Causal relationship between gut microbiota and pathological scars: a two-sample Mendelian randomization study.

Background: Pathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process. Methods: Utilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses. Results: By employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above. Conclusion: Overall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.

The causal relationship and potential mediators between plasma lipids and atopic dermatitis: a bidirectional two-sample, two-step mendelian randomization.

BACKGROUND: Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. METHODS: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. RESULTS: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. CONCLUSION: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.

Large Language Models for Social Determinants of Health Information Extraction from Clinical Notes - A Generalizable Approach across Institutions.

The consistent and persuasive evidence illustrating the influence of social determinants on health has prompted a growing realization throughout the health care sector that enhancing health and health equity will likely depend, at least to some extent, on addressing detrimental social determinants. However, detailed social determinants of health (SDoH) information is often buried within clinical narrative text in electronic health records (EHRs), necessitating natural language processing (NLP) methods to automatically extract these details. Most current NLP efforts for SDoH extraction have been limited, investigating on limited types of SDoH elements, deriving data from a single institution, focusing on specific patient cohorts or note types, with reduced focus on generalizability. This study aims to address these issues by creating cross-institutional corpora spanning different note types and healthcare systems, and developing and evaluating the generalizability of classification models, including novel large language models (LLMs), for detecting SDoH factors from diverse types of notes from four institutions: Harris County Psychiatric Center, University of Texas Physician Practice, Beth Israel Deaconess Medical Center, and Mayo Clinic. Four corpora of deidentified clinical notes were annotated with 21 SDoH factors at two levels: level 1 with SDoH factor types only and level 2 with SDoH factors along with associated values. Three traditional classification algorithms (XGBoost, TextCNN, Sentence BERT) and an instruction tuned LLM-based approach (LLaMA) were developed to identify multiple SDoH factors. Substantial variation was noted in SDoH documentation practices and label distributions based on patient cohorts, note types, and hospitals. The LLM achieved top performance with micro-averaged F1 scores over 0.9 on level 1 annotated corpora and an F1 over 0.84 on level 2 annotated corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. To foster collaboration, access to partial annotated corpora and models trained by merging all annotated datasets will be made available on the PhysioNet repository.

Comparative study on the magnetic properties of Fe-substituted Co2Sn1-xFexO4 spinel oxides and its exchange bias effect.

A series of Fe-substituted Co2Sn1-xFexO4 (0 ≤ x ≤ 0.4) inverse spinel's oxides was synthesized using the solid-state reaction method. X-ray analysis reveals a single-phase cubic structure with the space group Fd3m. The transition temperature is shown to increase with a higher Fe concentration in the Co2Sn1-xFexO4 spinel oxide. The ac susceptibility at different frequencies also confirms a spin-glassy state at lower temperatures. The sample with Fe substitution (x = 0.2) exhibits a significant exchange bias effect when subjected to a constant temperature of ~10 K. The susceptibility at high temperatures, as calculated using Curie-Wise fitting, suggests that the system undergoes a shift from antiferromagnetic exchange (x < 0.2) to ferromagnetic exchange (x > 0.2).

Bibliometric analysis and visualization of quorum sensing research over the last two decade.

