Practitioner perspectives on the use of acceptance and commitment therapy for bereavement support: a qualitative study.

BACKGROUND: There is currently a high demand for bereavement support coupled with inconclusive findings as to the efficacy of existing approaches. Acceptance and Commitment Therapy (ACT) aims to improve human functioning and has shown efficacy across a wide range of conditions. ACT may be a promising means of supporting bereaved people, yet evidence on the use of ACT for bereavement support is lacking. The aim of this study is to explore how ACT is currently used for bereavement support and practitioner perspectives of how it helps following bereavement. METHODS: Semi-structured interviews were conducted online via MS Teams with practitioners experienced in using ACT for bereavement support. Data were analysed thematically guided by a framework approach. RESULTS: Nine participants were recruited. Three themes were identified: (i) creating psychological space around grief; (ii) using psychological space for value-directed action in the midst of grieving, and (iii) adapting ACT for bereavement support. Practitioners indicated that ACT improves clients' relationship with distressing internal experiences. Metaphors and mindfulness techniques were used to encourage acceptance of grief responses, taking perspective on distressing thoughts and images, and contact with the present moment. Better relationships with distressing experiences were regarded as less psychologically taxing, improving coping and well-being, while providing the psychological space to engage in value-directed action. Values exploration, sometimes using metaphors and exercises, was seen as supporting the bereaved person to rediscover a sense of purpose and engage in meaningful activities alongside their grief. Practitioners used ACT flexibly, integrating other interventions, and adapted ACT to the perceived sensitivities of bereaved people, and age-related and developmental factors. CONCLUSION: ACT is used to support people who have been bereaved to live effectively with the difficult thoughts and feelings associated with grieving and to enable them to gradually identify, reconnect with, and act in line with their values after loss.

RFX6 Maintains Gene Expression and Function of Adult Human Islet α-Cells.

Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood. We developed a method for selective genetic targeting of human α-cells and assessed RFX6-dependent α-cell function. RFX6 suppression with RNA interference led to impaired α-cell exocytosis and dysregulated glucagon secretion in vitro and in vivo. By contrast, these phenotypes were not observed with RFX6 suppression across all islet cells. Transcriptomics in α-cells revealed RFX6-dependent expression of genes governing nutrient sensing, hormone processing, and secretion, with some of these exclusively expressed in human α-cells. Mapping of RFX6 DNA-binding sites in primary human islet cells identified a subset of direct RFX6 target genes. Together, these data unveil RFX6-dependent genetic targets and mechanisms crucial for regulating adult human α-cell function.

HNF1α maintains pancreatic α and ß cell functions in primary human islets.

HNF1A haploinsufficiency underlies the most common form of human monogenic diabetes (HNF1A-maturity onset diabetes of the young [HNF1A-MODY]), and hypomorphic HNF1A variants confer type 2 diabetes risk. But a lack of experimental systems for interrogating mature human islets has limited our understanding of how the transcription factor HNF1α regulates adult islet function. Here, we combined conditional genetic targeting in human islet cells, RNA-Seq, chromatin mapping with cleavage under targets and release using nuclease (CUT&RUN), and transplantation-based assays to determine HNF1α-regulated mechanisms in adult human pancreatic α and ß cells. Short hairpin RNA-mediated (shRNA-mediated) suppression of HNF1A in primary human pseudoislets led to blunted insulin output and dysregulated glucagon secretion after transplantation in mice, recapitulating phenotypes observed in patients with diabetes. These deficits corresponded with altered expression of genes encoding factors critical for hormone secretion, including calcium channel subunits, ATPase transporters, and extracellular matrix constituents. Additionally, HNF1A loss led to upregulation of transcriptional repressors, providing evidence for a mechanism of transcriptional derepression through HNF1α. CUT&RUN mapping of HNF1α DNA binding sites in primary human islets imputed a subset of HNF1α-regulated genes as direct targets. These data elucidate mechanistic links between HNF1A loss and diabetic phenotypes in mature human α and ß cells.

Future Work Self Salience and Future Time Perspective as Serial Mediators Between Proactive Personality and Career Adaptability.

