A chalcone-based ESIPT and AIE fluorophore for ß-gal imaging in living cells.

ß-Galactosidase (ß-gal), which is responsible for the hydrolysis of the glycosidic bond of lactose to galactose, has been recognized as an important biomarker of cell or organism status, especially cell senescence and primary ovarian cancer. Extensive efforts have been devoted to develop probes for detecting and visualizing ß-gal in cells. Herein, a fluorescent probe gal-HCA which possesses both excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) properties was prepared to monitor ß-gal in living cells. The probe consists of 2-hydroxy-4'-dimethylamino-chalcone (HCA) capped with a D-galactose group. The cleavage of the glycosidic bond in gal-HCA triggered by ß-gal releases HCA, which results in a significant bathochromic shift in fluorescence from 532 to 615 nm. The probe exhibited high selectivity and sensitivity toward ß-gal with a detection limit as low as 0.0122 U mL-1. The confocal imaging investigation demonstrated the potential of gal-HCA in monitoring the endocellular overexpressed ß-gal in senescent cells and ovarian cancer cells. This study provides a straightforward approach for the development of fluorescent probes to monitor ß-gal and detection of ß-gal-associated diseases.

A novel non-chemically amplified resist based on polystyrene-iodonium derivatives for electron beam lithography.

To break the resolution limitation of traditional resists, more work is needed on non-chemically amplified resists (non-CARs). Non-CARs based on iodonium salt modified polystyrene (PS-I) were prepared with controllable molecular weight and structure. The properties of the resist can be adjusted by the uploading of iodonium salts on the polymer chain, the materials with a higher proportion of iodonium salts show better lithography performance. By comparing contrast curves and quality of the lithographic patterns, the optimum developing condition of 4-methyl-2-pentanone and ethyl alcohol (v:v = 1:7) was selected. The high-resolution stripes of 15 nm half-pitch (HP) can be achieved by PS-I0.58in e-beam lithography (EBL). PS-I0.58shows the advanced lithography performance in the patterns of 16 nm HP and 18 nm HP stripes with low line edge roughness (3.0 nm and 2.4 nm). The resist shows excellent potential for further pattern transfer, the etch selectivity of resist PS-I0.58to the silicon was close to 12:1. The lithographic mechanism of PS-I was investigated by experimental and theoretical calculation, which indicates the polarity of materials changes results in the solubility switch. This work provides a new option and useful guidelines for the development of high-resolution resist.

Radiative pumping in a strongly coupled microcavity filled with a neat molecular film showing excimer emission.

Strong light-matter interactions have attracted much attention as a means to control the physical/chemical properties of organic semiconducting materials with light-matter hybrids called polaritons. To unveil the processes under strong coupling, studies on the dynamics of polaritons are of particular importance. While highly condensed molecular materials with large dipole density are ideal to achieve strong coupling, the emission properties of such films often become a mixture of monomeric and excimeric components, making the role of excimers unclear. Here, we use amorphous neat films of a new bis(phenylethynyl anthracene) derivative showing only excimer emission and investigate the excited-state dynamics of a series of strongly coupled microcavities, with each cavity being characterised by a different exciton-photon detuning. A time-resolved photoluminescence study shows that the excimer radiatively pumps the lower polariton in the relaxation process and the decay profile reflects the density of states. The delayed emission derived from triplet-triplet annihilation is not sensitive to the cavity environment, possibly due to the rapid excimer formation. Our results highlight the importance of controlling intermolecular interactions towards rational design of organic exciton-polariton devices, whose performance depends on efficient polariton relaxation pathways.

When 3D genome technology meets viral infection, including SARS-CoV-2.

