Intranasal oxytocin improves interoceptive accuracy and heart-beat evoked potentials in a cardiac interoceptive task.

BACKGROUND: Interoception represents perception of the internal bodily state which is closely associated with social/emotional processing and physical health in humans. Understanding the mechanism underlying interoceptive processing, particularly its modulation, is thus of great importance. Given overlap between oxytocinergic pathways and interoceptive signaling substrates in both peripheral visceral organs and the brain, intranasal oxytocin administration is a promising approach for modulating interoceptive processing. METHODS: In a double-blind, placebo-controlled, between-subject design, 72 healthy male participants performed a cardiac interoceptive task during electroencephalograph (EEG) and electrocardiograph (ECG) recording to examine whether intranasal administration of the neuropeptide oxytocin can modulate interoceptive processing. We also collected data in a resting state to examine whether we could replicate previous findings. RESULTS: Results showed that in the interoceptive task oxytocin increased interoceptive accuracy at the behavioral level which was paralleled by larger heartbeat-evoked potential amplitudes at frontocentral and central regions on the neural level. However, there were no significant effects of oxytocin on EEG or ECG during resting-state. CONCLUSIONS: These findings suggest that oxytocin may only have a facilitatory effect on interoceptive processing during task-based conditions. Our findings not only provide new insights into the modulation of interoceptive processing via targeting the oxytocinergic system but also provide proof of concept evidence for the therapeutic potential of intranasal oxytocin in mental disorders with dysfunctional interoception.

Halogenated Dibenzo[f,h]quinoxaline Units Constructed 2D-Conjugated Guest Acceptors for 19% Efficiency Organic Solar Cells.

Halogenation of Y-series small-molecule acceptors (Y-SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power-conversion-efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D-structured large π-fused core of guest Y-SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D-conjugated Y-SMAs (X-QTP-4F, including halogen-free H-QTP-4F, chlorinated Cl-QTP-4F, brominated Br-QTP-4F, and iodinated I-QTP-4F) by attaching different halogens into 2D-conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X-QTP-4F, Cl-QTP-4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8-BO host. Moreover, among ternary PM6:L8-BO:X-QTP-4F blends, PM6:L8-BO:Cl-QTP-4F obtains a more uniform and size-suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8-BO:Cl-QTP-4F-based OSCs achieve a 19.0% efficiency, which is among the state-of-the-art OSCs based on 2D-conjugated Y-SMAs and superior to these devices based on PM6:L8-BO host (17.70%) and with guests of H-QTP-4F (18.23%), Br-QTP-4F (18.39%), and I-QTP-4F (17.62%). The work indicates that halogenation in 2D-structured dibenzo[f,h]quinoxaline core of Y-SMAs guests is a promising strategy to gain efficient ternary OSCs.

Interpretable machine learning models for predicting the incidence of antibiotic- associated diarrhea in elderly ICU patients.

BACKGROUND: Antibiotic-associated diarrhea (AAD) can prolong hospitalization, increase medical costs, and even lead to higher mortality rates. Therefore, it is essential to predict the incidence of AAD in elderly intensive care unit(ICU) patients. The objective of this study was to create a prediction model that is both interpretable and generalizable for predicting the incidence of AAD in elderly ICU patients. METHODS: We retrospectively analyzed data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH) in China. We utilized the machine learning model Extreme Gradient Boosting (XGBoost) and Shapley's additive interpretation method to predict the incidence of AAD in elderly ICU patients in an interpretable manner. RESULTS: A total of 848 adult ICU patients were eligible for this study. The XGBoost model predicted the incidence of AAD with an area under the receiver operating characteristic curve (ROC) of 0.917, sensitivity of 0.889, specificity of 0.806, accuracy of 0.870, and an F1 score of 0.780. The XGBoost model outperformed the other models, including logistic regression, support vector machine (AUC = 0.809), K-nearest neighbor algorithm (AUC = 0.872), and plain Bayes (AUC = 0.774). CONCLUSIONS: While the XGBoost model may not excel in absolute performance, it demonstrates superior predictive capabilities compared to other models in forecasting the incidence of AAD in elderly ICU patients categorized based on their characteristics.

Modulating Dimensionality of 2D Perovskite Layers for Efficient and Stable 2D/3D Perovskite Photodetectors.

