RM2Target: a comprehensive database for targets of writers, erasers and readers of RNA modifications.

RNA modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Abnormal changes of WERs will disrupt the RNA modification homeostasis of their target genes, leading to the dysregulation of RNA metabolisms such as RNA stability and translation, and consequently to diseases such as cancer. A public repository hosting the regulatory relationships between WERs and their target genes will help in understanding the roles of RNA modifications in various physiological and pathological conditions. Previously, we developed a database named 'm6A2Target' to host targets of WERs in m6A, one of the most prevalent RNA modifications in eukaryotic cells. To host all RNA modification (RM)-related WER-target associations, we hereby present an updated database, named 'RM2Target' (http://rm2target.canceromics.org/). In this update, RM2Target encompasses 1 619 653 WER-target associations for nine RNA modifications in human and mouse, including m6A, m6Am, m5C, m5U, m1A, m7G, pseudouridine, 2'-O-Me and A-to-I. Extensive annotations of target genes are available in RM2Target, including but not limited to basic gene information, RNA modifications, RNA-RNA/RNA-protein interactions and related diseases. Altogether, we expect that RM2Target will facilitate further downstream functional and mechanistic studies in the field of RNA modification research.

Integrated analysis of the DNA methylome and RNA transcriptome during the development of skeletal muscle in Duroc pigs.

BACKGROUND: Skeletal muscle development plays a crucial role in yield and quality of pork; however, this process is influenced by various factors. In this study, we employed whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing to comprehensively investigate the longissimus dorsi muscle (LDM), aiming to identify key genes that impact the growth and development of Duroc pigs with different average daily gains (ADGs). RESULTS: Eight pigs were selected and divided into two groups based on ADGs: H (774.89 g) group and L (658.77 g) group. Each pair of the H and L groups were half-siblings. The results of methylation sequencing revealed 2631 differentially methylated genes (DMGs) involved in metabolic processes, signalling, insulin secretion, and other biological activities. Furthermore, a joint analysis was conducted on these DMGs and the differentially expressed genes (DEGs) obtained from transcriptome sequencing of the same individual. This analysis identified 316 differentially methylated and differentially expressed genes (DMEGs), including 18 DMEGs in promoter regions and 294 DMEGs in gene body regions. Finally, LPAR1 and MEF2C were selected as candidate genes associated with muscle development. Bisulfite sequencing PCR (BSP) and quantitative real-time PCR (qRT-PCR) revealed that the promoter region of LPAR1 exhibited significantly lower methylation levels (P < 0.05) and greater expression levels (P < 0.05) in the H group than in the L group. Additionally, hypermethylation was observed in the gene body region of MEF2C, as was a low expression level, in the H group (P < 0.05). CONCLUSIONS: These results suggest that the differences in the ADGs of Duroc pigs fed the same diet may be influenced by the methylation levels and expression levels of genes related to skeletal muscle development.

Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study.

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

Strong Electronic Interaction in High-Entropy Oxide Enhances Oxygen Evolution Reaction.

High-entropy oxides are a new type of material with significant application potential. However, the lack of a universal HEO preparation method severely limits the property study and application of HEOs. Herein, we report a universal approach of spray pyrolysis for the preparation of various HEOs and study the electrocatalytic performance of HEOs toward the oxygen evolution reaction. FeCoNiMoWOx HEO exhibits an overpotential of 281 mV at 10 mA cm-2 and a Tafel slope of 34.5 mV dec-1, which are far superior to those of the corresponding medium-entropy oxide and low-entropy oxide. It is found that the high entropy of the HEO greatly strengthens the interaction between Fe and Mo/W and produces abundant oxygen vacancies (OVs) around Mo and W. This work not only provides a universal preparation method for HEOs but also deepens our understanding of OER catalytic activity of HEOs.

Development of a universal antibiotic resistance screening reporter for improving efficiency of cytosine and adenine base editing.