Mammalian chromosomes undergo varying degrees of compression to form three-dimensional genome structures. These three-dimensional structures undergo dynamic and precise chromatin interactions to achieve precise spatial and temporal regulation of gene expression. Most eukaryotic DNA viruses can invade their genomes into the nucleus. However, it is still poorly understood how the viral genome is precisely positioned after entering the host cell nucleus to find the most suitable location and whether it can specifically interact with the host genome to hijack the host transcriptional factories or even integrate into the host genome to complete its transcription and replication rapidly. Chromosome conformation capture technology can reveal long-range chromatin interactions between different chromosomal sites in the nucleus, potentially providing a reference for viral DNA-host chromatin interactions. This review summarized the research progress on the three-dimensional interaction between virus and host genome and the impact of virus integration into the host genome on gene transcription regulation, aiming to provide new insights into chromatin interaction and viral gene transcription regulation, laying the foundation for the treatment of infectious diseases.

A bioluminescent probe for NQO1 overexpressing cancer cell imaging in vitro and in vivo.

NAD(P)H quinone oxidoreductase1 (NQO1) is a flavoenzyme that regulates the redox potential level in cells. Overexpression of NQO1 has been proven to be relevant to some malignant tumors. Herein a bioluminescent probe NQO1-Luc equipped with an NQO1-targeting group, trimethyl-locked quinone propionic acid (QPA), was constructed. The reduction of NQO1-Luc could be triggered by NQO1, resulting in the release of free D-luciferin, and concomitantly a bright bioluminescence emission. NQO1-Luc exhibits high selectivity and sensitivity toward NQO1 activity and the capability of distinguishing NQO1-overexpressing cells in vitro and in vivo, which offers a promising tool for investigations of NQO1 related biological processes including tumors in living organisms.

A Thermostable Protein Matrix for Spectroscopic Analysis of Organic Semiconductors.

Advances in protein design and engineering have yielded peptide assemblies with enhanced and non-native functionalities. Here, various molecular organic semiconductors (OSCs), with known excitonic up- and down-conversion properties, are attached to a de novo-designed protein, conferring entirely novel functions on the peptide scaffolds. The protein-OSC complexes form similarly sized, stable, water-soluble nanoparticles that are robust to cryogenic freezing and processing into the solid-state. The peptide matrix enables the formation of protein-OSC-trehalose glasses that fix the proteins in their folded states under oxygen-limited conditions. The encapsulation dramatically enhances the stability of protein-OSC complexes to photodamage, increasing the lifetime of the chromophores from several hours to more than 10 weeks under constant illumination. Comparison of the photophysical properties of astaxanthin aggregates in mixed-solvent systems and proteins shows that the peptide environment does not alter the underlying electronic processes of the incorporated materials, exemplified here by singlet exciton fission followed by separation into weakly bound, localized triplets. This adaptable protein-based approach lays the foundation for spectroscopic assessment of a broad range of molecular OSCs in aqueous solutions and the solid-state, circumventing the laborious procedure of identifying the experimental conditions necessary for aggregate generation or film formation. The non-native protein functions also raise the prospect of future biocompatible devices where peptide assemblies could complex with native and non-native systems to generate novel functional materials.

Ultrafast excitation energy transfer in a benzimidazole-naphthopyran donor-acceptor dyad.

The excited-state dynamics of a donor-acceptor dyad composed of 1-propyl-2-pyridinyl-benzimidazole (PPBI) as donor and the photochromic molecular switch diphenylnaphthopyran (DPNP) as acceptor linked via an ester bridge has been investigated by a combination of static and time-resolved spectroscopies and quantum chemical calculations. The UV absorption spectrum of the dyad is virtually identical to the sum of the spectra of its individual constituents, indicating only weak electronic coupling between the donor and acceptor in the electronic ground state. After selective photoexcitation of the PPBI chromophore in the dyad at λpump = 310 nm, however, a fast electronic energy transfer (EET) from the donor to the acceptor is observed, by which the lifetime of the normally long-lived excited state of PPBI is reduced to a few ps. Enabled by the EET, the acceptor switches from its ring-closed naphtopyran form to its ring-opened merocyanine form. The singular value decomposition-based global analyses of the measured femtosecond time-resolved transient absorption spectra of the dyad and its two building blocks as reference compounds allowed us to determine a value for the EET time constant in the dyad of τ = 2.90 ± 0.60 ps. For comparison, Förster theory predicts characteristic FRET times between 1.2 ps ≤ τ ≤ 4.2 ps, in good agreement with the experimental result.

