CDHu40: a novel marker gene set of neuroendocrine prostate cancer.

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression.

The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer.

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.

Progress of researches on the mechanisms of acupuncture intervention underlying improvement of ischemic stroke by regulating microRNAs. / 针刺调控微小RNAæ²»ç–—ç¼ºè¡€æ€§è„‘å’ä¸­æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

MicroRNAs play an important role in the occurrence and development of ischemic stroke (IS). A lot of researches have shown that acupuncture intervention can improve IS-induced neural dysfunction by regulating miRNA. In the present paper, we summarized the current progress of researches on the mechanisms of acupuncture underlying improvement of IS via regulation of miRNA from 1) promoting angiogenesis and increasing cerebral blood flow, 2) inhibiting inflammatory response, 3) maintaining blood-brain barrier homeostasis and relieving brain edema, 4) regulating programmed cell death, 5) promoting neuron regeneration, and 6) improving synaptic plasticity. These miRNA -related mechanisms may provide a reference for the follow-up research .

Combining vasoactive-inotropic score with lactate to predict mortality in post-cardiotomy patients supported with venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: To determine the predictive role of combined assessment of vasoactive-inotropic score and lactate for the prognosis of patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. METHODS: The data of adult patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation between January 2015 and December 2018 at a tertiary hospital was retrospectively analyzed. The incidence of in-hospital mortality and other clinical outcomes were analyzed. The associations of vasoactive-inotropic score and lactate and in-hospital mortality were assessed using logistic regression analysis. RESULTS: 222 patients were included and divided into four groups according to the cut-off points of vasoactive-inotropic score (24.3) and lactate level (6.85 mmol/L). The in-hospital mortality rates were 37.7%, 50.7%, 54.8% and 76.5% for the four groups (P < 0.001), while the rates of successful weaning off extracorporeal membrane oxygenation were 73.9%, 69%, 61.3% and 39.2% respectively (P = 0.001). The group 1 and group 2 exhibited significant differences compared to group 4 in both in-hospital mortality and weaning rates (P < 0.05). There was a statistically significant difference in the incidence of multiple organ dysfunction between group 1 and group 4 (P < 0.05). Groups 1, 2 and 3 demonstrated significantly improved cumulative 30-day survival compared with group 4 (log-rank test, P < 0.05). Logistic regression analysis revealed that age, vasoactive-inotropic score > 24.3 and lactate > 6.85 mmol/L were independently predictive of in-hospital mortality. CONCLUSIONS: Among patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation, the initiation before reaching vasoactive-inotropic score > 24.3 and lactate > 6.85 mmol/L was associated with improved in-hospital outcomes, suggesting that combined assessment of VIS and lactate may be instructive for determining the initiation of venoarterial extracorporeal membrane oxygenation.

Phenotyping Refractory Cardiogenic Shock Patients Receiving Venous-Arterial Extracorporeal Membrane Oxygenation Using Machine Learning Algorithms.

Background: This study used machine learning to categorize cardiogenic shock (CS) patients treated with venous-arterial extracorporeal membrane oxygenation (VA-ECMO) into distinct phenotypes. Subsequently, it aimed to clarify the wide mortality variance observed in refractory CS, attributing it to the condition's inherent heterogeneity. Methods: This study enrolled a cohort of CS patients who received VA-ECMO support. By employing rigorous machine learning (ML) techniques, we generated and validated clusters based on determinants identified through algorithmic analysis. These clusters, characterized by distinct clinical outcomes, facilitated the examination of clinical and laboratory profiles to enhance the understanding of patient responses to VA-ECMO treatment. Results: In a study of 210 CS patients undergoing VA-ECMO treatment, 70.5% were male with a median age of 62, ranging from 53 to 67 years. Survival rates were 67.6% during VA-ECMO and 49.5% post-discharge. Patients were classified into three phenotypes based on the clinical and laboratory findings: "platelet preserved (I)", those with stable platelet counts, "hyperinflammatory (II)", those indicating significant inflammation, and "hepatic-renal (III)", those showing compromised liver and kidney functions. Mortality rates (25.0%, 52.8%, and 55.9% for phenotypes I, Ⅱ, and Ⅲ, respectively (p = 0.005)) varied significantly among these groups, highlighting the importance of phenotype identification in patient management. Conclusions: This study identified three distinct phenotypes among refractory CS patients treated using VA-ECMO, each with unique clinical characteristics and mortality risks. Thus, highlighting the importance of early detection and targeted intervention, these findings suggest that proactive management could improve outcomes for those showing critical signs.

