Passive Fetal Movement Recognition Approaches Using Hyperparameter Tuned LightGBM Model and Bayesian Optimization.

Fetal movement is an important clinical indicator to assess fetus growth and development status in the uterus. In recent years, a noninvasive intelligent sensing fetal movement detection system that can monitor high-risk pregnancies at home has received a lot of attention in the field of wearable health monitoring. However, recovering fetal movement signals from a continuous low-amplitude background that is heavily contaminated with noise and recognizing real fetal movements is a challenging task. In this paper, fetal movement can be efficiently recognized by combining the strength of Kalman filtering, time and frequency domain and wavelet domain feature extraction, and hyperparameter tuned Light Gradient Boosting Machine (LightGBM) model. Firstly, the Kalman filtering (KF) algorithm is used to recover the fetal movement signal in a continuous low-amplitude background contaminated by noise. Secondly, the time domain, frequency domain, and wavelet domain (TFWD) features of the preprocessed fetal movement signal are extracted. Finally, the Bayesian Optimization algorithm (BOA) is used to optimize the LightGBM model to obtain the optimal hyperparameters. Through this, the accurate prediction and recognition of fetal movement are successfully achieved. In the performance analysis of the Zenodo fetal movement dataset, the proposed KF + TFWD + BOA-LGBM approach's recognition accuracy and F1-Score reached 94.06% and 96.85%, respectively. Compared with 8 existing advanced methods for fetal movement signal recognition, the proposed method has better accuracy and robustness, indicating its potential medical application in wearable smart sensing systems for fetal prenatal health monitoring.

Glutathione-Activated NO-/ROS-Generation Nanoparticles to Modulate the Tumor Hypoxic Microenvironment for Enhancing the Effect of HIFU-Combined Chemotherapy.

The combination of high-intensity focused ultrasound (HIFU) and chemotherapy has promising potential in the synergistic treatment of various types of solid tumors. However, the clinical efficacy of HIFU in combination chemotherapy is often impeded by the pre-existing hypoxia tumor microenvironment-induced multidrug resistance (MDR). Therefore, it is imperative for HIFU combined with chemotherapy to overcome MDR by improving the tumor hypoxic microenvironment. Hence, we developed highly stable nanoparticles (P@BDOX/ß-lapachone-NO-NPs) with intracellular nitric oxide (NO)- and reactive oxygen species (ROS)-generating capabilities at the tumor site to relieve the hypoxic tumor microenvironment in solid tumors. Doxorubicin prodrug (boronate-DOX, BDOX) and ß-lapachone were concurrently loaded onto actively targeted pH (low) insertion peptides (pHLIPs)-poly(ethylene glycol) and nitrated gluconic acid copolymers. Our results showed that the ability of P@BDOX/ß-lapachone-NO-NPs to generate NO and ROS simultaneously is vital for the sensitization of hypoxic solid tumors for chemotherapy, as evidenced by the suppression of tumor cells and tissues (in vitro and in the nude mice model). Thus, this combined therapy holds considerable potential in the management of hypoxic solid tumors.

Ultrasound Combined with Core Cross-Linked Nanosystem for Enhancing Penetration of Doxorubicin Prodrug/Beta-Lapachone into Tumors.

BACKGROUND: Nanosized drug delivery systems (NDDSs) have shown excellent prospects in tumor therapy. However, insufficient penetration of NDDSs has significantly impeded their development due to physiological instability and low passive penetration efficiency. METHODS: Herein, we prepared a core cross-linked pullulan-modified nanosized system, fabricated by visible-light-induced diselenide bond cross-linked method for transporting ß-Lapachone and doxorubicin prodrug (boronate-DOX, BDOX), to improve the physiological stability of the NDDSs for efficient passive accumulation in tumor blood vessels (ß-Lapachone/BDOX-CCS). Additionally, ultrasound (US) was utilized to transfer ß-Lapachone/BDOX-CCS around the tumor vessel in a relay style to penetrate the tumor interstitium. Subsequently, ß-Lapachone enhanced ROS levels by overexpressing NQO1, resulting in the transformation of BDOX into DOX. DOX, together with abundant levels of ROS, achieved synergistic tumor therapy. RESULTS: In vivo experiments demonstrated that ultrasound (US) + cross-linked nanosized drug delivery systems (ß-Lapachone/BDOX-CCS) group showed ten times higher DOX accumulation in the tumor interstitium than the non-cross-linked (ß-Lapachone/BDOX-NCS) group. CONCLUSION: Thus, this strategy could be a promising method to achieve deep penetration of NDDSs into the tumor.

A redox-sensitive core-crosslinked nanosystem combined with ultrasound for enhanced deep penetration of nanodiamonds into tumors.

Nanodiamonds (NDs) as drug delivery vehicles are of great significance in anticancer therapy through enhancing drug retention. However, the major barrier to clinical application of NDs is insufficient tumor penetration owing to their strong aggregation and low passive penetration efficiency. Herein, the core-crosslinked pullulan carrier, assembled using the visible light-induced diselenide (Se-Se) bond crosslinking method for encapsulating nanodiamonds-doxorubicin (NDX), is proposed to improve monodispersity. Furthermore, the core-crosslinked diselenide bond provides the nanosystem with redox-responsive capability and improved structural stability in a physiological environment, which prevents premature drug leakage and achieves tumor site-specific controlled release. What's more, ultrasound (US) is utilized to promote nanosystem intratumoral penetration via enlarged tumor vascular endothelium cell gaps. As expected, the nanosystem combined with ultrasound can enhance anti-tumor efficacy with deep penetration and excellent retention performance in a HepG2 xenograft mouse model. This study highlights the ability of the integrated therapeutic paradigm to overcome the limitation of nanodiamonds and the potential for further application in cancer therapy.