Levodopa modulates semantic fluency and uniqueness in non-demented patients with progressive supranuclear palsy.

INTRODUCTION: Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP. METHODS: Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. RESULTS: The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. CONCLUSIONS: These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.

Synthesis and Regioselective Functionalization of Tetrafluorobenzo-[α]-Fused BOPYPY Dyes.

The synthesis of a new bis-BF2 tetrafluorobenzo-[α]-fused BOPYPY dye from 4,5,6,7-tetrafluoroisoindole and 2-hydrazinopyrazine is reported. The regioselectivity of nucleophilic substitution reactions at the periphery of the tetrafluorinated BOPYPY and its α-bromo derivative were investigated using N-, O-, S-, and C-based nucleophiles. Among the aromatic fluorine atoms, the F2 atom is consistently regioselectively substituted, except when the α-position contains a thiophenol group; in this case, F4 is substituted instead due to stabilizing π-π-stacking between the two aromatic groups. The α-bromo BOPYPY derivative also reacts under Stille cross-coupling reaction conditions to produce the corresponding α-substituted product. The spectroscopic properties of these new fluorinated BOPYPYs were investigated and compared with nonfluorinated analogs.

Impaired sequence manipulation in non-demented patients with progressive supranuclear palsy.

PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.

A Multi-Level Operation Method for Improving the Resilience of Power Systems under Extreme Weather through Preventive Control and a Virtual Oscillator.

This paper proposes a multi-level operation method designed to enhance the resilience of power systems under extreme weather conditions by utilizing preventive control and virtual oscillator (VO) technology. Firstly, a novel model for predicting time intervals between successive failures of the power system during extreme weather is introduced. Based on this, this paper proposes a preventive control method considering the system ramping and transmission constraints prior to failures so as to ensure the normal electricity demand within the system. Further, a VO-based adaptive frequency control strategy is designed to accelerate the regulation speed and eliminate the frequency deviation. Finally, the control performance is comprehensively compared under different experimental conditions. The results verify that the method accurately predicted the time of the line fault occurrence, with a maximum error not exceeding 3 min compared to the actual occurrence; also, the virtual oscillator control (VOC) strategy outperformed traditional droop control in frequency stabilization, achieving stability within 2 s compared to the droop control's continued fluctuations beyond 20 s. These results highlight VOC's superior effectiveness in frequency stability and control in power systems.

Machine learning-aided hydrothermal carbonization of biomass for coal-like hydrochar production: Parameters optimization and experimental verification.

Biomass to coal-like hydrochar via hydrothermal carbonization (HTC) is a promising route for sustainability development. Yet conventional experimental method is time-consuming and costly to optimize HTC conditions and characterize hydrochar. Herein, machine learning was employed to predict the fuel properties of hydrochar. Random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) models were developed, presenting acceptable prediction performance with R2 at 0.825---0.985 and root mean square error (RMSE) at 1.119---5.426, and XGB outperformed RF and SVM. The model interpretation indicated feedstock ash content, reaction temperature, and solid to liquid ratio were the three decisive factors. The optimized XGB multi-task model via feature re-examination illustrated improved generalization ability with R2 at 0.927 and RMSE at 3.279. Besides, the parameters optimization and experimental verification with wheat straw as feedstock further demonstrated the huge application potential of machine learning in hydrochar engineering.

Smaller and Denser Speech Graphs in Nondemented Patients with Progressive Supranuclear Palsy.

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further examined the difference between patients with PSP and PD in their semantic fluency performance using a graph theory-based approach. Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), thirty-eight patients with PD, and fifty-one healthy controls (HC) were recruited. All participants completed a standard semantic fluency test (animals). Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. The speech graphs of the PSP-RS group showed higher density, shorter diameter, and shorter average shortest path than those of the PD and HC groups. It indicates that the PSP-RS group produced smaller and denser speech graphs than the PD and HC groups. In the PSP-RS group, moreover, the average shortest paths of the speech graphs correlated with the severity of motor symptoms. This study shows the potential of the graph theory-based approach in distinguishing the semantic fluency performance of nondemented patients with PSP-RS and PD.

CO2-mediated catalytic upcycling of plastic waste for H2-rich syngas and carbon nanomaterials.

