Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure.

Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.

Efficacy and safety of prophylactic balloon occlusion in the management of placenta accreta spectrum disorder: a retrospective cohort study.

OBJECTIVE: Placenta accreta spectrum disorder (PAS) is a serious obstetric complication associated with significant maternal morbidity and mortality. Prophylactic balloon occlusion (PBO), as an intravascular interventional therapies, has emerged as a potential management strategy for controlling massive hemorrhage in patients with PAS. However, current evidence about the clinical application of PBO in PAS patients are still controversial. This study aimed to evaluate the effectiveness and safety of PBO in the management of PAS. METHODS: A retrospective cohort study including PAS patients underwent cesarean delivery was conducted in a tertiary hospital from January 2015 to March 2022. Included PAS patients were further divided into balloon and control groups by whether PBO was performed. Groups were compared for demographic characteristics, intraoperative and postoperative parameters, maternal and neonatal outcomes, PBO-related complication and follow up outcomes. Additionally, multivariate-logistic regression analysis was performed to determine the definitive associations between PBO and risk of massive hemorrhage and hysterectomy. RESULTS: A total of 285 PAS patients met the inclusion criteria were included, of which 57 PAS patients underwent PBO (PBO group) and 228 women performed cesarean section (CS) without PBO (control group). Irrespective of the differences of baseline characteristics between the two groups, PBO intervention did not reduce the blood loss, hysterectomy rate and postoperative hospital stay, but it prolonged the operation time and increased the cost of hospitalization (All P < 0.05) Additionally, there were no significant differences in postoperative complications, neonatal outcomes, and follow-up outcomes(All P > 0.05). In particular, patients undergoing PBO were more likely to develop the venous thrombosis postoperatively (P = 0.001). However, multivariate logistic regression analysis showed that PBO significantly decreased the risk of massive hemorrhage (OR 0.289, 95%CI:0.109-0.766, P = 0.013). The grade of PAS and MRI with S2 invasion were the significant risk factors affecting massive hemorrhage(OR:6.232 and OR:5.380, P<0.001). CONCLUSION: PBO has the potential to reduce massive hemorrhage in PAS patients undergoing CS. Obstetricians should, however, be aware of potential complications arising from the PBO. Additionally, MRI with S2 invasion and PAS grade will be useful to identify PAS patients who at high risk and may benefit from PBO. In brief, PBO seem to be a promising alternative for management of PAS, yet well-designed randomized controlled trials are needed to convincingly demonstrate its benefits and triage the necessity of PBO.

The mediating role of menstrual irregularity on obesity and sexual function in Chinese women with pelvic floor disorders: a cross-sectional study.

BACKGROUND: Sexual problems are common among women with pelvic floor disorders (PFD). Few studies have explored the relationship between obesity and sexual function in women with PFD. This study aimed to prove that obesity was a risk factor for worse sexual function in women with PFD, and to investigate the mediating role of menstrual irregularity. METHODS: This was a cross-sectional study involving 783 women with PFD from Shandong Province, China between June 2020 and February 2021. Female sexual function was assessed using the Pelvic Organ Prolapse/UI Sexual Questionnaire-12 (PISQ-12). Obesity was defined as BMI ≥ 28.0. Menstrual irregularity was defined as menstrual cycles ≥ 35 or menstrual cycles < 25 days. Logistic regression and multiple linear regression were employed to explore the association among obesity, menstrual irregularity and sexual function. RESULTS: Obesity was associated with worse PISQ-12 scores compared with normal- weight women (mean score 28.14 ± 7.03 versus 32.75 ± 5.66, p < 0.001). After adjusting for controlling variables, women with obesity (ß= -3.74, p < 0.001) and menstrual irregularity (ß= -3.41, p < 0.001) had a worse sexual function. Menstrual irregularity had a mediation effect on the association between obesity and sexual function. CONCLUSIONS: This study provided evidence that obesity was associated with worse sexual function in women with PFDs, and the effect of obesity on sexual function was partially mediated by menstrual irregularity. Weight control may have potential benefits for improving sexual function and preventing female sexual dysfunction. It's also important to pay attention to the menstrual cycle.

Evaluation of the accuracy of cone-beam computed tomography image segmentation of isolated tooth roots based on the dynamic threshold method.

