Decimeter-depth and polarization addressable color 3D meta-holography.

Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

Evolution of treatment options for juvenile idiopathic arthritis.

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs (NSAIDs) for juvenile idiopathic arthritis (JIA). Herein, we outline the progress in drug therapy of JIA. NSAIDs have traditionally been the primary treatment for all forms of JIA. NSAIDs are symptom-relief medications, and well tolerated by patients. Additionally, the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs. Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect. However, the frequent adverse events limit the clinical use. Both NSAIDs and glucocorticoid fail to ease or prevent joint damage, and the breakthrough comes along with the disease-modifying antirheumatic drugs (DMARDs). DMARDs can prevent disease progression and reduce joint destruction. Particularly, the emergence of biologic DMARDs (bDMARDs) has truly revolutionized the therapeutics of JIA, compared with conventional synthetic DMARDs. As a newly developed class of drugs, the places of most bDMARDs in the management of JIA remain to be well established. Nevertheless, the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

Monosilicon Derivatives of Phenanthrene and Pyrene as Potential Singlet Fission Materials for High-Performance Solar Cells.

Singlet fission (SF) is a process in which the energy of a singlet-excited molecule is divided into two triplet excitations. This is a special case of an internal conversion that is spin-allowed and extremely fast. Ideally, this process utilizes one photon to produce two electron-hole pairs. In tandem with a layer of singlet fission material, conventional solar cells can achieve improved efficiency by utilizing higher-energy photons. This density functional theory study provides information about additional efficient SF chromophores that were theoretically modeled by functionalizing phenanthrene and pyrene via site-specific monosilicon substitutions. The SF capabilities of the derivatives were evaluated by calculating the SF thermodynamic driving force (ΔESF) and the excited state's molecular planarity. The most promising monosilicon derivatives with SF capabilities are 3-silaphenanthrene and 1-silapyrene for each family, respectively. All phenanthrene and pyrene monosilicon derivatives are strong closed-shell species, because their multiple diradical characteristics are close to zero. Based on these results, 3-silaphenanthrene and 1-silapyrene were selected for electron excitation analysis, which further demonstrated that the monosilicon functionalization of phenanthrene and pyrene led to a transfer from local excitation characters to hybridized local and charge-transfer characters of the excited states, resulting in a significant change from endoergic to exoergic in the SF chromophores.

Efficacy of Sacubitril Valsartan sodium tablets in patients with heart failure combined with pulmonary infection and long-term recurrence rate.

OBJECTIVE: To observe the therapeutic effect of Sacubitril Valsartan sodium tablets (SVST) on heart failure (HF) complicated by pulmonary infection (PI), and to provide a reference for future medication. METHODS: A total of 89 patients with HF complicated by PI who were treated at Dongying People's Hospital from January 2019 to May 2020 were selected as study subjects in this retrospective study. The control group consisted of 41 patients who received conventional treatment, while the study group included 48 patients who received SVST in addition to conventional treatment. The time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales in both groups were recorded. The levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and procalcitonin (PCT) were measured before and after treatment. Changes in cardiac function were observed, and the Clinical Pulmonary Infection Score (CPIS) and Sequential Organ Failure Assessment (SOFA) were used to assess PI. The clinical efficacy and adverse reactions were evaluated after treatment. Follow-up lasted 2 years, during which the readmission rate due to HF and mortality rate were calculated. RESULTS: Patients in the study group experienced a shorter time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales compared to the control group (all P<0.05). The study group also showed reduced levels of BNP, IL-6, TNF-α, and PCT, as well as lower CPIS and SOFA scores after treatment (all P<0.05), with significantly improved cardiac function (P<0.05). Additionally, the total effective rate was higher in the study group than in the control group (P<0.05), and there was no significant difference in adverse reactions between the two groups (P>0.05). Follow-up revealed no difference in mortality between the two groups (P>0.05), but the study group had a lower readmission rate (P<0.05). CONCLUSION: SVST is effective in treating HF complicated by PI, ensures a good prognosis for patients, and is recommended for clinical use.

Artesunate attenuates osteoarthritis in mice by promoting MTA1 transcription through a USP7/FoxO1 axis.

