Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis.

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

mRNA therapeutics: New vaccination and beyond.

The idea of mRNA therapy had been conceived for decades before it came into reality during the Covid-19 pandemic. The mRNA vaccine emerges as a powerful and general tool against new viral infections, largely due to its versatility and rapid development. In addition to prophylactic vaccines, mRNA technology also offers great promise for new applications as a versatile drug modality. However, realizing the conceptual potential faces considerable challenges, such as minimal immune stimulation, high and long-term expression, and efficient delivery to target cells and tissues. Here we review the applications of mRNA-based therapeutics, with emphasis on the innovative design and future challenges/solutions. In addition, we also discuss the next generation of mRNA therapy, including circular mRNA and self-amplifying RNAs. We aim to provide a conceptual overview and outlook on mRNA therapeutics beyond prophylactic vaccines.

A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation.

Thousands of proteins undergo arginine methylation, a widespread post-translational modification catalyzed by several protein arginine methyltransferases (PRMTs). However, global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each PRMT. Here, we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and translation. We demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing proteins. Different PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation motifs. Importantly, RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation regions. Moreover, inhibition of PRMTs globally alternates alternative splicing (AS) and suppresses translation. In particular, ribosomal proteins are extensively modified with methylarginine, and mutations in their methylation sites suppress ribosome assembly, translation, and eventually cell growth. Collectively, our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation.

Developing Student Evidence-Based Practice Questionnaire (S-EBPQ) for undergraduate nursing students: Reliability and validity of a Chinese adaptation.

RATIONALE, AIMS, AND OBJECTIVES: The assessment of evaluating undergraduate nursing students' evidence-based practice engagement is an important issue, yet few tools have been developed specifically in Mainland China. The purpose of this study was to adapt the Student Evidence-based Practice Questionnaire (S-EBPQ) to Mainland China's cultural context and to evaluate the psychometric properties of the newly adapted Chinese S-EBPQ. METHODS: Cross-cultural adaptation, including translation of the original S-EBPQ into Mandarin Chinese language, was performed according to published guidelines. A pilot study was conducted in Mainland China with 25 Chinese undergraduate nursing students. A subsequent validation study was conducted with 400 undergraduate nursing students from Mainland China. Construct validity was assessed by exploratory factor analysis (n = 190) and confirmatory factor analysis (n = 210). Reliability was determined using internal consistency and test-retest reliability. RESULTS: The split-half coefficient for the overall Chinese S-EBPQ was 0.858. A content validity index of 0.986 was achieved. Principal component analysis resulted in a 4-factor structure explaining 68.285% of the total variance. The comparative fit index was 0.927, and the root mean squared error of approximation was 0.072 from the confirmatory factor analysis. Known-group validity was supported by the significant differences according to various characteristics of participants. Internal consistency was high for the Chinese S-EBPQ reaching a Cronbach α value of 0.934. Test-retest reliability was 0.821. CONCLUSION: The newly cross-culturally adapted S-EBPQ possesses adequate validity, test-retest reliability, and internal consistency and therefore may be utilized in nursing education to assess EBP of undergraduate nursing students in Mainland China.

Psychometric Testing of the Evidence-Based Practice Nursing Leadership Scale and the Work Environment Scale After Cross-Cultural Adaptation in Mainland China.

Implementation and sustainability of the evidence-based practice (EBP) approach within systems of health-care delivery require leadership and organizational support, yet few instruments have been developed specifically in Mainland China. The purpose of this study was to adapt the EBP Nursing Leadership Scale and the EBP Work Environment Scale to Mainland China's cultural context and to evaluate the psychometric properties of the newly adapted Chinese version. A pilot study was conducted in Mainland China with 25 clinical nurses. A subsequent validation study was conducted with 419 nurses from Mainland China. A content validity index of .985 and .982 was achieved. The split-half coefficient was .890 for the EBP Nursing Leadership Scale and .892 for the EBP Work Environment Scale. Test-retest reliability was .871 and .855, respectively. Principal component analysis resulted in a one-factor structure explaining 62.069% of the total variance for the EBP Nursing Leadership Scale and 62.242% of the total variance for the EBP Work Environment Scale. Both of the newly cross-culturally adapted scales possess adequate internal consistency and test-retest reliability and validity and therefore may be utilized in health-care environments to assess leadership and organizational support for EBP in Mainland China.