In recent years, employment has become a growing problem for Chinese college students, who often face issues of slow employment and lazy employment. Guided by the framework of career construction theory, we explored how proactive personality strengthens career adaptability. A total of 423 Chinese college students effectively completed the online survey. The results showed a positive correlation between proactive personality, future work self salience, future time perspective, and career adaptability. Additionally, proactive personality can directly affect career adaptability through three indirect paths: the separate intermediary effect of future work self salience, future time perspective, and the continuous mediating role of future work self salience and future time perspective. The results indicate that proactive personality increases career adaptability through the mediating role of future work self salience and future time perspective. This study contributes to our understanding of the mechanisms underlying the relationship between proactive personality and career adaptability. Additionally, the findings have implications for the career development of college students.

m6 A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase-specific transcripts.

OBJECTIVES: Accumulating evidences show that the regulatory network of m6 A modification is essential for mammalian spermatogenesis. However, as an m6 A reader, the roles of YTHDF2 remain enigmatic due to the lack of a proper model. Here, we employed the germ cell conditional knockout mouse model and explored the function of YTHDF2 in spermatogenesis. MATERIALS AND METHODS: Ythdf2 germ cell conditional knockout mice were obtained by crossing Ythdf2-floxed mice with Vasa-Cre and Stra8-Cre mice. Haematoxylin and eosin (HE) staining, immunofluorescent staining and Western blotting were used for phenotyping. CASA, IVF and ICSI were applied for sperm function analysis. RNA-seq, YTHDF2-RIP-seq and quantitative real-time PCR were used to explore transcriptome changes and molecular mechanism analysis. RESULTS: Our results showed that YTHDF2 was highly expressed in spermatogenic cells. The germ cell conditional knockout males were sterile, and their sperm displayed malformation, impaired motility, and lost fertilization ability. During differentiated spermatogonia transiting to pachytene spermatocyte, most m6 A-modified YTHDF2 targets that were degraded in control germ cells persisted in pachytene spermatocytes of Ythdf2-vKO mice. These delayed mRNAs were mainly enriched in pathways related to the regulation of transcription, and disturbed the transcriptome of round spermatid and elongated spermatid subsequently. CONCLUSION: Our data demonstrate that YTHDF2 facilitates the timely turnover of phase-specific transcripts to ensure the proper progression of spermatogenesis, which highlights a critical role of YTHDF2 in spermatogenesis.

Efficient DNA interrogation of SpCas9 governed by its electrostatic interaction with DNA beyond the PAM and protospacer.

Streptococcus pyogenes Cas9 (SpCas9), a programmable RNA-guided DNA endonuclease, has been widely repurposed for biological and medical applications. Critical interactions between SpCas9 and DNA confer the high specificity of the enzyme in genome engineering. Here, we unveil that an essential SpCas9-DNA interaction located beyond the protospacer adjacent motif (PAM) is realized through electrostatic forces between four positively charged lysines among SpCas9 residues 1151-1156 and the negatively charged DNA backbone. Modulating this interaction by substituting lysines with amino acids that have distinct charges revealed a strong dependence of DNA target binding and cleavage activities of SpCas9 on the charge. Moreover, the SpCas9 mutants show markedly distinguishable DNA interaction sites beyond the PAM compared with wild-type SpCas9. Functionally, this interaction governs DNA sampling and participates in protospacer DNA unwinding during DNA interrogation. Overall, a mechanistic and functional understanding of this vital interaction explains how SpCas9 carries out efficient DNA interrogation.

Depletion of m6 A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin.

N6 -methyladenosine (m6 A) is the most prevalent modification in mRNA and engages in multiple biological processes. Previous studies indicated that m6 A methyltransferase METTL3 ('writer') and demethylase FTO ('eraser') play critical roles in heart-related disease. However, in the heart, the function of m6 A 'reader', such as YTH (YT521-B homology) domain-containing proteins remains unclear. Here, we report that the defect in YTHDC1 but not other YTH family members contributes to dilated cardiomyopathy (DCM) in mice. Cardiac-specific conditional Ythdc1 knockout led to obvious left ventricular chamber enlargement and severe systolic dysfunction. YTHDC1 deficiency also resulted in the decrease of cardiomyocyte contractility and disordered sarcomere arrangement. By means of integrating multiple high-throughput sequence technologies, including m6 A-MeRIP, RIP-seq and mRNA-seq, we identified 42 transcripts as potential downstream targets of YTHDC1. Amongst them, we found that Titin mRNA was decorated with m6 A modification and depletion of YTHDC1 resulted in aberrant splicing of Titin. Our study suggests that Ythdc1 plays crucial role in regulating the normal contractile function and the development of DCM. These findings clarify the essential role of m6 A reader in cardiac biofunction and provide a novel potential target for the treatment of DCM.

