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Extracellular vesicles (EVs), including exosomes, are increasingly recognized as potent mediators of intercellular communication due to their capacity to transport a diverse array of bioactive molecules. They assume vital roles in a wide range of physiological and pathological processes and hold significant promise as emerging disease biomarkers, therapeutic agents, and carriers for drug delivery. Exosomes encompass specific groups of membrane proteins, lipids, nucleic acids, cytosolic proteins, and other signaling molecules within their interior. These cargo molecules dictate targeting specificity and functional roles upon reaching recipient cells. Despite our growing understanding of the significance of exosomes in diverse biological processes, the molecular mechanisms governing the selective sorting and packaging of cargo within exosomes have not been fully elucidated. In this review, we summarize current insights into the molecular mechanisms that regulate the sorting of various molecules into exosomes, the resulting biological functions, and potential clinical applications, with a particular emphasis on their relevance in cancer and other diseases. A comprehensive understanding of the loading processes and mechanisms involved in exosome cargo sorting is essential for uncovering the physiological and pathological roles of exosomes, identifying therapeutic targets, and advancing the clinical development of exosome-based therapeutics. Exosome cargo sorting: insights into cellular communication and disease Extracellular vesicles (EVs)—tiny structures produced by cells that are important for cell-to-cell communication—contain various molecules, a process known as cargo sorting. However, how these molecules are selected and packaged into EVs is not fully understood. This research by Lee, Shin, and Chae provides a detailed analysis of our current knowledge of cargo sorting in exosome biogenesis. They reviewed the literature on the types of molecules in exosome cargo, the factors and machinery controlling cargo selection and packaging, and the role of cargo sorting in diseases. They found that understanding exosome cargo sorting is vital for managing diseases and developing exosome-based treatments. This could help design exosomes that can more effectively deliver therapeutic substances to specific cells or tissues, improving the effectiveness and accuracy of these treatments in clinical use. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

ARPC2 is a subunit of the Arp2/3 complex, which is essential for lamellipodia, invadopodia and filopodia, and ARPC2 has been identified as a migrastatic target molecule. To identify ARPC2 inhibitors, we generated an ARPC2 knockout DLD‐1 human colon cancer cell line using the clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) system and explored gene signature‐based strategies, such as a connectivity map (CMap) using the gene expression profiling data of ARPC2 knockout and knockdown cells. From the CMap‐based drug discovery strategy, we identified pimozide (a clinically used antipsychotic drug) as a migrastatic drug and ARPC2 inhibitor. Pimozide inhibited the migration and invasion of various cancer cells. Through drug affinity responsive target stability (DARTS) analysis and cellular thermal shift assay (CETSA), it was confirmed that pimozide directly binds to ARPC2. Pimozide increased the lag phase of Arp2/3 complex‐dependent actin polymerization and inhibited the vinculin‐mediated recruitment of ARPC2 to focal adhesions in cancer cells. To validate the likely binding of pimozide to ARPC2, mutant cells, including ARPC2F225A, ARPC2F247A and ARPC2Y250F cells, were prepared using ARPC2 knockout cells prepared by gene‐editing technology. Pimozide strongly inhibited the migration of mutant cells because the mutated ARPC2 likely has a larger binding pocket than the wild‐type ARPC2. Therefore, pimozide is a potential ARPC2 inhibitor, and ARPC2 is a new molecular target. Taken together, the results of the present study provide new insights into the molecular mechanism and target that are responsible for the antitumor and antimetastatic activity of pimozide. Pimozide is identified as a migrastatic drug and ARPC2 inhibitor from connectivity map‐based drug discovery strategy. Pimozide inhibits migration and invasion in various cancer cell lines, and suppresses metastasis in an in vivo antimetastatic assay. Through drug affinity responsive target stability (DARTS) analysis and cellular thermal shift assay (CETSA), it was confirmed that pimozide directly binds to ARPC2.

