Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Oral Curcumin-Thioketal-Inulin Conjugate Micelles against Radiation-Induced Enteritis.

Radiation-induced enteritis is an unavoidable complication associated with pelvic tumor radiotherapy, significantly influencing the prognosis of cancer patients. The limited availability of commercial gastrointestinal radioprotectors in clinical settings poses a substantial challenge in preventing radiation enteritis. Despite the inherent radioprotective characteristics of Cur in vitro, its poor solubility in water, instability, and low bioavailability lead to inferior therapeutic effects in vivo. Herein, we developed novel ROS-responsive micelles (CTI) from inulin and curcumin, aimed at mitigating radiation enteritis. CTI micelles had excellent solubility and stability. Importantly, CTI improved the cytotoxicity and bioavailability of curcumin, thereby showing enhanced effectiveness in neutralizing ROS induced by radiation, safeguarding against DNA damage, and reducing radiation-induced cellular mortality. Moreover, in a radiation enteritis mice model, CTI not only alleviated severe radiation-induced intestinal injury but also improved redox-related indicators and reduced inflammatory cytokine expression. Furthermore, CTI effectively increased gut microbiota abundance and maintained gut homeostasis. In conclusion, CTI could be a promising candidate for the clinical management of radiation enteritis. Our study provides a new perspective for radioprotection using natural antioxidants.

Emotion Regulation Use Varies Across Socioecological Levels of Pandemic Stress in Older Adults.

OBJECTIVES: COVID-19 escalated stress within family/neighborhood (local) and national/cultural (global) levels. However, the impact of socioecological levels of stress on pandemic emotion regulation remains largely unexplored. METHODS: Thirty older adults from the Northeast US (63-92 years) reported on pandemic stress and emotion regulation in semi-structured interviews. Responses were coded into socioecological sources of local and global stress, and associated use of cognitive emotion regulation strategies from the Cognitive Emotion Regulation Questionnaire was explored. RESULTS: Older adults experienced significant distress at global levels, and perception of lacking top-down safety governance may have exacerbated local distress of engaging in daily activities during the COVID-19 pandemic. Participants endorsed coping with local stressors via perspective-taking, acceptance, and other adaptive strategies, while global sources of stress were associated with greater use of maladaptive strategies, including other-blame and rumination. CONCLUSION: Quantitative assessments may underestimate significant older adult distress and maladaptive coping toward global stressors. Findings should be replicated with more diverse populations beyond the COVID-19 context.

LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer.

BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.

Incidence of Dementia and Alzheimer's Disease, Genetic Susceptibility, and Grip Strength Among Older Adults.

BACKGROUND: Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown. METHODS: This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers. RESULTS: The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314). CONCLUSIONS: Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.

Development and psychometric properties of the Couple Interaction Pattern Scale.

This study developed the Couple Interaction Pattern Scale (CIPS) based on the interpersonal theory, comprising five subscales: friendly complementary (FC), hostile complementary (HC), mutual hostile-dominant (MHD), friendly-dominant eliciting hostile-submissive (FDHS), and hostile-dominant eliciting friendly-submissive (HDFS). The psychometric properties of the CIPS were examined through three independent studies. Study one conducted item reduction and preliminary analysis using a sample of 662 married individuals, with an additional 80 married individuals for test-retest reliability assessment. Study two validated the scale through 1207 married individuals. In study three, the effect of couple interaction pattern (CIP) on marital quality was analyzed among 310 newlywed couples using the actor-partner interdependence model (APIM). Results supported the construct validity, acceptable internal consistency, and test-retest reliability of the CIPS. Besides, concurrent validity was also proved by associations with conflictual communication patterns, marital quality, stability, emotional connection, and perceived partner support. APIM analysis also supported the association between CIP and marital quality.

Exosome subpopulations: The isolation and the functions in diseases.

Exosomes are nanoscale extracellular vesicles secreted by cells. Exosomes mediate intercellular communication by releasing their bioactive contents (e.g., DNAs, RNAs, lipids, proteins, and metabolites). The components of exosomes are regulated by the producing cells of exosomes. Due to their diverse origins, exosomes are highly heterogeneous in size, content, and function. Depending on these characteristics, exosomes can be divided into multiple subpopulations which have different functions. Efficient enrichment of specific subpopulations of exosomes helps to investigate their biological functions. Accordingly, numerous techniques have been developed to isolate specific subpopulations of exosomes. This review systematically introduces emerging new technologies for the isolation of different exosome subpopulations and summarizes the critical role of specific exosome subpopulations in diseases, especially in tumor occurrence and progression.

Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.

HP1 proteins bind dynamically to H3K9 methylation and are essential for establishing and maintaining transcriptionally silent epigenetic states, known as heterochromatin. HP1 proteins can dimerize, forming a binding interface that interacts with and recruits diverse chromatin-associated factors. HP1 proteins rapidly evolve through sequence changes and gene duplications, but the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impact epigenetic inheritance, we performed a targeted mutagenesis screen of the dimerization and protein interaction domain of the S.pombe HP1 homolog Swi6. We discovered that substitutions mapping to an auxiliary motif in Swi6 outside the dimerization interface can lead to complete functional divergence. Specifically, we identified point mutations at a single amino acid residue that resulted in either persistent gain or loss of function in epigenetic inheritance without affecting heterochromatin establishment. These substitutions increase Swi6 chromatin occupancy in vivo and alter Swi6-protein interactions that selectively affect H3K9me inheritance. Based on our findings, we propose that relatively minor changes in Swi6 amino acid composition can lead to profound changes in epigenetic inheritance, underscoring the remarkable plasticity associated with HP1 proteins and their ability to evolve new functions.

Synthesis of Imidazole-Compound-Coated Copper Nanoparticles with Promising Antioxidant and Sintering Properties.

In this study, we present a facile method for preparing oxidation-resistant Cu nanoparticles through a liquid-phase reduction with imidazole compounds (imidazole, 2-methylimidazole, 2-phenylimidazole, and benzimidazole) that serve as protective and dispersing agents. Through a complexation reaction between Cu atoms, the imidazole compounds can form a protective film on the Cu nanoparticles to prevent the particles from rapidly oxidizing. We compared the effects of the four kinds of imidazole compounds on the oxidation resistance and sintering properties of Cu particles. The Cu particles prepared with benzimidazole could be stored in the air for 30 days without being oxidized. After sintering at 300 °C and 2 MPa, the joint of the particles could reach a shear strength of 32 MPa, which meets the requirements for microelectronic packaging.

Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation.

Background: Traumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI. Methods: A total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis. Results: The adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1ß and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi. Conclusion: Adolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction.

Green Solvent Processable, Asymmetric Dopant-Free Hole Transport Layer Material for Efficient and Stable n-i-p Perovskite Solar Cells and Modules.

The use of dopant-free hole transport layers (HTLs) is critical in stabilizing n-i-p perovskite solar cells (pero-SCs). However, these HTL materials are often processed with toxic solvents, which is not ideal for industrial production. Upon substituting them with green solvents, a trade-off emerges between maintaining the high crystallinity of the HTL materials and ensuring high solubility in the new solvents. In this paper, we designed a novel, linear, organic small molecule, BDT-C8-3O, by introducing an asymmetric polar oligo(ethylene glycol) side chain. This method not only overcomes the solubility limitations in green solvents but also enables stacking the conjugated main chains in two patterns, which further enhances crystallinity and hole mobility. As a result, the n-i-p pero-SCs based on chlorobenzene- or green (natural compound) solvent 3-methylcyclohexanone-processed BDT-C8-3O HTL that without any dopant delivered world-recorded power conversion efficiencies of 24.11 % (certified of 23.82 %) and 23.53 %, respectively. The devices also demonstrated remarkable operational and high-temperature stabilities, maintaining over 84 % and 79.5 % of their initial efficiency for 2000 h, respectively. Encouragingly, dopant-free BDT-C8-3O HTL exhibits significant advantages in large-area fabrication, achieving state-of-the-art PCEs exceeding 20 % for 5×5 cm2 modules (active area: 15.64 cm2 ), even when processed using green solvents.

Injectable multifunctional chitosan/dextran-based hydrogel accelerates wound healing in combined radiation and burn injury.

Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H2O2-induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI.

Reciprocal associations between commitment, forgiveness, and different aspects of marital well-being among Chinese newlywed couples.

