Functional force stimulation alters motor neuron discharge patterns.

Introduction: Beneficial effects have been observed for mechanical vibration stimulation (MVS), which are mainly attributed to tonic vibration reflex (TVR). TVR is reported to elicit synchronized motor unit activation during locally applied vibration. Similar effects are also observed in a novel vibration system referred to as functional force stimulation (FFS). However, the manifestation of TVR in FFS is doubted due to the use of global electromyography (EMG) features in previous analysis. Our study aims to investigate the effects of FFS on motor unit discharge patterns of the human biceps brachii by analyzing the motor unit spike trains decoded from the high-density surface EMG. Methods: Eighteen healthy subjects volunteered in FFS training with different amplitudes and frequencies. One hundred and twenty-eight channel surface EMG was recorded from the biceps brachii and then decoded after motion-artifact removal. The discharge timings were extracted and the coherence between different motor unit spike trains was calculated to quantify synchronized activation. Results and discussion: Significant synchronization within the vibration cycle and/or its integer multiples is observed for all FFS trials, which increases with increased FFS amplitude. Our results reveal the basic physiological mechanism involved in FFS, providing a theoretical foundation for analyzing and introducing FFS into clinical rehabilitation programs.

A Capacitive Electrocardiography System With Dedicated Noise-Cancellation Algorithms for Morphological Analysis.

OBJECTIVE: Capacitive electrocardiography (cECG) has been proposed for ambulatory cardiac health monitoring. However, due to the high sensitivity of capacitive electrodes to various noise sources, particularly the power-line interference (PLI) and motion artifacts (MA), the existing capacitive systems are only verified in terms of RR interval. The aim of the present study is to explore the feasibility of using cECG for morphological analysis, and thus to extract clinical meaningful parameters. METHODS: A capacitive electrode with active guarding is realized. A phase-locked-loop (PLL) based adaptive canceller is employed to remove PLI from the cECG. Wavelet analysis is adopted to cancel other noises. The developed capacitive system and algorithms are evaluated by real ECG measurements on 7 volunteers using 3-lead configuration. The correlation coefficient (CC) between the processed cECG and the wet ECG is calculated in two different conditions: with and without the QRS complex. Several frequently used diagnostic parameters, i.e., RR interval, QRS interval, P segment, T segment, ST segment, are extracted and compared with that obtained from the wet ECG. RESULTS: High CCs are observed between the cECG and the wet ECG in both conditions, i.e., 0.97±0.03 with the QRS complex and 0.92±0.07 without the QRS complex. Besides, RR interval extracted from the two different ECG signals are identical for each subject. Other diagnostic parameters are quite similar. SIGNIFICANCE: Our results suggest cECG to be reliable for ambulatory heart rate monitoring. The results also indicate the feasibility of using cECG for clinical diagnosis.

AHNAK2 is a biomarker and a potential therapeutic target of adenocarcinomas.

Adenocarcinoma is the second largest histological type of cervical cancer, second only to cervical squamous cell carcinoma. At present, despite the clinical treatment strategies of cervical adenocarcinoma and cervical squamous cell carcinoma being similar, the outcome and prognosis of cervical adenocarcinoma are significantly poor. Therefore, it is urgent to find specific biomarker and therapeutic target for cervical adenocarcinoma. In this study, we aim to reveal and verify the potential biomarkers and therapeutic targets of cervical adenocarcinoma. Weighted correlation network analysis (WGCNA) reveals the differentially-expressed genes significantly related to the histological characteristics of the two cervical cancer subtypes. We select the genes with the top 20 significance for further investigation. Through microarray and immunohistochemical (IHC) analyses of a variety of tumor tissues, we find that among these 20 genes, AHNAK2 is highly expressed not only in cervical adenocarcinoma, but also in multiple of adenocarcinoma tissues, including esophagus, breast and colon, while not in normal gland tissues. In vitro, AHNAK2 knockdown significantly inhibits cell proliferation and migration of adenocarcinoma cell lines. In vivo, AHNAK2 knockdown significantly inhibits tumor progression and metastasis of various adenocarcinomas. RNA-sequencing and bioinformatics analyses suggest that the inhibitory effect of AHNAK2 knockdown on tumor progression is achieved by regulating DNA replication and upregulating Bim expression. Together, we demonstrate that AHNAK2 is a biomarker and a potential therapeutic target for adenocarcinomas.

