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Abstract Purpose This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. Methods CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133−) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). Results The performance of CD133+OVCAR4 cells was much better than that of CD133−OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133−OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. Conclusion The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has serious consequences on global public health and social development. The binding of receptor binding domain (RBD) of spike protein to angiotensin converting enzyme 2 (ACE2) on the surface of SARS-CoV-2 host cell initiates the infection progress. Spike and ACE2 are both glycoproteins, the impact of glycosylation on protein structures and protein-protein interactions remains largely elusive. Characterizing the structural and dynamics of protein-protein binding progress will improve mechanism understanding of viral infection and facilitate targeted drug design. Structural mass spectrometry (MS) method is widely used in protein structural studies, providing complementary information to conventional biophysical methods, such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM). Native mass spectrometry (native MS) is an emerging technology that enables the study of intact protein, noncovalent protein-protein, and protein-ligand complexes in their biological state, which can provide structural stability, binding stoichiometry, and spatial arrangement information. Here, native MS was used to examine the interaction between RBD and ACE2 as well as the impact of deglycosylation on the interaction stability of the RBD-ACE2 complex. The results revealed that both RBD and ACE2 are highly glycosylated, ACE2 presents as a dimer while RBD as a monomer, and they form a (RBD-ACE2)2 complex. The conditions of using PNGase F to remove the N-glycan were optimized. At least two O-glycans including NeuAc(2) and GalNAc(1)Gal(1)NeuAc(2) or GlcNAc(1)Gal(1)NeuAc(2) were observed for the N-glycan removed RBD. Furthermore, the stability of the complexes formed by glycosylated and deglycosylated RBD with ACE2 was compared, and the results showed that the removal of N-glycan significantly drops the interaction stability of the RBD-ACE2 complex. Therefore, we -recommend that glycosylation should not be removed for structural and functional studies. Additional glycosylation, structural and dynamics studies on Spike (including separated RBD) and ACE2 complexes would help us to understand the process of viral infection, advance drug design and vaccine developments. Nowadays, a comprehensive MS-based toolbox has been developed for the analysis of protein structure, function, and dynamics, including hydrogen-deuterium exchange MS (HDX-MS), native top-down (nTD) MS, cross-linking MS (XL-MS), and covalent labelling MS (CL-MS), etc. Through integrating structural MS methods, more detailed and comprehensive structural information about glycoproteins and their complexes will be uncovered.

The Central Asian Orogenic Belt (CAOB) was formed by the aggregation and collage of numerous Paleozoic subduction‐accretion assemblages and Precambrian microcontinental blocks. However, the tectonic nature of the southeastern CAOB remains controversial, which complicates the reconstruction of the Paleo‐Asian Ocean. To address this issue, a deep seismic reflection survey was initiated across the southeastern CAOB and reveals broad gentle sub‐horizontal reflectors in the middle‐lower crust and a relatively transparent zone in the upper crust. Combining with the Precambrian geological outcrops and other geophysical features, we support a microcontinental block, the Xilinhot Block, existed in the Paleo‐Asian domain. Thus, the Paleo‐Asian Ocean was separated into two branches that underwent north‐dipping and double‐dipping oceanic plate subduction, respectively, to form the Hegenshan‐Heihe and Solonker sutures. Multiple relics beneath Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Plain Language Summary: During the consumption of the Paleo‐Asian Ocean, a great number of Paleozoic subduction‐related accretionary complexes were developed and combined with pre‐existing Precambrian continental fragments to form the Central Asian Orogenic Belt (CAOB). However, research on the tectonic evolution of this area has been limited, and the tectonic nature of the southeastern CAOB remains controversial. A deep seismic reflection survey along the southeastern CAOB shows the crustal architecture in detail. The broad gentle sub‐horizontal reflectors and a relatively transparent zone in the profile reveal a Precambrian continental fragment existed in the North Orogenic Belt of CAOB. The Paleo‐Asian Ocean was further separated into two parts, the fossil subduction zones of which show northward and bidirectional dipping characteristics beneath the Hegenshan‐Heihe and Solonker sutures, respectively. Several relics of the unidirectional subduction beneath the Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Key Points: A preserved microcontinental block has been revealed in the North Orogenic Belt of Central Asian Orogenic BeltThe Paleo‐Asian Ocean was separated into two branches, which were closed respectively by north‐dipping and double‐dipping subductionMultiple unidirectional subduction‐accretion and oceanic magmatism may contribute to continental growth [ABSTRACT FROM AUTHOR]

