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Two novel phenylenes (1,4-phenylene and 4,4′-biphenylene) bridged dimeric BOBPY (Boron complexed [Formula: see text]O-type benzopyrromethenes) were designed and synthesized from the one-pot condensation of pyrrole with formylisoindole and subsequent complexation with diboronic acid. These novel dyes were fully characterized by NMR spectroscopy, HRMS, absorption and fluorescence emission spectroscopy, and cyclic voltammetry. These resulting BOBPY dimers are highly photostable and show intense absorption and emission in the region of 618 to 644 nm with high absorption coefficients and solvent-dependent fluorescence quantum yields. The electronic interactions between BOBPY units are related with length of the linker. And the dimer with short 1,4-phenylene linker was more sensitive to the polarity of the solvents than that of the other dimer, suggesting that the short linkage allowed stronger electronic communication between the two BOBPY units.

Sulfoxide-bridged dimeric BODIPYs were developed as a new class of long-wavelength photoconvertible fluorophores. Upon visible-light irradiation, a sulfoxide moiety was released to generate the corresponding α,α-directly linked dimeric BODIPYs. The extrusion of SO from sulfoxides was mainly through an intramolecular fashion involving reactive triplet states. By this photoconversion, not only were more than 100 nm red shifts of absorption and emission maxima (up to 648/714 nm) achieved but also stable products with bright fluorescence were produced with high efficiency. The combination of photoactivation and red-shifted excitation/emission offered optimal contrast and eliminated the interference from biological autofluorescence. More importantly, the

A novel protocol of rhodium-catalyzed tandem C-H annulation of aldehyde and aniline with diazonaphthalen-1(2

Hydrazine-inserted pyrrole-based diboron fluorophores that display strong fluorescence in either the solution or solid state are widely used in biomedicine and optoelectronic materials science. A growing demand calls for multiple strategies for generating novel fluorophores to solve problems of small Stokes shifts and poor solid-state fluorescence. By changing their frameworks, several series of novel diboron compounds have recently been developed as increasingly valuable classes of fluorophores owing to their tunable structures and outstanding spectroscopic properties, such as high fluorescence quantum yields, large Stokes shifts, high photostability, and low LUMO energy levels due to the presence of electron-deficient BF2 groups. This review mainly highlights key synthetic strategies for the fluorophores BOPHY, BOPPY, and BOAPY developed by our group, together with the superior properties of these compounds. Significant photophysical data for these fluorophores in solution and solid states are included within the scope of this review. The facile functionalization of these fluorophores permits practical structural modifications to generate novel versatile dyes with excellent chemical and photophysical properties. We believe that these fluorophores hold promise to make important contributions in a wide range of applications.1 Introduction2 BOPHY Fluorophore2.1 Discovery of BOPHY and its Fundamental Properties2.2 Synthesis and Properties of Modified BOPHY Derivatives3 BOPPY and BOPYPY Fluorophores3.1 Discovery of BOPPY and BOPYPY, and Their Fundamental Properties3.2 Synthesis and Properties of Benzo-Fused BOPPYs from Isoindoles3.3 Nucleophilic Substitution and Cross-Coupling Reactions of Halogenated BOPPYs3.4 Knoevenagel Reaction4 BOAPY and BOPAHY Fluorophores5 Conclusion

Ischemic diseases are life-threatening, and the incidence increases as people's lifestyles change. Medications and surgical intervention offer limited benefit, and stem cell therapy has emerged as a potential approach for treating ischemic diseases. The exosomes secreted by stem cells have attracted more attention because they do not trigger the immune response and can be used as drug carriers. The non-coding RNA (ncRNA) carried by exosomes plays a key role in mediating exosome's beneficial effect, which can be further enhanced when combined with nanomaterials to improve its retention time. Here, we review the downstream target molecules and signal pathways of ncRNA and summarize recent advances of some nanomaterials used to encapsulate exosomes and promote ischemic tissue repair. We highlight the imprinting of exosomes from parent cells and discuss how the inflammasome pathway may be targeted for the development of novel therapy for ischemic diseases.

