Multi-omics and gut microbiome: Unveiling the pathogenic mechanisms of early-life pesticide exposure.

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.

Research progress on the association between glycemic variability index derived from CGM and cardiovascular disease complications.

Currently, glycated hemoglobin A1c (HbA1c) has been widely used to assess the glycemic control of patients with diabetes. However, HbA1c has certain limitations in describing both short-term and long-term glycemic control. To more accurately evaluate the glycemic control of diabetes patients, the continuous glucose monitoring (CGM) technology has emerged. CGM technology can provide robust data on short-term glycemic control and introduce new monitoring parameters such as time in range, time above range, and time below range as indicators of glycemic fluctuation. These indicators are used to describe the changes in glycemic control after interventions in clinical research or treatment modifications in diabetes patient care. Recent studies both domestically and internationally have shown that these indicators are not only associated with microvascular complications of diabetes mellitus but also closely related to cardiovascular disease complications and prognosis. Therefore, this article aims to comprehensively review the association between CGM-based glycemic parameters and cardiovascular disease complications by analyzing a large number of domestic and international literature. The purpose is to provide scientific evidence and guidance for the standardized application of these indicators in clinical practice, in order to better evaluate the glycemic control of diabetes patients and prevent the occurrence of cardiovascular disease complications. This research will contribute to improving the quality of life for diabetes patients and provide important references for clinical decision-making.

STON2 variations are involved in synaptic dysfunction and schizophrenia-like behaviors by regulating Syt1 trafficking.

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

Fragmented QRS complex could predict all-cause mortality in patients with connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVES: To investigate the prognostic impact and pathophysiological characteristics of fragmented QRS complex (fQRS) on patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). METHODS: This was a multicentre retrospective study recruiting 141 patients with CTD-PAH diagnosed by right heart catheterization (114 cases in the discovery cohort and 27 cases in the validation cohort). fQRS and ST-T change were detected on conventional 12-lead electrocardiogram (ECG). Patients were followed up every 3 months to update their status and the primary end point was all-cause death. Clinical information and ECG characteristics were compared between survival and death groups and Kaplan-Meier curve was used for survival analysis. RESULTS: There were significant differences in age, gender, 6-min walk distance, NT-proBNP, WHO class, presence of fQRS and presence of ST-T change in inferior leads between survival group and death group. Inferior fQRS and ST-T change were significantly associated with right ventricular (RV) dilatation and reduced RV ejection fraction (RVEF). Kaplan-Meier curve showed that all-cause mortality was higher in CTD-PAH with fQRS (p= 0.003) and inferior ST-T change (p= 0.012). Low- and intermediate-risk CTD-PAH with inferior ST-T change had higher all-cause mortality (p= 0.005). The prognostic value of fQRS and inferior ST-T change was validated in external validation cohort. CONCLUSION: The presence of inferior fQRS and ST-T change could predict poor prognosis in CTD-PAH. CLINICAL TRIAL REGISTRATION NUMBER: NCT05980728, https://clinicaltrials.gov.

Using eDNA to survey amphibians: Methods, applications, and challenges.

In recent years, environmental DNA (eDNA) has received attention from biologists due to its sensitivity, convenience, labor and material efficiency, and lack of damage to organisms. The extensive application of eDNA has opened avenues for the monitoring and biodiversity assessment of amphibians, which are frequently small and difficult to observe in the field, in areas such as biodiversity survey assessment and detection of specific, rare and threatened, or alien invasive species. However, the accuracy of eDNA can be influenced by factors such as ambient temperature, pH, and false positives or false negatives, which makes eDNA an adjunctive tool rather than a replacement for traditional surveys. This review provides a concise overview of the eDNA method and its workflow, summarizes the differences between applying eDNA for detecting amphibians and other organisms, reviews the research progress in eDNA technology for amphibian monitoring, identifies factors influencing detection efficiency, and discusses the challenges and prospects of eDNA. It aims to serve as a reference for future research on the application of eDNA in amphibian detection.