Satellite geodesy is capable of observing glacier height changes and most recent studies focus on the decadal scale due to limitations of data acquisition and precision. Glaciers at the Mt. Everest (Qomolangma), locating at the central Himalaya, have been studied from the 1970s to 2015. Here we obtained TerraSAR-X/TanDEM-X images observed in two epochs, a group around 2013 and another in 2017. Together with SRTM observed in 2000, we derived geodetic glacier mass balance between 2000 and 2013 and 2013 and 2017. We proposed two InSAR procedures for deriving the second period, which yields with basically identical results of geodetic glacier mass balance. The differencing between DEMs derived by TerraSAR-X/TanDEM-X shows better precision than that between TerraSAR-X/TanDEM-X formed DEM and SRTM, and it can capable of providing geodetic glacier mass balance at a sub-decadal scale. Glaciers at the Mt. Everest (Qomolangma) and its surroundings present obvious speeding up in mass loss rates before and after 2013 for both the Chinese and the Nepalese sides. The previous obtained spatial heterogeneous pattern for glacier downwasting between 2000 and 2013 generally kept the same after 2013. Glaciers with lacustrine terminus present the most rapid lost rates.

We evaluated the predictive value of the ex-vivo PharmaFlow PM platform in measuring the pharmacological activity of drug combinations consisting of 20 different chemotherapy regimens (20 Tx) administered in 104 acute myeloid leukemia (AML) patients. The predicted sensitivities of alternative treatments for each patient were ranked in five 20% categories, from resistant to sensitive (Groups 1–5). The complete remission (CR) rates of the five groups were 0%, 12.5%, 38.5%, 50.0%, and 81.3%, respectively. The heat map showed a good relationship between drug sensitivity with CR (Group 4 + 5 vs. Group 1 + 2+3: 77.5% vs. 27.3%, p = 0.002) and the European Leukemia Net risk group (22.6% vs. 63.6%, p = 0.015). The predicted coincidence rate was 90.9% in Group 1 + 2 and 81.3% in Group 5. According to the recommendations of the PharmaFlow PM platform, the CR rate would have increased by about 16.3% in one cycle. The overall survival (OS) was shorter in patients predicted to be resistant (Group 1 + 2 vs. Group 3 + 4+5, p = 0.086). In multivariable analysis, CR after one cycle was an independent prognostic factor for OS [p = 0.001; 95% CI 0.202 (0.080–0.511)], and ex-vivo chemosensitivity was a potential predictive factor for OS [p = 0.078; 95% CI 0.696 (0.465–1.041)]. To conclude, the PharmaFlow PM platform is a rapid and valuable tool for predicting clinical response and outcomes in AML patients.

BackgroundCulture influences personal health habits and behavior, and healthcare personnel possess different views of cultural perspectives. Currently, an appropriate instrument to assess cultural competence in clinical practice is limited. The present study aimed to develop and examine the psychometric properties of the Nursing Cultural Competence Scale (NCCS) for clinical nurses.MethodsDeveloping and assessing the scale was carried out in two phases: Phase I involved a qualitative research to explore the themes of nurses' cultural competence and instrument development; Phase II established construct validity of the scale using a sample of 246 nurses in Taiwan. Data from the questionnaire were analyzed using exploratory factor analysis, confirmatory factor analysis, internal consistency and test-retest reliability. Analysis results were used to determine the reliability and validity of the developed scale.ResultsThe results showed four factors including cultural awareness ability, cultural action ability, cultural resources application ability, and self-learning cultural ability were generated by exploratory factor analysis, and these factors explained 62.0% of total variance. Cronbach's α of the Nursing Cultural Competence Scale was .88, and test-retest reliability correlation was .70.ConclusionsThe establishment of the tool will facilitate accurate monitoring of the cultural competence among nurses and nursing managers, which can inform the construction of nursing policies aimed at pledge cultural competence expansion.

