SEED LIPID DROPLET PROTEIN1, SEED LIPID DROPLET PROTEIN2, and LIPID DROPLET PLASMA MEMBRANE ADAPTOR mediate lipid droplet-plasma membrane tethering.

Membrane contact sites (MCSs) are interorganellar connections that allow for the direct exchange of molecules, such as lipids or Ca2+ between organelles, but can also serve to tether organelles at specific locations within cells. Here, we identified and characterized three proteins of Arabidopsis thaliana that form a lipid droplet (LD)-plasma membrane (PM) tethering complex in plant cells, namely LD-localized SEED LD PROTEIN (SLDP) 1 and SLDP2 and PM-localized LD-PLASMA MEMBRANE ADAPTOR (LIPA). Using proteomics and different protein-protein interaction assays, we show that both SLDPs associate with LIPA. Disruption of either SLDP1 and SLDP2 expression, or that of LIPA, leads to an aberrant clustering of LDs in Arabidopsis seedlings. Ectopic co-expression of one of the SLDPs with LIPA is sufficient to reconstitute LD-PM tethering in Nicotiana tabacum pollen tubes, a cell type characterized by dynamically moving LDs in the cytosolic streaming. Furthermore, confocal laser scanning microscopy revealed both SLDP2.1 and LIPA to be enriched at LD-PM contact sites in seedlings. These and other results suggest that SLDP and LIPA interact to form a tethering complex that anchors a subset of LDs to the PM during post-germinative seedling growth in Arabidopsis.

Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases.

BACKGROUND: Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS: A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS: We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS: We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.

Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines.

The copper-catalyzed enantioselective allylation reaction of N-aryl aldimines has been developed using a combination of Cu(OAc)2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho-substituents on the N-aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N-aryl motif, three kinds of N-heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.

Development and validation of a nomogram for predicting refractory peritoneal dialysis related peritonitis.

OBJECTIVE: To identify the risk factors of refractory peritoneal dialysis related peritonitis (PDRP) and construct a nomogram to predict the occurrence of refractory PDRP. METHODS: Refractory peritonitis was defined as the peritonitis episode with persistently cloudy bags or persistent dialysis effluent leukocyte count >100 × 109/L after 5 days of appropriate antibiotic therapy. The study dataset was randomly divided into a 70% training set and a 30% validation set. Univariate logistic analysis, LASSO regression analysis, and random forest algorithms were utilized to identify the potential risk factors for refractory peritonitis. Independent risk factors identified using multivariate logistic analysis were used to construct a nomogram. The discriminative ability, calibrating ability, and clinical practicality of the nomogram were evaluated using the receiver operating characteristic curve, Hosmer-Lemeshow test, calibration curve, and decision curve analysis. RESULTS: A total of 294 peritonitis episodes in 178 patients treated with peritoneal dialysis (PD) were enrolled, of which 93 were refractory peritonitis. C-reactive protein, serum albumin, diabetes mellitus, PD duration, and type of causative organisms were independent risk factors for refractory peritonitis. The nomogram model exhibited excellent discrimination with an area under the curve (AUC) of 0.781 (95% CI: 0.716-0.847) in the training set and 0.741 (95% CI: 0.627-0.855) in the validation set. The Hosmer-Lemeshow test and calibration curve indicated satisfactory calibration ability of the predictive model. Decision curve analysis revealed that the nomogram model had good clinical utility in predicting refractory peritonitis. CONCLUSION: This nomogram can accurately predict refractory peritonitis in patients treated with PD.

Serum Human Epididymis Protein 4 as a Prognostic Predictor of New-Onset Heart Failure among Women after Acute Coronary Syndrome: A Single-Center Retrospective Study.

