SnapHiC-D: a computational pipeline to identify differential chromatin contacts from single-cell Hi-C data.

Single-cell high-throughput chromatin conformation capture technologies (scHi-C) has been used to map chromatin spatial organization in complex tissues. However, computational tools to detect differential chromatin contacts (DCCs) from scHi-C datasets in development and through disease pathogenesis are still lacking. Here, we present SnapHiC-D, a computational pipeline to identify DCCs between two scHi-C datasets. Compared to methods designed for bulk Hi-C data, SnapHiC-D detects DCCs with high sensitivity and accuracy. We used SnapHiC-D to identify cell-type-specific chromatin contacts at 10 Kb resolution in mouse hippocampal and human prefrontal cortical tissues, demonstrating that DCCs detected in the hippocampal and cortical cell types are generally associated with cell-type-specific gene expression patterns and epigenomic features. SnapHiC-D is freely available at https://github.com/HuMingLab/SnapHiC-D.

GaN integrated optical devices for glycerol viscosity measurement.

This Letter presents the fabrication and characterization of a chip-scale GaN optical device for measuring glycerol viscosity. The monolithically integrated GaN chip with a size of 1 × 1 mm2 comprises a light-emitting diode (LED) and a photodiode (PD) on a transparent sapphire substrate. The glycerol droplet applied to the device acts as a medium for coupling light from the LED to the PD. When a mechanical impulse is applied, the droplet undergoes a damped vibration that depends on its viscosity, causing a change in its shape and altering the path of light propagation. The viscosity of the glycerol sample can be determined by obtaining the rate of attenuation of the measured photocurrent signals. The proposed unit offers a fast time response in microseconds and requires only a small sample volume of 5 µl. The developed device is highly suitable for the practical measurement of glycerol viscosity due to its miniaturization, low cost, and ease of operation without the need for external optical components.

Structural Phase Transition and Decomposition of XeF2 under High Pressure and Its Formation of Xe-Xe Covalent Bonds.

Noble gases with inert chemical properties have rich bonding modes under high pressure. Interestingly, Xe and Xe form covalent bonds, originating from the theoretical simulation of the pressure-induced decomposition of XeF2, which has yet to be experimentally confirmed. Moreover, the structural phase transition and metallization of XeF2 under high pressure have always been controversial. Therefore, we conducted extensive experiments using a laser-heated diamond anvil cell technique to investigate the above issues of XeF2. We propose that XeF2 undergoes a structural phase transition and decomposition above 84.1 GPa after laser heating, and the decomposed product Xe2F contains Xe-Xe covalent bonds. Neither the pressure nor temperature alone could bring about these changes in XeF2. With our UV-vis absorption experiment, I4/mmm-XeF2 was metalized at 159 GPa. This work confirms the existence of Xe-Xe covalent bonds and provides insights into the controversy surrounding XeF2, enriching the research on noble gas chemistry under high pressure.

Psychometric assessment of the Adherence to Asthma Medication Questionnaire in asthma patients in China: a validation study.

BACKGROUND: Patients' medication adherence plays a critical role in the treatment and rehabilitation of disease. However, few tools are currently available that can be used to identify the reasons for their nonadherence with their medication regimens. It is possible to evaluate both the level of medication adherence of a patient as well as the reasons for it using the Adherence to Asthma Medication Questionnaire (AAMQ). The purpose of this study was to adapt the AAMQ for use in Chinese patients and a variety of asthma patients. METHODS: A total of 242 asthma patients were recruited from Jinzhou in China. The Adherence to Asthma Medication Questionnaire was translated and back-translated using the Brislin translation model. Test-retest reliability, internal consistency, and stability all play a large role in determining the reliability of a scale. Confirmatory factor analysis was used to examine the scale's construct validity, and expert consultation was used to verify the scale's content validity. Statistics were deemed significant at p < 0.05. RESULTS: The Cronbach's α value of the Chinese version of the AAMQ was 0.866, and the coefficient values for the three domains ranged between 0.702 and 0.798. The split-half reliability and stability values were 0.794 and 0.772, respectively. The content validity index of the scale (S-CVI) was 0.923, and the content validity index of the level of scale entry was 0.857-1.000. According to the confirmatory factor analysis, the chi-square degreed of freedom were 1.484, and the model fitting indices were all within normal limits. CONCLUSIONS: The AAMQ had good reliability and validity for asthmatic patients. The results of the scale's assessment can be used as a criterion for medication adherence among asthmatic patients and to understand the causes. This study provides a reference for solving the problem of medication adherence among asthma patients and implementing targeted nursing measures. PATIENT OR PUBLIC CONTRIBUTION: Gratitude is extended to all individuals collaborating in completing the survey and to the author.

