A planar electronic acceptor motif contributing to NIR-II AIEgen with combined imaging and therapeutic applications.

Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

A ratiometric fluorescent probe for rapid and specific detection of hypochlorite.

Hypochlorite (ClO- ), as a kind of essential reactive oxygen species, plays a crucial role in vitro and in vivo. Here, a ratiometric fluorescent probe (TPAM) was designed and constructed for sensing ClO- based on substituted triphenylamine and malononitrile, which exhibited obvious colour transfer from orange to colourless under daylight accompanied by noticeable fluorescence change from red to green in response to ClO- . TPAM could effectively monitor ClO- with the merits of fast response, excellent selectivity, high sensitivity and a low detection limit of 0.1014 µM. 1 H NMR, mass spectra and theoretical calculations proved that ClO- caused the oxidation of the carbon-carbon double bond in TPAM, resulting in compound 1 and marked changes in colour and fluorescence. In addition, TPAM was utilized for imaging ClO- in living cells successfully with good photostability and biocompatibility.

Effect of Sr on Microstructure and Strengthening Mechanism of Al-4.6Mg Alloy.

The as-cast Al-4.6Mg alloy was subjected to deformation and sensitization-desensitization heat treatment, and then the microstructure and the enhancement mechanism of Sr were investigated by optical microscopy, scanning electron microscopy-energy-dispersive spectroscopy, electron backscatter diffraction, and transmission electron microscopy. The precipitation phases of Al-4.6Mg alloy were mainly ß-Al3Mg2, Al6Mn, and Al6(Mn Cr), and the nanoscale precipitation phases were Al3Mn and Al11Mn4. The formation of ß-Al3Mg2 was hindered by the addition of 0.1 wt.% Sr. In addition, the precipitate phase Al4Sr and the nano-sized precipitate phase τ-Al38Mg58Sr4 were uniformly distributed in the spherical matrix. The addition of Sr promoted the redissolution of Mg atoms in Al-4.6Mg alloy, increasing the solubility of Mg in the α-Al matrix from 4.7 wt.% to 5.1 wt.%. The microstructure analysis showed that Sr addition inhibited the recovery and recrystallization of the alloy because the Sr element elevated the recrystallization temperature. As a result, the grain deformation was intensified, the grain size was decreased from 6.96 µm to 5.39 µm, the low-angle grain boundaries were increased from 78.7 at % to 84.6 at %, and the high-angle grain boundaries were increased from 21.3 at % to 15.4 at %. Furthermore, the mechanical properties of the alloy were significantly improved, and the plasticity degraded after the addition of the Sr element. The yield strength of the alloy was enhanced mainly through fine grain strengthening, dispersion strengthening, solid solution strengthening, and working hardening. The strengthening mechanisms were analyzed in detail.

Type I Photosensitization with Strong Hydroxyl Radical Generation in NIR Dye Boosted by Vigorous Intramolecular Motions for Synergistic Therapy.

Development of type I photosensitizers (PSs) with strong hydroxyl radical (· OH) formation is particularly important in the anaerobic tumor treatment. On the other hand, it is challenging to obtain an efficient solid-state intramolecular motion to promote the development of molecular machine and molecular motor. However, the relationship between them is never revealed. In this work, a pyrazine-based near-infrared type I PS with remarkable donor-acceptor effect is developed. Notably, the intramolecular motions are almost maximized by the combination of intramolecular and intermolecular engineering to simultaneously introduce the unlimited bond stretching vibration and boost the group rotation. The photothermal conversion caused by the intramolecular motions is realized with efficiency as high as 86.8%. The D-A conformation of PS can also induce a very small singlet-triplet splitting of 0.07 eV, which is crucial to promote the intersystem crossing for the triplet sensitization. Interestingly, its photosensitization is closely related to the intramolecular motions, and a vigorous motion may give rise to a strong · OH generation. In view of its excellent photosensitization and photothermal behavior, the biocompatible PS exhibits a superior imaging-guided cancer synergistic therapy. This work stimulates the development of advanced PS for the biomedical application and solid-state intramolecular motions.

In Situ Imaging and Anti-inflammation of 3D Printed Scaffolds Enabled by AIEgen.