Background: Quorum sensing (QS) research stands as a pivotal and multifaceted domain within microbiology, holding profound implications across various scientific disciplines. This bibliometric analysis seeks to offer an extensive overview of QS research, covering the period from 2004 to 2023. It aims to elucidate the hotspots, trends, and the evolving dynamics within this research domain. Methods: We conducted an exhaustive review of the literature, employing meticulous data curation from the Science Citation Index Extension (SCI-E) within the Web of Science (WOS) database. Subsequently, our survey delves into evolving publication trends, the constellation of influential authors and institutions, key journals shaping the discourse, global collaborative networks, and thematic hotspots that define the QS research field. Results: The findings demonstrate a consistent and growing interest in QS research throughout the years, encompassing a substantial dataset of 4,849 analyzed articles. Journals such as Frontiers in Microbiology have emerged as significant contributor to the QS literature, highlighting the increasing recognition of QS's importance across various research fields. Influential research in the realm of QS often centers on microbial communication, biofilm formation, and the development of QS inhibitors. Notably, leading countries engaged in QS research include the United States, China, and India. Moreover, the analysis identifies research focal points spanning diverse domains, including pharmacological properties, genetics and metabolic pathways, as well as physiological and signal transduction mechanisms, reaffirming the multidisciplinary character of QS research. Conclusion: This bibliometric exploration provides a panoramic overview of the current state of QS research. The data portrays a consistent trend of expansion and advancement within this domain, signaling numerous prospects for forthcoming research and development. Scholars and stakeholders engaged in the QS field can harness these findings to navigate the evolving terrain with precision and speed, thereby enhancing our comprehension and utilization of QS in various scientific and clinical domains.

Measuring General Health Literacy in Chinese adults: validation of the HLS19-Q12 instrument.

BACKGROUND: Health literacy measurement lays a solid foundation to identify associations with health outcomes and monitor population health literacy levels over time. In mainland China, most existing health literacy instruments are either knowledge-based or practice-based, making health literacy results incomparable between China and other countries. This study aimed to examine the reliability and validity of the 12-item Health Literacy Population Survey (HLS19-Q12) in a general population of Chinese adults. METHODS: A cross-sectional study was conducted to recruit primary carers of students from 11 schools in Zhengzhou, Henan Province, using convenience cluster sampling. Participants completed an online self-administered survey that collected information on key sociodemographics, health literacy (HLS19-Q12 and a comparison tool: Health Literacy Questionnaire (HLQ)), and health-related outcomes. Using the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist as a guideline, we tested internal consistency, test-retest reliability, content validity, structural validity, concurrent predictive validity, and convergent validity of the HLS19-Q12. RESULTS: Overall, 14,184 participants completed the full survey. The HLS19-Q12 showed excellent internal consistency (Cronbach's α = 0.93), moderate test-retest reliability (intra-class correlation coefficient = 0.54), satisfactory content validity (based on the 12-matrix health literacy model), and strong structural validity (comparative fit index = 0.94, Tucker and Lewis's index of fit = 0.93, root mean square error of approximation = 0.095). Concurrent predictive validity results showed health literacy was associated with both health determinants and health-related outcomes. The HLS19-Q12 had weak to strong correlations (coefficients = 0.24 to 0.42) with the nine scales of the HLQ. Respondents had an average score of 81.6 (± 23.0) when using the HLS19-Q12, with 35.0% and 7.5% having problematic and inadequate levels of health literacy, respectively. CONCLUSIONS: The HLS19-Q12 is a reliable and valid instrument to measure health literacy in our sample. Further validation is needed with a more nationally representative sample of Chinese adults. The HLS19-Q12 could be used as a comprehensive, skills-based, and easy-to-administer health literacy assessment tool integrated into population surveys and intervention evaluations.

microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation.

MicroRNAs (miRNAs) play a significant role in axon regeneration following spinal cord injury. However, the functions of numerous miRNAs in axon regeneration within the central nervous system (CNS) remain largely unexplored. Here, we elucidate the positive role of miR-2184 in axon regeneration within zebrafish Mauthner cells (M-cells). The upregulation of miR-2184 in the single M-cells facilitates axon regeneration, while the specific sponge-induced silencing of miR-2184 leads to impeded axon regeneration. We show that syt3, a downstream target of miR-2184, negatively regulates axon regeneration, and the regeneration suppression by syt3 depends on its binding to Ca2+. Furthermore, pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration. Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3, providing valuable insights into potential therapeutic strategies.

Rab11 promotes single Mauthner cell axon regeneration in vivo through axon guidance molecule Ntng2b.

