Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis. Methods: This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to December 2023. A disproportionality analysis was conducted to assess drug-related keratitis with positive signals, and drugs were classified and assessed with regard to their drug-induced timing and risk of drug-related keratitis. Results: A total of 1606 drugs were reported to pose a risk of drug-related keratitis in the FAERS database, and, after disproportionality analysis and screening, 17 drugs were found to significantly increase the risk of drug-related keratitis. Among them, seven were ophthalmic medications, including dorzolamide (reporting odds ratio [ROR] = 3695.82), travoprost (ROR = 2287.27), and brimonidine (ROR = 2118.52), and 10 were non-ophthalmic medications, including tralokinumab (ROR = 2609.12), trazodone (ROR = 2377.07), and belantamab mafodotin (ROR = 680.28). The top three drugs having the highest risk of drug-related keratitis were dorzolamide (Bayesian confidence propagation neural network [BCPNN] = 11.71), trazodone (BCPNN = 11.11), and tralokinumab (BCPNN = 11.08). The drug-induced times for non-ophthalmic medications were significantly shorter than those for ophthalmic medications (mean days, 141.02 vs. 321.96, respectively; P < 0.001). The incidence of drug-related keratitis reached its peak in 2023. Conclusions: Prevention of drug-related keratitis is more important than treatment. Identifying the specific risks and timing of drug-induced keratitis can support the development of preventive measures. Translational Relevance: Identifying the specific drugs related to medication-related keratitis is of significant importance for drug vigilance in the occurrence of drug-related keratitis.

A Recyclable Ionogel with High Mechanical Robustness Based on Covalent Adaptable Networks.

Ionogels are an emerging class of soft materials for flexible electronics, with high ionic conductivity, low volatility, and mechanical stretchability. Recyclable ionogels are recently developed to address the sustainability crisis of current electronics, through the introduction of non-covalent bonds. However, this strategy sacrifices mechanical robustness and chemical stability, severely diminishing the potential for practical application. Here, covalent adaptable networks (CANs) are incorporated into ionogels, where dynamic covalent crosslinks endow high strength (11.3 MPa tensile strength), stretchability (2396% elongation at break), elasticity (energy loss coefficient of 0.055 at 100% strain), and durability (5000 cycles of 150% strain). The reversible nature of CANs allows the ionogel to be closed-loop recyclable for up to ten times. Additionally, the ionogel is toughened by physical crosslinks between conducting ions and polymer networks, breaking the common dilemma in enhancing mechanical properties and electrical conductivity. The ionogel demonstrates robust strain sensing performance under harsh mechanical treatments and is applied for reconfigurable multimodal sensing based on its recyclability. This study provides insights into improving the mechanical and electrical properties of ionogels toward functionally reliable and environmentally sustainable bioelectronics.

Femoral version and its clinical relevance in adult hip preservation surgery for developmental dysplasia of the hip.

Femoral version (FV) is more widely adopted with the definition as the angle between the long axis of the femoral neck and the tangent line of the posterior femoral condyles on the axial plane, and the normal range between 5 and 20°. FV can be measured by imaging and functional tests. Cross-sectional CT including both the hip and the knee is the typically used imaging technique, yet variation exists according to the different landmarks used. As MRI investigations are routinely performed preoperatively, and protocols can be easily adopted to include version measurement, they are frequently used as an alternative to CT and offers several advantages. Abnormal FV has adverse effects on the biomechanics and musculoskeletal health of the whole lower limb. It affects the lever arm of muscles and the forces that the hip and patellofemoral joints suffer, and can lead to disorders such as osteoarthritis and impingement. In adult hip preservation surgery for developmental dysplasia of the hip (DDH), abnormal FV is sometimes accompanied by other morphological abnormities of the hip, a more severe DDH, and can help predict postoperative range of motion (ROM), and postoperative impingement. Currently, the most frequently used surgical technique for abnormal FV is femoral derotational osteotomy. Many controversies are left to be solved, including the specific origin of FV, the indication for femoral derotational osteotomy, especially in patients with combined DDH and abnormal FV, and the explicit compensation mechanism of abnormal FV by tibial torsion.

[Analysis of the therapeutic effect of trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture].