OBJECTIVE: Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. METHOD: We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P < 0.05) and Bland-Altman plots to analyze the consistency of the two measurement methods. RESULTS: The results of the paired t-test showed that there was no significant difference in the RSAs obtained using the dynamic threshold method and the optical scanning image reconstruction (t = 1.005, P = 0.325 > 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. CONCLUSION: In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA.

The mediating effect of the prolonged second stage of labor on delivery mode and urinary incontinence among postpartum women: evidence from Shandong, China.

INTRODUCTION AND HYPOTHESIS: This study was aimed at exploring the mediating role of the prolonged second stage of labor (PSSL) in the association between delivery mode and urinary incontinence (UI) among postpartum women in Shandong, China. METHODS: A cross-sectional study involving postnatal women from the Women's Pelvic Floor Functional Health Center in Shandong, China, was conducted. An electronic questionnaire was used to collect the data between June 2020 and February 2021. UI was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Logistic regression and multiple linear regression were employed to explore the association among delivery mode, PSSL, and UI, and the mediating role of PSSL. RESULTS: Among the total of 5,586 postpartum women included in this study, the prevalence of UI was 13.3%. Among the 742 patients with UI, the prevalence of stress urinary incontinence (78.3%) was greater than urge urinary incontinence (8.6%), mixed urinary incontinence (9.3%), and others (3.8%). After adjusting for controlling variables, delivery mode was found to be significantly associated with PSSL, whereby women with vaginal delivery were more likely to be in PSSL, and women with PSSL had a higher probability of suffering from UI. PSSL played a partial mediating effect in delivery mode and UI. CONCLUSIONS: This study provided evidence that the effect of delivery mode on UI was partially mediated by PSSL among postpartum women in Shandong, China. Strategies to prevent PSSL should be actively adopted to reduce the risk of UI in women.

Acute effect of fine particulate matter and respiratory mortality in Changsha, China: a time-series analysis.

BACKGROUND: Previous studies have confirmed that exposure to fine particulate matter (PM2.5) is associated with respiratory disease mortality. However, due to the differences in PM2.5 concentration, composition and population susceptibility within different regions, the estimates of the association between PM2.5 concentration and mortality are different. Moreover, few studies have examined the potential hazard of excessive PM2.5 exposure in terms of respiratory disease mortality. METHODS: Daily recorded data on meteorological indices, environmental pollutants, and causes of death data in Changsha from January 2015 to December 2018 were obtained. The potential relationship between PM2.5 concentrations and respiratory disease mortality was determined using distributed lag nonlinear model (DLNM), which includes the relative risk (RR) and cumulative relative risk (CRR) of the lagged effect. The synergistic effects of other air pollutants were also considered. RESULTS: A total of 8,825 cases of respiratory disease mortality occurred in Changsha between 2015 and 2018. The acute effect of PM2.5 concentration was associated with an increased risk of respiratory disease mortality. Regarding the lag specific effect, a 10 µg/m3 increase in PM2.5 concentration on respiratory disease mortality was statistically significant at lag day 0 and lag day 7 with a relative risk of 1.019 (95% CI 1.007- 1.031) and 1.013(95%CI: 1.002-1.024). As for the cumulative lag effect, a 4-day moving average of PM2.5 concentrations was significantly associated with a cumulative relative risk of 1.027 (95%CI: 1.011-1.031). The single-day lag effect and cumulative 4-day lag effect for male individuals were more significant than those observed in females. The effect of PM2.5 concentrations and respiratory disease mortality remained statistically significant in the multi-pollutant models (SO2, NO2, and O3). A higher risk was observed in the cold season than in the warm season. CONCLUSIONS: Our findings show a potential association between exposure to PM2.5 concentration and respiratory disease mortality in Changsha, with male individuals observed to have particularly higher risk.

Circulating noncoding RNAs as early predictive biomarkers in preeclampsia: a diagnostic meta-analysis.

