Discovery of deaminase functions by structure-based protein clustering.

The elucidation of protein function and its exploitation in bioengineering have greatly advanced the life sciences. Protein mining efforts generally rely on amino acid sequences rather than protein structures. We describe here the use of AlphaFold2 to predict and subsequently cluster an entire protein family based on predicted structure similarities. We selected deaminase proteins to analyze and identified many previously unknown properties. We were surprised to find that most proteins in the DddA-like clade were not double-stranded DNA deaminases. We engineered the smallest single-strand-specific cytidine deaminase, enabling efficient cytosine base editor (CBE) to be packaged into a single adeno-associated virus (AAV). Importantly, we profiled a deaminase from this clade that edits robustly in soybean plants, which previously was inaccessible to CBEs. These discovered deaminases, based on AI-assisted structural predictions, greatly expand the utility of base editors for therapeutic and agricultural applications.

SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.

Lysine lactylation (Kla) is a recently discovered histone mark derived from metabolic lactate. The NAD+ -dependent deacetylase SIRT3, which can also catalyze removal of the lactyl moiety from lysine, is expressed at low levels in hepatocellular carcinoma (HCC) and has been suggested to be an HCC tumor suppressor. Here we report that SIRT3 can delactylate non-histone proteins and suppress HCC development. Using SILAC-based quantitative proteomics, we identify cyclin E2 (CCNE2) as one of the lactylated substrates of SIRT3 in HCC cells. Furthermore, our crystallographic study elucidates the mechanism of CCNE2 K348la delactylation by SIRT3. Our results further suggest that lactylated CCNE2 promotes HCC cell growth, while SIRT3 activation by Honokiol induces HCC cell apoptosis and prevents HCC outgrowth in vivo by regulating Kla levels of CCNE2. Together, our results establish a physiological function of SIRT3 as a delactylase that is important for suppressing HCC, and our structural data could be useful for the future design of activators.

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53.

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown. Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53 binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this self-repression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25 as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53 from binding to W-box elements on the AtWRKY53 promoter and thus counteracted the self-repression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid (SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and NahG transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence, which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

Relationship between mental health literacy and professional psychological help-seeking attitudes in China: a chain mediation model.

BACKGROUND: Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes. METHODS: We collected data from 827 participants in seven regions of China (597 female; Mage = 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes. RESULTS: The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants' age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population. CONCLUSIONS: These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.

A review on the biology and properties of adipose tissue macrophages involved in adipose tissue physiological and pathophysiological processes.

Obesity exhibits a correlation with metabolic inflammation and endoplasmic reticulum stress, promoting the progression of metabolic disease such as diabetes, hyperlipidemia, hyperuricemia and so on. Adipose tissue macrophages (ATMs) are central players in obesity-associated inflammation and metabolic diseases. Macrophages are involved in lipid and energy metabolism and mitochondrial function in adipocytes. Macrophage polarization is accompanied by metabolic shifting between glycolysis and mitochondrial oxidative phosphorylation. Here, this review focuses on macrophage metabolism linked to functional phenotypes with an emphasis on macrophage polarization in adipose tissue physiological and pathophysiological processes. In particular, the interplay between ATMs and adipocytes in energy metabolism, glycolysis, OXPHOS, iron handing and even interactions with the nervous system have been reviewed. Overall, the understanding of protective and pathogenic roles of ATMs in adipose tissue can potentially provide strategies to prevent and treat obesity-related metabolic disorders.

Excessive daytime sleepiness in general hospital nurses: prevalence, correlates, and its association with adverse events.

OBJECTIVE: To investigate the prevalence and correlates of excessive daytime sleepiness (EDS) in a population of hospital nurses in South China as well as the influence of EDS on the occurrence of adverse events. METHODS: A total of 1102 nurses working in a large medical center were invited to participate in this cross-sectional study (96.9% females, mean age 29.6 years). They all completed a self-reported questionnaire consisting of items on demographic variables, lifestyle factors, insomnia, anxiety, depression, and both work-related and sleep-related characteristics. RESULTS: A total of 1048 nurses gave a valid response (response rate 95.1%). Among them, 169 (16.1%) reported EDS as defined as an Epworth Sleepiness Scale ≥ 14. Depression (adjusted odds ratio = 2.24, 95% confidence interval 1.51-3.31), anxiety (1.65; 1.02-2.67), insomnia (2.29; 1.56-3.36), rotating shift work (1.98; 1.03-3.83), and low interest in work (1.74; 1.01-2.99) were all independent risk factors of the occurrence of EDS. EDS is associated with the occurrence of adverse events after controlling for confounding factors (adjusted OR 1.83, CI 1.26 to 2.67). CONCLUSIONS: EDS was common among this relatively young and healthy nurse population in south China. There were clear associations between EDS and depression, anxiety, insomnia, rotating shift work, and low work-related interest. Furthermore, EDS was an independent risk factor in the occurrence of adverse events (AEs) in our subjects.

