Simultaneous Thermally Stimulated Delayed Phosphorescence (TSDP) and Thermally Activated Delayed Fluorescence (TADF) in a Two-Coordinated Au(I) Bimetallic Complex Featuring a Tandem Carbene Structure.

A bimetallic, two-coordinated carbene-metal-amine (cMa) Au(I) complex featuring a twisted tandem carbene structure (NHC1-Au-NHC2-Au-carbazolyl) was synthesized. The molecular structure in single crystals revealed a large dihedral angle between the two carbene ligands, while the bridged carbene NHC2 and carbazolyl (Cz) ligands were coplanar. A bluish green thermally stimulated delayed phosphorescence (TSDP) was observed in crystals with an emission lifetime over 70 µs, which can be attributed to the spin allowed diabatic population of a high-lying emissive triplet state from the 3LE characterized low-lying ones. The small rotation energy barrier of Cz along the coordination bond allowed conformers with large dihedral angles between NHC2 and Cz. The ICT characterized S1 state was consequently stabilized to achieve a thermally accessible energy gap to facilitate ISC between triplets and the S1, leading to the thermally activated delayed fluorescence (TADF). Simultaneous TSDP and TADF dual emission can be recorded in its doped polymer film owing to the coexistence of these different conformers.

Integrating metabolomics and bioinformatics to reveal the mechanism of Epimedium-induced liver injury.

Epimedium is a traditional Chinese medicine with a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years. The most common side effect of Epimedium is liver injury. In this study, the liquid chromatography-mass spectrometry (LC-MS) method has been established to study the components of Epimedium and to identify the components absorbed into the blood of rats. Bioinformatics was used to screen out potential toxic components, and the integrating metabolomics method was used to explore the molecular mechanism of Epimedium-induced liver injury. The chemical constituents of Epimedium were identified by LC-MS, and 62 compounds were obtained, including 57 flavonoids, four organic acids and one alkaloid. The toxicity network of "Epimedium-component-target-liver injury" was constructed using bioinformatics research methods, and then the key hepatotoxic component icaritin was identified. Integrating metabolomics was used to investigate the changes in the metabolic profile of L-02 cells with different durations of icaritin administration compared with the control group, and 106 different metabolites were obtained. A total of 14 potential biomarkers significantly associated with cell survival were screened by Pearson correlation analysis combined with the L-02 cell survival rate. Our study preliminarily revealed the mechanism of hepatotoxicity induced by Epimedium.

Solvent-Mediated, Reversible Ternary Graphite Intercalation Compounds for Extreme-Condition Li-Ion Batteries.

Traditional Li-ion intercalation chemistry into graphite anodes exclusively utilizes the cointercalation-free or cointercalation mechanism. The latter mechanism is based on ternary graphite intercalation compounds (t-GICs), where glyme solvents were explored and proved to deliver unsatisfactory cyclability in LIBs. Herein, we report a novel intercalation mechanism, that is, in situ synthesis of t-GIC in the tetrahydrofuran (THF) electrolyte via a spontaneous, controllable reaction between binary-GIC (b-GIC) and free THF molecules during initial graphite lithiation. The spontaneous transformation from b-GIC to t-GIC, which is different from conventional cointercalation chemistry, is characterized and quantified via operando synchrotron X-ray and electrochemical analyses. The resulting t-GIC chemistry obviates the necessity for complete Li-ion desolvation, facilitating rapid kinetics and synchronous charge/discharge of graphite particles, even under high current densities. Consequently, the graphite anode demonstrates unprecedented fast charging (1 min), dendrite-free low-temperature performance, and ultralong lifetimes exceeding 10 000 cycles. Full cells coupled with a layered cathode display remarkable cycling stability upon a 15 min charging and excellent rate capability even at -40 °C. Furthermore, our chemical strategies are shown to extend beyond Li-ion batteries to encompass Na-ion and K-ion batteries, underscoring their broad applicability. Our work contributes to the advancement of graphite intercalation chemistry and presents a low-cost, adaptable approach for achieving fast-charging and low-temperature batteries.

