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The article establishes a depositional model for lacustrine hyperpycnal flow by examining dynamics, transport factors, and laminae formation. The results show that several typical experimental phenomena such as fluid front mixing, double flow division, underwater leap, water skiing, and “new head” can be observed in the flume experiment. Based on the experimental observation of the flow process, three modes of transport of hyperpycnal flow in freshwater lake basins are summarized: bottom-bed loading, suspended loading, and uplift loading. Further, the change of fluid properties in hyperpycnal flow is summarized in three stages: a high-concentration stage, a low-concentration stage, and an uplifting stage. There are two main factors affecting the long-range transport of hyperpycnal flow: (1) the concentration difference between the head deposits and the ambient water body and (2) shear force of turbulence in the upper part of hyperpycnal flow. The simulation experiments of hyperpycnites laminae show that the laminae change from continuous to intermittent with the increase of the transportation distance. It is clear that the mode of transport of the hyperpycnal flow has a controlling effect on the degree of development of the laminae. Eventually, a depositional model of lake-facies hyperpycnal flow under experimental conditions was constructed.

This study investigated the effects of replacing flour with different proportions of mulberry fruit powder on the quality and antioxidant properties of steamed bread, with the goal of preparing steamed bread with high nutritional value and expanding the utilization of mulberries. The impact of varying amounts of mulberry powder on the color difference, texture, microstructure, and antioxidant effects of fermented dough and steamed bread was measured, and the correlation between dough characteristics and steamed bread quality was also analyzed. The results showed that as the amount of mulberry fruit powder increased, the dough's elasticity, L* value (lightness), b* value (yellowness), and w value (whiteness) significantly decreased, while the a* value (redness) increased. Changes in gluten protein structure led to a significant decrease in the specific volume of mulberry steamed bread and an increase in hardness, resulting in a decline in steamed bread quality. The moisture content, elasticity, and chewiness of the steamed bread initially increased and then decreased. Correlation analysis between the dough and steamed bread results revealed significant (P

【Objective】Due to its comb filter characteristics, Sampled optical Fiber Bragg Grating (SFBG) has attracted wide-spread attention and become a new focus in the research of optical fiber grating technology. The research work on designing optical filters with high channel numbers, flat tops, and narrow pass bands is of great importance in practical situation. Consequently, an Multi-Phase Shift Interpolated Sampling optical Fiber Grating (MPS-ISFBG) filter is proposed.【Methods】ISFBG has a large number of reflection channels and can introduce multiple flat top narrow transmission channels by inserting multi-phase shift. By optimizing the location of the two π phase-shift distributions of the inserted ISFBGs, an optical filters with 41 transmission channels was designed which covers the C-band with a channel interval of 100 GHz. Each channel has a flat-top response, a narrow 3 dB bandwidth (

4-hydroxybenzaldehyde (4-HBd) is one of the active compounds with neuroprotective effects, which has been confirmed to have anti cerebral ischemical reperfusion injury (CIRI) effect in previous study. In this study, we explored the protective effect of 4-HBd on the neurovascular unit (NVU) after CIRI and its mechanism through in vivo and in vitro experiments. Establish rat of middle cerebral artery occlusion/reproduction (MCAO/R) model, transwell chamber was used to establish an in vitro primary cell co-culture model to simulate NVU, causing oxygen glucose deprivation/reperfusion (OGD/R) injury, simulating the pathological of CIRI in vivo. Longa 5-point method was used to evaluate the neurological function of the rats, and transmission electron microscope was used to observe the ultrastructural changes of NVU. Western Blot was used to detect the expression of neuronal protein in rat brain. The mRNA expressions of ang-1/tie-2 signaling pathway and bdnf/trkb signaling pathway were detected by qPCR. In vivo results showed that 4-HBd reduced neurological function scores and improved the ultrastructure of NVU after MCAO/R rats. 4-HBd could up-regulate the expression of microtubule associated protein-2 (Map-2), glial fibrillary acidic protein (GFAP) and occludin. In vitro results showed that 4-HBd could activate ang-1/tie-2 signaling pathway, increased occludin mRNA expression and protect the blood brain barrier (BBB). 4-HBd can activate bdnf/trkb signaling pathway, up-regulate map-2 mRNA expression, and promote neuronal repair. In vitro and in vivo results indicated 4-HBd can affect the ang-1/tie-2 and bdnf/trkb signaling pathways, and BBB damage is alleviated and NVU homeostasis is maintained to improve CIRI.

A method for the quantification of 1,3-dioleyl-2-palmitoyl-glycerol (OPO) in infant formula was developed. The samples were treated with ammonia and extracted with organic solvents. The fat containing OPO was purified on a NH2 solid-phase extraction (SPE) cartridge packed with aminopropyl as the sorbent. The eluate was separated by silver ion chromatography using 0.55% acetonitrile-hexane as the mobile phase. The detection was carried out with a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). This novel procedure enabled the complete separation of OPO and its isomer 1,2-dioleyl-3-palmitoyl-glycerol (OOP), thus allowing for the accurate quantification of OPO. The developed method showed the desired linearity in the concentration range of 25–500 μg/mL with a determination coefficient (R2) of 0.999 6. The limits of detection (LOD) and limits of quantification (LOQ) were 0.30 and 0.90 g/kg, respectively. At spiked concentrations from 1 to 96 g/kg, the average recoveries of OPO varied from 97.1% to 104.2% with relative standard deviations (RSD) between 1.2% and 2.9%. The precision and accuracy of this method met the relevant requirements, and it passed the inter-laboratory collaborative validation. Our investigation analyzed 39 commercial samples of OPO-fortified infant formula in China, revealing that the measured OPO content only accounted for 28.4% to 59.7% of the labelled value, which is mainly due to the inconsistency of detection methods.

