Low-dose metformin targets the lysosomal AMPK pathway through PEN2.

Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.

Omics studies of DNA G-/C-quadruplexes in plants.

Genome-wide studies of DNA G- and C-quadruplexes (G4s and i-motifs, respectively) can boost the pace of progress towards a comprehensive understanding of their biological implications and practical applications in plants. We summarize the current state of knowledge about omics studies in order to highlight the current challenges and propose future directions to take studies of plant quadruplexes to the next step.

Prognosis of Acute HEV Infection in Patients With Liver Cirrhosis: A Retrospective Study of 628 Chinese Patients.

Acute hepatitis E virus infection is a serious global health problem, which a significant cause of morbidity and mortality. The aim of the present study was to characterise the clinical features and therapeutic response of patients with acute HEV infection and identify risk factors for poor prognosis. In a retrospective study from 01 January 2014 to 01 Januray 2022, we collected baseline data from all patients eligible for acute hepatitis E virus (HEV) infection and followed up with all patients via interviews and medical records. We explored the clinical feature of Chinese patients with acute HEV infection. The follow-up data of patients were used to identify risk factors for poor prognosis. In total, 628 acute hepatitis E (AHE) patients fulfilled the inclusion criteria and did not meet the exclusion criteria. Among them, 452 were males and 176 were females (M:F = 2.57:1). The median age at diagnosis was 57.0 years (interquartile range: 46-64 years). The median baseline serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were elevated in this cohort (642.3 U/L, 216.2 U/L, 104.1 µmol/L, respectively). The median hospitalisation duration was 16 days. Compared with patients without other liver diseases, patients with liver cirrhosis show lower baseline ALT and AST level, poorer coagulation indices and higher MELD scores. According to multivariate analysis, liver cirrhosis, high MELD score, low albumin concentration was found to be independent predictors of poor prognosis in patients with AHE. Our study used a lager sample size to validate that some demographic and serological features were quite different between patients with/without CLDs. Liver cirrhosis was a significant independent predictor of poor prognosis in acute HEV hepatitis.

R-loops act as regulatory switches modulating transcription of COLD-responsive genes in rice.

COLD is a major naturally occurring stress that usually causes complex symptoms and severe yield loss in crops. R-loops function in various cellular processes, including development and stress responses, in plants. However, how R-loops function in COLD responses is largely unknown in COLD susceptible crops like rice (Oryza sativa L.). We conducted DRIP-Seq along with other omics data (RNA-Seq, DNase-Seq and ChIP-Seq) in rice with or without COLD treatment. COLD treatment caused R-loop reprogramming across the genome. COLD-biased R-loops had higher GC content and novel motifs for the binding of distinct transcription factors (TFs). Moreover, R-loops can directly/indirectly modulate the transcription of a subset of COLD-responsive genes, which can be mediated by R-loop overlapping TF-centered or cis-regulatory element-related regulatory networks and lncRNAs, accounting for c. 60% of COLD-induced expression of differential genes in rice, which is different from the findings in Arabidopsis. We validated two R-loop loci with contrasting (negative/positive) roles in the regulation of two individual COLD-responsive gene expression, as potential targets for enhanced COLD resistance. Our study provides detailed evidence showing functions of R-loop reprogramming during COLD responses and provides some potential R-loop loci for genetic and epigenetic manipulation toward breeding of rice varieties with enhanced COLD tolerance.

Genomic variations combined with epigenetic modifications rewire open chromatin in rice.

Cis-regulatory elements (CREs) fine-tune gene transcription in eukaryotes. CREs with sequence variations play vital roles in driving plant or crop domestication. However, how global sequence and structural variations (SVs) are responsible for multilevel changes between indica and japonica rice (Oryza sativa) is still not fully elucidated. To address this, we conducted multiomic studies using MNase hypersensitivity sequencing (MH-seq) in combination with RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and bisulfite sequencing (BS-seq) between the japonica rice variety Nipponbare (NIP) and indica rice variety 93-11. We found that differential MNase hypersensitive sites (MHSs) exhibited some distinct intrinsic genomic sequence features between NIP and 93-11. Notably, through MHS-genome-wide association studies (GWAS) integration, we found that key sequence variations may be associated with differences of agronomic traits between NIP and 93-11, which is partly achieved by MHSs harboring CREs. In addition, SV-derived differential MHSs caused by transposable element (TE) insertion, especially by noncommon TEs among rice varieties, were associated with genes with distinct functions, indicating that TE-driven gene neo- or subfunctionalization is mediated by changes of chromatin openness. This study thus provides insights into how sequence and genomic SVs control agronomic traits of NIP and 93-11; it also provides genome-editing targets for molecular breeding aiming at improving favorable agronomic properties.