Two-dimensional (2D) perovskites have been widely adopted for improving the performance and stability of three-dimensional (3D) metal halide perovskite devices. However, rational manipulation of the phase composition of 2D perovskites for suitable energy level alignment in 2D/3D perovskite photodetectors (PDs) has been rarely explored. Herein, we precisely controlled the dimensionality of the 2D perovskite on CsPbI2Br films by tuning the polarity of the n-butylammonium iodide (BAI)-based solvents. In comparison to the pure n = 1 2D perovskite (ACN-BAI) formed by acetonitrile treatment, a mixture of n = 1 and n = 2 phases (IPA-BAI) generated by isopropanol (IPA) treatment guaranteed more robust defect passivation and favorable energy level alignment at the perovskite/hole transport layer interface. Consequently, the IPA-BAI PD exhibited a responsivity of 0.41 A W-1, a detectivity of 1.01 × 1013 Jones, and a linear dynamic range of 120 dB. Furthermore, the mixed-phase 2D layer effectively shielded the 3D perovskite from moisture. The IPA-BAI device retained 76% of its initial responsivity after 500 h of nonencapsulated storage at 10% relative humidity. This research provides valuable insights into the dimensional modulation of 2D perovskites for further enhancing the performance of 2D/3D perovskite PDs.

Fibroblast activation protein-sensitive polymeric nanobeacon for early diagnosis of renal fibrosis.

Early diagnosis and treatment of renal fibrosis (RF) significantly affect the clinical outcomes of chronic kidney diseases (CKDs). As the typical fibrotic ailment, RF is characterized by remodeling of the extracellular matrix, and the activation of fibroblast activation protein (FAP) plays a crucial role in the mediation of extracellular matrix protein degradation. Therefore, FAP can serve as a biomarker for RF. However, up to now, no effective tools have been reported to diagnose early-stage RF via detecting FAP. In this work, a polymeric nanobeacon integrating an FAP-sensitive amphiphilic polymer and fluorophores was proposed, which was used to diagnose early RF by sensing FAP. The FAP can be detected in the range of 0 to 200 ng/mL with a detection limit of 0.132 ng/mL. Furthermore, the fluorescence imaging results demonstrate that the polymeric nanobeacon can sensitively image fibrotic kidneys in mice with unilateral ureteral occlusion (UUO), suggesting its potential for early RF diagnosis and guidance of FAP-targeted treatments. Importantly, when employed alongside with non-invasive diagnostic techniques like magnetic resonance imaging (MRI) and serological tests, this nanobeacon exhibits excellent biocompatibility, low biological toxicity, and sustained imaging capabilities, making it a suitable fluorescent tool for diagnosing various FAP-related fibrotic conditions. To our knowledge, this study represents the first attempt to image RF in early stage by detecting FAP, offering a promising fluorescent molecular tool for diagnosing various FAP-associated diseases in the future.

Fossil evidence sheds light on sexual selection during the early evolution of birds.

The impact of sexual selection on the evolution of birds has been widely acknowledged. Although sexual selection has been hypothesized as a driving force in the occurrences of numerous morphological features across theropod evolution, this hypothesis has yet to be comprehensively tested due to challenges in identifying the sex of fossils and by the limited sample size. Confuciusornis sanctus is arguably the best-known early avialan and is represented by thousands of well-preserved specimens from the Early Cretaceous Jehol lagerstätte, which provides us with a chance to decipher the strength of sexual selection on extinct vertebrates. Herein, we present a morphometric study of C. sanctus based on the largest sample size of this taxon collected up to now. Our results indicate that the characteristic elongated paired rectrices is a sexually dimorphic trait and statistically robust inferences of the sexual dimorphism in size, shape, and allometry that have been established, providing the earliest known sexual dimorphism in avian evolution. Our findings suggest that sexual selection, in conjunction with natural selection, does act upon body size and limb length ratio in early birds, thereby promoting a deeper understanding of the role of sexual selection in large-scale phylogenetic evolution.

Glucose trend prediction model based on improved wavelet transform and gated recurrent unit.