This research aims to find out the tradition of appointing parents of the same family as a condition of Malay traditional marriage and to find out how the Rokan Hulu Ulama views on the tradition. This research is designed with a qualitative method to be able to explain in as much detail as possible about the appointment of parents of the same family as a condition of Malay traditional marriage. This research is a normative-empirical research with a sociological approach. Primary data sources are obtained from interviews with several respondents, while secondary data sources are obtained from several references that explain the tradition of the appointment of surname parents as a condition of Malay traditional marriage in Rokan Hulu. While the analysis technique is descriptive. The results of this study found that the Rokan Hulu ulama did not approve of the appointment of semarga parents as a condition of marriage. Based on the results of this study, the author concludes that the Rokan Hulu scholars agreed to disagree with the appointment of parents of the same family as a condition of marriage because it contradicts the law of shara' and makes it difficult for someone who wants to get married, then this tradition only applies in the Rokan Hulu area and does not apply universally to Muslims so it deserves to be disapproved by the scholars.

ObjectiveOur aim was to develop a nomogram that integrates clinical and radiological data obtained from computed tomography (CT) scans, enabling the prediction of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH).MethodA total of 318 patients diagnosed with subarachnoid hemorrhage (SAH) and admitted to the Department of Neurosurgery at the Affiliated People’s Hospital of Jiangsu University between January 2020 and December 2022 were enrolled in our study. We collected clinical characteristics from the hospital’s medical record system. To identify risk factors associated with chronic hydrocephalus, we conducted both univariate and LASSO regression models on these clinical characteristics and radiological features, accompanied with penalty parameter adjustments conducted through tenfold cross-validation. All features were then incorporated into multivariate logistic regression analyses. Based on these findings, we developed a clinical-radiological nomogram. To evaluate its discrimination performance, we conducted Receiver Operating Characteristic (ROC) curve analysis and calculated the Area Under the Curve (AUC). Additionally, we employed calibration curves, and utilized Brier scores as an indicator of concordance. Additionally, Decision Curve Analysis (DCA) was performed to determine the clinical utility of our models by estimating net benefits at various threshold probabilities for both training and testing groups.ResultsThe study included 181 patients, with a determined chronic hydrocephalus prevalence of 17.7%. Univariate logistic regression analysis identified 11 potential risk factors, while LASSO regression identified 7 significant risk factors associated with chronic hydrocephalus. Multivariate logistic regression analysis revealed three independent predictors for chronic hydrocephalus following aSAH: Periventricular white matter changes, External lumbar drainage, and Modified Fisher Grade. A nomogram incorporating these factors accurately predicted the risk of chronic hydrocephalus in both the training and testing cohorts. The AUC values were calculated as 0.810 and 0.811 for each cohort respectively, indicating good discriminative ability of the nomogram model. Calibration curves along with Hosmer-Lemeshow tests demonstrated excellent agreement between predicted probabilities and observed outcomes in both cohorts. Furthermore, Brier scores (0.127 for the training and 0.09 for testing groups) further validated the predictive performance of our nomogram model. The DCA confirmed that this nomogram provides superior net benefit across various risk thresholds when predicting chronic hydrocephalus. The decision curve demonstrated that when an individual’s threshold probability ranged from 5 to 62%, this model is more effective in predicting the occurrence of chronic hydrocephalus after aSAH.ConclusionA clinical-radiological nomogram was developed to combine clinical characteristics and radiological features from CT scans, aiming to enhance the accuracy of predicting chronic hydrocephalus in patients with aSAH. This innovative nomogram shows promising potential in assisting clinicians to create personalized and optimal treatment plans by providing precise predictions of chronic hydrocephalus among aSAH patients.

The in-lab incubation experiments were conducted to identify the passivation effect of corn vinasse biochar, which was prepared at different temperatures, on heavy metal Pb in paddy soil of the Pb-Zn mining area. The results showed that after 30 days of biochar amended to the soil, the soil pH and organic carbon content increased by 2.72%-8.47% and 27.79%-65.26%, respectively. The CO32- and OH- contained in corn vinasse biochar could react with Pb and generate carbonate and hydroxide of Pb. In comparison with the treatment control, the bioavailable fractions of Pb were reduced by 26.6%, 23.30%, 26.95%, and 35.33%, respectively, in biochar-amended treatments. Exchangeable fractions of Pb decreased by 21.50%, 21.33%, 22.58%, and 22.58% for the treatment 3% (300°C), 6% (300°C), 3% (600°C), and 6% (300°C) corn vinasse biochar, respectively, compared with the treatment control. As a whole, corn vinasse biochar could effectively promote the transformation of Pb in soil from the exchangeable fractions into the Fe-Mn oxide-bound fractions and residue fractions, with a significant passivation effect for Pb in soil and more effective passivation by high-temperature preparation and increased dosage of biochar.