Effective axon regeneration within the central nervous system (CNS) is pivotal for achieving functional recovery following spinal cord injury (SCI). Numerous extrinsic and intrinsic factors exert influences on the axon regeneration. While prior studies have demonstrated crucial involvement of specific members the Rab protein family in axon regeneration in the peripheral nervous system (PNS), the precise function of Rab11 in CNS axon regeneration in vivo remains elusive. Thus, our study aimed to elucidate the impact of Rab11 on the axon regeneration of Mauthner cells (M-cells) in zebrafish larvae. Our findings demonstrated that overexpression of Rab11bb via single-cell electroporation significantly promoted axon regeneration in individual M-cells. Conversely, knockdown of Rab11bb inhibited the axon regeneration of M-cells. RNA-seq analysis revealed an upregulation of ntng2b following Rab11bb overexpression. As we hypothesized, overexpression of Ntng2b markedly enhanced axon regeneration, while Ntng2b knockdown in the context of Rab11bb pro-regeneration substantially hindered axon regrowth. In conclusion, our study demonstrated that Rab11 promotes axon regeneration of single M-cell in the CNS through the Rab11/axon guidance/Ntng2b pathway.

MicroRNA-9 promotes axon regeneration of mauthner-cell in zebrafish via her6/ calcium activity pathway.

MicroRNA (miRNA), functioning as a post-transcriptional regulatory element, plays a significant role in numerous regulatory mechanisms and serves as a crucial intrinsic factor influencing axon regeneration. Prior investigations have elucidated the involvement of miRNA-9 in various processes, however, its specific contribution to axon regeneration in the central nervous system (CNS) remains uncertain. Hence, the zebrafish Mauthner axon regeneration model was employed to manipulate the expression of miRNA-9 in single cells, revealing that upregulation of miRNA-9 facilitated axon regeneration. Additionally, her6, a downstream target gene of miRNA-9, was identified as a novel gene associated with axon regeneration. Suppression of her6 resulted in enhanced Mauthner axon regeneration, as evidenced by the significantly improved regenerative capacity observed in her6 knockout zebrafish. In addition, modulation of her6 expression affects intracellular calcium levels in neurons and promoting her6 expression leads to a decrease in calcium levels in vivo using the new NEMOf calcium indicator. Moreover, the administration of the neural activity activator, pentylenetetrazol (PTZ) partially compensated for the inhibitory effect of her6 overexpression on the calcium level and promoted axon regeneration. Taken together, our study revealed a role for miRNA-9 in the process of axon regeneration in the CNS, which improved intracellular calcium activity and promoted axon regeneration by inhibiting the expression of downstream target gene her6. In our study, miRNA-9 emerged as a novel and intriguing target in the intricate regulation of axon regeneration and offered compelling evidence for the intricate relationship between calcium activity and the facilitation of axon regeneration.

Research hotspot and trend of chronic wounds: A bibliometric analysis from 2013 to 2022.

Chronic wounds have been confirmed as a vital health problem facing people in the global population aging process. While significant progress has been achieved in the study of chronic wounds, the treatment effect should be further improved. The number of publications regarding chronic wounds has been rising rapidly. In this study, bibliometric analysis was conducted to explore the hotspots and trends in the research on chronic wounds. All relevant studies on chronic wounds between 2013 and 2022 were collected from the PubMed database of the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI). The data were processed and visualised using a series of software. On that basis, more insights can be gained into hotspots and trends of this research field. Wound Repair and Regeneration has the highest academic achievement in the field of chronic wound research. The United States has been confirmed as the most productive country, and the University of California System ranks high among other institutions. Augustin, M. is the author of the most published study, and Frykberg, RG et al. published the most cited study. Furthermore, the hotspots of wound research over the last decade were identified (e.g., bandages, infection and biofilms, pathophysiology and therapy). This study will help researchers gain insights into chronic wound research's hotspots and trends accurately and quickly. Moreover, the exploration of bacterial biofilm and the pathophysiological mechanism of the chronic wound will lay a solid foundation and clear direction for treating chronic wounds.