Compilation and Application of the Scale of Sustainable Knowledge Sharing Willingness in Virtual Academic Community During the Times of the Coronavirus Pandemic (COVID-19).

With the outbreak of COVID-19, many offline academic activities have been turned online, and virtual academic communities have been further emphasized. Based on this situation, this study took the Eagly and Chaiken's Heuristic-System Model of Persuasion and the general rules of behavioral decision as a theoretical basis, established a theoretical model of sustainable knowledge sharing willingness in virtual academic communities. Firstly, this study developed the scale of willingness to share sustainable knowledge based on the heuristic system model of persuasion. After analyzing the data of 62 participants, the scale was revised. Secondly, 256 valid data were collected from China, the United States, Singapore, and Indonesia. Finally, the conceptual model and theoretical hypothesis were tested based on the data. The results show that knowledge sharing satisfaction is affected by heuristic factors (knowledge sharing quantity, knowledge source credibility) and system factors (knowledge sharing quality, knowledge sharing usefulness), and has a significant positive correlation with sustainable knowledge sharing willingness.

A critical role of nuclear m6A reader YTHDC1 in leukemogenesis by regulating MCM complex-mediated DNA replication.

YTHDC1 has distinct functions as a nuclear N6-methyladenosine (m6A) reader in regulating RNA metabolism. Here we show that YTHDC1 is overexpressed in acute myeloid leukemia (AML) and that it is required for the proliferation and survival of human AML cells. Genetic deletion of Ythdc1 markedly blocks AML development and maintenance as well as self-renewal of leukemia stem cells (LSCs) in vivo in mice. We found that Ythdc1 is also required for normal hematopoiesis and hematopoietic stem and progenitor cell (HSPC) maintenance in vivo. Notably, Ythdc1 haploinsufficiency reduces self-renewal of LSCs but not HSPCs in vivo. YTHDC1 knockdown has a strong inhibitory effect on proliferation of primary AML cells. Mechanistically, YTHDC1 regulates leukemogenesis through MCM4, which is a critical regulator of DNA replication. Our study provides compelling evidence that shows an oncogenic role and a distinct mechanism of YTHDC1 in AML.

PINK1 gene mutation by pair truncated sgRNA/Cas9-D10A in cynomolgus monkeys.

Mutations of PTEN-induced kinase I (PINK1) cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current PINK1 knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients. This suggests that generating PINK1 disease models in non-human primates (NHPs) that are close to humans is essential to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both of which can reduce off-target effects without compromising on-target editing, are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models. Here, we combined the two strategies and injected Cas9-D10A mRNA and two truncated sgRNAs into one-cell-stage cynomolgus zygotes to target the PINK1 gene. We achieved precise and efficient gene editing of the target site in three newborn cynomolgus monkeys. The frame shift mutations of PINK1 in mutant fibroblasts led to a reduction in mRNA. However, western blotting and immunofluorescence staining confirmed the PINK1 protein levels were comparable to that in wild-type fibroblasts. We further reprogramed mutant fibroblasts into induced pluripotent stem cells (iPSCs), which showed similar ability to differentiate into dopamine (DA) neurons. Taken together, our results showed that co-injection of Cas9-D10A nickase mRNA and sgRNA into one-cell-stage cynomolgus embryos enabled the generation of human disease models in NHPs and target editing by pair truncated sgRNA/Cas9-D10A in PINK1 gene exon 2 did not impact protein expression.

Resilience Coping in Preschool Children: The Role of Emotional Ability, Age, and Gender.