Three-dimensional (3D) printed bioactive scaffolds have been widely used in the field of bone tissue engineering. However, its in vivo visualization and bacterial inflammation are intractable issues during the surgery and treatment. Herein, we first synthesized an aggregation-induced emission-active luminogen (AIEgen) named 4BC with efficient reactive oxygen species (ROS) generation. Then, a series of 3D bioactive scaffolds loaded with 4BC were fabricated by a precipitation adsorption method, namely 4BC@scaffolds, which showed good in situ imaging performance for the implanted scaffolds by using simple UV light irradiation. Among them, the 4BC@TMP scaffold composed of trimagnesium phosphate (TMP) had excellent bactericidal ability for Escherichia coli and Staphylococcus aureus in vitro and resisted bacterial inflammation in vivo through photodynamic action. H&E and immunofluorescence staining were performed to further evaluate the inhibitory effect of bacterial inflammation in vivo. This work verified that AIEgen-based 3D scaffolds are promising bioactive frameworks for bioimaging and antibacterial applications.

Co3O4 Nanoparticle-Modified Porous Carbons with High Microwave Absorption Performances.

Carbon materials derived from natural biomaterials have received increasing attention because of their low cost, accessibility, and renewability. In this work, porous carbon (DPC) material prepared from D-fructose was used to make a DPC/Co3O4 composite microwave absorbing material. Their electromagnetic wave absorption properties were thoroughly investigated. The results show that the composition of Co3O4 nanoparticles with DPC had enhanced microwave absorption (-60 dB to -63.7 dB), reduced the frequency of the maximum reflection loss (RL) (16.9 GHz to 9.2 GHz), and had high reflection loss over a wide range of coating thicknesses (2.78-4.84 mm, highest reflection loss <-30 dB). This work provided a way for further research on the development of biomass-derived carbon as a sustainable, lightweight, high-performance microwave absorber for practical applications.

A randomized, placebo-controlled study of magnetic acupuncture for supplementary analgesia after laparoscopic appendectomy in children.

PURPOSE: Magnetic acupuncture (MA) is a noninvasive technique potentially useful for postoperative pain reduction. While anecdotal case series have reported analgesic effects, this has not been systematically studied. We evaluated the analgesic properties of supplemental MA versus placebo and standard treatment in children who underwent laparoscopic appendectomy (LA). METHODS: Children age 2-18 years who underwent LA for acute appendicitis were recruited from 2018 through 2020. Standardized postoperative pain medication including Ibuprofen, Acetaminophen, and narcotics were given as needed. Patients were randomized to 3 groups: Group 1 had adhesive acupuncture magnets placed on 5 predetermined meridian points for 48 h. Group 2 had corresponding non-magnetic adhesive metal disks placed in the same locations. Group 3 received no supplemental treatment. Pain was measured every 4 h using a 1-10 Visual-Analog-Scale (VAS). Cumulative demand of as-needed pain medication was calculated. Patients and families were handed open questionnaires upon discharge assessing satisfaction with treatment. RESULTS: A total of 126 patients were randomized. Groups were similar in age and gender distribution. Differences of means of cumulative VAS scores were significantly lower for group 1 (8.0,SD5.2) compared to group 2 (12.8,SD4.4; -4.8[95%CI -7.1 to -2.5], p < 0.01), and group 3 (19.8,SD7.7; -11.8[95%CI -15.0 to -8.6], p < 0.01). Cumulative acetaminophen and ibuprofen use per patient during the entire hospital stay was lower for group 1 (1510 mg, 20 mg) than for group 2 (2950 mg, 1800 mg), and group 3 (6100 mg; 2300 mg), respectively. In contrast to groups 2 and 3, none of the patients in group 1 asked for narcotics. Patients were highly satisfied with MA. CONCLUSIONS: Supplemental MA after LA in children had a beneficial effect on the postoperative pain perception and on-demand use of analgesics that could not be explained by placebo mechanism. MA is a safe, simple, and effective adjunct to standard postoperative care. Further studies are warranted. TYPE OF STUDY: Prospective randomized, placebo-controlled trial LEVEL OF EVIDENCE: Level I.

Mechanical Force-Induced Blue-Shifted and Enhanced Emission for AIEgens.

