Validation of the Capacity for the Psychotherapy Process Scale for Use in Adolescent Patients.

Although pre-treatment assessments of the capacity for the psychotherapy process can aid in identifying patients experiencing great difficulties in therapy and in tailoring therapies for individual patients, limited information exists for adolescents. To address this gap, this study followed the World Health Organization's age standards for adolescents (younger adolescents aged 10-14 years; older adolescents aged 15-19 years), examined the psychometric properties of the Capacity for Psychotherapy Process Scale (CFPPS; mainly used for adult patients) in these two groups of adolescents, and compared their capacities for the psychotherapy process. The participants were 434 younger adolescent (mean age = 13.00 ± 1.08 years; 70.0% female) and 883 older adolescent outpatients (mean age = 16.68 ± 1.29 years; 62.3% female) at the department of psychiatry of the hospital in Guangzhou, China. The results of exploratory and confirmatory factor analyses validated the 5-factor model (motivation, belief, self-revelation, persistence, and insight) in both groups. The scale also demonstrated good internal consistency. Furthermore, the CFPPS exhibited small or no associations with pre-treatment sleep problems, depression symptoms, or anxiety symptoms but was a significant predictor of working alliance and psychological benefit in therapy. The capacity for the psychotherapy process among younger adolescents was lower than that among older adolescents. The CFPPS appears to be a reliable and validated instrument for measuring the capacity for the psychotherapy process among adolescent outpatients in China. Therapists should provide therapy tailored to the Chinese adolescents' capacity. Future studies are needed to examine the predictive utility of the CFPPS for the whole sessions of the psychotherapy.

Is cognitive behavioral therapy for insomnia (CBTI) more cost-effective? New-perspective on economic evaluations: a systematic review and meta-analysis.

STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital cognitive behavioral therapy for insomnia (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trails studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long-term, especially in long-lasting efficacy and costs reduction. In addition, dCBTI is one of the cost-effective options for insomnia.

SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing.

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.

NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking.

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.

Discovery of Podofilox as a Potent cGAMP-STING Signaling Enhancer with Antitumor Activity.

Cyclic GMP-AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I IFNs and other cytokines. Pharmacologic activation of STING is considered a potent therapeutic strategy in cancer. In this study, we used a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP-STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP-STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.

Differential proteomic patterns of plasma extracellular vesicles show potential to discriminate ß-thalassemia subtypes.

The observed specificity of ß-thalassemia-subtype phenotypes makes new diagnostic strategies that complement current screening methods necessary to determine each subtype and facilitate therapeutic regimens for different patients. Here, we performed quantitative proteomics of plasma-derived extracellular vesicles (EVs) of ß-thalassemia major (TM) patients, ß-thalassemia intermedia (TI) patients, and healthy controls to explore subgroup characteristics and potential biomarkers. Plasma quantitative proteomics among the same cohorts were analyzed in parallel to compare the biomarker potential of both specimens. EV proteomics showed significantly more abnormalities in immunity and lipid metabolism in TI and TM, respectively. The differential proteomic patterns of EVs were consistent with but more striking than those of plasma. Notably, we also found EV proteins to have a superior performance for discriminating ß-thalassemia subtypes. These findings allowed us to propose a diagnostic model consisting of five proteins in EVs with subtyping potential, demonstrating the ability of plasma-derived EVs for the diagnosis of ß-thalassemia patients.

USP15 promotes cGAS activation through deubiquitylation and liquid condensation.

Double-stranded DNA (dsDNA) is recognized as a danger signal by cyclic GMP-AMP synthase (cGAS), which triggers innate immune responses. cGAS activity must be properly regulated to maintain immune homeostasis. However, the mechanism by which cGAS activation is controlled remains to be better understood. In this study, we identified USP15 as a cGAS-interacting partner. USP15 promoted DNA-induced cGAS activation and downstream innate immune responses through a positive feedback mechanism. Specifically, USP15 deubiquitylated cGAS and promoted its activation. In the absence of DNA, USP15 drove cGAS dimerization and liquid condensation through the USP15 intrinsic disordered region (IDR), which prepared cGAS for a rapid response to DNA. Upon DNA stimulation, USP15 was induced to express and boost cGAS activation, functioning as an efficient amplifier in innate immune signal transduction. In summary, the positive role played by USP15-mediated cGAS activation may be a novel regulatory mechanism in the fine-tuning of innate immunity.

[Clinical Efficacy and Survival Analysis of Adult Patients with Acute Myeloid Leukemia after Microtransplantation].

