from porphyrin and radical initiator is developed. Under near-infrared light irradiation, TPP-NN NPs will split and release alkyl radical, which could induce obvious cytotoxicity both in normal and hypoxia environment. The photothermal-controlled generation of alkyl radical could significantly inhibit the growth of cervical cancer and show ignorable systemic toxicity. This activatable radical therapy opens up new possibilities for the application of PDT in hypoxia condition.

Porphyrins and their derivatives have been widely exerted as potential phototherapeutic nanomaterials in biomedical fields because of their favorable biocompatibility as well as easy chemical modification. However, the intrinsic hydrophobic properties still limit their further clinical translation. Albumin has been developed as a promising carrier for chemotherapeutic and protein drugs. Except for enhanced water solubility, using human serum albumin (HSA) endows efficient cellular internalization, prolonged blood circulation time, intensive tissue penetration depth and favorable pharmacokinetics and biodistribution. Herein, we constructed supramolecular nanoparticles (HSA–porphyrin SNPs) by the rational assembly of hexadecyl chain bonded porphyrin with HSA in a 1 : 1 stoichiometry via a tight non-covalent interaction. The as-prepared SNPs exhibited robust photostability, a high photothermal conversion efficiency of 45% and recycled utilization. The SNPs can be endocytosed effectively, thus eliciting superb cancer cell inhibition in vitro and thermal ablation of tumors in vivo under illumination. We believe that this study can offer a new horizon to understand the interaction of small molecules with HSA, which highlights the opportunity to explore the next-generation HSA-binding nanomedicine for future cancer precision therapy.

Photosensitizer-based photothermal therapy (PTT) may be a good choice for the treatment of severe cervical intraepithelial neoplasia (CIN) compared with conventional thermal ablation. Vaginal delivery of photosensitizers is helpful to reach the maximal accumulation of photosensitizers in the lesion site but the penetration of drug through the mucus layer remains problematic. Boron-dipyrromethene (BODIPY or BDP) is one kind of highly stable and versatile organic dye. In the present study, we developed mucus-penetrating poly(ethylene glycol)–BDP nanoparticles (PEG–BDP/NPs) by using a solvothermal method, which is different from traditional protocols, such as amphiphilic copolymer encapsulation or covalent bonding of PEG. The results showed that PEG–BDP/NPs were much superior to BDP-loaded methoxy (polyethylene glycol)-b-poly(L-lactide) (MPEG–PLLA) micelles (BDP/M) in both cellular uptake and mucus penetration in vitro and in vivo. Then, the PEG–BDP/NPs with a high photothermal conversion efficiency of 48.3% were infused into the vaginas of mice with mock CIN for PTT. Although the nanoparticles couldn’t selectively be accumulated in the CIN lesion, accurate location of laser irradiation, ultralow laser intensity and great biocompatibility of the nanoparticles enabled great efficacy and safety to be achieved. Therefore, the mucus-penetrating PEG–BDP/NPs with PTT capacity represent a promising approach for the treatment of severe CIN, and this work opens doors toward practical application of phototherapy.

Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. MC-PTX NPs possess a favorable biological stability and can efficiently release the paclitaxel (PTX) activated by the heat of the photoactive material merocyanine under light illumination, as monitored using dynamic light scattering. The obtained MC-PTX NPs could be endocytosed into cancer cells and release PTX under laser irradiation in the cytoplasm, thus eliciting a satisfactory anticancer effect. Photothermal triggered degradation upon light illumination could enhance the chemotherapeutic efficacy of paclitaxel. The fluorescent nature of the NPs could visualize the internalization process. We believe that this robust nanomedicine offers a novel strategy to facilitate clinical translation for use as a small molecular chemotherapy nanomedicine.

Long retention of therapeutic agents in tumors is imperative for improving the therapeutic index. In this work, the GSH responsive porphyrin molecule (TPP 1) was synthesized, which is amphiphilic and linked by a disulfide bond. TPP 1 molecules could self-assemble into nanoparticles (TPP 1 NPs) with a size of about 100 nm in aqueous solution. The TPP 1 NPs exhibited high stability under different conditions and could form into large microparticles in the presence of glutathione (GSH). The TPP 1 NPs could be internalized by cancer cells, and they emitted enhanced red fluorescence compared to that of TPP 2 NPs (non-sensitive NPs) when cells were pretreated with GSH. In addition, in vitro MTT assays showed that TPP 1 NPs were biocompatible and could further be used as photosensitizers in nanoparticle formation. The cellular photodynamic activity of TPP 1 NPs was obviously higher than that of TPP 2 NPs, due to the increasing retention of TPP in cancer cells, which will generate more reactive oxygen species in cancer cells under light irradiation. These results highlight the potential of developing stimulus responsive nanoparticles for enhanced retention and improved therapeutic outcome.