Visualization analysis of research frontiers and trends in the treatment of sciatic nerve injury.

Objective: To visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and development trends of research in this field. Methods: Using CiteSpace and VOSviewer software, we searched the Web of Science database for literature related to the treatment of sciatic nerve injury. Then we analyzed and plotted visualization maps to show the number of publications, countries, institutions, authors, keywords, references, and journals. Results: A total of 2,653 articles were included in the English database. The annual number of publications exceeded 230, and the citation frequency increased yearly. The United States and China were identified as high-influence nations in this field. Nantong University was the leading institution in terms of close cooperation among institutions. The authors Wang Yu had the highest number of publications and were highly influential in this field. Keyword analysis and reference Burst revealed a research focus on nerve regeneration and neuropathic pain, which involve regenerative medicine and neural tissue engineering. Chronic pain resulting from sciatic nerve injury often manifests alongside anxiety, depression, cognitive-behavioral disorders, and other issues. Interventions such as stem cells, electrical stimulation, electroacupuncture, total joint replacement, pharmacological interventions, gene therapy, nerve conduits, chitosan scaffolds, and exercise promote nerve repair and alleviate pain. Schwann cells have been the focus of much attention in nerve repair and regeneration. Improving the outcome of sciatic nerve injury is a current research challenge and focus in this field. Based on keyword Burst, nerve conduits and grafts may become a potential research hotspot in the treatment of sciatic nerve injury. Conclusion: This visual analysis summarizes research trends and developments of sciatic nerve injury treatment and predicts potential research frontiers and hot directions.

Modeling 0.6 million genes for the rational design of functional cis-regulatory variants and de novo design of cis-regulatory sequences.

Rational design of plant cis-regulatory DNA sequences without expert intervention or prior domain knowledge is still a daunting task. Here, we developed PhytoExpr, a deep learning framework capable of predicting both mRNA abundance and plant species using the proximal regulatory sequence as the sole input. PhytoExpr was trained over 17 species representative of major clades of the plant kingdom to enhance its generalizability. Via input perturbation, quantitative functional annotation of the input sequence was achieved at single-nucleotide resolution, revealing an abundance of predicted high-impact nucleotides in conserved noncoding sequences and transcription factor binding sites. Evaluation of maize HapMap3 single-nucleotide polymorphisms (SNPs) by PhytoExpr demonstrates an enrichment of predicted high-impact SNPs in cis-eQTL. Additionally, we provided two algorithms that harnessed the power of PhytoExpr in designing functional cis-regulatory variants, and de novo creation of species-specific cis-regulatory sequences through in silico evolution of random DNA sequences. Our model represents a general and robust approach for functional variant discovery in population genetics and rational design of regulatory sequences for genome editing and synthetic biology.

Monolithic tunable dual-wavelength laser utilizing erbium-doped lithium niobate on an insulator.

We demonstrate a monolithic tunable dual-wavelength laser fabricated on erbium-doped lithium niobate on an insulator (Er:LNOI). The dual-wavelength laser enables independent tuning with a continuously linear electro-optic (EO)-modulated tuning range of 11.875 GHz at a tuning efficiency of 0.63 pm/V. Tunable microwave generation within 50 GHz with a maximum extinction ratio of 35 dB is experimentally demonstrated by further exploring the charge accumulation effect in LNOI. The monolithic design of this work paves the way for microscale integration of laser devices, presenting significant prospects in photonics research and applications.

PGC-1α/LDHA signaling facilitates glycolysis initiation to regulate mechanically induced bone remodeling under inflammatory microenvironment.