Artesunate (ART) is a derivative of artemisinin and has anti-inflammatory, anti-tumor, and anti-angiogenic properties. Although ART has been implicated in osteoarthritis (OA), the mechanism needs to be further dissected. Here, we explored the effects of ART on the development of OA and the underlying mechanism using destabilization of the medial meniscus (DMM) surgical instability model. Mice with OA were developed using DMM and treated with ART. The pathological morphology of knee joint tissues was examined, and the degeneration of joint cartilage was assessed. Mouse knee chondrocytes were isolated and induced with IL-1ß, followed by ART treatment. ART alleviates OA in mice by elevating ubiquitin carboxyl-terminal hydrolase 7 (USP7) expression, and USP7 inhibitor (P22077) treatment mitigated the protective effects of ART on chondrocytes. We also showed that USP7 mediated the deubiquitination of forkhead box protein O1 (FoxO1), while FoxO1 alleviated chondrocyte injury. In addition, FoxO1 promoted metastasis-associated protein MTA1 (MTA1) transcription, and downregulation of MTA1 exacerbated chondrocyte injury. Our study identifies that USP7/FoxO1/MTA1 is a key signaling cascade in the treatment of ART on OA.

Armored bicistronic CAR T cells with dominant-negative TGF-ß receptor II to overcome resistance in glioblastoma.

Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells used to eliminate tumor cells. The human transforming growth factor ß (TGF-ß) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. To mitigate TGF-ß-mediated suppressive activity, we combined a dominant-negative TGF-ß receptor II (dnTGFßRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFßRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggest that CART-EGFR-IL13Rα2-dnTGFßRII significantly augments T cell proliferation, enhances functional responses, and improves the fitness of bystander cells, particularly by decreasing the TGF-ß concentration in a TGF-ß-rich TME. In addition, in vivo studies validate the safety and efficacy of the dnTGFßRII cooperating with CARs in targeting and eradicating GBM in an NSG mouse model.

Patients' health related quality of life after massive weight loss reconstruction in the Netherlands.

OBJECTIVES: The present study aimed to evaluate the impact of undergoing massive weight loss reconstruction (MWR) on health-related quality of life (HR-QoL) in the Netherlands. METHOD: A retrospective study was performed among 131 Dutch bariatric patients, divided into two groups: an intervention group (93 patients who had undergone MWR) and a control group (38 patients who had not undergone MWR). HR-QoL was assessed by the validated BODY-q questionnaire. The sign test was used to measure the difference between the 0 and 12 months' measurements of HR-QoL in both groups, whereas multiple regression analysis was conducted to assess whether undergoing MWR significantly predicted participants' incremental HR-QoL. RESULTS: Whereas the intervention group showed a significance improvement on all parameters of the BODY-q between 0 and 12 months (all parameters p < .001), the control group did not. The multiple regression analysis showed that having undergone a MWR significantly and positively predicted incremental HR-QoL on all scales on the BODY-q (all parameters p < 0.05). CONCLUSION: The present study suggests a positive impact of MWR on the HR-QoL of bariatric patients.

Identification of potential biomarkers for atrial fibrillation and stable coronary artery disease based on WGCNA and machine algorithms.

BACKGROUND: Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. METHODS: Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. RESULTS: We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. CONCLUSION: COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

Increasing cotton lint yield and water use efficiency for subsurface drip irrigation without mulching.

