Synthetic Advances for Mechanistic Insights: Metal-Oxygen Intermediates with a Macrocyclic Pyridinophane System.

ConspectusMetalloenzymes, which are proteins containing earth-abundant transition-metal ions as cofactors in the active site, generate various metal-oxygen intermediates via activating a dioxygen molecule (O2) to mediate vital metabolic functions, such as the oxidative metabolism of xenobiotics and the biotransformation of naturally occurring molecules. By replicating the active sites of metalloenzymes, many bioinorganic chemists have studied the geometric and electronic properties and reactivities of model complexes to understand the nature of enzymatic intermediates and develop bioinspired metal catalysts. Among the reported model complexes, nonporphyrinic macrocyclic ligands are the predominant coordination system widely used in stabilizing and isolating diverse metal-oxygen intermediates, which allows us to extensively investigate the physicochemical characteristics of the analogs of reactive intermediates of metalloenzymes. In particular, it has been reported that the ring size of the macrocyclic ligands, defined by the number of atoms in the macrocyclic ring, drastically affects the identity of the metal-oxygen intermediate. Thus, systematic modification of the macrocyclic ligands has been a great subject being examined in various inorganic fields.In this Account, we describe synthetic advances of a macrocyclic ligand system by introducing pyridine donors into a 12-membered tetraazamacrocyclic ligand (12-TMC) that initially has 4 amine donors. Interestingly, the backbone of the pyridinophane ligand with 2 pyridine and 2 amine donors in a 12-membered ring is shown to be much more folded than in other macrocyclic ligands, thereby allowing the axial and equatorial donors to separately control the electronic structure of metal complexes. Then, we looked over independent electronic and steric effects on metal-oxygen species with thorough physicochemical analysis. The NiIII-peroxo complexes exhibit nucleophilic reactivity dependent on the steric hindrance of the second coordination sphere. Furthermore, the C-H bond strength of the second coordination sphere has also been an important factor in determining the stability of MnIV-bis(hydroxo) intermediates. Electronic tuning on CoIII-hydroperoxo intermediates results in a trend between the electron-donating abilities of para-substituents on pyridine in the pyridinophane ligand and electrophilic reactivities, from which mechanistic insights into the metal-hydroperoxo species have been gained. Importantly, the metal-oxygen intermediates supported by the pyridinophane ligand system have revealed quite challenging chemical reactions, including dioxygenase-like nitrile activation by CoIII-peroxo intermediates and the oxidation of aldehyde and aromatic compounds by manganese-oxygen intermediates. Based on the fine substitution of donors, we have addressed that those novel reactions originated from the unique framework of the pyridinophane system incorporating spin-crossover behavior and high redox potentials of the metal-oxygen intermediates. These results will be valuable for the structure-activity relationship of metal-oxygen intermediates, giving a better understanding on the enzymatic coordination system where amino acid ligands vary for specific chemical reactions.

Synthesis, Characterization, and Reactivity of a Highly Oxidative Mononuclear Manganese(IV)-Bis(Fluoro) Complex.

Recently, transition-metal terminal nonoxo complexes have shown a remarkable ability to activate and functionalize C-H bonds via proton-coupled electron transfer (PCET). Here we report the first example of a mononuclear manganese(IV) bis(fluoro) complex bearing a tetradentate pyridinophane ligand, [MnIV(TBDAP)(F)2]2+ (3), with an X-ray single crystal structure and physicochemical characterization. The manganese(IV) bis(fluoro) complex has a very high reduction potential of 1.61 V vs SCE, thereby enabling the four-electron oxidation of mesitylene to 3,5-dimethylbenzaldehyde. Kinetic studies, including the kinetic isotope effect and employment of other toluene derivatives, reveal the electron transfer (ET)-driven PCET in the C-H bond activation of mesitylene by 3. This novel metal halide intermediate would be prominently valuable for expanding transition-metal halide chemistry.

A Delphi Approach to Define Lucid Episodes in People Living With Dementia.

