Electronic properties of single vacancy defect in boron nitride nanoribbons with edge perturbation.

Two-dimensional material hexagonal boron nitride (h-BN), and its one-dimensional thin strips, boron nitride nanoribbons (BNNRs) are electrically insulating with high thermal stability, making them excellent thermal conductors suitable for high-temperature application. BNNRs are wide bandgap semiconductors with bandgaps ranging from 4 to 6 eV. This study investigates the electronic properties of BNNRs with single vacancy defects in armchair and zigzag configurations. The nearest-neighbour tight-binding model and numerical method were used to simulate the electronic properties of BNNRs with a single vacancy, including band structure and local density of states. The alpha and beta matrices were adjusted to account for missing boron or nitrogen atoms. Furthermore, a small perturbations were introduced to model the effects of impurities and edge imperfections. The simulation result from this work was compared with pristine BNNRs to examine the impact of a single vacancy on their electronic properties. The findings reveal that both armchair and zigzag BNNRs with single vacancy defects exhibit distorted band structures and local density of states due to the delocalization of pz orbitals. The valence bands show a higher concentration of nitrogen, while the conduction bands are richer in boron. These findings provide insights into how vacancy defects and edge perturbations can influence the electronic properties of BNNRs, which can guide the design and optimization of BNNR-based electronic devices in future research.

Molecular Engineering of a Doubly Quenched Fluorescent Probe Enables Ultrasensitive Detection of Biothiols in Highly Diluted Plasma and High-Fidelity Imaging of Dihydroartemisinin-Induced Ferroptosis.

The occurrence and development of diseases are accompanied by abnormal activity or concentration of biomarkers in cells, tissues, and blood. However, the insufficient sensitivity and accuracy of the available fluorescence probes hinder the precise monitoring of associated indexes in biological systems, which is generally due to the high probe intrinsic fluorescence and false-negative signal caused by the reactive oxygen species (ROS)-induced probe decomposition. To resolve these problems, we have engineered a ROS-stable, meso-carboxylate boron dipyrromethene (BODIPY)-based fluorescent probe, which displays quite a low background fluorescence due to the doubly quenched intrinsic fluorescence by a combined strategy of the photoinduced electron transfer (PET) effect and "ester-to-carboxylate" conversion. The probe achieved a high S/N ratio with ultrasensitivity and good selectivity toward biothiols, endowing its fast detection capability toward the biothiol level in 200×-diluted plasma samples. Using this probe, we achieved remarkable distinguishing of liver injury plasma from normal plasma even at 80× dilution. Moreover, owing to its good stability toward ROS, the probe was successfully employed for high-fidelity imaging of the negative fluctuation of the biothiol level in nonsmall-cell lung cancer (NSCLC) during dihydroartemisinin-induced ferroptosis. This delicate design of suppressing intrinsic fluorescence reveals insights into enhancing the sensitivity and accuracy of fluorescent probes toward the detection and imaging of biomarkers in the occurrence and development of diseases.

A New BODIPY-Based Receptor for the Fluorescent Sensing of Catecholamines.

The human body synthesizes catecholamine neurotransmitters, such as dopamine and noradrenaline. Monitoring the levels of these molecules is crucial for the prevention of important diseases, such as Alzheimer's, schizophrenia, Parkinson's, Huntington's, attention-deficit hyperactivity disorder, and paragangliomas. Here, we have synthesized, characterized, and functionalized the BODIPY core with picolylamine (BDPy-pico) in order to create a sensor capable of detecting these biomarkers. The sensing properties of the BDPy-pico probe in solution were studied using fluorescence titrations and supported by DFT studies. Catecholamine sensing was also performed in the solid state by a simple strip test, using an optical fiber as the detector of emissions. In addition, the selectivity and recovery of the sensor were assessed, suggesting the possibility of using this receptor to detect dopamine and norepinephrine in human saliva.

Nanoparticles destabilizing the cell membranes triggered by NIR light for cancer imaging and photo-immunotherapy.

Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (Pmt) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (PBodipy). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NPBodipy) which could further accumulate at the tumor and destroy cell membranes through electrostatic interactions, resulting in cell membrane destabilization. Meanwhile, the photosensitizer Bodipy produces ROS to induce damage to cell membranes, proteins, and DNAs to kill cancer cells concertedly, finally resulting in cell membrane lysis and cancer cell death. This work highlights the use of near-infrared light to spatially and temporarily control cationic polymers for photodynamic therapy, photo-immunotherapy, and NIR-II fluorescence for bio-imaging.

A highly fluorescent and readily accessible all-organic photosensitizer model for advancing image-guided cancer PDT.

