Roles of CcDFR and CcOMT9 in the cyanidin biosynthesis and development of Cordyceps cicadae.

Introduction: Cordyceps cicadae is a traditional Chinese medicinal fungus known for its rich production of bioactive substances, particularly cyanidin, an anthocyanin commonly found in plants with notable anti-inflammatory, anti-tumor, antiviral, and antibacterial properties. This study revealed two key genes, CcDFR and CcOMT9, affecting cyanidin biosynthesis in C. cicadae. Methods: The roles of these genes in cyanidin production, growth, and development were elucidated through the gene knockout method, phenotypic analysis, transcriptomics, and metabolomics. Results: CcDFR deletion led to reduced cyanidin-3-O-glucoside (C3G), suppressed expression of cyanidin biosynthesis genes, impaired synnemata formation, decreased polysaccharide and adenosine content, and diminished chitinase activity. Meanwhile, the ΔCcOMT9 mutant exhibited an increase in C3G production, promoted expression of cyanidin biosynthesis genes and rising bioactive compounds, suppressed RNA methylation, and led to phenylalanine accumulation with no effect on fruiting body formation. Discussion: We revealed a distinct anthocyanin biosynthesis pathway in C. cicadae and identified two genes with opposite functions, laying the foundation for future genetic modification of cyanidin-producing strains using modern biological techniques. This will shorten the production period of this valuable compound, facilitating the industrial-scale production of cyanidin.

A bibliometric analysis of research trends for missing persons globally and in East Asia from 2000 to 2021.

A bibliometric analysis was performed to explore the current research status and development trends for missing persons globally and in East Asia and to identify research hotspots and frontiers relating to this topic. A search was conducted to identify relevant literature on missing persons using the Web of Science Core Collection database for the period 2000-2021. Subsequently, a knowledge map was constructed using CiteSpace software to perform a visual analysis of the distribution of authors and institutions, journals, and national/regional distribution; citation frequency; high-frequency keywords; and emerging research hotspots. The results showed firstly that discussions on missing persons and related topics in East Asia are held at the regional scale. There is a paucity of research on this topic, which has been conducted on a limited scale, lacks depth and possibly innovation, and entails limited discussion in this region. Secondly, there is a lack of social science research on missing persons and related topics worldwide. Thirdly, relevant research in East Asia should continue to preserve its own characteristics, effectively addressing current issues and enabling more people to participate in social science-oriented discussions focusing on the topic of missing persons. This approach provides a promising direction for pursuing the sustainable development of the topic of missing persons. Key points: The strengths and weaknesses of current research on missing persons in East Asia were identified by comparing the respective literatures on missing persons and related topics in East Asia and worldwide during the period 2000-2021.Bibliometric analysis was performed using CiteSpace visual charts to explore keywords, authorship and co-authorship, intercountry collaboration, and other relevant co-citationities.Insights were obtained on current research breakthroughs relating to the topic of missing persons, and cutting-edge social science research on this topic was identified.

MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation.

CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.

The prevalence and factors associated with posttraumatic growth after 3-years outbreak of COVID-19 among resident physicians in China: a cross-sectional study.

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic is a global traumatic event that has profoundly struck individuals' mental health. However, this might potentially promote positive transformation such as posttraumatic growth (PTG). Studies have indicated that the COVID-19 pandemic negatively affected the well-being of resident physicians, but little is known about PTG among this vulnerable population in China. Therefore, this study investigated the prevalence and associated factors of PTG among Chinese resident physicians after 3-years outbreak of COVID-19. Methods: An online survey was conducted from 9 March to 20 March in 2023. PTG was assessed using the 10-item Posttraumatic Growth Inventory-Short Form (PTGI-SF). Scores ≥30 implied moderate-to-high PTG. We also collected possible associated factors for PTG, including socio-demographic and psychological variables. Data was analyzed by applying descriptive statistics, univariable and multivariable logistic regression models. Results: In total, 2267 Chinese resident physicians provided validated data. 38.7% of them reported moderate-to-high PTG. In the multivariable logistic regression models, age (odds ratio, OR = 1.039; 95% confidence interval, 95%CI = 1.008-1.070), female (OR = 1.383, 95%CI = 1.151-1.662), satisfied or neutral with annual income (OR = 2.078, 95%CI = 1.524-2.832; OR = 1.416, 95%CI = 1.157-1.732), sufficient support at work (OR = 1.432, 95%CI = 1.171-1.751) and resilience (OR = 1.171, 95%CI = 1.096-1.252) were significantly positively associated with moderate-to-high PTG. On the contrary, burnout (OR = 0.653, 95%CI = 0.525-0.812), depression symptoms (OR = 0.700, 95%CI = 0.552-0.889), and stress (OR = 0.757, 95%CI = 0.604-0.949) were significantly negatively associated with moderate-to-high PTG. Discussion: Overall, resident physicians in China experienced relatively high prevalence of PTG that could be associated with several psychosocial factors. Findings may provide evidence to develop interventions for resident physicians to systematically and constructively process traumatic events related to the pandemic and foster their PTG.