This study examined whether the East Sea sandlance is Ammodytes heian at the genomic level. A total of 48 sandlances were analyzed from five regions, “Baengnyeongdo (BA in the Yellow Sea), Tongyeong (TO in the Korea Strait), Gijang (GI in the East Sea), Jumunjin (JU in the East Sea) in Korea, and Wakkanai in Japan (JP in the Okhotsk Sea)”. Regional single nucleotide polymorphism (SNP) filtering resulted in a total of 10,545 SNPs, based on which the FST was calculated as follows: 0.501 between JP and TO, 0.446 between JP and BA, 0.003 between GI and JU, and 0.014 between GI and JP. Structure analysis based on 10,545 SNPs had optimal delta K values when K was 3. Two genotypes were dominant: one occurred at BA and TO and the other at GI, JU, and JP; the remaining one occurred in all regions. The PCA scatterplot based on 10,545 SNPs revealed two clear clusters, the Ammodytes japonicus group from BA and TO, and the Ammodytes heian group from GI, JU, and JP, which roughly corresponded to the phylogenetic analysis based on 55,026 SNPs. Our results indicate that the genetic traits based on SNPs are similar to the mt results, but somewhat inconsistent with the ms results, suggesting that the East Sea (GI and JU) sandlance is Ammodytes heian as hybrids are rare. Their complex relationships can be attributed to the accumulation of neutral polymorphism across the species or biases in spatiotemporal gene flow between lineages during glacial-interglacial cycles.

Background Effective collaboration and communication among health care team members are critical for providing safe medical care. Interprofessional education aims to instruct healthcare students how to learn with, from, and about healthcare professionals from different occupations to encourage effective collaboration to provide safe and high-quality patient care. The purpose of this study is to confirm the effectiveness of Interprofessional education by comparing students’ attitudes toward interprofessional learning before and after simulation-based interprofessional education, the perception of teamwork and collaboration between physicians and nurses, and the self-reported competency differences among students in interprofessional practice. Methods The survey responses from 37 5th-year medical students and 38 4th-year nursing students who participated in an interprofessional education program were analyzed. The Attitude Towards Teamwork in Training Undergoing Designed Educational Simulation scale, the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration, and the Interprofessional Education Collaborative competency scale were used for this study. The demographic distribution of the study participants was obtained, and the perception differences before and after participation in interprofessional education between medical and nursing students were analyzed. Results After interprofessional education, student awareness of interprofessional learning and self-competency in interprofessional practice improved. Total scores for the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration did not change significantly among medical students but increased significantly among nursing students. Additionally, there was no significant change in the perception of the role of other professions among either medical or nursing students. Conclusions We observed an effect of interprofessional education on cultivating self-confidence and recognizing the importance of interprofessional collaboration between medical professions. It can be inferred that exposure to collaboration situations through Interprofessional education leads to a positive perception of interprofessional learning. However, even after their interprofessional education experience, existing perceptions of the role of other professional groups in the collaboration situation did not change, which shows the limitations of a one-time short-term program. This suggests that efforts should be made to ensure continuous exposure to social interaction experiences with other professions.

The association between body size, weight change and depression has not been systematically summarised, especially for individuals who are underweight. To conduct a systematic review and a meta-analysis to examine the association between indices of body size, weight change and depression. A total of 183 studies were selected. Fully adjusted hazard ratios (HRs) or odds ratios (ORs) were extracted. A total of 76 studies contributed to data synthesis with a random-effect model, and subgroup analyses were conducted to evaluate the effect of potential moderators. In cohort studies, underweight at baseline increased the risk of subsequent depression (OR = 1.16, 95% CI 1.08-1.24). Overweight (BMI 25-29.9 kg/m ) showed no statistically significant relationship with depression overall; however, the subgroup analyses found different results according to gender (men: OR = 0.84, 95% CI 0.72-0.97, women: OR = 1.16, 95% CI 1.07-1.25). In cross-sectional designs, obesity with BMI >40 kg/m showed a greater pooled odds ratio than obesity with BMI >30 kg/m Both underweight and obesity increase the risk of depression. The association between overweight and depression differs by gender.

Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia’s influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.

Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway is a novel therapeutic strategy to treat human cancers with constitutively active STAT3. During the screening of natural products to find STAT3 inhibitors, we identified 2′‐hydroxycinnamaldehyde (HCA) as a STAT3 inhibitor, which was isolated from the stem bark of Cinnamomum cassia. In this study, we found that HCA inhibited constitutive and inducible STAT3 activation in STAT3‐activated DU145 prostate cancer cells. HCA selectively inhibited the STAT3 activity by direct binding to STAT3, which was confirmed by biochemical methods, including a pull‐down assay with biotin‐conjugated HCA, a drug affinity responsive target stability (DARTS) experiment and a cellular thermal shift assay (CETSA). HCA inhibited STAT3 phosphorylation at the tyrosine 705 residue, dimer formation, and nuclear translocation in DU145 cells, which led to a downregulation of STAT3 target genes. The downregulation of cell cycle progression and antiapoptosis‐related gene expression by HCA induced the accumulation of cells in the G0/G1 phase of the cell cycle and then induced apoptosis. We also found that reactive oxygen species (ROS) were involved in the HCA‐induced inhibition of STAT3 activation and cell proliferation because the suppressed p‐STAT3 level was rescued by glutathione or N‐acetyl‐L‐cysteine treatment, which are general ROS inhibitors. These results suggest that HCA could be a potent anticancer agent targeting STAT3‐activated tumor cells. 2′‐Hydroxycinnamaldehyde inhibits STAT3 activation and cell proliferation through STAT3‐dependent and ROS‐dependent pathways. 2′‐Hydroxycinnamaldehyde is highly effective in prostate cancer cells with activated‐STAT3 and also suppressed DU‐145 tumor growth in an animal model. 2′‐Hydroxycinnamaldehyde has low toxicity against normal human cells and selective toxicity toward cancer cells.

PHRF1 is an E3 ligase that promotes TGF-β signaling by ubiquitinating a homeodomain repressor TG-interacting factor (TGIF). The suppression of PHRF1 activity by PML-RARα facilitates the progression of acute promyelocytic leukemia (APL). PHRF1 also contributes to non-homologous end-joining in response to DNA damage by linking H3K36me3 and NBS1 with DNA repair machinery. However, its role in class switch recombination (CSR) is not well understood. In this study, we report the importance of PHRF1 in IgA switching in CH12F3-2A cells and CD19-Cre mice. Our studies revealed that Crispr-Cas9 mediated PHRF1 knockout and shRNA-silenced CH12F3-2A cells reduced IgA production, as well as decreased the amounts of PARP1, NELF-A, and NELF-D. The introduction of PARP1 could partially restore IgA production in PHRF1 knockout cells. Intriguingly, IgA, as well as IgG1, IgG2a, and IgG3, switchings were not significantly decreased in PHRF1 deficient splenic B lymphocytes isolated from CD19-Cre mice. The levels of PARP1 and NELF-D were not decreased in PHRF1-depleted primary splenic B cells. Overall, our findings suggest that PHRF1 may modulate IgA switching in CH12F3-2A cells.

Limnichthys koreanus sp. nov. is described on the basis of the holotype and 11 paratypes from subtidal waters of Seogwipo, Jeju Island, Korea. The new species had previously been regarded as the Northern Hemisphere population of the anti-equatorial L. fasciatus , but molecular analyses of mitochondrial COI and 16S genes recovers deep genetic divergences of 9.4% and 15.0% between the new species and topotypical specimens of L. fasciatus . Limnichthys koreanus sp. nov. is distinguished from all other species of Limnichthys based on the following combination of colouration and morphological characteristics: 38-40 vertebrae; 0–6 dorsal saddles joining mid-lateral stripe; small infraorbital sensory pores; a single median interorbital pore; and well-developed vomerine teeth. Summary characters for comparative congeneric species are provided.

One-carbon (C1) chemicals are potential building blocks for cheap and sustainable re-sources such as methane, methanol, formaldehyde, formate, carbon monoxide, and more. These resources have the potential to be made into raw materials for various products used in our daily life or precursors for pharmaceuticals through biological and chemical processes. Among the soluble C1 substrates, methanol is regarded as a biorenewable platform feedstock because nearly all bioresources can be converted into methanol through syngas. Synthetic methylotrophy can be exploited to produce fuels and chemicals using methanol as a feedstock that integrates natural or artificial methanol assimilation pathways in platform microorganisms. In the methanol utilization in methylotrophy, methanol dehydrogenase (Mdh) is a primary enzyme that converts methanol to formaldehyde. The discovery of new Mdhs and engineering of present Mdhs have been attempted to develop synthetic methylotrophic bacteria. In this review, we describe Mdhs, including in terms of their enzyme properties and engineering for desired activity. In addition, we specifically focus on the application of various Mdhs for synthetic methylotrophy.