The mechanosensitivity of inflammation can alter cellular mechanotransduction. However, the underlying mechanism remains unclear. This study aims to investigate the metabolic mechanism of inflammation under mechanical force to guide tissue remodeling better. Herein, we found that inflammation hindered bone remodeling under mechanical force, accompanied by a simultaneous enhancement of oxidative phosphorylation (OXPHOS) and glycolysis. The control of metabolism direction through GNE-140 and Visomitin revealed that enhanced glycolysis might act as a compensatory mechanism to resist OXPHOS-induced osteoclastogenesis by promoting osteogenesis. The inhibited osteogenesis induced by inflammatory mechanical stimuli was concomitant with a reduced expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α knockdown impeded osteogenesis under mechanical force and facilitated osteoclastogenesis by enhancing OXPHOS. Conversely, PGC-1α overexpression attenuated the impairment of bone remodeling by inflammatory mechanical signals through promoting glycolysis. This process benefited from the PGC-1α regulation on the transcriptional and translational activity of lactate dehydrogenase A (LDHA) and the tight control of the extracellular acidic environment. Additionally, the increased binding between PGC-1α and LDHA proteins might contribute to the glycolysis promotion within the inflammatory mechanical environment. Notably, LDHA suppression effectively eliminated the bone repair effect mediated by PGC-1α overexpression within inflammatory mechanical environments. In conclusion, this study demonstrated a novel molecular mechanism illustrating how inflammation orchestrated glucose metabolism through glycolysis and OXPHOS to affect mechanically induced bone remodeling.

Enhancing docosahexaenoic acid production from Schizochytrium sp. by using waste Pichia pastoris as nitrogen source based on two-stage feeding control.

To reduce the cost of docosahexaenoic acid (DHA) production from Schizochytrium sp., the waste Pichia pastoris was successfully used as an alternative nitrogen source to achieve high-density cultivation during the cell growth phase. However, due to the high oxygen consumption feature when implementing high-density cultivation, the control of both the nitrogen source and dissolved oxygen concentration (DO) at each sufficient level was impossible; thus, two realistic control strategies, including "DO sufficiency-nitrogen limitation" and "DO limitation-nitrogen sufficiency", were proposed. When using the strategy of "DO sufficiency-nitrogen limitation", the lowest maintenance coefficient of glucose (12.3 mg/g/h vs. 17.0 mg/g/h) and the highest activities of related enzymes in DHA biosynthetic routes were simultaneously obtained; thus, a maximum DHA concentration of 12.8 ± 1.2 g/L was achieved, which was 1.58-fold greater than that of the control group. Overall, two-stage feeding control for alternative nitrogen sources is an efficient strategy to industrial DHA fermentation.

Effects of chemical in vitro activation versus fragmentation on human ovarian tissue and follicle growth in culture.

