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يتميز كتاب \"نظرة تحليلية لفن الخط الصيني\" بتعمقه في تناول مصطلح الخط بدءا بمفهومه ثم تطوره، وتجسيده، وأسلوبه، انتهاء بالسمات العصرية لجماليات فن الخط،. حيث يتناول الكتاب الرموز الصينية من حيث تطورها وخصائصها، بدءا من نقشها على العظام ودروع السلاحف، ثم النقوش البرونزية، وخطوط الأختام، والنقوش على الجبال، مصحوبا بصور لوحات المخطوطات الصينية القديمة. ويفرد الكتاب بحثا حول كيفية الاستمتاع بفن الخط، عن طريق الصراع والتناقض بين الوعي الجمالي للعامة والوعي الجمالي للخبراء.

Pembrolizumab improved progression-free survival and overall survival versus ipilimumab in patients with advanced melanoma and is now a standard of care in the first-line setting. However, the optimal duration of anti-PD-1 administration is unknown. We present results from 5 years of follow-up of patients in KEYNOTE-006. KEYNOTE-006 was an open-label, multicentre, randomised, controlled, phase 3 study done at 87 academic institutions, hospitals, and cancer centres in 16 countries. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0 or 1, ipilimumab-naive histologically confirmed advanced melanoma with known BRAFV600 status and up to one previous systemic therapy were randomly assigned (1:1:1) to intravenous pembrolizumab 10 mg/kg every 2 weeks or every 3 weeks or four doses of intravenous ipilimumab 3 mg/kg every 3 weeks. Treatments were assigned using a centralised, computer-generated allocation schedule with blocked randomisation within strata. Exploratory combination of data from the two pembrolizumab dosing regimen groups was not protocol-specified. Pembrolizumab treatment continued for up to 24 months. Eligible patients who discontinued pembrolizumab with stable disease or better after receiving at least 24 months of pembrolizumab or discontinued with complete response after at least 6 months of pembrolizumab and then progressed could receive an additional 17 cycles of pembrolizumab. Co-primary endpoints were overall survival and progression-free survival. Efficacy was analysed in all randomly assigned patients, and safety was analysed in all randomly assigned patients who received at least one dose of study treatment. Exploratory assessment of efficacy and safety at 5 years' follow-up was not specified in the protocol. Data cutoff for this analysis was Dec 3, 2018. Recruitment is closed; the study is ongoing. This study is registered with ClinicalTrials.gov, number NCT01866319. Between Sept 18, 2013, and March 3, 2014, 834 patients were enrolled and randomly assigned to receive pembrolizumab (every 2 weeks, n=279; every 3 weeks, n=277), or ipilimumab (n=278). After a median follow-up of 57·7 months (IQR 56·7–59·2) in surviving patients, median overall survival was 32·7 months (95% CI 24·5–41·6) in the combined pembrolizumab groups and 15·9 months (13·3–22·0) in the ipilimumab group (hazard ratio [HR] 0·73, 95% CI 0·61–0·88, p=0·00049). Median progression-free survival was 8·4 months (95% CI 6·6–11·3) in the combined pembrolizumab groups versus 3·4 months (2·9–4·2) in the ipilimumab group (HR 0·57, 95% CI 0·48–0·67, p<0·0001). Grade 3–4 treatment-related adverse events occurred in 96 (17%) of 555 patients in the combined pembrolizumab groups and in 50 (20%) of 256 patients in the ipilimumab group; the most common of these events were colitis (11 [2%] vs 16 [6%]), diarrhoea (ten [2%] vs seven [3%]), and fatigue (four [<1%] vs three [1%]). Any-grade serious treatment-related adverse events occurred in 75 (14%) patients in the combined pembrolizumab groups and in 45 (18%) patients in the ipilimumab group. One patient assigned to pembrolizumab died from treatment-related sepsis. Pembrolizumab continued to show superiority over ipilimumab after almost 5 years of follow-up. These results provide further support for use of pembrolizumab in patients with advanced melanoma. Merck Sharp & Dohme.

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9.