Introduction: Planting without mulching can eliminate the residual film pollution caused by the long-term use of plastic film covers, but it will increase soil moisture evaporation and heat loss and severely reduce water use efficiency and cotton productivity in cotton (Gossypium hirsutum L.) fields in arid regions. It is unclear whether the advantages of subsurface drip irrigation and nighttime irrigation can be leveraged to reduce the amount of irrigation applied in fields, improve the soil and leaf hydrothermal environments, and increase the synchronicity of yield and water use efficiency (WUE). Methods: Therefore, in a two-year field experiment (2019-2020), cotton was grown under different irrigation treatments (I5, 3753 m3 ha-1; I4, 3477 m3 ha-1; I3, 3201 m3 ha-1; I2, 2925 m3 ha-1; and I1, 2649 m3 ha-1). The soil volumetric moisture content, soil temperature, leaf relative water content (RWC), daily changes in gas exchange parameters, lint yield, and WUE were evaluated. Results and discussion: The results showed that reducing irrigation can reduce the soil volumetric moisture content (0-40 cm soil layer), increase the soil temperature and soil temperature conductivity, and increase the leaf temperature, intercellular carbon dioxide concentration (Ci), and WUE; however, reducing irrigation is not conducive to increasing the leaf RWC, net photosynthetic rate (Pn), stomatal conductance (Gs), or transpiration rate (Tr). There was no significant difference in WUE between the I3 and I4 treatments from 8:00 to 20:00, but the lint yield in these treatments increased by 2.8-12.2% compared to that in the I5 treatment, with no significant difference between the I3 and I4 treatments. In addition, a related analysis revealed that the positive effects of the leaf hydrothermal environment on the Pn and soil temperature on the WUE occurs during the same period (10:00-16:00). Overall, an irrigation amount of 3201-3477 m3 ha-1 applied with a subsurface nighttime irrigation system without mulching can enhance the soil moisture content and soil temperature, maintain a high photosynthetic capacity, and increase the lint yield and WUE. These results revealed that the negative impacts of plastic film contamination in arid areas can be alleviated.

Ganoderma lucidum Polysaccharide Peptide Alleviates Cyclophosphamide-Induced Male Reproductive Injury by Reducing Oxidative Stress and Apoptosis.

Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. The Ganoderma lucidum polysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy.

Numerical simulation of blasting behavior of rock mass with cavity under high in-situ stress.

With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

Real-time citrus variety detection in orchards based on complex scenarios of improved YOLOv7.

Variety detection provides technical support for selecting XinHui citrus for use in the production of XinHui dried tangerine peel. Simultaneously, the mutual occlusion between tree leaves and fruits is one of the challenges in object detection. In order to improve screening efficiency, this paper introduces a YOLO(You Only Look Once)v7-BiGS(BiFormer&GSConv) citrus variety detection method capable of identifying different citrus varieties efficiently. In the YOLOv7-BiGS network model, initially, the BiFormer attention mechanism in the backbone of the YOLOv7-based network strengthens the model's ability to extract citrus' features. In addition, the introduction of the lightweight GSConv convolution in place of the original convolution within the ELAN of the head component effectively streamlines model complexity while maintaining performance integrity. To environment challenge validate the effectiveness of the method, the proposed YOLOv7-BiGS was compared with YOLOv5, YOLOv7, and YOLOv8. In the comparison of YOLOv7-BiGS with YOLOv5, YOLOv7, and YOLOv8, the experimental results show that the precision, mAP and recell of YOLOv7-BiGS are 91%, 93.7% and 87.3% respectively. Notably, compared to baseline methods, the proposed approach exhibited significant enhancements in precision, mAP, and recall by 5.8%, 4.8%, and 5.2%, respectively. To evaluate the efficacy of the YOLOv7-BiGS in addressing challenges posed by complex environmental conditions, we collected occluded images of Xinhui citrus fruits from the Xinhui orchard base for model detection. This research aims to fulfill performance criteria for citrus variety identification, offering vital technical backing for variety detection endeavors.

Metabolites from traditional Chinese botanical drugs with anti-hepatitis B virus activity - a review.

Hepatitis B virus (HBV)-related liver disease poses a major threat to human health worldwide. Although interferon and nucleoside analogues are commonly administered for treating chronic HBV infection, their use is limited by considerable side effects, drug resistance and incapacity for HBV elimination. Hence, novel HBV therapeutics are urgently required. For numerous years, traditional Chinese botanical drugs have been widely used to treat HBV-related diseases. The natural metabolites derived from these traditional drugs exhibit significant anti-HBV effects and serve as potential novel drugs for treating HBV. For overall understanding the therapeutic potential of these metabolites, the anti-HBV effects and mechanisms of action of 107 natural metabolites are summarized in this article. Mechanistically, these natural metabolites exert their anti-HBV effects by influencing the expression and function of host and/or viral genes, which differs from the mechanism of action of nucleoside analogues. Indeed, combining natural metabolites with nucleoside analogues can exert synergistic effects. Accordingly, natural metabolites or their chemically modified derivatives represent potential novel drugs and adjuvants for anti-HBV treatment.