Fluorescence bioimaging is very significant in studying biological processes. Fluorescent nanoparticles (NPs) manufactured from aggregation-induced emission (AIE) materials, as promising candidates, have attracted more attention. However, it is still a challenge to explore suitable AIE NPs for bioimaging. Herein, we synthesized pyrazoline-BODIPY (PZL-BDP) with a donor and acceptor (D–A) structure by a condensation reaction, cultured its single crystal, and studied its twisted intramolecular charge transfer (TICT) and AIE effects. PZL-BDP could self-assemble to form red fluorescent nanoparticles (PZL-BDP NPs) which showed a good fluorescence quantum yield of 15.8% in water. PZL-BDP NPs with excellent stability and biocompatibility exhibited a large Stokes shift (Δλ = 111 nm) which resulted in the reduction of external interference and enhancement of the fluorescence contrast. Furthermore, these nanoparticles could be readily internalized by HeLa cells and they stain the cells in just five seconds, indicating an ultrafast bioimaging protocol. Moreover, long-term tracking fluorescence signals in vivo for about 12 days were obtained. The bright red fluorescence, ultrafast cell staining ability, and long-term in vivo tracking competence outline the great potential of rational design nanomaterials with AIE characteristics for monitoring biological processes.

The introduction of multiple components into one crystalline metal–organic framework (MOF) provides a feasible approach to fully understand the correlation of component heterogeneity and the whole performance. Herein, photoactive tetratopic chlorin (TCPC) ligands with different geometry and connectivity have been successfully incorporated into the Hf-UiO-66 archetype structure without altering the underlying topology by a facile strategy. Unlike previous porphyrin-nanoscale-MOFs (porphyrin-NMOFs) with homogeneous periodical porphyrin arrangements typically for photodynamic therapy (PDT) usage, we demonstrate that TCPC component heterogeneity within as-synthesized TCPC-UiO possesses both PDT and photothermal therapy (PTT) simultaneously, but PTT takes a more potent antitumor efficacy as proven in several photophysical characterizations and biological experiments in vitro. The high photothermal conversion efficiency, favorable photostability and biocompatibility, and strong X-ray attenuating ability of the ...

Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report red blood cell membrane-camouflaged nanoparticles (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under appropriate light irradiation, the TPC can generate ROS, not only for PDT but also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy. In vivo results show that the coating of RBC membrane prolongs blood circulation and improves tumor accumulation. The combination of chemo- and photodynamic therapy enhances anticancer therapeutic activity, and light-triggered drug release reduces systematic toxicity. All these characteristics render the d...

Chemodynamic therapy can convert endogenous hydrogen peroxide (H2O2) at tumor localization into the toxic hydroxyl radical (˙OH) destroying tumor cells. Photodynamic therapy as a noninvasive method utilizes photosensitizers (PSs) to convert O2 into cytotoxic reactive oxygen species (e.g., 1O2) upon laser irradiation, which is dependent on the content of oxygen. The combination of the two therapeutic strategies on a single platform can enhance the anticancer effect. Herein, we report a porphyrin-ferrocene theranostic agent for combined photodynamic and chemodynamic therapy. Compared to monotherapy, the as-prepared porphyrin-ferrocene conjugates exhibit superior efficiency and potency in killing cancer cells at low drug doses. This study suggests the rational design of molecular structures as multifunctional therapeutics for potential clinic application.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

The development of a simple and straightforward strategy to synthesize multifunctional carbon dots for photodynamic therapy (PDT) has been an emerging focus. In this work, diketopyrrolopyrrole-based fluorescent carbon dots (DPP CDs) were designed and synthesized through a facile one-pot hydrothermal method by using diketopyrrolopyrrole (DPP) and chitosan (CTS) as raw materials. DPP CDs not only maintained the ability of DPP to generate singlet oxygen (1O2) but also have excellent hydrophilic properties and outstanding biocompatibility. In vitro and in vivo experiments demonstrated that DPP CDs greatly inhibited the growth of tumor cells under laser irradiation (540 nm). This study highlights the potential of the rational design of CDs for efficient cancer therapy.