The Development of Machine Learning Methods in Cell-Penetrating Peptides Identification: A Brief Review.

BACKGROUND: Cell-penetrating Peptides (CPPs) are important short peptides that facilitate cellular intake or uptake of various molecules. CPPs can transport drug molecules through the plasma membrane and send these molecules to different cellular organelles. Thus, CPP identification and related mechanisms have been extensively explored. In order to reveal the penetration mechanisms of a large number of CPPs, it is necessary to develop convenient and fast methods for CPPs identification. METHODS: Biochemical experiments can provide precise details for accurately identifying CPP, but these methods are expensive and laborious. To overcome these disadvantages, several computational methods have been developed to identify CPPs. We have performed review on the development of machine learning methods in CPP identification. This review provides an insight into CPP identification. RESULTS: We summarized the machine learning-based CPP identification methods and compared the construction strategies of 11 different computational methods. Furthermore, we pointed out the limitations and difficulties in predicting CPPs. CONCLUSION: In this review, the last studies on CPP identification using machine learning method were reported. We also discussed the future development direction of CPP recognition with computational methods.

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells.

The processing of most eukaryotic RNAs is mediated by RNA Binding Proteins (RBPs) with modular configurations, including an RNA recognition module, which specifically binds the pre-mRNA target and an effector domain. Previously, we have taken advantage of the unique RNA binding mode of the PUF domain in human Pumilio 1 to generate a programmable RNA binding scaffold, which was used to engineer various artificial RBPs to manipulate RNA metabolism. Here, a detailed protocol is described to construct Engineered Splicing Factors (ESFs) that are specifically designed to modulate the alternative splicing of target genes. The protocol includes how to design and construct a customized PUF scaffold for a specific RNA target, how to construct an ESF expression plasmid by fusing a designer PUF domain and an effector domain, and how to use ESFs to manipulate the splicing of target genes. In the representative results of this method, we have also described the common assays of ESF activities using splicing reporters, the application of ESF in cultured human cells, and the subsequent effect of splicing changes. By following the detailed protocols in this report, it is possible to design and generate ESFs for the regulation of different types of Alternative Splicing (AS), providing a new strategy to study splicing regulation and the function of different splicing isoforms. Moreover, by fusing different functional domains with a designed PUF domain, researchers can engineer artificial factors that target specific RNAs to manipulate various steps of RNA processing.

Pro54DB: a database for experimentally verified sigma-54 promoters.

Summary: In prokaryotes, the σ54 promoters are unique regulatory elements and have attracted much attention because they are in charge of the transcription of carbon and nitrogen-related genes and participate in numerous ancillary processes and environmental responses. All findings on σ54 promoters are favorable for a better understanding of their regulatory mechanisms in gene transcription and an accurate discovery of genes missed by the wet experimental evidences. In order to provide an up-to-date, interactive and extensible database for σ54 promoter, a free and easy accessed database called Pro54DB (σ54 promoter database) was built to collect information of σ54 promoter. In the current version, it has stored 210 experimental-confirmed σ54 promoters with 297 regulated genes in 43 species manually extracted from 133 publications, which is helpful for researchers in fields of bioinformatics and molecular biology. Availability and Implementation: Pro54DB is freely available on the web at http://lin.uestc.edu.cn/database/pro54db with all major browsers supported. Contacts: greatchen@ncst.edu.cn or hlin@uestc.edu.cn

Prediction of cell-penetrating peptides with feature selection techniques.

Cell-penetrating peptides are a group of peptides which can transport different types of cargo molecules such as drugs across plasma membrane and have been applied in the treatment of various diseases. Thus, the accurate prediction of cell-penetrating peptides with bioinformatics methods will accelerate the development of drug delivery systems. The study aims to develop a powerful model to accurately identify cell-penetrating peptides. At first, the peptides were translated into a set of vectors with the same dimension by using dipeptide compositions. Secondly, the Analysis of Variance-based technique was used to reduce the dimension of the vector and explore the optimized features. Finally, the support vector machine was utilized to discriminate cell-penetrating peptides from non-cell-penetrating peptides. The five-fold cross-validated results showed that our proposed method could achieve an overall prediction accuracy of 83.6%. Based on the proposed model, we constructed a free webserver called C2Pred (http://lin.uestc.edu.cn/server/C2Pred).