Aims: Clinical data supports electroacupuncture (EA) as an effective treatment for female reproductive disorders especially gonadotropin abnormalities. This study aims to detect the mechanism of EA that improves the neuroendocrine defects particularly the luteinizing hormone (LH) surge failure in early reproductive aging females., Materials and Methods: Middle-aged ovariectomized rats primed with hormone were treated by EA at acupoints CV4 and SP6 and undergone LH assay. Morphological experiments detected the activation of Kiss1 cells in the anteroventral periventricular nucleus (AVPV). Using targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA-sequencing, we determined the concentrations of neurotransmitter metabolites and transcriptomics in AVPV., Key Findings: EA significantly increased c-Fos and c-Fos-positive Kiss1 cells in the middle-aged AVPV as well as the total and peak LH release. Targeted LC-MS/MS and RNA-sequencing of AVPV identified differential neurotransmitters in the middle-aged females including Acetylcholine chloride, 5-Hydroxyindole-3-aceticacid, Kynurenine, Histamine, L-Histidine and L-Glycine, while EA decreased the concentration of Acetylcholine chloride. Totally 1255 differentially expressed genes modulated by EA were strongly implicated in neurotransmitter transport and KEGG pathways involved neuroactive ligand-receptor interaction, glutamatergic and gamma-aminobutyric acid-mediated synapse. Specifically, the mRNAs associated with the LH surge such as hormone receptor Pgr, adrenoceptor Adra1a, neurotransmitter transporters Slc17a6 and Slc32a1, glutamate decarboxylase Gad2 and Kiss1 were markedly altered by EA., Significance: These findings showed that the age-related reduction of LH surge occurred via differential neurotransmitter metabolisms and altered transcriptions in AVPV, which proposed EA-based therapy for improving responsiveness of the hypothalamus to hormone in women with advanced age., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this paper, a method for indirect diagnosis of transformer faults based on the fluorescence spectrum and characteristic wavelength screening of transformer oil has been proposed. Specifically, a hybrid strategy (BiPLS-RF) for establishing the fluorescence spectrum feature screening of transformer oil using backward interval partial least squares (BiPLS) and random forest (RF) has been proposed. Aiming at the problem of transformer fault diagnosis, the laser induced fluorescence (LIF) spectroscopy of transformer oil in different states was first collected, and it is found that the fluorescence spectrum intensity of normal transformer oil was stronger than that of faulty transformer oil. Then the characteristic bands of the original fluorescence spectra were screened by BiPLS. It is found that when the original fluorescence spectra were divided into 15 sub-intervals, the minimum root mean squares error of cross-validation can be obtained by selecting 3 sub-intervals (including 411 wavelengths). On this basis, RF was employed to further screen the characteristic wavelengths and realized the identification of the fluorescence spectrum. It is found that in the RF model composed of 54 trees, the selected 196 characteristic wavelengths of the fluorescence spectrum can minimize the analysis error (0.56%). In addition, the selected characteristic wavelength information was fed into other common classifiers to construct a fluorescence spectrum identification model, which further proved the effectiveness of BiPLS-RF for wavelength selection for LIF spectroscopy of power transformer oil. The results show that it is feasible to use BiPLS-RF to screen the characteristic wavelength of LIF spectroscopy and apply it to transformer fault diagnosis, which provides a new solution for transformer fault diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct., Aim of the Study: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective., Materials and Methods: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway., Results: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway., Conclusions: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Transition metal dichalcogenides like MoS 2 have been considered as crucial channel materials beyond silicon to continuously advance transistor scaling down owing to their two-dimensional structure and exceptional electrical properties. However, the undesirable interface morphology and vibrational phonon frequency mismatch between MoS 2 and the dielectric layer induce low thermal boundary conductance, resulting in overheating issues and impeding electrical performance improvement in the MoS 2 field-effect transistors. Here, we employed hybrid high- k dielectric layers of Al 2 O 3 /HfO 2 to simultaneously reduce the interfacial thermal resistance and improve device electrical performance. The enhanced contact, greater vibrational phonon overlapping region, and stronger interfacial bonding force between the top Al 2 O 3 layer and MoS 2 promote the heat removal efficiency across the interface to the substrate. Under the same input power density, the temperature profile of the MoS 2 transistor on the Al 2 O 3 /HfO 2 has been largely reduced compared to that of the device on HfO 2 , with a maximum reduction of 49.5 °C. In addition, the field-effect mobility and current of MoS 2 devices on the Al 2 O 3 /HfO 2 high- k dielectric layers have been significantly improved, attributed to the depressed electron scattering and trap states at the interface. The design of the hybrid high- k dielectric layers provides an efficient solution to simultaneously improve the thermal and electrical performance of the two-dimensional devices.