To establish a reliable disposal platform of plastic waste, this work developed a novel dual-stage CO2-medaited decomposition-catalysis route by applying multi-functional zeolite-supported bimetallic catalysts. Catalytic upcycling of plastic was first performed in Ar as a reference environment. Bimetallic Fe-Co/ZSM5 catalyst achieved the highest gas yield (53.98 mmol/g), with a H2 proportion of 62.17 vol%. It was evidenced that the Fe-Co alloy had an apparent positive synergistic effect on catalytic cracking and reforming of intermediate volatiles into H2-rich fuel gas and pure carbon nanotubes (CNTs). Regarding CO2-mediated decomposition-catalysis of plastic, there was an apparent synergistic effect between metallic Ni and Fe on gas production so that bimetallic Ni-Fe catalyst gained the maximum cumulative gas yield of 82.33 mmol/g, with a syngas purity of ∼74%. Ni-Fe/ZSM5 also achieved the maximum hydrogen efficiency (87.38%) and CO2-to-CO conversion efficiency (98.62%), implying hydrogen content in plastic and oxygen content in CO2 were essentially converted into gases. Additionally, bimetallic Ni-Fe catalyst revealed the highest carbon production (33.74 wt%), witnessing a synergistic enhancement of 43.45%; specially, approximately 257 mg/g CNTs were anchored on Ni-Fe/ZSM5, with a CNTs purity of over 76%. Overall, this study offers a superb solution in plastic waste valorization and greenhouse gas emission management.

Development and validation of a predictive nomogram for lower extremity deep vein thrombosis dislodgement in orthopedic patients.

Objective: To analyze the risk factors of lower extremity deep venous thrombosis (DVT) detachment in orthopedic patients, and to establish a risk nomogram prediction model. Methods: The clinical data of 334 patients with orthopedic DVT admitted to the Third Hospital of Hebei Medical University from January 2020 to July 2021 were retrospectively analyzed. General statistics included gender, age, BMI, thrombus detachment, inferior vena cava filter window type, filter implantation time, medical history, trauma history, operation, use of tourniquet, thrombectomy, anesthesia mode, anesthesia grade, operative position, blood loss during operation, blood transfusion, immobilization, use of anticoagulants, thrombus side, thrombus range, D-dimer content before filter implantation and during removal of inferior vena cava filter. Logistic regression was used to perform univariate and multivariate analysis on the possible factors of thrombosis detachment, screen out independent risk factors, establish a risk nomogram prediction model by variables, and internally verify the predictability and accuracy of the model. Results: Binary logistic regression analysis showed that Short time window filter (OR = 5.401, 95% CI = 2.338-12.478), lower extremity operation (OR = 3.565, 95% CI = 1.553-8.184), use of tourniquet (OR = 3.871, 95% CI = 1.733-8.651), non-strict immobilization (OR = 3.207, 95% CI = 1.387-7.413), non-standardized anticoagulation (OR = 4.406, 95% CI = 1.868-10.390), distal deep vein thrombosis (OR = 2.212, 95% CI = 1.047-4.671) were independent risk factors for lower extremity DVT detachment in orthopedic patients (P < 0.05). Based on these six factors, a prediction model for the risk of lower extremity DVT detachment in orthopedic patients was established, and the risk prediction ability of the model was verified. The C-index of the nomogram model was 0.870 (95% CI: 0.822-0.919). The results indicate that the risk nomogram model has good accuracy in predicting the loss of deep venous thrombosis in orthopedic patients. Conclusion: The nomogram risk prediction model based on six clinical factors, including filter window type, operation condition, tourniquet use, braking condition, anticoagulation condition, and thrombosis range, has good predictive performance.

In Vitro Effects of Waterborne Polyurethane 3D Scaffolds Containing Poly(lactic-co-glycolic acid)s of Different Lactic Acid/Glycolic Acid Ratios on the Inflammatory Response.