Identification of key genes as potential diagnostic biomarkers in sepsis by bioinformatics analysis.

Background: Sepsis, an infection-triggered inflammatory syndrome, poses a global clinical challenge with limited therapeutic options. Our study is designed to identify potential diagnostic biomarkers of sepsis onset in critically ill patients by bioinformatics analysis. Methods: Gene expression profiles of GSE28750 and GSE74224 were obtained from the Gene Expression Omnibus (GEO) database. These datasets were merged, normalized and de-batched. Weighted gene co-expression network analysis (WGCNA) was performed and the gene modules most associated with sepsis were identified as key modules. Functional enrichment analysis of the key module genes was then conducted. Moreover, differentially expressed gene (DEG) analysis was conducted by the "limma" R package. Protein-protein interaction (PPI) network was created using STRING and Cytoscape, and PPI hub genes were identified with the cytoHubba plugin. The PPI hub genes overlapping with the genes in key modules of WGCNA were determined to be the sepsis-related key genes. Subsequently, the key overlapping genes were validated in an external independent dataset and sepsis patients recruited in our hospital. In addition, CIBERSORT analysis evaluated immune cell infiltration and its correlation with key genes. Results: By WGCNA, the greenyellow module showed the highest positive correlation with sepsis (0.7, p = 2e - 19). 293 DEGs were identified in the merged datasets. The PPI network was created, and the CytoHubba was used to calculate the top 20 genes based on four algorithms (Degree, EPC, MCC, and MNC). Ultimately, LTF, LCN2, ELANE, MPO and CEACAM8 were identified as key overlapping genes as they appeared in the PPI hub genes and the key module genes of WGCNA. These sepsis-related key genes were validated in an independent external dataset (GSE131761) and sepsis patients recruited in our hospital. Additionally, the immune infiltration profiles differed significantly between sepsis and non-sepsis critical illness groups. Correlations between immune cells and these five key genes were assessed, revealing that plasma cells, macrophages M0, monocytes, T cells regulatory, eosinophils and NK cells resting were simultaneously and significantly associated with more than two key genes. Conclusion: This study suggests a critical role of LTF, LCN2, ELANE, MPO and CEACAM8 in sepsis and may provide potential diagnostic biomarkers and therapeutic targets for the treatment of sepsis.

DEKR-SPrior: An Efficient Bottom-Up Keypoint Detection Model for Accurate Pod Phenotyping in Soybean.

The pod and seed counts are important yield-related traits in soybean. High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner. Recent advances in artificial intelligence, especially deep learning (DL) models, have provided new avenues for high-throughput phenotyping of crop traits with increased precision. However, the available DL models are less effective for phenotyping pods that are densely packed and overlap in in situ soybean plants; thus, accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge. To address this challenge, the present study proposed a bottom-up model, DEKR-SPrior (disentangled keypoint regression with structural prior), for in situ soybean pod phenotyping, which considers soybean pods and seeds analogous to human people and joints, respectively. In particular, we designed a novel structural prior (SPrior) module that utilizes cosine similarity to improve feature discrimination, which is important for differentiating closely located seeds from highly similar seeds. To further enhance the accuracy of pod location, we cropped full-sized images into smaller and high-resolution subimages for analysis. The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models, viz., Lightweight-OpenPose, OpenPose, HigherHRNet, and DEKR, reducing the mean absolute error from 25.81 (in the original DEKR) to 21.11 (in the DEKR-SPrior) in pod phenotyping. This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping, and we hope that DEKR-SPrior will help future plant phenotyping.

Urea transporter UT-A1 as a novel drug target for hyponatremia.

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.

DG2GAN: improving defect recognition performance with generated defect image sample.