BACKGROUND: We designed a meta-analysis to evaluate the clinical significance and efficacy of circulating noncoding RNAs (ncRNAs) in the early prediction of preeclampsia. METHODS: PubMed, Embase and the Cochrane Library were used to search for literature. The combined prediction performance was evaluated by calculating the area under the summary receiver operator characteristic (SROC) curve. The potential sources of heterogeneity were analysed by meta-regression analysis and subgroup analysis. All statistical analyses and mapping were performed by RevMan 5.3 and Stata 12.0. RESULTS: A total of 41 studies from 14 articles, including 557 preeclampsia patients and 842 controls, were included in our meta-analysis. All studies collected blood before onset. NcRNAs in blood performed relatively well in predicting preeclampsia. The combined sensitivity was 0.71, the specificity was 0.84, and the area under the SROC curve (AUC) was 0.86. Peripheral blood mononuclear cell (PBMC) samples showed the best diagnostic accuracy. The combined AUC was 0.93. Combined detection was better than single detection, and miRNA was better than circRNA. The heterogeneity of the study was determined by sample size, lncRNA characteristics, lncRNA source and race. CONCLUSION: Circulating ncRNAs can be valuable biomarkers used as candidates for noninvasive early predictive biomarkers of preeclampsia and have great clinical application prospects. The clinical value of ncRNAs needs to be tested by further multicentre, comprehensive and prospective studies, and the test criteria should be established.

Characterization of Rhopalosiphum padi takeout-like genes and their role in insecticide susceptibility.

Due to the extensive use of chemical insecticides, the field populations of Rhopalosiphum padi, a serious wheat pest worldwide, have developed resistance to insecticides. Therefore, deep understanding of the mechanisms of the aphid's physiological response to insecticides would be of importance for the management of insecticide resistance in pests. Takeout belongs to a protein superfamily found exclusively in insects. Previous research showed that the takeout gene had various functions in insect physiology and behavior. However, few studies have explored the functions of takeout in insect insecticide susceptibility. The susceptibility of R. padi to imidacloprid and beta-cypermethrin was tested. Thirteen takeout-like genes were identified based on the genome database of R. padi. The number of exons was variable in these takeout-like genes, and nine highly conserved amino acids (two Cysteine, two Proline, four Glycine and one Aspartic acid) were identified. Expression levels of takeout-like-2, takeout-like-3, takeout-like-5, takeout-like-8, takeout-like-10 and takeout-like-11 were significantly increased after imidacloprid treatment; seven genes (takeout-like-1, takeout-like-2, takeout-like-5, takeout-like-6, takeout-like-7, takeout-like-8 and takeout-like-11) tended to be upregulated after beta-cypermethrin treatment. RNA interference results showed that the mortalities of R. padi injected with dsTOL-2, dsTOL-5, dsTOL-8, dsTOL-10 and dsTOL-11 were significantly increased after exposure to imidacloprid in comparison with control (injection of dsGFP). Under two sublethal concentrations of beta-cypermethrin, the silencing of takeout-like-2, takeout-like-5 and takeout-like-11 significantly increased the mortalities of R. padi. These results provide evidence for the involvement of takeout-like genes in insecticide susceptibility of R. padi, which improves our understanding the determinant of insecticide susceptibility.

Lack of evidence of hepatitis in patients with oral lichen planus in China: A case control study.

BACKGROUND: China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China. MATERIAL AND METHODS: A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on. RESULTS: The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same. CONCLUSIONS: Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in China.

Interferon-γ regulates the function of mesenchymal stem cells from oral lichen planus via indoleamine 2,3-dioxygenase activity.

BACKGROUND: Little is known about mesenchymal stem cells (MSCs) in normal or inflammatory oral mucosal tissues, such as in oral lichen planus (OLP). Our objectives were to identify, isolate, and characterize MSCs from normal human oral mucosa and OLP lesions, and to evaluate indoleamine 2,3 dioxygenase (IDO) activity in mediating immunomodulation of MSCs from these tissues. METHODS: Expressions of MSCs-related markers were examined in isolated cells by flow cytometry. Self-renewal and multilineage differentiations were studied to characterize these MSCs. Interferon-γ (IFN-γ), IDO, and STRO-1 were assessed by immunofluorescence. MSCs from oral mucosa and OLP or IFN-γ-pretreated MSCs were co-cultured with allogeneic mixed lymphocyte reaction assays (MLR). Proliferation and apoptosis of MLR or MSCs were detected by CCK8 and the annexin V-FITC apoptosis detection kit, respectively. IDO expression and activity were measured by real-time PCR, Western blotting, and high-performance liquid chromatography. RESULTS: Isolated cells from oral mucosa and OLP expressed MSC-related markers STRO-1, CD105, and CD90 but were absent for hematopoietic stem cell markers CD34. Besides, they all showed self-renewal and multilineage differentiation capacities. MSCs in OLP presented STRO-1/IDO+ phenotype by immunofluorescence. MSCs and IFN-γ-pretreated MSCs could inhibit lymphocyte proliferation via IDO activity, but not via cell apoptosis. Long-term IFN-γ could also inhibit MSC proliferation via IDO activity. CONCLUSIONS: Mesenchymal stem cells can be isolated from human oral mucosa and OLP tissues. Besides self-renewal and multilineage differentiation properties, these cells may participate in immunomodulation mediated by IFN-γ via IDO activity in human OLP.