The physical and chemical properties of tissue engineering scaffolds have considerable effects on the inflammatory response at the implant site in soft tissue repair. The development of inflammation-modulating polymer scaffolds for soft tissue repair is attracting increasing attention. In this study, in order to regulate the inflammatory response at the implant site, a series of waterborne polyurethane (WPU) scaffolds with different properties were synthesized using polyethylene glycol (PEG), polycaprolactone (PCL) and poly (lactic acid)-glycolic acid copolymers (PLGAs) with three lactic acid/glycolic acid (LA/GA) ratios as the soft segments. Then, scaffolds were obtained using freeze-drying. The WPU scaffolds exhibited a porous cellular structure, high porosity, proper mechanical properties for repairing nerve tissue and an adjustable degradation rate. In vitro cellular experiments showed that the degradation solution possessed high biocompatibility. The in vitro inflammatory response of C57BL/6 mouse brain microglia (immortalized) (BV2) cells demonstrated that the LA/GA ratio of the PLGA in WPU scaffolds can regulate the external inflammatory response by altering the secretion of IL-10 and TNF-α. Even the IL-10/TNF-α of PU5050 (3.64) reached 69 times that of the control group (0.053). The results of the PC12 culture on the scaffolds showed that the scaffolds had positive effects on the growth, proliferation and differentiation of nerve cells and could even promote the formation of synapses. Overall, these scaffolds, particularly the PU5050, indeed prevent BV2 cells from differentiating into a pro-inflammatory M1 phenotype, which makes them promising candidates for reducing the inflammatory response and repairing nerve tissue. Furthermore, PU5050 had the best effect on preventing the transformation of BV2 cells into the pro-inflammatory M1 phenotype.

Directional emission of nanoscale chiral sources modified by gap plasmons.

Efficient manipulation of the emission direction of a chiral nanoscale light source is significant for information transmission and on-chip information processing. Here, we propose a scheme to control the directionality of nanoscale chiral light sources based on gap plasmons. The gap plasmon mode formed by a gold nanorod and a silver nanowire realizes the highly directional emission of chiral light sources. Based on the optical spin-locked light propagation, the hybrid structure enables the directional coupling of chiral emission to achieve a contrast ratio of 99.5%. The emission direction can be manipulated by tailoring the configuration of the structure, such as the positions, aspect ratios, and orientation of the nanorod. Besides, a great local field enhancement exists for highly enhanced emission rates within the nanogap. This chiral nanoscale light source manipulation scheme provides a way for chiral valleytronics and integrated photonics.

Computational Study of Mechanisms and Tether Length Effects of Rh-Catalyzed [3+2] and [3+2+1] Reactions of Ene/Yne-Vinylcyclopropanes.

DFT calculations have been applied to study the mechanisms of [3+2] and [3+2+1] reactions of ene/yne-vinylcyclopropanes (shorted as ene/yne-VCPs). The [3+2] reactions of ene/yne-VCPs start from C-C cleavage of cyclopropane (CP cleavage) to form six-membered rhodacycle, followed by alkene/alkyne insertion and reductive elimination. The [3+2+1] reactions have two competing pathways, one is the [3+2+1] pathway (CP cleavage, ene/yne insertion, CO insertion and reductive elimination) and the other is the [3+1+2] pathway (CP cleavage, CO insertion, ene/yne insertion and reductive elimination). The length of tether in substrates affects the ene/yne insertion steps in these cycloadditions, making some reactions fail or changing the reaction pathways. The reasons for these tether length effects are discussed.

Dual Activation Strategy to Achieve C-C Cleavage of Cyclobutanes: Development and Mechanism of Rh and Zn Cocatalyzed [4 + 2] Cycloaddition of Yne-Vinylcyclobutanones.

Reported here is the Rh and Zn cocatalyzed [4 + 2] cycloaddition of newly designed yne-vinylcyclobutanones, which can generate 5/6 or 6/6 bicyclic products with an all-carbon quaternary bridgehead center. The reaction has a broad scope and can realize chirality transfer from enantioenriched substrates to the cycloadducts. The key to the success of this [4 + 2] reaction is the introduction of a vinyl group to cyclobutanones, which helps the C-C cleavage of vinylcyclobutanones via oxidative addition. This C-C cleavage step is synergistically aided by Zn coordination to the carbonyl group of vinylcyclobutanones. Of the same importance, visual kinetic analysis and computational studies have been carried out to support the dual activation in the rate-determining C-C cleavage, to derive the rate law of the [4 + 2] reaction, to understand another role of Zn in helping the in situ generation of the cationic Rh catalyst and preventing catalyst deactivation, and to analyze the key transition states and intermediates involved.

Metasurface Enabled Photothermoelectric Photoresponse of Semimetal Cd3As2 for Broadband Photodetection.