Specific Imaging of Tyrosinase in Vivo with 3-Hydroxybenzyl Caged D-Luciferins.

Tyrosinase (TYR), a key enzyme in biosynthesis of melanin, usually functions as a biomarker of severe skin diseases such as vitiligo and melanoma cancer. Accurate detection of TYR activity in vivo is urgent but still challenging. Inspired by the advantages of bioluminescence in vivo strategy in imaging and the specific hydroxylation of 3-hydroxybenzyloxy group by TYR, a bioluminogenic probe, TYR-LH2, was designed and synthesized through caging D-luciferin with 3-hydroxybenzyl. The probe exhibits high selectivity and sensitivity toward TYR with a detection limit of 0.11 U/mL in a small detection volume of 100 µL. Bioluminescence imaging results show that TYR-LH2 is fully competent for monitoring the dynamic changes of TYR in living cells and model animals and possesses the capability of discriminating melanocytes from other cell lines, thus offering a promising approach for investigation and diagnosis of melanoma cancer and other TYR-related diseases in vivo.

Ultrafast dynamics of UV-excited trans- and cis-ferulic acid in aqueous solutions.

The ultrafast UV-induced processes of the neutral, anionic and dianionic forms of trans- and cis-ferulic acid (FA) in aqueous solution were studied by static and femtosecond time-resolved emission and absorption spectroscopy combined with quantum chemical calculations. In all cases, initial excitation populates the first 1ππ* state. For the dianionic cis-isomer cFA2-, electronic deactivation takes place with a time constant of only 1.4 ps, whereas in all other cases, excited-state deactivation happens more than ten times slower, on a time scale of ≈20 ps. The data suggest sequential de-excitation pathways, where initial sub-picosecond solvent rearrangement and structural changes are followed by internal conversion to an intermediate excited electronic state from which deactivation to the ground state proceeds. Considering the time scales, barrierless excited-state pathways are suggested only in the case of cFA2-, where the observed formation of the isomerisation photoproduct tFA2- provides clear evidence for a cis ⇄ trans isomerisation coordinate. In the other cases, pathways with an excited-state energy barrier, presumably along the same coordinate, are likely, given the longer excited-state lifetimes.

Molecular Engineering of Aqueous Soluble Triarylboron-Compound-Based Two-Photon Fluorescent Probe for Mitochondria H2S with Analyte-Induced Finite Aggregation and Excellent Membrane Permeability.

Hydrogen sulfide (H2S) is a multifunctional signaling molecule that participates in many important biological processes. Herein, by functionalizing triarylboron with cyclen and diphenylamine, we synthesized TAB-1, TAB-2, and TAB-3 for H2S recongnization by rational design of molecular structures. Among them, aqueous soluble TAB-2 possesses excellent properties, including large two-photon action cross section, membrane permeability and can effectively complex with Cu(2+). The complex of TAB-2-Cu(2+) can selectively detect H2S with an instant response and mitochondria targeted. Moreover, the H2S-induced finite aggregation of indicators enhances their photostability and causes variation of the fluorescence lifetime. TAB-2-Cu(2+) has also been successfully applied for the mitochondria H2S imaging in NIH/3T3 fibroblast cells by TPM and FLIM.

Axially substituted phthalocyanine/naphthalocyanine doped in glass matrix: an approach to the practical use for optical limiting material.

A novel glass matrix doped with phthalocyanine or naphthalocyanine is prepared by a modified sol-gel technique. The photophysical and optical limiting properties of the phthalocyanine compounds both in glass matrix and in THF solution were investigated. The obtained glass matrix is homogeneous and transparent, as well as mechanically and thermodynamically stable enough to withstand very high laser fluence; the optical limiting performances of these compound samples are better than that of benchmark materials like C60 in toluene, carbon black in water, and graphene oxide in water or ethanol under nanosecond pulsed laser at 532 nm. Two prototypes of optical limiters doped in the glass matrix have very good optical limiting performances, which may provide potential practical use for optical limiting materials in a near future.

