Intelligent skin-removal photoacoustic computed tomography for human based on deep learning.

Photoacoustic computed tomography (PACT) has centimeter-level imaging ability and can be used to detect the human body. However, strong photoacoustic signals from skin cover deep tissue information, hindering the frontal display and analysis of photoacoustic images of deep regions of interest. Therefore, we propose a 2.5 D deep learning model based on feature pyramid structure and single-type skin annotation to extract the skin region, and design a mask generation algorithm to remove skin automatically. PACT imaging experiments on the human periphery blood vessel verified the correctness our proposed skin-removal method. Compared with previous studies, our method exhibits high robustness to the uneven illumination, irregular skin boundary, and reconstruction artifacts in the images, and the reconstruction errors of PACT images decreased by 20% ~ 90% with a 1.65 dB improvement in the signal-to-noise ratio at the same time. This study may provide a promising way for high-definition PACT imaging of deep tissues.

Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial.

PURPOSE: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes. METHODS: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events. RESULTS: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12-14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2-8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42-0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37-0.86), and for mortality was 0.63 (0.42-0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups. CONCLUSION: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Jellyfish-Inspired Visual and Sensory Bubbling Robots with Automatic 3D Morphable Films for Underwater Environmental Interactions.

Coelenterates, such as Atolla jellyfish, are capable of integrating color, communication, and motion in a sophisticated manner, thereby enabling them to function as intelligent biological systems that can adapt to the challenges of the underwater environment. Extensive efforts have been dedicated to exploiting underwater visual, sensory, actuating, or combined systems. However, current biomimetic soft systems are still limited by the lack of comprehensive, integrated functional skins that can automatically deform, dynamically sense, and further send color signals when diving into underwater conditions. Here, we propose the synthetic soft skins composed of assembled entangled carbon nanotube networks and fluorescent unit-embedded elastomers which can be applied in a suspended form to allow autonomic 3D deformation, real-time perception, and dynamic fluorescence color transformation. The capabilities of the sensory and color display thresholds were controlled through the entanglement density of carbon nanotubes and the suspended area. As a demonstration, the soft thin skin was integrated into an artificial jellyfish robot, enabling the realization of a closed-loop feedback system for dynamic sensory processing, signal processing, and further 3D morphing-induced fluorescent color change, demonstrating significant potentials in underwater visual display, danger warning, and environmental exploration.

Autophagy in erectile dysfunction: focusing on apoptosis and fibrosis.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.

Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.

Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, arthromyalgia, sore throat, and disrupted sleep patterns. CFS is defined by its persistent or recurrent manifestation for a minimum duration of six months, marked by an enduring and unrelenting fatigue that remains refractory to rest. In recent decades, this condition has garnered significant attention within the medical community. While the precise etiology of CFS remains elusive, it is postulated to be multifactorial. CFS is potentially associated with various contributory factors such as infections, chronic stress, genetic predisposition, immune dysregulation, and psychosocial influences. The pathophysiological underpinnings of CFS encompass viral infections, immune system dysregulation, neuroendocrine aberrations, heightened oxidative stress, and perturbations in gut microbiota. Presently, clinical management predominantly relies on pharmaceutical interventions or singular therapeutic modalities, offering alleviation of specific symptoms but exhibiting inherent limitations. Traditional Chinese Medicine (TCM) interventions have emerged as a promising paradigm, demonstrating notable efficacy through their multimodal, multi-target, multi-pathway approach, and holistic regulatory mechanisms. These interventions effectively address the lacunae in contemporary medical interventions. This comprehensive review synthesizes recent advancements in the understanding of the etiological factors, pathophysiological mechanisms, and interventional strategies for CFS, drawing from a corpus of domestic and international literature. Its aim is to furnish valuable insights for clinicians actively involved in diagnosing and treating CFS, as well as for pharmaceutical researchers delving into innovative drug development pathways. Moreover, it seeks to address the intricate challenges confronted by clinical practitioners in managing this incapacitating condition.