PURPOSE: Lucid episodes (LEs: unexpected episodes of spontaneous, meaningful, and relevant communication or behavior) in Alzheimer disease and related dementias are a new area of scientific inquiry that lacks clinical consensus and require more conceptual attention. METHODS: We aimed to measure consensus from an expert group on: (1) potential medical or clinical explanations for LEs; (2) necessary medical and clinical context to LEs; and (3) interpretation of LEs. PATIENTS: We convened 13 experts from different disciplines (neurology, psychiatry, psychology, pharmacy, palliative care, hospice, nursing, social work, primary care, geriatrics, and professional home caregivers) to identify elements of LEs. RESULTS: Experts provided a range of opinions on medical and clinical explanations and questions to understand LEs. Consensus on LEs when presented with clinical vignettes was not reached. Panelists highlighted key medical and contextual factors needed to make a definitive judgement about LEs. CONCLUSION: There is variability in how LEs are interpreted by clinical experts, which complicates the identification of LEs in Alzheimer disease and related dementias.

Wetting behavior of stainless-steel surface with zinc oxide nanorod coatings: modulations in nanorod alignment through atomic layer deposition.

This study investigated the hydrophobic-hydrophilic characteristics of zinc oxide (ZnO) nanorod coatings for potential biomedical applications. We examined the effects of different alignments of ZnO nanorods on the wetting and mechanical characteristics of the coatings. ZnO seed layers were prepared on stainless-steel plates using atomic layer deposition (ALD) at five different temperatures ranging from 50 to 250 °C. The ZnO nanorod coatings were then deposited on these seed layers through chemical bath deposition. The polycrystalline structure of the seed layers and the morphology of the nanorods were analyzed using grazing incidence angle x-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Mechanical and wetting properties of the nanorod coatings were examined using nanoindentation and water-droplet tests. The seed layers produced at 50 and 250 °C showed stronger (0 0 2) peaks than the other layers. ZnO nanorods on these seed layers exhibited greater vertical orientation and lower water contact angles indicating a more hydrophilic surface. Additionally, vertically oriented nanorod coatings demonstrated greater elastic modulus and hardness than those of oblique nanorods. Our findings indicate that ALD technology can be used to control the spatial arrangement of ZnO nanorods and optimize the hydrophobic-hydrophilic and mechanical properties of coating surfaces.

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing.

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.

Variational quantum eigensolver for closed-shell molecules with non-bosonic corrections.

The realization of quantum advantage with noisy-intermediate-scale quantum (NISQ) machines has become one of the major challenges in computational sciences. Maintaining coherence of a physical system with more than ten qubits is a critical challenge that motivates research on compact system representations to reduce algorithm complexity. Toward this end, the variational quantum eigensolver (VQE) used to perform quantum simulations is considered to be one of the most promising algorithms for quantum chemistry in the NISQ era. We investigate reduced mapping of one spatial orbital to a single qubit to analyze the ground state energy in a way that the Pauli operators of qubits are mapped to the creation/annihilation of singlet pairs of electrons. To include the effect of non-bosonic (or non-paired) excitations, we introduce a simple correction scheme in the electron correlation model approximated by the geometrical mean of the bosonic (or paired) terms. Employing it in a VQE algorithm, we assess ground state energies of H2O, N2, and Li2O in good agreement with full configuration interaction (FCI) models respectively, using only 6, 8, and 12 qubits with quantum gate depths proportional to the squares of the qubit counts. With the adopted seniority-zero approximation that uses only one half of the qubit counts of a conventional VQE algorithm, we find that our non-bosonic correction method reaches reliable quantum chemistry simulations at least for the tested systems.

Association of loneliness with mental disorders in Korean adults: national mental health survey of Korea 2021.