Intracellular fluorescent temperature probe based on triarylboron substituted poly N-isopropylacrylamide and energy transfer.

A novel hydrophilic fluorescence temperature probe (PNDP) based on polarity-sensitive triarylboron compound (DPTB) and PNIPAM is designed and synthesized. In order to overcome the shortcomings of the single-intensity-based sensing mechanism and obtain more robust signals, ratiometric readout is achieved by designing an efficient FRET system (PNDP-NR) between DPTB and Nile Red (NR). PNDP-NR possesses some excellent features, including wide temperature range, good linear relationship, high temperature resolution, excellent reversibility, and stability. Within a sensing temperature range of 30-55 °C, the fluorescence color of PNDP-NR experiences significant change from red to green-blue. PNDP-NR is also introduced into NIH/3T3 cells to sense the temperature at the single-cell level. It gave excellent photostability and low cytotoxicity in vivo.

Excited-State Deactivation of Branched Phthalocyanine Compounds.

The excited-state relaxation dynamics and chromophore interactions in two phthalocyanine compounds (bis- and trisphthalocyanines) are studied by using steady-state and femtosecond transient absorption spectral measurements, where the excited-state energy-transfer mechanism is explored. By exciting phthalocyanine compounds to their second electronically excited states and probing the subsequent relaxation dynamics, a multitude of deactivation pathways are identified. The transient absorption spectra show the relaxation pathway from the exciton state to excimer state and then back to the ground state in bisphthalocyanine (bis-Pc). In trisphthalocyanine (tris-Pc), the monomeric and dimeric subunits are excited and the excitation energy transfers from the monomeric vibrationally hot S1 state to the exciton state of a pre-associated dimer, with subsequent relaxation to the ground state through the excimer state. The theoretical calculations and steady-state spectra also show a face-to-face conformation in bis-Pc, whereas in tris-Pc, two of the three phthalocyanine branches form a pre-associated face-to-face dimeric conformation with the third one acting as a monomeric unit; this is consistent with the results of the transient absorption experiments from the perspective of molecular structure. The detailed structure-property relationships in phthalocyanine compounds is useful for exploring the function of molecular aggregates in energy migration of natural photosynthesis systems.

[A case of Sneddon syndrome started with neurological symptoms].

Sneddon syndrome(SS) is a rare clinical syndrome characterized by ischemic cerebrovascular disease and livedo reticularis, which involves the heart, kidney, fundus and other organs. We reported a case of a 45-year old male patient with recurrent ischemic cerebrovascular accidents as the first manifestation, accompanied by significant declines in cognitive function and livedo reticularis in trunk and limbs. The final diagnosis was SS. This article summarized the possible etiology, clinical characteristics, diagnosis and treatment for SS. Clinicians should improve the understanding of the disease to make the correct diagnosis and treatment and to prevent the occurrence of severe neurologic impairment and vascular dementia.

Water-soluble triarylboron compound for ATP imaging in vivo using analyte-induced finite aggregation.

Adenosine 5'-triphosphate (ATP) is a multifunctional molecule that participates in many important biological processes. Currently, fluorescence indicators for ATP with high performance are in demand. Reported herein is a novel water-soluble triarylboron compound which displays an apparent ATP-dependent fluorescence enhancement when dispersed in water. It can selectively recognize ATP from other bioactive substances in vitro and in vivo. The ATP-induced finite aggregation endows the indicator with appreciable photostability and superior tolerance to environmental electrolytes. This indicator has been successfully applied to the ATP imaging in NIH/3T3 fibroblast cells. The difference in the ATP levels within the membrane and cytosol is clearly visible.

An organic state trace element solution for rheumatoid arthritis treatment by modulating macrophage phenotypic from M1 to M2.