BACKGROUND: In the process of children's physical and mental development, emotional ability is an important part of their cognitive and social ability. Resilience in the face of difficulties or setbacks and other adversity will also produce differences in adaptability, thus affecting physical and mental development. OBJECTIVES: This study aimed to measure the effect of children's emotional ability on resilience and to provide an in-depth analysis based on age and gender differences. METHODOLOGY: A total of 300 preschool children aged 3-6 years old in kindergartens of China were randomly selected as the research subjects. Through a combination of experiments and questionnaires, the emotional ability and resilience of children were measured, and differences were analyzed according to the actual situation, using age and gender. RESULTS: Children of different ages have significant differences in the dimensions and total scores of emotional ability and resilience, but only some of the resilience dimensions have significant gender differences. Moreover, the emotional ability has a significant positive effect on resilience. DISCUSSIONS: The results confirm the influence of children's emotional ability on resilience, but the research hypothesis has not been fully verified. LIMITATIONS: This study has the limitations of a single measurement method and a more effective research tool.

CRISPR-based genome editing in primary human pancreatic islet cells.

Gene targeting studies in primary human islets could advance our understanding of mechanisms driving diabetes pathogenesis. Here, we demonstrate successful genome editing in primary human islets using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). CRISPR-based targeting efficiently mutated protein-coding exons, resulting in acute loss of islet ß-cell regulators, like the transcription factor PDX1 and the KATP channel subunit KIR6.2, accompanied by impaired ß-cell regulation and function. CRISPR targeting of non-coding DNA harboring type 2 diabetes (T2D) risk variants revealed changes in ABCC8, SIX2 and SIX3 expression, and impaired ß-cell function, thereby linking regulatory elements in these target genes to T2D genetic susceptibility. Advances here establish a paradigm for genetic studies in human islet cells, and reveal regulatory and genetic mechanisms linking non-coding variants to human diabetes risk.

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic ß cells.

The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic ß cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions improve in the years after birth. This coincides with expression of the transcription factors SIX2 and SIX3, whose functions in native human ß cells remain unknown. Here, we show that shRNA-mediated SIX2 or SIX3 suppression in human pancreatic adult islets impairs insulin secretion. However, transcriptome studies revealed that SIX2 and SIX3 regulate distinct targets. Loss of SIX2 markedly impaired expression of genes governing ß-cell insulin processing and output, glucose sensing, and electrophysiology, while SIX3 loss led to inappropriate expression of genes normally expressed in fetal ß cells, adult α cells, and other non-ß cells. Chromatin accessibility studies identified genes directly regulated by SIX2. Moreover, ß cells from diabetic humans with impaired insulin secretion also had reduced SIX2 transcript levels. Revealing how SIX2 and SIX3 govern functional maturation and maintain developmental fate in native human ß cells should advance ß-cell replacement and other therapeutic strategies for diabetes.

An Online Career Intervention for Promoting Chinese High School Students' Career Readiness.

To assist Chinese high school students in improving their career readiness and tackling career decision-making difficulties, we designed a synchronous online career intervention based on the Cognitive Information Processing (CIP) theory during the Covid-19 pandemic. The online career intervention consisted of a series of career courses to develop high school students' knowledge and skills in career planning, career assessments for exploring their vocational interests and academic self-concept, and a database providing basic information about university majors. To evaluate the intervention's effectiveness, 957 10th grade students were recruited in the study, 601 participants (girls = 227, boys = 324) were randomly assigned to the experimental group (online career intervention), and 356 (girls = 159, boys = 197) participants were randomly assigned to the control group (no any career interventions). All participants completed a pre- and post-intervention assessment of their career maturity, vocational identity and career decision-making difficulties. Results indicated that the online intervention significantly increased high school students' career readiness and reduced their career decision-making difficulties. The practical implications of this research for online career interventions directed at Chinese high school students are also discussed.