PURPOSE: Loneliness is a risk factor for mental and physical disorders. Rapid individualization, with increasing associated social burden, is a contributing factor to loneliness among Koreans. This study aimed to investigate the relationship between loneliness and mental disorders, as well as to determine whether long-term loneliness is a factor predicting the occurrence of mental disorders in adults. METHODS: The National Mental Health Survey of Korea 2021, a nationally representative survey on mental disorders, was conducted. Responses from 5511 participants were collected using the Korean version of the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition, Structured Clinical Interview for Internet Gaming Disorder, and the World Health Organization Adult Attention-deficit Hyperactivity Disorder (ADHD) self-report scale. Loneliness and its duration were investigated among these participants. RESULTS: Loneliness was reported by approximately 2.9% of the general population. Loneliness was associated with an increased adulthood prevalence of alcohol use disorders, nicotine use disorders, depressive disorders, anxiety disorders, adult ADHD, and internet gaming disorders. Long-term loneliness was significantly associated with an elevated risk of alcohol use disorders, nicotine use disorders, depressive disorders, and anxiety disorders. Internet gaming disorder was associated with loneliness lasting > 1 year. CONCLUSION: Various adult psychiatric disorders were associated with loneliness. The significant dose-effect relationship indicated the importance of early detection of and intervention for loneliness to reduce its negative consequences on mental health.

Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Empathy and support exchanges in couples coping with early-stage Alzheimer's disease.

OBJECTIVES: Research has extensively examined spousal caregiving in Alzheimer's disease (AD), but it remains unclear how people with AD help spousal caregivers. We aimed to describe emotional and practical support that people with AD and their spouses provide to each other and test the role their empathy plays in these support experiences. METHODS: Seventy-two people with early-stage AD and their spousal caregivers independently reported empathy (personal distress, empathic concern, perspective taking) and the frequency and appraisal of support provision. Caregivers reported both partners' sociodemographic characteristics. RESULTS: People with early-stage AD and their spousal caregivers provided support to each other often. Caregivers provided more support but people with AD appraised support provision as more pleasant and less stressful. Lower personal distress in both partners and greater caregiver empathic concern were associated with more frequent caregiver support to people with AD. Greater empathic concern and perspective taking were associated with more pleasant appraisals of helping. Personal distress was positively associated with stress of helping. CONCLUSION: Findings describe support reciprocity in early-stage AD and debunk the myth of people with AD being only recipients of care. We identify risk and resilience in couples per empathy and inform the design of dyadic interventions to promote mutually beneficial relationships in AD.

PVS-GEN: Systematic Approach for Universal Synthetic Data Generation Involving Parameterization, Verification, and Segmentation.

Synthetic data generation addresses the challenges of obtaining extensive empirical datasets, offering benefits such as cost-effectiveness, time efficiency, and robust model development. Nonetheless, synthetic data-generation methodologies still encounter significant difficulties, including a lack of standardized metrics for modeling different data types and comparing generated results. This study introduces PVS-GEN, an automated, general-purpose process for synthetic data generation and verification. The PVS-GEN method parameterizes time-series data with minimal human intervention and verifies model construction using a specific metric derived from extracted parameters. For complex data, the process iteratively segments the empirical dataset until an extracted parameter can reproduce synthetic data that reflects the empirical characteristics, irrespective of the sensor data type. Moreover, we introduce the PoR metric to quantify the quality of the generated data by evaluating its time-series characteristics. Consequently, the proposed method can automatically generate diverse time-series data that covers a wide range of sensor types. We compared PVS-GEN with existing synthetic data-generation methodologies, and PVS-GEN demonstrated a superior performance. It generated data with a similarity of up to 37.1% across multiple data types and by 19.6% on average using the proposed metric, irrespective of the data type.

Developing and describing a typology of lucid episodes among people with Alzheimer's disease and related dementias.

INTRODUCTION: This study examined lucid episodes among people living with late-stage Alzheimer's disease and related dementias (PLWD) and then developed a typology of these episodes to help characterize them. METHODS: Family caregivers of PLWD provided information about witnessed episodes, including proximity to death, cognitive status, duration, communication quality, and circumstances prior to lucid episodes on up to two episodes (caregiver N = 151; episode N = 279). Latent class analysis was used to classify and characterize empirically distinct clusters of lucid episodes. RESULTS: Four lucid episode types were identified. The most common type occurred during visits with family and among PLWD who lived > 6 months after the episode. The least common type coincided with family visits and occurred within 7 days of the PLWD's death. DISCUSSION: Findings suggest that multiple types of lucid episodes exist; not all signal impending death; and some, but not all, are precipitated by external stimuli.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Gendered Trends in Formal and Informal Care Utilization Among Older Adults in South Korea.