Factors associated with the level of self-management in elderly patients with chronic diseases: a pathway analysis.

BACKGROUND: To analyze the effects and pathways of factors such as psychological capital, family functioning, and sources of meaning in life on the level of self-management in elderly patients with chronic diseases and to provide a basis for the development of relevant nursing interventions in the future. METHODS: Convenience sampling was used to select elderly patients with chronic diseases who underwent medical checkups and consultations at three community hospitals in Jinzhou city from March 2023 to October 2023, and the self-designed General Information Questionnaire (GIS), Psychological Capital of the Elderly Scale (PCE), Family Functioning Index Questionnaire (APGAR), Sources of Meaning of Life Scale for Older Adults(SMSE), and Self-Management Behavior of Chronic Patients Scale (SMCS) were used. SPSS 26.0 was used for data entry, one-way analysis, Pearson correlation analysis, and multiple linear regression were used to analyze the data, and Amos 17.0 was used to construct the structural equation model. RESULTS: A total of 355 elderly patients with chronic diseases were included, and their self-management score was 74.75 ± 12.93, which was moderate. The results of the influencing factor analysis showed that the influencing factors of the self-management level of elderly chronic disease patients were age, years of illness, psychological capital, family functioning, and sources of meaning in life (p < 0.05). Path analysis revealed that sources of meaning in life were a partial mediator of the relationship between psychological capital and self-management, with an effect value of 0.166 (95% CI: 0.042,0.391), accounting for 37.6% of the total effect; life meaning was a partial mediator of family functioning and self-management level, with an effect value of 0.231 (95% CI: 0.040,0.452), accounting for 54.0% of the total effect. accounting for 54.0% of the total effect. CONCLUSION: The self-management of elderly patients with chronic diseases is intermediate. Healthcare professionals should actively implement holistic healthcare management measures from the family aspect to help patients understand the meaning of life and improve the level of patients' psychological capital to improve the self-management level of elderly patients with chronic diseases.

Development and validation of a risk prediction model for mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) is steadily increasing among elderly people with type 2 diabetes (T2DM). This study aimed to create and validate a predictive model based on a nomogram. METHODS: This cross-sectional study collected sociodemographic characteristics, T2DM-related factors, depression, and levels of social support from 530 older adults with T2DM. We used LASSO regression and multifactorial logistic regression to determine the predictors of the model. The performance of the nomogram was evaluated using calibration curves, receiver operating characteristics (ROC), and decision curve analysis (DCA). RESULTS: The nomogram comprised age, smoking, physical activity, social support, depression, living alone, and glycosylated hemoglobin. The AUC for the training and validation sets were 0.914 and 0.859. The DCA showed good clinical applicability. CONCLUSIONS: This predictive nomogram has satisfactory accuracy and discrimination. Therefore, the nomogram can be intuitively and easily used to detect MCI in elderly adults with T2DM.

The transcultural adaptation and validation of the Chinese version of the Oral Health Literacy Scale for Diabetic Patients.