Base editing has emerged as a revolutionary technology for single nucleotide modifications. The cytosine and adenine base editors (CBEs and ABEs) have demonstrated great potential in clinical and fundamental research. However, screening and isolating target-edited cells remains challenging. In the current study, we developed a universal Adenine and Cytosine Base-Editing Antibiotic Resistance Screening Reporter (ACBE-ARSR) for improving the editing efficiency. To develop the reporter, the CBE-ARSR was first constructed and shown to be capable of enriching cells for those that had undergone CBE editing activity. Then, the ACBE-ARSR was constructed and was further validated in the editing assays by four different CBEs and two versions of ABE at several different genomic loci. Our results demonstrated that ACBE-ARSR, compared to the reporter of transfection (RoT) screening strategy, improved the editing efficiency of CBE and ABE by 4.6- and 1.9-fold on average, respectively. We found the highest CBE and ABE editing efficiencies as enriched by ACBE-ARSR reached 90% and 88.7%. Moreover, we also demonstrated ACBE-ARSR could be employed for enhancing simultaneous multiplexed genome editing. In conclusion, both CBE and ABE activity can be improved significantly using our novel ACBE-ARSR screening strategy, which we believe will facilitate the development of base editors and their application in biomedical and fundamental research studies.

Deterministic manipulation of steering between distant quantum network nodes.

Multipartite Einstein-Podolsky-Rosen (EPR) steering is a key resource in a quantum network. Although EPR steering between spatially separated regions of ultracold atomic systems has been observed, deterministic manipulation of steering between distant quantum network nodes is required for a secure quantum communication network. Here, we propose a feasible scheme to deterministically generate, store, and manipulate one-way EPR steering between distant atomic cells by a cavity-enhanced quantum memory approach. While optical cavities effectively suppress the unavoidable noises in electromagnetically induced transparency, three atomic cells are in a strong Greenberger-Horne-Zeilinger state by faithfully storing three spatially separated entangled optical modes. In this way, the strong quantum correlation of atomic cells guarantees one-to-two node EPR steering is achieved, and can perserve the stored EPR steering in these quantum nodes. Furthermore, the steerability can be actively manipulated by the temperature of the atomic cell. This scheme provides the direct reference for experimental implementation for one-way multipartite steerable states, which enables an asymmetric quantum network protocol.

Unveiling the Effect of Organic Sulfur Sources on Synthesized MoS2 Phases and Electrocatalytic Hydrogen Evolution Performances.

Metallic-phase MoS2 exhibits Pt-comparable electrocatalytic hydrogen evolution reaction (HER) performance in acidic conditions. However, the controllable synthesis of metallic-phase MoS2 is quite challenging because the key factor determining the phase types of MoS2 during synthesis is still unclear. Herein, the effect of organic sulfur sources on the formed MoS2 phase is studied by use of thioacetamide (TAA), l-cysteine, and thiourea as sulfur sources. The TAA and l-cysteine produce metallic MoS2, while thiourea gives rise to semiconducting MoS2. Owing to the metallic phase and smaller size, the MoS2 prepared with TAA and l-cysteine has a higher electrocatalytic HER activity than the MoS2 obtained from thiourea. The HER overpotential of MoS2 synthesized with TAA is only 210 mV for reaching the current density of 10 mA/cm2, and the corresponding Tafel slope is 44 mV/decade. Further studies find that the decomposition temperature of sulfur precursors is the key factor for the formation of metallic MoS2. Sulfur precursors with a lower decomposition temperature release sulfur ions quickly, which in turn stabilize the metallic phase and inhibit the growth of MoS2 into large sizes. Our findings unveil the key factor for controlling the phase type of MoS2 synthesized from organic sulfur precursors and will be very helpful for the synthesis of MoS2 with high electrocatalytic activity.

Advances in detecting N6-methyladenosine modification in circRNAs.

Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently single-stranded closed loop structures derived from back-splicing event of linear precursor mRNAs (pre-mRNAs). N6-methyladenosine (m6A), the most abundant epigenetic modification in eukaryotic RNAs, has been shown to play a crucial role in regulating the fate and biological function of circRNAs, and thus affecting various physiological and pathological processes. Accurate identification of m6A modification in circRNAs is an essential step to fully elucidate the crosstalk between m6A and circRNAs. In recent years, the rapid development of high-throughput sequencing technology and bioinformatic methodology has propelled the establishment of a multitude of approaches to detect circRNAs and m6A modification, including in vitro-based and in silico methods. Based on this, the research community has started on a new journey to develop methods for identification of m6A modification in circRNAs. In this review, we provide a comprehensive review and evaluation of the existing methods responsible for detecting circRNAs, m6A modification, and especially, m6A modification in circRNAs, which mainly focused on those developed based on high-throughput technologies and methodology of bioinformatics. This handy reference can help researchers figure out towards which direction this field will go.

Interpretation of the coupling mechanism of ecological security and urbanization based on a Computation-Verification-Coupling framework: Quantitative analysis of sustainable development.

In recent decades, China's rapid urbanization has produced numerous economic benefits while simultaneously creating substantial risks to ecological security. China's 14th Five-Year Plan and the United Nations Sustainable Development Goals (SDGs) have recently explicitly called for the coordinated development of ecological security and urbanization. Given this context, it is important to explore the mechanism by which ecological security and urbanization are coupled and coordinated to promote sustainable development. In this study, an index of the relationship between ecological security and urbanization was established via high-resolution data, and a "Computation-Verification-Coupling" (CVC) framework was constructed. The accuracy of the ecological security index was verified using a linear regression model, and the coordination level between ecological security and urbanization was analyzed via a coupled coordination model (CCM). The results revealed a steady increase in the ecological security index from 2010 to 2020; the proportion of the area above the medium level increased from 63.1 % to 74.1 %. The urbanization index in core counties exhibited rapid growth, with level V urbanized areas expanding from 5.5 % to 9.9 %. The ecological security verification model produced a coefficient of determination (R²) of 0.75685, indicating a satisfactory degree of predictive capability. From 2010-2020, the coupled coordination improved, with the high coordination area accounting for 48.8 % and the extreme discoordination area decreasing from 1.8 % to 1.0 %. Coordinated development exhibited a stable progression, characterized by a cyclical evolution from initial coupling to antagonistic coupling and finally to coordinated development. This framework can be used not only to investigate the relationship between ecological security and urbanization but also to provide a quantifiable measure of progress toward achieving the SDGs.

The relationship between medication literacy and skin adverse reactions in non-small-cell lung cancer patients undergoing targeted EGFR-TKI therapy.

BACKGROUND: High medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS: This is a cross-sectional study conducted from May to September 2020. In total, 296 NSCLC patients undergoing targeted EGFR-TKI therapy were recruited from hospitals in Henan, China. Structured questionnaires were used to evaluate skin adverse drug reactions and medication literacy. Pearson correlation analysis and binary logistic regression analysis were carried out to identify the correlations between medication literacy and the severity of skin adverse drug reactions in the recruited patients. RESULTS: The research sample consisted of 296 patients with a response rate of 92.5%. The mean score of skin adverse drug reactions and the mean score of medication literacy were 1.83 ± 0.91 and 6.54 ± 2.78, respectively. In total, 188 patients (63.5%) were considered to have moderate medication literacy. According to the binary logistic regression analysis, the following factors were associated with severe skin adverse drug reactions: age (B = - 3.929, P = 0.000), sex (B = -4.062, P = 0.000), educational level (B = 2.712, P = 0.002), comorbidity (B = 3.297, P = 0.001), eczema history (B = 2.996, P = 0.001), nutritional status (B = -4.891, P = 0.000), blood interleukin-6 level (B = -2.143, P = 0.013), blood high-sensitivity C-reactive protein level (B = -4.015, P = 0.000), combination of drugs (B = -3.183, P = 0.048) and medication literacy (B = - 1.503, P = 0.000). Subgroup analysis showed that in addition to medication literacy, some other factors including education level, comorbidity, nutritional status, blood interleukin-6 level and combined drug application were common factors that contributed to various adverse skin drug reactions in NSCLC patients under targeted EGFR-TKI therapy. CONCLUSION: The low medication literacy of the investigated NSCLC patients undergoing targeted EGFR-TKI therapy was correlated with a high proportion of severe skin adverse drug reactions. In addition, factors other than medication literacy including education level, comorbidity, nutritional status, blood interleukin-6 level and the combinatorial application of drugs were also related to the severity of various adverse skin drug reactions. A comprehensive and targeted intervention may be beneficial to improve medication literacy and control severe skin adverse drug reactions in NSCLC patients.