Neuropathic pain arises from impairments or malfunctions within the nervous system, resulting in atypical transmission and interpretation of pain signals. In the present study, we examined the neuroprotective effects of agomelatine (AGM) and agomelatine-loaded nanostructured lipid carriers (AGM-NLCs) in neuropathic animal models induced by chronic constriction injury (CCI) of the sciatic nerve. Male Sprague Dawley rats were divided into seven experimental groups to compare the effects of AGM and AGM-NLCs, which were administered at 20 mg/kg for 14 consecutive days after CCI. Our finding demonstrated that CCI triggered the onset of analgesia in these animals, corroborated by mechanical allodynia and thermal hyperalgesia. Furthermore, CCI induced an elevation in inflammatory mediators such as interleukin (IL)-1β and inducible nitric oxide synthase (iNOS), and downregulated heme oxygenase-1 (HO-1) and nuclear factor E2-related factor (Nrf2). Treatment with AGM and AGM-NLCs reversed inflammatory cascades and elevated antioxidant enzyme levels, leading to a reduction in paw withdrawal latency and threshold in rats. To further investigate the effect of AGM and AGM-NLCs, all-trans retinoic acid (ATRA) was administered, which antagonizes Nrf2. ATRA substantially downregulated Nrf2 expression and exacerbated thermal hyperalgesia, whereas Nrf2 and HO-1 expressions were significantly upregulated after AGM-NLCs administration. Overall, the results demonstrated that AGM-NLCs offer promising antinociceptive and anti-inflammatory properties in alleviating neuropathic pain symptoms, which can be attributed to improved drug delivery and therapeutic outcomes compared with AGM alone., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: The risk of cardiovascular complications is significantly elevated in patients with diabetic kidney disease (DKD). Recognizing the link between the progression of DKD and an increased risk of cardiovascular disease (CVD), it is crucial to focus on the early prediction and management of CVD risk factors among these patients to potentially enhance their health outcomes., Objective: This study sought to bridge the existing gap by developing and validating machine learning (ML) models that utilize clinical data and shear wave elastography (SWE) radiomics features to identify patients at risk of CVD, ultimately aiming to improve the management of DKD., Materials and Methods: This study conducted a retrospective analysis of 586 patients with DKD, dividing them into training and external validation cohorts. We categorized patients based on the presence or absence of CVD. Utilizing SWE imaging, we extracted and standardized radiomics features to develop multiple ML models. These models underwent internal validation using radiomics features alone, clinical data, or a combination thereof. The optimal model was then identified, and its feature importance was assessed through the Shapley Additive Explanations (SHAP) method, before proceeding to external validation., Results: Among the 586 patients analyzed, 30.7% (180/586) were identified as at risk for CVD. The study pinpointed six significant radiomics features related to CVD, alongside six critical pieces of clinical data. The Support Vector Machine (SVM) model outperformed others in both internal and external validations. Further, SHAP analysis highlighted five principal determinants of CVD risk, comprising three clinical indicators and two SWE radiomics features., Conclusions: This study highlights the effectiveness of an SVM model that combines clinical and radiomics features in predicting CVD risk among DKD patients. It enables early prediction of CVD in this patient group, thereby supporting the implementation of timely and suitable interventions., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Concerns regarding membrane fouling and suboptimal bioenergy recovery have constrained the implementation of anaerobic membrane bioreactor (AnMBR) for treating low-strength municipal wastewater. This study presents a novel anaerobic cathodic dynamic membrane bioreactor (AnCDMBR) designed to address these challenges. A self-formed cathodic dynamic membrane (CDM) on inexpensive carbon cloth was developed to function as both a membrane and biocathode to achieve dual-function effects of mitigating membrane fouling and accelerating organics conversion. Compared with common dynamic membrane (1.52 kPa/d) and commercial membranes (7.52 kPa/d), the developed CDM presented a significantly reduced fouling rate (1.02 kPa/d), exhibiting the potential as a substitute for high-cost conductive membranes. Furthermore, efficient and stable biomethanation occurred in AnCDMBR with a superior methane yield rate of 0.26 L-CH 4 /g-COD (CH 4 content > 95 %), which was 1.42 times higher than the control, linked to the higher activities of microbial metabolism and methanogenic-related key enzymes. Further analysis revealed that electrostimulation-induced niche differentiation of microbiota regulated interspecies interactions between electroactive microorganisms and complex anaerobic digestion microbiomes, facilitating organic matter conversion to methane and leading to superior bioenergy recovery. This study offered a new strategy for effectively mitigating fouling and recovering bioenergy from low-strength wastewater, potentially expanding the application of AnMBRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. Wuzhi tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient data support the dose recommendation of TAC when co-administered with Wuzhi ., Materials and Methods: A total of 305 adult renal transplant patients with 2,541 TAC trough concentrations (C 0 ) were enrolled for population pharmacokinetic (PPK) modeling. CYP3A5 polymorphism was genotyped, and corresponding clinical factors were recorded. Nonlinear mixed-effects modeling and Monte Carlo simulation were used for dose recommendation. PK parameters were calculated based on one-compartment model with first-order absorption and elimination., Results: The estimated total clearance (CL/F) and volume of distribution (V d /F) of TAC were 23.84 L/h and 1,075.96 L, respectively. Wuzhi , CYP3A5 genotype, hematocrit (HCT), and weight were found to have a significant influence on CL/F. CL/F was significantly lower in the individuals who were CYP3A5 non-expressers and received TAC together with Wuzhi . CYP3A5 genotype (expressers or non-expressers), body weight (40 - 80 kg), and hematocrit (20 - 40%) were selected as the specific clinical scenarios, and the starting dose of TAC ranged from 1.5 to 4.5 mg when co-administered with Wuzhi ., Conclusion: We establish a TAC PPK model comprising Wuzhi as a covariate in renal transplant recipients and recommend an initial dose of TAC when co-administered with Wuzhi , which could provide reference for the individualized regimens of TAC.