The artificial engineering of photoresponse is crucial for optoelectronic applications, especially for photodetectors. Here, we designed and fabricated a metasurface on a semimetallic Cd3As2 nanoplate to improve its thermoelectric photoresponse. The metasurface can enhance light absorption, resulting in a temperature gradient. This temperature gradient can contribute to thermoelectric photoresponse through the photothermoelectric effect. Furthermore, power-dependent measurements showed a linearly dependent photoresponse of the Cd3As2 metasurface device, indicating a second-order photocurrent response. Wavelength-dependent measurements showed that the metasurface can efficiently separate photoexcited carriers in the broadband range of 488 nm to 4 µm. The photoresponse near the metasurface boundaries exhibits a responsivity of ∼1 mA/W, which is higher than that near the electrode junctions. Moreover, the designed metasurface device provided an anisotropic polarization-dependent photoresponse rather than the isotropic photoresponse of the original Cd3As2 device. This study demonstrates that metasurfaces have excellent potential for artificial controllable photothermoelectric photoresponse of various semimetallic materials.

Steam Gasification of Torrefied/Carbonized Wheat Straw for H2-Enriched Syngas Production and Tar Reduction.

Torrefaction/carbonization integrated with steam gasification of agricultural biomass for gas production and tar reduction was not investigated. The aim of this study was to evaluate the influence of the torrefaction/carbonization severity on H2-enriched syngas production and tar reduction during steam gasification of wheat straw (WS). The torrefaction/carbonization experiments were initially performed at 220-500 °C to examine the effect of pretreated temperature on the fuel properties of torrefied/carbonized WS. Then, the gasification temperature (700-900 °C) was optimized at 900 °C in terms of gas formation behaviors. Afterward, steam gasification of raw and torrefied/carbonized WS feedstocks was conducted. WS carbonized at 500 °C (WS-500) possessed the highest H2 concentration (54.21 vol%) and syngas purity (85.59%), while the maximum H2/CO molar ratio (1.83), high carbon conversion efficiency (90.33 C%) and cold gas efficiency (109.24%) were observed for WS torrefied at 280 °C. Notably, the cumulative gas yield, H2 yield, and syngas yield respectively reached 102.68 mmol/g, 55.66 mmol/g, and 87.89 mmol/g from steam gasification of WS-500. In addition, the carbonized WS feedstocks, especially WS-500, revealed a lower tar content. Simply put, integrating torrefaction/carbonization with steam gasification provided a novel and effective route to manufacture H2-enriched syngas with extremely low tar content from agricultural biomass.

A Comprehensive Hydrothermal Co-Liquefaction of Diverse Biowastes for Energy-Dense Biocrude Production: Synergistic and Antagonistic Effects.

Hydrothermal co-liquefaction (co-HTL) is a promising technology to valorize binary or even ternary biowastes into bioenergy. However, the complex biochemical compositions and unclear synergistic effect prevent the development of this technology. Thus, this study explored a comprehensive co-HTL of representative biowastes to investigate the synergistic and antagonistic effects. An apparent synergistic effect on biocrude yield was observed when sewage sludge was co-liquefied with cow manure or wheat straw. Further, the co-HTL of sewage sludge-cow manure was investigated in a detailed manner. The highest yield (21.84 wt%) of biocrude, with a positive synergistic effect (11.37%), the highest energy recovery (47.48%), and a moderate biocrude HHV (34.31 MJ/kg) were achieved from co-HTL at 350 °C for 30 min. Hydrochar and gas products were also characterized to unravel the reaction pathways. Accordingly, this work indicates that sewage sludge co-liquefied with other biowastes can serve as a multi-purpose solution for biowaste treatment and bioenergy production.

Graph Theoretical Analysis of Semantic Fluency in Patients with Parkinson's Disease.

Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic memory, working memory, and executive function. Semantic disfluency is a common problem in Parkinson's disease (PD) and Alzheimer's disease (AD). We demonstrated a graph theoretical analysis of semantic fluency in patients with PD (N = 86), patients with AD (N = 40), and healthy controls (HC, N = 88). All participants completed a standard animal fluency test. Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. Patients with PD generated fewer correct words than HC and more correct words than patients with AD. Patients with PD showed higher density, shorter diameter, and shorter average shortest path length than HC, but lower density, longer diameter, and longer average shortest path length than patients with AD. It suggests that patients with PD produced relatively smaller and denser speech graphs. Moreover, in PD, the densities of speech graphs correlated with the severity of non-motor symptoms, but not the severity of motor symptoms. The graph theoretical analysis revealed new features of semantic disfluency in patients with PD.