The limitation for the biomedical application of porous organic polymers (POPs) is the big size and poor dispersibility in aqueous media. Herein, a nanoscale metal–organic framework (MOF)@POP composite, named UNM, has been synthesized by epitaxial growth of the photoactive porphyrin-POPs (H2P-POP) on the outer surface of amine containing UiO-66 (UiO-AM). After the growth of POPs, the crystallization, pore structure, and size distribution of UNM are retained well. The formed UNM possesses a small size of less than 200 nm and could be internalized by cancer cells. Such light-activated UNM exhibits efficient ability to generate 1O2 under various experimental conditions, which can be further applied for PDT efficacy. The present work demonstrates the great potential of nanoscale porous polymers in biomedical fields and cancer treatment.

Smart responsive nanomaterials, which are sensitive to biological signals, are promising therapeutic formulations. It has been well studied that redox potential is much different at both tissue and cellular level. In this work, three organic nanoparticles with variable redox sensitivity were fabricated, and their redox sensitivity was evaluated and compared in detail. First, diselenide, disulfide, and carbon–carbon bond containing porphyrin dimers TPP-SeSe/TPP-SS/TPP-CC were synthesized. Then, the corresponding self-assembled nanoparticles (TPP-SeSe/TPP-SS/TPP-CC NPs) were prepared via nanoprecipitation method. As-synthesized nanoparticles were utilized to systematically compare the stimuli responsiveness to reductive agents (e.g., glutathione) in different conditions, especially in the living cells, through the singlet oxygen generation ability and the cytotoxicity. A series of experimental results demonstrated that the diselenide bond shows better superiority in reduction sensitivity than that of the di...

The development of long-term tumor imaging is of great importance for effective theranostic systems. In this study, a temperature-responsive poly(ether amine) with a phase transition temperature around 43 °C was used to encapsulate indocyanine green (ICG), which is a near infrared fluorescent and photothermal agent. Upon photothermal treatment, the polymeric nanoparticles underwent an increase in size from the nano- to the microscale. The prepared ICG-loaded PEAs exhibited significant stability against photobleaching and excellent NIR imaging ability. The increase in particle size resulted in the accumulation and retention of nanoparticles at the tumor site upon photothermal treatment. The accumulation of nanoparticles facilitated long-term imaging of the tumor for up to 30 days after one injection. This study highlights the potential of the rational design of polymer nanoparticles for bioimaging and diagnostics.

Polymer-modified metal-organic frameworks combine the advantages of both soft polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge to develop simple methods for surface modification of MOFs. In this work, MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)-imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity, smaller size distribution, well-retained pore integrity, and available functional sites. After folic acid grafting, the enhanced intracellular uptake and bioimaging was validated.

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by healthy skeletal muscle, and recently published research linked this outcome to exercise-induced elevation in γ3-AMPK activity which leads to greater phosphorylation of Akt substrate of 160 kDa (pAS160) on an AMPK-phosphomotif (Ser704), which in turn favors greater insulin-stimulated pAS160 on a key Akt-phosphomotif (Thr642) that regulates ISGU. Studying healthy muscle is important, but a more urgent need is to understand the mechanisms for enhanced ISGU in insulin resistant muscle. Our primary goal was to determine if exercise, which increases ISGU, also increases γ3-AMPK activity and pAS160 on key regulatory sites at 3-hours post-exercise (3hPEX) in insulin resistant muscle. Rats fed a high fat diet (HFD; 2 week) known to cause muscle insulin resistance performed acute swim exercise (2 h) or remained sedentary (SED). Other chow-fed (low fat diet, LFD; 2 week) SED rats served as healthy controls. Isolated epitrochlearis muscles from 3hPEX rats (and SED controls) were used for ISGU, pAS160 and γ1- and γ3-AMPK isoform-specific activity. ISGU was lower in HFD SED muscles compared to LFD SED, but this decrement was eliminated in the HFD 3hPEX group. The γ3-AMPK activity, but not γ1-AMPK activity, was elevated in HFD 3hPEX muscles versus both SED controls. In addition, insulin-stimulated pAS160 on Thr642 and Ser704 in HFD 3hPEX muscles was elevated above HFD SED controls and equal to values in LFD SED muscles. These novel results demonstrated, for the first time in an insulin-resistant model, that the post-exercise increase in ISGU was accompanied by enhanced pAS160Ser704 and γ3-AMPK activation. Our working hypothesis is that these key signaling events are necessary for acute exercise to restore the ISGU of insulin resistant muscles to values equal to normal LFD SED controls. Disclosure M.W. Pataky: None. E.B. Arias: None. X. Zheng: None. H. Wang: None. G.D. Cartee: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Porphyrin-based porous organic polymers are highly potential candidates for cancer theranostics. However, un-controllable particle size and unclear photoactive mechanisms have been deemed to be “Achilles’ heels” for their biomedical application. Herein, a facile self-template strategy has been applied to integrate two types of porous materials to build the MOF@POP-PEG nanocomposite (named HUC-PEG). As-synthesized HUC-PEG exhibited controllable particle shape and size, good biocompatibility, and better colloidal stability. Importantly, synergy “0 + 1 > 1” interface effects have been demonstrated to simultaneously enhance both the generation of more singlet oxygen (1O2) for photodynamic therapy (PDT) and local hyperthermia for photothermal therapy (PTT), thus to achieve favorable proliferation inhibition of tumor cell both in vitro and in vivo. Moreover, the strong X-ray attenuating ability of Hf element and excellent photothermal conversion efficacy endow this nanocomposite with computed tomography (CT)/photothermal imaging functions. We believe that our ingenious design may open a new horizon for the preparation of nanoscale POP-based therapeutic agents and also realize a paradigm shift in the understanding of photoactive mechanism in porous materials.

