Development of a Novel Contrast-Enhanced Ultrasound-Based Nomogram for Superficial Lymphadenopathy Differentiation: Postvascular Phase Value.

OBJECTIVE: The aim of this study was to develop and prospectively validate a prediction model for superficial lymphadenopathy differentiation using Sonazoid contrast-enhanced ultrasound (CEUS) combined with ultrasound (US) and clinical data. METHODS: The training cohort comprised 260 retrospectively enrolled patients with 260 pathological lymph nodes imaged between January and December 2020. Two clinical US-CEUS models were created using multivariable logistic regression analysis and compared using receiver operating characteristic curve analysis: Model 1 included clinical and US characteristics; Model 2 included all confirmed predictors, including CEUS characteristics. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) algorithm. Data from 172 patients were prospectively collected between January and May 2021 for model validation. RESULTS: Age, tumor history, long-axis diameter of lymph node, blood flow distribution, echogenic hilus, and the mean postvascular phase intensity (MPI) were identified as independent predictors for malignant lymphadenopathy. The area under the curve (AUC), sensitivity, specificity, and accuracy of MPI alone was 0.858 (95% confidence interval [CI], 0.817-0.891), 86.47%, 74.55%, and 81.2%, respectively. Model 2 had an AUC of 0.919 (95% CI, 0.879-0.949) and good calibration in training and validation cohorts. The incorporation of MPI significantly enhanced diagnostic capability (p < 0.0001 and p = 0.002 for training and validation cohorts, respectively). Decision curve analysis indicated Model 2 as the superior diagnostic tool. SHAP analysis highlighted MPI as the most pivotal feature in the diagnostic process. CONCLUSION: The employment of our straightforward prediction model has the potential to enhance clinical decision-making and mitigate the need for unwarranted biopsies.

Effects of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity and sexual function of cervical cancer survivors.

BACKGROUND: Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. METHODS: A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. RESULTS: Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. CONCLUSIONS: Cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment.

Cervical cancer survivors can experience vaginal condition deterioration and sexual dysfunction after treatment. Vaginal dilation can help improve vaginal stenosis, vaginal length and sexual function of these patients. However, some medical institutions in China do not provide timely vaginal dilation for this population. This study aimed to explore whether vaginal dilation was still effective for cervical cancer survivors who had not received timely vaginal dilation. The results showed that these patients still benefitted from vaginal dilation, irrespective of the treatment methods they received. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilation. The findings of the study is an indication to developing countries that more attention should be given to sexual issue of cervical cancer survivors in clinical practice, and vaginal dilation therapy should be performed promptly after treatment.

Seven new triterpenoids from the roots of Adenophora tetraphylla (Thub.) Fisch.

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.

Effects of vaginal dilation therapy on vaginal condition and sexual function of endometrial cancer patients treated with radiotherapy after surgery.

OBJECTIVE: This study aimed to evaluate the effect of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity, and sexual function of endometrial cancer patients treated with radiotherapy after surgery. METHODS: A total of 117 women were enrolled in this study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal length, vaginal diameter, vaginal elasticity, and sexual function before radiotherapy, after radiotherapy, and after 6 months of vaginal dilation therapy. Their vaginal condition was assessed by customized vaginal dilating molds. Their sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyze all the data. RESULTS: According to multivariate analysis, vaginal diameter (ß = 0.300, 95% CI [0.217-1.446], p = 0.010) and sexual intercourse frequency before diagnosis (ß = 0.424, 95% CI [0.164-0.733], p = 0.006) were significantly correlated with female sexual function after radiotherapy. Vaginal dilation therapy helped increase vaginal length, improve vaginal stenosis and sexual function (p < 0.05), though most of the figures at the end of the intervention did not fully return to those before radiotherapy. Noticeably, vaginal dilation therapy was ineffective in improving vaginal elasticity and the incidence rate of female sexual dysfunction (p > 0.05). Moreover, patients with medium or good vaginal elasticity benefited more from vaginal dilation therapy than patients with poor vaginal elasticity (p < 0.05). CONCLUSION: Vaginal dilation therapy should be carried out timely and preventatively in endometrial cancer patients treated with radiotherapy after surgery to improve their vaginal condition and sexual function.