OBJECTIVE: Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture. METHODS: Between January 2020 and December 2022, 20 patients with high acetabular posterior wall fractures were retrospectively analyzed, including 12 males and 8 females, aged 18 to 75 years old. They were divided into two groups according to the different surgical methods. Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group, including 5 males and 5 females, aged from 18 to 75 years old. Ten patients were treated with Kocher-Langenbeck approach alone as the control group, including 7 males and 3 females, aged from 18 to 71 years old. Matta reduction criteria were used to evaluate the reduction quality of the two groups, and Harris score was used to compare the hip function of the two groups at the latest follow-up. The operation time, blood loss and postoperative complications of the two groups were analyzed. RESULTS: All patients were followed up for 10 to 24 months. According to the Matta fracture reduction quality evaluation criteria, the observation group achieved anatomical reduction in 6 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 1 case, while the control group only achieved anatomical reduction in 3 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 4 cases. At the final follow-up, the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group. According to the results of Harris score. The hip joint function of the observation group was excellent in 6 cases, good in 3 cases, and fair in 1 case. The hip joint function of the control group was excellent in 2 cases, good in 3 cases, fair in 3 cases, and poor in 2 cases. In the observation group, the intraoperative blood loss ranged from 300 to 700 ml, and the operation duration ranged from 120 to 180 min;in the control group, the intraoperative blood loss ranged from 300 to 650 ml, and the operation duration ranged from 100 to 180 min. Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification, while complications in the control group included 3 cases of traumatic arthritis, 3 cases of heterotopic ossification and 1 case of hip abduction weakness. CONCLUSION: Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates, enhanced excellent and good hip joint function outcomes, and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone. Clinical application of this combined approach is promising, although larger studies are needed for further validation.

Recommendations of the Blue Ribbon Committee II for the Optimization of Surgical Education and Training in the United States: The Surgical Trainee Perspective.

OBJECTIVE: This study aims to appraise recommendations from an expert panel of surgical educators on optimizing surgical education and training in the setting of contemporary challenges. BACKGROUND: The Blue Ribbon Committee (BRC II), a group of surgical educators, was convened to make recommendations to optimize surgical training considering the current changes in the landscape of surgical education. Surgical trainees were recruited to assess their impressions of the recommendations. METHODS: A mixed-methods study design was employed, with a survey, followed by focus group interviews. Participating residents and fellows were recruited through a purposeful sampling approach. Descriptive statistics were applied to analyze the survey data, and a thematic data analysis on interview transcripts was employed. RESULTS: The majority of trainee respondents (n=16) thought that all of the subcommittee recommendations should be included in the final BRC II recommendations and paper. According to the interviews, overall, the feedback from the trainees was positive, with particular excitement around work-life integration, education support and faculty development, and funding pitfalls. Some themes about concerns included a lack of clarity about the recommendations, concern about some recommendations being in conflict with one another, and a disconnect between the initial BRC II survey and the subsequent recommendations. CONCLUSIONS: The residents gathered for this focus group were encouraged by the thought, effort, and intention that gathered the surgical leaders across the country to make the recommendations. While there were areas the trainees wanted clarity on, the overall opinion was in agreement with the recommendations.

Muscle-Inspired Formable Wood-Based Phase Change Materials.

Phase change materials (PCMs) are crucial for sustainable thermal management in energy-efficient construction and cold chain logistics, as they can store and release renewable thermal energy. However, traditional PCMs suffer from leakage and a loss of formability above their phase change temperatures, limiting their shape stability and versatility. Inspired by the muscle structure, formable PCMs with a hierarchical structure and solvent-responsive supramolecular networks based on polyvinyl alcohol (PVA)/wood composites are developed. The material, in its hydrated state, demonstrates low stiffness and pliability due to the weak hydrogen bonding between aligned wood fibers and PVA molecules. Through treatment of poly(ethylene glycol) (PEG) into the PVA/wood PEG gel (PEG/PVA/W) with strengthened hydrogen bonds, the resulting wood-based PCMs in the hard and melting states elevate the tensile stress from 10.14 to 80.86 MPa and the stiffness from 420 MPa to 4.8 GPa, making it 530 times stiffer than the PEG/PVA counterpart. Capable of morphing in response to solvent changes, these formable PCMs enable intricate designs for thermal management. Furthermore, supported by a comprehensive life cycle assessment, these shape-adaptable, recyclable, and biodegradable PCMs with lower environmental footprint present a sustainable alternative to conventional plastics and thermal management materials.