The Rab GTPase activating protein known as Akt substrate of 160 kDa (AS160 or TBC1D4) regulates insulin-stimulated glucose uptake in skeletal muscle, the heart, and white adipose tissue (WAT). A novel rat AS160-knockout (AS160-KO) was created with CRISPR/Cas9 technology. Because female AS160-KO versus wild type (WT) rats had not been previously evaluated, the primary objective of this study was to compare female AS160-KO rats with WT controls for multiple, important metabolism-related endpoints. Body mass and composition, physical activity, and energy expenditure were not different between genotypes. AS160-KO versus WT rats were glucose intolerant based on an oral glucose tolerance test (P

The oxygen-dependent feature of most photosensitizers (PSs) and the aggravated hypoxia tumor microenvironment seriously impede the photodynamic therapy (PDT) effectiveness. However, this undesirable impediment can be utilized to further trigger the activation of hypoxia-sensitive prodrugs. Moreover, a combined therapy can be used by associating PDT with hypoxia-activated chemotherapy. Herein, a multifunctional Hf-porphyrin nanoscale metal-organic framework (NMOF) platform [Hf/tetra(4-carboxyphenyl)porphine (TCPP)] has been synthesized, with a high porphyrin loading capacity and a well-ordered coordination array preventing porphyrin self-quenching, thus greatly improving the generation efficiency of reactive oxygen species (ROS), which is helpful for PDT. As-synthesized Hf-TCPP nanoparticles possess more than 50 wt % of TCPP PS content, good crystallization, and a large Brunauer-Emmett-Teller surface for further loading the hypoxia-activated prodrug [tirapazamine (TPZ)] in a high-loading content. Additionally, subsequent surface modification with a dopamine-derived polymer (DOPA-PIMA-mPEG) significantly improves their dispersibility and structural stability, and the controlled release kinetics of TPZ. Such a nanoplatform can efficiently produce ROS for PDT upon irradiation, and also the depletion of the oxygen could further aggravate the hypoxic environment of tumors to induce the activation of TPZ for achieving an enhanced treatment efficacy. This work demonstrates the great advantages of an NMOF-based platform in antitumor therapies for combined PDT and hypoxia-activated chemotherapy.

To assess the risk of foodborne disease caused by Salmonella in broiler chickens from retail to table, and to find effective preventive measures according to the risk assessment results.Using dose-response model and Combase database, to evaluate the chicken-Salmonella poisoning risk through the crosscontamination in the kitchen with @ RISK by combining monitoring data of broiler chickens in Heilongjiang Province and related data.According to the results of the quantitative risk assessment, there was a high risk of chicken-Salmonella poisoning because of cross-contamination in the kitchen. Scenario analysis suggested that, if the raw chicken was frozen or refrigerated storage in retail, the average risk of chicken-Salmonella poisoning can be reduced 1/5.The risk of Chinese residents suffering from chicken-Salmonella poisoning will be reduced effectively by using cold chain management of raw chicken in retail.