Dual CRISPR/Cas13a Cascade Strand Displacement-Triggered Transcription for Point-of-Care Detection of Plasmodium in Asymptomatic Malaria.

Asymptomatic infections of Plasmodium parasites are major obstacles to malaria control and elimination. A sensitive, specific, and user-friendly method is urgently needed for point-of-care (POC) Plasmodium diagnostics in asymptomatic malaria, especially in resource-limited settings. In this work, we present a POC method (termed Cas13a-SDT) based on the cascade sequence recognition and signal amplification of dual Cas13a trans-cleavage and strand displacement-triggered transcription (SDT). Cas13a-SDT not only achieves exceptional specificity in discriminating the target RNA from nontarget RNAs with any cross-interaction but also meets the sensitivity criterion set by the World Health Organization (WHO) for effective malaria detection. Remarkably, this novel method was successfully applied to screen malaria in asymptomatic infections from clinical samples. The proposed method provides a user-friendly and visually interpretable output mode while maintaining high accuracy and reliability comparable to RT-PCR. These excellent features demonstrate the significant potential of Cas13a-SDT for POC diagnosis of Plasmodium infections, laying a vital foundation for advancing malaria control and elimination efforts.

Ligand-induced native G-quadruplex stabilization impairs transcription initiation.

G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type-specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases.

A MnO2 nanosheet-mediated CRISPR/Cas12a system for the detection of organophosphorus pesticides in environmental water.

Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.

Nurse-led sequential multiple assignment randomized trial of nudging intervention for early antiretroviral therapy initiation among patients with HIV/AIDS: Implementation study protocol.

AIMS: In China, more than 30% of patients have not initiated treatment within 30 days of HIV diagnosis. Delayed initiation has a detrimental influence on disease outcomes and increases HIV transmission. The study aims to evaluate the effectiveness of a nurse-led antiretroviral therapy initiation nudging intervention for people newly diagnosed with HIV in China to find the optimal intervention implementation strategy. METHODS: A Hybrid Type II sequential multiple assignment randomized trial will be conducted at four Centers for Disease Control and Prevention in Hunan, China. This study will recruit 447 people newly diagnosed with HIV aged ≥18 years and randomly assign them into two intervention groups and one control group. On top of the regular counselling services and referrals, intervention groups will receive a 4-week, 2-phase intervention based on the dual-system theory and the nudge theory. The control group will follow the currently recommended referral procedures. The primary outcomes are whether treatment is initiated, as well as the length of time it takes. The study outcomes will be measured at the baseline, day 15, day 30, week 12, week 24 and week 48. Generalized estimating equations and survival analysis will be used to compare effectiveness and explore factors associated with antiretroviral therapy initiation. Both qualitative and quantitative information will be collected to assess implementation outcomes. DISCUSSION: Existing strategies mostly target institutional-level factors, with little consideration given to patients' decision-making. To close this gap, we aim to develop an effective theory-driven nudging strategy to improve early ART initiation. IMPACT: This nurse-led study will help to prevent delayed initiation by employing implementation science strategies for people newly diagnosed with HIV. This study contributes to the United Nations' objective of ending the AIDS pandemic by 2030. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070140. The trial was prospectively registered before the first participant was recruited. PATIENT AND PUBLIC INVOLVEMENT: The nudging intervention was finalized through the Nominal Group Technique where we invited five experts in the related field and five people living with HIV to participate.

The role of the nursing work environment, head nurse leadership and presenteeism in job embeddedness among new nurses: a cross-sectional multicentre study.

BACKGROUND: The retention of new nurses has become a major challenge for medical institutions. Job embeddedness has been seen as a valuable lens for examining nurse turnover, but greater details about job embeddedness are rarely disclosed, especially among new nurses. This study aimed to reveal how the nursing work environment, head nurse leadership and presenteeism shape job embeddedness in this population from the perspective of conservation of resources (COR) theory. METHOD: A cross-sectional multicentre study involving 436 participants from 10 cities and 33 hospitals was conducted over 4 months. Samples were selected using a two-stage convenience sampling method. A sequential multiple mediation model performed with SPSS-PROCESS was used to analyse the relationships among the nursing work environment, head nurse leadership, presenteeism and job embeddedness. RESULTS: The nursing work environment not only directly affects the job embeddedness of new nurses (ß = 0.480, p < 0.001) but also indirectly affects it through the sequential multiple mediating effects of head nurse leadership and presenteeism (R2 = 0.535, F = 82.160, p < 0.001). CONCLUSIONS: New nurses' job embeddedness needs to be improved. These results suggest that preserving adequate resources for new nurses, such as work environment resources, head nurse leadership resources, and individual productivity resources, is an effective way to shape their job embeddedness. In addition, when a certain resource is insufficient, fully considering the principles of investment and buffering between resources and providing reciprocal, alternative, or buffer resources in a timely manner are necessary to improve new nurses' job embeddedness. LARGE LANGUAGE MODELS: Large language models (LLMs), such as ChatGPT, were not used during the writing of this article. An expert native English speaker performed language revision.