The health-related quality of life of lung cancer patients with EGFR-TKI-related skin adverse drug reactions and its relationship with coping style and self-management.

PURPOSE: The status and associated factors of the health-related quality of life of non-small-cell lung cancer (NSCLC) patients under targeted anti-cancer therapy have not been investigated. Self-management and coping style have been proven to be closely related to patients' health-related quality of life. Based on these observations, this study was designed to firstly assess the status of health-related quality of life, and then explore the relationships among coping styles, self-management, and health-related quality of life of NSCLC patients with skin adverse drug reactions under targeted therapy. METHODS: We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions under targeted therapy in cancer clinics of three hospitals in China between May 2020 and May 2021. Structured questionnaires, including the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18, Cancer Patient Self-management Evaluation Scale, and Medical Coping Modes Questionnaire, were used to collect data. Relationships among coping style, self-management, and health-related quality of life were identified by Pearson correlation analysis and a multiple linear regression algorithm. RESULTS: The total score of health-related quality of life was 46 ± 12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. Health-related quality of life was positively correlated with self-management (r = 0.785, P < 0.01) and facing (r = 0.807, P < 0.01) and negatively correlated with yield (r = - 0.718, P < 0.01), avoidance (r = - 0.711, P < 0.01), and the severity of skin adverse reactions (r = - 0.722, P = 0.000). Via multiple linear regression analysis, we identified some significant factors associated with health-related quality of life, including age, education level, combination of medicine, Charlson Comorbidity Index, stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy, and self-management (P < 0.05). CONCLUSIONS: NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised health-related quality of life. The critical factors that were associated with the status of health-related quality of life were age, education level, comorbidity, the combinatorial application of drugs, stage of disease, self-management, and coping styles.

Simultaneous Evaluation of Dissolution and Absorption Study of Compound Danshen Tablets and Capsules Based on Cellular Electrical Sensing Model.

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.

[Synchronous evaluation of continuous dynamic dissolution and absorption of Compound Danshen Dropping Pills based on cellular bioelectrical effect].

The real-time cell-based assay(RTCA) was used to establish the bioelectrical sensing model of Compound Danshen Dripping Pills with rat cardiomyocytes(H9 c2). The time/dose-dependent cell response profiles(TCRPs) of in vitro dissolution and absorption of the pills were determined to establish the continuous dynamic dissolution and absorption kinetic models. Thereby, the cell index(CI)-based dissolution and absorption kinetic curves and kinetic models of Compound Danshen Dripping Pills were obtained. The optimal dissolution kinetic model was Weibull model. The similarity factors f_2 of dissolution curves were greater than 50 and the correlation coefficients of absorption curves were larger than 0.95. With the experiment about the efficacy on mice, percentages of the bleeding time of mice administrated with Compound Danshen Dripping Pills were calculated, and there was a correlation among dissolution, absorption, and efficacy curves(r > 0.9). RTCA is applicable to the study of the dissolution and absorption kinetics of solid compound Chinese medicine preparations. Thus, it is an innovative and feasible method to evaluate the quality and batch consistency of compound Chinese medicine preparations.

The stationary phase regulator CpcR activates cry gene expression in non-sporulating cells of Bacillus thuringiensis.

