Honokiol-induced SIRT3 upregulation protects hippocampal neurons by suppressing inflammatory processes in pilocarpine-induced status epilepticus.

Status epilepticus (SE), a continuous and self-sustaining epileptic seizure lasting more than 30 min, is a neurological emergency that can cause severe brain injuries and increase the risk for the development of epilepsy. Over the past few decades, accumulating evidence has suggested the importance of brain inflammation in the pathogenesis of epilepsy. Honokiol (HNK), a pharmacological activator of sirtuin 3 (SIRT3), is a bioactive compound extracted from the bark or leaves of Magnolia plants that possesses therapeutic benefits for preventing the development of inflammatory injury. However, the therapeutic effects of HNK against epileptic brain injury via regulating molecular mechanisms related to neuroinflammation remains elusive. Therefore, the present study investigated the effects of HNK on pilocarpine-induced status epilepticus (PCSE) and the therapeutic benefits of HNK in regulating inflammatory processes in the hippocampus. Treatment with HNK before PCSE induction attenuated the initiation of behavioral seizures. Post-treatment with HNK after SE onset increased SIRT3 expression, which mitigated glial activation, including reactive astrocytes and activated microglia, in the hippocampus following PCSE. Moreover, HNK treatment reduced the activation of the nuclear factor-κB/nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 inflammasome pathway, thereby inhibiting the production of interleukin-1ß pro-inflammatory cytokine, subsequently alleviating PCSE-triggered apoptotic neuronal death in the hippocampus. These results indicate that HNK-induced SIRT3 upregulation has the potential to prevent the progression of epileptic neuropathology through its anti-inflammatory properties. Therefore, the present study suggests that HNK is a natural therapeutic agent for epileptic brain injury.

Regenerative capacity of alveolar type 2 cells is proportionally reduced following disease progression in idiopathic pulmonary fibrosis-derived organoid cultures.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology. PURPOSE: This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. METHOD: Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells. RESULTS: FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells. CONCLUSION: This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Changes in mandibular width and frontal-lower facial profile after orthognathic surgery using sagittal split ramus osteotomy with removal of internal bone interference in patients with class III skeletal malocclusion.

BACKGROUND: The purpose of this study is to analyze changes in mandibular width and frontal view ramus inclination using cone beam CT in patients with skeletal class III malocclusion who underwent BSSRO, with the removal of bone interference between segments. METHODS: For all 20 subjects, cone-beam CT imaging was performed prior to surgery (T1), immediately post-surgery (T2), and 6 months after surgery (T3). Reorientation was performed using R2GATE software (MegaGen, Seoul, Korea). The gonion and antegonial notch were used as reference points in the sagittal view, and the most lateral point of the condyle head was used as the reference point in the frontal view. All measurements were recorded in the frontal view. RESULTS: Inter-gonial width decreased by 2.64 mm at T3-T2 (P < .001) and by 2.58 mm at T3-T1 (P < .05). Inter-antegonial width decreased by 1.75 mm at T3-T2 (P < .05) and by 3.5 mm at T3-T1 (P < .001). In the frontal view, the right ramus inclination based on the gonion increased by 2.07° at T3-T1 (P < .05). The left ramus inclination based on gonion increased by 2.45° at T2-T1 (P < .05) and by 3.94° at T3-T1 (P < .001). The right ramus inclination based on antegonial notch increased by 2.35° at T2-T1 (P < .05) and by 3.04° at T3-T1 (P < .01). The left ramus inclination based on antegonial notch increased by 2.73° at T2-T1 (P < .001) and by 3.18° at T3-T1 (P < .001). CONCLUSIONS: During bilateral sagittal split osteotomy, removing bone interference between the proximal and distal segments results in a reduction of postoperative mandibular width and an increase in frontal view ramus inclination.

Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway.

Protocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.

Orthognathic surgery with removal of lipoma in the asymmetric mandibular prognathism of a patient with a mandibular bone defect due to intramuscular lipoma on the medial aspect of the ramus: a case report.