Sudden unexpected death in epilepsy: A bibliometric overview.

The mechanism of sudden unexpected death in epilepsy (SUDEP) is elusive and many questions remain unanswered. Autopsy is generally unhelpful in providing evidence for the cause of death, as pathological changes may be on the molecular level. Although histopathological examination occasionally demonstrates pathology such as vascular malformation, old traumatic injury, and tumor, in most cases of SUDEP, the examination is negative. We examined the current status of SUDEP research by performing a bibliometric analysis of studies in the Web of Science Core Collection database published between 2002 and 2022. Our aim was to demonstrate areas of interest and frontiers of SUDEP research. A total of 1803 papers were included in the analysis. The number of published papers focused on SUDEP has been increasing since 2002. Main areas of interest include clinical manifestations, prevalence, treatment, and underlying mechanisms. Research teams from the United States and Europe are leading the way in SUDEP research, while Asia trails behind. Future studies regarding the mechanism and neuropathology of SUDEP are warranted.

A fluorescent sensor for selective detection of hypochlorite and its application in Arabidopsis thaliana.

Hypochlorite, as one of reactive oxygen species, has drawn much attention due to its essential roles in special biological events and disorders. The exogenous hypochlorite remains a risk for human, animals and plants. In this work, a novel water soluble quinolin-containing nitrone derivative T has been developed for fluorometric sensing hypochlorite. The response mechanism of T towards ClO- was reported for the first time. In comparison with the reported sensors for ClO-, the sensor T in this work exhibited advantages including high selectivity (80 fold over other analytes), rapid response (within 5 s) and lipid-water distribution transformation (LogP from 2.979 to 6.131). Further biological applications suggested that T was capable of monitoring both exogenous and endogenous ClO- in living cells. The imaging in Arabidopsis thaliana indicated that the absorption and transmission of ClO- in plant could be monitored by this sensor through the chlorine-related mechanism. This work might raise referable information for further investigations in the physiological and pathological events in both tumor and plants.

Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica.

The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis.

Multiplexed detection and the establishment of a novel high-throughput method for human germ cell quality screening based on aggregation-induced emission.

We report a rapid, sensitive, and high-throughput method for quality control of human sperm cells and oocytes staining based on the aggregation-induced emission feature of the tetraphenylethylene-based luminogen (TPE-Ph-In), which is mitochondria-specific. Germ cells are evaluated to assess fertility and to facilitate assisted reproduction. In regular clinical practice, sperm quality is determined on the basis of visual examination and mathematical models of the sperm cell number, motility, and morphology. The maturation of the oocyte is crucial for the developmental competence of the resulting embryo. Human in vitro fertilization (IVF) have indicated that delaying insemination improves fertilization rates, presumably by allowing the completion of cytoplasmic maturation for those oocytes that have not completely matured at the time. Therefore, a more reliable method to determine germ cell quality is needed. The mitochondrial membrane potential (MMP) of spermatozoa reflects the function and status of those cells. In oocytes, the distribution of mitochondria indicates the readiness of the cell for fertilization. Aggregation-induced emission luminogens (AIEgens) have good biocompatibility and photostability and produce low levels of background signal. There are about 100,000 mitochondria per fully-grown human oocyte. Mitochondria in mammalian oocytes are spherical with little cristae, supplying large scale of ATP for embryo development. Here, we expanded the use of TPE-Ph-Into determine germ cell quality on the basis of the MMP and the intracellular distribution of mitochondria. We stained clinical sperm samples from 36 patients with infertility, as well as four oocytes, with TPE-Ph-In and examined the cells by confocal microscopy and cell sorting analysis. Our results showed a positive correlation between the MMP and sperm cell motility, as well as the different distribution of mitochondria in oocyte. Thus, staining with TPE-Ph-In could be used to quickly determine germ cell quality in vivo, bringing new possibilities for applications of AIEgens in biomedical research and clinical trials.