Mechanochromic (MC) luminescence of organic molecules has been emerging as a promising smart material for optical recording and memory devices. At the same time, pressure-induced blue-shifted and enhanced luminescence are rarely reported now. Herein, a series of cyanostilbene-based AIEgens with different substituents were synthesized to evaluate the influence of morphology transformation and push-pull electronic effect on the MC luminescence. Among these luminophores, compound 1 with one cyano group and diethylamino group was more susceptible to mechanical stimuli and obtained blue-shifted and enhanced fluorescence in response to anisotropic grinding. Powder X-ray diffraction patterns indicated that the MC behaviors were ascribed to the solid-state morphology transition from crystal-to-crystal. Analysis of crystal structures revealed that loose molecular packing is a key factor for high high-contrast MC luminescence. The smart molecular design, together with the excellent performance, verified that luminophores with twisted structures are ideal candidates for MC luminogens.

Understanding Physical Activity and Exercise Behavior in China University Students: An Application of Theories of the Flow and Planned Behavior.

Objectives: The purpose of this study was to examine a extended model of the theory of planned behavior (TPB) model by adding the variables of the flow theory and to investigate Chinese university students' exercise behavior and its influence factors. Methods: The hypothesized model was validated through testing three competing models using a sample collected from 248 Chinese university students involving 165 males and 83 females. Results: The three competitive models fitted well and predicted exercise behavior significantly. Among them, the enjoyment + TPB model is the optimal model. Conclusions: Enjoyment and concentration can all predicting exercise behavior directly or indirectly. Enjoyment is stronger than concentration in predicting TPB constructs and exercise behavior, and it is a more important predictor than concentration in the field of exercise behavior research. Values. Research provides insights to better understand the exercise behavior of Chinese university students as well as useful information for designing exercise interventions and developing university students' education and training.

Visualization of Enantiorecognition and Resolution by Chiral AIEgens.

Enantioselective recognition and separation have attracted much attention in pharmaceutical analysis, food chemistry, and life science. Herein, we propose an efficient strategy to achieve such purposes using optically active luminogens with aggregation-induced emission (AIE) characteristics. These AIE luminogens (AIEgens) show strong enantiomeric discrimination for 12 kinds of chiral acids and unprotected amino acids. In particular, an exceptionally high enantioselectivity for d/l-Boc-glutamic acid was observed, as demonstrated by the large difference between the formed AIEgen/acid complexes. Due to the AIE effect, enantioselective separation was achieved by aggregation of the AIEgens with one enantiomer in the mixed acid solution. Through analysis of the fluorescence standard curve, the aggregates of AIEgen/chiral acid possessed 90% d-analyte, from which the enantiomeric excess (ee) value was assessed to be 80% ee. Such a result is in good agreement with that (91% d-analyte and 82% ee) by chiral HPLC analysis. Thus, this simple one-step aggregation method can serve as a preliminary screening tool for high-throughput analysis or separation of chiral chemicals.

OGA activated glycopeptide-based nano-activator to activate PKM2 tetramerization for switching catabolic pathways and sensitizing chemotherapy resistance.

Tumor cells intensively engage in metabolic reprogramming for enhancing the availability of glycolytic metabolites and support cell proliferation. As the most important rate-limiting enzyme in aerobic glycolysis, activating the pyruvate kinase muscle isoform 2 (PKM2) from dimers to tetramers has become a key tumor chemotherapy method to control glucose metabolism. Herein, we developed a glycopeptide-based PKM2 nano-activator, which could induce the tetramerization of PKM2 based on serine bonding to Domain C of PKM2. The bound and trapped PKM2 tetramers significantly hindered glycolytic intermediates, prevented the nucleus translocation of dimeric PKM2, and ultimately inhibited the proliferation, chemoresistance and metastasis of tumor. The glycopeptide assembled into nanoparticles under aqueous conditions and in the circulation, which in situ transformed into PKM2 nano-activator with nanofibrillar structure after specifically activated by O-GlcNAcase recognition upregulated in a wide range of human tumors. Moreover, the glycopeptide-based PKM2 nano-activator successfully accumulated at the tumor sites and boosted the chemo-drug sensitivity against prostate and breast cancers. Attributed to these intriguing results, the newly developed glycopeptide-based PKM2 nano-activator can be envisioned a promising candidate for the treatment of tumors by switching catabolic pathways.

Chiral assembly of organic luminogens with aggregation-induced emission.