INTRODUCTION: Little is known about the prognostic factors among women with acute coronary syndrome (ACS), partly due to the small number of women included in heart failure (HF) clinical trials. Human epididymis protein 4 (HE4) has been proven to be a new biomarker for acute and chronic HF over the years. We hypothesize that HE4 could be a promising predictor. METHODS: This retrospective study analyzed data from Zhejiang Provincial People's Hospital. This study included 302 female patients with ACS between January 1, 2021, and December 1, 2021. The primary outcome was new-onset HF after ACS during the 12-month follow-up period. We used a logistic regression model to evaluate the association between serum HE4 levels and the incidence of HF. Serum HE4 levels were measured at baseline (within 24 h after admission). RESULTS: Of the 302 female patients, 70 (23.2%) developed new-onset HF within 12 months. Serum HE4 levels in patients with adverse events were significantly higher than those in patients without events (8.9 [7.3-11.5] pmol/dL versus 5.9 [5.0-6.8] pmol/dL, p < 0.001). The levels of HE4, troponin I peak, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) were validated as independent predictors, with HE4 being the best laboratory predictor (area under the curve, 0.863; 95% confidence interval, 0.817-0.909). Serum HE4 concentrations of >6.93 pmol/dL distinguished patients at risk of HF with 82.9% sensitivity and 78.0% specificity (maximum Youden index J, 0.609). Moreover, HE4 levels were associated with an increased risk of HF. DISCUSSION: We found a strong relationship between HE4 and the occurrence of HF after ACS among women, which might help identify patients at high risk of HF for whom close or intense management should be mandatory.

Elevated triglyceride-glucose index predisposes to the initial episode of peritonitis in chronic peritoneal dialysis patients.

OBJECTIVE: The serum triglyceride-glucose (TyG) index is a marker of inflammation. However, the relationship between TyG index and peritoneal dialysis-related peritonitis (PDRP) is unclear. This study aimed to investigate the potential relationship between the baseline TyG index and the initial episode of PDRP. METHODS: A total of 208 peritoneal dialysis (PD) patients were enrolled from January 1, 2012, to December 31, 2019 and followed up until December 31, 2022. They were divided into 2 groups according to the median TyG. The primary outcome was the occurrence of the initial episode of PDRP while on PD therapy. Kaplan-Meier curves and Cox regression analyses were used to examine the association between them. RESULTS: Eighty-five initial episodes of PDRP were identified. The risk of PDRP was higher in the high-TyG index group (p = 0.030). Multivariate Cox regression analysis showed a higher risk of PDRP in patients with a high TyG index (HR = 1.800, 95% CI 1.511-2.815, p = 0.010). CONCLUSION: The baseline serum TyG index was an independent risk factor for the initial episode of PDRP in chronic PD patients.

Guizhi longgu muli decoction ameliorates pathological changes in heart and bone in ovariectomized rats.

The aim of this study is to investigate the pathological changes in cardiac function, blood pressure, blood lipids and bone metabolism in ovariectomized (OVX) rats, as well as the intervention effect of Guizhi Longgu Muli decoction (GZLM). Bilateral oophorectomy was used to establish an OVX menopausal model. Four groups of rats were randomly selected: Sham surgery group, OVX group, estradiol (0.018g/L) and GZLM group (20g/kg). Cardiac function was assessed using ultrasound, blood pressure was measured using the tail cuff method. The oxidase method was used to determine the total cholesterol (TC) and triglycerides in serum. Direct measurement of high-density lipoprotein and low-density lipoprotein levels (LDL-C). Hematoxylin eosin staining and electron microscopy examination of myocardial structure. Microscopic CT was used to determine the bone microstructure. GZLM improved pathological cardiac changes and reduced the LVIDs, LVVols and LVVold. There was a decrease in systolic pressure, diastolic pressure and mean blood pressure in GZLM group. A decrease in serum TC and LDL-C levels was observed in the GZLM group. The BMD, BV/TV, Tb.Th, Tb.N of GZLM group raised, while Tb.SP and SMI significantly decreased or decreased. GZLM may have the effect of improving abnormal cardiac structure and function, promoting bone metabolism in OVX rats.