The design and development of wide band gap (WBG) polymer donors are critical for achieving high power conversion efficiencies (PCEs) in polymer solar cells. In this work, four WBG polymer donors, Q4, Q5, Q6, and Q7, with different numbers and positions of fluorine substitution (

This study focused genetic pathogenesis and tumor microenvironment of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCL) in patients without immunodeficiency. DNA samples from these cases were sequenced by next generation sequencing (NGS) using a selected gene panel. Results revealed that most gene mutations were not specific for EBV positive DLBCL. However, B2M (β2-microglobulin) mutations were significantly increased and HLA-I or HLA-II expression was decreased in these cases, which was related to patient's poor outcome. B2M mutations and deregulation of B2M expression were further confirmed by Sanger sequencing and immunohistochemistry. Reducing the infiltration of CD8+ T lymphocytes, related to decreased expression of HLA-I or HLA-II was found in these patients. These results suggest that the mutations of B2M could cause the disruption of the expression and functions of this important subunit of HLA, leading to decreased expression of HLA-I or HLA-II and subsequently to reduce T lymphocyte infiltration in tumor tissues. The consequence of this event lessens the recognition and elimination of EBV+ tumor cells by host immunity and paves the way for the host immune tolerance to EBV+ tumor cells by evading immune recognition and escaping the T lymphocyte killing.

A new family of π-extended BODIPY derivatives were obtained through the condensation of aldehyde and pyrrole in aqueous solution in the presence of HCl. The new rigid π-framework extends beyond the dipyrromethene unit, which is significantly different from classical BODIPYs in the electronic configuration. Both π-extended BODIPYs displayed intense absorption and moderate emission with maxima around 565 and 620 nm, respectively, and showed interesting reactivity toward various nucleophiles. Moreover, these π-extended BODIPYs were developed as fluorescent probes for rapid and selective detection of GSH and were successfully applied for live-cell imaging.

We describe a straightforward, postmodification synthesis for a family of thiophene-fused BODIPY dimers and tetramers through transforming flexible sulfur bridges into coplanar thiophene fusions. FeCl3 was used as a bifunctional oxidant for both intramolecular and intermolecular oxidative aromatic coupling reactions. Oxidative fusion and dimerization gave strong red-shift absorptions from 509 nm for a BODIPY monomer to 830 nm for a tetramer.

Two pyrrolyl-BODIPY dyes with 3,5-di-[Formula: see text]-butyl-4-hydroxyphenyl group were synthesized through stepwise S[Formula: see text]Ar reactions of 3,5-dibromoBODIPYs, which were used as a fluorescent sensor for basic anions. The intermediate pyrrolyl-BODIPYs 2a–2b were regioselectively synthesized through an efficient S[Formula: see text]Ar reaction between 3,5-dibromoBODIPY 1a and pyrroles. The target pyrrolyl-BODIPYs 3a–3b with a 3,5-di-[Formula: see text]-butyl-4-hydroxyphenyl group at 3-position and a pyrrole substituent at 5-position were obtained through a second S[Formula: see text]Ar reaction between pyrrolyl-BODIPYs 2a–2b and high steric hindrance 2,6-dibutylphenol in 90% and 88% yields, respectively. In contrast, the reaction between pyrrolyl-BODIPYs 2a–2b and phenol gave pyrrolyl-BODIPYs 3c–3d with phenoxy substituent at 3-position. These pyrrolyl-BODIPYs 3a–2d show strong, sharp absorptions (551–604 nm) and emissions (564–634 nm) with high fluorescence quantum yields up to 0.86 in dichloromethane. Importantly, the 3,5-di-[Formula: see text]-butyl-4-hydroxyphenyl group of pyrrolyl-BODIPY 3a showed a turn-off fluorescent response toward fluoride anion.