Modification of the electrokinetic motion of microalgae through light illumination for viability assessment.

The viability detection of microalgae with the electrokinetic (EK) technique shows vast applications in the biology and maritime industry. However, due to the slight variations in the EK properties between alive and dead microalgae cells, the accuracy and practicability of this technique is limited. In this paper, the light illumination pretreatment was conducted to modify the EK velocity of microalgae for enhancing the EK difference. The effects of the illumination time and light color on the EK velocities of Chlorella vulgaris and Isochrysis galbana were systematically measured, and the EK differences between alive and dead cells were calculated and compared. The results indicate that under light illumination, the photosynthesis of the alive cells leads to the amplification of the zeta potential, leading toward increase in the EK difference along with the illumination time. By using light with different color spectra to treat the microalgae, it was found that the EK difference changes with the light color according to the following order: white light > red light > blue light > green light. The difference in EK potential with exposure to white light treatment surpasses over 10-fold in comparison to those without such treatment. The light pretreatment technique, as illustrated in this study, offers an advantageous strategy to enhance the EK difference between living and dead cells, proving beneficial in the field of microalgae biotechnology.

Causal relationship between lipid-lowering drugs and ovarian cancer, cervical cancer: a drug target mendelian randomization study.

BACKGROUND: The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. METHODS: This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. RESULTS: The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. CONCLUSION: HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.

Synthesis of Antifouling Poly(ethylene glycol) Brushes via "Grafting to" Approach for Improved Biodistribution.

Polyethylene glycol (PEG) modification of materials has been identified to mitigate the challenge of biofouling. However, the practical application of PEGylation has been hampered by a low PEGylation density on the material surface. Therefore, developing efficient strategies to promote the PEGylation density is crucial. In this study, PEG brushes (PBs) with various structures were synthesized and their physicochemical properties and biomedical applications were investigated. Compared to benzaldehyde (BA), o-phthalaldehyde (OPA) exhibited higher reactivity with amine groups, resulting in increased grafting density (as high as 96.3%) and improved antifouling properties of PEG brushes. Bottlebrushes fabricated by PEG-OPA and polylysine demonstrated a prolonged circulation time in blood and enhanced potential for magnetic resonance imaging of tumors. Furthermore, the rigidity of the backbone was found to be crucial for the antifouling properties of PEG brushes both in vitro and in vivo. These findings are significant and provide valuable insights into designing biomaterials with superior antifouling performance.

Analysis of characteristic and postexposure practices of occupational blood and body fluid exposures among health care workers in Chinese tertiary hospitals: a retrospective ten-year study.

BACKGROUND: Occupational blood and body fluid exposure (OBEs) is a highly concerning global health problem in health facilities. Improper or inadequate post-exposure practices increase the risk of infection with bloodborne pathogens. Understanding risk factors for OBEs and evaluating the post-exposure practices will contribute to healthcare workers' (HCWs) well-being. METHODS: This study retrospectively synthesized and reviewed the 10-year data (from 2010 to 2020) on OBEs in a tertiary teaching hospital. RESULTS: A total of 519 HCWs have reported OBEs, increasing yearly from 2010 to 2020. Of these, most were nurses (247 [47.2%]), female (390 [75.1%]), at 23-27 years old (207 [39.9%]). The hepatitis B was the primary bloodborne pathogen exposed to HCWs, with 285 (54.9%) cases, internal medicine was the main exposure site (161 [31.0%]), and sharp injury was the main exposure route (439 [84.6%]). Data analysis shows that there are significant differences between exposure route, exposed pathogens, and exposure site among the different occupational categories (X2 = 14.5, 43.7, 94.3, all P < 0.001). 3.3% of HCWs did not take any post-exposure practices. For percutaneous exposure, 4.7% did not rinse the wound, 3.3% did not squeeze out the wound, and 2.3% did not disinfect the wound. In the case of mucosal exposure, 90.4% clean the exposure area immediately. CONCLUSIONS: The data from the past decade underscores the seriousness of current situation of OBEs in Chinese tertiary hospital, particularly among young HCWs, and with hepatitis B as the predominant blood-borne pathogen. This study also identifies HCWs may take incorrect post-exposure practices. It's crucial in the future to discuss the effectiveness of main groups targeted for focused specialty-specific guidance for the prevention of such accidents, meanwhile, to include blood-borne disease immunity testing in mandatory health check-ups. Additionally, focus on optimizing post-exposure practices, offering significant steps toward prevention of such incidents and reducing infection risks should also be considered in future studies.