BACKGROUND: Diabetic patients' oral health concerns are a reality for every diabetic patient in China. The attitudes of diabetic patients toward early identification of oral literacy influence oral literacy in diabetes patients. Diabetes patients' oral health literacy is critical for providing focused education and therapies. However, no instrument exists to measure oral health literacy in Chinese diabetic patients. In this study, the English version of the oral health literacy among people living with diabetes (OHLD) scale was cross-culturally validated to provide a reliable tool for assessing the oral health literacy of diabetic patients in China. OBJECTIVE: The oral literacy among people living with diabetes (OHLD) scale was Chineseized and its reliability and validity tested, and the OHLD scale was revised to test the reliability and validity of the Chinese version of the OHLD scale and to provide a tool for assessing the oral health literacy of diabetic patients in China. METHODS: A modified version of the Brislin translation model was used, cross-cultural adaptation was performed through expert consultation and pre-survey, and expert opinion was used to assess content validity to form the Chinese version of the Oral Health Literacy Scale for Diabetic Patients, which was administered to 420 diabetic patients in two tertiary hospitals in Liaoning Province from March to August 2023. The reliability of the scale was tested. SPSS 25.0 and AMOS 23.0 were used to analyze the data. RESULTS: The Chinese version of the OHLD scale consisted of three dimensions and 10 entries. Structure of the validity analysis: three factors were extracted from the exploratory factors with a cumulative variance contribution of 79.794%; Content validity results:An item's content validity index (I-CVI) was 0.857 to 1 at the entry level, and the content validity index of the scale (S-CVI) was 0.928 at the scale level. The results of the reliability analyses were: the Cronbach's alpha coefficient for the total scale was 0.908; the Cronbach's alpha coefficients for the factors and dimensions were 0.853 to 0.922; the split-half reliability was 0.827; and the test-retest reliability was 0.848. The results of the validation factor analysis showed that (χ2/df) was 1.430, the root mean square of the error of approximation (RMSEA) was 0.045, the comparative fit index (CFI) was 0.989, and the Tucker Lewis index (TLI) was 0.985, which showed that the model had an overall good fit. CONCLUSION: The Chinese version of the OHLD scale has good reliability and validity and can be used as a valid tool for assessing diabetes mellitus patients in China.

In vitro and in vivo analyses on anti-NSCLC activity of apatinib: rediscovery of a new drug target V600E mutation.

BACKGROUND: Apatinib (YN968D1) is the first small-molecule-targeting drug with anti-tumor activity created in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It showed significant variation in the efficacy for treating cancers, including advanced non-squamous non-small-cell lung cancer (NSCLC). Whether its efficacy could be optimized by subgrouping patients with certain genetic variation remains elusive. METHODS: Here, we firstly used kinase screening to identify any possible target of apatinib against 138 kinases. The effects of apatinib on proliferation rates, cell cycle, cell apoptosis, and cell migration on cancer cell lines were analyzed; the in vitro potential pathways of apatinib on cancer cell lines were screened. The effect of apatinib on mouse cancer models in vivo was also analyzed. RESULTS: Based on HCC364 cells with BRAF V600E mutation, we have shown that apatinib could inhibit their growth, migration, cell cycle, and induce their apoptosis. Based on mice with transplanted HCC364 cells, we have also shown that apatinib could inhibit the tumor growth. Based on immunohistochemistry, we have demonstrated that apatinib could suppress the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase and extracellular regulated protein kinases. This may account at least part of the apatinib's inhibitory effect on HCC364 cancer cells. CONCLUSIONS: BRAF V600E protein kinase is a target of apatinib by kinase screening. We have demonstrated that apatinib can effectively inhibit tumor cells with BRAF V600E mutation by in vitro and in vivo experiments. Our results have demonstrated that targeting BRAF V600E mutation, apatinib appears to be effective and safe for treating NSCLC and possibly other cancers with the same mutation.

'I'm still young it doesn't matter' - A qualitative study on the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.