Bibliometric analysis and visualization of transdermal drug delivery research in the last decade: global research trends and hotspots.

Background: Transdermal delivery has become a crucial field in pharmaceutical research. There has been a proliferation of innovative methods for transdermal drug delivery. In recent years, the number of publications regarding transdermal drug delivery has been rising rapidly. To investigate the current research trends and hotspots in transdermal drug delivery, a comprehensive bibliometric analysis was performed. Methods: An extensive literature review was conducted to gather information on transdermal drug delivery that had been published between 2003 and 2022. The articles were obtained from the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI) databases. Subsequently, the collected data underwent analysis and visualization using a variety of software tools. This approach enables a deeper exploration of the hotspots and emerging trends within this particular research domain. Results: The results showed that the number of articles published on transdermal delivery has increased steadily over the years, with a total of 2,555 articles being analyzed. The most frequently cited articles were related to the optimization of drug delivery and the use of nanotechnology in transdermal drug delivery. The most active countries in the field of transdermal delivery research were the China, United States, and India. Furthermore, the hotspots over the past 2 decades were identified (e.g., drug therapy, drug delivery, and pharmaceutical preparations and drug design). The shift in research focus reflects an increasing emphasis on drug delivery and control release, rather than simply absorption and penetration, and suggests a growing interest in engineering approaches to transdermal drug delivery. Conclusion: This study provided a comprehensive overview of transdermal delivery research. The research indicated that transdermal delivery would be a rapidly evolving field with many opportunities for future research and development. Moreover, this bibliometric analysis will help researchers gain insights into transdermal drug delivery research's hotspots and trends accurately and quickly.

Effects of supplementation of cryopreservation media with cysteine on the post-thaw quality and fertility of brown-marbled grouper (Epinephelus fuscoguttatus) spermatozoa.

The cryopreservation process is associated with the generation of excessive reactive oxygen species, which causes a series of cellular damage to spermatozoa. The objective of the current study was to investigate the effect of different concentrations of cysteine on post-thaw sperm quality of brown-marbled grouper sperm. Semen samples were frozen with cysteine supplemented at 0.5, 1, 2, 5, 10 mM and the control group (no additive). After thawing, sperm quality parameters were analyzed. In comparison to the control, cysteine treatment groups yielded relatively higher sperm total motility, progressive motility, and curvilinear velocity. Different concentrations of cysteine had no effect on average path velocity, straight linear velocity and viability (P > 0.05), while an increase in the concentration of cysteine resulted in a significant improvement in the mitochondrial membrane potential, SOD activity, and ATP content (P < 0.05). As for lipid peroxidation, the extent of which in cysteine treated spermatozoa was less than the control, although the differences were not statistically significant (P > 0.05). In terms of fertilizing capacity, a greater hatching rate (91.7 ± 1.2%) was obtained in thawed sperm treated with 2 mM cysteine, compared to the control (84.3 ± 4.2%; P < 0.05). Overall, it is concluded that the addition of cysteine is helpful in maintaining the function of frozen-thawed brown-marbled grouper sperm, which can be recommended as an effective antioxidant to improve the semen cryopreservation efficiency.

Logistics hub location for high-speed rail freight transport with road-rail intermodal transport network.

In this paper, we propose a new freight mode to describe how the designed HSR freight train serve for express delivery. We introduce the functions of the hubs and design the hybrid hub-and-spoke network of road-rail intermodal transportation from the perspective of planners, which features as single allocation rule and configures varying levels of hubs. The problem is accurately described by a mixed integer programming model with the objective to minimize total construction cost and total operation cost. We develop a hybrid heuristic algorithm based on a greedy strategy to obtain the levels of hubs, customer allocation and cargo routing. Taking the example of HSR freight network consisting of 50 cities in China, numerical experiments are conducted on the basis of forecasting data from the real-life express market to obtain the hub location schemes. The validity of the model and the performance of the algorithm are verified.

The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis.

Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses.