Chirality is important to chemistry, biology and optoelectronic materials. The study on chirality has lasted for more than 170 years since its discovery. Recently, chiral materials with aggregation-induced emission (AIE) have attracted increasing interest because of their fascinating photophysical properties. In this review, we discussed the recent development of chiral materials with AIE properties, including their molecular structures, self-assembly and functions. Generally, the most effective strategy to design a chiral AIE luminogen (AIEgen) is to attach a chiral scaffold to an AIE-active fluorophore through covalent bonds. Moreover, some propeller-like or shell-like AIEgens without chiral units exhibit latent chirality upon mirror image symmetry breaking. The chirality of achiral AIEgens can also be induced by some optically active molecules through non-covalent interactions. The introduction of an AIE unit into chiral materials can enhance the efficiency of their circularly polarized luminescence (CPL) in the solid state and the dissymmetric factors of their helical architectures formed through self-assembly. Thus, highly efficient circularly polarized organic light-emitting diodes (CPOLEDs) with AIE characteristics are developed and show great potential in 3D displays. Chiral AIEgens are also widely utilized as "turn on" sensors for rapid enantioselective determination of chiral reagents. It is anticipated that the present review can entice readers to realize the importance of chirality and attract much more chemists to contribute their efforts to chirality and AIE study.

A Highly Efficient Fluorescent Sensor Based on AIEgen for Detection of Nitrophenolic Explosives.

The detection of nitrophenolic explosives is important in counterterrorism and environmental protection, but it is still a challenge to identify the nitroaromatic compounds among those with a similar structure. Herein, a simple tetraphenylethene (TPE) derivative with aggregation-induced emission (AIE) characteristics was synthesized and used as a fluorescent sensor for the detection of nitrophenolic explosives (2, 4, 6-trinitrophenol, TNP and 2, 4-dinitrophenol, DNP) in water solution and in a solid state with a high selectivity. Meanwhile, it was found that only hydroxyl containing nitrophenolic explosives caused obvious fluorescence quenching. The sensing mechanism was investigated by using fluorescence titration and 1H NMR spectra. This simple AIE-active probe can potentially be applied to the construction of portable detection devices for explosives.

A synergy between the push-pull electronic effect and twisted conformation for high-contrast mechanochromic AIEgens.

Mechanochromic (MC) luminogens in response to external stimulus have shown promising applications as pressure sensors and memory devices. Meanwhile, research on their underlying mechanism is still in the initial stage. Here, three pyridinium-functionalized tetraphenylethylenes bearing n-pentyloxy, hydrogen and nitro groups, namely TPE-OP, TPE-H and TPE-NO, are designed to systematically investigate the influence of the push-pull electronic effect and molecular conformation on MC luminescence. Upon anisotropic grinding and isotropic hydrostatic compression, TPE-OP with strong intramolecular charge transfer (ICT) affords the best MC behavior among them. Analysis of three polymorphs of TPE-H clearly indicates that planarization of the molecular conformation plays an important role in their bathochromic shifts under mechanical stimuli. Theoretical calculations also verify that high twisting stress of AIEgens can be released under high pressure. This study presents a mechanistic insight into MC behaviour and an effective strategy to achieve high-contrast MC luminescence.

Enantioselective recognition of chiral acids by supramolecular interactions with chiral AIEgens.

Novel chiral AIEgens bearing optically pure amino groups were synthesized and showed excellent discrimination for a series of chiral acidic compounds and amino acids. Interestingly, after supramolecular assembly with 4-sulfocalix[4]arene, the obtained complexes showed enhanced enantioselectivity for chiral acids.

Glycopeptide-Conjugated Aggregation-Induced Emission Luminogen: A pH-Responsive Fluorescence Probe with Tunable Self-Assembly Morphologies for Cell Imaging.

pH values play an important role in various cell biological processes. Abnormal pH values in living systems are frequently associated with the development of diseases such as cancers, infection, and other diseases. Real-time monitoring of the changes of pH values in vivo will give us the significant indication for these diseases' progression. Within those pH-sensitive imaging probes, aggregation-induced emission (AIE) molecules exhibit great potential in aqueous imaging environment due to their high fluorescence quantum yield and stability. However, the modulation of the AIE probe with pH sensitivity and light-up property face challenges. Here, we introduced a new glycopeptide-modified AIE probe (TGO) based on the optimized solid-phase peptide synthesis approach. The response to pH of the peptide: DDDD progression changed hydrophobicity and hydrophilicity, resulting in the change of the amphipathicity balance. When modulating the pH from 5.5 to 8.0, the adverse protonation of the peptide induced assembled nanostructure transformation from nanolamellae to nanomicelles. Meanwhile, the pH-induced charge change in peptides can greatly influence the microenvironment of the AIEgen, resulting in the increase of fluorescence intensity.