Design, synthesis and optimization of pyrazolo[3,4-b] pyridine derivatives as Hsp110-STAT3 interaction disruptors for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal cardiovascular disorder that is characterized by pulmonary vascular remodeling. Our previous results demonstrated that heat shock protein (Hsp110) was significantly activated to induce vascular remodeling by enhancing the Hsp110-STAT3 interaction. The development of inhibitors that disrupt this association represents a novel strategy for the treatment of PAH. This study is committed to finding new inhibitors targeting the Hsp110-STAT3 interaction based on the structure of the lead compound 2h. A fusion design principle was employed in conjunction with structural optimization in the identification of the compound 10b. In vitro data indicates that 10b exhibited greater potency in the inhibition of pulmonary vascular cells malignant phenotypes via impeding the chaperone function of Hsp110 and the Hsp110-STAT3 interaction. In hypoxia-induced PAH rats, administration of 10b significantly attenuated vascular remodeling and right ventricular hypertrophy by inhibiting the Hsp110-STAT3 association. In short, this work identified a novel and promising lead compound for the development of anti-PAH drugs targeting the Hsp110-STAT3 interaction.

ß-arrestin2: an emerging player and potential therapeutic target in inflammatory immune diseases.

ß-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that ß-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-ß pathways of non-GPCRs. Earlier studies have identified that ß-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, ß-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of ß-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of ß-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases.

Impacts of cardiometabolic risk factors and alcohol consumption on all-cause mortality among MASLD and its subgroups.

BACKGROUND AND AIMS: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been introduced. However, research on this new nomenclature and definition remains limited. This study aims to assess the impact of cardiometabolic risk factors and alcohol consumption on all-cause mortality in MASLD and its subgroups. METHODS AND RESULTS: We included 2408 participants with MASLD in NHANES III and their linked mortality through 2019. MASLD patients were divided into two groups based on alcohol consumption: Pure MASLD and MetALD. The Cox proportional hazard model was used to assess the association between factors and all-cause mortality. During the median 26.0-year follow-up, there were 1040 deaths. The multivariable Cox regression analysis revealed a significant increase of over two-fold in the all-cause mortality rate among patients with four or more cardiometabolic risk factors compared to those with only one. When focusing on each component of cardiometabolic risk factors individually, only diabetes and hypertension were significantly associated with all-cause mortality (p < 0.05). In a subgroup analysis, each additional cardiometabolic factor was linked to an increase in all-cause mortality in both pure MASLD (hazard ratio 1.16; 95% CI 1.06-1.28; p = 0.002) and MetALD (HR 1.77; 95% CI 1.26-2.49; p = 0.001). Notably, an elevation in alcohol consumption was significantly associated with an increase in all-cause mortality rate only in the MetALD (p < 0.001). CONCLUSIONS: This study found that the presence of diabetes or hypertension was significantly associated with all-cause mortality. We also explored the different impacts of these factors and alcohol consumption within MASLD subgroups.

Serum uric acid and mortality in metabolic dysfunction-associated steatotic liver disease: Subgroup differences.

BACKGROUND AND AIMS: This study aims to investigate the association between serum uric acid (SUA) and both the risk and long-term mortality of dysfunction-associated steatotic liver disease (MASLD), and to explore differences between the pure MASLD and metabolic and alcohol related/associated liver disease (MetALD) subgroups. METHODS AND RESULTS: We included 11,675 participants from the Third National Health and Nutrition Examination Survey, with matched mortality data up to 2019. Logistic regression and Cox proportional hazards regression evaluated the relationship between SUA and both the risk and mortality of MASLD. Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. We found that SUA was positively associated with the risk of MASLD [odds ratio (OR): 1.19, 95 % confidence interval (CI) 1.12-1.27]. For pure MASLD, SUA showed a positive association with all-cause mortality [<4.7 mg/dL: hazard ratio (HR): 1.34, 95 % CI 1.04-1.73; ≥4.7 mg/dL: HR: 1.08, 95 % CI 1.02-1.15] and cardiovascular mortality (HR: 1.12, 95 % CI 1.02-1.22). For MetALD, there was an inverse J-shaped relationship (threshold: 6.6 mg/dL) between SUA and all-cause mortality. Below the threshold, SUA was negatively correlated with all-cause mortality (HR: 0.42, 95 % CI 0.19-0.93), but no association was found above it (HR: 0.81, 95 % CI 0.54-1.21). Additionally, no association was observed between SUA and cardiovascular mortality. CONCLUSIONS: SUA serves as an independent predictor of the risk and all-cause mortality of MASLD. The relationship between SUA and both all-cause and cardiovascular mortality differs between the pure MASLD and MetALD subgroups.