Lipomas, the most common soft-tissue mesenchymal neoplasms in adults, are characterized by the proliferation of mature white adipocytes without cytologic atypia. Lipomas are rarely observed in the head and neck region. We present a case of resection and orthognathic surgical removal of an intramuscular lipoma of the mandible with involvement of the mandibular ramus and condylar head and neck. An 18-year-old female patient was referred to our hospital for orthognathic surgery for the management of facial asymmetry and mandibular prognathism. The patient did not present with facial swelling, pain, or temporomandibular dysfunction; however, on radiographic examination, including cone-beam computed tomography and magnetic resonance imaging, an infiltrative fatty lesion was observed in the masticator space inside the right mandible, and the adjacent mandible exhibited bone thinning and deformity. Resection of the lipoma was performed along with orthognathic surgery, including a Le Fort I osteotomy for the maxilla and bilateral sagittal split ramus osteotomy (BSSRO). In this case, because the ramus was split using BSSRO, accessing the lipoma intraorally was easy. Consequently, aesthetic scarring was avoided, and no complications, such as unfavorable splitting or pathologic fracture, occurred. Although recurrence has not been observed about 1 year, long-term follow-up should be performed.

Photocatalytic Conversion of CO2 to Formate/CO by an (η6-para-Cymene)Ru(II) Half-Metallocene Catalyst: Influence of Additives and TiO2 Immobilization on the Catalytic Mechanism and Product Selectivity.

The catalytic efficacy of the monobipyridyl (η6-para-Cymene)Ru(II) half-metallocene, [(p-Cym)Ru(bpy)Cl]+ was evaluated in both mixed homogeneous (dye + catalyst) and heterogeneous hybrid systems (dye/TiO2/Catalyst) for photochemical CO2 reduction. A series of homogeneous photolysis experiments revealed that the (p-Cym)Ru(II) catalyst engages in two competitive routes for CO2 reduction (CO2 to formate conversion via RuII-hydride vs CO2 to CO conversion through a RuII-COOH intermediate). The conversion activity and product selectivity were notably impacted by the pKa value and the concentration of the proton source added. When a more acidic TEOA additive was introduced, the half-metallocene Ru(II) catalyst leaned toward producing formate through the RuII-H mechanism, with a formate selectivity of 86%. On the other hand, in homogeneous catalysis with TFE additive, the CO2-to-formate conversion through RuII-H was less effective, yielding a more efficient CO2-to-CO conversion with a selectivity of >80% (TONformate of 140 and TONCO of 626 over 48 h). The preference between the two pathways was elucidated through an electrochemical mechanistic study, monitoring the fate of the metal-hydride intermediate. Compared to the homogeneous system, the TiO2-heterogenized (p-Cym)Ru(II) catalyst demonstrated enhanced and enduring performance, attaining TONs of 1000 for CO2-to-CO and 665 for CO2-to-formate.

Mosaicism-independent mechanisms contribute to Pcdh19-related epilepsy and repetitive behaviors in Xenopus.

Protocadherin19 (PCDH19)-related epilepsy syndrome is a rare disorder characterized by early-onset epilepsy, intellectual disability, and autistic behaviors. PCDH19 is located on the X chromosome and encodes a calcium-dependent single-pass transmembrane protein, which regulates cell-to-cell adhesion through homophilic binding. In human, 90% of heterozygous females, containing PCDH19 wild-type and mutant cells due to random X inactivation, are affected, whereas mutant males, containing only mutant cells, are typically not. The current view, the cellular interference, is that the altered interactions between wild-type and mutant cells during development, rather than loss of function itself, are responsible. However, studies using Pcdh19 knockout mice showed that the complete loss of function also causes autism-like behaviors both in males and females, suggesting that other functions of PCDH19 may also contribute to pathogenesis. To address whether mosaicism is required for PCDH19-related epilepsy, we generated Xenopus tropicalis tadpoles with complete or mosaic loss of function by injecting antisense morpholino oligonucleotides into the blastomeres of neural lineage at different stages of development. We found that either mosaic or complete knockdown results in seizure-like behaviors, which could be rescued by antiseizure medication, and repetitive behaviors. Our results suggest that the loss of PCDH19 function itself, in addition to cellular interference, may also contribute to PCDH19-related epilepsy.

Sirtuin 3 regulates astrocyte activation by reducing Notch1 signaling after status epilepticus.