Timeframe for Conversion to Psychosis From Individuals at Clinical High-Risk: A Quantile Regression.

BACKGROUND AND HYPOTHESIS: The time taken for an individual who is at the clinical high-risk (CHR) stage to transition to full-blown psychosis may vary from months to years. This temporal aspect, known as the timeframe for conversion to psychosis (TCP), is a crucial but relatively underexplored dimension of psychosis development. STUDY DESIGN: The sample consisted of 145 individuals with CHR who completed a 5-year follow-up with a confirmed transition to psychosis within this period. Clinical variables along with functional variables such as the Global Assessment of Function (GAF) score at baseline (GAF baseline) and GAF-drop from the highest score in the past year. The TCP was defined as the duration from CHR identification to psychosis conversion. Participants were categorized into 3 groups based on TCP: "short" (≤6 months, ≤33.3%), "median" (7-17 months, 33.3%-66.6%), and "long" (≥18 months, ≥66.6%). The quantile regression analysis was applied. STUDY RESULTS: The overall sample had a median TCP of 11 months. Significant differences among the three TCP groups were observed, particularly in GAF-drop (χ2 = 8.806, P = .012), disorganized symptoms (χ2 = 7.071, P = .029), and general symptoms (χ2 = 6.586, P = .037). Greater disorganized symptoms (odds ratio [OR] = 0.824, P = .009) and GAF-drop (OR = 0.867, P = .011) were significantly associated with a shorter TCP, whereas greater general symptoms (OR = 1.198, P = .012) predicted a longer TCP. Quantile regression analysis demonstrated a positive association between TCP and GAF baseline above the 0.7 quantile and a negative association between TCP rank and GAF drop below the 0.5 quantile. CONCLUSIONS: This study underscores the pivotal role of functional characteristics in shaping TCP among individuals with CHR, emphasizing the necessity for a comprehensive consideration of temporal aspects in early prevention efforts.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

SlMDH3 Interacts with Autophagy Receptor Protein SlATI1 and Positively Regulates Tomato Heat Tolerance.

Autophagy, a highly conserved protein degradation system, plays an important role in protecting cells from adverse environmental conditions. ATG8-INTERACTING PROTEIN1 (ATI1) acts as an autophagy receptor, but its functional mechanisms in plants' heat stress tolerance remain unclear. In this study, using LC-MS/MS, we identified malate dehydrogenase (SlMDH3) as a SlATI1-interacting protein. Further studies showed that heat stress induced the expression of SlMDH3 and SlMDH3 co-localized with SlATI1 under both 22 °C and 42 °C heat treatment conditions. Moreover, silencing of SlMDH3 increased the sensitivity of tomato to heat stress, as evidenced by exacerbated degradation of chlorophyll; accumulation of MDA, H2O2, and dead cells; increased relative conductivity; and inhibition of stress-related gene expression. Conversely, overexpression of SlMDH3 improved tomato's heat tolerance, leading to opposite effects on physiological indicators and gene expression compared to SlMDH3 silencing. Taken together, our study suggests that SlMDH3 interacts with SlATI1 and positively regulates tomato heat tolerance.

Engineering Corynebacterium glutamicum for the efficient production of 3-hydroxypropionic acid from glucose via the ß-alanine pathway.

3-Hydroxypropionic Acid (3-HP) is recognized as a high value-added chemical with a broad range of applications. Among the various biosynthetic pathways for 3-HP production, the ß-alanine pathway is particularly noteworthy due to its capacity to generate 3-HP from glucose at a high theoretical titer. In this study, the ß-alanine biosynthesis pathway was introduced and optimized in Corynebacterium glutamicum. By strategically regulating the supply of precursors, we successfully engineered a strain capable of efficiently synthesizing 3-HP through the ß-alanine pathway, utilizing glucose as the substrate. The engineered strain CgP36 produced 47.54 g/L 3-HP at a yield of 0.295 g/g glucose during the fed-batch fermentation in a 5 L fermenter, thereby attaining the highest 3-HP titer obtained from glucose via the ß-alanine pathway.