Tetracoordinated organoboron dyes exhibiting strong fluorescence in either solution or the solid state are currently receiving much attraction in view of their photovoltaic, optoelectronic, and biological applications. Herein, a series of aromatic-ring-fused BOPPY dyes have been developed by one-pot condensation of formylated isoindoles or indoles and pyridinylhydrazine followed by subsequent borylation coordination. The facile synthesis provides excellent diversity of these unsymmetrical α-benzo- and β-benzothiophene-fused BOPPY dyes with intriguing photophysical properties owing to their rigid and planar structure and extended π-conjugation while containing a reactive site. They display intense green to orange fluorescence in solution and red-to-near-infrared emission in the solid state, with high fluorescence quantum yields up to 92 and 21%, respectively, relatively large Stokes shifts, and excellent photostability. Furthermore, two representative benzo-fused BOPPY probes with morpholine or benzenesulfonamide groups were developed and used to selectively "light up" the subcellular organelles such as lysosomes and endoplasmic reticulum under ultralow concentration, respectively.

Organic small-molecule fluorescent chromophores have become essential to modern chemical, biological, and materials related investigations. Herein, a straightforward synthesis and subsequent borylation were presented to form a novel family of bisBF2-anchoring acyl-pyridinylhydrazine, which we named BOAPH. The chromophore enjoys outstanding structural diversities owing to varied acyl chlorides and N-heteroarenylhydrazides. These resultant BOAPH dyes are confirmed by NMR, HRMS, and single-crystal X-ray structure analysis. Their spectroscopic properties were studied, and most of the strong absorbance and bright fluorescence with maximum wavelengths centered in the range of 400 and 650 nm. More importantly, they exhibit promising fluorescence quantum yields up to 0.79 in solution and solid states, good photostability, and large Stokes shifts. Furthermore, a respective BOAPH dye with a para-dimethylaminophenyl group exhibited the interesting ability of ultrafast staining and two-photon imaging, which can specifically label lipid droplets of living cells immediately without the need for incubation.

Hypoxia severely impedes the therapeutic efficacies of tumor chemotherapy, radiotherapy and conventional photodynamic therapy (type II PDT). Herein, we proposed a nonplanar near-infrared (NIR)-absorbing hyperthermia and superoxide radical (O2−•) photogenerator (TB) against hypoxic tumors. TB particularly possessed a favorable O2−• generation capability under 808 nm laser irradiation with the donor-acceptor-donor (D-A-D) molecular structure. Moreover, owing to molecular rotation, potent hyperthermia was realized under continuous laser irradiation. For the usage of hypoxic tumor treatment, TB was encapsulated by a block copolymer, poly(ethylene glycol)-b-poly(latic acid) (PEG45-b-PLA24), to fabricate phototheranostic nanoparticles (TB NPs). Due to the twisted molecular structure and the shielding effect of long alkyl chains, the π-π stacking-induced quenching of O2−• could be reduced after the fabrication of nano-assemblies. Significantly, TB NPs exhibited satisfactory O2−• generation for type I PDT and a simultaneously distinct photothermal conversion efficiency (PCE, 62%) for photothermal therapy (PTT) to combat hypoxic tumor cells. Moreover, the high PCE endowed TB NPs with high performance photoacoustic (PA) and photothermal imaging capability. In vivo experiments demonstrated that TB NPs possessed an outstanding phototherapeutic efficacy for eradicating hypoxic tumors. This study established a novel approach for constructing oxygen-independent phototherapeutic reagent against hypoxic tumors.

A new family of N2O-type hydrazine-containing bipyrrole boron complexes has been developed via a one-pot condensation of formylisoindole, hydrazine, and various organoboronic acids. Because of the conformation-restricted coplanar structure and the axial-substituted aryl groups, these novel dyes show deep-red absorption, bright near-infrared (NIR) fluorescence in both solution and solid states, and good solubility in organic solvents. The derivative with pyridinium ions also has been synthesized as an NIR mitochondrially targetable fluorescent probe.