Glucose trend prediction based on continuous glucose monitoring (CGM) data is a crucial step in the implementation of an artificial pancreas (AP). A glucose trend prediction model with high accuracy in real-time can greatly improve the glycemic control effect of the artificial pancreas and effectively prevent the occurrence of hyperglycemia and hypoglycemia. In this paper, we propose an improved wavelet transform threshold denoising algorithm for the non-linearity and non-smoothness of the original CGM data. By quantitatively comparing the mean square error (MSE) and signal-to-noise ratio (SNR) before and after the improvement, we prove that the improved wavelet transform threshold denoising algorithm can reduce the degree of distortion after the smoothing of CGM data and improve the extraction effect of CGM data features at the same time. Based on this finding, we propose a glucose trend prediction model (IWT-GRU) based on the improved wavelet transform threshold denoising algorithm and gated recurrent unit. We compared the root mean square error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination ($ {\mathrm{R}}^{2} $) of Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support vector regression (SVR), Gated Recurrent Unit (GRU) and IWT-GRU on the original CGM monitoring data of 80 patients for 7 consecutive days with different prediction horizon (PH). The results showed that the IWT-GRU model outperformed the other four models. At PH = 45 min, the RMSE was 0.5537 mmol/L, MAPE was 2.2147%, $ {\mathrm{R}}^{2} $ was 0.989 and the average runtime was only 37.2 seconds. Finally, we analyze the limitations of this study and provide an outlook on the future direction of blood glucose trend prediction.

Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: a retrospective study from Northern China.

BACKGROUND: Contradictory relationships have been observed between thyroid function and gestational diabetes mellitus (GDM). Previous studies have indicated that pre-pregnancy BMI (pBMI) could modify their relationships. Few studies have illustrated the role of thyroid hormone sensitivity on GDM. We aimed to explore the effect of pre-pregnancy obesity on the association between early pregnancy thyroid hormone sensitivity and GDM in euthyroid pregnant women. METHODS: This study included 1310 women with singleton gestation. Subjects were classified into pre-pregnancy obese and non-obese subgroups by pBMI levels with a cutoff of 25 kg/m2. Sensitivity to thyroid hormone was evaluated by Thyroid Feedback Quartile-Based Index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH Index (TSHI) and Thyrotrophic T4 Resistance Index (TT4RI). The associations between these composite indices and GDM were analyzed using multivariate regression models in the two subgroups, respectively. RESULTS: In pre-pregnancy non-obese group, early pregnancy TFQI, PTFQI, TSHI and TT4RI levels were higher in subjects with incident GDM compared to those without GDM (all P < 0.05). By contrast, obese women with GDM exhibited lower levels of those indices (all P < 0.05). The occurrence of GDM were increased with rising TFQI, PTFQI, TSHI and TT4RI quartiles in non-obese women ( all P for trend < 0.05), while exhibited decreased trend across quartiles of those indices in obese women (all P for trend < 0.05). Further logistic analysis indicated contrary relationships between thyroid hormone sensitivity and the occurrence of GDM in the two groups, respectively. The OR of the fourth versus the first quartile of TFQI for GDM was 1.981 (95% CI 1.224, 3.207) in pre-pregnancy non-obese group, while was 0.131 (95% CI 0.036, 0.472) in pre-pregnancy obese group. PTFQI and TSHI yielded similar results. CONCLUSIONS: The association between maternal sensitivity to thyroid hormones during early gestation and the occurrence of GDM was modified by pre-pregnancy obesity.

Improved Deep Residual Shrinkage Network for Intelligent Interference Recognition with Unknown Interference.

In complex battlefield environments, flying ad-hoc network (FANET) faces challenges in manually extracting communication interference signal features, a low recognition rate in strong noise environments, and an inability to recognize unknown interference types. To solve these problems, one simple non-local correction shrinkage (SNCS) module is constructed. The SNCS module modifies the soft threshold function in the traditional denoising method and embeds it into the neural network, so that the threshold can be adjusted adaptively. Local importance-based pooling (LIP) is introduced to enhance the useful features of interference signals and reduce noise in the downsampling process. Moreover, the joint loss function is constructed by combining the cross-entropy loss and center loss to jointly train the model. To distinguish unknown class interference signals, the acceptance factor is proposed. Meanwhile, the acceptance factor-based unknown class recognition simplified non-local residual shrinkage network (AFUCR-SNRSN) model with the capacity for both known and unknown class recognition is constructed by combining AFUCR and SNRSN. Experimental results show that the recognition accuracy of the AFUCR-SNRSN model is the highest in the scenario of a low jamming to noise ratio (JNR). The accuracy is increased by approximately 4-9% compared with other methods on known class interference signal datasets, and the recognition accuracy reaches 99% when the JNR is -6 dB. At the same time, compared with other methods, the false positive rate (FPR) in recognizing unknown class interference signals drops to 9%.

A Reversible Fluorescent Probe for In Situ Monitoring Redox Imbalance during Mitophagy.