Functional requirement of the Arabidopsis importin-α nuclear transport receptor family in autoimmunity mediated by the NLR protein SNC1.

IMPORTIN-α3/MOS6 (MODIFIER OF SNC1, 6) is one of nine importin-α isoforms in Arabidopsis that recruit nuclear localization signal-containing cargo proteins to the nuclear import machinery. IMP-α3/MOS6 is required genetically for full autoimmunity of the nucleotide-binding leucine-rich repeat immune receptor mutant snc1 (suppressor of npr1-1, constitutive 1) and MOS6 also contributes to basal disease resistance. Here, we investigated the contribution of the other importin-α genes to both types of immune responses, and we analyzed potential interactions of all importin-α isoforms with SNC1. By using reverse-genetic analyses in Arabidopsis and protein-protein interaction assays in Nicotiana benthamiana, we provide evidence that among the nine α-importins in Arabidopsis, IMP-α3/MOS6 is the main nuclear transport receptor of SNC1, and that IMP-α3/MOS6 is required selectively for autoimmunity of snc1 and basal resistance to mildly virulent Pseudomonas syringae in Arabidopsis.

NLR we there yet? Nucleocytoplasmic coordination of NLR-mediated immunity.

Plant intracellular nucleotide-binding leucine-rich repeat immune receptors (NLRs) perceive the activity of pathogen-secreted effector molecules that, when undetected, promote colonisation of hosts. Signalling from activated NLRs converges with and potentiates downstream responses from activated pattern recognition receptors (PRRs) that sense microbial signatures at the cell surface. Efficient signalling of both receptor branches relies on the host cell nucleus as an integration point for transcriptional reprogramming, and on the macromolecular transport processes that mediate the communication between cytoplasm and nucleoplasm. Studies on nuclear pore complexes (NPCs), the nucleoporin proteins (NUPs) that compose NPCs, and nuclear transport machinery constituents that control nucleocytoplasmic transport, have revealed that they play important roles in regulating plant immune responses. Here, we discuss the contributions of nucleoporins and nuclear transport receptor (NTR)-mediated signal transduction in plant immunity with an emphasis on NLR immune signalling across the nuclear compartment boundary and within the nucleus. We also highlight and discuss cytoplasmic and nuclear functions of NLRs and their signalling partners and further consider the potential implications of NLR activation and resistosome formation in both cellular compartments for mediating plant pathogen resistance and programmed host cell death.

A simple APACHE IV risk dynamic nomogram that incorporates early admitted lactate for the initial assessment of 28-day mortality in critically ill patients with acute myocardial infarction.

BACKGROUND: Early risk stratification is important for patients with acute myocardial infarction (AMI). We aimed to develop a simple APACHE IV dynamic nomogram, combined with easily available clinical parameters within 24 h of admission, thus improving its predictive power to assess the risk of mortality at 28 days. METHODS: Clinical information on AMI patients was extracted from the eICU database v2.0. A preliminary XGBoost examination of the degree of association between all variables in the database and 28-day mortality was conducted. Univariate and multivariate logistic regression analysis were used to perform screening of variables. Based on the multifactorial analysis, a dynamic nomogram predicting 28-day mortality in these patients was developed. To cope with missing data in records with missing variables, we applied the multiple imputation method. Predictive models are evaluated in three main areas, namely discrimination, calibration, and clinical validity. The discrimination is mainly represented by the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Calibration is represented by the calibration plot. Clinical validity is represented by the decision curve analysis (DCA) curve. RESULTS: A total of 504 people were included in the study. All 504 people were used to build the predictive model, and the internal validation model used a 500-bootstrap method. Multivariate analysis showed that four variables, APACHE IV, the first sample of admission lactate, prior atrial fibrillation (AF), and gender, were included in the nomogram as independent predictors of 28-day mortality in AMI. The prediction model had an AUC of 0.819 (95%CI 0.770-0.868) whereas the internal validation model had an AUC of 0.814 (95%CI 0.765-0.860). Calibration and DCA curves indicated that the dynamic nomogram in this study were reflective of real-world conditions and could be applied clinically. The predictive model composed of these four variables outperformed a single APACHE IV in terms of NRI and IDI. The NRI was 16.4% (95% CI: 6.1-26.8%; p = 0.0019) and the IDI was 16.4% (95% CI: 6.0-26.8%; p = 0.0020). Lactate accounted for nearly half of the total NRI, which showed that lactate was the most important of the other three variables. CONCLUSION: The prediction model constructed by APACHE IV in combination with the first sample of admission lactate, prior AF, and gender outperformed the APACHE IV scoring system alone in predicting 28-day mortality in AMI. The prediction dynamic nomogram model was published via a website app, allowing clinicians to improve the predictive efficacy of the APACHE IV score by 16.4% in less than 1 min.