Regulatory networks of the F-box protein FBX206 and OVATE family proteins modulate brassinosteroid biosynthesis to regulate grain size and yield in rice.

F-box proteins participate in the regulation of many processes, including cell division, development, and plant hormone responses. Brassinosteroids (BRs) regulate plant growth and development by activating core transcriptional and other multiple factors. In rice, OVATE family proteins (OFPs) participate in BR signalling and regulate grain size. Here we identified an F-box E3 ubiquitin ligase, FBX206, that acts as a negative factor in BR signalling and regulates grain size and yield in rice. Suppressed expression of FBX206 by RNAi leads to promoted plant growth and increased grain yield. Molecular analyses showed that the expression levels of BR biosynthetic genes were up-regulated, whereas those of BR catabolic genes were down-regulated in FBX206-RNAi plants, resulting in the accumulation of 28-homoBL, one of the bioactive BRs. FBX206 interacted with OsOFP8, a positive regulator in BR signalling, and OsOFP19, a negative regulator in BR signalling. SCFFBX206 mediated the degradation of OsOFP8 but suppressed OsOFP19 degradation. OsOFP8 interacted with OsOFP19, and the reciprocal regulation between OsOFP8 and OsOFP19 required the presence of FBX206. FBX206 itself was ubiquitinated and degraded, but interactions of OsOFP8 and OsOFP19 synergistically suppressed the degradation of FBX206. Genetic interactions indicated an additive effect between FBX206 and OsOFP8 and epistatic effects of OsOFP19 on FBX206 and OsOFP8. Our study reveals the regulatory networks of FBX206, OsOFP8, and OsOFP19 in BR signalling that regulate grain size and yield in rice.

Bifidobacterium mediate gut microbiota-remedied intestinal barrier damage caused by cyproconazole in zebrafish (Danio rerio).

The widespread use of cyproconazole (CPZ) enhances food security but may pose potential risks to non-target organisms. Therefore, we applied Multi-omics techniques to reveal the response of the intestinal barrier to CPZ exposure and explore whether the Bifidobacterium intervention experiment can repair the damage. First, we found that exposure to CPZ at environmentally relevant concentrations led to intestinal injury phenotype, significantly down-regulated intestinal protein gene expression, and up-regulated pro-inflammatory gene expression, further causing intestinal dysbacteriosis and metabolic disorders. In particular, by combining analysis of gut microbiota and metabolites, we noticed acetate, a key metabolite, which decreased sharply after exposure to high concentration of CPZ. Expectedly, after supplementing with Bifidobacterium (a core bacterium that produces acetate), we noticed that the acetate content was quickly restored. Further, we also verified that the increase in acetate content after Bifidobacterium supplementation at least partially promoted IL-22 secretion, which in turn stimulated the secretion of ß-defensins (zfbd-1, zfbd-2, zfbd-3), thereby repairing the intestinal damage. In conclusion, our work confirms the potential of Bifidobacterium to improve intestinal damage and metabolic dysbiosis caused by CPZ exposure. It provides directional recommendations for the application of probiotics to repair the toxicological risk of pesticide exposure.

The mediating role of psychological empowerment in perceptions of decent work and work immersion among Chinese nurses: A cross-sectional study.