Iron Chelator Deferiprone Restores Iron Homeostasis and Inhibits Retinal Neovascularization in Experimental Neovascular Age-Related Macular Degeneration.

Purpose: Retinal neovascularization is a significant feature of advanced age-related macular degeneration (AMD) and a major cause of blindness in patients with AMD. However, the underlying mechanism of this pathological neovascularization remains unknown. Iron metabolism has been implicated in various biological processes. This study was conducted to investigate the effects of iron metabolism on retinal neovascularization in neovascular AMD (nAMD). Methods: C57BL/6J and very low-density lipoprotein receptor (VLDLR) knockout (Vldlr-/-) mice, a murine model of nAMD, were used in this study. Bulk-RNA sequencing was used to identify differentially expressed genes. Western blot analysis was performed to test the expression of proteins. Iron chelator deferiprone (DFP) was administrated to the mice by oral gavage. Fundus fluorescein angiography was used to evaluate retinal vascular leakage. Immunofluorescence staining was used to detect macrophages and iron-related proteins. Results: RNA sequencing (RNA-seq) results showed altered transferrin expression in the retina and RPE of Vldlr-/- mice. Disrupted iron homeostasis was observed in the retina and RPE of Vldlr-/- mice. DFP mitigated iron overload and significantly reduced retinal neovascularization and vascular leakage. In addition, DFP suppressed the inflammation in Vldlr-/- retinas. The reduced signals of macrophages were observed at sites of neovascularization in the retina and RPE of Vldlr-/- mice after DFP treatment. Further, the IL-6/JAK2/STAT3 signaling pathway was activated in the retina and RPE of Vldlr-/- mice and reversed by DFP treatment. Conclusions: Disrupted iron metabolism may contribute to retinal neovascularization in nAMD. Restoring iron homeostasis by DFP could be a potential therapeutic approach for nAMD.

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor: A systematic review and meta-analysis.

BACKGROUND: Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action. AIM: To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST. METHODS: The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024. RESULTS: A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg's funnel plot in all studies. CONCLUSION: RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Utilizing machine learning to integrate single-cell and bulk RNA sequencing data for constructing and validating a novel cell adhesion molecules related prognostic model in gastric cancer.

BACKGROUND: Cell adhesion molecules (CAMs) play a vital role in cell-cell interactions, immune response modulation, and tumor cell migration. However, the unique role of CAMs in gastric cancer (GC) remains largely unexplored. METHODS: This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model. RESULTS: Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score. CONCLUSION: Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.

Finite element analysis of anterior cruciate ligament reconstruction techniques: A comparison of the mechanical properties of all-inside fixation and traditional fixation.

Objective: The main purpose of this study was to explore the mechanical properties of the anterior cruciate ligament and its attachments following reconstruction with the all-inside technique after anterior cruciate ligament injury. Methods: Knee joint computed tomography data were collected from healthy volunteers, and knee joint models were created using Mimics software. A normal knee joint model, an all-inside reconstructed anterior cruciate ligament model, and a traditional reconstructed anterior cruciate ligament model were established. A tensile force of 134 N and a bending moment of 5 N/m were applied at the anterior aspect of the proximal tibia in these three models. The knee joint was subjected to external rotation, internal rotation, varus, valgus, flexion, and extension under this bending moment. The magnitude and distribution of stress on the ligament or graft and the magnitude and distribution of stress on the graft attachments were observed under different loading conditions. Results: Under different external forces, the maximum stress on the ligament in the normal model fluctuated from 1.949 to 18.302 MPa, with an uncertain distribution of maximum stress. The maximum stress on the graft in the all-inside reconstructed anterior cruciate ligament model fluctuated from 0.705 to 3.465 MPa and was mainly distributed at the junction of the graft and the tibial footprint. In the traditional reconstructed anterior cruciate ligament model, the maximum stress on the graft fluctuated from 5.012 to 59.269 MPa and was primarily distributed at the junction of the interference screw and the graft. The concentration of stress on the loop and plate in the all-inside reconstructed anterior cruciate ligament model fluctuated from 70.461 to 346.363 MPa, with maximum stress distributed at the junction of the loop and the tibial surface. The maximum stress on the interference screw in the traditional reconstructed anterior cruciate ligament model fluctuated from 10.184 to 92.298 MPa, with maximum stress primarily distributed at the end of the interference screw. Conclusion: Under different external forces, the graft used in all-inside anterior cruciate ligament reconstruction is subjected to fewer external forces than that used in traditional anterior cruciate ligament reconstruction, which may indicate a relatively stable mechanical environment. The strength of the loop and plate can theoretically tolerate daily knee joint movements of patients without injury.