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study.

BACKGROUND: Thyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators. METHODS: This retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital's treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1). RESULTS: Compared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment. CONCLUSIONS: Low FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

Orthodontic compressive force modulates Ets-1/Tks5 pathway to promote the formation of circumferential invadopodia and the fusion of osteoclast precursors.

During orthodontic treatment a mechanical force is applied to the teeth. However, it remains unclear how mechanical force promotes the maturation and fusion of osteoclast precursors into osteoclasts. In this study, we aimed to explore the mechanism by which orthodontic compressive force promotes osteoclast maturation. We used a RAW264.7 macrophage-like cell line derived from Balb/c mice as the experimental model. We found that compressive force promoted the maturation of osteoclasts based on tartrate-resistant acid phosphatase staining and the formation of invadopodia based on immunstaining of Tks5 and F-actin. Moreover, we found that compressive force upregulated the expression of Ets-1 and Tks5 and promoted the activation of Ets-1 in RAW264.7 cells. Furthermore, we identified Tks5 as a transcription target of Ets-1 in RAW264.7 cells and demonstrated that Ets-1 mediates the effects of compressive force on Tks5 upregulation, invadopodia formation and cell fusion in osteoclasts. In conclusion, Ets-1 is upregulated by compressive force and it is essential to transducing the mechanical signal to promote invadopodia formation and osteoclast fusion. Our findings provide novel insight into the mechanism underlying osteoclast maturation and fusion during orthodontic treatment.

Elemental analysis and imaging of sunscreen fingermarks by X-ray fluorescence.

Chemical composition in fingermarks could provide useful information for forensic studies and applications. Here, we evaluate the feasibility of analysis and imaging of fingermarks via elements by synchrotron radiation X-ray fluorescence (SRXRF) and commercial X-ray fluorescence (XRF). As a proof of concept, we chose four brands of sunscreens to make fingermarks on different substrates, including plastic film, glass, paper, and silicon wafer. We obtained an evident image of fingermarks via zinc and titanium by XRF methods. In addition, the ratios of element concentrations in sunscreen fingermarks were obtained, which were in accordance with the results obtained by acid digestion and ICP-OES analysis. In comparison, commercial XRF offers the most advantages in terms of non-destructive detection, easy accessibility, fast element images, and broad applicability. The possibility to acquire fingermark images simultaneously with element information opens up new avenues for forensic science. Graphical abstract.

A rare endoscopic appearance of granulomatosis with polyangiitis involving the intestine: a case report.

BACKGROUND: The involvement of granulomatosis with polyangiitis is less frequent in the intestine. CASE PRESENTATION: We present a case of Wegener's granulomatosis with unusual endoscopic appearance, involvement in a young man's gastrointestinal tract. A 45-year-old man was diagnosed with Wegener's granulomatosis 11 years ago, and relapsed with abdominal pain and melena. A colonoscopy was performed, and the appearance of mucosal lesions with an unusual annular black membrane was observed. A black ring-shaped membranous tissue adhered to the surface of the colon wall, which could be traversed by an endoscopic forepart. CONCLUSION: Biopsy of the black membrane revealed degenerative colonic mucosal tissues, while deep colonic biopsy revealed inflammatory granulation tissues. This has not been reported in previous documents.