STUDY QUESTION: What is the effect of the chemical in vitro activation (cIVA) protocol compared with fragmentation only (Frag, also known as mechanical IVA) on gene expression, follicle activation and growth in human ovarian tissue in vitro? SUMMARY ANSWER: Although histological assessment shows that cIVA significantly increases follicle survival and growth compared to Frag, both protocols stimulate extensive and nearly identical transcriptomic changes in cultured tissue compared to freshly collected ovarian tissue, including marked changes in energy metabolism and inflammatory responses. WHAT IS KNOWN ALREADY: Treatments based on cIVA of the phosphatase and tensin homolog (PTEN)-phosphatidylinositol 3-kinase (PI3K) pathway in ovarian tissue followed by auto-transplantation have been administered to patients with refractory premature ovarian insufficiency (POI) and resulted in live births. However, comparable effects with mere tissue fragmentation have been shown, questioning the added value of chemical stimulation that could potentially activate oncogenic responses. STUDY DESIGN SIZE DURATION: Fifty-nine ovarian cortical biopsies were obtained from consenting women undergoing elective caesarean section (C-section). The samples were fragmented for culture studies. Half of the fragments were exposed to bpV (HOpic)+740Y-P (Frag+cIVA group) during the first 24 h of culture, while the other half were cultured with medium only (Frag group). Subsequently, both groups were cultured with medium only for an additional 6 days. Tissue and media samples were collected for histological, transcriptomic, steroid hormone, and cytokine/chemokine analyses at various time points. PARTICIPANTS/MATERIALS SETTING METHODS: Effects on follicles were evaluated by counting and scoring serial sections stained with hematoxylin and eosin before and after the 7-day culture. Follicle function was assessed by quantification of steroids by ultra-performance liquid chromatography tandem-mass spectrometry at different time points. Cytokines and chemokines were measured by multiplex assay. Transcriptomic effects were measured by RNA-sequencing (RNA-seq) of the tissue after the initial 24-h culture. Selected differentially expressed genes (DEGs) were validated by quantitative PCR and immunofluorescence in cultured ovarian tissue as well as in KGN cell (human ovarian granulosa-like tumor cell line) culture experiments. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to the Frag group, the Frag+cIVA group exhibited a significantly higher follicle survival rate, increased numbers of secondary follicles, and larger follicle sizes. Additionally, the tissue in the Frag+cIVA group produced less dehydroepiandrosterone compared to Frag. Cytokine measurement showed a strong inflammatory response at the start of the culture in both groups. The RNA-seq data revealed modest differences between the Frag+cIVA and Frag groups, with only 164 DEGs identified using a relaxed cut-off of false discovery rate (FDR) <0.1. Apart from the expected PI3K-protein kinase B (Akt) pathway, cIVA also regulated pathways related to hypoxia, cytokines, and inflammation. In comparison to freshly collected ovarian tissue, gene expression in general was markedly affected in both the Frag+cIVA and Frag groups, with a total of 3119 and 2900 DEGs identified (FDR < 0.001), respectively. The top enriched gene sets in both groups included several pathways known to modulate follicle growth such as mammalian target of rapamycin (mTOR)C1 signaling. Significant changes compared to fresh tissue were also observed in the expression of genes encoding for steroidogenesis enzymes and classical granulosa cell markers in both groups. Intriguingly, we discovered a profound upregulation of genes related to glycolysis and its upstream regulator in both Frag and Frag+cIVA groups, and these changes were further boosted by the cIVA treatment. Cell culture experiments confirmed glycolysis-related genes as direct targets of the cIVA drugs. In conclusion, cIVA enhances follicle growth, as expected, but the mechanisms may be more complex than PI3K-Akt-mTOR alone, and the impact on function and quality of the follicles after the culture period remains an open question. LARGE SCALE DATA: Data were deposited in the GEO data base, accession number GSE234765. The code for sequencing analysis can be found in https://github.com/tialiv/IVA_project. LIMITATIONS REASONS FOR CAUTION: Similar to the published IVA protocols, the first steps in our study were performed in an in vitro culture model where the ovarian tissue was isolated from the regulation of hypothalamic-pituitary-ovarian axis. Further in vivo experiments will be needed, for example in xeno-transplantation models, to explore the long-term impacts of the discovered effects. The tissue collected from patients undergoing C-section may not be comparable to tissue of patients with POI. WIDER IMPLICATIONS OF THE FINDINGS: The general impact of fragmentation and short (24 h) in vitro culture on gene expression in ovarian tissue far exceeded the effects of cIVA. Yet, follicle growth was stimulated by cIVA, which may suggest effects on specific cell populations that may be diluted in bulk RNA-seq. Nevertheless, we confirmed the impact of cIVA on glycolysis using a cell culture model, suggesting impacts on cellular signaling beyond the PI3K pathway. The profound changes in inflammation and glycolysis following fragmentation and culture could contribute to follicle activation and loss in ovarian tissue culture, as well as in clinical applications, such as fertility preservation by ovarian tissue auto-transplantation. STUDY FUNDING/COMPETING INTERESTS: This study was funded by research grants from European Union's Horizon 2020 Research and Innovation Programme (Project ERIN No. 952516, FREIA No. 825100), Swedish Research Council VR (2020-02132), StratRegen funding from Karolinska Institutet, KI-China Scholarship Council (CSC) Programme and the Natural Science Foundation of Hunan (2022JJ40782). International Iberian Nanotechnology Laboratory Research was funded by the European Union's H2020 Project Sinfonia (857253) and SbDToolBox (NORTE-01-0145-FEDER-000047), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund. No competing interests are declared.