Efficacy of stromal vascular fraction in the treatment of scars: A systematic review and meta-analysis.

OBJECTIVE: Our aim was to assess the effectiveness of stromal vascular fraction (SVF) in treating scars using the latest meta-analysis. METHODS: We used PubMed, Embase, Cochrane, and Web of Science to search the studies used to evaluate the efficacy of SVF in scar treatment. At least one of the following outcome measures were reported: vascularity, pigmentation, thickness, relief, pliability, surface area, pain, itching and color. RESULTS: A total of four eligible articles comprising 145 patients (64 SVF patients and 81 non-SVF patients) were included. The findings of this meta-analysis indicated that SVF had significant therapeutic effects in terms of vascularity (SMD/MD, 95% CI: -1.12, -0.02; p = 0.04), itching (SMD/MD, 95% CI: -0.61, -0.13; p = 0.002), POSAS (SMD/MD, 95% CI: -5.93, -1.47; p = 0.001), and thickness (SMD/MD, 95% CI: -1.04, -0.35; p < 0.001). In terms of OSAS (SMD/MD, 95% CI: -9.14, 0.59; p = 0.09), pigmentation (SMD/MD, 95% CI: -1.02, 0.06; p = 0.08), relief (SMD/MD, 95% CI: -1.14, 0.16; p = 0.14), surface area (SMD/MD, 95% CI: -0.91, 0.26; p = 0.27), PSAS (SMD/MD, 95% CI: -7.20, 0.49; p = 0.09), pain (SMD/MD, 95% CI: -0.87, 0.07; p = 0.10), pliability (SMD/MD, 95% CI: -0.57, 0.01; p = 0.06), and color (SMD/MD, 95% CI: -1.78, 0.48; p = 0.26), there were no significant statistical differences. CONCLUSION: In view of the heterogeneity and potential selective bias, further large-scale, prospective, and multicenter clinical trials are needed to confirm the efficacy and reliability of SVF in the treatment of scars.

Retinex theory-based nonlinear luminance enhancement and denoising for low-light endoscopic images.

BACKGROUND: The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. METHODS: In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. RESULTS: Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. CONCLUSIONS: It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.

Genome-Wide Identification and Expression Analysis of SlNRAMP Genes in Tomato under Nutrient Deficiency and Cadmium Stress during Arbuscular Mycorrhizal Symbiosis.

Arbuscular mycorrhizal (AM) fungi are well known for enhancing phosphorus uptake in plants; however, their regulating roles in cation transporting gene family, such as natural resistance-associated macrophage protein (NRAMP), are still limited. Here, we performed bioinformatics analysis and quantitative expression assays of tomato SlNRAMP 1 to 5 genes under nutrient deficiency and cadmium (Cd) stress in response to AM symbiosis. These five SlNRAMP members are mainly located in the plasma or vacuolar membrane and can be divided into two subfamilies. Cis-element analysis revealed several motifs involved in phytohormonal and abiotic regulation in their promoters. SlNRAMP2 was downregulated by iron deficiency, while SlNRAMP1, SlNRAMP3, SlNRAMP4, and SlNRAMP5 responded positively to copper-, zinc-, and manganese-deficient conditions. AM colonization reduced Cd accumulation and expression of SlNRAMP3 but enhanced SlNRAMP1, SlNRAMP2, and SlNRMAP4 in plants under Cd stress. These findings provide valuable genetic information for improving tomato resilience to nutrient deficiency and heavy metal stress by developing AM symbiosis.