Sirtuin3 (Sirt3) is a nicotinamide adenine dinucleotide enzyme that contributes to aging, cancer, and neurodegenerative diseases. Recent studies have reported that Sirt3 exerts anti-inflammatory effects in several neuropathophysiological disorders. As epilepsy is a common neurological disease, in the present study, we investigated the role of Sirt3 in astrocyte activation and inflammatory processes after epileptic seizures. We found the elevated expression of Sirt3 within reactive astrocytes as well as in the surrounding cells in the hippocampus of patients with temporal lobe epilepsy and a mouse model of pilocarpine-induced status epilepticus (SE). The upregulation of Sirt3 by treatment with adjudin, a potential Sirt3 activator, alleviated SE-induced astrocyte activation; whereas, Sirt3 deficiency exacerbated astrocyte activation in the hippocampus after SE. In addition, our results showed that Sirt3 upregulation attenuated the activation of Notch1 signaling, nuclear factor kappa B (NF-κB) activity, and the production of interleukin-1ß (IL1ß) in the hippocampus after SE. By contrast, Sirt3 deficiency enhanced the activity of Notch1/NF-κB signaling and the production of IL1ß. These findings suggest that Sirt3 regulates astrocyte activation by affecting the Notch1/NF-κB signaling pathway, which contributes to the inflammatory response after SE. Therefore, therapies targeting Sirt3 may be a worthy direction for limiting inflammatory responses following epileptic brain injury.

Investigation of Interface Characteristics and Physisorption Mechanism in Quantum Dots/TiO2 Composite for Efficient and Sustainable Photoinduced Interfacial Electron Transfer.

Owing to their superior stability compared to those of conventional molecular dyes, as well as their high UV-visible absorption capacity, which can be tuned to cover the majority of the solar spectrum through size adjustment, quantum dot (QD)/TiO2 composites are being actively investigated as photosensitizing components for diverse solar energy conversion systems. However, the conversion efficiencies and durabilities of QD/TiO2-based solar cells and photocatalytic systems are still inferior to those of conventional systems that employ organic/inorganic components as photosensitizers. This is because of the poor adsorption of QDs onto the TiO2 surface, resulting in insufficient interfacial interactions between the two. The mechanism underlying QD adsorption on the TiO2 surface and its relationship to the photosensitization process remain unclear. In this study, we established that the surface characteristics of the TiO2 semiconductor and the QDs (i.e., surface defects of the metal oxide and the surface structure of the QD core) directly affect the QD adsorption capacity by TiO2 and the interfacial interactions between the QDs and TiO2, which relates to the photosensitization process from the photoexcited QDs to TiO2 (QD* → TiO2). The interfacial interaction between the QDs and TiO2 is maximized when the shape/thickness-modulated triangular QDs are composited with defect-rich anatase TiO2. Comprehensive investigations through photodynamic analyses and surface evaluation using X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and photocatalysis experiments collectively validate that tuning the surface properties of QDs and modulating the TiO2 defect concentration can synergistically amplify the interfacial interaction between the QDs and TiO2. This augmentation markedly improved the efficiency of photoinduced electron transfer from the photoexcited QDs to TiO2, resulting in significantly increased photocatalytic activity of the QD/TiO2 composite. This study provides the first in-depth characterization of the physical adhesion of QDs dispersed on a heterogeneous metal-oxide surface. Furthermore, the prepared QD/TiO2 composite exhibits exceptional adsorption stability, resisting QD detachment from the TiO2 surface over a wide pH range (pH = 2-12) in aqueous media as well as in nonaqueous solvents during two months of immersion. These findings can aid the development of practical QD-sensitized solar energy conversion systems that require the long-term stability of the photosensitizing unit.

Synergistic toxicity with copper contributes to NAT2-associated isoniazid toxicity.

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5-13.2], P = 7.2 × 10-6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5-1423], P = 7.5 × 10-6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

Observation of Coherent Symmetry-Breaking Vibration by Polarization-Dependent Femtosecond Spectroscopy.

