Biological characteristics of a new long-chain fatty acid transport protein 1 from Trichinella spiralis and its participation in lipid metabolism, larval moulting, and development.

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

Development and application of an artificial intelligence-assisted endoscopy system for diagnosis of Helicobacter pylori infection: a multicenter randomized controlled study.

BACKGROUND: The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection. MATERIALS AND METHODS: A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model. RESULTS: The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05). CONCLUSION: Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020)   ( www.chictr.org.cn ; registration number: ChiCTR2000037801).

Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis.

The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of pre-functionalized ketones facilitated by N-heterocyclic carbene and photo dual catalysis. This protocol features excellent substrate tolerance and can be applied to the convergent synthesis and late-stage functionalization of structurally complex bioactive ketones. Mechanistic investigations, including experimental studies and density functional theory (DFT) calculations, shed light on the reaction mechanism and elucidate the basis of the regioselectivity.

Structure and performance regulation of energetic complexes through multifunctional molecular self-assembly.

The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.

Comparison of bacterial species and clinical outcomes in patients with diabetic hand infection in tropical and nontropical regions.

Hand infection is a rare complication in patients with diabetes. Its clinical outcomes depend on the severity of hand infection caused by bacteria, but the difference in bacterial species in the regional disparity is unknown. The purpose of this study was to explore the influence of tropical and nontropical regions on bacterial species and clinical outcomes for diabetic hand. A systematic literature review was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Moreover, the bacterial species and clinical outcomes were analyzed with respect to multicenter wound care in China (nontropical regions). Both mixed bacteria (31.2% vs. 16.6%, p = 0.014) and fungi (7.5% vs. 0.8%, p = 0.017) in the nontropical region were significantly more prevalent than those in the tropical region. Staphylococcus and Streptococcus spp. were dominant in gram-positive bacteria, and Klebsiella, Escherichia coli, Proteus and Pseudomonas in gram-negative bacteria occupied the next majority in the two regions. The rate of surgical treatment in the patients was 31.2% in the nontropical region, which was significantly higher than the 11.4% in the tropical region (p = 0.001). Although the overall mortality was not significantly different, there was a tendency to be increased in tropical regions (6.3%) compared with nontropical regions (0.9%). However, amputation (32.9% vs. 31.3%, p = 0.762) and disability (6.3% vs. 12.2%, p = 0.138) were not significantly different between the two regions. Similar numbers of cases were reported, and the most common bacteria were similar in tropical and nontropical regions in patients with diabetic hand. There were more species of bacteria in the nontropical region, and their distribution was basically similar, except for fungi, which had differences between the two regions. The present study also showed that surgical treatment and mortality were inversely correlated because delays in debridement and surgery can deteriorate deep infections, eventually leading to amputation and even death.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

Association between body fat distribution and age at menarche: a two sample Mendelian randomization study.

Background: Numerous studies have examined the association between obesity and age at menarche (AAM), with most focusing on traditional obesity indicators such as body mass index. However, there are limited studies that explored the connection between body fat distribution and AAM, as well as a scarcity of Mendelian randomization (MR) studies. Methods: In this study, we conducted a two-sample MR study to evaluate the causal effects of eight body fat distribution indicators on AAM. Inverse variance weighted (IVW) method was used for primary analysis, while supplementary approaches such as MR-Egger and weighted median were also utilized. Considering that the eight exposures were highly correlated, we performed an MR Bayesian model averaging (MR-BMA) analysis to prioritize the effect of major exposure on AAM. A series of sensitivity analyses were also performed. Results: From a range of 82-105 single nucleotide polymorphisms (SNPs) were utilized as genetic instrumental variables for each of the exposure factors. After Bonferroni correction, we found that whole body fat mass (ß: -0.17; 95% CI: -0.24, -0.11), left leg fat percentage (ß: -0.14; 95% CI: -0.21, -0.07), left leg fat mass (ß: -0.20; 95% CI: -0.27, -0.12), left arm fat percentage (ß: -0.18; 95% CI: -0.26, -0.11) and left arm fat mass (ß: -0.18; 95%CI: -0.26, -0.10) were associated with decreased AAM using random effects IVW method. And the beta coefficients for all MR evaluation methods exhibited consistent trends. MR-BMA method validated that left arm fat percentage plays a dominant role in AAM. Conclusions: Our MR study suggested that body fat has broad impacts on AAM. Obtaining more information on body measurements would greatly enhance our comprehension of pubertal development.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia.