Automatic tooth periodontal ligament segmentation of cone beam computed tomography based on instance segmentation network.

Objective: The three-dimensional morphological structures of periodontal ligaments (PDLs) are important data for periodontal, orthodontic, prosthodontic, and implant interventions. This study aimed to employ a deep learning (DL) algorithm to segment the PDL automatically in cone-beam computed tomography (CBCT). Method: This was a retrospective study. We randomly selected 389 patients and 1734 axial CBCT images from the CBCT database, and designed a fully automatic PDL segmentation computer-aided model based on instance segmentation Mask R-CNN network. The labels of the model training were 'teeth' and 'alveolar bone', and the 'PDL' is defined as the region where the 'teeth' and 'alveolar bone' overlap. The model's segmentation performance was evaluated using CBCT data from eight patients outside the database. Results: Qualitative evaluation indicates that the PDL segmentation accuracy of incisors, canines, premolars, wisdom teeth, and implants reached 100%. The segmentation accuracy of molars was 96.4%. Quantitative evaluation indicates that the mIoU and mDSC of PDL segmentation were 0.667 ± 0.015 (>0.6) and 0.799 ± 0.015 (>0.7) respectively. Conclusion: This study analysed a unique approach to AI-driven automatic segmentation of PDLs on CBCT imaging, possibly enabling chair-side measurements of PDLs to facilitate periodontists, orthodontists, prosthodontists, and implantologists in more efficient and accurate diagnosis and treatment planning.

Selection, inheritance, life-history traits, and flight capacity of Grapholita molesta (Lepidoptera: Tortricidae) resistant to lambda-cyhalothrin.

Grapholita molesta (Busck) (Lepidoptera: Tortricidae) is a globally significant fruit pest traditionally managed using chemical insecticides such as lambda-cyhalothrin. However, repeated applications have led to the development of resistance in field populations. The mechanisms and fitness costs associated with lambda-cyhalothrin resistance in G. molesta remain poorly understood. In this study, we established a lambda-cyhalothrin-resistant strain (RS) of G. molesta through continuous selection with lambda-cyhalothrin in the laboratory for 21 generations, resulting in a 249.6-fold increase in resistance. Bioassay data from the F1 progeny (F1RS and F1SR) of reciprocal crosses between RS and susceptible strain (SS) showed similar degrees of dominance (0.40 for F1RS and 0.32 for F1SR). Significant differences between observed and expected mortalities of backcross individuals suggested that resistance to lambda-cyhalothrin is polygenic. Compared to the SS strain, the RS strain exhibited significantly prolonged periods of larval, prepupal, and pupal stages, as well as a significant decrease in larval weight. In addition, the RS strain showed significant reductions in fecundity, cumulative flight distance, maximum flight distance, cumulative flight time, maximum flight time, and average flight speed. These results suggest that resistance to lambda-cyhalothrin in G. molesta is autosomal, incompletely dominant, and polygenic. Life-history traits such as fecundity and flight capacity were significantly reduced in RS strains compared with the SS strain. These findings provide valuable insights for mitigating lambda-cyhalothrin resistance development and promoting sustainable control of G. molesta in the field.