Background. The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results. Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (β = −0.0559, 95% CI −0.1060 to −0.0059,) and FT3/FT4 (β = −0.0920, 95% CI −0.1667 to −0.0173,). There was a positive correlation between lnSII and TT4 (β = 0.1499, 95% CI 0.0722–0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion. Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this. [ABSTRACT FROM AUTHOR]

The aging of the world population and increasing stress levels in life are the major cause of the increased incidence of neurological disorders. Alzheimer's disease (AD) creates a huge burden on the lives and health of individuals and has become a big concern for society. Triterpenoid saponins (TS), representative natural product components, have a wide range of pharmacological bioactivities such as anti‐inflammation, antioxidation, antiapoptosis, hormone‐like, and gut microbiota regulation. Notably, some natural TS exhibited promising neuroprotective activity that can intervene in AD progress, especially in the early stage. Recently, studies have indicated that TS play a pronounced positive role in the prevention and treatment of AD. This review discusses the recent research on the neuroprotection of TS and proceeds to detail the action mechanisms of TS against AD, hoping to provide a reference for drug development for anti‐AD. [ABSTRACT FROM AUTHOR]

The Central Asian Orogenic Belt (CAOB) is the most significant accretionary orogenic belt since the Phanerozoic and the most ideal site for studying continental growth evolution processes. A 460‐km‐long high‐resolution crustal‐scale seismic reflection study was conducted across the eastern CAOB in North‐Central China to constrain the closure mode and location of the Paleo‐Asian Ocean, that is, the previous ocean of the CAOB. The resultant seismic reflection profile revealed opposite‐dipping reflectors in the northern and southern parts of the profile, which converge at the profile center to form an inverted U‐shaped reflector pattern near the crust–mantle transition zone beneath the Solonker Suture. The dipping reflectors represent bidirectional fossil subduction zones sloping to the north and south, and the convergence reflector pattern represents the ocean closure location. Integration of these results with available geological data facilitated model construction whereby Paleo‐Asian Ocean closure was accomplished by divergent subduction of the Paleo‐Asian oceanic plate, with northward subduction beneath the southern margin of the Mongolian Block and southward subduction beneath the northern margin of the North China Craton. The oceanic lithosphere contracted and deformed, yielding the observed inverted U‐shaped reflector pattern, representing Paleo‐Asian Ocean closure. This subsurface location lies beneath the Solonker Suture surface exposure, suggesting that this suture marks the ocean closure location, rather than the previously proposed Hegenshan–Heihe Suture to the north or Xar Moron Suture to the south. Our study suggests that divergently dipping subduction and associated accretion and magmatism may constitute the primary continental growth mode for accretionary‐type orogens. Plain Language Summary: The Central Asian Orogenic Belt (CAOB) is Earth's largest Phanerozoic accretionary orogenic belt, but its tectonic history remains uncertain, including the Paleo‐Asian Ocean closure location and mode. Here, we present a 460‐km‐long crustal‐scale seismic reflection survey across the eastern CAOB. According to the generated seismic profile, near‐symmetrical north‐ and south‐dipping reflectors occur in the crust–mantle transition zone, which are interpreted combined with published geological data to reveal that the Paleo‐Asian oceanic plate underwent divergent subduction beneath the South Mongolian Block and North China Craton. The inferred Paleo‐Asian Ocean closure location, the Solonker Suture, is identified by converging seismic reflectors in the central part of the profile. During oceanic subduction, newly formed accretionary complexes experienced soft collision with preexisting continental fragments. Therefore, we suggest that the eastern CAOB mainly comprises Paleozoic accretionary complexes with incorporated Precambrian fragments. We consider that divergently dipping oceanic subduction and associated accretion and magmatism constitute the main mode of CAOB continental growth and possibly of accretionary orogenic belts in general. Key Points: A crustal‐scale seismic profile reveals that the Paleo‐Asian Ocean was closed by double‐dipping subduction in the eastern Central Asian Orogenic BeltThe closure location of the ocean occurs between the Xar Moron and Hegenshan–Heihe sutures and extends eastward to central SongliaoOceanic double‐dipping subduction–accretion and magmatism are important mechanisms for accretionary orogens [ABSTRACT FROM AUTHOR]