Background The yield obtained from next generation sequencers has increased almost exponentially in recent years, making sample multiplexing common practice. While barcodes (known sequences of fixed length) primarily encode the sample identity of sequenced DNA fragments, barcodes made of random sequences (Unique Molecular Identifier or UMIs) are often used to distinguish between PCR duplicates and transcript abundance in, for example, single-cell RNA sequencing (scRNA-seq). In paired-end sequencing, different barcodes can be inserted at each fragment end to either increase the number of multiplexed samples in the library or to use one of the barcodes as UMI. Alternatively, UMIs can be combined with the sample barcodes into composite barcodes, or with standard Illumina® indexing. Subsequent analysis must take read duplicates and sample identity into account, by identifying UMIs. Results Existing tools do not support these complex barcoding configurations and custom code development is frequently required. Here, we present Je, a suite of tools that accommodates complex barcoding strategies, extracts UMIs and filters read duplicates taking UMIs into account. Using Je on publicly available scRNA-seq and iCLIP data containing UMIs, the number of unique reads increased by up to 36 %, compared to when UMIs are ignored. Conclusions Je is implemented in JAVA and uses the Picard API. Code, executables and documentation are freely available at http://gbcs.embl.de/Je . Je can also be easily installed in Galaxy through the Galaxy toolshed.

Purpose To analyze health-related quality of life (HRQoL) and related factors among elderly persons receiving community-based home care and institutional care in Guangzhou, a large city of mainland China. Methods A representative sample of 1600 subjects aged 60 years and over residing in communities and nursing homes was randomly selected through stratified sampling. The 12-item Short Form Health Survey version 2 (SF-12v2) was used to assess HRQoL. Results In total, 1014 elderly persons under different aged care models responded to the survey (response rate 63.4%) and 1000 were eligible for data analyses. Compared with the elderly receiving community-based home care or private institutional care, those in public institutional care had the lowest scores on the physical component summary (PCS, 36.89 ± 10.44) and the mental component summary (MCS, 47.16 ± 11.14). Number of chronic diseases, loneliness, and age were the most common significant factors ( P  < 0.05) affecting PCS and MCS. The interaction term between aged care model and number of chronic diseases significantly affected PCS ( β  = − 0.165, P  < 0.05), indicating a stronger association between these factors for participants receiving community-based home care than institutional care. The interaction term between aged care model and loneliness had a significant effect on MCS ( β  = 0.189, P  < 0.05), indicating a weaker association between loneliness and MCS for participants receiving community-based home care. Conclusions This study found poor HRQoL among the elderly in Guangzhou. The main factors associated with the physical and mental HRQoL of elderly persons included number of chronic diseases, loneliness, age, and education level. It also revealed the moderating effects of aged care model on HRQoL, suggesting specific health management strategies for elderly in community-based home care and institutional care, respectively.

The progression of hepatocellular carcinoma (HCC) is coincident with aberrant splicing of numerous tumor‐related genes. Identification of the tumor‐specific splice variants that facilitate HCC metastasis may provide a more comprehensive insight into the mechanisms of HCC metastasis. Through RNA sequencing and bioinformatic analyses, PPM1G was identified as a biomarker associated with HCC metastasis. Our data mapped a transcriptome‐wide landscape of alternative splicing events modulated by PPM1G in HCC. Notably, we characterized the exon six‐skipping transcript of TBL1X as an onco‐splice variant regulated by PPM1G. Experimental validation revealed the enrichment of TBL1X‐S in response to PPM1G overexpression. Moreover, mRNA stability analyses revealed that PPM1G prolonged the half‐life of the TBL1X‐S transcript. Both PPM1G and TBL1X‐S exhibited metastasis‐promoting phenotypes, with PPM1G‐driven metastasis in HCC being partially dependent on TBL1X‐S. Mechanistically, different TBL1X splice variants showed varying affinities for ZEB1, with TBL1X‐S significantly enhancing ZEB1 activation and repressing CDH1 transcription, potentially accelerating the epithelial‐mesenchymal transition (EMT) process. In conclusion, our study highlights the biological role of PPM1G and TBL1X‐S in tumor metastasis. The PPM1G/TBL1X‐S signaling axis presents a new view for investigating liver cancer metastasis mechanisms. In this study, we highlight the biological role of the PPM1G and TBL1X‐S variants in tumor metastasis. The PPM1G/TBL1X‐S signaling axis presents a new view for investigating liver cancer metastasis mechanisms.