Academic-practice partnerships in evidence-based nursing practice: A theory-guided scoping review.

BACKGROUND: Academic-practice partnerships have the potential to solve many challenges in evidence-based nursing practice which is crucial for high-quality care. AIMS: To identify the existing knowledge on academic-practice partnerships in evidence-based nursing practice. METHODS: We conducted this review following the Joanna Briggs Institute scoping review methodology. We performed a comprehensive literature search of nine databases as well as five websites for gray literature. Two researchers independently conducted literature screening and data extraction and analysis. A third researcher was involved when needed. RESULTS: Dedicated time, dedicated resources, and compatible goals were found to be the top three inputs in academic-practice partnerships for evidence-based nursing practice. Meeting and discussion were the most popular forms of activities. Sufficient resources were the most important facilitators. Insufficient resources, insufficient time, and communication issues were the top three barriers. CONCLUSIONS: The assumption proposed in the practice-academic partnership logic model (i.e., inputs plus activities can lead to outputs and outcomes) was preliminarily verified by the results of this review in the context of evidence-based nursing practice. Academic-practice partnerships can leverage the advantages of both sides to overcome barriers and promote evidence-based nursing practice. However, it is essential to conduct a broader range of high-quality studies. Such endeavors could offer more comprehensive evidence for refining the framework of academic-practice partnerships in evidence-based nursing practice. IMPLICATIONS FOR NURSING EDUCATION, PRACTICE, POLICY AND RESEARCH: The "theoretical framework of academic-practice partnerships in evidence-based nursing practice" could theoretically guide academic and clinical nursing staff to collaborate on evidence-based nursing practice and related research and education programs. The academic-practice partnerships in evidence-based nursing practice could lead to a win-win situation for both the academic and the clinical sides. Furthermore, the results of this study provide an evidence-based foundation for policymakers to develop supportive policies for academic-practice partnerships in evidence-based nursing practice.

CRISPR-Cas-Driven Single Micromotor (Cas-DSM) Enables Direct Detection of Nucleic Acid Biomarkers at the Single-Molecule Level.

The target-dependent endonuclease activity (also known as the trans-cleavage activity) of CRISPR-Cas systems has stimulated great interest in the development of nascent sensing strategies for nucleic acid diagnostics. Despite many attempts, the majority of the sensitive CRISPR-Cas diagnostics strategies mainly rely on nucleic acid preamplification, which generally needs complex probes/primers designs, multiple experimental steps, and a longer testing time, as well as introducing the risk of false-positive results. In this work, we propose the CRISPR-Cas-Driven Single Micromotor (Cas-DSM), which can directly detect the nucleic acid targets at a single-molecule level with high specificity. We have demonstrated that the Cas-DSM is a reliable and practical method for the quantitative detection of DNA/RNA in various complex clinical samples as well as in individual cells without any preamplification processes. Due to the excellent features of the CRISPR/Cas system, including constant temperature, simple design, high specificity, and flexible programmability, the Cas-DSM could serve as a simple and universal platform for nucleic acid detection. More importantly, this work will provide a breakthrough for the development of next-generation amplification-free CRISPR/Cas sensing toolboxes.

ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1.