Unrecoverable lattice rotation governs structural degradation of single-crystalline cathodes.

Transitioning from polycrystalline to single-crystalline nickel-rich cathodes has garnered considerable attention in both academia and industry, driven by advantages of high tap density and enhanced mechanical properties. However, cathodes with high nickel content (>70%) suffer from substantial capacity degradation, which poses a challenge to their commercial viability. Leveraging multiscale spatial resolution diffraction and imaging techniques, we observe that lattice rotations occur universally in single-crystalline cathodes and play a pivotal role in the structure degradation. These lattice rotations prove unrecoverable and govern the accumulation of adverse lattice distortions over repeated cycles, contributing to structural and mechanical degradation and fast capacity fade. These findings bridge the previous knowledge gap that exists in the mechanistic link between fast performance failure and atomic-scale structure degradation.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

BACKGROUND: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. PATIENTS AND METHODS: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. RESULTS: The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). CONCLUSION: In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

The profile of steroid hormones in human fetal and adult ovaries.

BACKGROUND: Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. METHODS: We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. RESULTS: Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17ß-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures. CONCLUSIONS: Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.

Decoding Active Sites for Highly Efficient Semihydrogenation of Acetylene in Palladium-Copper Nanoalloys.

Accurately decoding the three-dimensional atomic structure of surface active sites is essential yet challenging for a rational catalyst design. Here, we used comprehensive techniques combining the pair distribution function and reverse Monte Carlo simulation to reveal the surficial distribution of Pd active sites and adjacent coordination environment in palladium-copper nanoalloys. After the fine-tuning of the atomic arrangement, excellent catalytic performance with 98% ethylene selectivity at complete acetylene conversion was obtained in the Pd34Cu66 nanocatalysts, outperforming most of the reported advanced catalysts. The quantitative deciphering shows a large number of active sites with a Pd-Pd coordination number of 3 distributed on the surface of Pd34Cu66 nanoalloys, which play a decisive role in highly efficient semihydrogenation. This finding not only opens the way for guiding the precise design of bimetal nanocatalysts from atomic-level insight but also provides a method to resolve the spatial structure of active sites.

Persistent organic pollutants dysregulate energy homeostasis in human ovaries in vitro.

Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs - hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3',4,4',5-hexachlorobiphenyl (PCB156), 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) - and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.

Regulating the Electron Distribution of Metal-Oxygen for Enhanced Oxygen Stability in Li-rich Layered Cathodes.

Li-rich Mn-based layered oxides (LLO) hold great promise as cathode materials for lithium-ion batteries (LIBs) due to their unique oxygen redox (OR) chemistry, which enables additional capacity. However, the LLOs face challenges related to the instability of their OR process due to the weak transition metal (TM)-oxygen bond, leading to oxygen loss and irreversible phase transition that results in severe capacity and voltage decay. Herein, a synergistic electronic regulation strategy of surface and interior structures to enhance oxygen stability is proposed. In the interior of the materials, the local electrons around TM and O atoms may be delocalized by surrounding Mo atoms, facilitating the formation of stronger TM─O bonds at high voltages. Besides, on the surface, the highly reactive O atoms with lone pairs of electrons are passivated by additional TM atoms, which provides a more stable TM─O framework. Hence, this strategy stabilizes the oxygen and hinders TM migration, which enhances the reversibility in structural evolution, leading to increased capacity and voltage retention. This work presents an efficient approach to enhance the performance of LLOs through surface-to-interior electronic structure modulation, while also contributing to a deeper understanding of their redox reaction.

Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro.

Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between exposure and disease in humans. To address this gap, we tested the effects of a common phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), on adult human ovaries in vitro using an epidemiologically determined human-relevant concentration range (2.05 nM - 20.51 mM). Histomorphological assessments, steroid and cytokine measurements were performed on human ovarian tissue exposed to MEHP for 7 days in vitro. Cell viability and gene expression profile were investigated following 7 days of MEHP exposure using the human granulosa cancer cell lines KGN, and COV434, the germline tumor cell line PA-1, and human ovarian primary cells. Selected differentially expressed genes (DEGs) were validated by RT-qPCR and immunofluorescence in human ovarian tissue. MEHP exposure reduced follicular growth (20.51 nM) and increased follicular degeneration (20.51 mM) in ovarian tissue, while not affecting steroid and cytokine production. Out of the 691 unique DEGs identified across all the cell types and concentrations, CSRP2 involved in cytoskeleton organization and YWHAE as well as CTNNB1 involved in the Hippo pathway, were chosen for further validation. CSRP2 was upregulated and CTNNB1 downregulated in both ovarian tissue and cells, whereas YWHAE was downregulated in cells only. In summary, one-week MEHP exposure of human ovarian tissue can perturb the development and survival of human follicles through mechanisms likely involving dysregulation of cytoskeleton organization and Hippo pathway.

Correlation of circulating fibroblast growth factor 21 levels with inflammatory factors and the degree of coronary artery stenosis in patients with acute myocardial infarction.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a secreted protein that plays an important role in atherosclerosis and pathological cardiac remodeling. However, the correlation between FGF21 and the degree of coronary artery stenosis and its potential role in acute myocardial infarction (AMI) remain unclear. We examined whether changes in FGF21 levels in AMI correlate with the degree of coronary artery stenosis and the levels of inflammatory factors, and preliminarily investigated the effects of FGF21 on inflammatory factor levels and myocardial injury in rats with AMI. METHODS: Serum levels of FGF21 and inflammatory factors in the AMI group and control group were measured, and the correlation between FGF21 and clinical indicators and inflammatory factors was analyzed. The effects of FGF21 on cardiac function and inflammatory response were evaluated through echocardiography and measurement of inflammatory factors. RESULTS: Multivariate logistic regression analysis showed that neutrophil percentage (NEUT%, odds ratio [OR]: 1.232; 95 % confidence interval [CI]: 1.028-1.477; p = 0.024) and FGF21 levels (OR: 2.063; 95 % CI: 1.187-3.586; p = 0.01) had independent effects on AMI. Spearman's rank correlation test showed that FGF21 levels were positively correlated with leukocyte count, NEUT%, neutrophil count, neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and Gensini scores (p < 0.01), but negatively correlated with lymphocyte count (p < 0.01). FGF21 levels in myocardial tissues and serum levels of FGF21, IL-6, TNF-a, and MCP-1 were significantly higher in AMI rats than in the sham-operated group (p < 0.01). After overexpression of FGF21, serum levels of IL-6, TNF-a, and MCP-1 in rats were significantly decreased (p < 0.01), and cardiac function improved significantly. CONCLUSIONS: FGF21 levels were independently associated with AMI and may be related to the severity of coronary artery stenosis. Overexpression of FGF21 reduced serum inflammatory factor levels and improved cardiac function in AMI rats.

Mediating effects of sleep quality between clinical characteristics and quality of life in children with epilepsy: A cross-sectional study from Southwest China.