The potential of using image-guided photodynamic therapy (ig-PDT) for cancer, especially with highly biocompatible fluorescent agents free of heavy atoms, is well recognized. This is due to key advantages related to minimizing adverse side effects associated with standard cancer chemotherapy. However, this theragnostic approach is strongly limited by the lack of synthetically-accessible and easily-modulable chemical scaffolds, enabling the rapid design and construction of advanced agents for clinical ig-PDT. In fact, there are still very few ig-PDT agents clinically approved. Herein we report a readily accessible, easy-tunable and highly fluorescent all-organic small photosensitizer, as a model design for accelerating the development and translation of advanced ig-PDT agents for cancer. This scaffold is based on BODIPY, which assures high fluorescence, accessibility, and ease of performance adaptation by workable chemistry. The optimal PDT performance of this BODIPY dye, tested in highly resistant pancreatic cancer cells, despite its high fluorescent behavior, maintained even after fixation and cancer cell death, is based on its selective accumulation in mitochondria. This induces apoptosis upon illumination, as evidenced by proteomic studies and flow cytometry. All these characteristics make the reported BODIPY-based fluorescent photosensitizer a valuable model for the rapid development of ig-PDT agents for clinical use.

Ixazomib in POEMS syndrome: 'Ixa'ctly what we need?

The role of the proteasome inhibitor ixazomib in the treatment of POEMS syndrome continues to evolve. He and colleagues present the results of a study investigating ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed POEMS patients. The triplet showed excellent efficacy and tolerability, and constitutes an effective treatment option for patients with POEMS. Commentary on: He et al. An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly-diagnosed POEMS syndrome. Br J Haematol 2024;205:478-482.

Constructing Heavy-Atom-Free Photosensitizers for Hypoxic Tumor Phototherapy Based on Donor-Excited Photoinduced Electron-Transfer-Driven Type-I and Type-II Mechanisms.

The spin-orbit charge transfer intersystem crossing (SOCT-ISC) photophysical process has shown great potential for constructing heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) of tumors. However, for almost all such PSs reported to date, the SOCT-ISC is driven by the acceptor-excited photoinduced electron transfer (a-PeT). In this work, for the first time the donor-excited photoinduced electron transfer (d-PeT)-driven SOCT-ISC mechanism is utilized to construct the heavy-atom-free PSs for PDT of tumors by directly installing the electron-deficient N-alkylquinolinium unit (as an electron acceptor) into the meso-position of the near-infrared (NIR) distyryl Bodipy chromophore (as an electron donor). In the less polar environment, the PSs exist as the monomer and promote the production of singlet oxygen (1O2) (Type-II) relying on the d-PeT-driven population of the triplet excited state via SOCT-ISC, whereas in the aqueous environment, they exist as nanoaggregates and induce the generation of superoxides (O2-•) and hydroxyl radicals (HO•) (Type-I) via the d-PeT-driven formation of the delocalized charge-separated state. The PSs could rapidly be internalized into cancer cells and induce the simultaneous production of intracellular 1O2, O2-•, and HO• upon NIR light irradiation, endowing the PSs with superb photocytotoxicity with IC50 values up to submicromolar levels whether under normoxia or under hypoxia. Based on the PSs platform, a tumor-targetable PS is developed, and its abilities in killing cancer cells and in ablating tumors without damage to normal cells/tissues under NIR light irradiation are verified in vitro and in vivo. The study expands the design scope of PSs by introducing the d-PeT conception, thus being highly valuable for achieving novel PSs in the realm of tumor PDT.

BODIPY in Alzheimer's disease diagnostics: A review.

Timely diagnosis and therapy of Alzheimer's disease remains one of the greatest questions in medicinal chemistry of neurodegenerative disease. The lack of low-cost sensors capable of reliable detection of structural changes in AD-related proteins is the driving factor for the development of novel molecules with affinity for AD hallmarks. The development of cheap, safe diagnostic methods is a highly sought-after area of research. Optical fluorescent probes are of great interest due to their non-radioactivity, low cost, and ability of the real-time visualization of AD hallmarks. Boron dipyrromethene (BODIPY)-based fluorophore is one promising fluorescent unit for in vivo labeling due to its high photostability, easy modification, low toxicity, and cell-permeability. In recent years, many fluorescent BODIPY-based probes capable of Aß plaque, Aß soluble oligomers, neurofibrillary tangles (NFT) optical detection, as well as probes with copper ion chelating units and viscosity sensors have been developed. In this review, we summarized BODIPY derivatives as fluorescent sensors capable of detecting pathological features of Alzheimer's disease, published from 2009 to 2023, as well as their design strategies, optical properties, and in vitro and in vivo activities.