Sensing Properties of a Novel Temperature Sensor Based on Field Assisted Thermal Emission.

The existing temperature sensors using carbon nanotubes (CNTs) are limited by low sensitivity, complicated processes, or dependence on microscopy to observe the experimental results. Here we report the fabrication and successful testing of an ionization temperature sensor featuring non-self-sustaining discharge. The sharp tips of nanotubes generate high electric fields at relatively low voltages, lowering the work function of electrons emitted by CNTs, and thereby enabling the safe operation of such sensors. Due to the temperature effect on the electron emission of CNTs, the collecting current exhibited an exponential increase with temperature rising from 20 °C to 100 °C. Additionally, a higher temperature coefficient of 0.04 K-1 was obtained at 24 V voltage applied on the extracting electrode, higher than the values of other reported CNT-based temperature sensors. The triple-electrode ionization temperature sensor is easy to fabricate and converts the temperature change directly into an electrical signal. It shows a high temperature coefficient and good application potential.

Association of perceived stress and sleep quality among medical students: the mediating role of anxiety and depression symptoms during COVID-19.

COVID-19 has intensified the influence on medical students by changing the lifestyle, online study and clinical practice which bring out series of stress, sleep disturbance and mental health problems. This cross-sectional study aim to explore the association between perceived stress and sleep quality among medical students and investigated whether anxiety and depression mediated this association during pandemic. A total of 1,021 medical students in two universities who were from Guangdong Province, China participated this study and from January to September 2020 through the online question are, with 28.80% reporting sleep disturbances. The medical students were finished various self-reported questionnaires, including the Perceived Stress Scale-10, Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 Scale, and Patient Health Questionnaire-9, the study found positive correlations among sleep quality, perceived stress, anxiety, and depression. The data was analyzed with The Amos 26.0 system. Result demonstrated that perceived stress was associated with poor sleep quality. Anxiety and depression partially mediated the association between perceived stress and poor sleep quality, explaining 73.08% of the association. This study's structural equation model offers a useful framework for assessing mechanisms mediating associations between perceived stress and sleep quality. The findings emphases the importance of addressing psychological factors in high-pressure situations, which can exacerbate sleep disturbances among medical students. It is important to screen the level of stress, mental health problems and investigate the risk factors of sleep quality among medical students during emergency public health events.

STING modulates iron metabolism to promote liver injury and inflammation in acute immune hepatitis.

The pathogenesis of Autoimmune Hepatitis (AIH) is closely associated with perturbations in iron ion metabolism, during which Stimulator of Interferon Genes (STING) plays an important role. However, the precise regulatory mechanism remains elusive. In this study, we investigated the relationship between iron dysregulation and STING activation in Concanavalin A (ConA)-induced AIH liver injury. STING knockout (STING-/-) mice and AAV (Adeno-Associated virus)-Sting1-RNAi-treated mice were involved and subjected in AIH. We observed that increased iron dysregulation was linked with STING activation, but this effect was effectively reversed by the administration of iron chelating agent Desferoxamine (DFO) and the antioxidant Ferrostatin-1 (Fer-1). Notably, the iron transport protein Transferrin (TF) and Transferrin Receptor (TfR) exhibited significant accumulation in AIH along with upregulated expression of ferritin protein. Additionally, the deficiency of STING reduced hepatic iron accumulation, mitigated oxidative stress, and attenuated macrophage activation during ConA treatment. Furthermore, liver-specific knockdown of STING using AAV-Sting1-RNAi significantly ameliorated liver iron dysregulation and oxidative stress response induced by Kupffer cells (KCs). KC-derived STING exacerbates liver damage severity in AIH through promoting disturbances in hepatic iron ion metabolism as well as oxidative stress response. These findings provide valuable insights into the pathogenesis of AIH and may pave the way for potential therapeutic strategies targeting STING and iron metabolism in the future.