OBJECTIVE: To investigate the clinical efficacy and survival factors of microtransplantation (MST) in adult patients with acute myeloid leukemia (AML). METHODS: For a retrospective analysis of 27 adult patients with AML receiving MST from July 2014 to October 2021, the median age was 59(29-77) years old, 13 cases were ≥60 years old, 14 case were <60 years old, 13 cases were male and 14 cases were female. Classification by FAB: AML-M2 6 cases, AML-M4 6 cases, AML-M5 2 cases, AML-M6 2 cases, AML（Undivided type） 9 cases, AML myeloid sarcoma 2 cases (primary AML 21 cases, AML secondary to MDS 6 cases). Cytogenetic analysis showed 25 patients with a normal karyotype, 2 patients with an abnormal karyotype, and 20 patients with an abnormal molecular biology. Induction chemotherapy regimens mainly include: IA, DA, MA or HA regimen, including CAG or CIG in combination with decitabine, and single-agent decitabine. 17 patients achieved complete remission (CR) after 1 course of induction chemotherapy and 4 patients achieved CR after 2 courses of induction chemotherapy. 3 patients received CR by four courses of decitabine, 2 patients received no remission, and 1 patient underwent no induction chemotherapy and were treated direct MST. There were 16 patients with pretransplant CR and 11 patients were not in remission before transplantation. Follow-up mainly used consult patient's medical records and telephone inquiry to observe the adverse effects and efficacy of MST treatment. Survival analysis was performed by Kaplan-Meier method, with the main observation indicators overall survival(OS) and leukemia-free survival(LFS), and performed with the Log-rank test. Multivariate analysis was performed by the Cox regression model. RESULTS: A total of 79 MST were performed in 27 AML patients with good overall safety and no special serious adverse effects. The median time of leukocyte recovery was 13(4-28) days, and the median time of platelet recovery was 13(4-30) days. There were 50 cases of infection, 5 cases of abnormal liver function and 3 cases of abnormal cardiac function. Except for abnormal cardiac function, all other complications did not affect the treatment and were cure. Acute or chronic GVHD, renal insufficiency, abnormal coagulation function, and severe bleeding were not observed during treatment or during follow-up. As of the follow-up date, the median follow-up time of the 27 patients was 79(14-171) months, the median OS time was 62(1-171) months, and the median LFS time was 15(0-171) months. The 2-year OS rate was 65.7%（17/27）, and the 2-year LFS rate was 47.4%（12/27） . The complete response rate of 27 patients treated with MST was 48.1% (13/27). 8 patients relapsed during MST treatment, including 7 patients after the completion of the first MST course and 1 patient after the completion of the second MST course. 2 patients relapsed after the end of the course of MST. 13 patients died, including 10 patients because of disease progression, two patients from severe infection, and one patient from cardiac damage. CONCLUSION: MST has the advantages of small toxic side effects, complete compatibility of HLA matching is not required, effective avoidance of GVHD and rapid hematopoietic recovery, which can improve OS and LFS in elderly AML and young AML patients, and is one of the treatment options for patients without HLA matching.

LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity.

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.

Predicting first session working alliances using deep learning algorithms: A proof-of-concept study for personalized psychotherapy.

OBJECTIVE: The aim of this proof-of-concept study is to develop a predictive model based on deep learning algorithms to predict working alliances after the first therapeutic session and to provide a basis for clinical decisions. METHODS: Using a sample of 325 patients and 32 psychotherapists from three university counseling centers, a deep learning algorithm known as fully connected neural networks (FCNNs) was adopted to construct data-driven predictive models. The performance differences between the model including only patient indicators and the model including both patient and therapist indicators were compared. The optimal model was further tested in a general hospital sample of 85 patients and 8 therapists. RESULTS: The model incorporating both patient indicators and therapist-level indicators (R²: 0.30 ± 0.02) performed better than the model incorporating only patient indicators (R²: 0.11 ± 0.02). The performance of this model decreased when being transferred to the independent general hospital sample, but still retained some predictive value (R² = 0.11). CONCLUSION: This study showed that the inclusion of therapist-level indicators can improve the performance of a predictive model in predicting working alliances. This model could assist clinical decisions on choosing psychotherapists for patients and may also initiate new possibilities for future research.

Anxiety, depression, psychological stress and coping style in medical postgraduates in southeastern China when restricted to commuting between the campus and hospital during the COVID-19 pandemic.