Effectiveness and pharmacological mechanisms of Chinese herbal medicine for coronary heart disease complicated with heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is widely used for treating coronary heart disease complicated with heart failure (CHD-HF). However, the exact mechanisms involved are still not fully understood. AIM OF THE STUDY: To assess the clinical effectiveness and potential pharmacological mechanisms of CHM for treating CHD-HF. METHODS: Eight databases were retrieved for Randomized Controlled Trials of CHM for CHD-HF published from their inception to March 2023. Quality assessment of include studies was performed by the Cochrane risk-of-bias. Meta-analysis was used to assess the effectiveness of CHM for CHD-HF, and then core drugs and active ingredients were selected by data mining and network pharmacology. Finally, cluster and enrichment analysis were adopted to explore the potential targets and signaling pathways. RESULTS: A total of 52 studies enrolling 5216 patients were included. Meta-analysis revealed that CHM treatment groups significantly improved left ventricular ejection fraction (LVEF), 6-min walk test (6-MWT), left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD) than control groups: [LVEF: SMD = 0.7, 95%CI (0.54, 0.87), p < 0.00001, I2 = 80%; 6-MWT: SMD = 0.72, 95%CI (0.58, 0.86), p < 0.0001, I2 = 67%; LVEDD: SMD = -0.79, 95%CI (-0.89, -0.69), p < 0.0001, I2 = 49%; LVESD: SMD = -0.6 (-0.74, -0.46), p < 0.0001, I2 = 0%]. The results of various biological information analysis showed the internal relationship between prescriptions, core drugs, active ingredients and therapeutic targets. Twelve core herbs with the most commonly use and high correlation were selected from 110 CHMs of 52 prescriptions for CHD-HF treatment, and further 65 effective components were screened out according to the most strength value, which were divided into 12 compounds such as terpenoids, flavonoids, steroids and alkaloids and etc. At the same time, 67 therapeutic targets of active ingredients in CHD-HF were filtrated. On these bases, cluster and enrichment analysis of the components and targets were used to explore relevant pharmacological mechanisms, mainly including anti-myocardial cell damage, anti-inflammation, anti-apoptosis, anti-fibrosis, regulation of oxidative stress, anticoagulation and angiogenesis, and improvement of glucose and fatty acid metabolism. CONCLUSION: CHM are effective in treating CHD-HF compared with conventional treatment. Some of the included studies have high risks in the implementation of blinding, so more high-quality studies are needed. The active ingredients of CHM could protect the myocardium and improve pathological environment of CHD-HF in various ways. And CHM has the advantage of multi-component and multi-target treatment for complex diseases.

METTL16 participates in haemoglobin H disease through m6A modification.

BACKGROUND: Haemoglobin H (HbH) disease is caused by a disorder of α-globin synthesis, and it results in a wide range of clinical symptoms. M6A methylation modification may be one of the mechanisms of heterogeneity. Therefore, this article explored the role of methyltransferase like 16 (METTL16) in HbH disease. METHOD: The results of epigenetic transcriptome microarray were analysed and verified through bioinformatic methods and qRT-PCR, respectively. The overexpression or knock down of METTL16 in K562 cells was examined to determine its role in reactive oxygen species (ROS), cell cycle processes or iron overload. YTH domain family protein 3 (YTHDF3) was knocked down in K562 cells and K562 cells overexpressing METTL16 via siRNA to investigate its function. In addition, haemoglobin expression was detected through benzidine staining. qRT-PCR, WB, methylated RNA Immunoprecipitation (MeRIP) and (RNA Immunoprecipitation) RIP experiments were conducted to explore the mechanism of intermolecular interaction. RESULTS: METTL16, YTHDF3 and solute carrier family 5 member 3 (SLC5A3) mRNA and the methylation level of SLC5A3 mRNA were downregulated in HbH patients. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA expression was negatively correlated with HGB content among patients with HbH-CS disease. Overexpression of METTL16 increased ROS and intracellular iron contents in K562 cells, changed the K562 cell cycle, reduced hemin-induced haemoglobin synthesis, increased the expressions of SLC5A3 and HBG and increased SLC5A3 mRNA methylation levels. Knockdown of METTL16 reduced ROS and intracellular iron contents in K562 cells. Hemin treatment of K562 cells for more than 14 days reduced the protein expressions of METTL16 and SLC5A3 and SLC5A3 mRNA methylation levels. Knockdown of YTHDF3 rescued the intracellular iron content changes induced by the overexpression of METTL16. The RIP experiment revealed that SLC5A3 mRNA can be enriched by METTL16 antibody. CONCLUSION: METTL16 may affect the expression of SLC5A3 by changing its m6A modification level and regulating ROS synthesis, intracellular iron and cycle of red blood cells. Moreover, METTL16 possibly affects the expression of haemoglobin through IGF2BP3, which regulates the clinical phenotype of HbH disease.