Whole genome resequencing reveals significant genetic differentiation between Exserohilum turcicum populations from maize and sorghum and candidate effector genes related to host specificity (Retracted).

After the manuscript was accepted, inconsistencies in the analyses were detected. These inconsistencies affected the general conclusion of the manuscript. This article was retracted on 27 March 2024. A peer-reviewed revised version was subsequently accepted: https://doi.org/10.1094/PHYTO-05-24-0172-R. Exserohilum turcicum is a devastating fungal pathogen that infects both maize and sorghum, leading to severe leaf diseases of the two crops. According to host specificity, pathogenic isolates of E. turcicum are divided into two formae speciales, namely E. turcicum f. sp. zeae and E. turcicum f. sp. sorghi. To date, the molecular mechanism underlying the host specificity of E. turcicum is marginally known. In this study, the whole genomes of 60 E. turcicum isolates collected from both maize and sorghum were resequenced, which enabled identification of 147,847 high-quality SNPs in total. Based on the SNPs, all isolates were clustered into four genetic groups that had a close relationship with host source. This observation was validated by the result of principal component analysis. The analysis of population structure revealed that there was obvious genetic differentiation between maize and sorghum host populations. Further analysis showed that 5,431 SNPs, including 612 nonsynonymous SNPs, were completely co-segregated with host source. These nonsynonymous SNPs were located in 539 genes in which 18 genes were predicted to encode secretory proteins, including six putative effector genes. The sequence polymorphism analysis of the six effector genes in 60 isolates indicated that these genes were perfectly co-segregated with host source. All SNVs in the coding regions of these genes were non-synonymous substitutions, suggesting that these genes were subject to strong positive selection pressure. These findings provide new insights into the molecular basis of host specificity in E. turcicum.

Whole-Genome Resequencing Reveals Significant Genetic Differentiation Between Exserohilum turcicum Populations from Maize and Sorghum and Candidate Effector Genes Related to Host Specificity.

Exserohilum turcicum is a devastating fungal pathogen that infects both maize and sorghum, leading to severe leaf diseases of the two crops. According to host specificity, pathogenic isolates of E. turcicum are divided into two formae speciales, namely E. turcicum f. sp. zeae and E. turcicum f. sp. sorghi. To date, the molecular mechanism underlying the host specificity of E. turcicum is marginally known. In this study, the whole genomes of 60 E. turcicum isolates collected from both maize and sorghum were resequenced, which enabled identification of 233,022 single-nucleotide polymorphisms (SNPs) in total. Phylogenetic analysis indicated that all isolates are clustered into four genetic groups that have a close relationship with host source. This observation is validated by the result of principal component analysis. Analysis of population structure revealed that there is obvious genetic differentiation between two populations from maize and sorghum. Further analysis showed that 5,431 SNPs, including 612 nonsynonymous SNPs, are completely co-segregated with the host source. These nonsynonymous SNPs are located in 539 genes, among which 18 genes are predicted to encode secretory proteins, including six putative effector genes named SIX13-like, Ecp6, GH12, GH28-1, GH28-2, and CHP1. Sequence polymorphism analysis revealed various numbers of SNPs in the coding regions of these genes. These findings provide new insights into the molecular basis of host specificity in E. turcicum.

Effect of a Mindfulness and Motivational Interviewing-Oriented Physical-Psychological Integrative Intervention for Community-Dwelling Spinal Cord Injury Survivors: A Mixed-Methods Randomized Controlled Trial.

OBJECTIVE: To evaluate the feasibility, acceptability, and efficacy of a mindfulness and motivational interviewing-oriented physical-psychological integrated intervention in community-dwelling spinal cord injury (SCI) survivors. DESIGN: A mixed-methods randomized controlled trial. SETTING: Local organizations for handicapped in Hong Kong. PARTICIPANTS: Community-dwelling adults with SCI (N=72). INTERVENTIONS: Participants in the intervention group (n=36) received video-guided exercise for daily practice and online group psychological (mindfulness and motivational interviewing-oriented) weekly sessions for 8 weeks. Participants in the control group (n=36) received an 8-week online group didactic education on lifestyle discussions and general health suggestions. MAIN OUTCOMES MEASURES: Primary outcomes included quality of life, physical activity, depression, and chronic pain. Secondary outcomes included exercise self-efficacy and mindfulness. Outcomes were measured at baseline, postintervention, and 3-month follow-up. Focus-group interviews were conducted postintervention. RESULTS: The recruitment, retention, and adherence rates were 84.7%, 100%, and 98.6%, respectively. The intervention showed significant positive effects on preventing declines in quality of life at 3-month follow-up (Cohen d=0.70, 95% CI=0.22-1.18). Positive trends manifested in physical activity, depression, chronic pain, and exercise self-efficacy. Three qualitative categories were identified: subjective improvements in exercise, physical, and social well-being; perceived changes in mindfulness and mental well-being; and intervention facilitators and barriers. CONCLUSIONS: The mindfulness and motivational interviewing-oriented physical-psychological integrated intervention is feasible and acceptable. The significant prolonged effect in maintaining quality of life and positive effects on physical and psychosocial well-being indicate its value to address major health challenges of community-dwelling SCI survivors.