Understanding photoinduced chemical reactions beyond the Born-Oppenheimer paradigm requires a comprehensive examination of vibronic interactions. Although femtosecond studies have unveiled the influence of vibrational modes strongly coupled to ultrafast intramolecular reactions in the excited state, they often lack direct observations of how vibrations modulate electronic properties due to the rapid disappearance of reactants. To address this gap, our research investigates the dynamics of photoexcited molecules that do not react. Specifically, we focus on the coherent librational motion of molecular transition dipole moments, discovering that the coherent libration primarily originates from symmetry-breaking components in vibronically excited vibrational modes. Symmetry breaking motion can significantly impact the excited-state dynamics of highly symmetric molecules, potentially leading to nonadiabatic transitions. In essence, the data analysis framework introduced in this study can be harnessed to uncover potential reactivity in photoexcited molecules, further enhancing our understanding of the mechanisms governing these reactions.

Association of Muscle Mass Loss with Diabetes Development in Liver Transplantation Recipients.

BACKGRUOUND: Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development. METHODS: A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3-L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model. RESULTS: During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034). CONCLUSION: Muscle depletion after liver transplantation is associated with increased risk of PTDM development.

Quantitative and Qualitative Analysis of Neurotransmitter and Neurosteroid Production in Cerebral Organoids during Differentiation.

In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.

Synergistic Effect of Size-Tailored Structural Engineering and Postinterface Modification for Highly Efficient and Stable Dye-Sensitized Solar Cells.

Despite significant progress in device performance, dye-sensitized solar cells (DSSCs) continue to fall short of their theoretical potential. Moreover, research in recent years needs to pay more attention to improving the device fabrication process. To achieve the theoretical efficiency limit, it is crucial to optimize the interface between the dye and TiO2 nanoparticles in the entire device stack. Our study indicates that optimizing the structure or size of the coadsorbents and implementing a monolayer adsorption process can be an effective strategy to reduce charge recombination and enhance light-harvesting properties. Our research aims to develop a surface-coating adsorbent plan that controls the TiO2 nanoparticle interface to achieve the radiative limit of power conversion efficiency (PCE). Specifically, we utilized 2-thiophenecarboxylic acid (THCA) or chenodeoxycholic acid (CDCA) as postinterfacial surface-coating adsorbents. Our results demonstrate that this approach effectively achieves the desired PCE limit. Combined with the coadsorbent structure engineering and interface optimization, the device increased the packing area on the TiO2 nanoparticles' surface, reaching an improved PCE of over 13.17% under simulated sunlight (1.5G), which is the highest efficiency of a porphyrin single dye-based DSSC. In particular, this practical approach was also applied to a large-area DSSC with an area of 3 cm2, yielding a remarkable PCE of 9.04%. Furthermore, when applied to a polymer gel electrolyte, this novel approach recorded the highest PCE of 11.16% with a long-term operational stability of up to 1000 h for the quasi-solid-state DSSCs. Our research findings provide a promising avenue for achieving high-performance DSSCs with ease of access and demonstrate practical applications as alternatives to conventional power sources.

Hyperpolarized [1-13C]pyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice.

PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer's disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1-13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism. MATERIALS AND METHODS: ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1-13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells. RESULTS: As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1-13C]pyruvate to [1-13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ratio and lactate generation. CONCLUSION: Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1-13C]pyruvate to HP [1-13C]lactate.

Amplified Triplet Emission of Organic Periphery Groups by Exothermic Triplet-Triplet Energy Transfer from the 3MLCT State of an Ir(pmi)3 Core Complex to the 3LC State of Geometrically Confined Carbazole/Naphthyl Tethers.

To investigate the excited-state properties of metal-organic bichromophores, including energy transfer mechanisms, a series of new homoleptic N-heterocyclic carbene (NHC)-based iridium(III) complexes were prepared by incorporating a peripheral naphthalene (Np) (Ir(Nppmi)3: fac-/mer-Ir(1-Nppmi)3 and fac-/mer-Ir(2-Nppmi)3) or carbazole (Cz) (Ir(Czpmi)3: fac-/mer-Ir(o-Czpmi)3, fac-/mer-Ir(m-Czpmi)3, and fac-/mer-Ir(p-Czpmi)3) unit to the phenyl moiety of the phenylimidazole (pmi) ligand. Through a series of photophysical analyses and femtosecond time-resolved absorption (fs-TA) spectroscopy, it was discovered that the phosphorescence of the Ir core, (Ir(pmi)3), was considerably quenched, while intense phosphorescence peaks arising from the excited triplet Np (3Np*)/Cz (3Cz*) species were primarily observed at room temperature (r.t.) and low temperature. Such amplified phosphorescence of the tethered organic Np and Cz units originated from triplet-triplet energy transfer (TTET) from the high-lying metal-to-ligand charge transfer (3MLCT) state of the Ir(pmi)3 core to the ligand-centered triplet state (3LC) of the peripheral Np and Cz units. This result indicates that the exothermic intramolecular energy transfer (IET) in the excited triplet state realizes the efficient phosphorescent emission of geometrically confined organic tethers.