Novel Multichannel Entropy Features and Machine Learning for Early Assessment of Pregnancy Progression Using Electrohysterography.

OBJECTIVE: Preterm birth is the leading cause of morbidity and mortality involving over 10% of infants. Tools for timely diagnosis of preterm birth are lacking and the underlying physiological mechanisms are unclear. The aim of the present study is to improve early assessment of pregnancy progression by combining and optimizing a large number of electrohysterography (EHG) features with a dedicated machine learning framework. METHODS: A set of reported EHG features are extracted. In addition, novel cross and multichannel entropy and mutual information are employed. The optimal feature set is selected using a wrapper method according to the accuracy of the leave-one-out cross validation. An annotated database of 74 EHG recordings in women with preterm contractions was employed to test the ability of the proposed method to recognize the onset of labor and the risk of preterm birth. Difference between using the contractile segments only and the whole EHG signal was compared. RESULTS: The proposed method produces an accuracy of 96.4% and 90.5% for labor and preterm prediction, respectively, much higher than that reported in previous studies. The best labor prediction was observed with the contraction segments and the best preterm prediction achieved with the whole EHG signal. Entropy features, particularly the newly-employed cross entropy contribute significantly to the optimal feature set for both labor and preterm prediction. SIGNIFICANCE: Our results suggest that changes in the EHG, particularly the regularity, might manifest early in pregnancy. Single-channel and cross entropy may therefore provide relevant prognostic opportunities for pregnancy monitoring.

CDK16 promotes the progression and metastasis of triple-negative breast cancer by phosphorylating PRC1.

BACKGROUND: Cyclin-dependent kinase 16 (CDK16) is an atypical PCTAIRE kinase, and its activity is dependent on the Cyclin Y (CCNY) family. Ccnys have been reported to regulate mammary stem cell activity and mammary gland development, and CCNY has been recognized as an oncoprotein in various cancers, including breast cancer. However, it remains unclear whether CDK16 has a role in breast cancer and whether it can be used as a therapeutic target for breast cancer. METHODS: Publicly available breast cancer datasets analyses and Kaplan-Meier survival analyses were performed to reveal the expression and clinical relevance of atypical CDKs in breast cancer. CDK16 protein expression was further examined by immunohistochemical and immunoblot analyses of clinical samples. Cell proliferation was measured by colony formation and MTT analyses. Cell cycle and apoptosis were examined by fluorescence-activated cell sorting (FACS) analysis. Wound-healing and trans-well invasion assays were conducted to test cell migration ability. The functions of CDK16 on tumorigenesis and metastasis were evaluated by cell line-derived xenograft, patient-derived organoid/xenograft, lung metastasis and systemic metastasis mouse models. Transcriptomic analysis was performed to reveal the potential molecular mechanisms involved in the function of CDK16. Pharmacological inhibition of CDK16 was achieved by the small molecular inhibitor rebastinib to further assess the anti-tumor utility of targeting CDK16. RESULTS: CDK16 is highly expressed in breast cancer, particularly in triple-negative breast cancer (TNBC). The elevated CDK16 expression is correlated with poor outcomes in breast cancer patients. CDK16 can improve the proliferation and migration ability of TNBC cells in vitro, and promote tumor growth and metastasis of TNBC in vivo. Both genetic knockdown and pharmacological inhibition of CDK16 significantly suppress the tumor progression of TNBC. Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis. CONCLUSION: CDK16 plays a critical role in TNBC and is a novel promising therapeutic target for TNBC.

Water-Extracted Ganoderma lucidum Induces Apoptosis and S-Phase Arrest via Cyclin-CDK2 Pathway in Glioblastoma Cells.

Glioblastoma is one of the most common and most aggressive brain cancers. The current treatment is mainly surgery, chemotherapy, and radiation therapy, but the results are not satisfactory. Ganoderma lucidum (G. lucidum), also called "Lingzhi", is a medicinal mushroom that has been used as a therapeutic agent for the treatment of numerous diseases, including cancer. However, whether it is effective for treating cancer is still unclear. In the present study, the anti-tumor effect of a water extract of G. lucidum was investigated using brain tumor cells. We used an analysis of cell viability, flow cytometry, the IncuCyte live-cell analysis system, and Western blotting to study its effects. The water extract from G. lucidum inhibited cell proliferation in a dose- and time-dependent manner, and it induced mitochondria-mediated apoptosis and cell cycle arrest at S phase via the cyclin-CDK2 pathway in human brain tumor cells. In addition, the G. lucidum extract significantly inhibited cell migration and mesenchymal marker expression based on the IncuCyte live-cell assay and qRT-PCR analysis. In summary, these anti-tumor effects in brain tumor cells suggest that G. lucidum may be useful for treating brain tumors.

