Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2.

Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of nf2a/b, the zebrafish homolog of human NF2. Analysis of nf2a and nf2b expression reveals ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displays lower expression levels. Induction of nf2a/b knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggers the development of a spectrum of tumors, including vestibular schwannomas, spinal schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

Construction and implementation effect of pressure injury nursing linkage platform under the medical consortium model in athletic patients

Purpose: To discover the training effectiveness of community nurses' cognition of pressure injury on the nursing linkage Methods: Guided by KAP (Knowledge, Attitude and Practice) Theory, and under the background of medical consortium in our hospital, we built a pressure injury nursing linkage platform dominated by mobile learning, supplemented by offline guidance and sharing of high-quality resources in the hospital, and trained 66 clinical nurses in 6 community health service centers of the medical consortium The theoretical knowledge, attitude, and clinical care behavior questionnaire of community nurses with pressure injury were surveyed after 18 months of platform operation and measured nurses' satisfaction with the platform and self- Results: The theoretical knowledge, attitude, and clinical nursing behavior of 66 community nurses with pressure The theoretical knowledge, attitude, and clinical nursing behavior of 66 community nurses with pressure injury compared before and after the platform operation, and the difference was statistically significant (P<0.05) ; Satisfaction with the platform was 91% for 5 items; Among the 10 items of self-evaluation of community nurses, the highest percentage of "agree" was to gain new knowledge and Among the 10 items of self-evaluation of community nurses, the highest percentage of "agree" was to gain new knowledge and change philosophy, which was 100%. And 80% of the nurses agreed that they would change their incorrect nursing behaviors after the training. (AU)

Construction and implementation effect of pressure injury nursing linkage platform for improved care of athletic patients

Purpose: To discover the training effectiveness of community nurses' cognition of pressure injury on the nursing linkage. Methods: Guided by KAP (Knowledge, Attitude and Practice) Theory, and under the background of medical consortium in our hospital, we built a pressure injury nursing linkage platform dominated by mobile learning, supplemented by offline guidance and sharing of high-quality resources in the hospital, and trained 66 clinical nurses in 6 community health service centers of the medical consortium The theoretical knowledge, attitude, and clinical care behavior questionnaire of community nurses with pressure injury were surveyed after 18 months of platform operation and measured nurses' satisfaction with the platform and self. Results: The theoretical knowledge, attitude, and clinical nursing behavior of 66 community nurses with pressure The theoretical knowledge, attitude, and clinical nursing behavior of 66 community nurses with pressure injury compared before and after the platform operation, and the difference was statistically significant (P<0.05) ; Satisfaction with the platform was 91% for 5 items; Among the 10 items of self-evaluation of community nurses, the highest percentage of "agree" was to gain new knowledge and Among the 10 items of self-evaluation of community nurses, the highest percentage of "agree" was to gain new knowledge and change philosophy, which was 100%. And 80% of the nurses agreed that they would change their incorrect nursing behaviors after the training. (AU)

Coupling of N7-methyltransferase and 3'-5' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading.

The capping of mRNA and the proofreading play essential roles in SARS-CoV-2 replication and transcription. Here, we present the cryo-EM structure of the SARS-CoV-2 replication-transcription complex (RTC) in a form identified as Cap(0)-RTC, which couples a co-transcriptional capping complex (CCC) composed of nsp12 NiRAN, nsp9, the bifunctional nsp14 possessing an N-terminal exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase), and nsp10 as a cofactor of nsp14. Nsp9 and nsp12 NiRAN recruit nsp10/nsp14 into the Cap(0)-RTC, forming the N7-CCC to yield cap(0) (7MeGpppA) at 5' end of pre-mRNA. A dimeric form of Cap(0)-RTC observed by cryo-EM suggests an in trans backtracking mechanism for nsp14 ExoN to facilitate proofreading of the RNA in concert with polymerase nsp12. These results not only provide a structural basis for understanding co-transcriptional modification of SARS-CoV-2 mRNA but also shed light on how replication fidelity in SARS-CoV-2 is maintained.

Current state and future perspective of cardiovascular medicines derived from natural products.

The contribution of natural products (NPs) to cardiovascular medicine has been extensively documented, and many have been used for centuries. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 40 years, approximately 50% of newly developed cardiovascular drugs were based on NPs, suggesting that NPs provide essential skeletal structures for the discovery of novel medicines. After a period of lower productivity since the 1990s, NPs have recently regained scientific and commercial attention, leveraging the wealth of knowledge provided by multi-omics, combinatorial biosynthesis, synthetic biology, integrative pharmacology, analytical and computational technologies. In addition, as a crucial part of complementary and alternative medicine, Traditional Chinese Medicine has increasingly drawn attention as an important source of NPs for cardiovascular drug discovery. Given their structural diversity and biological activity NPs are one of the most valuable sources of drugs and drug leads. In this review, we briefly described the characteristics and classification of NPs in CVDs. Then, we provide an up to date summary on the therapeutic potential and the underlying mechanisms of action of NPs in CVDs, and the current view and future prospect of developing safer and more effective cardiovascular drugs based on NPs.