AIM: The purpose of this study was to explore the relationships among perceptions of decent work, psychological empowerment, and work immersion among nurses, hypothesizing that psychological empowerment mediates the relationship between perceptions of decent work and work immersion. BACKGROUND: At present, there are many studies on nurses' perceptions of decent labor and work immersion in China, but the relationship between them has not been discussed from a psychological perspective. METHODS: The sample consisted of clinical nurses in Jiangxi, Zhejiang, Hubei, and Guangdong provinces, China, and the nurses' general information, decent labor perception, psychological empowerment, and work immersion scores were assessed using the General Information Scale, Decent Labor Perception Scale, Psychological Empowerment Scale, and Work Immersion Scale, respectively. Pearson correlation analysis and structural equation modeling were used to analyze the data. RESULTS: The total scores of nurses' perceptions of decent work, psychological empowerment, and work immersion were at a moderate level. The total nurse work immersion score and each dimension score were positively correlated with the total nurse decent work perception score and the total psychological empowerment score. Decent work perception and psychological empowerment directly and positively predicted work immersion; decent work perception also indirectly acted on work immersion through psychological empowerment. CONCLUSIONS AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurses' work immersion was moderate, and this study explored the mechanisms by which perceptions of decent work affect nurses' work immersion from a psychological perspective, validating the mediating role of psychological empowerment. This study emphasizes that nursing managers should fully understand the importance of nurses' work immersion, continuously improve nurses' decent labor perceptions, enhance their psychological empowerment level, improve their work immersion, and enhance the quality of nursing services.

The expansion of newborn neurons in hippocampus improves social recognition deficit in a mouse model of autism.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by core symptoms of impaired social interaction and communication. The pathological mechanism and treatment are not clear and need further study. Our previous study found that the deletion of high-risk gene Autism Susceptibility 2 (AUTS2) in mice led to dentate gyrus (DG) hypoplasia that highly associated with impaired social novelty recognition. Here we aim to improve the social deficit through increasing the neurogenesis in the subgranular zone (SGZ) and expanding the newborn granule neurons in DG. Methods: Three approaches including repeated oxytocin administration, feeding in enriched environment and overexpression of cyclin-dependent kinase 4 (Cdk4)-CyclinD1 complex in DG neural stem cells (NSCs) at the post-weaning stage were conducted. Results: We found that the number of EdU labeled proliferative NSCs or retrovirus labeled newborn neurons was significantly increased after manipulations. The social recognition deficit was also significantly improved. Discussion: Our findings suggested a possible strategy to restore the social deficit through expansion of newborn neurons in hippocampus, which might provide a new insight into the treatment of autism.

An ingenious designed dual mode self-powered biosensing platform based on graphdiyne heterostructure substrate for instant hepatocarcinoma marker detection.

We report here for the first time a self-powered biosensing platform based on graphene/graphdiyne/graphene (GDY-Gr) heterostructure substrate material for ultrasensitive hepatocarcinoma marker (microRNA-21) detection in both electrochemical and colorimetric test modes. The dual-mode signal intuitively displayed on a smartphone fundamentally improves the detection accuracy. In electrochemical mode, the calibration curve is established in the linear range of 0.1-10000 fM, and the detection limit is as low as 0.333 fM (S/N = 3). Simultaneously, colorimetric analysis of the miRNA-21 is realized by using ABTS as an indicator. The detection limit is confirmed as 32 fM (S/N = 3), and miRNA-21 of concentration from 0.1 pM to 1 nM exhibit a linear relationship with R2 = 0.9968. Overall, the combination of GDY-Gr and multiple signal amplification strategy significantly improved the sensitivity by 310 times compared with traditional enzymatic biofuel cells (EBFCs) based detection platform, showing broad application prospects for on-site analysis and future mobile medical services.

ClockRay: A Wrist-Rotation based Technique for Occluded-Target Selection in Virtual Reality.

Target selection is one of essential operation made available by interaction techniques in virtual reality (VR) environments. However, effectively positioning or selecting occluded objects is under-investigated in VR, especially in the context of high-density or a high-dimensional data visualization with VR. In this paper, we propose ClockRay, an occluded-object selection technique that can maximize the intrinsic human wrist rotation skills through the integration of emerging ray selection techniques in VR environments. We describe the design space of the ClockRay technique and then evaluate its performance in a series of user studies. Drawing on the experimental results, we discuss the benefits of ClockRay compared to two popular ray selection techniques - RayCursor and RayCasting. Our findings can inform the design of VR-based interactive visualization systems for high-density data.