The miR172c-NNC1 module modulates root plastic development in response to salt in soybean.

BACKGROUND: Plant roots are highly plastic to high salinity. However, the molecular mechanism by which root developmental plasticity is regulated remains largely unknown. Previously we reported that miR172c-NNC1 module plays a key role in soybean-rhizobial symbiosis. The fact that the miR172c promoter contains several stress-related cis elements indicates that miR172c may have a role in root response to abiotic stress. RESULTS: Here we showed that miR172c is greatly induced by salt stress in soybean. Overexpression of miR172c and knockdown of miR172c activity resulted in substantially increased and reduced root sensitivity to salt stress, respectively. Furthermore, we show that the target gene NNC1 (Nodule Number Control 1) of miR172c was downregulated by salt stress. The transgenic roots overexpressing or knocking down NNC1 expression also exhibited the altered root sensitivity to salt stress. CONCLUSION: The study reveals the crucial role of miR172c-NNC1 module in root stress tolerance to salt stress in soybean.

JANet: A joint attention network for balancing accuracy and speed in left ventricular ultrasound video segmentation.

Multiple cardiac diseases are closely associated with functional parameters of the left ventricle, but functional parameter quantification still requires manual involvement, a time-consuming and less reproducible task. We develop a joint attention network (JANet) and expand it into two versions (V1 and V2) that can be used to segment the left ventricular region in echocardiograms to assist physicians in diagnosis. V1 is a smaller model with a size of 56.3 MB, and V2 has a higher accuracy. The proposed JANet V1 and V2 achieve a mean dice score (DSC) of 93.59/93.69(V1/V2), respectively, outperforming the state-of-the-art models. We grade 1264 patients with 87.24/87.50 (V1/V2) accuracy when using the 2-level classification criteria and 83.62/84.18 (V1/V2) when using the 5-level classification criteria. The results of the consistency analysis show that the proposed method is comparable to that of clinicians.

Adipose-derived stem cell exosomes loaded with icariin attenuated M1 polarization of macrophages via inhibiting the TLR4/Myd88/NF-κB signaling pathway.

Abnormal macrophage polarization is one of the common pathological bases of various inflammatory diseases. The current research focus involves targeting macrophages to remodel their phenotype as a treatment approach for inflammatory diseases. Notably, exosomes can be delivered to specific types of cells or tissues or inflammatory area to realize targeted drug delivery. Although icariin (ICA) exhibits regulatory potential in macrophage polarization, the practical application of ICA is impeded by its water insolubility, poor permeability, and low bioavailability. Exploiting the inherent advantages of exosomes as natural drug carriers, we introduce a novel drug delivery system-adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA. High-performance liquid chromatography analysis confirmed a loading rate of 92.7 ± 0.01 % for ADSCs-EXO-ICA, indicating the successful incorporation of ICA. As demonstrated by cell counting kit-8 assays, ADSCs-EXO exerted a significantly higher promotion effect on macrophage proliferation. The subsequent experimental results revealed the superior anti-inflammatory effect of ADSCs-EXO-ICA compared to individual treatments with EXO or ICA in the lipopolysaccharide + interferon-gamma-induced M1 inflammation model. Additionally, results from enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and western blot analyses revealed that ADSCs-EXO-ICA effectively inhibited macrophage polarization toward the M1-type and concurrently promoted polarization toward the M2-type. The underlying mechanism involved the modulation of macrophage polarization through inhibition of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-kappa B signaling pathway, thereby mitigating inflammation. These findings underscore the potential therapeutic value of ADSCs-EXO-ICA as a novel intervention for inflammatory diseases.