Rapidly screening of pancreatic lipase inhibitors from Clematis tangutica using affinity ultrafiltration-HPLC-QTOFMS technique combined with targeted separation, in vitro validation, and molecular docking.

INTRODUCTION: Screening of novel pancreatic lipase inhibitors from complex natural products is a meaningful task. OBJECTIVES: Through accurately screening and separating pancreatic lipase inhibitors from Clematis tangutica (C. tangutica), to discover new leading compounds for slimming and accelerate the development and utilization of Tibetan medicine resources. METHODS: An integrated strategy that combines affinity ultrafiltration and high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (AU-HPLC-QTOFMS), targeted separation, in vitro validation, and molecular docking was developed to screen pancreatic lipase inhibitors from C. tangutica. The AU-HPLC-QTOFMS technique was performed to fish for the potential active substances. Macroporous resin, preparative liquid chromatography, and high-speed countercurrent chromatography were implemented for the accurate and targeted separation of active compounds. The inhibitory activities of target compounds to pancreatic lipase were detected by the inhibition experiments in vitro. The binding affinities and binding sites were analyzed using molecular docking. RESULTS: A total of eleven kinds of pancreatic lipase inhibitory substances were screened from C. tangutica. Seven triterpenoid saponins were screened for the first time as lipase inhibitors and successfully prepared with purities higher than 97%. Tanguticoside B, clematangoticoside J, hederoside H1, and rutin showed stronger inhibitory effects with IC50 values of 1.539 ± 0.048, 1.661 ± 0.092, 1.793 ± 0.069, and 1.792 ± 0.094 mmol/l. Moreover, they have the lowest ΔG values of -10.84, -9.97, -10.87, and -9.39 kcal/mol to pancreatic lipase. CONCLUSION: The integrated strategy using AU-HPLC-QTOFMS, targeted separation, in vitro validation, and molecular docking was feasible for rapidly screening and directionally isolating pancreatic lipase inhibitors from C. tangutica.

One-Step Hydrothermal Deposition of AgSbS2-xSex Thin Films for Solar Cell Applications.

AgSbS2-xSex is a promising light-harvesting material for thin film solar cells, characterized by nontoxicity, high chemical stability, and excellent optoelectronic properties. However, the complex chemical composition of AgSbS2-xSex poses significant challenges to thin film preparation, giving rise to an intensive dependence on multi-step preparation methods. Herein, a hydrothermal method is developed for depositing AgSbS2-xSex films and achieves one-step preparation of this kind of thin film materials for the first time. This method can provide sufficient energy for atomic nucleation and adsorption on the substrate surface to promote nuclei aggregation and grow into films. Meanwhile, it achieves control of the chemical kinetics of the deposition solution by introducing EDTA-2Na as an additive and suppressing the enrichment of Ag2Se impurities at the substrate interface. As a result, a high-purity AgSbS2-xSex film with compact and flat morphology is prepared and assembled into solar cells. The device delivers a power conversion efficiency of 3.04% under standard illumination, which is currently the highest efficiency for AgSbS2-xSex solar cells fabricated by the one-step method. This study provides a facile and promising method for the controllable preparation of high-quality AgSbS2-xSex thin films and promoting their application in solar cells.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Comparison of the Impact of a 6 French GlideSheath Slender® and a Conventional Sheath on Distal Radial Artery Occlusion: A Randomized Controlled Trial.