Advancements in Spatial Transcriptomics (ST) technologies in recent years have transformed the analysis of tissue structure and function within spatial contexts. However, accurately identifying spatial domains remains challenging due to data sparsity and noise. Traditional clustering methods often fail to capture spatial dependencies, while spatial clustering methods struggle with batch effects and data integration. We introduce GraphCVAE, a model designed to enhance spatial domain identification by integrating spatial and morphological information, correcting batch effects, and managing heterogeneous data. GraphCVAE employs a multi-layer Graph Convolutional Network (GCN) and a variational autoencoder to improve the representation and integration of spatial information. Through contrastive learning, the model captures subtle differences between cell types and states. Extensive testing on various ST datasets demonstrates GraphCVAE's robustness and biological contributions. In the dorsolateral prefrontal cortex (DLPFC) dataset, it accurately delineates cortical layer boundaries. In glioblastoma, GraphCVAE reveals critical therapeutic targets such as TF and NFIB. In colorectal cancer, it explores the role of the extracellular matrix in colorectal cancer. The model's performance metrics consistently surpass existing methods, validating its effectiveness. GraphCVAE's advanced visualization capabilities further highlight its precision in resolving spatial structures, making it a powerful tool for spatial transcriptomics analysis and offering new insights into disease studies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Enamel adhesion is acknowledged as durable; however, achieving long-lasting dentin adhesion remains a formidable challenge due to degradation of exposed collagen matrix after acid-etching of dentin. The idea of developing an enamel-like adhesion interface holds great promise in achieving enduring dentin adhesion. In this study, we constructed an enamel-like adhesion interface using a rapid remineralization strategy comprising an acidic primer and a rapid remineralization medium. Specifically, the acidic primer of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and epigallocatechin-3-gallate (EGCG) nanocomplex (MDP@EGCG primer) was utilized to partially demineralize dentin within 30 s, and the MDP@EGCG nanocomplex showed a strong interaction with exposed collagen, enhancing collagen remineralization properties. Then, the rapid remineralization medium containing polyaspartate (Pasp) stabilized amorphous calcium and phosphorus nanoclusters (rapid Pasp-CaP) was applied to modified dentin collagen for 1 min, which caused rapid collagen remineralization within a clinically acceptable time frame. This strategy successfully generated an inorganic rough and porous adhesive interface resembling etched enamel, fundamentally addressed issues of collagen exposure, and achieved durable dentin adhesion in vitro and in vivo while also ensuring user-friendliness. It exhibited potential in prolonging the lifespan of adhesive restorations in clinical settings. In addition, it holds significant promise in the fields of caries and dentin sensitivity treatment and collagen-based tissue engineering scaffolds.

Metabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis., (© 2024. The Author(s).)

Lakes are essential for estimating the global CO 2 budget. However, approximately 50 % of lakes undergo periodic freezing, and there is limited research on the factors influencing the CO 2 cycle and ice formation in freshwater lakes located in middle- and high-latitude plateaus during ice-covered periods. Using high-frequency meteorological-flux data collected over six consecutive months during the 2018-2019 freezing period of Lake Wuliangsuhai, this study explored the diurnal variation, daily accumulation, and monthly accumulation of the CO 2 cycle and its influencing mechanisms at a half-hour scale. The key findings are as follows. Lakes are CO 2 sinks during the ice-covered period, with the fluxes being -1.28 ± 4.79 gCm -2 d -1 . Net CO 2 exchange (NEE), gross primary productivity (GPP), and ecosystem respiration (RECO) during the monitoring period were -116.93 gCm -2 ,190.36 gCm -2 , and 86.09 gCm -2 , respectively. The lake ice-air CO 2 cycle exhibited significant (p < 0.05) diurnal variation, with daytime contributing 92.89 %, 78.31 %, and 56.91 % to NEE, GPP, and RECO, respectively. From December 2018 to March 2019, the monthly total GPP in the whole lake exceeded 10,000 tons, and high autotrophy was observed in February 2019. During the freezing period, 45.22 % of plant assimilation was consumed by autotrophic and heterotrophic respiration. The capacity of the lake CO 2 sink was primarily driven by evaporation, latent heat, radiative sensible heat, and air pressure inhibition, whereas snow cover reduced the CO 2 sink capacity by 73.01 %. CO 2 capture by surface ice was mainly affected by external factors such as snow cover and solar radiation, whereas bottom ice capture was influenced by internal factors such as acid-base balance, the carbonate pump, and biological primary production. Bubble storage and ice crevice transport significantly affected CO 2 migration. In summary, further research should focus on elucidating the CO 2 capture mechanisms in seasonally frozen lakes located at middle and high latitudes, within subsequent lake‑carbon sink studies., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Overactive bladder (OAB) is a common syndrome in children, which may affect the patient's quality of life (QoL). This study aimed to evaluate the effect of standard urotherapy (SU) given on the quality of life for children diagnosed with OAB., Methods: The study was conducted on 107 children aged 2 to 13 years who applied to the urology clinic of a hospital in China and were diagnosed with OAB. The QoL was assessed using the Pediatric Incontinence Questionnaire (PINQ). The QoL was evaluated before and 1 month later SU given., Results: Of the 107 children, at baseline, the children with OAB revealed a total mean PINQ score of 27.40 ± 13.19, and the total mean PINQ score was 13.72 ± 9.63 at 1 month later. PINQ score showed a statistically significant difference between before and after 1 month treatment (P < 0.001)., Conclusions: The QoL of children with OAB increased may due to SU provided outpatient clinics. And it is important for children and their parents to investigate and monitor to what extent the QoL of children diagnosed with OAB is affected., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