The ATP-binding cassette transporter subfamily G member 4 mediates cuticular hydrocarbon transport to regulate drought tolerance in Acyrthosiphon pisum.

ABC transporters are a highly conserved membrane protein class that promote the transport of substances across membranes. Under drought conditions, insects primarily regulate the content of cuticular hydrocarbon (CHC) to retain water and prevent evaporative loss. Involvement of ABC transporter protein G (ABCG) subfamily genes in insect CHC transport has been relatively understudied. In this study, we demonstrated that ABCG4 gene in Acyrthosiphon pisum (ApABCG4) is involved in CHC transport and affects drought tolerance by regulating CHC accumulation. ApABCG4 is strongly expressed in the abdominal cuticle and embryonic stages of A. pisum. Effective silencing of ApABCG4 was achieved using RNAi, and the silencing duration was analyzed. ApABCG4 silencing resulted in a significant decrease in the total and component contents of the CHC and cuticular waxy coatings of A. pisum. Nevertheless, the internal hydrocarbon content remained unchanged. The lack of cuticular hydrocarbons significantly reduced the drought tolerance of A. pisum, shortening its survival time under drought stress. Drought stress caused significant upregulation of ApABCG4. Molecular docking showed that ApABCG4 has a high binding affinity for nine n-alkanes of CHC through electrostatic interactions. These results indicate that ApABCG4 is a novel RNAi target with key applications in aphid biological control.

MiRNA-494 induces trophoblast senescence by targeting SIRT1.

OBJECTIVE: Although the mechanism underlying preeclampsia (PE) has been widely explored, the mechanisms related to senescence have not yet been fully revealed. Therefore, we investigated the role of the miR-494/longevity protein Sirtuin 1 (SIRT1) axis in PE. METHODS: Human placental tissue was obtained from severe preeclampsia (SPE) (n = 20) and gestational age-matched normotensive pregnancies (n = 20), and senescence-associated ß-galactosidase (SAßG) and SIRT1 expression levels were measured. The TargetScan and miRDB databases predicted candidate miRNAs targeting SIRT1, and intersected with differentially expressed miRNAs in the GSE15789 dataset (p < 0.05, |log2FC|≥1.5). Subsequently, we showed that miRNA (miR)-494 expression was significantly elevated in SPE, revealing miR-494 as a candidate SIRT1-binding miRNA. A dual-luciferase assay confirmed the targeting relationship between miR-494 and SIRT1. The senescence phenotype, migration, cell viability, reactive oxygen species (ROS) production levels and inflammatory molecule expression levels were measured after miR-494 expression was altered. We conducted a rescue experiment using SIRT1 plasmids to further demonstrate the regulatory relationship. RESULTS: SIRT1 expression was lower(p < 0.01) and miR-494 expression was higher (p < 0.001) in SPE, and SaßG staining showed premature placental aging in SPE (p < 0.001). Dual-luciferase reporter assays revealed that miR-494 targeted SIRT1. Compared to control cells, HTR-8/SVneo cells with upregulation of miR-494 had remarkably downregulated SIRT1 expression (p < 0.001), more SAßG-positive cells (p < 0.001), cell cycle arrested (p < 0.05), and upregulated P21 and P16 expression (p < 0.01). miR-494 overexpression also decreased HTR-8/SVneo cell migration (p < 0.05) and ATP synthesis (p < 0.001), increased ROS levels (p < 0.001), and upregulated NLRP3 and IL-1ß expression (p < 0.01). SIRT1-overexpressing plasmids partially reversed the effects of miR-494 overexpression in HTR-8/SVneo cells. CONCLUSION: The miR-494/SIRT1 interaction plays a role in the mechanism of premature placental aging in PE patients.

Overexpression of the Chemosensory Protein CSP7 Gene Contributed to Lambda-Cyhalothrin Resistance in the Bird Cherry-Oat Aphid Rhopalosiphum padi.