BACKGROUND: There is a lack of randomized clinical trials investigating whether the 6-Fr Glidesheath Slender (GSS) is superior to the 6-Fr conventional radial sheath (CS) with respect to the early-term incidence of distal radial artery occlusion (dRAO) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) via distal transradial access (dTRA). METHODS: This was a prospective, single-centre trial of patients who were randomized to undergo CAG and/or PCI with either a 6-Fr GSS or a 6-Fr CS. The primary endpoint was the incidence of dRAO at 24 h postoperatively, as evaluated by Doppler ultrasound. RESULTS: A total of 620 patients were included in the study. The baseline patient and procedural characteristics were similar between the two groups. For the primary endpoint, the incidence of dRAO at 24 h after the procedure was 1.0% (3/314) in the GSS group and 3.6% (11/306) in the CS group (RR= 0.266, 95% CI= 0.075-0.943, P= 0.027) according to the intention-to-treat (ITT) analysis. For the secondary endpoints, the incidence of proximal RAO was 0.3% (1/314) in the GSS group and 2.3% (7/306) in the CS group (P= 0.029). Other secondary endpoints, including the puncture success rate, procedural outcomes, other puncture-related outcomes and access-related complications, were not significantly different between the two groups. CONCLUSION: The use of a thin-walled and hydrophilic coating sheath can reduce the incidence of early-term dRAO in patients who undergo CAG and/or PCI via the dTRA.

High-n Phase Suppression for Efficient and Stable Blue Perovskite Light-Emitting Diodes.

Quasi-2D perovskites light-emitting diodes (PeLEDs) have achieved significant progress due to their superior optical and electronic properties. However, the blue PeLEDs still exist inefficient energy transfer and electroluminescence performance caused by mixed multidimensional phase distribution. In this work, transition metal salt (zinc bromide, ZnBr2) is introduced to modulate phase distributions by suppressing the nucleation of high n phase perovskites, which effectively shortens the energy transfer path for blue emission. Moreover, ZnBr2 also facilitates energy level matching and reduces non-radiative recombination, thus improving electroluminescence (EL) efficiency. Benefiting from these combined improvements, an efficient blue PeLEDs is obtained with a maximum external quantum efficiency (EQE) of 16.2% peaking located at 486 nm. This work provides a promising approach to tune phase distribution of quasi-2D perovskites and achieving highly efficient blue PeLEDs.

Unveiling Mechanistic Insight into Accelerating Oxygen Molecule Activation by Oxygen Defects in Co3O4-x/g-C3N4 p-n Heterojunction for Efficient Photo-Assisted Uranium Extraction from Seawater.

Photo-assisted uranium extraction from seawater (UES) is regarded as an efficient technique for uranium resource recovery, yet it currently faces many challenges, such as issues like biofouling resistance, low charge separation efficiency, slow carrier transfer, and a lack of active sites. Based on addressing the above challenges, a novel oxygen-deficient Co3O4-x/g-C3N4 p-n heterojunction is developed for efficient photo-assisted uranium extraction from seawater. Relying on the defect-coupling heterojunction synergistic effect, the redistribution of molecular charge density formed the built-in electric field as revealed by DFT calculations, significantly enhancing the separation efficiency of carriers and accelerating their migration rate. Notably, oxygen vacancies served as capture sites for oxygen, effectively promoting the generation of reactive oxygen species (ROS), thereby significantly improving the photo-assisted uranium extraction performance and antibacterial activity. Thus, under simulated sunlight irradiation with no sacrificial reagent added, Co3O4-x/g-C3N4 extracted a high uranium extraction amount of 1.08 mg g-1 from 25 L of natural seawater after 7 days, which is superior to most reported carbon nitride-based photocatalysts. This study elaborates on the important role of surface defects and inerface engineering strategies in enhancing photocatalytic performance, providing a new approach to the development and design of uranium extraction material from seawater.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and kidney stone: evidence from NHANES 2007-2018.

BACKGROUND: As an innovative lipid parameter, NHHR (the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol) can serve as a valuable tool for assessing cardiovascular disease risk. Nevertheless, the relationship between NHHR and the risk of kidney stones remains unexplored. METHODS: A cross-sectional survey utilized data from the National Health and Population Survey (NHANES) database in the United States spanning from 2007 to 2018. Distinct statistical analyses were applied, including weighted logistic regression, stratified and interaction analysis and restricted cubic spline curve (RCS) models, to examine the correlation between NHHR and the incidence of kidney stones. RESULTS: This analysis encompassed 24,664 participants, with 9.63% reporting incidents of kidney stones. Following multivariate logistic regression and comprehensive adjustments, participants in NHHR quartile 4 (OR 1.34; 95% CI 1.12, 1.60, P < 0.01) exhibited a significantly increased risk of kidney stones compared to those in NHHR quartile 1 (Q1). The RCS result further illustrated a non-linear correlation between NHHR and the incidence of kidney stones. The result of subgroup analysis manifested that participants without diabetes had a higher risk of kidney stones when measured high NHHR levels compared those with diabetes (p for interaction < 0.05). CONCLUSION: Elevated NHHR levels were found to be associated with an increased risk of kidney stones. Based on these findings, NHHR appears to be a promising predictive indicator for the occurrence of kidney stones.