Post partum depression and the psychosocial predictors in first-time fathers from northwestern China.

BACKGROUND: there is growing evidence that fathers also experience post partum depression (PPD). However, paternal PPD has been less studied than maternal PPD. Very few studies have investigated PPD in first-time fathers from northwestern China. OBJECTIVE: the purpose of this study was to investigate the occurrence and predictors of depressive symptoms in first-time fathers from northwestern China. METHODS: a longitudinal study was conducted involving 180 couples who were assessed at three time periods: 3 days, 2 weeks and 6 weeks after childbirth. Self-reported questionnaires including Edinburgh Postnatal Depression Scale (EPDS), Parenting Sense of Competence Scale (PSOC), and Kansas Marital Satisfaction Scale (KMSS) were administered to all participants during each time period. FINDINGS: after childbirth 35 (21.1%) of the fathers at 3 days, 32 (20.4%) at 2 weeks and 20 (13.6%) at 6 weeks, indicated that they suffered from PPD. Paternal parental sense of competence, paternal marital satisfaction, and maternal depressive symptoms were among the main predictors for paternal PPD. CONCLUSION: the study results suggest that paternal PPD is a significant public health concern. Health professionals should focus attention on the psychological health among new fathers during the postpartum period; and, the psychosocial predictors should be considered and incorporated into clinical assessment and intervention of paternal PPD.

Cross-cultural adaptation and validation of the osteoporosis assessment questionnaire short version (OPAQ-SV) for Chinese osteoporotic fracture females.

The Osteoporosis Assessment Questionnaire Short Version (OPAQ-SV) was cross-culturally adapted to measure health-related quality of life in Chinese osteoporotic fracture females and then validated in China for its psychometric properties. Cross-cultural adaptation, including translation of the original OPAQ-SV into Mandarin Chinese language, was performed according to published guidelines. Validation of the newly cross-culturally adapted OPAQ-SV was conducted by sampling 234 Chinese osteoporotic fracture females and also a control group of 235 Chinese osteoporotic females without fractures, producing robust content, construct, and discriminant validation results. Major categories of reliability were also met: the Cronbach alpha coefficient was 0.975, indicating good internal consistency; the test-retest reliability was 0.80; and principal component analysis resulted in a 6-factor structure explaining 75.847 % of the total variance. Further, the Comparative Fit Index result was 0.922 following the modified model confirmatory factor analysis, and the chi-squared test was 1.98. The root mean squared error of approximation was 0.078. Moreover, significant differences were revealed between females with fractures and those without fractures across all domains (p < 0.001). Overall, the newly cross-culturally adapted OPAQ-SV appears to possess adequate validity and reliability and may be utilized in clinical trials to assess the health-related quality of life in Chinese osteoporotic fracture females.

Primary adenomatoid tumor of the testis: report of a case and review of literature.

Adenomatoid tumor (AT) is an extremely rare benign tumor in the testis of infants. A case of 14-month-old boy with testicular adenomatoid tumor was reported in this study. On physical examination, a smooth solid nodule sized 8 mm could be palpated with little tenderness on the head of the right testis. It could be clearly revealed by B ultrasonic scanning and computerized tomography. The patient underwent right radical orchiectomy. In postoperative histopathological study, the tumor was characterized by diffuse sheets of epithelioid cell and desmo-stroma structures. There was positive immunohistochemical staining of mesothelioma-associated antigens. The tumor should be differentiated from the tumor of the male genital tract including benign and malignant tumors of both epithelial and stromal origin. And we followed the case and no nodule was found in his scrotum by physical examination and scrotal ultrasonography after 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months. These findings have important implications that the histogenesis of adenomatoid tumor of the testis is unclear yet. The diagnosis depends on pathologic studies, and should be differentiated from paratesticular malignant mesothelioma and sclerosed lipogranuloma. Radical surgery is the common choice, and as a result of getting a good prognosis.