This study examined the reciprocal prospective associations between commitment, forgiveness, and different aspects of marital well-being (marital satisfaction and marital instability) among Chinese newlywed couples and the gender differences in these associations. The Vulnerability-Stress-Adaptation (VSA) model posits reciprocal associations between adaptive processes and relationship satisfaction. However, the directionality of the associations between adaptive processes and marital satisfaction may differ from the associations between adaptive processes and marital instability in Chinese societies due to the emphasis on relationship maintenance. Based on three annual waves of data from 268 Chinese newlywed couples (Mage = 29.59, SD = 3.25 for husbands; Mage = 28.08, SD = 2.51 for wives), a cross-lagged approach was used to examine the reciprocal associations between commitment, forgiveness, and marital satisfaction/instability. We found: (a) reciprocal associations between commitment/forgiveness and marital satisfaction (wives only); (b) reciprocal associations between forgiveness and marital instability (husbands only); and (c) wives' commitment at Wave 2 mediated the association between wives' commitment at Wave 1 and wives' marital satisfaction at Wave 3. Extending the VSA model, findings suggest different reciprocal associations between commitment, forgiveness, and different aspects of marital well-being among Chinese newlywed couples. Results highlight the important role of culture and gender in marital relationships and clinical practice.

Effects of crown-to-implant ratio on marginal bone level and bone density in non-splinted single implants: a cross-sectional study.

BACKGROUND: Few studies have evaluated the effects of the crown-to-implant (C/I) ratio on the marginal bone level (MBL) and bone density in non-splinted single implants. The aim of this study was to assess the effect of C/I ratio on MBL and density of peri-implant bone in non-splinted posterior implants. METHODS: The C/I ratio, MBL, and grayscale values (GSVs) for bone density were measured from X-rays. Four areas of interest (two at the apical area and two at the middle of the peri-implant area) and two control areas were selected for evaluation. Follow-up radiographs were calibrated according to the control areas. RESULTS: In all, 117 non-splinted posterior implants in 73 patients followed up for a mean duration of 36.23 ± 10.40 (range 24-72) months were considered. The mean anatomical C/I ratio was 1.78 ± 0.43 (range 0.93 to 3.06). The mean change in MBL was 0.28 ± 0.97 mm. There were no significant associations between the C/I ratio and MBL changes (r = -0.028, p = 0.766). Pearson correlation showed a significant correlation between changes in GSV and the C/I ratio in the middle peri-implant area (r = 0.301, p = 0.001) and apical area (r = 0.247, p = 0.009). CONCLUSIONS: A higher C/I ratio of single non-splinted posterior implants is associated with increased peri-implant bone density, but not correlated with changes in MBL.

Bidirectional or unidirectional? Longitudinal associations between external stressors, perceived spousal support, and marital instability.

Based on three annual waves of data from 268 Chinese newlyweds (Mage = 29.59, SD = 3.25 for husbands; Mage = 28.08, SD = 2.51 for wives), the present study examined the bidirectional associations between external stressors, perceived spousal support, and marital instability by using a three-wave, cross-lagged approach. Results indicated bidirectional associations between external stressors and marital instability, and a unidirectional association linking marital instability to perceived spousal support. Additionally, external stressors at Wave 2 mediated the association between external stressors at Wave 1 and marital instability at Wave 3. Taken together, the present study contributes to an emerging body of research aimed at clarifying: (a) the directionality of the associations between external stressors, perceived spousal support, and marital instability; (b) how external stressors cumulatively affect the development of marital instability. Our study extends the Vulnerability-Stress-Adaptation (VSA) model and has developmental implications for promoting marital relationships in non-Western couples.

Does vestibular incision improve the outcomes of vestibular incision subperiosteal tunnel technique: A randomized clinical trial for treatment of multiple adjacent type 1 gingival recession.