Survivin inhibition attenuates EGF-induced epithelial mesenchymal transformation of human RPE cells via the EGFR/MAPK pathway.

PURPOSE: The abnormal growth factors-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells was known as a vital pathogenesis of proliferative vitreoretinopathy (PVR). This study aims to explore how survivin inhibition affects EMT induced by epidermal growth factor (EGF) in RPE cells. METHODS: Human primary RPE cells were identified in vitro. EMT in RPE cells was induced by EGF. Inhibition of survivin in RPE cells was accomplished through the use of a survivin inhibitor (YM155) and survivin siRNA. The viability, proliferation and migration of RPE cells was detected by methylthiazol tetrazolium assay, bromodeoxyuridine labeling assay, and wound healing assay, respectively. The EGF receptor /mitogen-activated protein kinase (EGFR/MAPK) proteins and EMT-related proteins were measured by western blot and immunofluorescence assay. RESULTS: EGF induced significant EMT in RPE cells, activated the phosphorylation of EGFR/MAPK signaling proteins, and caused changes to EMT-related proteins. YM155 suppressed RPE cells' viability, proliferation, and migration; induced the phosphorylation of EGFR, JNK, and P38MAPK; and down regulated EGFR and phosphorylated ERK. YM155 also increased expression of E-cadherin and ZO-1 proteins and reduced expression of N-cadherin, Vimentin, and α-SMA proteins. The EGF-induced increase of RPE cell proliferation and migration was constrained by survivin inhibition. Moreover, survivin inhibition in RPE cells suppressed the EGF-caused phosphorylation of EGFR/MAPK proteins and attenuated the EGF-induced reduction of E-cadherin and ZO-1 proteins and increase of N-cadherin, Vimentin, and α-SMA proteins. CONCLUSIONS: Survivin inhibition attenuates EGF-induced EMT of RPE cells by affecting the EGFR/MAPK signaling pathway. Survivin might be a promising target for preventing PVR.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

Interfacing Neuron-Motor Pathways with Stretchable and Biocompatible Electrode Arrays.

ConspectusIn the field of neuroscience, understanding the complex interactions within the intricate neuron-motor system depends crucially on the use of high-density, physiological multiple electrode arrays (MEAs). In the neuron-motor system, the transmission of biological signals primarily occurs through electrical and chemical signaling. Taking neurons for instance, when a neuron receives external stimuli, it generates an electrical signal known as the action potential. This action potential propagates along the neuron's axon and is transmitted to other neurons via synapses. At the synapse, chemical signals (neurotransmitters) are released, allowing the electrical signal to traverse the synaptic gap and influence the next neuron. MEAs can provide unparalleled insights into neural signal patterns when interfacing with the nerve systems through their excellent spatiotemporal resolution. However, the inherent differences in mechanical and chemical properties between these artificial devices and biological tissues can lead to serious complications after chronic implantation, such as body rejection, infection, tissue damage, or device malfunction. A promising strategy to enhance MEAs' biocompatibility involves minimizing their thickness, which aligns their bending stiffness with that of surrounding tissues, thereby minimizing damage over time. However, this solution has its limits; the resulting ultrathin devices, typically based on plastic films, lack the necessary stretchability, restricting their use to organs that neither stretch nor grow.For practical deployments, devices must exhibit certain levels of stretchability (ranging from 20 to 70%), tailored to the specific requirements of the target organs. In this Account, we outline recent advancements in developing stretchable MEAs that balance stretchability with sufficient electrical conductivity for effective use in physiological research, acting as sensors and stimulators. By concentrating on the neuron-motor pathways, we summarize how the stretchable MEAs meet various application needs and examine their effectiveness. We distinguish between on-skin and implantable uses, given their vastly different requirements. Within each application scope, we highlight cutting-edge technologies, evaluating their strengths and shortcomings. Recognizing that most current devices rely on elastic films with a Young's modulus value between ∼0.5 and 5 MPa, we delve into the potential for softer MEAs, particularly those using multifunctional hydrogels for an optimizing tissue-device interface and address the challenges in adapting such hydrogel-based MEAs for chronic implants. Additionally, transitioning soft MEAs from lab to fab involves connecting them to a rigid adapter and external machinery, highlighting a critical challenge at the soft-rigid interface due to strain concentration, especially in chronic studies subject to unforeseen mechanical strains. We discuss innovative solutions to this integration challenge, being optimistic that the development of durable, biocompatible, stretchable MEAs will significantly advance neuroscience and related fields.