Investigations on the Synthesis, Reactivity, and Properties of Perfluoro-α-Benzo-Fused BOPHY Fluorophores.

The synthesis and reactivity of 3,8-dibromo-dodecafluoro-benzo-fused BOPHY 2 are reported, via SN Ar with O-, N- S- and C-nucleophiles, and in Pd(0)-catalyzed cross-coupling reactions (Suzuki and Stille). The resulting perfluoro-BOPHY derivatives were investigated for their reactivity in the presence of various nucleophiles. BOPHY 3 displays reversible color change and fluorescence quenching in the presence of bases (Et3 N, DBU), whereas BOPHY 7 reacts preferentially at the α-pyrrolic positions, and BOPHY 8 undergoes regioselective fluorine substitution in the presence of thiols. The structural and electronic features of the fluorinated BOPHYs were studied by TD-DFT computations. In addition, their spectroscopic and cellular properties were investigated; BOPHY 10 shows the most red-shifted absorption/emission (λmax 659/699 nm) and 7 the highest fluorescence (Φf =0.95), while all compounds studied showed low cytotoxicity toward human HEp2 cells and were efficiently internalized.

First-in-human safety, tolerability, and pharmacokinetics of SY-007, a prolonged action neuroprotective drug for ischemic stroke, in healthy Chinese subjects.

BACKGROUND AND PURPOSE: SY-007 is an interfering peptide designed to disrupt the cell death signaling of phosphatase and tensin homolog deleted on chromosome ten (PTEN) nuclear translocation during ischemic stroke. Preclinical studies indicated that rats treated with 1.5 mg/kg SY-007 in the middle cerebral artery occlusion (MACO) model had significantly reduced stroke lesion size even when administered 6 h after the stroke onset. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of ascending doses of SY-007 administered intravenously in healthy Chinese subjects. METHODS: A total of 78 healthy Chinese subjects were enrolled in the single ascending dose study (1-60 mg) and received a 15-min intravenous infusion SY-007 or placebo. Plasma concentrations of SY-007 were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined using non-compartmental and compartment analyses. A model based on target-mediated drug disposition was applied. Model evaluation was performed through visual predictive checks and bootstrap analysis. RESULTS: Across doses of 1-60 mg, SY-007 was well tolerated. All adverse events (AEs) were mild or moderate in intensity, and all resolved without intervention. After infusion, SY-007 plasma concentrations decreased quickly with the mean terminal half-life was shorter than 0.78 h. The area under the concentration-time curve increased with a greater than dose-dependent manner from 1 to 30 mg and resulted in a dose-dependent increased from 30 to 60 mg. The nonlinear phenomenon was well described by a simplified target-mediated drug disposition (TMDD) model. CONCLUSIONS: Intravenous dosing of SY-007 appears to be safe up to a dose of 60 mg. Nonlinear pharmacokinetics was observed across the evaluated doses and TMDD might be the primary reason. The effective dose of SY-007 for neuroprotective effect in patients with ischemic stroke is expected to be 10-30 mg and was recommended for the later multiple ascending dose study of SY-007. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04111523.

Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Syntheses and Investigations of Conformationally Restricted, Linker-Free α-Amino Acid-BODIPYs via Boron Functionalization.

A series of α-amino acid-BODIPY derivatives were synthesized using commercially available N-Boc-l-amino acids, via boron functionalization under mild conditions. The mono-linear, mono-spiro, and di-amino acid-BODIPY derivatives were obtained using an excess of basic (histidine, lysine, and arginine), acidic (aspartic acid), polar (tyrosine, serine), and nonpolar (methionine) amino acid residues, in yields that ranged from 37 to 66%. The conformationally restricted mono-spiro- and di-amino acid-BODIPYs display strong absorptions in the visible spectral region with high molar extinction coefficients and significantly enhanced fluorescence quantum yields compared with the parent BF2-BODIPY. Cellular uptake and cytotoxicity studies using the human HEp2 cell line show that both the presence of an N,O-bidentate spiro-ring and basic amino acids (His and Arg) increase cytotoxicity and enhance cellular uptake. Among the series of BODIPYs tested, the spiro-Arg- and spiro-His-BODIPYs were found to be the most cytotoxic (IC50 ∼ 22 µM), while the spiro-His-BODIPY was the most efficiently internalized, localizing preferentially in the cell lysosomes, ER, and mitochondria.