The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

Lipid droplets (LDs) and lysosomes, as two important subcellular organelles, play specific and indispensable roles in various cellular processes. The development of efficient LD- and lysosome-specific fluorescent bio-probes is of great importance. However, current commercial lipid droplet- (LD) and lysosome-specific fluorescent specific bio-probes often suffer from the aggregation-caused quenching (ACQ) effect, short absorption and emission wavelengths, poor photostability and low specificity. Herein, a typical ACQ luminogen BODIPY was directly conjugated to strong electron donating triarylamine units at its α-positions, giving near-infrared (NIR) fluorescent materials TPAB and 2TPAB with aggregation-induced emission (AIE). Both TPAB and 2TPAB nanoparticles were obtained by self-assembly, and showed NIR emissions, large Stokes shifts, good photostability and two-photon absorption. These nanoparticles presented remarkable bioimaging performances and were shown to specifically localize in LDs or lysosomes, respectively, depending on the number of triarylamine units attached. They have been successfully used to detect endogenous LD overproduction, and monitor abnormal activities of LDs/lysosomes, as well as real-time track the lipophagy process in cells. Their far NIR emission and two-photon excitation further supported their promising bioimaging application for lipid droplet tracking in liver tissue and live zebrafish larvae. Our work here enriches BODIPY based NIR AIE dyes and provides organelle specific bio-probes which are superior to currently used commercial ones.

A new class of tailor-made push-pull isoindole fluorophores has been synthesized through the combination of Suzuki coupling and Knoevenagel reactions. The efficient synthetic strategy rendered the isoindole scaffold as the π-bridge and the isolation spacer and provided dyes bearing various types of electron donors and electron acceptors for manipulating their energy gaps and tuning their absorptions and emissions. Most of the

Primary central nervous system lymphomas (PCNSLs) often present a unique histopathological feature of aggregative perivascular tumor cells (APVT). Our previous studies showed that patients of PCNSL with APVTs exhibited poor long-term outcomes and increased expression of the endoplasmic reticulum stress (ERS) factor X-box-binding protein (XBP1). However, very little is known about molecular mechanism of the APVT formation in PCNSLs. The aim of this study is to determine if hypoxia-induced ERS is related to the APVT formation in PCNSLs. In this study, cell culture was used to observe the interplay between diffuse large B cell lymphoma (DLBCL) tumor cells and human brain microvascular endothelial cells (HBMECs) in different oxygen conditions. The expression of XBP1, CXCR and CD44 was manipulated by molecular cloning and siRNA technology. Mouse in vivo experiments and clinical studies were conducted to confirm our hypothesis. Our results showed that activated B-cell type-DLBCL cells easily migrated and invaded, and expressed high levels of XBP1 and stromal molecules CXCR4 and CD44 during hypoxia-induced ERS and dithiothreitol unfolded protein response (UPR). The gene upregulation (using overexpression vector) and downregulation (siRNA gene knock-out) in cultured cells and in mouse models further confirmed a close relation of the expression of XBP1, CXCR4, and CD44 with APVT formation, which is coincided with our clinical observation that increased expression of XBP1, CXCR4, and CD44 in the APVT cells in PCNSLs were associated with poor clinical outcomes. The results suggest that hypoxia-induced ERS and UPR might be associated with APVTs formation in PCNSL and its poor clinical outcomes. The results will help us better understand the progression of PCNSL with APVTs feature in daily pathological work and could be valuable for future target treatment of PCNSLs.

The 1D microwires based on π-extended azaBODIPY were successfully prepared and characterized for the first time. The bisphenanthrene-fused azaBPP-12C with four hydrophobic chains was prepared through de novo synthesis method involving the Suzuki reaction and subsequent oxidative ring-fused coupling. The microwires and aggregation behavior were studied using SEM, XRD and absorption spectroscopy. Finally, an H-type aggregation was confirmed in the solution process.

The direct 3,3'-dimerization of BODIPYs lacking substituent groups in the 1,2,6, and 7 positions was developed by oxidative coupling with FeCl3. This regioselective dimerization was achieved for BODIPYs substituted only in the 5-position with Cl or aryl groups. Further functionalization of the 5,5'-dichloride dimer gave the corresponding pyrrole or 4-(2-aminoethyl)morpholine disubstituted dimers 2f and 2g, respectively. While dimer 2f exhibited intense NIR absorption/emission maxima at 773/827 nm in toluene, dimer 2g showed favorable lysosome-targeting NIR fluorescence in living cells.