Triglyceride-glucose index correlates with the occurrence and prognosis of acute myocardial infarction complicated by cardiogenic shock: data from two large cohorts.

BACKGROUND: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. METHODS: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. RESULTS: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. CONCLUSIONS: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.

Bidirectional Inhibiting Interfacial Ion Migration in the Inorganic Hole Transport Layer for Perovskite Light-Emitting Diodes.

Cu2ZnSnS4 (CZTS) is strong candidate for hole transport in perovskite light emitting diodes (PeLEDs) due to their cost-effectiveness, deep highest occupied molecular orbital (HOMO), and high hole mobility. However, its inherent polymetallic ions usually deteriorate the quality of the perovskite emission layer (EML) affecting device performance. In this study, a bidirectional anchoring strategy is proposed by adding 15-crown-5 ether (15C5) into CZTS hole transport layer (HTL) to suppress the reaction between HTL and EML. The 15C5 molecule interacts with Cu+, Zn2+ and Sn2+ cations forming host-guest complexes to impede their migration, which is elucidated by density functional theory calculations. Additionally, 15C5 can neutralize lead (Pb) defects by the abundant oxygen (O) and high electronegative cavities to reduce the nonradiative recombination of FAPbBr3 film. This bidirectional anchoring strategy effectively improves hole charge transport efficiency and suppresses nonradiative recombination at the HTL/EML interface. As a result, the optimized PeLEDs present a 3.5 times peak external quantum efficiency (EQE) from 3.12% to 11.08% and the maximum luminance (Lmax) increased from 24495 to 50584 cd m-2. These findings offer innovative insights into addressing the metal ion migration issue commonly observed in inorganic HTLs.

Development of Novel Indole-Based Covalent Inhibitors of TEAD as Potential Antiliver Cancer Agents.

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

MiR-199a-5p aggravates against renal ischemia-reperfusion and transplant injury by targeting AKAP1 to disrupt mitochondrial dynamics.

Renal ischemia-reperfusion injury (IRI) is a major cause of delayed graft function (DGF) after transplantation. Currently, a targeted therapy for this important clinical disorder is still lacking. MicroRNA (miRNA) has important roles in the pathogenesis of IRI and may therapeutic approaches to mitigate renal IRI. METHODS: Small RNA sequencing was performed to profile microRNA expression in mouse kidneys after transplantation. Lentivirus incorporating a miR-199a-5p modulator was injected into mouse kidney in situ before unilateral IRI and syngenetic transplantation, to determine the effect of miR-199a-5p in vivo. miR-199a-5p mimic or inhibitor was transfected cultured tubular cells before renal tubular ATP depletion recovery treatment to the examine the role of miR-199a-5p in vitro. RESULTS: Sequencing showed upregulation of miR-199a-5p in post-transplantation mouse kidney following renal IRI was localized to renal tubular epithelial cells. Lentivirus incorporating a miR-199a-5p mimic aggravated renal IRI and opposing effects were obtained with a miR-199a-5p inhibitor. Treatment with the miR-199a-5p inhibitor ameliorated graft function loss, tubular injury and immune response after cold storage transplantation. In vitro experiments demonstrated aggravation of cell death caused by ATP depletion and repletion when the miR-199a-5p mimic was present while the miR-199a-5p inhibitor reduced cell death. miR-199a-5p was shown to target a-kinase anchoring protein 1(AKAP1) by double luciferase assay and miR-199a-5p activation reduced dynamin related protein 1 (Drp1)-s637 phosphorylation and mitochondrial length. Overexpression of AKAP1 preserved Drp1-s637 phosphorylation and reduced mitochondrial fission. CONCLUSION: MiR-199a-5p activation reduced AKAP1 expression, promoted Drp1-s637 dephosphorylation, aggravated the disruption of mitochondrial dynamics and contributed to ischemic kidney injury.

Optimizing motion detection performance: Harnessing the power of squeeze and excitation modules.