Drawing on data from two waves of the Korean Longitudinal Study of Ageing (2010 and 2018), this study examined how community-dwelling older men and women (65+) with functional limitations utilized formal and informal sources of care and how their patterns of care utilization changed over time. The usage patterns of formal and informal caregiving services were categorized into three groups: (a) informal help only, (b) formal-informal mix, and (c) no help from either. More men and women used both formal and informal help for their care needs in 2018 than in 2010 (15% compared to 7%). The proportion of older men who relied on informal help only remained similar across survey years, whereas a smaller proportion of older women relied on informal help only in 2018. Although formal care use has been expanded in South Korea, older men continue to utilize help from their families. However, for older women, the proportion who did not receive any help increased - despite an increase in formal care utilization. These findings highlight the importance of considering gendered resources in caregiving in Korea.

Halotolerant endophytic bacteria alleviate salinity stress in rice (oryza sativa L.) by modulating ion content, endogenous hormones, the antioxidant system and gene expression.

Excessive salinity reduces crop production and negatively impacts agriculture worldwide. We previously isolated endophytic bacterial strains from two halophytic species: Artemisia princeps and Chenopodium ficifolium. We used three bacterial isolates: ART-1 (Lysinibacillus fusiformis), ART-10 (Lysinibacillus sphaericus), and CAL-8 (Brevibacterium pityocampae) to alleviate the impact of salinity stress on rice. The impact of 160 mM NaCl salinity on rice was significantly mitigated following inoculation with these bacterial strains, resulting in increased growth and chlorophyll content. Furthermore, OsNHX1, OsAPX1, OsPIN1 and OsCATA expression was increased, but OsSOS expression was decreased. Inductively coupled plasma mass spectrometry (ICP-MS) revealed reduced K+ and Na+ levels in shoots of bacteria-inoculated plants, whereas that of Mg2+ was increased. Bacterial inoculation reduced the content of total flavonoids in rice leaves. Salinized plants inoculated with bacteria showed reduced levels of endogenous salicylic acid (SA) and abscisic acid (ABA) but increased levels of jasmonic acid (JA). In conclusion, the bacterial isolates ART-1, ART-10, and CAL-8 alleviated the adverse effect of salinity on rice growth, which justifies their use as an eco-friendly agricultural practice.

Fully Automated MRI Segmentation and Volumetric Measurement of Intracranial Meningioma Using Deep Learning.

BACKGROUND: Accurate and rapid measurement of the MRI volume of meningiomas is essential in clinical practice to determine the growth rate of the tumor. Imperfect automation and disappointing performance for small meningiomas of previous automated volumetric tools limit their use in routine clinical practice. PURPOSE: To develop and validate a computational model for fully automated meningioma segmentation and volume measurement on contrast-enhanced MRI scans using deep learning. STUDY TYPE: Retrospective. POPULATION: A total of 659 intracranial meningioma patients (median age, 59.0 years; interquartile range: 53.0-66.0 years) including 554 women and 105 men. FIELD STRENGTH/SEQUENCE: The 1.0 T, 1.5 T, and 3.0 T; three-dimensional, T1 -weighted gradient-echo imaging with contrast enhancement. ASSESSMENT: The tumors were manually segmented by two neurosurgeons, H.K. and C.-K.P., with 10 and 26 years of clinical experience, respectively, for use as the ground truth. Deep learning models based on U-Net and nnU-Net were trained using 459 subjects and tested for 100 patients from a single institution (internal validation set [IVS]) and 100 patients from other 24 institutions (external validation set [EVS]), respectively. The performance of each model was evaluated with the Sørensen-Dice similarity coefficient (DSC) compared with the ground truth. STATISTICAL TESTS: According to the normality of the data distribution verified by the Shapiro-Wilk test, variables with three or more categories were compared by the Kruskal-Wallis test with Dunn's post hoc analysis. RESULTS: A two-dimensional (2D) nnU-Net showed the highest median DSCs of 0.922 and 0.893 for the IVS and EVS, respectively. The nnU-Nets achieved superior performance in meningioma segmentation than the U-Nets. The DSCs of the 2D nnU-Net for small meningiomas less than 1 cm3 were 0.769 and 0.780 with the IVS and EVS, respectively. DATA CONCLUSION: A fully automated and accurate volumetric measurement tool for meningioma with clinically applicable performance for small meningioma using nnU-Net was developed. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Systematic Electronic Tuning on the Property and Reactivity of Cobalt-(Hydro)peroxo Intermediates.