Precise integration of large DNA sequences in plant genomes using PrimeRoot editors.

A technique for chromosomal insertion of large DNA segments is much needed in plant breeding and synthetic biology to facilitate the introduction of desired agronomic traits and signaling and metabolic pathways. Here we describe PrimeRoot, a genome editing approach to generate targeted precise large DNA insertions in plants. Third-generation PrimeRoot editors employ optimized prime editing guide RNA designs, an enhanced plant prime editor and superior recombinases to enable precise large DNA insertions of up to 11.1 kilobases into plant genomes. We demonstrate the use of PrimeRoot to accurately introduce gene regulatory elements in rice. In this study, we also integrated a gene cassette comprising PigmR, which confers rice blast resistance driven by an Act1 promoter, into a predicted genomic safe harbor site of Kitaake rice and obtain edited plants harboring the expected insertion with an efficiency of 6.3%. We found that these rice plants have increased blast resistance. These results establish PrimeRoot as a promising approach to precisely insert large segments of DNA in plants.

Mechanism of Reactive Oxygen/Nitrogen Species in Liver Ischemia-Reperfusion Injury and Preventive Effect of Chinese Medicine.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.

Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Editorial for the Special Issue on Smart Devices and Systems for Vibration Sensing and Energy Harvesting.

The Internet of things (IoT) poses new challenges for sensors and their power systems [...].

Exploring Practical Metrics to Support Automatic Speech Recognition Evaluations.

Recent studies into the evaluation of automatic speech recognition for its quality of output in the form of text have shown that using word error rate to see how many mistakes exist in English does not necessarily help the developer of automatic transcriptions or captions. Confidence levels as to the type of errors being made remain low because mistranslations from speech to text are not always captured with a note that details the reason for the error. There have been situations in higher education where students requiring captions and transcriptions have found that some academic lecture results are littered with word errors which means that comprehension levels drop and those with cognitive, physical and sensory disabilities are particularly affected. Despite the incredible improvements in general understanding of conversational automatic speech recognition, academic situations tend to include numerous domain specific terms and the lecturers may be non-native speakers, coping with recording technology in noisy situations. This paper aims to discuss the way additional metrics are used to capture issues and feedback into the machine learning process to enable enhanced quality of output and more inclusive practices for those using virtual conferencing systems. The process goes beyond what is expressed and examines paralinguistic aspects such as timing, intonation, voice quality and speech understanding.

Family Subjective Socioeconomic Status and University Students' Online Shopping Addiction: A Gender-Based Analysis.

Online shopping addiction has surged among today's university students. Previous studies have focused on individual and network factors, whereas neglecting family-related roles. This study examined the relationship between subjective socioeconomic status (SSES) and university students' online shopping addiction (OSA) using the life course model of consumer behavior, and explored the chain-mediating role of vanity and materialism, and the moderating role of gender. We surveyed 635 students from two universities in Henan Province, China, using self-administered scales and questionnaires assessing subjective SES (SSES), OSA, materialism, and vanity. The results showed that SSES is negatively associated with OSA. Materialism played a mediating role, whereas vanity and vanity-materialism played a suppressing role between SSES and OSA. A direct relationship between SSES and OSA was found only in men, whereas the indirect path of SSES-vanity-materialism-OSA was found only in women. These results enable better recognition and understanding of the family's role, including family economic status, in university students' gender-specific OSA. They also advance the understanding of the transmission mechanism between family economic status and university students' OSA and promote better recognition and awareness of the family's role in university students' gender-specific OSA.

Impact of Multiple Vitrification-Warming Procedures and Insemination Methods on Pregnancy and Neonatal Outcomes in Preimplantation Genetic Testing for Aneuploidy.