D-π-A Structured Porphyrin and Organic Dyes with Easily Synthesizable Donor Units for Low-Cost and Efficient Dye-Sensitized Solar Cells.

This study aimed to develop low-cost D-π-A structured porphyrin and organic dyes with easily synthesizable donor units instead of the conventional complex multistep synthetic donor unit of Hexyloxy-BPFA [bis(7-(2,4-bis(hexyloxy)phenyl)-9,9-dimethyl-9H-fluoren-2-yl)amine] used in SGT-021 and SGT-149 as well-known record cosensitizers with an extremely high power conversion efficiency (PCE). The design strategy concerned the easier synthesis of low-cost donor units with inversion structures in donor groups via donor structural engineering, particularly by changing the position of the fluorene and phenylene units in the donor moiety while keeping the π-bridge and acceptor unit unchanged, leading to the synthesis of two D-π-A structured porphyrins [SGT-021(D0) and SGT-021(D)] and one D-π-A structured organic sensitizer [SGT-149(D)] for dye-sensitized solar cells (DSSCs). Specifically, porphyrin SGT-021(D0) incorporated two hexyl chains into the 9-position of each fluorene, while SGT-021(D) and SGT-149(D) substituted two hexyloxy chain units to the terminal position of each fluorene in the donor groups of porphyrin dyes. The effect of the position of the fluorene and phenylene units in the donor moiety on the photochemical and electrochemical properties, as well as the photovoltaic performance, was compared with the reference dyes of SGT-021 and SGT-149, previously reported by the research group. After optimizing the DSSC devices, SGT-021(D) and SGT-021(D0) achieved a high PCE of 11.6 and 10.5%, respectively, while SGT-149(D) exhibited a little lower PCE of 10.3% under the standard AM 1.5G light intensity. The cell performance of DSSC devices based on SGT-021(D) and SGT-149(D) was inferior to the corresponding reference dyes of SGT-021 and SGT-149 due to their lower donating ability of Hexyloxy-BPFA than Hexyloxy-BFPA.

Accumulative Charge Separation in a Modular Quaterpyridine Bridging Ligand Platform and Multielectron Transfer Photocatalysis of π-Linked Dinuclear Ir(III)-Re(I) Complex for CO2 Reduction.