Mitophagy is the lysosome-dependent degradation of damaged and dysfunctional mitochondria, which is closely associated with H2O2-related redox imbalance and pathological processes. However, development of fast-responding and highly sensitive reversible fluorescent probes for monitoring of mitochondrial H2O2 dynamics is still lacking. Herein, we report a reversible fluorescent probe (M-HP) that enables real-time imaging of H2O2-related redox imbalance. In vitro studies demonstrated that M-HP had a rapid response and high sensitivity to the H2O2/GSH redox cycle, with a detection limit of 17 nM for H2O2. M-HP was applied to imaging of H2O2 fluctuation in living cells with excellent reversibility and mitochondrial targeting. M-HP reveals an increase in mitochondrial H2O2 under lipopolysaccharide stimulation and a decrease in H2O2 following the combined treatment with rapamycin. This suggests that the level of oxidative stress is significantly suppressed after the enhancement of mitophagy. The rationally designed M-HP offers a powerful tool for understanding redox imbalance during mitophagy.

The Failure Mechanical Properties of Cemented Paste Backfill with Recycled Rubber.

Understanding the mechanical properties and failure process of cemented paste backfill with recycled rubber (RCPB) is the foundation of backfill design in underground mining. In this study, physical and mechanical tests were conducted on RCPB to obtain its mechanical property parameters, such as its uniaxial compressive strength (UCS), toughness, and peak strain. The influence of the rubber dosage on the mechanical properties of RCPB was also analyzed. In addition, the deformation behavior, fracture development, and failure process of RCPB with different rubber contents were observed using the digital image correlation (DIC) technique. The experimental results suggested that, although the UCS of RCPB is reduced as more rubber is added, its toughness and ability to absorb energy is increased. Moreover, the impact resistance of RCPB is improved by this increased toughness. With the increase in the rubber content, the deformation corresponding to the plastic yield stage of RCPB increased, which resulted in better ductility and improved impact resistance. The failure of the RCPB specimens mainly showed an "X" shape. The results of this study help us to better understand the mechanical behavior of RCPB after backfilling underground.

Monitoring H2S fluctuation during autophagic fusion of lysosomes and mitochondria using a lysosome-targeting fluorogenic probe.

Hydrogen sulfide (H2S) plays a cytoprotective role during mitophagy by detoxifying superfluous reactive oxygen species (ROS), and its concentration fluctuates in this process. However, no work has been reported to reveal the variation in H2S levels during autophagic fusion of lysosomes and mitochondria. Herein, we present a lysosome-targeted fluorogenic probe, named NA-HS, for real-time monitoring of H2S fluctuation for the first time. The newly synthesized probe exhibits good selectivity and high sensitivity (detection limit of 23.6 nM). Fluorescence imaging results demonstrated that NA-HS could image exogenous and endogenous H2S in living cells. Interestingly, the colocalization results revealed that the level of H2S was upregulated after autophagy began because of the cytoprotective effect, and was finally gradually reduced during subsequent autophagic fusion. This work not only affords a powerful fluorescence tool to monitor the variations in H2S levels during mitophagy, but also offers new insights into targeting small molecules for elaborating the complex cellular signal pathways.

Rigidity-Dependent Emission: Inspired Selection of an ATP-Specific Polyvalent Hydrogen Binding-Lighted Fluorophore for Intracellular Amplified Imaging.

ATP, a small molecule with high intracellular concentration (mM level), provides a fuel to power signal amplification, which is meaningful for biosensing. However, traditional ATP-powered amplification is based on ATP/aptamer recognition, which is susceptible to the complex biological microenvironment (e.g., nuclease). In this work, we communicate a signaling manner termed as ATP-specific polyvalent hydrogen binding (APHB), which is mimetic to ATP/aptamer binding but can avoid interference from biomolecules. The key in APHB is a functional fluorophore that can selectively bind with ATP via polyvalent hydrogen, and the fluorescence was lighted with the changes of the molecular structure from flexibility to rigidity. By designing, synthesizing, and screening a series of compounds, we successfully obtained an ATP-specific binding-lighted fluorophore (ABF). Experimental verification and a complex analogue demonstrated that two melamine brackets in the ABF dominate the polyvalent hydrogen binding between the ABF and ATP. Then, to achieve amplification biosensing, fibroblast activation protein (FAP) in activated hepatic stellate cells was taken as a model target, and a nanobeacon consisting of an ABF, a quencher, and an FAP-activated polymer shell was constructed. Benefiting from the ATP-powered amplification, the FAP was sensitively detected and imaged, and the potential relationship between differentiation of hepatocytes and FAP concentration was first revealed, highlighting the great potential of APHB-mediated signaling for intracellular sensing.