Preparation of a PEGylated liposome that co-encapsulates l-arginine and doxorubicin to achieve a synergistic anticancer effect.

Strategies that combine chemotherapies with unconventional agents such as nitric oxide (NO) have been shown to enhance cancer therapies. Compared with small molecule chemotherapy drugs, nanosized particles have improved therapeutic efficacies and reduced systemic side effects because of the enhanced permeability and retention effect. In this report, we prepared PEGylated liposomes (LP) that incorporated l-arginine (Arg) and the anticancer drug doxorubicin (Dox) to yield a co-delivery system (Dox-Arg-LP). On the basis of our previous research, we hypothesized that Dox-Arg-LP should achieve a synergistic anticancer effect because Arg conversion to NO by activated M1 macrophages augments the chemotherapeutic activity of Dox. Dox-Arg-LP showed comparable physical properties to those of conventional Dox-only liposomes (Dox-LP). In vitro assessment revealed that the cytotoxicity of Dox-Arg-LP toward cancer cells was significantly higher than that of Dox-LP. In vivo application of Dox-Arg-LP in mice enhanced the chemotherapeutic effect with a 2 mg kg-1 dose of Dox-Arg-LP achieving the same therapeutic efficacy as a two-fold higher dose of Dox-LP (i.e., 4 mg kg-1). Therefore, co-encapsulation of dual agents into a liposome formulation is an efficient strategy to enhance chemotherapy while reducing systemic toxicity.

Targeting autophagy by natural product Ursolic acid for prevention and treatment of osteoporosis.

With the growth of the aging population, osteoporosis is becoming a global health problem. Ursolic acid (UA) is an active ingredient existed in a variety of foods and nature plants and owns plenty of pharmacological effects especially in treating metabolic disease. Our predication from network pharmacology hinted that UA has potential for ameliorating osteoporosis. Firstly through in vivo experiment, we confirmed that UA administration obviously protected against ovariectomy (OVX)-induced osteoporosis in rats by improving microarchitectural deterioration of trabecular bone (P < 0.001), decreasing numbers of TRAP positive osteoclast in vertebra (P < 0.001), as well as decreasing serum osteoclast-specific cytokines release (P < 0.001). Besides, UA ameliorated kidney damage secondary to OVX-induced osteoporosis by ameliorating glomerular atrophy, decreasing BUN and creatinine levels in OVX rats. In vitro, UA noticeably decreased osteoclastic-special marker proteins c-Fos and NFATc1 expressions (P < 0.001) in response to RANKL stimulation in macrophagy. Importantly, autophagy pathway was activated in the process of osteoclast differentiation and blocked by UA pretreatment. Furthermore, autophagy inhibitors suppressed osteoclast differentiation (P < 0.001). Collectively, UA may ameliorate osteoporosis by suppressing osteoclast differentiation mediated by autophagy. Our research provides scientific support for UA treating osteoporosis and offers an optimal dose for daily intake of UA safely to prevent bone diseases.

Effect of an Endothelin B Receptor Agonist on the Tumor Accumulation of Nanocarriers.

Enhancing blood flow to tumors is a prominent strategy for improving the tumor accumulation of macromolecular drugs through the enhanced permeability and retention (EPR) effect. IRL-1620 is an agonist of the endothelin B receptor, and is a promising molecule to enhance tumor blood flow by activating endothelial nitric oxide synthase. However, contradictory effects on tumor blood flow modulation have been reported because the effects of IRL-1620 may differ in different animal models. Here, we examined for the first time the effect of IRL-1620 on the EPR effect for PEGylated liposomes in a CT-26 murine colon cancer model. Co-injection of IRL-1620 at an optimum dose (3 nmol/kg) nearly doubled the tumor accumulation of liposomes compared with controls, indicating that IRL-1620 enhanced the EPR effect in the present colon cancer model. Co-injection of IRL-1620 is a promising strategy to improve the therapeutic effects of macromolecular drugs while reducing their side effects.