A series of cobalt(III)-peroxo complexes, [CoIII(R2-TBDAP)(O2)]+ (1R2; R2 = Cl, H, and OMe), and cobalt(III)-hydroperoxo complexes, [CoIII(R2-TBDAP)(O2H)(CH3CN)]2+ (2R2), bearing electronically tuned tetraazamacrocyclic ligands (R2-TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)-p-R2-pyridinophane) were prepared from their cobalt(II) precursors and characterized by various physicochemical methods. The X-ray diffraction and spectroscopic analyses unambiguously showed that all 1R2 compounds have similar octahedral geometry with a side-on peroxocobalt(III) moiety, but the O-O bond lengths of 1Cl [1.398(3) Å] and 1OMe [1.401(4) Å] were shorter than that of 1H [1.456(3) Å] due to the different spin states. For 2R2, the O-O bond vibration energies of 2Cl and 2OMe were identical at 853 cm-1 (856 cm-1 for 2H), but their Co-O bond vibration frequencies were observed at 572 cm-1 for 2Cl and 550 cm-1 for 2OMe, respectively, by resonance Raman spectroscopy (560 cm-1 for 2H). Interestingly, the redox potentials (E1/2) of 2R2 increased in the order of 2OMe (0.19 V) < 2H (0.24 V) < 2Cl (0.34 V) according to the electron richness of the R2-TBDAP ligands, but the oxygen-atom-transfer reactivities of 2R2 showed a reverse trend (k2: 2Cl < 2H < 2OMe) with a 13-fold rate enhancement at 2OMe over 2Cl in a sulfoxidation reaction with thioanisole. Although the reactivity trend contradicts the general consideration that electron-rich metal-oxygen species with low E1/2 values have sluggish electrophilic reactivity, this could be explained by a weak Co-O bond vibration of 2OMe in the unusual reaction pathway. These results provide considerable insight into the electronic nature-reactivity relationship of metal-oxygen species.

Efficient identification of palatability-related genes using QTL mapping in rice breeding.

The gelatinization temperature of rice is an important factor in determining the eating and cooking quality, and it affects consumer preference. The alkali digestion value (ADV) is one of the main methods used to test the quality of rice and has a high correlation with the gelatinization temperature. For the development of high-quality rice, it is important to understand the genetic basis of palatability-related traits, and QTL analysis is a statistical method linking phenotypic data and genotype data and is an effective method to explain the genetic basis of variation in complex traits. QTL mapping related to the ADV of brown and milled rice was performed using the 120 Cheongcheong/Nagdong double haploid (CNDH) line. As a result, 12 QTLs related to ADV were detected, and 20 candidate genes were selected from the RM588-RM1163 region of chromosome 6 through screening by gene function analysis. The comparison of the relative expression level of candidate genes showed that OsSS1q6 is highly expressed in CNDH lines with high ADV in both brown rice and milled rice. In addition, OsSS1q6 has high homology with the starch synthase 1 protein and interacts with various starch biosynthesis-related proteins, such as GBSSII, SBE, and APL. Therefore, we suggest that OsSS1q6 identified through QTL mapping could be one of the various genes involved in the gelatinization temperature of rice by regulating starch biosynthesis. This study can be used as basic data for breeding high-quality rice and provides a new genetic resource that can increase the palatability of rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01392-2.

Photosensitizing deep-seated cancer cells with photoprotein-conjugated upconversion nanoparticles.

To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.

Hormones and the antioxidant transduction pathway and gene expression, mediated by Serratia marcescens DB1, lessen the lethality of heavy metals (As, Ni, and Cr) in Oryza sativa L.