Cell differentiation within an isogenic population allows the specialisation of subpopulations and a division of labour. Bacillus thuringiensis is a spore-forming bacterium that produces insecticidal crystal proteins (Cry proteins) in sporulating cells. We recently reported that strain B. thuringiensis LM1212 presents the unique ability to differentiate into two subpopulations during the stationary phase: spore-formers and crystal-producers. Here, we characterised the transcriptional regulator CpcR responsible for this differentiation and the expression of the cry genes. cpcR is located on a plasmid that also harbours cry genes. The alignment of LM1212 cry gene promoters revealed the presence of a conserved DNA sequence upstream from the -35 region. This presumed CpcR box was also found in the promoter of cpcR and we showed that cpcR transcription is positively autoregulated. Electrophoretic mobility shift assays suggested that CpcR directly controls the transcription of its target genes by binding to the CpcR box. We showed that CpcR was able to direct the production of a crystal consisting of a heterologous insecticidal Cry protein in non-sporulating cells of a typical B. thuringiensis kurstaki strain. Moreover, the expression of cpcR induced a reduction in the sporulation of this B. thuringiensis strain, suggesting an interaction between CpcR and the sporulation regulatory networks.

Water-Induced Formation of Ni2 P-Ni12 P5 Interfaces with Superior Electrocatalytic Activity toward Hydrogen Evolution Reaction.

The interface between two material phases typically exhibits unique electronic states distinct from their pure phases, thus, providing a very promising channel to construct catalysts with excellent activity and stability. Here, water-induced formation of Ni2 P-Ni12 P5 through a one-step phosphorization of nickel foam (NF) is demonstrated for the first time. The abundant interfaces endow Ni2 P-Ni12 P5 /NF with excellent electrocatalytic hydrogen evolution reaction (HER) activity in alkaline condition, with an overpotential of 76 mV at a current density of 10 mA cm-2 and of 147 mV at a current density of 100 mA cm-2 , and a Tafel slope of 68.0 mV dec-1 . The Ni2 P-Ni12 P5 /NF also exhibits better durability than Pt/C/NF during HER at relatively large overpotential. Density functional theory calculations show that the electronic states at the Ni2 P-Ni12 P5 interface are greatly altered, which enables optimal hydrogen adsorption, accelerates the charge transfer kinetics, and thus enhances the HER electrocatalytic activity. Superior overall water-splitting performance is also obtained by combining Ni2 P-Ni12 P5 /NF with NiFe-layered double hydroxide (LDH) oxygen evolution reaction (OER) catalyst. Overpotentials of the cell for achieving 10 mA cm-2 are only 324 mV. This work provides a facile method for the preparation of interfaces between different nickel phosphide polymorphs toward HER.

Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China.

BACKGROUND: The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. METHODS: A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. RESULTS: A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. CONCLUSION: The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

The α-Fe2O3/graphite anode composites with enhanced electrochemical performance for lithium-ion batteries.

The α-Fe2O3/graphite composites were prepared by a thermal decomposition method using the expanded graphite as the matrix. The α-Fe2O3 nanoparticles with the size of 15-30 nm were embedded into interlayers of graphite, forming a laminated porous nanostructure with a main pore distribution from 2 to 20 nm and the Brunauer-Emmett-Teller surface area of 33.54 m2 g-1. The porous structure constructed by the graphite sheets can alleviate the adverse effects caused by the huge volume change of the α-Fe2O3 grains during the charge/discharge process. The composite electrode exhibits a high reversible capacity of 1588 mAh g-1 after 100 cycles at 100 mA g-1, 702 mAh g-1 at 5 A g-1, 460 mAh g-1 at 10 A g-1 after 160 cycles, respectively, showing good cycle stability and outstanding rate capability at high current densities.

Health-related quality of life and associated factors in patients with myocardial infarction after returning to work: a cross-sectional study.