Background: As the COVID-19 epidemic was gradually brought under control, a new autumn semester began in 2020. How was the mental health of postgraduates as they experienced quarantine at home, only commuting between the school and hospital? Methods: The research was conducted in a cross-sectional online survey in October 2020. The data were collected from 1,645 medical postgraduates (master's and doctoral students) by using the demographic information questionnaire, the Self-rating Depression Scale (SDS), the Self-rating Anxiety Scale (SAS), the Questionnaire on Psychological Stressors of Postgraduates (QPSP), the Simplified Coping Style Questionnaire (SCSQ) and the Social Support Rate Scale (SSRS). One-way ANOVA and Pearson correlation were used to explore the relationships among anxiety, depression, psychological stressors, social support and coping style. Structural equation modeling (SEM) was conducted to assess the mediation model. Results: Among the total of 1,645 medical postgraduates, 21.6% (n = 356) had self-rated depression symptoms, and 9.4% (n = 155) had self-rated anxiety symptoms. The main disturbances they experienced were employment, academic and interpersonal pressure. The master of third grade students had the highest employment pressure, and the master of second grade students had the highest academic and interpersonal pressure. Negative coping played a negative mediating role and social support played a positive mediating role in the relationships between perceived stress and anxiety (ß = 0.027, P < 0.01; ß = 0.124, P < 0.01) and depression (ß = 0.016, P < 0.01; ß = 0.193, P < 0.01). Conclusion: Medical postgraduates in China restricted to studies on campus and in the hospital experienced psychological distress. Our results suggest that providing employment and learning guidance, while strengthening social support and guiding positive coping may be effective at improving the mental health of the medical graduate students, mediating their perceived stress and negative emotions.

Personality Characteristics and Emotional Distress Among Chinese Pregnant Women: A Moderated Mediation Model.

Previous studies have suggested that certain personality characteristics are associated with emotional distress during pregnancy. However, the underlying mechanism of this association is rarely understood. The current study investigated the links between personality and pregnant women's emotional distress (depressive and anxiety symptoms), tested the chain mediating effects of two resilience factors-social support and positive coping, and explored whether socioeconomic status (SES) could moderate the effects (including direct and/or indirect effects) of personality on their emotional distress. Results of a relatively large sample of pregnant women in China (N = 1157) showed positive associations for psychoticism and neuroticism with depressive and anxiety symptoms as well as negative associations for extraversion with depression and anxiety. After controlling for four important variables (the first pregnancy or not, having adverse pregnancy experience or not, being pregnant as planned or not, and number of weeks of pregnancy), social support and positive coping acted as chain mediators on the associations of personality with depressive symptoms as well as of personality with anxiety. Overall, the association of personality and depressive symptoms demonstrated invariance across socioeconomic status (SES). However, SES moderated the relationship between personality and anxiety. Specifically, the negative association of positive coping with anxiety symptoms was weaker for low SES women than for high SES ones. Results highlight the importance of social support and positive coping to decrease personality-related depressive and anxiety symptom among pregnant women. Furthermore, identifying other resilience factors that alleviate anxiety in women with low SES is urgently called for.

Influential Factors of Non-suicidal Self-Injury in an Eastern Cultural Context: A Qualitative Study From the Perspective of School Mental Health Professionals.

Background: Adolescent non-suicidal self-injury (NSSI) is becoming a serious public health concern worldwide. In recent years, there has seen a significant increase in both the growth rate and cases of NSSI in Eastern countries, such as Japan, India, and China. In China, most schools have a mental health office that comprises mental health professionals (MHPs), who are the first to respond to student mental health problems, which include NSSI. MHPs possess comprehensive knowledge as well as unique insight into adolescent NSSI. However, very few studies on NSSI have incorporated their perspectives. In this work, we seek to add novel insight by conducting a study focusing on adolescent NSSI from the perspective of MHPs. Methods: We recruited a total of 24 MHPs from different schools using purposive sampling and conducted a semi-structured interview on NSSI-related issues. Each interview was voice recorded and lasted ~30 min. A thematic analysis was performed for the responses to study the most common and concerning issues underlying NSSI. Results: We extracted three major themes and eight sub-themes from the interview records, which included (1) the impact of Chinese culture on NSSI (sex-bias discrimination, overly high expectations, and inappropriate parenting style); (2) life events in school (internet use, academic pressure, and romantic relationships); and (3) opinions on the status quo of NSSI in China (ignorance and stigma). Conclusion: Results showed that culturally sensitive influential factors, such as sex-bias discrimination, the imposing of unrealistic expectations for personal achievement, and inappropriate parenting style, should be given more attention to prevent, assess, and intervene in NSSI. Emerging factors of modern society and adolescent lifestyles, such as academic pressure, internet use, and romantic relationships, should also be considered for treatments.