Adenosine deaminases acting on RNA1 (ADAR1) are involved in the occurrence and development of cancers. Although the role of ADAR1 in gastric cancer metastasis has been reported, the role of ADAR1 in the mechanism of cisplatin resistance in gastric cancer is not clear. In this study, human gastric cancer tissue specimens were used to construct cisplatin-resistant gastric cancer cells; the results indicated that the mechanism underlying the inhibition of gastric cancer metastasis and reversal of cisplatin-resistant gastric cancer by ADAR1 inhibits gastric cancer occurs through the antizyme inhibitor 1 (AZIN1) pathway. We assessed ADAR1 and AZIN1 expression in the tissues of patients with low to moderately differentiated gastric cancer. Gastric cancer cells (human gastric adenocarcinoma cell line [AGS] and HGC-27 cells) and gastric cancer cisplatin-resistant cells (AGS CDDP and HGC-27 CDDP ) were selected, and the protein expression of ADAR1 and AZIN1 was detected using immunocytochemistry and immunocytofluorescence. The effects of ADAR1 small interfering RNA (siRNA) on the invasion, migration and proliferation of cisplatin-resistant gastric cancer cells were investigated. Western blot assays were used to assess the protein expression levels of ADAR1, AZIN1 and epithelial-mesenchymal transition (EMT)-related markers. In-vivo experiments, a subcutaneous tumor formation model of nude mice was established, and the effects of ADAR1 on tumor growth and AZIN1 expression level were detected by hematoxylin and eosin, immunohistochemistry and western blot. The expression of ADAR1 and AZIN1 in human gastric cancer tissue was significantly higher than that in paracancerous tissues. The colocalization of ADAR1, AZIN1 and E-cadherin expression in immunofluorescence assays indicated a significant correlation between the three. In in-vitro experiments, ADAR1 knockout not only reduced the invasion and migration ability of AGS and HGC-27 cells but also reduced that of cisplatin-resistant gastric cancer cells. ADAR1 siRNA inhibited the proliferation and decreased the colony number of cisplatin-resistant gastric cancer cells. ADAR1 siRNA decreased the expression of AZIN1 and EMT-related marker proteins (vimentin, N-cadherin, ß-catenin, MMP9, MMP2 and TWIST). The effect of ADAR1 siRNA combined with AZIN1 siRNA was more significant. In-vivo, the knockdown of ADAR1 significantly inhibited tumor growth and AZIN1 expression. ADAR1 and AZIN1 are antimetastatic targets of gastric cancer, and AZIN1 is a downstream regulatory target of ADAR1. ADAR1 knockout can inhibit the metastasis of gastric cancer cells and reverse the cisplatin resistance of gastric cancer cells by downregulating the expression of AZIN1, potentially resulting in increased treatment efficacy.

Specific multiplexed detection of mRNA splice variants based on size-coding DNA probes and universal PCR amplification.

Alternative messenger RNA (mRNA) splicing is a vital regulatory process during the gene expression of higher eukaryotes. The specific and sensitive quantification of disease-related mRNA splice variants in biological and clinical samples is becoming particularly important. Reverse transcription polymerase chain reaction (RT-PCR), the most classical strategy for the assay of mRNA splice variants, cannot avoid false positive signals, which poses a challenge to the specificity of mRNA splice variant detection. In this paper, by rationally designing two DNA probes with double recognition at the splice site and different lengths, different mRNA splice variants could generate amplification products of unique lengths. Combined with capillary electrophoresis (CE) separation, the product peak of the corresponding mRNA splice variant can be specifically detected, which can avoid false-positive signals caused by non-specific amplification of PCR, greatly improving the specificity of the mRNA splice variant assay. In addition, universal PCR amplification eliminates amplification bias caused by different primer sequences and improves quantitative accuracy. Furthermore, the proposed method can simultaneously detect multiple mRNA splice variants as low as 100 aM in a one-tube reaction and has been successfully applied to the assay of variants in cell samples, which will provide a new strategy for mRNA splice variant-based clinical diagnosis and research.

Specific recognition and sensitive quantification of mRNA splice variants via one-pot ligation-dependent loop-mediated isothermal amplification.

Specific recognition and sensitive quantification of mRNA alternative splice variants have been a necessity for exploring the regulatory mechanism of RNA splicing and revealing the association between pre-mRNA splicing and transcriptome function, as well as disease diagnosis. However, their wide abundance range and high sequence homology pose enormous challenges for high sensitivity and selectivity quantification of splice variants. Herein, taking advantage of the excellent specificity of ligation and the powerful nucleic acid replication feature of loop-mediated isothermal amplification (LAMP), we developed a one-pot method (termed one-pot ligation-LAMP) for specific recognition and sensitive quantification of mRNA splicing variants based on two splicing junction-specific stem-loop DNA probe ligation and the subsequently initiating LAMP. The one-pot ligation-LAMP can specifically detect as low as 100 aM mRNA splice variants without any nonspecific signals and quantify them with a wide dynamics range spanning at least six orders of magnitude. We have demonstrated that the one-pot ligation-LAMP is a versatile and practical strategy for accurately quantifying different splicing variants in complex biological samples with high sensitivity all in one tube within 90 min, thereby providing an attractive tool for mRNA splice variant-related studies.