AIM: To explore why young- and middle-aged adults ignore prodromal myocardial infarction symptoms from a life course and sociocultural perspective. DESIGN: A qualitative descriptive study. METHODS: We applied purposeful sampling to recruit participants from a tertiary hospital in Guangzhou from July to November 2021. Face-to-face interviews were performed. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods. RESULTS: Twenty-four young- and middle-aged adults diagnosed with acute myocardial infarction participated in this study. Analysis revealed three main themes: I'm still young, it will not happen to me; to be somebody and different roles, multiple pressures. Age-related self-confidence led to inappropriate perceptions and responses to prodromal symptoms among young- and middle-aged adults. These individuals strived to align their behaviours and attention with social expectations and self-expectations, underestimating the importance of perceiving the warning signs of acute myocardial infarction and seeking medical treatment. Pressure from social roles also prevented them from paying enough attention to prodromal symptoms. CONCLUSION: Targeted social support, public education and technologies should be provided to these individuals since they are pillars of the family and society. We also highlight how nurses can function these strategies appropriately. IMPACTS: This study contributes to a better understanding of the neglect of prodromal symptoms among young- and middle-aged adults. Its results enhance our understanding of the perception of and coping with prodromal symptoms among this population, which will help avoid the burden caused by acute myocardial infarction. PATIENT OR PUBLIC CONTRIBUTION: The patients involved in our study shared their experiences and insights to provide new perspectives regarding the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.

Experiences and perceptions of acute myocardial infarction patients with a prolonged decision-making phase of treatment seeking: A meta-synthesis.

AIMS: To describe the experiences and perceptions of acute myocardial infarction (AMI) patients with a prolonged decision-making phase of treatment-seeking. BACKGROUND: Previous attempts to reduce the treatment-seeking time of AMI have been less than optimal. Due to the coronavirus disease 2019 (COVID-19) pandemic, the situation of prehospital delay is possibly worse. Decisions to seek treatment are influenced by multiple factors and need individualised interventions. Understanding patients' external and internal experiences and psychological perceptions is essential. DESIGN: Meta-synthesis. DATA SOURCES: We searched PubMed, Embase, Cochrane Library, Web of Science, Scopus and four Chinese databases from inception to April 2022. METHODS: We screened the retrieved articles with predetermined inclusion and exclusion criteria, and reviewed articles using Thomas and Harden's (BMC Medical Research Methodology, 2008 8, 45) qualitative thematic synthesis approach. The Joanna Briggs Institute critical appraisal tool for qualitative research was used to assess the quality of studies. RESULTS: Twenty-one studies were included, identifying four themes and nine sub-themes. The four primary themes were difficulty recognising and attributing symptoms, attempt to act, unwillingness to change and self-sacrifice. CONCLUSION: Deciding to seek treatment is a complex social and psychological process, which needs comprehensive interventions considering personal and sociocultural factors and factors related to the COVID-19 pandemic. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Details of interventions for decisions to seek treatment in AMI patients need to be further designed and evaluated. IMPACT: Results would help healthcare professionals to implement individualised management of decision-making of treatment-seeking among AMI patients, and improve medical records of patients' prehospital experiences. REPORTING METHOD: The Preferred Reporting Items for Systematic Reviews 2020 checklist was used to report the findings. PATIENT OR PUBLIC CONTRIBUTION: Two AMI patients contributed to the data synthesis by giving simple feedback about the final themes.

Exploring the Potential of ChatGPT-4 in Responding to Common Questions About Abdominoplasty: An AI-Based Case Study of a Plastic Surgery Consultation.

BACKGROUND: With the increasing integration of artificial intelligence (AI) in health care, AI chatbots like ChatGPT-4 are being used to deliver health information. OBJECTIVES: This study aimed to assess the capability of ChatGPT-4 in answering common questions related to abdominoplasty, evaluating its potential as an adjunctive tool in patient education and preoperative consultation. METHODS: A variety of common questions about abdominoplasty were submitted to ChatGPT-4. These questions were sourced from a question list provided by the American Society of Plastic Surgery to ensure their relevance and comprehensiveness. An experienced plastic surgeon meticulously evaluated the responses generated by ChatGPT-4 in terms of informational depth, response articulation, and competency to determine the proficiency of the AI in providing patient-centered information. RESULTS: The study showed that ChatGPT-4 can give clear answers, making it useful for answering common queries. However, it struggled with personalized advice and sometimes provided incorrect or outdated references. Overall, ChatGPT-4 can effectively share abdominoplasty information, which may help patients better understand the procedure. Despite these positive findings, the AI needs more refinement, especially in providing personalized and accurate information, to fully meet patient education needs in plastic surgery. CONCLUSIONS: Although ChatGPT-4 shows promise as a resource for patient education, continuous improvements and rigorous checks are essential for its beneficial integration into healthcare settings. The study emphasizes the need for further research, particularly focused on improving the personalization and accuracy of AI responses. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reply to the 'Comment on "High-temperature superconductivity in transition metallic hydrides MH11 (M = Mo, W, Nb, and Ta) under high pressure"' by X. Zheng and J. Zheng, Phys. Chem. Chem. Phys., 2022, 24, DOI: 10.1039/D1CP01474A.