Advancements in boron difluoride formazanate dyes for biological imaging.

In the past decade, boron difluoride formazanate dyes have gained considerable attention due to their redox activity, high absorption and emission intensities, chemical stability across a broad range of conditions, and the ease to fine-tune their optical and electronic characteristics. Over the past five years, boron difluoride formazanate dyes have demonstrated their extended emission wavelengths in the near-infrared region, suggesting their potential applications in the field of biological imaging. This review provides an overview of the evolution of boron difluoride formazanate dyes, encompassing the structural variations and corresponding optical properties, while also highlighting their current applications in biological imaging fields.

Conductive/Insulating Bioinks with Multitechnology Compatibility and Adjustable Performance.

Conducting/insulating inks have received significant attention for the fabrication of a wide range of additive manufacturing technology. However, current inks often demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. Here, conductive/insulating bioinks based on two-dimensional materials are proposed. The conductive bioink, graphene (GR)-poly(lactic-co-glycolic acid) (PLGA), is prepared by introducing conductive GR into a degradable polymer matrix, PLGA, while the insulating bioink, boron nitride (BN)-PLGA, is synthesized by adding insulating BN. By optimizing the material ratios, this work achieves precise control of the electromechanical properties of the bioinks, thereby enabling the flexible construction of conductive networks according to specific requirements. Furthermore, these bioinks are compatible with a variety of manufacturing technologies such as 3D printing, electrospinning, spin coating, and injection molding, expanding their application range in the biomedical field. Overall, the results suggest that these conducting/insulating bioinks offer improved mechanical, electronic, and biological properties for various emerging biomedical applications.

Cell-cycle dependence on the biological effects of boron neutron capture therapy and its modification by polyvinyl alcohol.

Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.

Protein aggregation monitoring in cells under oxidative stress: a novel fluorescent probe based on a 7-azaindole-BODIPY derivative.

The development of new fluorescent probes as molecular sensors is a critical step for the understanding of molecular mechanisms. BODIPY-based probes offer versatility due to their high fluorescence quantum yields, photostability, and tunable absorption/emission wavelengths. Here, we report the synthesis and evaluation of a novel 7-azaindole-BODIPY derivative to probe hydrophobic proteins as well as protein misfolding and aggregation. In organic solvents, this compound shows two efficiently interconverting emissive excited states. In aqueous environments, it forms molecular aggregates with unique photophysical properties. The complex photophysics of the 7-azaindole-BODIPY derivative was explored for sensing applications. In the presence of albumin, the compound is stabilized in hydrophobic protein regions, significantly increasing its fluorescence emission intensity and lifetime. Similar effects occur in the presence of protein aggregates but not with other macromolecules like pepsin, DNA, Ficoll 40, and coconut oil. Fluorescence lifetime imaging microscopy (FLIM) and two-photon fluorescence microscopy on breast (MCF-7) and lung (A549) cancer cells incubated with this compound display longer fluorescence lifetimes and higher emission intensity under oxidative stress. Synchrotron FTIR micro spectroscopy confirmed that the photophysical changes observed were due to protein misfolding and aggregation caused by the oxidative stress. These findings demonstrate that this compound can serve as a fluorescent probe to monitor protein misfolding and aggregation triggered by oxidative stress.

A golgi targeting viscosity rotor for cancer diagnosis in living cells and tissues.

Unveiling the intricate relationship between cancer and Golgi viscosity remains an arduous endeavor, primarily due to the lack of Golgi-specific fluorescent probes tailored for viscosity measurement. Considering this formidable obstacle, we have triumphed over the challenge by devising a bespoke Golgi-specific viscosity probe, aptly named GOL-V. This ingenious innovation comprises the viscosity rotor BODIPY intricately tethered to the Golgi-targeting moiety benzsulfamide. GOL-V exhibits remarkable sensitivity to fluctuations in viscosity, the fluorescence intensity of GOL-V increased 114-fold when the viscosity value was increased from 2.63 to 937.28 cP. Owing to its remarkable capacity to suppress the TICT state under conditions of heightened viscosity. Moreover, its efficacy in sensitively monitoring Golgi viscosity alterations within living cells is also very significant. Astonishingly, our endeavors have culminated in not only the visualization of Golgi viscosity at the cellular and tissue levels but also in the clinical tissue samples procured from cancer patients. Harnessing the prowess of GOL-V, we have successfully demonstrated that Golgi viscosity could serve as a discerning marker for detecting the presence of cancer. The convergence of these exceptional attributes firmly establishes GOL-V as an immensely potent instrument, holding immense potential in the realm of cancer diagnosis.