BACKGROUND: Return to work following myocardial infarction (MI) represents an important indicator of recovery. However, MI can cause patients to feel pressure, loneliness and inferiority during work and even detachment from employment after returning to work, which may affect their quality of life. The aims of this study were to identify the influencing factors of Health-related quality of life (HRQoL) in patients with MI after returning to work and explore the correlations between these factors and HRQoL. METHOD: This was a cross-sectional study. All participants were recruited from tertiary hospitals in China from October 2017 to March 2018. The general data questionnaire, Short-Form Health Survey-8 (SF-8), Health Promoting Lifestyle ProfileII (HPLPII), Medical Coping Modes Questionnaire (MCMQ) and Social Supporting Rating Scale (SSRS) were used to assess 326 patients with myocardial infarction returned to work after discharge. Multiple linear regression analysis was performed to explore factors related to HRQoL in patients with MI after returning to work. RESULTS: The sample consisted of 326 patients. The mean total score of quality of life was 28.03 ± 2.554. According to the multiple linear regression analysis, next factors were associated with better HRQoL: younger age (B = - 0.354, P = 0.039), higher income (B = 0.513, P = 0.000), less co-morbidity (B = - 0.440, P = 0.000), the longer time taken to return to work (B = 0.235, P = 0.003), fewer stents installed (B = - 0.359, P = 0.003), participation in cardiac rehabilitation (CR) (B = - 1.777, P = 0.000), complete CR (B = - 1.409, P = 0.000), better health behaviors such as more health responsibility (B = 0.172, P = 0.000) and exercise (B = 0.165, P = 0.000), better nutrition (B = 0.178, P = 0.000) and self-realization (B = 0.165, P = 0.000), stress response (B = 0.172, P = 0.000), more social support such as more objective support (B = 0.175, P = 0.000), subjective support (B = 0.167, P = 0.000) and better utilization of social support (B = 0.189, P = 0.028), positive copping strategies such as more coping (B = 0.133, P = 0.000) and less yield (B = - 0.165, P = 0.000). CONCLUSIONS: HRQoL of MI patients after returning to work is not satisfactory. Health behavior, coping strategies, social support are factors which can affect HRQoL. A comprehensive and targeted guide may be a way to improve HRQoL and to assist patients' successful return to society.

Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro.

Alpha-l-Locked nucleic acid (α-l-LNA) is a stereoisomeric analogue of locked nucleic acid (LNA), which possesses excellent biophysical properties and also exhibits high target binding affinity to complementary oligonucleotide sequences and resistance to nuclease degradations. Therefore, α-l-LNA nucleotides could be utilised to develop stable antisense oligonucleotides (AO), which can be truncated without compromising the integrity and efficacy of the AO. In this study, we explored the potential of α-l-LNA nucleotides-modified antisense oligonucleotides to modulate splicing by inducing Dmd exon-23 skipping in mdx mouse myoblasts in vitro. For this purpose, we have synthesised and systematically evaluated the efficacy of α-l-LNA-modified 2'-O-methyl phosphorothioate (2'-OMePS) AOs of three different sizes including 20mer, 18mer and 16mer AOs in parallel to fully-modified 2'-OMePS control AOs. Our results demonstrated that the 18mer and 16mer truncated AO variants showed slightly better exon-skipping efficacy when compared with the fully-23 modified 2'-OMePS control AOs, in addition to showing low cytotoxicity. As there was no previous report on using α-l-LNA-modified AOs in splice modulation, we firmly believe that this initial study could be beneficial to further explore and expand the scope of α-l-LNA-modified AO therapeutic molecules.

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. METHODS: This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. RESULTS: A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR = 1.621, 95%CI 1.379-1.905; CT + TT vs CC. OR = 1.541, 95%CI 1.351-1.758; TT vs CT + CC, OR = 2.897, 95%CI 1.690-4.966; CC + TT vs TC, OR = 0.693, 95%CI 0.576-0.834). The Egger's test revealed no significant publication bias. CONCLUSION: The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.