Our paper is concerned with the specific hydrogen compound MoH11. The authors of the Comment advocate investigating the role of umklapp processes (UP). For the hydrogen compounds, the main contribution to the strength of the pairing interaction is provided not by acoustic, but by optical phonons. This key factor leads to a diminishing role of the UP for the compound of interest.

Prospective association between depressive symptoms and hip fracture and fall among middle-aged and older Chinese individuals.

BACKGROUND: The effect of depressive symptoms on hip fracture (HF) and falls among the Chinese population is unclear. This study aims to examine the prospective association between depressive symptoms and HF as well as fall accidents in a nationally representative Chinese population. METHODS: We used data from 10,596 participants in the Chinese Health and Retirement Longitudinal Study (from 2011 to 2018) who were aged ≥45 years and had no HFs at baseline. Depressive symptoms were assessed using the 10-item version of the Center for Epidemiological Studied Depression scale (cutoff for distinguishing high versus low at ≥12). Logistic regression analyses adjusted for demographic characteristics, lifestyle factors and physical comorbidities were performed. RESULTS: For the analysis of baseline depressive symptoms and HF, 399 (3.8%) participants reported HF accidents in the following 7-year period. Individuals with elevated depressive symptoms at baseline experienced a markedly higher HF risk (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 1.06-1.67) than those without elevated depressive symptoms, after adjusting for a wide range of potential confounders. For the analysis of baseline depressive symptoms and falls, 3974 (37.5%) experienced fall accidents during the follow-up. The presence of elevated depressive symptoms was independently associated with an increased risk of fall events (OR = 1.21, 95% CI = 1.10-1.33). These associations were consistent across multiple characteristics. CONCLUSIONS: In conclusion, elevated depressive symptoms were associated with an increased risk of HF and falls, which may have considerable clinical and preventive implications.

Nurses' perceptions regarding barriers to implementing the Internet Plus Nursing Service programme: A qualitative study.

AIM: The aim of this work is to investigate nurses' perceptions of barriers constraining the implementation of the Internet Plus Nursing Service program. BACKGROUND: The Internet Plus Nursing Service programme helps meet the demands of an ageing population, people with chronic diseases, the disabled, and home convalescents, and affirms the value of nurses. However, this programme has failed to elicit nurses' active participation, and there is limited knowledge regarding nurses' perceptions of the barriers to the programme's implementation. METHODS: A qualitative study was conducted. Thematic analysis of the data was performed. RESULTS: The analysis yielded three main themes: a sense of insecurity, role conflict, and a lack of support. CONCLUSION: This study explores nurses' perspectives on the factors impeding the implementation of the programme, which are identified as being insufficient protection and support on nurses at personal, sociocultural, infrastructural, and organizationallevels. IMPLICATIONS FOR NURSING MANAGEMENT: The study results will guide the department of nursing management to foster supportive work and social environment for nurses, which will decrease their feeling of insecurity and role conflicts and provides them enough infrastructural and organizational supports through proposing emergency code system and improving training system and team collaboration.

High-temperature superconductivity in transition metallic hydrides MH11 (M = Mo, W, Nb, and Ta) under high pressure.