This paper introduces an innovative segmentation model that extends the U-Net architecture with a Squeeze and Excitation (SE) mechanism, designed to enhance the detection of moving objects in video streams. By integrating this model into the ViBe motion detection algorithm, we have significantly improved detection accuracy and reduced false positive rates. Our approach leverages adaptive techniques to increase the robustness of the segmentation model in complex scenarios, without requiring extensive manual parameter tuning. Despite the notable improvements, we recognize that further training is necessary to optimize the model for specific applications. The results indicate that our method provides a promising direction for real-time motion detection systems that require high precision and adaptability to varying conditions.

Generation of a human induced pluripotent stem cell (iPSC, DVSi001-A) with a heterozygous mutation in KRAS (A209T).

Human varicose veins are commonly claimed to be responsible for lower limb symptoms. Mutation in KRAS gene has been implicated in various diseases, including cancers and vascular diseases. While little known about the novel mutation in KRAS gene and its contribution to the development of varicose veins. Here, we have generated human induced pluripotent stem cell (iPSC) line, which harboured a novel mutation in KRAS (c.209A>T) gene. This cell line provided a novel tool for understanding the mechanism of KRAS mutation in the pathogenesis of varicose veins.

Rational Design of a Novel 6H-Benzo[c]chromen Series as Selective PI3Kα Inhibitors.

The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A selective PI3Kα inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a novel series of selective PI3Kα inhibitors using structure-based drug design and molecular docking to inform the design of 6H-benzo[c]chromen inhibitors. XJTU-L453 (21) was identified with PI3Kα inhibitory potency and unique selectivity over other PI3K isoforms and all other kinases tested. Further evaluation of pharmacokinetic properties and in vivo efficacy led to the identification of the preclinical potential of XJTU-L453 (21).

Exploring Degradation of Intrinsically Disordered Protein Yes-Associated Protein Induced by Proteolysis TArgeting Chimeras.

Yes-associated protein (YAP) is a key oncogene in the Hippo tumor suppression pathway, historically challenging to target due to its intrinsically disordered nature. Leveraging recent advances in high-throughput screening that identified several YAP binders, we employed proteolysis-targeting chimera technology to develop a series of YAP degraders. Utilizing NSC682769, a known YAP binder, linked with VHL ligand 2 or pomalidomide via diverse linkers, we synthesized degraders including YZ-6. This degrader not only recruits the E3 ligase VHL for the rapid and sustained degradation of YAP but also effectively inhibits its nuclear localization, curtailing YAP/TEAD-mediated transcription in cancer cell lines such as NCI-H226 and Huh7. This dual action significantly diminishes YAP's oncogenic activity, contributing to the potent antiproliferative effects observed both in vitro and in a Huh7 xenograft mouse model. These results underscore the potential of PROTAC-mediated YAP degradation as a strategy for treating YAP-driven cancers.

Electroacupuncture protects against cerebral ischemia-reperfusion injury through mitochondrial dynamics.

Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury. Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining. Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury. Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.

Chloroformate-mediated ring cleavage of indole alkaloids leads to re-engineered antiplasmodial agents.

Natural product ring distortion strategies have enabled rapid access to unique libraries of stereochemically complex compounds to explore new chemical space and increase our understanding of biological processes related to human disease. Herein is described the development of a ring-cleavage strategy using the indole alkaloids yohimbine, apovincamine, vinburnine, and reserpine that were reacted with a diversity of chloroformates paired with various alcohol/thiol nucleophiles to enable the rapid synthesis of 47 novel small molecules. Ring cleavage reactions of yohimbine and reserpine produced two diastereomeric products in moderate to excellent yields, whereas apovincamine and vinburnine produced a single diastereomeric product in significantly lower yields. Free energy calculations indicated that diastereoselectivity regarding select ring cleavage reactions from yohimbine and apovincamine is dictated by the geometry and three-dimensional structure of reactive cationic intermediates. These compounds were screened for antiplasmodial activity due to the need for novel antimalarial agents. Reserpine derivative 41 was found to exhibit interesting antiplasmodial activities against Plasmodium falciparum parasites (EC50 = 0.50 µM against Dd2 cultures), while its diastereomer 40 was found to be three-fold less active (EC50 = 1.78 µM). Overall, these studies demonstrate that the ring distortion of available indole alkaloids can lead to unique compound collections with re-engineered biological activities for exploring and potentially treating human disease.

