The complex roles of m 6 A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases.

N6-methyladenosine (m 6 A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m 6 A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m 6 A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m 6 A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m 6 A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m 6 A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m 6 A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m 6 A's role in neurodegenerative processes. The roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the time-specific nature of m 6 A and its varying effects on distinct brain regions and in different environments.

Does the Angulation of the Screws in the Zero-P Implant Affect the Clinical and Radiological Outcomes of Patients?

OBJECTIVE: When implanting the Zero-P device, the screws of Zero-P form a bone wedge with a 40 ± 5° cranial and caudal angle (CCA). However, no study has been performed in the optimal CCA of the Zero-P implant. To investigate whether the cranial/caudal angles (CCA) of the screws affect the clinical and radiological outcomes in patients undergoing ACDF with the Zero-P implant. METHODS: From January 2016 to December 2023, we retrospectively analyzed 186 patients who underwent 1-level ACDF with the Zero-P device. The patients were divided into four groups: group A (cranial angle ≤40°, caudal angle ≤40°); group B (cranial angle ≤40°, caudal angle >40°); group C (cranial angle >40°, caudal angle ≤40°); and group D (cranial angle >40°, caudal angle >40°). The clinical outcomes, including Japanese Orthopaedic Association (JOA), neck disability index (NDI), and visual analogue scale (VAS) scores, the radiological parameters, including cervical lordosis (CL), cervical lordosis of operated segments (OPCL), intervertebral space height (ISH) and fusion rate (FR), and the complications, were evaluated and compared. Parametric tests, non-parametric tests, and chi-square tests were conducted to analyze the data. RESULTS: The OPCL of group A was significantly less than that of the other groups at the final follow-up (p < 0.05). The ISH of group D was significantly less than that of group A at the final follow-up (p < 0.05). The subsidence rate of group A was significantly less than that of group D at the final follow-up (p < 0.05). At the final follow-up, the upper adjacent-level degeneration (ASD) of group D was significantly less severe than that of groups A and B (p < 0.05). The clinical outcomes do not differ among groups (p > 0.05). CONCLUSION: A larger CCA of the screws (cranial angle >40°, caudal angle >40°) was better for maintaining OPCL and reducing the incidence of ASD. A smaller CCA of the screws (cranial angle ≤40°, caudal angle ≤40°) was better for maintaining ISH and reducing the rate of subsidence.

Construction of an IFNAR1 knockout MDBK cell line using CRISPR/Cas9 and its effect on bovine virus replication.

The type I interferon (IFN) pathway is important for eukaryotic cells to resist viral infection, as well as an impediment to efficient virus replication. Therefore, this study aims to create an IFNAR1 knockout (KO) Madin-Darby bovine kidney (MDBK) cell line using CRISPR/Cas9 and investigate its application and potential mechanism in increasing viral replication of bovines. The IFNAR1 KO cells showed increased titers of bovine viral diarrhea virus (BVDV) (1.5 log10), with bovine enterovirus and bovine parainfluenza virus type 3 (0.5-0.8 log10). RNA-seq revealed reduced expression of the genes related IFN-I pathways including IFNAR1, STAT3, IRF9, and SOCS3 in IFNAR1 KO cells compared with WT cells. In WT cells, 306 differentially expressed genes (DEGs) were identified between BVDV-infected and -uninfected cells. Of these, 128 up- and 178 down-regulated genes were mainly associated with growth cycle and biosynthesis, respectively. In IFNAR1 KO cells, 286 DEGs were identified, with 82 up-regulated genes were associated with signaling pathways, and 204 down-regulated genes. Further, 92 DEGs were overlapped between WT and IFNAR1 KO cells including ESM1, IL13RA2, and SLC25A34. Unique DEGs in WT cells were related to inflammation and immune regulation, whereas those unique in IFNAR1 KO cells involved in cell cycle regulation through pathways such as MAPK. Knocking down SLC25A34 and IL13RA2 in IFNAR1 KO cells increased BVDV replication by 0.3 log10 and 0.4 log10, respectively. Additionally, we constructed an IFNAR1/IFNAR2 double-knockout MDBK cell line, which further increased BVDV viral titers compared with IFNAR1 KO cells (0.6 log10). Overall, the IFNAR1 KO MDBK cell line can support better replication of bovine viruses and therefore provides a valuable tool for bovine virus research on viral pathogenesis and host innate immune response.

A metabolomics perspective reveals the mechanism of the uric acid-lowering effect of Prunus salicina Lindl. cv. "furong" polyphenols in hypoxanthine and potassium oxybate-induced hyperuricemic mice.