Comparison of mental health status between freshmen with and without disabilities / 中国学校卫生

Objective@#To explore the differences in mental health between freshmen with and without disabilities.@*Methods@#A comparative analysis of 6 114 freshmen with and without disabilities from an undergraduate college in Nanjing from 2018 to 2020 was measured by the SCL-90 Mental Health Symptom Self Rating Scale.@*Results@#The positive detection rate of SCL-90 was 23.29%, and the positive rate of disabled students was significantly higher than healthy students( χ 2= 28.35 , P <0.01); Disabled freshmen were significantly higher than healthy freshmen in the levels of all factors( P <0.05); A longitudinal comparison of the positive detection rate of SCL-90 between the two groups of freshmen in three years, there was no statistical difference between the disabled freshmen( χ 2=5.82, P =0.06), there was a statistical difference in healthy freshmen( χ 2=29.43, P <0.01); After interview with positive factor students, the composition ratio of freshmen with disabled of A and B was higher than that of healthy freshmen( χ 2= 7.09 , P <0.05).@*Conclusion@#Mental health level of freshmen with disabled is lower than that of healthy freshmen. Mental health among freshmen without disabilities is worsening. The mental health of disabled freshmen is relatively stable, however, the proportion of students with psychological problems is relatively high, which requires attention.

Are You Tired of Working amid the Pandemic? The Role of Professional Identity and Job Satisfaction against Job Burnout.

With the outbreak of novel coronavirus in 2019, most universities changed from traditional offline teaching to online teaching, which brought about a large amount of problems, including teachers' physical and mental problems. Because of teaching on the computer screen for a long period of time, the teacher lacks communication and can act casually. With long-term accumulation, the problem of teachers' job burnout has become increasingly serious. The main purpose of this study was to examine the influence of professional identity on job burnout during the period of the novel coronavirus. At the same time, this study also discussed the moderating effect of job satisfaction on professional identity and job burnout, and its relationship between job satisfaction and job burnout. During the peak period of the COVID-19 epidemic, we conducted an online survey-483 Chinese university teachers with online teaching experience completed the Teacher Professional Identity Scale, Job Satisfaction Scale, and Job Burnout Scale. The results of this study found professional identity and job satisfaction of university teachers to be significantly negative predictors of job burnout, with job satisfaction playing a moderating role between professional identity and job burnout. This study also confirmed that professional identity and job satisfaction are important factors affecting job burnout of university teachers. Therefore, this study proposed that schools should adopt more effective strategies to improve university teachers' professional identity and job satisfaction in order to reduce the practical problems of job burnout, ensure the effectiveness of online teaching, and maintain the sustainable development during the epidemic.

Career Adaptability Research: A Literature Review with Scientific Knowledge Mapping in Web of Science.

With the rapid development of society and technology, personal adaptability is becoming more and more important. Learning how to adapt to a changing world is becoming one of the necessary conditions for success. Career adaptability can help individuals to smoothly adapt to changes when coping with their career roles, and maintain their ability to balance their career roles, which will affect their important psychological resources for career development and achieve more meaning in life. In recent years, career adaptability has gradually attracted the attention of researchers. Therefore, in order to explore the main factors, such as research focus, the main researchers, its evolution, and the important results of career adaptability in the last ten years, this study used the scientific knowledge mapping software CiteSpace as a research tool, and select related articles from the Web of Science between 2010 to 2020 under the theme of "career adaptability" for data analysis, which can help future researchers to understand current and future career adaptability research and control the research direction of career adaptability. The results of this research indicate that there are direct or indirect connections between different themes, such as the career adaptability scale, career construction, positive personalities, and so on, but few articles integrate multiple research topics. At the same time, the main researchers, research frontiers and network relationships were also obtained. Based on the above findings, the correlative main concept, theoretical structure, evolution, and research progress of career adaptability in the past ten years are discussed.

In vivo studies of glucagon secretion by human islets transplanted in mice.

Little is known about regulated glucagon secretion by human islet α-cells compared to insulin secretion from ß-cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulins in humans and mice permit in vivo studies of human ß-cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogous in vivo measures of glucagon output from human α-cells. Here, we use CRISPR-Cas9 editing to remove glucagon codons 2-29 in immunocompromised NSG mice, preserving the production of other proglucagon-derived hormones. Glucagon knockout NSG (GKO-NSG) mice have metabolic, liver and pancreatic phenotypes associated with glucagon-signalling deficits that revert after transplantation of human islets from non-diabetic donors. Glucagon hypersecretion by transplanted islets from donors with type 2 diabetes revealed islet-intrinsic defects. We suggest that GKO-NSG mice provide an unprecedented resource to investigate human α-cell regulation in vivo.