Daytime Napping, Incident Atrial Fibrillation, and Dynamic Transitions With Dementia.

Background: Associations between napping and incident atrial fibrillation (AF) remain unknown, and few studies have accounted for dynamic transitions between AF and dementia. Objectives: The purpose of this study was to evaluate associations between napping with incident AF and the dynamic transitions of AF and dementia, as well as the mediation pathway of left ventricular (LV) size and function. Methods: A total of 476,588 participants from UK Biobank were included. Napping frequency and other sleep behaviors were evaluated. Incident AF, dementia, and mortality were ascertained via linkage to external registry databases. LV size and function indices were obtained from cardiovascular magnetic resonance imaging phenotypes. A multistate survival analysis was conducted to examine daytime napping in relation to dynamic transitions. Weighed AF genetic risk score was calculated. Results: Frequent daytime napping, compared to never/rarely napping, was associated with a 1.17-fold AF risk (HR: 1.17; 95% CI: 1.12-1.22), which persisted after controlling for other sleep behaviors. Genetic predisposition significantly modified associations between napping and AF (P for interaction <0.001), with stronger associations observed in those of low and moderate genetic risk. LV ejection fraction significantly mediated 26.2% (95% CI: 4.2%-74.1%) of associations between napping and AF. Frequent napping was also associated with a 1.27-fold risk of transition from AF to comorbidity of AF and dementia. Conclusions: Our findings highlight the potential importance of screening for napping in view of the association with incident AF and dementia. Routine evaluations of the LV ejection fraction could be warranted to timely identify early indications of AF onset among habitual nappers.

Role of Microglial Mitophagy in Alleviating Postoperative Cognitive Dysfunction: a Mechanistic Study.

Postoperative cognitive dysfunction (POCD), a common complication following anesthesia and surgery, is influenced by hippocampal neuroinflammation and microglial activation. Mitophagy, a process regulating inflammatory responses by limiting the accumulation of damaged mitochondria, plays a significant role. This study aimed to determine whether regulating microglial mitophagy and the cGAS-STING pathway could alleviate cognitive decline after surgery. Exploratory laparotomy was performed to establish a POCD model using mice. Western blotting, immunofluorescence staining, transmission electron microscopy, and mt-Keima assays were used to examine microglial mitophagy and the cGAS-STING pathway. Quantitative polymerase chain reaction (qPCR) was used to detect inflammatory mediators and cytosolic mitochondrial DNA (mtDNA) levels in BV2 cells. Exploratory laparotomy triggered mitophagy and enhanced the cGAS-STING pathway in mice hippocampi. Pharmacological treatment reduced microglial activation, neuroinflammation, and cognitive impairment after surgery. Mitophagy suppressed the cGAS-STING pathway in mice hippocampi. In vitro, microglia-induced inflammation was mediated by mitophagy and the cGAS-STING pathway. Small interfering RNA (siRNA) of PINK1 hindered mitophagy activation and facilitated the cytosolic release of mtDNA, resulting in the initiation of the cGAS-STING pathway and innate immune response. Microglial mitophagy inhibited inflammatory responses via the mtDNA-cGAS-STING pathway inducing microglial mitophagy and inhibiting the mtDNA-cGAS-STING pathway may be an effective therapeutic approach for patients with POCD.

Hormone Therapy and Biological Aging in Postmenopausal Women.