Bilin-dependent regulation of chlorophyll biosynthesis by GUN4.

Biosyntheses of chlorophyll and heme in oxygenic phototrophs share a common trunk pathway that diverges with insertion of magnesium or iron into the last common intermediate, protoporphyrin IX. Since both tetrapyrroles are pro-oxidants, it is essential that their metabolism is tightly regulated. Here, we establish that heme-derived linear tetrapyrroles (bilins) function to stimulate the enzymatic activity of magnesium chelatase (MgCh) via their interaction with GENOMES UNCOUPLED 4 (GUN4) in the model green alga Chlamydomonas reinhardtii A key tetrapyrrole-binding component of MgCh found in all oxygenic photosynthetic species, CrGUN4, also stabilizes the bilin-dependent accumulation of protoporphyrin IX-binding CrCHLH1 subunit of MgCh in light-grown C. reinhardtii cells by preventing its photooxidative inactivation. Exogenous application of biliverdin IXα reverses the loss of CrCHLH1 in the bilin-deficient heme oxygenase (hmox1) mutant, but not in the gun4 mutant. We propose that these dual regulatory roles of GUN4:bilin complexes are responsible for the retention of bilin biosynthesis in all photosynthetic eukaryotes, which sustains chlorophyll biosynthesis in an illuminated oxic environment.

The health benefits of dietary polyphenols on pediatric intestinal diseases: Mechanism of action, clinical evidence and future research progress.

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.

CX43 and oxidative stress are the targets of BCB staining to predict the developmental potential of buffalo oocytes.

This study used the brilliant cresyl blue (BCB) staining method to group buffalo oocytes (BCB+ and BCB-) and perform in vitro maturation, in vitro fertilization and embryo culture. At the same time, molecular biology techniques were used to detect gap junction protein expression and oxidative stress-related indicators to explore the molecular mechanism of BCB staining to predict oocyte developmental potential. The techniques of buffalo oocytes to analyse their developmental potential and used immunofluorescence staining to detect the expression level of CX43 protein, DCFH-DA probe staining to detect ROS levels and qPCR to detect the expression levels of the antioxidant-related genes SOD2 and GPX1. Our results showed that the in vitro maturation rate, embryo cleavage rate and blastocyst rate of buffalo oocytes in the BCB+ group were significantly higher than those in the BCB- group and the control group (p < .05). The expression level of CX43 protein in the BCB+ group was higher than that in the BCB- group both before and after maturation (p < .05). The intensity of ROS in the BCB+ group was significantly lower than that in the BCB- group (p < .05), and the expression levels of the antioxidant-related genes SOD2 and GPX1 in the BCB+ group were significantly higher than those in the BCB- group (p < .05). Brilliant cresyl blue staining could effectively predict the developmental potential of buffalo oocytes. The results of BCB staining were positively correlated with the expression of gap junction protein and antioxidant-related genes and negatively correlated with the reactive oxygen species level, suggesting that the mechanism of BCB staining in predicting the developmental potential of buffalo oocytes might be closely related to antioxidant activity.

Interfacial galvanic replacement strategy for Pd-doped NiFe MOF nanosheets with highly efficient dopamine detection.

An interfacial galvanic replacement strategy to controllable synthesize palladium nanoparticles (Pd NPs)-modified NiFe MOF nanocomposite on nickel foam, which served as an efficient sensing platform for quantitative determination of dopamine (DA). Pd NPs grown in situ on the nanosheets of NiFe MOF via self-driven galvanic replacement reaction (GRR) and well uniform distribution was achieved. This method effectively reduced the aggregation of metallic nanoparticles and significantly promoted the electron transfer rate during the electrochemical process, leading to improved electrocatalytic activity for DA oxidation. Remarkably, the precisely constructed biosensor achieved a low detection limit (LOD) of 0.068 µM and recovery of 94.1% (RSD 6.7%, N = 3) for simulated real sample detection and also exhibited superior selectivity and stability. The results confirmed that the as-fabricated Pd-NiFe/NF composite electrode could realize the quantitative determination of DA and showed promising prospects in real sample biosensing.