A Fluorescent Probe Based on the Hydrazone Schiff Base for the Detection of Zn2+ and its Application on Test Strips.

A novel fluorescent probe SHK for Zn2+ detection was designed based on the hydrazone Schiff base, successfully synthesized by Suzuki coupling and condensation reactions. The probe SHK in DMSO/H2O showed extremely weak fluorescence. However, the solution exhibited an intensive yellow-green emission with the introduction of Zn2+. In contrast, negligible fluorescence change was observed when other metal ions were added, suggesting a high selectivity of SHK for Zn2+ detection. The Job's Plot analysis revealed that a 1:1 stoichiometric adduct SHK-Zn2+ formed during the Zn2+ sensing. The binding constant of the complex was determined to be 184 M- 1, and the detection limit for Zn2+ was calculated to be 112 µM. Moreover, the probe SHK achieved selective fluorescence sensing for Zn2+ on test strips, which guaranteed its practical application prospect.

Circularly polarized luminescence of pinene-modified tetradentate platinum(II) enantiomers containing fused 5/6/6 metallocycles.

In this study, a couple of tetradentate Pt(II) enantiomers ((-)-1 and (+)-1) and a couple of tetradentate Pt(IV) enantiomers ((-)-2 and (+)-2) containing fused 5/6/6 metallocycles have been synthesized by controlling reaction conditions. Two valence forms could transform into each other through mild chemical oxidants and reductants. Single-crystal X-ray diffraction confirms the structures of (-)-1 and (-)-2. The coordination sphere of the Pt(II) cation in (-)-1 displays a distorted square-planar geometry and a platinum centroid helix chirality. In contrast, the structure of (-)-2 reveals a distorted octahedral geometry. The solution and the solid of (-)-1 are highly luminescent. Complex (-)-1 shows a prominent aggregation-induced emission enhancement (AIEE) behavior in DMSO/water solution with emission quantum yield (Φ em) up to 73.2%. Furthermore, highly phosphorescent Pt(II) enantiomers exhibit significant circularly polarized luminescence (CPL) with a dissymmetry factor (g lum) of order 10-3 in CH2Cl2 solutions at room temperature. Symmetrically appreciable CPL signals are observed for the enantiomers (-)-1 and (+)-1.

Research hotspot and trend of microneedles in biomedical field: A bibliometric analysis from 2011 to 2020.

BACKGROUND: Microneedles composed of arrays of micro-sized needles assembled on a patch, has attracted increasing interest in transdermal drug delivery due to its ease of use and lack of painful responses. Here, a bibliometric analysis was conducted to determine a hotspot and trend of microneedles in the biomedical field. METHODS: All relevant articles about microneedles between 2011 and 2020 were obtained from the databases of Web of Science (WOS) and PubMed of the National Center for Biotechnology Information (NCBI). A series of software such as VOSviwewer, the online bibliometric analysis website, CiteSpace, BICOMB and gCLUTO were used to process the data and get visual images. Processed data and visualized images were conducted to predict the trend of this research field. RESULTS: The number of articles published over the last decade had increased rapidly (37 in 2011, 165 in 2020), the Journal of Controlled Release was the most productive journal in microneedle studies. The United States was the most productive country, while the Queens Univ Belfast topped the other institutions. Ryan F Donnelly was the most productive author in the field, while the two most cited articles were published by Gu Zhen group. More importantly, the research trend of microneedles had ranged from physicochemical properties and pharmacokinetics to insulin transdermal injection and vaccine development over the past decade. The four hot spots in microneedle studies, including skin rejuvenation, vaccines, fabrication technology and insulin delivery, were identified. Microneedle vaccination shows promising application prospects, and polymers are considered as the most promising materials for microneedles manufacturing. CONCLUSIONS: This study will help researchers understand the hot spots and trends of microneedles in the biomedical field accurately and quickly. Moreover, the exploitation of novel polymeric microneedles will be a solid direction for subsequent research and development of transdermal drug delivery.