Structure of LRRK1 and mechanisms of autoinhibition and activation.

Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, their disease associations are strikingly different: LRRK2 is involved in familial Parkinson's disease while LRRK1 is linked to bone diseases. Furthermore, Parkinson's disease-linked mutations in LRRK2 are typically autosomal dominant gain-of-function while those in LRRK1 are autosomal recessive loss-of-function. Here, to understand these differences, we solved cryo-EM structures of LRRK1 in its monomeric and dimeric forms. Both differ from the corresponding LRRK2 structures. Unlike LRRK2, which is sterically autoinhibited as a monomer, LRRK1 is sterically autoinhibited in a dimer-dependent manner. LRRK1 has an additional level of autoinhibition that prevents activation of the kinase and is absent in LRRK2. Finally, we place the structural signatures of LRRK1 and LRRK2 in the context of the evolution of the LRRK family of proteins.

Ultrafine Pt Nanoparticles Anchored on 2D Metal-Organic Frameworks as Multifunctional Electrocatalysts for Water Electrolysis and Zinc-Air Batteries.

Multifunctional electrocatalysts are crucial to cost-effective electrochemical energy conversion and storage systems requiring mutual enhancement of disparate reactions. Embedding noble metal nanoparticles in 2D metal-organic frameworks (MOFs) are proposed as an effective strategy, however, the hybrids usually suffer from poor electrochemical performance and electrical conductivity in operating conditions. Herein, ultrafine Pt nanoparticles strongly anchored on thiophenedicarboxylate acid based 2D Fe-MOF nanobelt arrays (Pt@Fe-MOF) are fabricated, allowing sufficient exposure of active sites with superior trifunctional electrocatalytic activity for hydrogen evolution, oxygen evolution, and oxygen reduction reactions. The interfacial Fe─O─Pt bonds can induce the charge redistribution of metal centers, leading to the optimization of adsorption energy for reaction intermediates, while the dispersibility of ultrafine Pt nanoparticles contributes to the high mass activity. When Pt@Fe-MOF is used as bifunctional catalysts for water-splitting, a low voltage of 1.65 V is required at 100 mA cm-2 with long-term stability for 20 h at temperatures (65 °C) relevant for industrial applications, outperforming commercial benchmarks. Furthermore, liquid Zn-air batteries with Pt@Fe-MOF in cathodes deliver high open-circuit voltages (1.397 V) and decent cycling stability, which motivates the fabrication of flexible quasisolid-state rechargeable Zn-air batteries with remarkable performance.

Development of Innovative Online Modularized Device for Turbidity Monitoring.

Given progress in water-quality analytical technology and the emergence of the Internet of Things (IoT) in recent years, compact and durable automated water-quality monitoring devices have substantial market potential. Due to susceptibility to the influence of interfering substances, which lowers measurement accuracy, existing automated online monitoring devices for turbidity, a key indicator of a natural water body, feature a single light source and are thus insufficient for more complicated water-quality measurement. The newly developed modularized water-quality monitoring device boasts dual light sources (VIS/NIR), capable of measuring the intensity of scattering, transmission, and reference light at the same time. Coupled with a water-quality prediction model, it can attain a good estimate for continuing monitoring of tap water (<2 NTU, error < 0.16 NTU, relative error < 19.6%) and environmental water samples (<400 NTU, error < 3.86 NTU, relative error < 2.3%). This indicates the optical module can both monitor water quality in low turbidity and provide water-treatment information alerts in high turbidity, thereby materializing automated water-quality monitoring.

2D Metal-Organic Frameworks as Competent Electrocatalysts for Water Splitting.