Lipid droplets (LDs) have been found to be innate immune first-responders integrating cell metabolism and host defense. The abnormal changes of LDs have been believed to be highly associated with many diseases such as metabolic diseases, cardiovascular disease, viral infections and cancer. Two organic LD-specific nanoprobes have been self-assembled from α-tetraphenyletheneBODIPYs, which exhibited bright near-infrared aggregated state emission with high fluorescence quantum yields up to 0.81 in aqueous system and high photostability, as well as large Stokes shifts up to 130 nm. In the solid powder state, they showed strong NIR fluorescence with red-shifted emission peaks at 700 and 790 nm. The recorded high NIR fluorescence in solid state and in water-induced aggregates can be ascribed to the steric hindrance provided by the TPE groups, which prohibits the π–π interactions of BODIPY planes and avoids the aggregation-caused quenching (ACQ) effect in the BODIPY emission. More importantly, these NIR-emitting nanoprobes exhibit higher LD-specificity than commercial LD-specific BODIPY 493/503 and have been applied for the real-time imaging of intracellular LD and lipid-rich yolk sac of the zebrafish larvae, and monitoring of the LD–lysosome interplay in living cells, which is useful for the early diagnosis of LD-related diseases.

A direct and regioselective C-H/P-H cross-coupling of dialkyl phosphites, and diphenylphosphine oxide to easily available BODIPYs through an Ag-mediated radical addition, resulted in a series of new α-phosphorylated BODIPY fluorophores under mild conditions. Hydrolysis of the phosphonate gave the corresponding BODIPY phosphoric acid, which is soluble and fluorescent in water with a high quantum yield of 0.83.

By taking advantage of their intense visible-light absorptions, a photoinduced, AgI promoted oxidative dimerization of BODIPY dyes was developed to give structurally unprecedented α,α- and α,γ-linked dimers. In contrast to classical oxidative aromatic coupling, this methodology does not need a strong oxidant and relies on the singlet electron transfer process between excited-state BODIPYs and an electron acceptor to generate BODIPY based radical species.

Azadipyrromethene derived polycyclic aromatic complexes (HBPs) containing thirteen fused rings have been synthesized, which show highly selective intense absorption in the near infrared spectrum (NIR) region with high photo- and thermo-stability. The periphery alkoxy and alkyl substituents greatly affect their molecular packing structures in thin films and their thin film transistor performances. With the simple changes of the alkyl substituents, the packing structures changed from discrete-grain with H -aggregation type absorption to lamellar packing with J -aggregation type absorption, and the semiconducting properties were modulated from p -type to interesting ambipolar-type in solution-processed organic field effect transistors (OFETs) with hole and electron mobilities reaching to 0.42 and 0.17 cm2 V−1 s−1, respectively.

A photoredox-mediated route to enamination of boron dipyrromethene (BODIPY) dyes with aliphatic amines is reported by activating both the β-C­(sp3)–H bond of amines and the α-C­(sp2)–H bond of BODIPYs under visible light illumination. Dehydrogenation of amines by excited-state BODIPYs and/or photoredox catalyst gave enamine intermediates, which were further trapped by BODIPYs to give a series of α-enamineBODIPYs. These resultant α-enamineBODIPYs showed red-shifted absorption and emission maxima with ratiometric pH-dependent fluorescence.