The effects of cadmium stress on the growth, antioxidative enzymes and lipid peroxidation in two kenaf plants, Fuhong 991 and ZM412, were analysed under control (0.5-strength Hoagland's nutrient solution) or five levels of cadmium stress (0.5-strength Hoagland's nutrient solution containing different concentrations of Cd2+). The leaves and roots of control and cadmium-stressed plants were harvested after 3 wk. At the same Cd concentration, the Cd tolerance index of Fuhong 991 was higher than that of ZM412, indicating that Fuhong 991 may be more tolerant to Cd than ZM412. The superoxide dismutase (SOD), catalase activity (CAT) and peroxidase (POD) activities fluctuated in the leaves of the Cd-stressed plants compared to the control, whereas the glutathione reductase activity (GR) was much larger than the control for Fuhong 991, ensuring that sufficient quantities of GSH were available to respond to the cadmium stress. In comparison to the control, the dynamic tendency of the SOD, CAT and POD activities in roots of the Cd-stressed plants all increased and then declined, but the POD activity of Fuhong 991 remained nearly unchanged at all of the stress levels. The increase in the enzyme activities demonstrated that Fuhong 991 was more tolerant to cadmium than ZM 412. The lipid peroxidation was enhanced only in the leaves of Cd-stressed ZM 412. These findings indicated that antioxidative activities may play important roles in Cd-stressed Fuhong 991 and ZM 412 and that the leaf and root cell membranes of Fuhong 991 have a greater stability than those of ZM 412. For pollution monitoring purposes, the GR activity in the roots and leaves may serve as a biomarker of Cd for Fuhong 991, whereas lipid peroxidation may serve as biomarker for ZM 412.

Introduction: Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. The structures and neural bioactivities of triterpenoid saponins (TS), which are the major constituents of ESF, have not been comprehensively analyzed thus far. Objective: We conducted a complete in‐depth MS/MS molecular networking (MN)‐based targeted analysis of TS from the crude extract of ESF and investigated its neuroprotective value. Methods: An MS/MS MN‐guided strategy was used to rapidly present a series of precursor ions (PIs) of TS in a compound cluster as TS‐targeted information used in the discovery and characterization of TS. In addition, a prepared TS‐rich fraction of ESF was assayed for its restraining effects on β‐amyloid‐induced inhibition of neurite outgrowth. Results: A total of 87 TS were discovered using a PI tracking strategy, 28 of which were characterized as potentially undescribed structures according to their high‐resolution MS values. Furthermore, the TS‐rich fraction can significantly reduce β‐amyloid‐induced damage to neural networks by promoting the outgrowth of neurites and axons. Conclusion: Our findings reveal the richness of TS in ESF and will accelerate their application in the treatment of neurodegenerative diseases. Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. In this paper, a comprehensive LC‐MS analysis of triterpene saponins (TS) from ESF was performed using an MS/MS molecular networking strategy, and 87 TS were finally tracked, of which 28 TS were potential new saponins. In addition, the TS‐rich fraction of ESF was prepared and assayed for their restraining effect on the β‐amyloid‐induced destruction of neurite outgrowth. [ABSTRACT FROM AUTHOR]

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women. [ABSTRACT FROM AUTHOR]