Lambda-cyhalothrin is one of the most important pyrethroids used for controlling wheat aphids. Extensive spraying of lambda-cyhalothrin has led to the development of high resistance to this pyrethroid inRhopalosiphum padi. The mechanisms of resistance are complex and not fully understood. In this study, we found that a laboratory-selected strain of R. padi showed extremely high resistance to lambda-cyhalothrin and cross-resistance to bifenthrin and deltamethrin. The expression level of RpCSP7 was significantly elevated in the resistant strain compared to that in the susceptible strain. Knockdown of RpCSP7 increased the susceptibility of R. padi to lambda-cyhalothrin, whereas the susceptibility to bifenthrin and deltamethrin was not significantly changed. The recombinant RpCSP7 displayed a high affinity for lambda-cyhalothrin but no affinities to bifenthrin and deltamethrin. These findings suggest that the overexpression of RpCSP7 contributes to the resistance of R. padi to lambda-cyhalothrin. This study provides valuable insights into CSP-mediated insecticide resistance in insects.

The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy.

Background/aims: To investigate the specific effects of s odium-glucose transporter 2 inhibitor (SGLT2i) on cardiac energy metabolism. Methods: A systematic literature search was conducted in eight databases. The retrieved studies were screened according to the inclusion and exclusion criteria, and relevant information was extracted according to the purpose of the study. Two researchers independently screened the studies, extracted information, and assessed article quality. Results: The results of the 34 included studies (including 10 clinical and 24 animal studies) showed that SGLT2i inhibited cardiac glucose uptake and glycolysis, but promoted fatty acid (FA) metabolism in most disease states. SGLT2i upregulated ketone metabolism, improved the structure and functions of myocardial mitochondria, alleviated oxidative stress of cardiomyocytes in all literatures. SGLT2i increased cardiac glucose oxidation in diabetes mellitus (DM) and cardiac FA metabolism in heart failure (HF). However, the regulatory effects of SGLT2i on cardiac FA metabolism in DM and cardiac glucose oxidation in HF varied with disease types, stages, and intervention duration of SGLT2i. Conclusion: SGLT2i improved the efficiency of cardiac energy production by regulating FA, glucose and ketone metabolism, improving mitochondria structure and functions, and decreasing oxidative stress of cardiomyocytes under pathological conditions. Thus, SGLT2i is deemed to exert a benign regulatory effect on cardiac metabolic disorders in various diseases. Systematic review registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023484295).

GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome branching through gibberellic acid signaling in Arabidopsis.

Cell differentiation generally corresponds to the cell cycle, typically forming a non-dividing cell with a unique differentiated morphology, and Arabidopsis trichome is an excellent model system to study all aspects of cell differentiation. Although gibberellic acid is reported to be involved in trichome branching in Arabidopsis, the mechanism for such signaling is unclear. Here, we demonstrated that GLABROUS INFLORESCENCE STEMS (GIS) is required for the control of trichome branching through gibberellic acid signaling. The phenotypes of a loss-of-function gis mutant and an overexpressor showed that GIS acted as a repressor to control trichome branching. Our results also show that GIS is not required for cell endoreduplication, and our molecular and genetic study results have shown that GIS functions downstream of the key regulator of trichome branching, STICHEL (STI), to control trichome branching through the endoreduplication-independent pathway. Furthermore, our results also suggest that GIS controls trichome branching in Arabidopsis through two different pathways and acts either upstream or downstream of the negative regulator of gibbellic acid signaling SPINDLY (SPY).

Effects of Adult Feeding Treatments on Longevity, Fecundity, Flight Ability, and Energy Metabolism Enzymes of Grapholita molesta Moths.

The oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae) is one of the most severe fruit tree pests in China, causing huge economic losses to fruit production. So far, there are few detailed reports on the rearing protocols of G. molesta. In this study, we compared the longevity, 10-d fecundity, flight ability, and the activity of major energy metabolism enzymes in the flight muscles of G. molesta under three feeding regimes (supplement with sterile water, supplement with 10% honey solution and starvation) of the adult moths. The results showed that the longevity, 10-d fecundity, and flight parameters (cumulative flight distance and time, maximum flight distance and duration, and the average flight speed) of adult moths when supplemented with sterile water or honey solution were significantly higher than those of moths that were starved. There were no significant differences in the 10-d fecundity, flight parameters, and the activity of major energy metabolism enzymes of flight muscles between moths that were supplemented with sterile water or 10% honey solution. The flight muscles of G. molesta mainly used carbohydrates as an energy source when sterile water and honey solution were supplemented, and the moth mainly used lipids as an energy source under starvation. Considering the cost and potential for diet contamination during mass-rearing, supplying sterile water is considered a cost effective option for food substitution of adult G. molesta.