Multi-Task Learning for Pulmonary Arterial Hypertension Prognosis Prediction Via Memory Drift and Prior Prompt Learning on 3D Chest CT.

Pulmonary arterial hypertension (PAH) prognosis prediction on 3D non-contrast CT images is one of the most important tasks for PAH treatment. It will help clinicians stratify patients into different groups for early diagnosis and timely intervention via automatically extracting the potential biomarkers of PAH to predict mortality. However, it is still a task of great challenges due to the large volume and low-contrast regions of interest in 3D chest CT images. In this paper, we propose the first multi-task learning-based PAH prognosis prediction framework, P 2-Net, which effectively optimizes the model and powerfully represents task-dependent features via our Memory Drift (MD) and Prior Prompt Learning (PPL) strategies. 1) Our MD maintains a large memory bank to provide a dense sampling of the deep biomarkers' distribution. Therefore, although the batch size is very small caused by our large volume, a reliable (negative log partial) likelihood loss is still able to be calculated on a representative probability distribution for robust optimization. 2) Our PPL simultaneously learns an additional manual biomarkers prediction task to embed clinical prior knowledge into our deep prognosis prediction task in hidden and explicit ways. Therefore, it will prompt the prediction of deep biomarkers and improve the perception of task-dependent features in our low-contrast regions. Our P 2-Net achieves a high prognostic correlation of the prediction and great generalization with the highest 70.19% C-index and 2.14 HR. Extensive experiments with promising results on our PAH prognosis prediction reveal powerful prognosis performance and great clinical significance in PAH treatment. All of our code will be made publicly available online Opened source: https://github.com/YutingHe-list/P2-Net.

Identification of key biomarkers associated with immune cells infiltration for myocardial injury in dermatomyositis by integrated bioinformatics analysis.

BACKGROUND: Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood. METHODS: In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein-protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples. RESULTS: Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009). CONCLUSION: Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM.

A longan yield estimation approach based on UAV images and deep learning.

Longan yield estimation is an important practice before longan harvests. Statistical longan yield data can provide an important reference for market pricing and improving harvest efficiency and can directly determine the economic benefits of longan orchards. At present, the statistical work concerning longan yields requires high labor costs. Aiming at the task of longan yield estimation, combined with deep learning and regression analysis technology, this study proposed a method to calculate longan yield in complex natural environment. First, a UAV was used to collect video images of a longan canopy at the mature stage. Second, the CF-YD model and SF-YD model were constructed to identify Cluster_Fruits and Single_Fruits, respectively, realizing the task of automatically identifying the number of targets directly from images. Finally, according to the sample data collected from real orchards, a regression analysis was carried out on the target quantity detected by the model and the real target quantity, and estimation models were constructed for determining the Cluster_Fruits on a single longan tree and the Single_Fruits on a single Cluster_Fruit. Then, an error analysis was conducted on the data obtained from the manual counting process and the estimation model, and the average error rate regarding the number of Cluster_Fruits was 2.66%, while the average error rate regarding the number of Single_Fruits was 2.99%. The results show that the method proposed in this paper is effective at estimating longan yields and can provide guidance for improving the efficiency of longan fruit harvests.

A new strategy to alleviate the obesity induced by endocrine disruptors-A unique lysine metabolic pathway of nanoselenium Siraitia grosvenorii to repair gut microbiota and resist obesity.