A Simple Nomogram for Predicting Hospital Mortality of Patients Over 80 Years in ICU: An International Multicenter Retrospective Study.

OBJECTIVES: This study aimed to develop and validate an easy-to-use intensive care unit (ICU) illness scoring system to evaluate the in-hospital mortality for very old patients (VOPs, over 80 years old). METHODS: We performed a multicenter retrospective study based on the electronic ICU (eICU) Collaborative Research Database (eICU-CRD), Medical Information Mart for Intensive Care Database (MIMIC-III CareVue and MIMIC-IV), and the Amsterdam University Medical Centers Database (AmsterdamUMCdb). Least Absolute Shrinkage and Selection Operator regression was applied to variables selection. The logistic regression algorithm was used to develop the risk score and a nomogram was further generated to explain the score. RESULTS: We analyzed 23 704 VOPs, including 3 726 deaths (10 183 [13.5% mortality] from eICU-CRD [development set], 12 703 [17.2%] from the MIMIC, and 818 [20.8%] from the AmsterdamUMC [external validation sets]). Thirty-four variables were extracted on the first day of ICU admission, and 10 variables were finally chosen including Glasgow Coma Scale, shock index, respiratory rate, partial pressure of carbon dioxide, lactate, mechanical ventilation (yes vs no), oxygen saturation, Charlson Comorbidity Index, blood urea nitrogen, and urine output. The nomogram was developed based on the 10 variables (area under the receiver operating characteristic curve: training of 0.792, testing of 0.788, MIMIC of 0.764, and AmsterdamUMC of 0.808 [external validating]), which consistently outperformed the Sequential Organ Failure Assessment, acute physiology score III, and simplified acute physiology score II. CONCLUSIONS: We developed and externally validated a nomogram for predicting mortality in VOPs based on 10 commonly measured variables on the first day of ICU admission. It could be a useful tool for clinicians to identify potentially high risks of VOPs.

A Reaction-Based Ratiometric Bioluminescent Platform for Point-of-Care and Quantitative Detection Using a Smartphone.

Fluorescent probes have emerged as powerful tools for the detection of different analytes by virtue of structural tenability. However, the requirement of an excitation source largely hinders their applicability in point-of-care detection, as well as causing autofluorescence interference in complex samples. Herein, based on bioluminescence resonance energy transfer (BRET), we developed a reaction-based ratiometric bioluminescent platform, which allows the excitation-free detection of analytes. The platform has a modular design consisting of a NanoLuc-HaloTag fusion as an energy donor, to which a synthetic fluorescent probe is bioorthogonally labeled as recognition moiety and energy acceptor. Once activated by the target, the fluorescent probe can be excited by NanoLuc to generate a remarkable BRET signal, resulting in obvious color changes of luminescence, which can be easily recorded and quantitatively analyzed by a smartphone. As a proof of concept, a fluorescent probe for HOCl was synthesized to construct the bioluminescent system. Results demonstrated the system showed a constant blue/red emission ratio which is independent to the signal intensity, allowing the quantification of HOCl concentration with high sensitivity (limit of detection (LOD) = 13 nM) and accuracy. Given the universality, this reaction-based bioluminescent platform holds great potential for point-of-care and quantitative detection of reactive species.

Pelvic ultrasound finding of late-onset bladder erosion after transobturator tape for female stress urinary incontinence: A case report.

RATIONALE: Mid-urethral sling is a gold-standard procedure for stress urinary incontinence because of its high efficacy and low complication incidence. Moreover, mesh erosion into the bladder is a rare complication. PATIENT CONCERNS: The 63-year-old patient visited our gynecology clinic with complaints of gross hematuria and was diagnosed with bladder erosion by ultrasound 6 months after transobturator tape procedure. DIAGNOSES: The 2D ultrasound found the sling in the bladder wall perforation, which can lead to the formation of bladder stones. Meanwhile, 3D ultrasound showed the left side of the sling crossed the bladder mucosa at 5 o'clock. INTERVENTIONS: The sling and bladder stones were removed by holmium laser. OUTCOMES: The patient underwent a follow-up pelvic ultrasound at 6 months, which showed no erosion mesh under the bladder mucosa. LESSONS: Pelvic ultrasound could accurately evaluate the location and shape of the tape, which is important for a reasonable surgical plan.

Activation of glucagon-like peptide-1 receptor in microglia exerts protective effects against sepsis-induced encephalopathy via attenuating endoplasmic reticulum stress-associated inflammation and apoptosis in a mouse model of sepsis.