Development and validation of a machine learning-based 18F-fluorodeoxyglucose PET/CT radiomics signature for predicting gastric cancer survival.

BACKGROUND: Survival prognosis of patients with gastric cancer (GC) often influences physicians' choice of their follow-up treatment. This study aimed to develop a positron emission tomography (PET)-based radiomics model combined with clinical tumor-node-metastasis (TNM) staging to predict overall survival (OS) in patients with GC. METHODS: We reviewed the clinical information of a total of 327 patients with pathological confirmation of GC undergoing 18 F-fluorodeoxyglucose (18 F-FDG) PET scans. The patients were randomly classified into training (n = 229) and validation (n = 98) cohorts. We extracted 171 PET radiomics features from the PET images and determined the PET radiomics scores (RS) using the least absolute shrinkage and selection operator (LASSO) and random survival forest (RSF). A radiomics model, including PET RS and clinical TNM staging, was constructed to predict the OS of patients with GC. This model was evaluated for discrimination, calibration, and clinical usefulness. RESULTS: On multivariate COX regression analysis, the difference between age, carcinoembryonic antigen (CEA), clinical TNM, and PET RS in GC patients was statistically significant (p < 0.05). A radiomics model was developed based on the results of COX regression. The model had the Harrell's concordance index (C-index) of 0.817 in the training cohort and 0.707 in the validation cohort and performed better than a single clinical model and a model with clinical features combined with clinical TNM staging. Further analyses showed higher PET RS in patients who were older (p < 0.001) and those who had elevated CEA (p < 0.001) and higher clinical TNM (p < 0.001). At different clinical TNM stages, a higher PET RS was associated with a worse survival prognosis. CONCLUSIONS: Radiomics models based on PET RS, clinical TNM, and clinical features may provide new tools for predicting OS in patients with GC.

The gut mycobiome signatures in long-lived populations.

Long-lived individuals have been extensively studied as a model to investigate the role of the gut microbiota in aging, but their gut fungi remain almost unexplored. Here, we recruited a community-dwelling cohort of 251 participants (24-108 years, including 47 centenarians) from Guangxi in China to characterize the gut mycobiome signatures. We found gut mycobiome markedly varied during aging and determined aging as a predominant factor driving these variations. For long-lived individuals, core taxa, including Penicillium and Aspergillus, were maintained and Candida enterotype was enriched when compared with old counterparts. Individuals with this enterotype were more likely to possess Bacteroides enterotype enriched in young and centenarians. Moreover, the drivers from Candida enterotype were positively linked with the bacteria components dominated in Bacteroides enterotype. We also identified potentially beneficial yeasts-enriched features to differentiate long-lived individuals from others. Our findings suggest that the gut mycobiome develops with aging, and long-lived individuals possess unique fungal signatures.

Effect of airflow rate on droplet deposition of an impinging-jet inhaler in the human respiratory tract.

This paper presents a numerical investigation to understand the transport and deposition of sprays emitted by an impinging-jet inhaler in the human respiratory tract under different inhalation flow rates. An injection model is used for the numerical simulations considering the spreading angles of the spray in the two directions, which are measured from experiments. The model parameter is adjusted to match the mean droplet size measured in the previous experiment. A time-varying sinusoidal inhalation flow rate is utilized as airflow conditions, which is closer to the actual situation when using an inhaler. The results demonstrate that the inhalation airflow rate significantly affects the spray's transport behavior and deposition results in the respiratory tract. Both excessively high and low inhalation flow rates lead to an increase in deposition in the mouth-throat. A moderate inhalation flow rate reduces throat deposition while maximizing lung deposition. Higher inhalation flow rates enable faster delivery of the droplets to the lungs, whereas lower inhalation flow rates achieve a more uniform deposition over time in the lungs. The amount of deposition in different parts of the lung lobes follows a fixed order. This study provides valuable insights for optimizing the inhalation flow rate conditions of the impinging-jet inhaler for clinical applications.