The Impact of Providing Free HIV Self-testing on Sexual Risk Behaviors Among Men who have Sex with Men in Hunan, China: A Randomized Controlled Trial.

HIV self-testing (HIVST) increases testing frequency among men who have sex with men (MSM). However, its impact on sexual risk behaviors is unclear. In a randomized controlled trial conducted in Hunan Province, China, HIV-negative MSM were randomized to receive one of two interventions for one year: (1) facility-based HIV testing, or (2) facility-based HIV testing augmented with free HIVST. From April to June 2018, 230 MSM were enrolled. They self-reported sexual behaviors every 3 months for 12 months. Among 216 MSM with follow-ups (intervention: 110; control: 106), adjusting for potential confounders in Generalized Estimating Equation models, there were no statistically significant differences in consistent condom use with male partners (regular/casual) or female partners, nor on number of male or female sexual partners. Provision of free HIVST kits does not increase risky sex and should be included in comprehensive HIV prevention packages, particularly for sexual minority men in China.

Psychological pathways to HIV-related posttraumatic stress disorder symptoms among people living with HIV in China: the mediating role of rumination.

The occurrence of HIV-related posttraumatic stress disorder (PTSD) compromises the physical and mental health of people living with HIV (PLWH). This study examined the psychological pathways of HIV-related PTSD symptoms considering the influence of rumination in PLWH of China. A cross-sectional survey was conducted in Changsha, China. The data were collected using the PTSD Checklist-Civilian Version, the Ruminative Response Scale, the Multidimensional Scale of Perceived Social Support, and measures of sociodemographic and HIV-related clinic characteristics. A total of 602 PLWH were surveyed. The average score of HIV-related PTSD symptoms was (34.54 ± 13.58). The mediation model showed that perceived social stigma and physical health exhibited direct associations with PTSD symptoms (ß = 0.093, -0.145, respectively), while the direct relations of family support, friend support and significant others support to PTSD symptoms were not significant. Rumination mediated the effect of perceived social stigma (ß = 0.077), physical health (ß = -0.150), family support (ß = -0.144) and friend support (ß = -0.105) on PTSD symptoms. The study findings underscore the importance of routinely assessing PTSD for PLWH, and developing trauma-focused interventions that alleviate HIV-related PTSD symptoms and reduce rumination while improving social support and physical health and reducing social stigma.

Fluorescent enzyme-based biosensor for sensitive analysis of DNA damage in cryopreserved sperm.

The freeze-thaw process can induce irreversible structural and functional changes in human sperm, particularly sperm DNA damage. Selecting a more accurate and sensitive detection method for evaluating sperm DNA integrity is crucial. To accurately assess sperm DNA integrity following the freeze-thaw process and significantly improve the clinical and scientific utilization of cryopreserved sperm. In this study, we utilized a novel fluorescent biosensor, assisted by terminal deoxynucleotidyl transferase (TdT) and Endonuclease IV, to detect DNA breakpoints during sperm cryopreservation. We evaluated the biosensor's performance by comparing it with the conventional DNA fragmentation index (DFI) measured using sperm chromatin structure analysis (SCSA). The cryopreserved group exhibited a significantly higher sperm DFI compared to the fresh group. No significant difference was observed between the antioxidant group and the cryopreserved group. However, the new method revealed a significant reduction in the number of DNA breakpoints in the antioxidant group compared to the cryopreserved group. The novel biosensor demonstrated superior accuracy and effectiveness in assessing sperm DNA integrity during cryopreservation compared to the conventional SCSA method. We believe that the biosensor holds significant potential for widespread use in the field of reproductive medicine.

Profiles of depressive symptoms and influential factors among people living with HIV in China.

BACKGROUND: Depressive symptoms are highly prevalent among people living with HIV (PLWH). We leveraged Latent Profile Analysis (LPA) to identify profiles of depressive symptoms among PLWHs. We also investigated differences in psychological factors of interest, demographic characteristics, and HIV-related factors across patients' profiles. METHODS: A cross-sectional study was conducted at one hospital and two designated prison facilities in Hunan province, China. A total sample of 533 PLWHs (320 recruited from the hospital, 213 recruited from prisons) completed the survey. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Family function, resilience, childhood trauma, demographic characteristics, and HIV-related factors were also evaluated. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for depressive symptoms; 2) identify demographic characteristics, and HIV-related, and psychological factors predicting PLWHs' likelihood to express a specific profile. RESULTS: We identified three distinct profiles of depressive symptoms among PLWHs: severe symptoms (11.8%), moderate symptoms (40.5%), and low/no symptoms (47.7%). Moderate/ severe family dysfunction, low resilience, experiencing emotional abuse and neglect were more likely to fall in the "severe symptoms" rather than the "low/no symptoms" profile. In addition, severe family dysfunction, low resilience, and experiencing emotional neglect indicated a higher likelihood of being classified in the "moderate symptoms" profile, compared to the "low/no symptoms" profile. CONCLUSION: Identifying profiles of depressive symptoms among PLWHs using the PHQ-9 items allows for understanding of the distinct paths of development of depressive symptoms and for developing tailored prevention and intervention programs for PLWHs.