This article aims to improve the deep-learning-based surface defect recognition. In actual manufacturing processes, there are issues such as data imbalance, insufficient diversity, and poor quality of augmented data in the collected image data for product defect recognition. A novel defect generation method with multiple loss functions, DG2GAN is presented in this paper. This method employs cycle consistency loss to generate defect images from a large number of defect-free images, overcoming the issue of imbalanced original training data. DJS optimized discriminator loss is introduced in the added discriminator to encourage the generation of diverse defect images. Furthermore, to maintain diversity in generated images while improving image quality, a new DG2 adversarial loss is proposed with the aim of generating high-quality and diverse images. The experiments demonstrated that DG2GAN produces defect images of higher quality and greater diversity compared with other advanced generation methods. Using the DG2GAN method to augment defect data in the CrackForest and MVTec datasets, the defect recognition accuracy increased from 86.9 to 94.6%, and the precision improved from 59.8 to 80.2%. The experimental results show that using the proposed defect generation method can obtain sample images with high quality and diversity and employ this method for data augmentation significantly enhances surface defect recognition technology.

Cost-effectiveness of a multicomponent-adherence intervention in fracture liaison services.

BACKGROUND: This study aims to assess the lifetime cost-effectiveness of a multi-component adherence intervention (MCAI), including a patient decision aid and motivational interviewing, compared to usual care in patients with a recent fracture attending fracture liaison services (FLS) and eligible for anti-osteoporosis medication (AOM). RESEARCH DESIGN AND METHODS: Data on AOM initiation and one-year persistence were collected from a quasi-experimental study conducted between 2019 and 2023 in two Dutch FLS centers. An individual level, state-transition Markov model was used to simulate lifetime costs and quality-adjusted life years (QALYs) with a societal perspective of MCAI vs usual care. One-way and probabilistic sensitivity analyses were conducted including variation in additional FLS and MCAI costs (no MCAI cost in baseline). RESULTS: MCAI was associated with gain in QALYs (0.0012) and reduction in costs (-€16) and is therefore dominant. At the Dutch willingness-to-pay threshold of €50,000/QALY, MCAI remained cost-effective when increasing costs of the FLS visit or the yearly maintenance cost for MCAI up to +€60. Probabilistic sensitivity analysis demonstrated MCAI to be dominant in 54% of the simulations and cost-effective in 87% with a threshold of €50,000/QALY. CONCLUSIONS: A MCAI implemented in FLS centers may lead to cost-effective allocation of resources in FLS care, depending on extra costs.

HIF-1 induced tiRNA-Lys-CTT-003 is protective against cisplatin induced ferroptosis of renal tubular cells in mouse AKI model.

HIF-1 activation is protective in acute kidney injury (AKI), but its underlying mechanism is not fully understood. Stress-induced tRNA derived small RNAs play an emerging role in cellular processes. This study investigated the role of HIF-1 associated tiRNA-Lys-CTT-003 (tiR-Lys) in an AKI mouse model. Our sequencing results showed that ischemia can promote the production of renal tiR-Lys by activating HIF-1α. FG-4592, a HIF-1 inducer, can also upregulate the expression of tiR-Lys in renal tubular cells. Both overexpression of tiR-Lys and FG-4592 pre-treatment could improve mitochondrial damage and lipid peroxidation with alleviated renal function and morphological damage in cisplatin-induced AKI mice. While the anti-ferroptosis effect of FG-4592 were largely eliminated by tiR-Lys inhibitor. Notably, tiR-Lys directly alleviated cell death and MDA accumulation induced by the ferroptosis inducer Erastin, accompanied with restored expression of GPX4. RNA-Pulldown and RIP-qPCR results revealed that tiR-Lys can interact with the RNA-binding protein GRSF1.tiR-lys overexpression can preserve protein expression of GRSF1 decreased by cisplatin. Inhibiting Grsf1 via shRNA eliminated the upregulation of GPX4 by tiR-Lys. In conclusion, our study demonstrates that HIF-1α-induced tiR-Lys is protective in cisplatin-induced AKI, primarily by upregulating the level of GPX4 through interaction with GRSF1, thereby inhibiting ferroptosis in renal tubular epithelial cells.