Prostate-specific membrane antigen (PSMA) is overexpressed in 80-90 % of prostate cancers (PCa) and is widely used as a diagnostic and therapeutic biomarker. Docetaxel (DTX), an FDA-approved anti-microtubule drug, is commonly employed to manage metastatic castration-resistant PCa; however, DTX therapy is often associated with severe side effects. One promising strategy to mitigate these side effects is the development of nanomedicine by loading small molecules into biocompatible vectors. Poly (ethylene glycol) (PEG) has been extensively used in clinical settings for this purpose, with PEGylated drugs demonstrating significant success. Compared to linear PEG, branched PEG (multi-arm PEG) provides enhanced stability for nanomedicines. In this study, we developed a novel nanoprodrug 4armPEG-Docetaxel DCL (4armPEG-DD) by conjugating a 4-arm PEG with DTX via a reduction-sensitive disulfide bond and further modifying it with 2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (DCL), a PSMA-targeting ligand. Both in vitro and in vivo results demonstrated that the designed nanoprodrug specifically recognized PSMA-positive PCa cells and effectively released DTX in response to the intracellular reducing environment, leading to potent cytotoxic effects on PSMA-positive prostate tumors. Importantly, 4armPEG-DD exhibited improved in vivo safety compared to small-molecule DTX. Thus, we propose that 4armPEG-DD represents a promising candidate for the clinical treatment of PSMA-positive PCa., Competing Interests: Declaration of competing interest The authors have no known competing financial interests or personal relationships that could influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Batracomorphus is the most diverse and widely distributed genus of Iassinae. Nevertheless, there has been no systematic analysis of the genome structure and phylogenetic relationships of the genus. To determine the characteristics of the mitogenomes of Batracomorphus species as well as the phylogenetic relationships between them, we sequenced and compared the mitogenomes of 11 representative Batracomorphus species. The results revealed that the mitogenomes of the 11 Batracomorphus species exhibited highly similar gene and nucleotide composition, and codon usage compared with other reported mitogenomes of Iassinae. Of these 11 species, we found that the mitogenomes of four species were rearranged in the region from trnI - trnQ - trnM to trnQ - trnI - trnM , whereas the remaining species presented a typical gene order. The topologies of six phylogenetic trees were in agreement. Eurymelinae consistently formed paraphyletic groups. Ledrinae and Evacanthinae formed sister taxa within the same clade. Similarly, Typhlocybinae and Mileewinae consistently clustered together. All phylogenetic trees supported the monophyly of Iassinae, indicating its evolutionary distinctiveness while also revealing its sister relationship with Coelidiinae. Notably, the nodes for all species of the genus Batracomorphus were well supported and these taxa clustered into a large branch that indicated monophyly. Within this large branch, four Batracomorphus species with a gene rearrangement ( trnQ - trnI - trnM ) exhibited distinctive clustering, which divided the large branch into three minor branches. These findings expand our understanding of the taxonomy, evolution, genetics, and systematics of the genus Batracomorphus and broader Iassinae groups., Competing Interests: The authors declare they have no competing interests., (©2024 Lu et al.)

Understanding the occurrence, sources, and ecological risks of polychlorinated biphenyls (PCBs), which are universal persistent organic pollutants, is critical for improving the sustainability and ecological safety of lake systems. Herein, to determine PCB contamination levels and formulate control strategies in lake sediments, 210 sediment samples were collected from 21 lakes along a latitudinal gradient (18-45°N, ∼3000 km) across eastern China and were analyzed for all 209 PCB congeners. The results showed that the total PCB concentration varied greatly from 0.26 to 163.82 ng/g dry weight and exhibited a latitudinal trend of central > north/south. Spatial variations were affected mainly by the organic carbon fraction and local population density. Most lakes had similar PCB profiles, with lower chlorinated PCBs dominating. Notably, non-Aroclor PCB 11 was the most abundant congener. Moreover, unintentionally produced PCBs (UP-PCBs) accounted for ∼31 % of all PCBs. These findings highlight that the significance of UP-PCBs has been overlooked in past studies and that full-congener analysis is necessary for future monitoring. According to the ecological risk assessment of PCBs, zero to moderate risk existed in lake sediments. Therefore, effective strategies are needed to mitigate the impact of PCBs (especially UP-PCBs) from multiple sources on lakes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The CHILD Cohort Study is an active multi-center longitudinal, prospective, population pregnancy cohort study following Canadian infants from fetal life until adulthood. We hypothesized that early life physical and psychosocial environments interact with biological factors (e.g. immunologic, genetic, physiologic, and metabolic) influencing burdensome non-communicable disease outcomes, including asthma and allergic disorders, growth and development, cardio-metabolic health, and neurodevelopmental outcomes that manifest during the life-course. Detailed clinical and physiologic phenotyping at strategic intervals was complemented by environmental sampling, actigraphy and global positioning system measures, biological sampling including gut, breastmilk and nasal microbiome, nutritional studies, genetics, and epigenetic profiling. Of 3,454 families recruited from 2008 to 2012, study retention was 96.0% at 1-year, 93.2% at 5-years and 90.7% at 8-years. Data collection during the SARS-2 COVID-19 pandemic was partially completed via virtual visits. A sub-cohort was implemented, capturing detailed information on the prevalence and predictors of SARS-CoV-2 infection and the health and psychosocial impact of the pandemic on Canadian families. The 13-year clinical assessment launched in 2022 will be completed in 2025. Ultimately, the CHILD Cohort Study provides a data science platform designed to enable a deep understanding of early life factors associated with the development of chronic non-communicable diseases and multimorbidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