Self-efficacy mediates the effect of providing HIV self-testing kits on HIV testing frequency among Chinese men who have sex with men: results from a randomised controlled trial.

BACKGROUND: HIV self-testing (HIVST) could promote HIV tests; however, knowledge about the mechanisms by which providing HIVST kits impacts the uptake of HIV testing is limited. This study aimed to examine how self-efficacy mediates the association between providing HIVST kits and HIV testing frequency. METHODS: In this randomised controlled trial, HIV-negative men who have sex with men (MSM) were recruited in China and randomly assigned 1:1 into intervention and control groups. MSM in the control group could access site-based HIV testing services (SBHT). MSM in the intervention group could access SBHTs plus free HIVST kits. HIV testing self-efficacy, number of SBHTs, number of HIVSTs, and the total number of HIV tests were assessed every 3months for 1year. RESULTS: Data from 216 MSM (intervention group: 110; control group: 106) were included in analysis. Results from Pearson's correlations and point-biserial correlations showed that participants with higher self-efficacy scores underwent a higher number of HIV tests (r =0.241, P <0.001), more HIVSTs (r =0.162, P <0.001), and more SBHTs (r =0.138, P <0.001). Bootstrap tests using PROCESS indicated self-efficacy partially mediated the effect of providing HIVST on the number of HIVSTs (indirect effect: 0.018, 95% bias-corrected confidence interval [BC CI]: 0.003-0.035; direct effect: 0.440, 95% BC CI: 0.366-0.513) and on total HIV tests (indirect effect 0.053 (0.030-0.787); direct effect 0.452 (0.365-0.539)), and completely mediated the effect of providing HIVST on the number of SBHTs (indirect effect 0.035 (0.019-0.056); direct effect 0.012 (-0.059 to 0.083)). CONCLUSIONS: Our findings indicated self-efficacy mediated the effect of HIVST provision on HIV testing frequency, suggesting improving self-efficacy might be an effective way to promote HIV testing among Chinese MSM.

Differences in evidence-based nursing practice competencies of clinical and academic nurses in China and opportunities for complementary collaborations: A cross-sectional study.

AIMS AND OBJECTIVES: To explore the evidence-based nursing practice (EBNP) competencies of clinical and academic nurses and their collaboration needs for supporting EBNP. BACKGROUND: Academic-practice partnerships have strong potential to overcome the key barriers to EBNP. However, there is little known about the collaboration needs of clinical and academic nurses for EBNP. DESIGN: A cross-sectional study. METHODS: We recruited clinical and academic nurses online during November 2021 to January 2022. Using a reliable and validated scale and adapted questionnaires, data were collected relating to demographic information, EBNP-related resources availability, EBNP competencies and EBNP collaboration needs. These data were described using descriptive statistical methods. The t test, χ2 test and Mann-Whitney U test were used to evaluate if the different responses between clinical and academic nurses were statistically significant. This study was reported following the STROBET checklist. RESULTS: Two 240 clinical nurses and 232 academic nurses submitted questionnaires. There was no difference in overall EBNP competence between clinical and academic nurses. However, clinical nurses reported lower levels of competence and stronger intentions to collaborate with academic nurses when searching for, appraising, and synthesising evidence. Academic nurses reported lower levels of competence and stronger intentions to collaborate with clinical nurses for disseminating and implementing evidence. CONCLUSION: Clinical and academic nurses both reported high needs for collaborating to overcome their perceived role limitations. Clinical and academic nurses have different strengths and limitations in EBNP. These role differences and intentions to collaborate for different dimensions of EBNP competence suggest that clinical and academic nursing roles could be complementary to each other, offering opportunities for synergistic collaborations to better support overall EBNP. RELEVANCE TO CLINICAL PRACTICE: Healthcare and academic institutions should promote academic-practice partnerships as opportunities to gain complementary expertise on different dimensions of EBNP, and to improve nurses' competencies and confidence in EBNP overall.