GOLT1A-KISS1 fusion is associated with metastasis in adenoid cystic carcinomas.

Genetic alterations can drive carcinogenesis. Numerous studies have shown that gene fusion is associated with cancer progression and could provide valuable biomarkers for clinical diagnosis or targets for cancer therapy. Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma, characterized by frequent local recurrence and high rates of distant metastasis, ultimately resulting in low survival rates. Owing to the lack of effective therapeutic targets and limited biomarkers for diagnosis, a deeper understanding of the molecular basis of ACC is urgently needed. Here, we show that gene fusion is associated with ACC metastasis. We identified a metastasis suppressor KISS1 fused with a close-by gene, GOLT1A, in highly metastatic ACC cell lines and human specimens. Such fusion blocks KISS1 translation, but not transcription, by introducing 5' upstream open reading frames (uORFs) in the GOLT1A-KISS1 fusion transcript. Deletion of these uORFs rescued KISS1 expression and reduced invasion and migration of metastatic ACC cells. We also detected GOLT1A-KISS1 fusion transcripts in other types of highly metastatic cancer cell lines. Taken together, our results highlight the significance of this novel GOLT1A-KISS1 gene fusion in tumor metastasis and provide a valuable biomarker for clinical diagnosis and future therapeutic targeting of ACC.

Immunomodulatory and antioxidant effects of Astragalus polysaccharide liposome in large yellow croaker (Larimichthys crocea).

Astragalus polysaccharides (APS) have been widely used as immunopotentiators in aquaculture, however, the best way of their administration remains to be explored. In the present study, APS liposome (APSL) was prepared by film dispersion-ultrasonic method. The optimal conditions of APSL preparation were determined by response surface methodology, with a ratio of 10:1 (w/w) for soybean lecithin to APS and 8:1 (w/w) for soybean lecithin to cholesterol, and an ultrasound time of 15 min, which produced an encapsulation efficiency of 73.88 ± 0.88% of APSL. In vivo feeding experiments in large yellow croaker showed that both APS and APSL could enhance the contents of serum total protein (TP) and albumin (ALB), activities of serum non-specific immune enzymes such as acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM), and phagocytic activity of head kidney macrophages. Meanwhile, they both increased the activities of serum antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and reduced the content of final lipid peroxidation product malondialdehyde (MDA) in serum, thus exhibiting the antioxidant effects. In vitro experiments on primary head kidney macrophages (PKM) showed that both APS and APSL inhibited ROS production, but obviously enhanced NO production and phagocytic activity of PKM. Furthermore, expression levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α), IFN-γ, and iNOS in PKM were significantly up-regulated after APS and APSL treatments, but no expression change of IFN-h was observed. Taken together, our results showed that both APS and APSL could improve several immune parameters and antioxidant ability of large yellow croaker either in vivo or in vitro, and the efficacy of APSL was markedly better than APS. These findings therefore indicated that the immunomodulatory and antioxidant activities of APS could be enhanced after encapsulated with liposome, and APSL may represent a potential drug delivery system of APS for development of immunoenhancers in aquaculture.

Copper-catalyzed domino coupling reaction: an efficient method to synthesize oxindoles.

An efficient and novel procedure for a copper catalyzed domino coupling reaction has been developed, which afforded various oxindoles in good to excellent yields with tolerance of various substituents. In addition, this method could be applied to synthesize horsfiline and coerulescine in few steps with high total yields.

Nickel-catalyzed intermolecular insertion of aryl iodides to nitriles: a novel method to synthesize arylketones.

A novel procedure for the NiCl(2)(DME)/dppp/Zn system catalyzed intermolecular insertion of aryl iodides to nitriles was developed, which afforded variously substituted arylketone derivatives in moderate to good yields with tolerance of a wide variety of functional groups.