Sepsis-induced encephalopathy (SAE) is a detrimental complication in patients with severe sepsis, while there is still no effective treatment. Previous studies have elucidated the neuroprotective effects of glucagon-like peptide-1 receptor (GLP-1R) agonists. However, the role of GLP-1R agonists in the pathological process of SAE is unclear. Here, we found that GLP-1R was up-regulated in the microglia of septic mice. The activation of GLP-1R with Liraglutide could inhibit endoplasmic reticulum stress (ER stress) and associated inflammatory response as well as apoptosis triggered by LPS or tunicamycin (TM) in BV2 cells. In vivo experiments confirmed the benefits of Liraglutide in the regulation of microglial activation, ER stress, inflammation, and apoptosis in the hippocampus of septic mice. Additionally, the survival rate and cognitive dysfunction of septic mice were also improved after Liraglutide administration. Mechanically, cAMP/PKA/CREB signaling is involved in the protection of ER stress-induced inflammation and apoptosis in cultured microglial cells under LPS or TM stimulations. In conclusion, we speculated that GLP-1/GLP-1R activation in microglia might be a potential therapeutic target for the treatment of SAE.

Bibliometric analysis of ferroptosis in acute kidney injury from 2014 to 2022.

INTRODUCTION: Acute kidney injury (AKI) is a global disease with high morbidity and mortality. At present, the treatment of AKI still lacks targeted measures. Ferroptosis, a form of regulated cell death, plays an essential role in the initiation and progression of AKI. Current evidence proves that targeting ferroptosis is supposed to be a novel potential strategy to cure AKI. In this study, we aim to use bibliometric analysis to identify research trends and hotspots in the field of "ferroptosis in AKI". METHODS: We chose the Science Citation Index Expanded (SCI-EXPANDED) index of the Web of Science Core Collection (WoSCC) as the source database for data retrieval. Data were retrieved from the WoSCC on May 24, 2022. Full records and cited references of all the documents in WoSCC were collected. The R software and the Online Analysis Platform of Literature Metrology were used for data analysis and visual analysis. RESULTS: There were 120 documents on "ferroptosis in AKI" in the WOSCC from 2014 to 2022 (May 24, 2022). There was a clear upward trend each year in the number of documents published. According to WoS report, China, the United States, and Germany were the top three countries involved in this research area, the majority of publications were included in the subject area "Cell Biology". Technical University of Dresden contributed the most publications, followed by Central South University and University of Pittsburgh. The Journal of Cell Death and Disease had the highest H-index and contributed the most publications. Linkermann A authored 16 articles and had the highest H-index. Multifactorial analysis of the keywords show that the research field is divided into two clusters. The most contributing publications and the most cited publications were also determined by factorial analysis. CONCLUSION: This bibliometric analysis provides a comprehensive analysis of research trends and hot spots on the topic of "ferroptosis in AKI". The study of ferroptosis-related AKI research remains in its early stages. There will be a dramatically increasing number of publications on this field. Further research should focus on exploring the mechanisms of crosstalk between ferroptosis and other programmed cell deaths, and improves clinical applications and therapeutic effects against AKI.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Dienogest in Healthy Subjects Under Fasting and Fed Conditions.

Dienogest is effective in reducing endometriosis-related pain symptoms. This study aims to investigate and compare the pharmacokinetic profiles and safety of test formulations to reference formulations of dienogest in healthy Chinese female volunteers under fasting or fed conditions. The purpose of this single-center, randomized, open-label, 2-sequence, 2-period crossover clinical trial was to evaluate the safety and pharmacokinetic profiles of the 2 formulations under fasting and fed conditions. Additionally, 48 healthy female volunteers were selected and divided at random into the fasting and the fed group. After dosing, the venous blood was collected through indwelling catheters. Dienogest plasma concentrations were measured using liquid chromatography-tandem mass spectrometry after the plasma samples were prepared with the protein precipitation method. Under either fasting or fed conditions, the pharmacokinetic parameters (maximum observed concentration, area under the concentration-time curve [AUC] from time 0 to the last measurable concentration, and AUC from time 0 to infinity) for dienogest between the test and reference products, geometric mean ratio, and 90%CI were all within the range of 80%-125%. The 2 dienogest products were bioequivalent. Based on maximum observed concentration and AUC from time 0 to the last measurable concentration, the generic dienogest was bioequivalent to the original dienogest in this study conducted under fasting and fed conditions in healthy Chinese women (study CTR20190063 on chinadrugtrials.org.cn registry).