Targeting a microbiota Wolbachian aminoacyl-tRNA synthetase to block its pathogenic host.

The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or heighten their likelihood. This relationship extends beyond humans; microbiota play vital roles in other organisms, including eukaryotic pathogens causing severe diseases. Notably, Wolbachia, a bacterial microbiota, is essential for parasitic worms responsible for lymphatic filariasis and onchocerciasis, devastating human illnesses. Given the lack of rapid cures for these infections and the limitations of current treatments, new drugs are imperative. Here, we disrupt Wolbachia's symbiosis with pathogens using boron-based compounds targeting an unprecedented Wolbachia enzyme, leucyl-tRNA synthetase (LeuRS), effectively inhibiting its growth. Through a compound demonstrating anti-Wolbachia efficacy in infected cells, we use biophysical experiments and x-ray crystallography to elucidate the mechanism behind Wolbachia LeuRS inhibition. We reveal that these compounds form adenosine-based adducts inhibiting protein synthesis. Overall, our study underscores the potential of disrupting key microbiota to control infections.

Boron Dipyrromethene-Based Nanotheranostic System for Sonophotoassisted Therapy and Simultaneous Monitoring of Tumor Immune Microenvironment Reprogramming.

Therapy-induced modulation of the tumor microenvironment (TME) to overcome the immunosuppressive TME is considered to be an opportunity for cancer treatment. However, monitoring of TME modulation during the therapeutic process to accurately determine immune responses and adjust treatment plans in a timely manner remains to be challenging. Herein, we report a carrier-free nanotheranostic system (CANPs) assembled by two boron dipyrromethene (BODIPY) dyes, a sonophotosensitizer C-BDP, and a nitric oxide (NO) probe amino-BODIPY (A-BDP). CANPs can exert combined sonophototherapeutic effects of C-BDP under ultrasound and light irradiation and simultaneously induce inflammatory TME, as well as emit bright fluorescence via A-BDP by monitoring tumor-associated macrophages (TAMs) repolarization through the released NO in vitro and in vivo. Of note, transforming growth factor-ß (TGF-ß) could be the key cytokine involved in the sonophototherapy-induced TME reprogramming. By virtue of high physiological stability, good biocompatibility, and effective tumor targetability, CANPs could be a potential nanotheranostic system for the simultaneous induction and detection of TME reprogramming triggered by sonophototherapy.

An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly diagnosed POEMS syndrome.

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

Gastrointestinal toxicities of proteasome inhibitor therapy.

PURPOSE: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib. METHODS: We conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characteristics of PI-related gastrointestinal adverse events. RESULTS: Our sample comprised 973 patients with PI exposure and stool studies ordered between January 2017 and December 2022. Of these, 193 patients (20%) had PI-related gastrointestinal toxicity based on clinical symptoms and stool study results. The most common symptom was diarrhea, present in 169 (88% of those with gastrointestinal toxicity). Twenty-two (11%) required hospitalization, and 71 (37%) developed recurrence of symptoms. Compared to bortezomib or carfilzomib, ixazomib had a longer interval from PI initiation to the onset of gastrointestinal symptoms (313 days vs 58 days vs 89 days, p = 0.002) and a significantly lower percentage of diarrhea-predominant presentation of gastrointestinal toxicity (71% vs 96% vs 91%, p = 0.048). CONCLUSION: While PI-related gastrointestinal toxicities have various presentations and courses based on different regimens, the vast majority of patients presented with milder disease behavior. Despite a considerably high rate of hospitalization and recurrence after treatment necessitating optimization of clinical management, our cohort demonstrates favorable outcomes without long-term consequences.

Molecular temperature descriptors as a novel approach for QSPR analysis of Borophene nanosheets.

Borophene nanosheets appear in various sizes and shapes, ranging from simple planar structures to complicated polyhedral formations. Due to their unique chemical, optical, and electrical properties, Borophene nanosheets are theoretically and practically attractive and because of their high thermal conductivity, boron nanosheets are suitable for efficient heat transmission applications. In this paper, temperature indices of borophene nanosheets are computed and these indices are employed in QSPR analysis of attributes like Young's modulus, Shear modulus, and Poisson's ratio of borophene nanosheets and borophene ß12 sheets. The regression model for the F-Temperature index is discovered to be the best fit for shear modulus, the reciprocal product connectivity temperature index is discovered to be fit for Poisson's ratio and the second hyper temperature index is discovered to be fit for Young's modulus based on the correlation coefficient.

A Pt nanoenzyme- and BODIPY-loaded nanoscale covalent organic framework for relieving intratumoural hypoxia to enhance photodynamic therapy.

Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.