BACKGROUND: Although sleep quality (SQ) reportedly affects the health-related quality of life (QOL) of patients with epilepsy, little is known about the potential association between SQ and QOL, particularly in children with epilepsy (CWE). Our study aimed to investigate the mediating effect of SQ on the QOL of CWE to obtain more information for the prevention and treatment of epilepsy in children. METHODS: We collected general demographic and clinical data of 212 CWE and 79 controls (children who visited the Health Examination Department), and their guardians were instructed to answer the Children's Sleep Habits Questionnaire (CSHQ) and the optimized Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16). The t-test, analysis of variance, chi-square test, and Fisher's exact test were used for between group comparisons. The Pearson correlation was used to analyze the correlation between variables. The direct, indirect, and total effects of predictors on the QOL of CWE were estimated based on an adjusted mediation model. RESULTS: CWE had significantly smaller long-term urban residence rates, less educated guardians, higher total CSHQ score, higher incidence of poor SQ, higher bedtime resistance, more sleep anxiety, worse sleep-disordered breathing, increased parasomnia, more daytime sleepiness, more frequent night waking, and greater sleep onset delay than controls (P < 0.05 for all). The univariable analysis showed significant differences in total CSHQ scores between CWE with different seizure frequency in the last month, whether or not drug-resistant epilepsy (DRE), and with different video electroencephalogram (VEEG) findings (P < 0.05 for all). Differences in QOLCE-16 scores between CWE with different guardian's employment status, age at diagnosis, number of anti-seizure medication (ASM) types, seizure frequency in the last month, DRE status, seizure type, VEEG findings, neuropsychological evaluation findings, magnetic resonance imaging (MRI) findings, and etiology were statistically significant (P < 0.05 for all). The correlation study indicated that the total CSHQ score was negatively correlated with the QOLCE-16 score (P < 0.05). The mediation analysis showed that DRE and VEEG abnormalities had a standardized direct effect on the QOL. Seizure frequency in the last month, DRE, and VEEG abnormalities had an indirect effect on the QOL through SQ, and their mediating effect values of SQ were 31.61 %, 13.45 %, and 14.35 %, respectively. CONCLUSION: Our findings uncovered the relationship of some clinical characteristics with SQ and QOL and characterized the nature of factors affecting the QOL of CWE. SQ could be a key factor in the prognosis of CWE experiencing epileptic seizures, and more attention should be paid on the management of SQ in interventions for epilepsy.

An isotropic zero thermal expansion alloy with super-high toughness.

Zero thermal expansion (ZTE) alloys with high mechanical response are crucial for their practical usage. Yet, unifying the ZTE behavior and mechanical response in one material is a grand obstacle, especially in multicomponent ZTE alloys. Herein, we report a near isotropic zero thermal expansion (αl = 1.10 × 10-6 K-1, 260-310 K) in the natural heterogeneous LaFe54Co3.5Si3.35 alloy, which exhibits a super-high toughness of 277.8 ± 14.7 J cm-3. Chemical partition, in the dual-phase structure, assumes the role of not only modulating thermal expansion through magnetic interaction but also enhancing mechanical properties via interface bonding. The comprehensive analysis reveals that the hierarchically synergistic enhancement among lattice, phase interface, and heterogeneous structure is significant for strong toughness. Our findings pave the way to tailor thermal expansion and obtain prominent mechanical properties in multicomponent alloys, which is essential to ultra-stable functional materials.

Two-Coordinate Thermally Activated Delayed Fluorescence Coinage Metal Complexes: Molecular Design, Photophysical Characters, and Device Application.

Since the emergence of the first green light emission from a fluorescent thin-film organic light emitting diode (OLED) in the mid-1980s, a global consumer market for OLED displays has flourished over the past few decades. This growth can primarily be attributed to the development of noble metal phosphorescent emitters that facilitated remarkable gains in electrical conversion efficiency, a broadened color gamut, and vibrant image quality for OLED displays. Despite these achievements, the limited abundance of noble metals in the Earth's crust has spurred ongoing efforts to discover cost-effective electroluminescent materials. One particularly promising avenue is the exploration of thermally activated delayed fluorescence (TADF), a mechanism with the potential to fully harness excitons in OLEDs. Recently, investigations have unveiled TADF in a series of two-coordinate coinage metal (Cu, Ag, and Au) complexes. These organometallic TADF materials exhibit distinctive behavior in comparison to their organic counterparts. They offer benefits such as tunable emissive colors, short TADF emission lifetimes, high luminescent quantum yields, and reasonable stability. Impressively, both vacuum-deposited and solution-processed OLEDs incorporating these materials have achieved outstanding performance. This review encompasses various facets on two-coordinate TADF coinage metal complexes, including molecular design, photophysical characterizations, elucidation of structure-property relationships, and OLED applications.