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.

Correlations between multimodal neuroimaging and peripheral inflammation in different subtypes and mood states of bipolar disorder: a systematic review.

BACKGROUND: Systemic inflammation-immune dysregulation and brain abnormalities are believed to contribute to the pathogenesis of bipolar disorder (BD). However, the connections between peripheral inflammation and the brain, especially the interactions between different BD subtypes and episodes, remain to be elucidated. Therefore, we conducted the present study to provide a comprehensive understanding of the complex association between peripheral inflammation and neuroimaging findings in patients with bipolar spectrum disorders. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023447044) and conducted according to the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework. Online literature databases (PubMed, Web of Science, Scopus, EMBASE, MEDLINE, PsycINFO, and the Cochrane Library) were searched for studies that simultaneously investigated both peripheral inflammation-related factors and magnetic resonance neurography of BD patients up to July 01, 2023. Then, we analysed the correlations between peripheral inflammation and neuroimaging, as well as the variation trends and the shared and specific patterns of these correlations according to different clinical dimensions. RESULTS: In total, 34 publications ultimately met the inclusion criteria for this systematic review, with 2993 subjects included. Among all patterns of interaction between peripheral inflammation and neuroimaging, the most common pattern was a positive relationship between elevated inflammation levels and decreased neuroimaging measurements. The brain regions most susceptible to inflammatory activation were the anterior cingulate cortex, amygdala, prefrontal cortex, striatum, hippocampus, orbitofrontal cortex, parahippocampal gyrus, postcentral gyrus, and posterior cingulate cortex. LIMITATIONS: The small sample size, insufficiently explicit categorization of BD subtypes and episodes, and heterogeneity of the research methods limited further implementation of quantitative data synthesis. CONCLUSIONS: Disturbed interactions between peripheral inflammation and the brain play a critical role in BD, and these interactions exhibit certain commonalities and differences across various clinical dimensions of BD. Our study further confirmed that the fronto-limbic-striatal system may be the central neural substrate in BD patients.

An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.

Preparation and optimization of an eggshell membrane-based biomaterial for GTR applications.

OBJECTIVES: Guided Tissue Regeneration (GTR) is a popular clinical procedure for periodontal tissue regeneration. However, its key component, the barrier membrane, is largely collagen-based and is still quite expensive, posing a financial burden to the patients as well as healthcare systems and negatively impacting the patient's decision-making. Thus, our aim is to prepare a novel biomimetic GTR membrane utilizing a natural biomaterial, soluble eggshell membrane protein (SEP), which is economical as it comes from an abundant industrial waste from food and poultry industries, unlike collagen. Additive polymer, poly (lactic-co-glycolic acid) (PLGA), and a bioceramic, nano-hydroxyapatite (HAp), were added to improve its mechanical and biological properties. METHODS: For this barrier membrane preparation, we initially screened the significant factors affecting its mechanical properties using Taguchi orthogonal array design and further optimized the significant factors using response surface methodology. Furthermore, this membrane was characterized using SEM, EDAX, and ATR-FTIR, and tested for proliferation activity of human periodontal ligament fibroblasts (HPLFs). RESULTS: Optimization using response surface methodology predicted that the maximal tensile strength of 3.1 MPa and modulus of 39.9 MPa could be obtained at membrane composition of 8.9 wt% PLGA, 7.2 wt% of SEP, and 2 wt% HAp. Optimized PLGA/SEP/HAp membrane specimens that were electrospun on a static collector showed higher proliferation activity of HPLFs compared to tissue culture polystyrene and a commercial collagen membrane. SIGNIFICANCE: From the results observed, we can conclude that SEP-based nanofibrous GTR membrane could be a promising, environment-friendly, and cost-effective alternative for commercial collagen-based GTR membrane products.