Targeting the TLR2 Receptor With a Novel Thymopentin-Derived Peptide Modulates Immune Responses.

The innate and adaptive immune systems act in concert to protect us from infectious agents and other harmful substances. As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system. It takes a long time to develop new immunomodulatory agents to prevent and treat immunosuppressive diseases, with slow progress. Toll-like receptor 2 (TLR2) agonists have been reported as potential immunomodulatory candidates due to their effective activation of immune responses. It has been demonstrated that thymopentin (TP5) could modulate immunity by binding to the TLR2 receptor. However, the fairly short half-life of TP5 greatly reduces its pharmacological potential for immunosuppression therapy. Although peptide cathelicidin 2 (CATH2) has a long half-life, it shows poor immunomodulatory activity and severe cytotoxicity, which seriously hampers its clinical development. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In this study, to overcome all these challenges faced by the parental peptides, six hybrid peptides (CaTP, CbTP, CcTP, TPCa, TPCb, and TPCc) were designed by combining the full-length TP5 with different active fragments of CATH2. CbTP, the most potent TLR2 agonist among the six hybrid peptides, was effectively screened through in silico analysis and in vitro experiments. The CbTP peptide exhibited lower cytotoxicity than either CATH2 or TP5. Furthermore, the immunomodulatory effects of CbTP were confirmed in a CTX-immunosuppressed mouse model, which showed that CbTP has increased immunopotentiating activity and physiological stability compared to the parental peptides. CbTP successfully inhibited immunosuppression and weight loss, increased immune organ indices, and improved CD4+/CD8+ T lymphocyte subsets. In addition, CbTP significantly increased the production of the cytokine TNF-α and IL-6, and the immunoglobulins IgA, IgM, and IgG. The immunoenhancing effects of CbTP were attributed to its TLR2-binding activity, promoting the formation of the TLR2 cluster, the activation of the TLR2 receptor, and thus activation of the downstream MyD88-NF-кB signaling pathway.

Psychotherapy Style Scale: Development and Validation.

Psychotherapy style is conceptualized as the therapeutic method that a therapist employs while working with clients during treatment. It influences both the therapeutic process and results of therapeutic actions. The present study developed and validated the Psychotherapy Style Scale (PSS). By following a systematic psychometric development process, a three-factor structure of the PSS was identified. Exploratory factor analysis and confirmatory factor analysis provided evidence of multidimensional structure and validity of the PSS. Cronbach's α suggested that the resulting scale was highly reliable. Criterion validity was also satisfactory, demonstrated by correlations between the scale and criterion validity measures. The PSS has the potential to help better understand therapists' behavioral characteristics and select the most appropriate therapists for clients who undergo psychotherapy.

The capacity for psychotherapy process scale: development and psychometric validation of patient self-reports.

Objective: Studies were conducted to develop and validate the Capacity for Psychotherapy Process Scale (CFPPS), a self-rating measure of capacity for the psychotherapy process from a trans-theoretical perspective. Method: In Study 1, a two-round Delphi methodology consulting 27 and 15 experts, respectively, was used to select items and identify content validity. In Study 2, 279 clients were recruited for exploratory factor analysis (EFA). In Study 3, confirmatory factor analysis and internal consistency analysis were conducted among 390 outpatients; the discriminant validity and predictive validity were studied in 270 outpatients and 82 psychotherapy outpatients, respectively. Results: The Delphi method resulted in 52 items. Through EFA, the CFPPS was reduced to 20 items, focusing on five factors: motivation, belief, self-revelation, persistence, and insight; the internal consistencies were good (0.92 for total scale and 0.82-0.91 for the factors). The CFPPS was not or was only weakly associated with symptoms. The Bonferroni-corrected partial correlation analyses revealed that the CFPPS was positively related to working alliance and session impact. Conclusions: The CFPPS is a preliminary step toward the self-report assessment of the capacity for psychotherapy process from a trans-theoretical perspective and may potentially be used to predict the working alliance and session impact.

Parenting Style and Emotional Distress Among Chinese College Students: A Potential Mediating Role of the Zhongyong Thinking Style.