Microorganisms have recently gained recognition as efficient biological tool for reducing heavy metal toxicity in crops. In this experiment, we isolated a potent heavy metal (As, Ni, and Cr) resistant rhizobacterium Serratia marcescens DB1 and detected its plant growth promoting traits such as phosphate solubilization, gibberellin synthesis, organic acid production and amino acid regulation. Based on these findings, DB1 was further investigated for application in a rice var. Hwayeongbyeo subjected to 1 mM As, 4 mM Ni, and 4 mM Cr stress. The rice plants treated with Cr and Ni appeared healthy but were lethal, indicating unfitness for consumption due to toxic metal deposition, whereas the plants treated with > 1 mM As instantaneously died. Our results showed that DB1 inoculation significantly decreased metal accumulation in the rice shoots. Particularly, Cr uptake dropped by 16.55% and 22.12% in (Cr + DB1) and (Cr + As + Ni + DB1), respectively, As dropped by 48.90% and 35.82% in (As + DB1) and (Cr + As + Ni + DB1), respectively, and Ni dropped by 7.95% and 19.56% in (Ni + DB1) and (Cr + As + Ni + DB1), respectively. These findings were further validated by gene expression analysis results, which showed that DB1 inoculation significantly decreased the expression of OsPCS1 (a phytochelatin synthase gene), OsMTP1 (a metal transporting gene), and OsMTP5 (a gene for the expulsion of excess metal). Moreover, DB1 inoculation considerably enhanced the morphological growth of rice through modulation of endogenous phytohormones (abscisic acid, salicylic acid, and jasmonic acid) and uptake of essential elements such as K and P. These findings indicate that DB1 is an effective biofertilizer that can mitigate heavy metal toxicity in rice crops.

The Relationship Between Childhood Trauma Experience and Complicated Grief: The Importance of Psychological Support for Individuals Coping With Pet Loss in Korea.

BACKGROUND: Loss of companion animals can result in various psychological reactions, including complicated grief, depression, anxiety, and insomnia. However, research on the prevalence of patients requiring clinical intervention is limited. Moreover, research examining the relationship between childhood trauma and psychological symptoms after pet loss is lacking. Therefore, this study aimed to investigate the rates of clinically significant psychological distress after pet loss and the impact of childhood trauma on adults who have experienced pet loss. METHODS: An online survey was conducted with non-clinical adult participants who had experienced the loss of a companion animal. Psychiatric characteristics were evaluated using standardized assessments, including the Inventory of Complicated Grief (ICG), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and the Insomnia Severity Index (ISI). Childhood trauma was evaluated using the Childhood Trauma Questionnaire (CTQ). RESULTS: In a sample of 137 individuals who had experienced pet loss, the percentages of those who exceeded the cutoff points were 55% for the ICG, 52% for the PHQ-9, 40% for the GAD-7, and 32% for the ISI. The group that reported childhood trauma exhibited significantly higher scores on the ICG (t = 2.16, P = 0.032), PHQ-9 (t = 3.05, P = 0.003), GAD-7 (t = 2.61, P = 0.010), and ISI (t = 2.11, P = 0.037) than in the group without childhood trauma. For participants who experienced pet loss for less than one year, there was no significant difference in the ICG between the trauma and non-trauma groups, as both had extremely high scores. However, the trauma group had a significantly higher PHQ-9 (t = 2.58, P = 0.012) than the non-trauma group. In contrast, for participants who experienced pet loss for more than one year, the trauma group had a significantly higher ICG (t = 2.22, P = 0.03) than the non-trauma group, while there was no significant difference in the PHQ-9. Additionally, the emotional abuse scores on the CTQ were most significantly correlated with the ICG scores even after controlling for depressive symptoms. CONCLUSION: People who experienced pet loss had significant psychological symptoms, ranging from 32% to 55%. Childhood trauma experiences affect complicated grief, depressive symptoms, anxiety symptoms, insomnia and prolonged grief disorder after pet loss. After pet loss, people with childhood trauma may require more psychological help than those without trauma.