Application of 3D bioprinting technology apply to assessing Dangguiniantongtang (DGNT) decoctions in arthritis.

The aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1ß, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.

Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this condition. One of the mechanisms through which SONFH operates is the disruption of normal differentiation in bone marrow adipocytes and osteoblasts due to prolonged and extensive use of glucocorticoids (GCs). In vitro, it was observed that atorvastatin (ATO) effectively suppressed the impact of dexamethasone (DEX) on bone marrow mesenchymal stem cells (BMSCs), specifically by augmenting their lipogenic differentiation while impeding their osteogenic differentiation. To investigate the underlying mechanisms further, we conducted transcriptome sequencing of BMSCs subjected to different treatments, leading to the identification of Wnt5a as a crucial gene regulated by ATO. The analyses showed that ATO exhibited the ability to enhance the expression of Wnt5a and modulate the MAPK pathway while regulating the Wnt canonical signaling pathway via the WNT5A/LRP5 pathway. Our experimental findings provide further evidence that the combined treatment of ATO and DEX effectively mitigates the effects of DEX, resulting in the upregulation of osteogenic genes (Runx2, Alpl, Tnfrsf11b, Ctnnb1, Col1a) and the downregulation of adipogenic genes (Pparg, Cebpb, Lpl), meanwhile leading to the upregulation of Wnt5a expression. So, this study offers valuable insights into the potential mechanism by which ATO can be utilized in the prevention of SONFH, thereby holding significant implications for the prevention and treatment of SONFH in clinical settings.

Comprehensive analysis and experimental verification reveal the molecular characteristics of EGLN3 in pan-cancer and its relationship with the proliferation and apoptosis of lung cancer.

Background: Egl-9 family hypoxia-inducible factor 3 (EGLN3) is involved in the regulation of tumor microenvironment and tumor progression. However, its biological function and clinical significance in various cancers remain unclear. Methods: RNA-seq, immunofluorescence, and single-cell sequencing were used to investigate the expression landscape of EGLN3 in pan-cancer. The TISCH2 and CancerSEA databases were used for single-cell function analysis of EGLN3 in tumors. TIMER2.0 database was used to explain the relationship between EGLN3 expression and immune cell infiltration. In addition, the LinkedOmics database was used to perform KEGG enrichment analysis of EGLN3 in pan-cancer. siRNA was used to silence gene expression. CCK8, transwell migration assay, flow cytometry analysis, RT-PCR, and western blotting were used to explore biological function of EGLN3. Results: The results showed that EGLN3 was highly expressed in a variety of tumors, and was mainly localized to the cytosol. EGLN3 expression is associated with immunoinfiltration of a variety of immune cells, including macrophages in the tumor immune microenvironment and tumor-associated fibroblasts. Functional experiments revealed that EGLN3 knockdown could inhibit cell proliferation, migration, and promote cell apoptosis. In addition, we found that Bax expression was up-regulated and Bcl-2 expression was down-regulated in the si-EGLN3 group. Taken together, as a potential oncogene, EGLN3 is involved in the regulation of tumor malignant process, especially tumor cell apoptosis. Conclusion: We comprehensively investigated the expression pattern, single-cell function, immune infiltration level and regulated signaling pathway of EGLN3 in pan-cancer. We found that EGLN3 is an important hypoxia and immune-related gene that may serve as a potential target for tumor immunotherapy.