Photodynamic therapy (PDT) is a minimally invasive technique for the treatment of target malignant tumors via the generation of highly reactive singlet oxygen species. PDT treatment of cancer/tumor tissues greatly relies on the development of suitable stable, highly specific and efficient photosensitizers. BODIPY (Boron dipyrromethene) derivatives, as a class of well-developed, versatile fluorescent dyes, has emerged as a new class of PDT agents over the past decade. Many elegant strategies have been developed to enhance the singlet oxygen generation efficiency and the cancer/tumor cell selectivity of BODIPY-based photosensitizers to improve the therapeutic outcomes as well as to minimize the side effects. Many of the currently reported BODIPY-based photosensitizers are valuable dual imaging and therapeutic agents, which can efficiently generate singlet oxygen for PDT and emit fluorescence for in vivo imaging. Although the currently approved PDT agents used for clinical trials do not feature BODIPYs, this situation is expected to change. In this review, we provide an overview of the various strategies that have been used to improve the singlet oxygen generation efficiency for tuning BODIPY fluorophores into photosensitizers and dual imaging/therapeutic agents. Their photophysical properties and photocytotoxic activity including the absorption/emission wavelengths, the singlet oxygen generation efficiency ([Formula: see text] and the half maximal inhibitory concentration [Formula: see text] of these currently reported photosensitizers are summarized. We believe these newly developed BODIPY-based photosensitizers will broaden current concepts of strategies for PDT agent design, and promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer.

A new family of pyrrolyl–acylhydrazones anchored with two BF2 units, named BOAPY, have been developed as BODIPY-like and unsymmetrical bis(BF2) chromophores via a simple one-pot reaction. The easil...

Estrogen deficiency is considered to be an important factor leading to cardiovascular diseases (CVDs). Indeed, the prevalence of CVDs in postmenopausal women exceeds that of premenopausal women and men of the same age. Recent research findings provide evidence that estrogen plays a pivotal role in the regulation of calcium homeostasis and therefore fine-tunes normal cardiomyocyte contraction and relaxation processes. Disruption of calcium homeostasis is closely associated with the pathological mechanism of CVDs. Thus, this paper maps out and summarizes the effects and mechanisms of estrogen on calcium handling proteins in cardiac myocytes, including L-type Ca2+ channel, the sarcoplasmic reticulum Ca2+ release channel named ryanodine receptor, sarco(endo)plasmic reticulum Ca2+-ATPase, and sodium-calcium exchanger. In so doing, we provide theoretical and experimental evidence for the successful design of estrogen-based prevention and treatment therapies for CVDs.

Far-red and near-infrared (NIR) absorbing/emitting dyes have found diverse applications in biomedicine and material science. However, the absorption and emission of classical BODIPY chromophores at short wavelength hamper their applications. Several strategies have been adopted to modify the structure of the BODIPY core to design NIR dyes. Among these, the most efficient approach to expand the π-conjugation of the BODIPY core is via fusion of aromatic rings. So far, many novel BODIPY skeletons fused to aromatic hydrocarbons and heterocycles at the b bond have been reported. This review comprehensively describes the recent advances regarding the development of aromatic [b]-fused BODIPY dyes with the focus on the design and synthesis, the relationships between their photophysical/spectroscopic properties and molecular structures, and the potential applications in bioassays and optoelectronic devices.

Here, we report the synthesis of two isomeric BODIPY-based fluorescent molecules with a diethylamino donor group and an acetyl acceptor group at positions 5 and 2 (or 3), respectively, on the boron dipyrromethene core. The structure of the new BODIPY dyes is similar to Prodan, probably the most widely used solvatochromic probe, but with the donor and acceptor groups attached to an electron-poor heteroaromatic core. Interestingly, these BODIPY dyes exhibit unusual spectroscopic and photophysical properties, involving inverse solvatochromic behavior. An in-depth study of the solvent effects and quantum-chemical calculations have been performed to assess the basis for such spectroscopic properties and the effect of the position of the substitution. This work points towards a rational design of new fluorescent probes, based on understanding their spectroscopic and photophysical behavior.

A series of five BODIPY derivatives with triarylamine (TPA) moieties on their 3-, 5-, or 8-positions were reported, which showed wide-range fluorescence emissions across red and near infrared regions in their aggregation states. The influences of numbers and substituted positions of TPA groups on the optical and aggregation-induced emission (AIE) properties of these BODIPYs as well as organelle-specific imaging in live cells were investigated. The TPA groups installed at 3-/5-positions of BODIPY could effectively enlarge the conjugated system and red-shift the absorption and emission bands (λ