This study was to determine whether multiple vitrification-warming procedures and insemination method are associated with pregnancy and neonatal outcomes in preimplantation genetic testing for aneuploidy (PGT-A). This was a retrospective, single-center, observational study of 112 patients who underwent standard PGT-A practice and 154 patients who desired PGT-A for their vitrified unbiopsied blastocysts. A total of 97 euploid blastocysts biopsied and vitrified-warmed once and 117 euploid blastocysts biopsied once but vitrified-warmed twice (83 in vitro fertilization [IVF]-derived and 34 intracytoplasmic sperm injection [ICSI]-derived euploid blastocysts) were transferred. The primary outcome was the blastocyst survival rate for transfer, live birth rate, and neonatal outcomes. The results showed that an additional vitrification-warming procedure on blastocysts resulted in a lower but not statistically different survival rate for transfer. Compared with euploid blastocysts vitrified-warmed once, those vitrified-warmed twice provided statistically similar live birth rate. Neonatal outcomes, including the sex ratio, gestational age, birthweight, preterm birth rate, and low birthweight rate, did not differ between single and double vitrification. No significant differences were observed in rates of blastocyst survival, blastocyst euploid and live birth, and neonatal outcomes resulting from either conventional IVF or ICSI. The neonatal follow-up of babies live-born so far did not report any congenital malformations. In conclusion, an additional vitrification-warming on blastocysts had no detectable adverse impact on clinical outcomes after frozen-thawed single euploid blastocyst transfer in PGT-A cases; and ICSI did not confer any benefit in improving clinical outcomes compared with conventional IVF in cases requiring PGT-A on already vitrified nonbiopsied blastocysts.

Zexie decoction reduce glucose-dependent lipid accumulation and oxidative stress in Caenorhabditis elegans.

BACKGROUND: Obesity has become a global public health problem. Zexie decoction (ZXT) is a classic formula from Synopsis of the Golden Chamber. However, the long-term effect of ZXT in lipid accumulation remain unclear. PURPOSE: This study aims to investigate the effect of ZXT on aging, lipid metabolism and oxidative stress. METHODS: Different concentration of ZXT was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or the high glucose nematode growth media (GNGM). The lifespan, heat stress resistance, lipid accumulation and related mRNA expression of the worms were examined. Oil Red staining and triglyceride were used to evaluated the lipid accumulation. Nhr-49, fat-5/fat-7, fat-5/fat-6 or skn-1 knockout mutants were used to clarify the effect on lipid metabolism of ZXT. GFP-binding mutants were used to observe the changes in protein expression. RESULTS: ZXT improved the survival rate of C. elegans in lifespan test and heat stress test. ZXT also reduced lipid accumulation in C. elegans and significantly changed the expression of fatty acid synthesis related genes and lipid metabolism related genes. In addition, ZXT-treated C. elegans showed a higher expression of anti-oxidative protein, and reduced the expression of oxidative stress and mitochondrial dysfunction marker. However, when skn-1 was knockdown, ZXT no longer had the effect of maintaining the mitochondria membrane potential and lipid lowering but still effectively decreased the O2·- induced by high glucose. CONCLUSIONS: ZXT reduced fat accumulation by regulating lipid metabolism via multiple targets and enhanced stress resistance by its antioxidant effect in C. elegans.

Ginsenosides Rg1 regulate lipid metabolism and temperature adaptation in Caenorhabditis elegans.

Background: Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance. Methods: Rg1 was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression. Results: We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans. Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans. However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance. Conclusion: Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans.

RAGE promotes dysregulation of iron and lipid metabolism in alcoholic liver disease.

Alcoholic liver disease (ALD) is associated with hepatic inflammatory activation and iron overload. The receptor for advanced glycation end products (RAGE) is an important metabolic mediator during the development of ALD. The aim of this study was to determine the effect of RAGE on iron homeostasis in ALD. We found increased circulating transferrin, hepcidin and ferritin in ALD patients and positively correlated with RAGE level. RAGE knockout (RAGE-/-) and wild-type mice were subjected to chronic alcoholic feeding for 6 weeks to induce ALD, and RAGE inhibitor, iron chelator or lipid peroxidation inhibitor were administered. We showed that chronic alcohol administration triggered hepatic steatosis, inflammation, and oxidative stress, which were eliminated by deficiency or inhibition of RAGE. Surprisingly, pathways of hepatic iron metabolism were significantly altered, including increased iron uptake (Tf/TfR) and storage (Ferritin), as well as decreased iron export (FPN1/Hepcidin). In vitro experiments confirmed that RAGE had different effects on the mechanism of iron metabolism of hepatocytes and macrophages respectively. In conclusion, our data revealed preclinical evidence for RAGE inhibition as an effective intervention for alleviating alcohol-induced liver injury.