Previous studies suggested that parenting style was associated with college student's emotional distress. However, little is known about the underlying mechanisms of this relation in Chinese culture. The present study investigated the associations between parenting style and college student's emotional distress (depression and anxiety symptoms), examined the mediating effects of Confucian personality-Zhongyong thinking, and explored whether gender, age, and socioeconomic status (SES) moderated the direct and/or indirect effects of parenting style on emotional distress. Results from a large representative sample of Chinese college students (n = 3943) indicated that (a) parental rejection and overprotection was positively and mildly associated with depressive and anxiety symptoms and negatively and mildly related to Zhongyong thinking. Parental warmth significantly correlated with the three variables in the opposite direction; Zhongyong thinking correlated negatively and moderately with depression, and mildly with anxiety; (b) Zhongyong thinking partially mediated the associations of parental rejection and warmth with emotional distress. Specifically, to the extent that students perceived less rejection and more warmth, they were more likely to develop Zhongyong thinking associated with decreased emotional distress; (c) gender and SES moderated the association between parenting style and Zhongyong thinking. Specifically, for students with low SES, the negative relationship between parental overprotection and Zhongyong thinking was stronger; for males and high SES students, the positive link between parental warmth and Zhongyong thinking were stronger. Results highlight the importance of researching potential effects of college student's Zhongyong thinking within the family system in Chinese culture.

BRF Negatively Regulates Thermotolerance Defect of fes1a in Arabidopsis.

FES1A is a heat shock protein 70 binding protein. Mutation of FES1A leads to a defect in thermotolerance of Arabidopsis; however, independent fes1a mutants exhibit a range in the extent of thermosensitivity. Here, we found that BRF2, a gene adjacent to FES1A and encoding a component of transcription factor IIIB, affects the thermosensitivity of fes1a mutants. Knockout of BRF2 suppressed fes1a thermosensitivity, while overexpression of BRF2 increased thermosensitivity of fes1a. BRF2 in fes1a mutants regulates the transcriptional strength of RNA Polymerase II and accumulation of heat shock proteins and eventually affects the thermotolerance of fes1a. There is a cross-talking between RNA Pol III and Pol II. The cross-talking is initiated by BRF, magnified by the mutation of FES1A, and finally has an effect on thermotolerance.

C-Terminal Amination of a Cationic Anti-Inflammatory Peptide Improves Bioavailability and Inhibitory Activity Against LPS-Induced Inflammation.

Lipopolysaccharide (LPS) has been implicated as a major cause of inflammation and an uncontrolled LPS response increases the risk of localized inflammation and sepsis. While some native peptides are helpful in the treatment of LPS-induced inflammation, the use of these peptides is limited due to their potential cytotoxicity and poor anti-inflammatory activity. Hybridization is an effective approach for overcoming this problem. In this study, a novel hybrid anti-inflammatory peptide that combines the active center of Cathelicidin 2 (CATH2) with thymopentin (TP5) was designed [CTP, CATH2 (1-13)-TP5]. CTP was found to have higher anti-inflammatory effects than its parental peptides through directly LPS neutralization. However, CTP scarcely inhibited the attachment of LPS to cell membranes or suppressed an established LPS-induced inflammation due to poor cellular uptake. The C-terminal amine modification of CTP (CTP-NH2) was then designed based on the hypothesis that C-terminal amidation can enhance the cell uptake by increasing the hydrophobicity of the peptide. Compared with CTP, CTP-NH2 showed enhanced anti-inflammatory activity and lower cytotoxicity. CTP-NH2 not only has strong LPS neutralizing activity, but also can significantly inhibit the LPS attachment and the intracellular inflammatory response. The intracellular anti-inflammatory effect of CTP-NH2 was associated with blocking of LPS binding to the Toll-like receptor 4-myeloid differentiation factor 2 complex and inhibiting the nuclear factor-kappa B pathway. In addition, the anti-inflammatory effect of CTP-NH2 was confirmed using a murine LPS-induced sepsis model. Collectively, these findings suggest that CTP-NH2 could be developed into a novel anti-inflammatory drug. This successful modification provides a design strategy to improve the cellular uptake and anti-inflammatory activity of peptide agents.

Applicability of the Dual-Factor Model of Mental Health in the Mental Health Screening of Chinese College Students.

Traditional mental health models focus on psychopathological symptoms. In contrast, a dual-factor model of mental health integrates psychopathology and subjective well-being into a mental health continuum, and it is adjustment and supplement for traditional mental health research paradigm. The present study explores the applicability of a dual-factor model of mental health in mental health screening of Chinese college students. To assess mental health statuses of 2,065 college students, we used Flourishing Scale Chinese Version, Satisfaction With Life Scale, the seven-item Patient Health Questionnaire, the Mental Health Continuum-Short Form, and Purpose in Life Test-Short Form. Results showed that the dual-factor model of mental health has a good fit index. Also, a feasible screening scale was addressed. The results indicate the importance of addressing both subjective well-being and psychopathology in evaluating mental health screening of college students.