As the largest family of dicotyledon, the Asteraceae family comprises a variety of economically important crops, ornamental plants and numerous medicinal herbs. Advancements in genomics and transcriptomic have revolutionized research in Asteraceae species, generating extensive omics data that necessitate an efficient platform for data integration and analysis. However, existing databases face challenges in mining genes with specific functions and supporting cross-species studies. To address these gaps, we introduce the Asteraceae Multi-omics Information Resource (AMIR; https://yanglab.hzau.edu.cn/AMIR/), a multi-omics hub for the Asteraceae plant community. AMIR integrates diverse omics data from 74 species, encompassing 132 genomes, 4 408 432 genes annotated across seven different perspectives, 3897 transcriptome sequencing samples spanning 131 organs, tissues and stimuli, 42 765 290 unique variants and 15 662 metabolites genes. Leveraging these data, AMIR establishes the first pan-genome, comparative genomics and transcriptome system for the Asteraceae family. Furthermore, AMIR offers user-friendly tools designed to facilitate extensive customized bioinformatics analyses. Two case studies demonstrate AMIR's capability to provide rapid, reproducible and reliable analysis results. In summary, by integrating multi-omics data of Asteraceae species and developing powerful analytical tools, AMIR significantly advances functional genomics research and contributes to breeding practices of Asteraceae., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

High levels of antibiotic accumulation and the difficulty of degradation can have serious consequences for the environment and, therefore, require urgent attention. To solve this problem, a synergistic Er and Cd ion-codoped Bi 4 O 5 Br 2 photocatalyst was proposed. The degradation rate of sulfamethoxazole (SMX) by Er/Cd-Bi 4 O 5 Br 2 was eight times higher than that of pure Bi 4 O 5 Br 2 , exceeding that of single Er-doped or Cd-doped Bi 4 O 5 Br 2 , which was attributed to the ability of Er/Cd-Bi 4 O 5 Br 2 to generate a variety of free radicals. Experimental results and theoretical calculations suggested a possible mechanism for the improved photocatalytic degradation rate. The reduction of the band gap can facilitate the production of electron-hole pairs, which play a significant role in the production of reactive radicals. Furthermore, an optimal stabilized structure of the ErCd-Bi 4 O 5 Br 2 dopant system was identified based on the formation energy formulas of different ligand configurations. These findings offer promising potential for the degradation of broad-spectrum antibiotics and provide valuable insights for the design and modification of photocatalytic materials.

Research on brain expression quantitative trait loci (eQTLs) has illuminated the genetic underpinnings of schizophrenia (SCZ). Yet most of these studies have been centered on European populations, leading to a constrained understanding of population diversities and disease risks. To address this gap, we examined genotype and RNA-seq data from African Americans (AA, n = 158), Europeans (EUR, n = 408), and East Asians (EAS, n = 217). When comparing eQTLs between EUR and non-EUR populations, we observed concordant patterns of genetic regulatory effect, particularly in terms of the effect sizes of the eQTLs. However, 343,737 cis-eQTLs linked to 1,276 genes and 198,769 SNPs were found to be specific to non-EUR populations. Over 90% of observed population differences in eQTLs could be traced back to differences in allele frequency. Furthermore, 35% of these eQTLs were notably rare in the EUR population. Integrating brain eQTLs with SCZ signals from diverse populations, we observed a higher disease heritability enrichment of brain eQTLs in matched populations compared to mismatched ones. Prioritization analysis identified five risk genes (SFXN2, VPS37B, DENR, FTCDNL1, and NT5DC2) and three potential regulatory variants in known risk genes (CNNM2, MTRFR, and MPHOSPH9) that were missed in the EUR dataset. Our findings underscore that increasing genetic ancestral diversity is more efficient for power improvement than merely increasing the sample size within single-ancestry eQTLs datasets. Such a strategy will not only improve our understanding of the biological underpinnings of population structures but also pave the way for the identification of risk genes in SCZ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute coronary syndromes (ACS) are one of the leading causes of mortality worldwide, with atherosclerotic plaque rupture and subsequent thrombus formation as the main underlying substrate. Thrombus burden evaluation is important for tailoring treatment therapy and predicting prognosis. Coronary optical coherence tomography (OCT) enables in-vivo visualization of thrombus that cannot otherwise be achieved by other image modalities. However, automatic quantification of thrombus on OCT has not been implemented. The main challenges are due to the variation in location, size and irregularities of thrombus in addition to the small data set. In this paper, we propose a novel dual-coordinate cross-attention transformer network, termed DCCAT, to overcome the above challenges and achieve the first automatic segmentation of thrombus on OCT. Imaging features from both Cartesian and polar coordinates are encoded and fused based on long-range correspondence via multi-head cross-attention mechanism. The dual-coordinate cross-attention block is hierarchically stacked amid convolutional layers at multiple levels, allowing comprehensive feature enhancement. The model was developed based on 5,649 OCT frames from 339 patients and tested using independent external OCT data from 548 frames of 52 patients. DCCAT achieved Dice similarity score (DSC) of 0.706 in segmenting thrombus, which is significantly higher than the CNN-based (0.656) and Transformer-based (0.584) models. We prove that the additional input of polar image not only leverages discriminative features from another coordinate but also improves model robustness for geometrical transformation.Experiment results show that DCCAT achieves competitive performance with only 10% of the total data, highlighting its data efficiency. The proposed dual-coordinate cross-attention design can be easily integrated into other developed Transformer models to boost performance., Competing Interests: Declaration of competing interest S Tu reported research grants and consultancy from Pulse Medical. A Banning reports institutional research grant from Boston Scientific. G De Maria reports research grant from Miracor, Medtronic, Terumo, Abbott, Philips and consultant fee from Miracor. R Kotronias, K Channon, A Banning, and G De Maria acknowledge support/funding from the Oxford NIHR Biomedical Research center. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening., (© 2024. The Author(s).)