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Protective effect of Angelica sinensis polysaccharide on pregnant rats suffering from iron deficiency anemia via regulation of the hepcidin-FPN1 axis.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with deleterious maternal and fetal outcomes. Angelica sinensis polysaccharide (ASP) has been shown to reduce hepcidin expression in IDA rats. However, the role of ASP in the treatment of IDA during pregnancy and its potential mechanisms have not been investigated. Moreover, the effect of ASP on duodenal iron absorption is not clear. The aim of this study was to investigate the preventive efficacy of ASP against IDA during pregnancy and clarify the underlying mechanisms. Our results showed that ASP improved maternal hematological parameters, increased serum iron, maternal tissue iron, and fetal liver iron content, and improved pregnancy outcomes. Additionally, ASP combated oxidative stress caused by iron deficiency by improving the body's antioxidant capacity. Western blot results demonstrated that ASP downregulated hepcidin expression by blocking the BMP6/SMAD4, JAK2/STAT3 and TfR2/HFE signaling pathways, which in turn increased the expression of FPN1 in the liver, spleen, and duodenum and promoted iron cycling in the body. Furthermore, ASP increased the expression of DMT1 and Dcytb in the duodenum, thereby facilitating duodenal iron uptake. Our results suggest that ASP is a potential agent for the prevention and treatment of IDA during pregnancy.

Hemispheric coupling between structural and functional asymmetries in clinically asymptomatic carotid stenosis with cognitive impairment.

Advanced carotid stenosis is a known risk factor for ischemic stroke and vascular dementia, and it is associated with multidomain cognitive impairment as well as asymmetric alterations in hemispheric structure and function. Here we introduced a novel measure-the asymmetry index of amplitude of low-frequency fluctuations (ALFF_AI)-derived from resting-state functional magnetic resonance imaging. This measure captures the hemispheric asymmetry of intrinsic brain activity using high-dimensional registration. We aimed to investigate functional brain asymmetric alterations in patients with severe asymptomatic carotid stenosis (SACS). Furthermore, we extended the analyses of ALFF_AI to different frequencies to detect frequency-specific alterations. Finally, we examined the coupling between hemispheric asymmetric structure and function and the relationship between these results and cognitive tests, as well as the white matter hyperintensity burden. SACS patients presented significantly decreased ALFF_AI in several clusters, including the visual, auditory, parahippocampal, Rolandic, and superior parietal regions. At low frequencies (0.01-0.25 Hz), the ALFF_AI exhibited prominent group differences as frequency increased. Further structure-function coupling analysis indicated that SACS patients had lower coupling in the lateral prefrontal, superior medial frontal, middle temporal, superior parietal, and striatum regions but higher coupling in the lateral occipital regions. These findings suggest that, under potential hemodynamic burden, SACS patients demonstrate asymmetric hemispheric configurations of intrinsic activity patterns and a decoupling between structural and functional asymmetries.

Genetic variants and effect modifiers of QT interval prolongation in patients with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD. METHODS: In SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals. RESULTS: Out of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0 ms (95% CI: [2.0, 6.1]; p-value: <0.001) in the additive model and 9.4 ms in the recessive model (95% CI: [4.6, 14.1]; p-value: <0.001). Serum ALT showed a modification effect on PRS-QTc prolongation under the recessive model. In the normal ALT group, each PRS unit increased QTc interval by 11.7 ms (95% CI: [6.3, 17.1]; p-value: 2.60E-5), whereas this effect was not observed in the elevated ALT group (0.9 ms; 95% CI: [-7.0, 8.8]; p-value: 0.823). CONCLUSION: Several candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.

Ratiometric fluorescence determination of alkaline phosphatase activity based on carbon dots and Ce3+-crosslinked copper nanoclusters.

A new ratiometric fluorescent probe for efficient determination of ALP was developed. The probe was constructed by combining Ce3+-crosslinked copper nanoclusters (Ce3+-CuNCs) which exhibit the aggregation-induced emission (AIE) feature with carbon dots (CDs). The introduction of phosphate (Pi) induced the generation of CePO4 precipitation, resulting in significant decrease of fluorescence emission of CuNCs at 634 nm. At the same time, the fluorescence of CDs at 455 nm was obviously enhanced, thus generating ratiometric fluorescence response. Based on the fact that the hydrolysis of pyrophosphate (PPi) by ALP can produce Pi, the CD/Ce3+-CuNCs ratiometric probe was successfully used to determine ALP. A good linear relationship between the ratiometric value of F455/F634 and ALP concentrations ranging from 0.2 to 80 U·L- 1 was obtained, with a low detection limit of 0.1 U·L- 1. The ratiometric responses of the probe resulted in the visible fluorescence color change from orange red to blue with the increase of ALP concentration. The smartphone-based RGB recognition of the fluorescent sample images was used for ALP quantitative determination. A novel ratiometric fluorescent system based on Ce3+-CuNCs with AIE feature and CDs were constructed for efficient detection of ALP.