The Biological Applications of Two Aggregation-Induced Emission Luminogens.

Fluorescence imaging, as a commonly used scientific tool, is widely applied in various biomedical and material structures through visualization technology. Highly selective and sensitive luminescent biological probes, as well as those with good water solubility, are urgently needed for biomedical research. In contrast to the traditional aggregation-caused quenching of fluorescence, in the unique phenomenon of aggregation-induced emission (AIE), the individual luminogens have extremely weak or no emissivity because they each have free intramolecular motion; however, when they form aggregates, these components immediately "light up". Since the discovery of "turn-on" mechanism, researchers have been studying and applying AIE in a variety of fields to develop more sensitive, selective, and efficient strategies for the AIE dyes. There are numerous advantages to the use of AIE-based methods, including low background interference, strong contrast, high performance in intracellular imaging, and the ability for long-term monitoring in vivo. In this review, two typical examples of AIEgens, TPE-Cy and TPE-Ph-In, are described, including their structure properties and applications. Recent progress in the biological applications is mainly focused on. Undoubtedly, in the near future, an increasing number of encouraging and practical ideas will promote the development of more AIEgens for broad use in biomedical applications.

Imaging Macrophage Phagocytosis Using AIE Luminogen-Labeled E.†coli.

Phagocytosis of bacteria is an important biological process. Gaining insight into this process may greatly benefit related pathological studies and further contribute to development of therapies for infectious diseases. Tools for studying these internalization processes, however, are limited. Herein, we demonstrate the feasibility of employing an environmentally sensitive aggregation-induced emission (AIE) probe for bacteria labeling and imaging. By tracking the fluorescence variation of the stained bacteria, the pH changes of its microenvironment can be monitored. In this way, the phagocytic entry of these bacteria into the macrophage cells and the intravacuolar acidification can be visualized in real-time.

Chronic high-dosage fish oil exacerbates gut-liver axis injury in alcoholic steatohepatitis in mice: the roles of endotoxin and IL-4 in Kupffer cell polarization imbalance.

In the present study, intestinal tight junctions (TJs) and Kupffer cell polarization were investigated in an alcoholic steatohepatitis (ASH) mouse model to uncover the potential side effects of overexposure to fish oil or omega-3 fatty acids. The mice were fed ad libitum with a liquid diet containing ethanol and fish oil. In the meantime, ethanol was given every 5-7 days by gavage to simulate binge drinking. After the 7th binge, steatosis, necrosis, inflammatory infiltration, and bridging fibrosis were observed in the liver by histological staining. After the 13th binge, the inducers, markers and other downstream genes/proteins of the Kupffer cell M1/M2 phenotype in the liver, serum, and small intestine were analysed. The results suggested that a chronic high dosage of fish oil alone reduced the mRNA levels of most genes tested and showed a tendency to damage the intestinal zonula occludens-1 localization and reduce the number of M2 Kupffer cells. Meanwhile, the combination of fish oil and ethanol damaged the intestinal TJs, resulting in an increased endotoxin level in the liver. Gut-derived endotoxin polarized Kupffer cells to the M1 phenotype, whereas the number of cells with the M2 phenotype (markers: CD163 and CD206) was decreased. Interleukin-4 (IL-4), an M2 Kupffer cell inducer, was also decreased. Moreover, in vitro experiments showed that IL-4 reversed eicosapentaenoic acid-induced CD163 and CD206 mRNA suppression in RAW 264.7 cells. Overall, our results showed that a chronic high dosage of fish oil exacerbated gut-liver axis injury in alcoholic liver disease in mice, and endotoxin/IL-4-induced Kupffer cell polarization imbalance might play an important role in that process.