OBJECTIVE: The purpose of this study was to compare the clinical outcomes of vestibular incision subperiosteal tunnel technique (VISTA) and tunnel approach combined with connective tissue graft (CTG) for treatment of type 1 (RT1) multiple gingival recession. MATERIALS AND METHODS: Twenty-four patients with a total of 59 nonmolar recession teeth were randomly allocated to VISTA + CTG or Tunnel + CTG group. Recession depth and width, probing depth, clinical attachment level, width of keratinized tissue, gingival thickness, flap tension, mean root coverage (MRC), complete root coverage (CRC), patient-centered, and esthetic outcomes (root coverage esthetic scores, RES) were assessed at baseline and 12 months after surgery. RESULTS: At 12 months, MRC of 91.13 ± 16.96% and 91.40 ± 13.53%, CRC of 70.97% and 67.86% were observed for VISTA + CTG and Tunnel + CTG group respectively, with no significant difference between the two groups (p > 0.05). High RES of 8.52 ± 1.46 and 8.82 ± 1.44 was obtained in VISTA + CTG and Tunnel + CTG group respectively, without showing a significant difference (p = 0.245), while less scar formation was observed in Tunnel + CTG group (p < 0.01). CONCLUSIONS: Both procedures were effective for root coverage in RT1 multiple gingival recession at 12 months. Better esthetic result with less scar formation was obtained in tunnel approach combined with CTG without vestibular incision. (Registration number: ChiCTR-INR-16007845, registered on 19/12/2015, http://www.chictr.org.cn). CLINICAL SIGNIFICANCE: VISTA + CTG and Tunnel + CTG were both effective for root coverage in RT1 multiple gingival recession, with satisfying esthetic outcomes. However, it is suggested in critical esthetic areas, treatment options of making vertical incisions should be carefully considered.

Charge order driven by multiple-Q spin fluctuations in heavily electron-doped iron selenide superconductors.

Intertwined spin and charge orders have been widely studied in high-temperature superconductors, since their fluctuations may facilitate electron pairing; however, they are rarely identified in heavily electron-doped iron selenides. Here, using scanning tunneling microscopy, we show that when the superconductivity of (Li0.84Fe0.16OH)Fe1-xSe is suppressed by introducing Fe-site defects, a short-ranged checkerboard charge order emerges, propagating along the Fe-Fe directions with an approximately 2aFe period. It persists throughout the whole phase space tuned by Fe-site defect density, from a defect-pinned local pattern in optimally doped samples to an extended order in samples with lower Tc or non-superconducting. Intriguingly, our simulations indicate that the charge order is likely driven by multiple-Q spin density waves originating from the spin fluctuations observed by inelastic neutron scattering. Our study proves the presence of a competing order in heavily electron-doped iron selenides, and demonstrates the potential of charge order as a tool to detect spin fluctuations.

Neuroprotection of NRF2 against Ferroptosis after Traumatic Brain Injury in Mice.

Ferroptosis and iron-related redox imbalance aggravate traumatic brain injury (TBI) outcomes. NRF2 is the predominant transcription factor regulating oxidative stress and neuroinflammation in TBI, but its role in iron-induced post-TBI damage is unclear. We investigated ferroptotic neuronal damage in the injured cortex and observed neurological deficits post-TBI. These were ameliorated by the iron chelator deferoxamine (DFO) in wild-type mice. In Nrf2-knockout (Nrf2-/-) mice, more sever ferroptosis and neurological deficits were detected. Dimethyl fumarate (DMF)-mediated NRF2 activation alleviated neural dysfunction in TBI mice, partly due to TBI-induced ferroptosis mitigation. Additionally, FTH-FTL and FSP1 protein levels, associated with iron metabolism and the ferroptotic redox balance, were highly NRF2-dependent post-TBI. Thus, NRF2 is neuroprotective against TBI-induced ferroptosis through both the xCT-GPX4- and FTH-FTL-determined free iron level and the FSP1-regulated redox status. This yields insights into the neuroprotective role of NRF2 in TBI-induced neuronal damage and its potential use in TBI treatment.

Tracking live-cell single-molecule dynamics enables measurements of heterochromatinassociated protein-protein interactions.

Visualizing and measuring molecular-scale interactions in living cells represents a major challenge, but recent advances in microscopy are bringing us closer to achieving this goal. Single-molecule super-resolution microscopy enables high-resolution and sensitive imaging of the positions and movement of molecules in living cells. HP1 proteins are important regulators of gene expression because they selectively bind and recognize H3K9 methylated (H3K9me) histones to form heterochromatin-associated protein complexes that silence gene expression. Here, we extended live-cell single-molecule tracking studies in fission yeast to determine how HP1 proteins interact with their binding partners in the nucleus. We measured how genetic perturbations that affect H3K9me alter the diffusive properties of HP1 proteins and each of their binding partners based on which we inferred their most likely interaction sites. Our results indicate that H3K9me promotes specific complex formation between HP1 proteins and their interactors in a spatially restricted manner, while attenuating their ability to form off-chromatin complexes. As opposed to being an inert platform or scaffold to direct HP1 binding, our studies propose a novel function for H3K9me as an active participant in enhancing HP1-associated complex formation in living cells.