The discovery of H3S and LaH10 is an important step towards the development of room temperature superconductors which fuels the enthusiasm for finding promising superconductors among hydrides at high pressure. In the present study, three new and stable stoichiometric MoH5, MoH6 and MoH11 compounds were found in the pressure range of 100-300 GPa. The highly hydrogen-rich phase of Cmmm-MoH11 has a layered structure that contains various forms of hydrogen: H, H2- and H3- units. It is a high-Tc material with an estimated Tc value in the range of 165-182 K at 250 GPa. The same structures are also found in NbH11, TaH11, and WH11, each material showing Tc ranging from 117 to 168 K. By combining the method of using two coupling constants λopt and λac, and two characteristic frequencies (optical and acoustic) with first-principle calculations, we found that the high values of Tc are mainly caused by the presence of high frequency optical modes, but the acoustic modes also play a noticeable role.

MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression.

Normally, there are multiple microRNAs involved in the pathogenesis of liver fibrosis. In our work, we aimed at identifying the role of miR-34c in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. Our results have shown that during natural activation of HSC, the level of miR-34c was increased significantly whereas acyl-CoA synthetase long-chain family member-1(ACSL1), which is a key enzyme can affect fatty acid(FA) synthesis, was decreased. A double fluorescence reporter assay further confirmed that ACSL1 is a direct target gene of miR-34c. Moreover, the inhibition of miR-34C can attenuate the synthesis of collagen in HSC-T6. In our rescue assay, ACSL1 expression was 1.49-fold higher compared to normal control cells which were transfected with the miR-34c inhibitor in a stable low expression ACSL1 cell line. While at the same time, α-SMA and Col1α expression decreased by 18.22% and 2.58%, respectively. Moreover, we performed an in vivo model using dimethylnitrosamine (DMN) in conjunction with the miR-34c agomir, combined with the treatment of DMN and the miR-34c agomir can increase liver fibrosis. Meanwhile, the degree of hepatic fibrosis was increased and lipid droplets reduced dramatically in rats and HSC-T6 cell treated with miR-34c mimics alone compared to untreated groups. Our results indicate that miR-34c plays an essential role in liver fibrosis by targeting ACSL1 closely associated with lipid droplets, and it might be used as a potential therapeutic target.

Spin Hamiltonians in Magnets: Theories and Computations.

The effective spin Hamiltonian method has drawn considerable attention for its power to explain and predict magnetic properties in various intriguing materials. In this review, we summarize different types of interactions between spins (hereafter, spin interactions, for short) that may be used in effective spin Hamiltonians as well as the various methods of computing the interaction parameters. A detailed discussion about the merits and possible pitfalls of each technique of computing interaction parameters is provided.

Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study.

BACKGROUND: No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma. METHODS: We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18-75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn, ChiCTR-OIC-17013586. FINDINGS: Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4-19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0-11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3-43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3-34) according to RECIST and 18 months (3-33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed. INTERPRETATION: To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma. FUNDING: None.

EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation in Ewing sarcoma.

BACKGROUND: The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear. METHODS: TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored. RESULTS: TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5ß1 signalling might be correlated with YAP dephosphorylation and nuclear translocation. CONCLUSIONS: TNC may promote ES tumour progression by targeting MALAT1 through integrin α5ß1-mediated YAP activation.

Unique Phase Diagram and Superconductivity of Calcium Hydrides at High Pressures.

Structure prediction studies on Ca-H binary systems under high pressures were carried out, and the structures of calcium hydrides in earlier works were reproduced. The previously unreported composition of CaH9 was found to be stable and experienced the phase transition series Cm → P21/ m → C2/ m from 100 to 400 GPa. To the best of our knowledge, CaH9 may be the only alkaline earth hydride with an odd H content. At 400 GPa, the metastable R3̅ m-CaH10 phase shares the same space group with the R3̅ m-SrH10 phase with puckered honeycomb H layers. The C2/ m phase of CaH9 and the R3̅ m phase of CaH10 are excellent superconductors with Tc values of about 240-266 and 157-175 K at 300 and 400 GPa, respectively. The high contributions of H-derived states at the Fermi level play an important role in the superconductivity of calcium hydrides.