Evaluation of a novel saliva-based epidermal growth factor receptor mutation detection for lung cancer: A pilot study.

BackgroundThis article describes a pilot study evaluating a novel liquid biopsy system for non-small cell lung cancer (NSCLC) patients. The electric field-induced release and measurement (EFIRM) method utilizes an electrochemical biosensor for detecting oncogenic mutations in biofluids.MethodsSaliva and plasma of 17 patients were collected from three cancer centers prior to and after surgical resection. The EFIRM method was then applied to the collected samples to assay for exon 19 deletion and p.L858 mutations. EFIRM results were compared with cobas results of exon 19 deletion and p.L858 mutation detection in cancer tissues.ResultsThe EFIRM method was found to detect exon 19 deletion with an area under the curve (AUC) of 1.0 in both saliva and plasma samples in lung cancer patients. For L858R mutation detection, the AUC of saliva was 1.0, while the AUC of plasma was 0.98. Strong correlations were also found between presurgery and post-surgery samples for both saliva (0.86 for exon 19 and 0.98 for L858R) and plasma (0.73 for exon 19 and 0.94 for L858R).ConclusionOur study demonstrates the feasibility of utilizing EFIRM to rapidly, non-invasively, and conveniently detect epidermal growth factor receptor mutations in the saliva of patients with NSCLC, with results corresponding perfectly with the results of cobas tissue genotyping

Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations.Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized.Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h−1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL.Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding

Funding Information: The investigators were supported by grants from the NIH (R01DK114279, R01DK109934, and R21NS108091 to QT; R01ES027544 and R01DK111436 to ZS; R00DK107008 to PX; R01DK109194 and R56DK109194 to QW; P01DK113954, R01DK115761, R01DK117281, and R01DK125480 to YX; R01DK120858 to QT and YX; K01DK119471 to CW; and P20GM135002 to YH), USDA/CRIS (51000-064-01 S to YX and QW), American Diabetes Association (1-17-PDF-138 to YH, 7-13-JF-61 to QW, and 1-15-BS-184 to QT), American Heart Association awards (16POST27260254 to CW), the Pew Charitable Trust awards to QW (0026188), Baylor Collaborative Faculty Research Investment Program grants to QW, the Faculty Start-up grants from USDA/ ARS to QW, the Biotechnology and Biological Sciences Research Council (BB/ K001418/1 and BB/NO17838/1 to LKH), and the Medical Research Council (MC/PC/ 15077 to LKH). QW is the Pew Scholar of Biomedical Sciences and the Kavli Scholar. The anxiety tests (e.g., open-field test, light–dark test, and elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. The Ad-iN/ WED virus was kindly provided by Dr. Martin Myers (University of Michigan). The AAV9-CBA-DIO-WGA-zsGreen virus was kindly provided by Dr. Richard Palmiter (University of Washington).Peer reviewedPublisher PD

A Novel Approach for Underwater Vehicle Localization and Communication Based on Laser Reflection

This study presents a device for tracking, locating and communicating underwater vehicles as they work near the seabed. The system includes a base station placed on the seabed and a reflective module mounted on a hybrid underwater profiler (HUP). The base station localizes and communicates with the HUP working near the seabed based on laser reflections of corner cube retroreflectors. A tracking method based on the particle filter algorithm is then presented. Localization is performed using the least-squares method with refraction compensation. Lost tracking links are retrieved via a recovering approach based on the interpolation method. Finally, a communication method using a modulating retroreflector installed on the reflection module is proposed. The proposed tracking, localization, and communication approach provides higher localization accuracy with lower power consumption at low cost compared with the commonly used acoustic methods. The effectiveness of the proposed approach was clarified via tracking, localization, and communication experiments

Autologous Costal Osteochondral Transplantation for Cystic Osteochondral Lesions of the Talus: Feasible and Effective

Objective Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. Methods From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t‐test was used for preoperative and postoperative comparison of the paired‐design dataset. Results The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow‐up. Conclusion ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short‐term follow‐up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3

Background. With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. Methods. A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. Results. We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNAMEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. Conclusion. Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosi

Transcriptional and post-transcriptional control of autophagy and adipogenesis by YBX1

Abstract Obesity is strongly associated with metabolic diseases, which have become a global health problem. Exploring the underlying mechanism of adipogenesis is crucial for the treatment of excess white fat. Oncogene YBX1 is a multifunctional DNA- and RNA-binding protein that regulates brown adipogenesis. However, the role of YBX1 in white adipogenesis and adipose tissue expansion remains unknown. Here, we showed that YBX1 deficiency inhibited murine and porcine adipocyte differentiation. YBX1 positively regulated adipogenesis through promoting ULK1- and ULK2-mediated autophagy. Mechanistically, we identified YBX1 serves as a 5-methylcytosine (m5C)-binding protein directly targeting m5C-containing Ulk1 mRNA by using RNA immunoprecipitation. RNA decay assay further proved that YBX1 upregulated ULK1 expression though stabilizing its mRNA. Meanwhile, YBX1 promoted Ulk2 transcription and expression as a transcription factor, thereby enhancing autophagy and adipogenesis. Importantly, YBX1 overexpression in white fat enhanced ULK1/ULK2-mediated autophagy and promoted adipose tissue expansion in mice. Collectively, these findings unveil the post-transcriptional and transcriptional mechanism and functional importance of YBX1 in autophagy and adipogenesis regulation, providing an attractive molecular target for therapies of obesity and metabolic diseases

Mannan Oligosaccharides Promoted Skeletal Muscle Hypertrophy through the Gut Microbiome and Microbial Metabolites in Mice

Mannan oligosaccharides (MOSs) have been implicated in the animal growth rate, health indices, and lipid oxidative stability. MOSs have been indicated to maintain intestinal health and anti-inflammatory effects via modulation of gut microbiota. Furthermore, the role of MOSs in modulating skeletal muscle function is largely unknown. Here, this study aimed to investigate the effects of MOS supplementation on muscle function and muscle mass in mice. Additionally, the possible underlying mechanisms, including the contributions of gut microbiota and microbial metabolites, were explored. In our study, 3-week-old C57BL/6J male mice (body weight of approximately 10.7 ± 1.1 g) were given pure water or pure water with 1% MOS. To study the effect of MOSs on gut-microbiota-derived metabolites, serum metabolic profiles were analyzed through untargeted metabolomic profiling. Moreover, we detected the downstream signals of differential metabolites, and decanoic acid (DA) was selected as our target spot. Then, DA was used to treat C2C12 cells, and we found that DA promotes C2C12 cell differentiation via the GPR84 and PI3K/AKT signaling pathways. In conclusion, these results showed that MOS supplementation improves muscle function and muscle mass. Additionally, gut microbiome and microbial metabolites were regulated by MOSs, and DA may be one of the most important links between the gut microbiome and skeletal muscle function regulation