•Both harm action/outcome aversion involve the rGMV/rGMD in the right IFG.•rGMV/rGMD in the precuneus was associated with harm action aversion.•rGMD in the SFG and rGMV in the cerebellum contribute to harm action aversion.•rGMD in the S1 was associated with harm outcome aversion.•Empathy mediated links between brain structures and harm action/outcome aversion. Harm aversion is essential for normal human functioning; however, the neuroanatomical mechanisms underlying harm aversion remain unclear. To explore this issue, we examined the brain structures associated with the two distinct dimensions of harm aversion (harm action/outcome aversion) and the potential mediating role of the four aspects of empathy: fantasy, perspective-taking, empathic concern, and personal distress. A sample of 214 healthy young adults underwent structural magnetic resonance imaging. Voxel-based morphometry was used to assess regional gray matter volume (rGMV) and regional gray matter density (rGMD). Whole-brain multiple regression analysis revealed significant correlations between harm action aversion and rGMV/rGMD in various brain regions, including the inferior frontal gyrus (IFG) and precuneus for both rGMV and rGMD, the cerebellum for rGMV, and the superior frontal gyrus for rGMD. The rGMV/rGMD in the IFG and the rGMD in the primary somatosensory cortex (S1) were correlated with harm outcome aversion. Utilizing 10-fold balanced cross-validation analysis, we confirmed the robustness of these significant associations between rGMV/rGMD in these brain regions and harm action/outcome aversion. Importantly, mediation analysis revealed that empathic concern mediated the relationship between rGMV/rGMD in the precuneus and harm action aversion. Additionally, empathic concern, personal distress, and total empathy mediated the relationship between rGMD in the S1 and harm outcome aversion. These findings enhance our understanding of the neural mechanism of harm aversion by integrating insights from the brain structure, harm aversion, and the personality hierarchy models while also extending the frontal asymmetry model of Emotion

All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing déstabilisation of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.

A high percentage of women who undergo the transition to postmenopause experience both menopausal symptoms and genitourinary syndrome of menopause (GSM). However, GSM is often underdiagnosed. This research aims to identify risk factors that may influence the number of GSM symptoms and whether they cause distress in Taiwanese women > 45 years of age who experienced at least one GSM symptom. Data were collected using a self‐developed questionnaire, the Taiwanese Greene Climacteric Scale, and the Genitourinary Symptoms Scale. Participants reported a low frequency and low level of distress related to menopause symptoms (14.33 ± 9.12; 10.75 ± 10.01, respectively) with an average of 3.64 genitourinary symptoms experienced. The majority of participants (59.7%) reported experiencing distress regarding GSM. Multivariate analyses indicated that the distress level of menopause symptoms ( p < 0.001), distress caused by genitourinary symptoms ( p < 0.001), BMI > 24.0 kg/m 2 ( p = 0.034) and seeking medical consultation for incontinence ( p < 0.001) were significantly associated with the number of genitourinary symptoms. Notably, a higher level of distress regarding menopause symptoms ( p = 0.022), a greater number of genitourinary symptoms ( p < 0.001), and having sought medical consultation due to genitourinary symptoms ( p = 0.007) were significantly associated with experiencing distress caused by genitourinary symptoms. This study highlights the importance of patient education, proactive discussions, and addressing barriers to healthcare and cultural factors in GSM management. Healthcare professionals might consider providing additional assessments for GSM in older women who are admitted to the hospital for other diseases and highlight the distress caused by genitourinary symptoms, as GSM is frequently underreported yet treatable.

In recent years, live streaming has become a popular application, which uses TCP as its primary transport protocol. Quick UDP Internet Connections (QUIC) protocol opens up new opportunities for live streaming. However, how to leverage QUIC to transmit live videos has not been studied yet. This paper first investigates the achievable quality of experience (QoE) of streaming live videos over TCP, QUIC, and their multipath extensions Multipath TCP (MPTCP) and Multipath QUIC (MPQUIC). We observe that MPQUIC achieves the best performance with bandwidth aggregation and transmission reliability. However, network fluctuations may cause heterogeneous paths, high path loss, and bandwidth degradation, resulting in significant QoE deterioration. Motivated by the above observations, we investigate the multipath packet scheduling problem in live streaming and design 4D-MAP, a multipath adaptive packet scheduling scheme over QUIC. Specifically, a linear upper confidence bound (LinUCB)-based online learning algorithm, along with four novel scheduling mechanisms, i.e., Dispatch, Duplicate, Discard, and Decompensate, is proposed to conquer the above problems. 4D-MAP has been evaluated in both controlled emulation and real-world networks to make comparison with the state-of-the-art multipath transmission schemes. Experimental results reveal that 4D-MAP outperforms others in terms of improving the QoE of live streaming.