[Research progress of the regulation of orphan nuclear receptors on chronic liver diseases].

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Exploration of adaptation process and experience among the HIV/AIDS patients based on the comprehensive task-based adaptation model. / 基于综合任务模型探索HIV/AIDSæ‚£è€ çš„ç–¾ç— é€‚åº”è¿‡ç¨‹å’Œä½“éªŒ.

OBJECTIVES: Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) confront multiple difficulties during the disease adaptation process. Based on the comprehensive task-based adaptation model, this study aims to explore the process and experience of adapting to living with HIV among HIV/AIDS patients and to provide evidence for promoting the adaptation of this population. METHODS: With the design of the phenomenon study, we purposefully recruited 43 HIV/AIDS patients and conducted semi-structural interviews. The qualitative data was analyzed by Van Manen method. RESULTS: There were 1 307 significant quotes and 6 themes with 14 sub-themes. "The shadow comes along with the sunshine" was proposed to describe the process of adapting to life with HIV. Another 5 themes emerged to represent the tasks as follows: the direction of the mental anchor, the management of physical tasks, social network and support, the occupational dilemma and benefits, and the consideration of the future. CONCLUSIONS: The adapting process possesses both common and personalized characteristics. Future intervention development should address the integrality and interaction of the adaptation tasks, contributing to the positive adaptation outcomes of HIV/AIDS patients.

One-step and highly sensitive quantification of fusion genes with isothermal amplification initiated by a fusion-site anchored stem-loop primer.

As causative oncogenes and drug targets, fusion genes play critical roles in tumorigenesis, development, and treatment and thus are regarded as tumor-specific molecular biomarkers. Specific identification and sensitive quantification of fusion genes are of great significance in cancer diagnosis, classification, and prognosis as well as minimal residual disease (MRD) monitoring. Herein, we proposed a specific and sensitive method for the quantitative detection of fusion transcripts by designing stem-loop primers to directly track fusion junctions of fusion genes and subsequently initiate reverse transcript loop-mediated isothermal amplification (LAMP). Benefitting from the specific and direct mechanism of stem-loop primers and the high amplification efficiency of LAMP, the proposed method can sensitively measure fusion gene transcripts with a detection limit of 100 aM (1 zmol) and achieve a wide linear dynamic range spanning at least six orders of magnitude (100 aM-100 pM). Significantly, the whole fusion transcript assay can be accomplished in one step under isothermal conditions, greatly simplifying the operation and detection processes. Meanwhile, the one-step analysis method in one tube may effectively eliminate false-positive results from product cross-contamination during multiple experimental operations and cover-opening measurements. We have demonstrated that the proposed method is practical and accurate for the quantitation of fusion transcripts in biological samples. Owing to the outstanding features of high sensitivity, excellent specificity, and simple operation, the new strategy may provide a robust and attractive platform for the quantification of fusion genes.

The efficacy and mechanism of positive psychological intervention on well-being for colostomy patients: a randomized controlled trial.

AIMS: The positive psychology intervention (PPI) is an effective therapy designed to motivate individuals' positive quality and power, to help them survive in an adverse situation, and to establish a high-quality personal and social life. This study aims to evaluate the efficacy and mechanism of PPI on the psychological capital, psychological distress, and life satisfaction among colostomy patients. METHODS: Patients (n = 120) with permanent stomas were recruited and randomly assigned into two groups. Patients in the experimental group (n = 60) received standard care and PPI, whereas patients in the control group (n = 60) only received standard care. The psychological capital, psychological distress, and life satisfaction were measured and compared between two groups before the intervention, the immediate post-intervention, and follow-up. RESULTS: All 120 patients completed the study. The hope, optimism, resilience, psychological distress, and life satisfaction score of the experimental group were significantly higher than those of the control group at T1 and T2 (P < 0.05). Self-efficacy score of the experimental group had no significant difference at the two time points after the intervention than the control group (P > 0.05). Changes in hope and resilience which belong to psychological capital mediated the intervention's efficacy on changes in PPI on life satisfaction (ß = 0.265, P = 0.005; ß = 0.686, P = 0.002). CONCLUSIONS: PPI could effectively improve psychological capital, psychological distress, and life satisfaction among patients with stomas. Besides, our findings add novel support that increased hope and resilience are the active ingredients that promote intervention change.