Importance: Menopause is associated with biological aging, and hormone therapy (HT) is associated with health outcomes in postmenopausal women. Objective: To evaluate the association between HT use and discrepancies between chronological and biological age in postmenopausal women as well as the potential modifying role of socioeconomic status (SES). Design, Setting, and Participants: This population-based, retrospective cohort study included postmenopausal women registered in the UK Biobank. A baseline survey on HT use and biological aging biomarkers was conducted from March 2006 to October 2010. Data analyses were conducted in December 2023. Exposures: Information regarding HT use, the age at starting HT, and HT duration was collected via a touchscreen questionnaire. SES was evaluated by education, family income, occupation, and the Townsend Deprivation Index. Main Outcomes and Measures: Biological aging discrepancy was evaluated using validated phenotypic age, which was calculated using chronological age and 9 biomarkers measured at baseline. All-cause and cause-specific mortality were also assessed. Results: Among the 117 763 postmenopausal women (mean [SD] age, 60.2 [5.4] years), 47 461 (40.3%) ever used HT. The mean phenotypic age was 52.1 (7.9) years. Ever use of HT was associated with a smaller biological aging discrepancy than never use of HT (ß, -0.17 years; 95% CI, -0.23 to -0.10 years). This smaller aging discrepancy was more evident in those who started HT at age 55 years or older (ß, -0.32 years; 95% CI, -0.48 to -0.15 years) and in those who used HT for 4 to 8 years (ß, -0.25 years; 95% CI, -0.35 to -0.15 years). The association between HT and a smaller aging discrepancy was more evident in women with low SES, with a significant interaction observed for education (higher education: ß, -0.08 years [95% CI, -0.17 to 0.01]; other education: ß, -0.23 [95% CI, -0.32 to -0.14] years; P for interaction = .02). Phenotypic aging discrepancy mediated 12.7% (95% CI, 6.3% to 23.9%) of the association between HT and all-cause mortality and cause-specific mortality. Conclusions and Relevance: In this study, postmenopausal women with historical HT use were biologically younger than those not receiving HT, with a more evident association observed in those with low SES. The biological aging discrepancy mediated the association between HT and decreased mortality. Promoting HT in postmenopausal women could be important for healthy aging.

Biomimetic Exploration and Reflection on Switchable Coordination and Narrow-Band Electrofluorochromic Devices.

Electrofluorochromic (EFC) materials and devices with controllable fluorescence properties show great application potential in advanced anticounterfeiting, information storage and display. However, the low color purity caused by the broad emission spectra and underperforming switching time of the existing EFC materials limit their application. Through biomimetic exploration and the study of reversible electrochemical responsive coordination reactions, boron-nitrogen embedded polyaromatics (B,N-PAHs) with narrow-band emission and high color purity have been successfully integrated into EFC systems, which also help to better understand the role of boron in biological activity. The EFC device achieve good performance containing quenching efficiency greater than 90% within short switching time (ton: 0.6 s, toff: 2.4 s), and nearly no performance change after 200 cycles test. Three primary color (red, green, and blue) EFC devices are successfully prepared. In addition, new phenomena are obtained and discussed in this biomimetic exploration of related boron reactions. The success and harvest of this exploration are expected to provide new ideas for optimizing properties and broadening applications of EFC materials. Moreover, it may provide ideas and reference significance for further exploring and understanding the function of boron compounds in biological systems.

A Lu3Sc2Ga3O12: Eu3+ red-emitting phosphor with excellent optical properties and thermal stability was obtained by partially replacing Lu3+ with Gd3+ / Y3.

A novel red phosphor Lu3(1-x)Sc2Ga3O12: xEu3+(0 ≤ x ≤ 0.3) was successfully prepared by high temperature solid state method. The Lu2.4Sc2Ga3O12: 0.2Eu3+ phosphor shows strong high internal quantum efficiency and thermal stability with values of 64.79 % and 87.0 %, respectively. Based on Lu2.4Sc2Ga3O12: 0.2Eu3+ phosphor, the partial replacement of Lu3+ ions in the host by Gd3+ / Y3+ ions changes the local crystal field environment of Eu3+ ions, resulting in wonderful changes in the luminous center, and the luminous intensity at 593 nm is increased by 3.66 and 3.54 times, respectively. The decay time of Eu3+ ions is analyzed from the perspective of dynamics, and the reasons for the enhancement of luminescence after partial replacement of Lu3+ ions are discussed in detail from two aspects of phosphor structure and crystal field effect around Eu3+ ions. In addition, with the substitution of Gd3+ / Y3+ ions, the thermal stability of the sample is 90.3 %/89.4 % with excellent low thermal quenching. The thermal quenching mechanism is described by combining Debye temperature and activation energy. The sample also has a high internal quantum efficiency IQE=79.03 % / 78.24 %. Finally, under the excitation of 365 nm chip, the phosphors of Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Gd3+ and Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Y3+ synthesized R-LED device has extremely high color rendering index, Ra is 78.23/77.15 and color temperature is 1640.38 K/1642.97 K. The experimental results show that the Lu2.34Sc2Ga3O12: 0.2Eu3+, 0.02Gd3+ / Y3+ phosphors prepared has a wide application prospect in w-LED devices.