Hydrogen, a clean and flexible energy carrier, can be efficiently produced by electrocatalytic water splitting. To accelerate the sluggish hydrogen evolution reaction and oxygen evolution reaction kinetics in the splitting process, highly active electrocatalysts are essential for lowering the energy barriers, thereby improving the efficiency of overall water splitting. Combining the distinctive advantages of metal-organic frameworks (MOFs) with the physicochemical properties of 2D materials such as large surface area, tunable structure, accessible active sites, and enhanced conductivity, 2D MOFs have attracted intensive attention in the field of electrocatalysis. Different strategies, such as improving the conductivities of MOFs, reducing the thicknesses of MOF nanosheets, and integrating MOFs with conductive particles or substrates, are developed to promote the catalytic performances of pristine MOFs. This review summarizes the recent advances of pristine 2D MOF-based electrocatalysts for water electrolysis. In particular, their intrinsic electrocatalytic properties are detailly analyzed to reveal important roles of inherent MOF active centers, or other in situ generated active phases from MOFs responsible for the catalytic reactions. Finally, the challenges and development prospects of pristine 2D MOFs for the future applications in overall water splitting are discussed.

Structural basis for Parkinson's disease-linked LRRK2's binding to microtubules.

Leucine-rich repeat kinase 2 (LRRK2) is one of the most commonly mutated genes in familial Parkinson's disease (PD). Under some circumstances, LRRK2 co-localizes with microtubules in cells, an association enhanced by PD mutations. We report a cryo-EM structure of the catalytic half of LRRK2, containing its kinase, in a closed conformation, and GTPase domains, bound to microtubules. We also report a structure of the catalytic half of LRRK1, which is closely related to LRRK2 but is not linked to PD. Although LRRK1's structure is similar to that of LRRK2, we find that LRRK1 does not interact with microtubules. Guided by these structures, we identify amino acids in LRRK2's GTPase that mediate microtubule binding; mutating them disrupts microtubule binding in vitro and in cells, without affecting LRRK2's kinase activity. Our results have implications for the design of therapeutic LRRK2 kinase inhibitors.

Piezoelectric effect stimulates the rearrangement of chondrogenic cells and alters ciliary orientation via atypical PKCζ.

Therapeutic ultrasound was administered to patients suffering from bone fracture with FDA approval. Bone and cartilage are piezoelectric materials. To investigate the effects of piezoelectricity on the cells of chondrogenic lineage, we applied ultrasound stimulation on an AT-cut quartz coverslip to generate electric field fluctuations. The bone-marrow-derived mesenchymal stem cells (BMMSC) and primary chondrocytes were cultured on either glass or quartz coverslips for ultrasound stimulation. The cells were immunofluorescent-labeled for the assessment of cell arrangement and ciliary orientation. Ultrasound and piezoelectricity both stimulate cell migration and disrupt ciliary orientation induced by directional migration. In particular, piezoelectric effects on cell rearrangement can be abolished by the inhibitor specifically targeting atypical Protein kinase C zeta (PKCζ). Our findings shed light on the possibility of cellular modulation by using piezoelectric manipulation.

Urban sediment pollutants alternate human cell essential behaviour through promoting oxidative damage.

The main objective of this study was to establish a human cell-based platform to assess the effects of sediment toxicity on oxidative damage and cell essential behaviour. Since sediment pollution has increased as a consequence of including but not limited to industrialisation, the contaminants accumulated in sediments have already led to human health concerns. The Hsinchu Science Park is one of the most prominent semiconductor manufacturing centres in the world, and the Ke-Ya River flows through Hsinchu Science Park and the Hsinchu urban district. Because semiconductor wastes potentially contribute to higher-than-normal rates of cancers, birth defects, and serious diseases, the quality assessment of the Ke-Ya River has prompted widespread concerns. While previous studies have shown an association between the degradation of fish populations and sediment pollutants, very little is known about the issues on human health. Herein, the effects of sediment from three sediment sampling sites of the Ke-Ya River on 11 different human cell lines were directly evaluated. The upstream represents the undeveloped zone, the middle-stream represents the household/industrial wastewater zone, and the downstream represents the accumulation zone. Our results indicated that the sediment pollution of the downstream Ke-Ya River was more cytotoxic than that of the middle stream and upstream. Downstream sediment extract (DSE) significantly increased reactive oxygen species (ROS) levels across all cell types. Accordingly, oxidative stress can trigger redox-sensitive pathways and alter essential biological processes such as cell viability, cell adhesion, and cell motility. Importantly, the MTT assay indicated that DSE significantly decreased the viability of brain, oral, lung, breast, liver, pancreatic, cervical, prostate, and colorectal cells. Furthermore, the adhesive ability and wound healing ability of most cells were greatly reduced in the presence of DSE compared to other conditions. Thus, this study shows the results of the first analyses completed on the sediment cytotoxicity in human cells, and stimulated ROS levels are crucial for cellular life. In future research, the detailed cause and effect mechanisms of the abundant ROS generated in DSE will be further investigated. We sincerely hope that our study provides a scientific basis for further investigations with a global perspective on public health challenges.