Obesity caused by endocrine disruptors (EDCs) has become a hot topic threatening human health. Recently, Nanoselenium Siraitia grosvenorii (NSG) has been shown to have potential health-modulating uses. Based on the results of 16S rRNA sequencing and metabolomics analysis, NSG has the unique function of improving gut microbiota and inhibiting obesity. Specifically, NSG can enhance gut microbiota diversity and change their composition. A significant positive correlation exists between the liver change in lysine and the high-importance dominant species ([Ruminococcus]_gnavus, Alistipes_finegoldii, etc.). NSG metabolites analysis showed that the lysine level increased by 44.45% and showed a significantly negatively correlated with (TG, TC, Leptin, etc.). Significantly, NSG reduces the degradation of lysine metabolism in the liver and inhibits fatty acid ß-oxidation. In addition, NSG decreased Acetyl-CoA levels by 24% and regulated the downregulation of TCA genes (CS, Ogdh, Fh1, and Mdh2) and the upregulation of ketone body production genes (BDH1). NSG may have a positive effect on obesity by reducing the participation of Acetyl-CoA in the TCA cycle pathway and enhancing the ketogenic conversion of Acetyl-CoA. In conclusion, the results of this study may provide a new dietary intervention strategy for preventing endocrine disruptor-induced obesity.

Model construction of factors influencing intensive care unit nurses' medical device-related pressure injury knowledge, attitude, and practice.

The ability of knowledge, attitude, and practice of intensive care unit (ICU) nurses to perform medical device-related pressure injuries (MDRPIs) can affect the incidence of MDRPI in ICU patients. Therefore, in order to improve ICU nurses' understanding and nursing ability of MDRPIs, we investigated the non-linear relationship (synergistic and superimposed relationships) between the factors influencing ICU nurses' ability of knowledge, attitude, and practice. A Clinical Nurses' Knowledge, Attitude, and Practice Questionnaire for the Prevention of MDRPI in Critically Ill Patients was administered to 322 ICU nurses from tertiary hospitals in China from January 1, 2022 to June 31, 2022. After the questionnaire was distributed, the data were collected and sorted out, and the corresponding statistical analysis and modelling software was used to analyse the data. IBM SPSS 25.0 software was used to conduct Single factor analysis and Logistic regression analysis on the data, so as to screen the statistically significant influencing factors. IBM SPSS Modeler18.0 software was used to construct a decision tree model of the factors influencing MDRPI knowledge, attitude, and practice of ICU nurses, and ROC curves were plotted to analyse the accuracy of the model. The results showed that the overall passing rate of ICU nurses' knowledge, attitude, and practice score was 72%. The statistically significant predictor variables ranked in importance were education background (0.35), training (0.31), years of working (0.24), and professional title (0.10). AUC = 0.718, model prediction performance is good. There is a synergistic and superimposed relationship between high education background, attended training, high years of working and high professional title. Nurses with the above factors have strong MDRPI knowledge, attitude, and practice ability. Therefore, nursing managers can develop a reasonable and effective scheduling system and MDRPI training program based on the study results. The ultimate goal is to improve the ability of ICU nurses to know and act on MDRPI and to reduce the incidence of MDRPI in ICU patients.

Intergenerational reproductive toxicity of parental exposure to prothioconazole and its metabolite on offspring and epigenetic regulation associated with DNA methylation in zebrafish.

Prothioconazole (PTC) is a widely used agricultural fungicide, and its parent and metabolite prothioconazole-desthio (dPTC) have been detected in diverse environmental media. This study was aimed at investigating the gender-dependent effects on adult zebrafish reproduction and intergenerational effects on offspring development following parental exposure to PTC and dPTC. The results showed that after the adult zebrafish (F0) was exposed to 0.5 and 10 µg/L PTC and dPTC for 21 days, the fertility and gametogenesis of female zebrafish were decreased more significantly than that of male zebrafish. After that, three fecundity tests were conducted in the exposure period to explore the development endpoints of F1 embryos/larvae without further treatment with PTC and dPTC exposure. However, PTC and dPTC exposure did lead to abnormal development of F1 embryos, including delayed hatching, shortened body length, abnormal development and significant changes in locomotor behavior. These changes were related to the abnormal expression of sex hormones and the regulation of DNA methylation in F0 fish. In a word, the results of this study showed that parental PTC and dPTC interference have sex-dependent reproductive toxicity on F0 zebrafish, which may be passed on to the next generation through epigenetic modification involving DNA methylation, resulting in alternations in growth phenotype of offspring.