Propolin G-Suppressed Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer Cells via Glycogen Synthase Kinase 3ß-Mediated Snail and HDAC6-Regulated Vimentin Degradation.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer with a poor prognosis. The incidence and mortality rate of TNBC are frequently found in younger women. Due to the absence of a good therapeutic strategy, effective remedies for inhibiting TNBC have been developed for improving the cure rate. Epithelial-to-mesenchymal transition (EMT) is a critical mechanism to regulate cancer cell motility and invasion. Furthermore, ectopic expression of EMT molecules correlates with the metastasis and poor prognosis of TNBC. Targeting EMT might be a strategy for the therapy and prevention of TNBC. Propolin G, an active c-prenylflavanone in Taiwanese propolis, has been shown to possess anti-cancer activity in many cancers. However, the anti-metastasis activity of propolin G on TNBC is still unclear. The present study showed that the migration and invasion activities of TNBC cells was suppressed by propolin G. Down-regulated expression of Snail and vimentin and up-regulated expression of E-cadherin were dose- and time-dependently observed in propolin G-treated MDA-MB-231 cells. Propolin G inhibited Snail and vimentin expressions via the signaling pathways associated with post-translational modification. The activation of glycogen synthase kinase 3ß (GSK-3ß) by propolin G resulted in increasing GSK-3ß interaction with Snail. Consequently, the nuclear localization and stability of Snail was disrupted resulting in promoting the degradation. Propolin G-inhibited Snail expression and the activities of migration and invasion were reversed by GSK-3ß inhibitor pretreatment. Meanwhile, the outcomes also revealed that histone deacetylase 6 (HDAC6) activity was dose-dependently suppressed by propolin G. Correspondently, the amounts of acetyl-α-tubulin, a down-stream substrate of HDAC6, were increased. Dissociation of HDAC6/Hsp90 with vimentin leading to increased vimentin acetylation and degradation was perceived in the cells with the addition of propolin G. Moreover, up-regulated expression of acetyl-α-tubulin by propolin G was attenuated by HDAC6 overexpression. On the contrary, down-regulated expression of vimentin, cell migration and invasion by propolin G were overturned by HDAC6 overexpression. Conclusively, restraint cell migration and invasion of TNBC by propolin G were activated by the expression of GSK-3ß-suppressed Snail and the interruption of HDAC6-mediated vimentin protein stability. Aiming at EMT, propolin G might be a potential candidate for TNBC therapy.

Successful short-term sperm cryopreservation in brown-marbled grouper (Epinephelus fuscoguttatus) with the utility of ultra-freezer (-80°C).

Production of cryopreserved semen in fish generally requires liquid nitrogen (LN), which is not always easily available in remote areas. To reduce reliance on LN, the aim of the present study was to evaluate whether electric freezer could be a feasible LN-free alternative to cryopreserve brown-marbled grouper sperm. After loading, semen straws were put directly into freezers (-30 or -80°C) for freezing and then transferred to LN for storage. Compared with the conventional LN vapour freezing (straws were put horizontally 3 cm above the surface of LN), there was a significant reduction in all tested post-thaw sperm quality parameters in samples frozen at -30°C for 10 min, including kinetic parameters (total motility: 85.0% vs. 48.6%), viability (84.7% versus 51.7%), high mitochondrial membrane potential (86.4% vs. 63.7%), ATP content (106.9 nM/109 cells vs. 72.9 nM/109 cells) and hatching rate (86.3% vs. 45.7%), accompanied with an increasing lipid peroxidation level (MDA content: 11.9 nM/109 cells vs. 4.9 nM/109 cells). In contrast, frozen with -80 °C ultra-freezer (10 min or 12 hr) produced similar sperm quality parameters to those using LN, except that temporary storage (12 hr) at -80°C yielded lower average path velocity. In conclusion, this study confirmed that -80°C ultra-freezer is an effective alternative to LN for sperm freezing in brown-marbled grouper.