Four sterically distorted quaterpyridyl (qpy) ligand-bridged Ir(III)-Re(I) heterometallic complexes (Ir-qpymm-Re, Ir-qpymp-Re, Ir-qpypm-Re, and Ir-qpypp-Re), in which the position of the coupling pyridine unit of the two 2,2'-bipyridine ligands was varied (meta (m)- or para (p)-position), pypyx-pyxpy (x = m and m, qpymm; x = m and p, qpymp; x = p and m, qpypm; x = p and p, qpypp), were prepared, along with the fully π-conjugated Ir(III)-[π linker]-Re(I) complexes (π linker = 2,2'-bipyrimidine (bpm), Ir-bpm-Re; π linker = 2,5-di(pyridin-2-yl)pyrazine (dpp), Ir-dpp-Re) to elucidate the electron mediating and accumulative charge separation properties of the bridging π-linker in a bimetallic system (photosensitizer-π linker-catalytic center). From the photophysical and electrochemical studies, it was found that the quaterpyridyl (qpy) bridging ligand (BL), in which the two planar Ir/Re metalated bipyridine (bpy) ligands were connected but slightly canted relative to each other, linking the heteroleptic Ir(III) photosensitizer, [(piqC^N)2IrIII(bpy)]+, and catalytic Re(I) complex, (bpy)ReI(CO)3Cl, minimized the energy lowering of the qpy BL, which hampers the forward photoinduced electron transfer (PET) process from [(piqC^N)2IrIII(N^N)]+ to (N^N)ReI(CO)3Cl (Ered1 = -(0.85-0.93) V and Ered2 = -(1.15-1.30) V vs SCE). This result contrasts with the fully π-delocalized bimetallic systems (Ir-bpm-Re and Ir-dpp-Re) that show a significant energy reduction due to the considerable π-extension and deshielding effect caused by the neighboring Lewis acidic metals (Ir and Re) on the electrochemical scale (Ered1 = -0.37 V and Ered2 = -1.02 and -0.99 V vs SCE). Based on a series of anion absorption studies and spectroelectrochemical (SEC) analyses, all Ir(III)-BL-Re(I) bimetallic complexes were found to exist as dianionic form (Ir(III)-[BL]2--Re(I)) after a fast reductive-quenching process in the presence of excess electron donor. In the photolysis experiment, the four Ir-qpy-Re complexes displayed the reasonable photochemical CO2-to-CO conversion activities (TON of 366-588 for 19 h) owing to the moderated electronic coupling between two functional Ir(III) and Re(I) centers through the slightly distorted qpy ligand, whereas Ir-bpm-Re and Ir-dpp-Re displayed negligible performances as a result of the strong electronic coupling via π-conjugation between the two functional components resulting in the energetic constraints for PET and an unwanted side reactions competing with the forward processes. These results confirm that the qpy unit can be utilized as an efficient BL platform in π-linked bimetallic systems.

Dynamics of Photoinduced Intramolecular and Intermolecular Electron Transfers in Ligand-Conjugated Ir(III)-Re(I) Photocatalysts.

We report the electron transfer (ET) dynamics in a series of Ir(III)-Re(I) photocatalysts where two bipyridyl ligands of Ir and Re moieties are conjugated at the meta (m)- or para (p)-position of each side. Femtosecond transient absorption (TA) measurements identify the intramolecular ET (IET) dynamics from the Ir to Re moiety, followed by the formation of one-electron-reduced species (OERS) via the intermolecular ET with a sacrificial electron donor (SED). The IET rate depends on the bridging ligand (BL) structures (∼25 ps for BLmm/mp vs ∼68 ps for BLpm/pp), while the OERS formation happens on an even slower time scale (∼1.4 ns). Connecting the Re moiety at the meta-position of the bipyridyl of the Ir moiety can restrict the rotation around a covalent bond between two bipyridyl ligands by steric hindrances and facilitate the IET process. This highlights the importance of BL structures on the ET dynamics in photocatalysts.

NQO1 regulates cell cycle progression at the G2/M phase.

Rationale: Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is associated with tumor cell proliferation and growth in several human cancer types. However, the molecular mechanisms underlying the activity of NQO1 in cell cycle progression are currently unclear. Here, we report a novel function of NQO1 in modulation of the cell cycle regulator, cyclin-dependent kinase subunit-1 (CKS1), at the G2/M phase through effects on the stability of c­Fos. Methods: The roles of the NQO1/c-Fos/CKS1 signaling pathway in cell cycle progression were analyzed in cancer cells using synchronization of the cell cycle and flow cytometry. The mechanisms underlying NQO1/c-Fos/CKS1-mediated regulation of cell cycle progression in cancer cells were studied using siRNA approaches, overexpression systems, reporter assays, co-immunoprecipitation, pull-down assays, microarray analysis, and CDK1 kinase assays. In addition, publicly available data sets and immunohistochemistry were used to investigate the correlation between NQO1 expression levels and clinicopathological features in cancer patients. Results: Our results suggest that NQO1 directly interacts with the unstructured DNA-binding domain of c-Fos, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival, and inhibits its proteasome-mediated degradation, thereby inducing CKS1 expression and regulation of cell cycle progression at the G2/M phase. Notably, a NQO1 deficiency in human cancer cell lines led to suppression of c-Fos-mediated CKS1 expression and cell cycle progression. Consistent with this, high NQO1 expression was correlated with increased CKS1 and poor prognosis in cancer patients. Conclusions: Collectively, our results support a novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on c­Fos/CKS1 signaling.