Developmental Toxicity of Fine Particulate Matter: Multifaceted Exploration from Epidemiological and Laboratory Perspectives.

Particulate matter of size ≤ 2.5 µm (PM2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health.

Fructus Ligustri Lucidi inhibits ferroptosis in ovariectomy­induced osteoporosis in rats via the Nrf2/HO­1 signaling pathway.

Postmenopausal osteoporosis (PMOP) has increased in prevalence in recent years, thus researchers have evaluated alternative medicine therapies. Fructus Ligustri Lucidi (FLL) can inhibit bone loss, and ferroptosis serves an important role in osteoporosis. Therefore, the present study assessed the presence of ferroptosis in PMOP and whether FLL could inhibit ferroptosis to improve bone microstructure in ovariectomized rats. Ovariectomized rats were treated with FLL (1.56 g/kg/day) for 12 weeks. Micro-CT was performed to evaluate the bone microstructure and bone mineral density. Western blotting and reverse transcription-quantitative PCR were performed to assess the relative expression levels of proteins and mRNA. Subsequently, malondialdehyde (MDA) and Fe2+ assay kits were used to quantify the MDA and Fe2+ content, respectively. The results demonstrated that ovariectomy (OVX) resulted in iron overload and the accumulation of lipid peroxide. Furthermore, the expression of key factors that inhibited ferroptosis, glutathione peroxidase 4 and solute carrier family 7 member 11 was significantly downregulated in ovariectomized rats, which was significantly reversed by FLL treatment. Furthermore, bone formation was assessed using the expression of osteogenesis-related genes, runt-related transcription factor 2 and osterix, which revealed significantly higher levels in FLL-treated rats compared with ovariectomized rats. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also significantly recovered following FLL treatment. In the present study, OVX of postmenopausal osteoporotic rats was found to induce ferroptosis by enhancing lipid peroxidation and Fe2+ levels. FLL significantly suppressed ferroptosis, protected the osteogenic ability of ovariectomized rats and promoted the Nrf2/HO-1 signaling pathway.

Association of Hemoglobin to Red Blood Cell Distribution Width-Standard Deviation (RDW-SD) Ratio and 3-Month Readmission in Elderly Chinese Patients with Heart Failure: A Retrospective Cohort Study.

Purpose: Hemoglobin (Hb) and red blood cell distribution width-standard deviation (RDW-SD) have clinical significance in the prognosis of heart failure (HF). Little is known regarding the prognostic value of the Hb/RDW-SD ratio in patients with HF. This study sought to investigate the association between Hb/RDW-SD ratio and HF 3-month readmission in Chinese elderly patients. Patients and Methods: The present study was a retrospective cohort study. A total of 1816 HF patients were extracted from the Chinese HF database. A generalized linear model was used to explore the association between Hb/RDW-SD and 3-month readmission in HF. The generalized additive model was used to explore the nonlinear relationship, and a two-piecewise linear regression model was used to find the inflection point. Subgroup analysis explored interactions and whether each subgroup was consistent with the primary outcome direction. Results: Result showed Hb/RDW-SD was negatively associated with HF 3-month readmission (OR = 0.70, 95% CI: 0.55 to 0.89, P = 0.0031). A non-linear relationship was detected between Hb/RDW-SD and HF 3-month readmission with two inflection points (1.78 and 2.17). Both Hb/RDW-SD < 1.78 and Hb/RDW-SD > 2.17 showed a significant correlation between them, with corresponding effect values of (OR = 0.38, 95% CI: 0.17 to 0.87, P = 0.0209) and (OR = 0.44, 95% CI: 0.27 to 0.71, P = 0.0007), respectively. Conclusion: Hb/RDW-SD is negatively associated with HF 3-month readmission. The relationship between Hb/RDW-SD and HF 3-month readmission is also non-linear. Both Hb/RDW-SD < 1.78 and Hb/RDW-SD > 2.17 were strong negatively associated with HF 3-month readmission.