Piezoelectric stimulation by ultrasound facilitates chondrogenesis of mesenchymal stem cells.

A cellular stimulation device utilizing an AT-cut quartz coverslip mounted on an ultrasonic live imaging chamber is developed to investigate the effect of piezoelectric stimulation. Two types of chambers deliver ultrasound at intensities ranging from 1 to 20 mW/cm2 to mesenchymal stem cells (MSCs) seeded on the quartz coverslip. The quartz coverslip imposes additionally localized electric charges as it vibrates with the stimulation. The device was applied to explore whether piezoelectric stimulation can facilitate chondrogenesis of MSCs. The results suggest piezoelectric stimulation drove clustering of MSCs and consequently facilitated chondrogenesis of MSCs without the use of differentiation media.

Protective effects of antioxidant egg-chalaza hydrolysates against chronic alcohol consumption-induced liver steatosis in mice.

BACKGROUND: Reactive oxygen species (ROS) overproduction is highly related to some human chronic diseases. There are approximately 400 metric tons of chalazae produced yearly after the processing of the liquid-egg production, which are disposed of as waste. The objectives of this study were to look for the optimal production condition of antioxidant crude chalaza hydrolysates and evaluate the in vivo antioxidant capacity via a chronic alcohol consumption mouse model. RESULTS: Antioxidant crude chalaza hydrolysates (CCH-As) could be produced by protease A at 1:100 ratio (w/w) and 0.5 h hydrolytic period. After our analyses, CCH-As were rich in leucine, arginine, phenylalanine, valine, lysine and antioxidant dipeptides (anserine and carnosine), and the major molecular masses were lower than 15 kDa. Regarding protective effects of CCH-As against oxidative damage in alcoholic-liquid-diet-fed mice, alcohol-fed mice had lower (P < 0.05) liver antioxidant capacities, and higher (P < 0.05) liver lipid contents, serum lipid/liver damage indices and IL-1ß/IL-6 values. CCH-A supplementation reversed (P < 0.05) liver antioxidant capacities and reduced (P < 0.05) serum/liver lipids in alcohol-fed mice, which may result from increased (P < 0.05) fecal lipid output, upregulated (P < 0.05) fatty acid ß-oxidation and downregulated (P < 0.05) lipogenesis in the liver. CONCLUSION: Taken together, this CCH-A should benefit the liquid-egg industry, while also offering consumers a choice of healthy ingredients from animal sources. © 2018 Society of Chemical Industry.

Midazolam induces apoptosis in MA-10 mouse Leydig tumor cells through caspase activation and the involvement of MAPK signaling pathway.

PURPOSE: The present study aims to investigate how midazolam, a sedative drug for clinical use with cytotoxicity on neuronal and peripheral tissues, induced apoptosis in MA-10 mouse Leydig tumor cells. METHODS: The apoptotic effect and underlying mechanism of midazolam to MA-10 cells were investigated by flow cytometry assay and Western blotting methods. RESULTS: Data showed that midazolam induced the accumulation of the MA-10 cell population in the sub-G1 phase and a reduction in the G2/M phase in a time- and dose-dependent manner, suggesting an apoptotic phenomenon. Midazolam could also induce the activation of caspase-8, -9, and -3 and poly (ADP-ribose) polymerase proteins. There were no changes in the levels of Bax and cytochrome-c, whereas Bid was significantly decreased after midazolam treatment. Moreover, midazolam decreased both pAkt and Akt expression. In addition, midazolam stimulated the phosphorylation of p38 and c-Jun NH2-terminal kinase but not extracellular signal-regulated kinase. CONCLUSION: Midazolam could induce MA-10 cell apoptosis through the activation of caspase cascade, the inhibition of pAkt pathway, and the induction of p38 and c-Jun NH2-terminal kinase pathways.