Trace elements (TEs) are essential for the treatment of rheumatoid arthritis (RA). This study aimed to prepare a TEs solution enriched with various organic states to evaluate its preventive, therapeutic effects, and mechanism of action in RA and to provide a treatment method for RA treatment. The TEs in natural ore were extracted and added to 0.5% (W/V) L-alanyl-L-glutamine (LG) to obtain a TEs solution (LG-WLYS), which was examined for its concentration and quality. The antioxidant properties and effects of LG-WLYS on cell behavior were evaluated at the cellular level. The preventive and therapeutic effects and mechanism of action of LG-WLYS in rats with RA were explored. The LG-WLYS solution was clear, free from visible foreign matter, and had a pH of 5.33 and an osmolality of 305.67 mOsmol/kg. LG-WLYS inhibited cell migration and angiogenesis. LG-WLYS solution induced macrophages to change from M1-type to M2-type, increased the content of antioxidant enzymes (glutathione, superoxide dismutase, and IL-10), decreased the levels of nitric oxide, malondialdehyde, TNF-α, IL-1ß, IL-6, COX-2, and iNOs, scavenging reactive oxygen species from the lesion site, inhibiting the apoptosis of chondrocytes, regulating inflammatory microenvironment, and decreasing inflammation response to exert the therapeutic effect for RA. In conclusion, LG-WLYS has outstanding therapeutic and preventive effects against RA and has enormous potential for further development.

A self-targeting MOFs nanoplatform for treating metastatic triple-negative breast cancer through tumor microenvironment remodeling and chemotherapy potentiation.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer with disappointing treatment and high mortality. Tumor microenvironment (TME) plays an important role in the invasion and metastasis of TNBC through multiple complex processes. Most anti-metastatic therapies only focus on cancer cells themselves or interfering with single factors of the metastasis process, which is often related to poor outcomes. Thus, effective TNBC treatment relies on regulating multiple key metastasis-related aspects of the TME. Herein, a self-targeting Metal-Organic Frameworks (MOFs) nanoplatform (named as MTX-PEG@TPL@ZIF-8) was designed to improve treatment of TNBC through tumor microenvironment remodeling and chemotherapy potentiation. The self-targeting MOF nanoplatform is consist of ZIF-8 nanoparticles loaded triptolide (TPL) and followed by the coating with methotrexate-polyethylene glycol conjugates (MTX-PEG). Due to MTX's affinity for the overexpressed folate receptor on tumor cell surfaces, MTX-PEG@TPL@ZIF-8 enables effective accumulation and deep penetration in the tumor area by an MTX-mediated self-targeting strategy. This MOF nanoplatform could promptly release the medication after penetrating the tumor cell, due to pH-triggered degradation. Its anti-metastasis mechanism is to inhibit tumor invasion and metastasis by down-regulating the expression of Vimentin, MMP-2 and MMP-9 and increasing the expression of E-cadherin, upregulation of cleaved caspase-3 and cleaved caspase-9 protein expression promote the apoptosis of tumor cells, thereby reducing their migration. It also downregulated the expression of VEGF and CD31 protein to inhibit the generation of neovascularization. Overall, these findings suggest the self-targeting MOF nanoplatform offers new insights into the treatment of metastatic TNBC by TME remodeling and potentiating chemotherapy.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and -27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel.

Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.

Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 µg HP and 20 µg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children.

Introduction: Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 µg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 µgChinese hamster ovary cell HepB (HepB-CHO). Methods: A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 µg HepB-HP at birth, Homo or Heteroprime-boost with 10 µg HepB-HP and 20 µg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results: A total of 359 children were included; 119 childrenreceived two doses of 10 µg HepB-HP and 120 children receivedtwo doses of 20 µg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 µg HepB-HP and 20µg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 µg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 µg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 µg HP-20 µg CHO and 20 µg CHO-10 µgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 µg CHO Homoprime-boost group was 2.087 times than that of the 10 µg HPHomo group. Discussion: The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 µg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.