Ythdf2 promotes pulmonary hypertension by suppressing Hmox1-dependent anti-inflammatory and antioxidant function in alveolar macrophages.

Pulmonary hypertension (PH) is a devastating disease characterized by irreversible pulmonary vascular remodeling (PVR) that causes right ventricular failure and death. The early alternative activation of macrophages is a critical event in the development of PVR and PH, but the underlying mechanisms remain elusive. Previously we have shown that N6-methyladenosine (m6A) modifications of RNA contribute to phenotypic switching of pulmonary artery smooth muscle cells and PH. In the current study, we identify Ythdf2, an m6A reader, as an important regulator of pulmonary inflammation and redox regulation in PH. In a mouse model of PH, the protein expression of Ythdf2 was increased in alveolar macrophages (AMs) during the early stages of hypoxia. Mice with a myeloid specific knockout of Ythdf2 (Ythdf2Lyz2 Cre) were protected from PH with attenuated right ventricular hypertrophy and PVR compared to control mice and this was accompanied by decreased macrophage polarization and oxidative stress. In the absence of Ythdf2, heme oxygenase 1 (Hmox1) mRNA and protein expression were significantly elevated in hypoxic AMs. Mechanistically, Ythdf2 promoted the degradation of Hmox1 mRNA in a m6A dependent manner. Furthermore, an inhibitor of Hmox1 promoted macrophage alternative activation, and reversed the protection from PH seen in Ythdf2Lyz2 Cre mice under hypoxic exposure. Together, our data reveal a novel mechanism linking m6A RNA modification with changes in macrophage phenotype, inflammation and oxidative stress in PH, and identify Hmox1 as a downstream target of Ythdf2, suggesting that Ythdf2 may be a therapeutic target in PH.

Substantial Improvement of an Epimerase for the Synthesis of D-Allulose by Biosensor-Based High-Throughput Microdroplet Screening.

Biosynthesis of D-allulose has been achieved using ketose 3-epimerases (KEases), but its application is limited by poor catalytic performance. In this study, we redesigned a genetically encoded biosensor based on a D-allulose-responsive transcriptional regulator for real-time monitoring of D-allulose. An ultrahigh-throughput droplet-based microfluidic screening platform was further constructed by coupling with this D-allulose-detecting biosensor for the directed evolution of the KEases. Structural analysis of Sinorhizobium fredii D-allulose 3-epimerase (SfDAE) revealed that a highly flexible helix/loop region exposes or occludes the catalytic center as an essential lid conformation regulating substrate recognition. We reprogrammed SfDAE using structure-guided rational design and directed evolution, in which a mutant M3-2 was identified with 17-fold enhanced catalytic efficiency. Our research offers a paradigm for the design and optimization of a biosensor-based microdroplet screening platform.

Application study of RGB color extraction in water toxicity detection.

In this work, a colorimetric biosensor based on the rapid color change of Escherichia coli DH 5α (E. coli) and p-benzoquinone (BQ) was introduced to evaluate water toxicity. Here, dark brown quinhydroquinone (QHQ) was obtained from the reaction between E. coli and BQ. The inhibition ratios were calculated by RGB (red, green, blue) values of samples or oxidation current of hydroquinone (HQ). Here, RGB technology was used for biotoxicity assessment for the first time. The results suggested that the biosensor-based RGB has an obvious dose-dependent response. The IC20 values of Hg2+ and Cu2+ obtained based on RGB values were 1.0 and 1.5 mg L-1, respectively. This biosensor can be used to detect quickly toxicity of the Cu2+ and Hg2+ in water without complicated operation steps. Therefore, the biosensor has potential application value in the field of water toxicity detection.