The development of nanoassemblies, activated by the tumor microenvironment, capable of generating photothermal therapy (PTT) and amplifying the "ROS (·OH) storm," is essential for precise and effective synergistic tumor treatment. Herein, an innovative cascade-amplified nanotheranostics based on biodegradable Pd-BSA-GOx nanocomposite for NIR-II photoacoustic imaging (PAI) guides self-enhanced NIR-II PTT/chemodynamic therapy (CDT)/starvation synergistic therapy. The Pd-BSA-GOx demonstrates the ability to selectively convert overexpressed H 2 O 2 into strongly toxic ·OH by a Pd/Pd 2+ -mediated Fenton-like reaction at a lower pH level. Simultaneously, the GOx generates H 2 O 2 and gluconic acid, effectively disrupting nutrient supply and instigating tumor starvation therapy. More importantly, the heightened levels of H 2 O 2 and increased acidity greatly enhance the Fenton-like reactivity, generating a significant "·OH storm," thereby achieving Pd 2+ -mediated cascade-amplifying CDT. The specific PTT facilitated by undegraded Pd accelerates the Fenton-like reaction, establishing a positive feedback process for self-enhancing synergetic PTT/CDT/starvation therapy via the NIR-II guided-PAI. Therefore, the multifunctional nanotheranostics presents a simple and versatile strategy for the precision diagnosis and treatment of tumors., (© 2024 Wiley‐VCH GmbH.)

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N 3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn 2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair., (© 2024 Wiley‐VCH GmbH.)

Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85α protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85α in mice activates the Akt-GSK3β/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85α silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3β/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85α triggers the ubiquitination and degradation of p85α, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85α and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: While coronavirus disease 2019 (COVID-19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic., Methods: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID-19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID-19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT., Results: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID-19-associated outcomes over time. In both non-SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID-19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group., Conclusions: Our study provides a longitudinal view of the risks associated with adverse COVID-related outcomes amongst SOT and non-SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high-risk patients., (© 2024 Wiley Periodicals LLC.)

Cardiac glycosides (CGs), which are traditionally used for heart disease, show promise for cancer therapy. However, there is a lack of a comprehensive review of clinical studies in this area, and so far, CGs have not been widely integrated into clinical cancer treatment. This review covers clinical studies from the past five years, highlighting the potential of CGs to reduce cancer risk, enhance chemotherapy effectiveness, mitigate chemotherapy-induced side effects and improve quality of life. Future clinical trials should personalize the dosage of CGs, integrate molecular testing and investigate immunogenic cell death induction and the potential of CGs for treating bone cancer and metastasis. Optimizing the repurposing of CGs for anticancer treatment requires consideration of specific CGs, cancer types and concurrent medications., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

There was arising osteoporosis from an imbalance in bone remodeling, with excessive differentiation of bone marrow mesenchymal stem cells (BMSCs) into adipocytes instead of osteoblasts. In this study, we found IKKε was upregulated in osteoporotic bone and Ikbke knockdown promoted osteoblast differentiation. We explored amlexanox (AM), a novel IKKε inhibitor, for its effects on osteogenic differentiation and bone homeostasis. AM treatment in mice decreased bone loss, reduced marrow fat, and improved bone microarchitecture, leading to enhanced bone strength. In vitro, AM promoted osteogenesis and suppressed adipogenesis of BMSCs in a dose-dependent manner. Moreover, AM controlled RANKL/OPG expression of BMSC which regulated osteoclast differentiation. Mechanistic explorations revealed AM reinforced Wnt/β-catenin pathway by suppressing ubiquitin-proteasome-dependent degradation of β-catenin. Importantly, AM stimulated osteogenesis in human BMSCs. By promoting osteogenesis at the expense of adipogenesis and hindering osteoclastogenesis, AM offers a promising therapeutic strategy for osteoporosis due to its established safety profile., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)