The incidence of hyperuricemia (HUA) shows a gradually increasing trend towards affecting younger individuals, and it can significantly harm the overall health status of the body. Based on a metabolomics perspective, this study reveals the mechanism of the uric acid-lowering action of Prunus salicina Lindl. cv. "furong" polyphenols (PSLP) on a hyperuricemia mouse model induced by hypoxanthine and potassium oxybutyrate. The results demonstrate that PSLP comprise an effective treatment strategy for reducing the levels of serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) in HUA mice (p < 0.05), wherein the maximum decrease rates are up to 44.50%, 29.46%, and 32.95%, respectively. PSLP are observed to exert a pronounced inhibitory effect on the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the livers of HUA mice, with reductions of up to 16.36% and 20.13%, respectively. These findings illustrate that PSLP exert a significant uric acid-lowering effect. Subsequent metabolomic analysis of mouse serum identified 28 potential biomarkers for hyperuricemia, whose levels were markedly diminished by PSLP. This process involved alterations in purine, glycine, the pentose phosphate pathway, and galactose metabolism. Twenty-eight potential biomarkers were identified for hyperuricemia by subsequent metabolomic analysis of mouse serum, whose levels were markedly reversed by PSLP intervention. The regulation of HUA by PSLP involved alterations in purine metabolism, glycerolipid metabolism, the pentose phosphate pathway, and galactose metabolism. The mechanism of PSLP ameliorated hyperuricemia might be attributed to reduction of the level of the uric acid precursor ribose-5-phosphate in the pentose phosphate pathway, the inhibition of the activities of uric acid synthase XOD and ADA in purine metabolism, and reduction of the synthesis of the end product uric acid. This study provides a theoretical basis for the development of functional foods based on PSLP, which can potentially reduce uric acid levels.

Effects of Different Test Positions on Quantitative Muscle Strength of Wrist and Finger Flexor Muscle Groups and Its Standardization.

OBJECTIVES: To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group. METHODS: Forty healthy subjects (12 males and 28 females) were recruited. A portable digital quantitative muscle strength tester, Micro FET2TM, was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension, 0° neutral, and 30° flexion, respectively. Palmar abduction strength of the thumb was measured at 30° and 60°, respectively. Ten subjects were randomly selected from the 40 subjects, and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days. RESULTS: Except for the fact that in males, there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position, the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics：30° of wrist extension > neutral 0° position > 30° of flexion, and the PAST was 30°>60°; The flexor muscle strength of all the subjects was thumb > index finger > middle finger > ring finger > little finger; All muscle strength values of male were greater than those of female, and the difference was statistically significant (P<0.05); There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05). The reliability of muscle strength values measured at different times in 10 subjects was good. CONCLUSIONS: The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position, and a standardized and uniformed test position should be adopted in the actual identification. Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing. The 30° extension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint. The 30° position can be used as the best standardized test position for PAST.

Examination tolerance, pre-examination anxiety, knowledge needs and cooperation in gastroscopic examinees: A prospective, correlational analysis in a health screening population.

AIM: To explore the correlations between examination tolerance and anxiety, knowledge needs and examination cooperation in sedation-free gastroscopy examinees. DESIGN: Cross-sectional survey using convenience sampling. METHODS: A total of 170 healthy adults who underwent sedation-free gastroenteroscopy were asked to complete a visual analogue scale (VAS) to rate their examination tolerance, the state anxiety questionnaire (S-AI), a newly designed knowledge needs questionnaire and a cooperation questionnaire. RESULTS: The VAS score was 4.47 ± 1.96, the state anxiety score was 39.46 ± 9.81, the total score for knowledge needs was 44.89 ± 11.02, and the average cooperation score was 2.47 ± 0.38. The VAS score during the examination positively correlated with the pretest state anxiety score and pretest knowledge needs score and negatively correlated with the examination cooperation score. The results of multiple linear regression analysis showed that after undergoing the examination for the first time, anxiety, body position and swallowing control were the main factors influencing the examination tolerance of sedation-free gastroscopy examinees. PATIENT OR PUBLIC CONTRIBUTION: We would like to thank the staff and patients of the participating hospital for their assistance and cooperation in performing the current study.

Kaempferol inhibited invasion and metastasis of gastric cancer cells by targeting AKT/GSK3ß pathway based on network pharmacology and molecular docking.

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.

Immobilizing Ordered Oxophilic Indium Sites on Platinum Enabling Efficient Hydrogen Oxidation in Alkaline Electrolyte.

Addressing the sluggish kinetics in the alkaline hydrogen oxidation reaction (HOR) is a pivotal yet challenging step toward the commercialization of anion-exchange membrane fuel cells (AEMFCs). Here, we have successfully immobilized indium (In) atoms in an orderly fashion into platinum (Pt) nanoparticles supported by reduced graphene oxide (denoted as O-Pt3In/rGO), significantly enhancing alkaline HOR kinetics. We have revealed that the ordered atomic matrix enables uniform and optimized hydrogen binding energy (HBE), hydroxyl binding energy (OHBE), and carbon monoxide binding energy (COBE) across the catalyst. With a mass activity of 2.3066 A mg-1 at an overpotential of 50 mV, over 10 times greater than that of Pt/C, the catalyst also demonstrates admirable CO resistance and stability. Importantly, the AEMFC implementing this catalyst as the anode catalyst has achieved an impressive power output compared to Pt/C. This work not only highlights the significance of constructing ordered oxophilic sites for alkaline HOR but also sheds light on the design of well-structured catalysts for energy conversion.

Segmentation and Vascular Vectorization for Coronary Artery by Geometry-based Cascaded Neural Network.

Segmentation of the coronary artery is an important task for the quantitative analysis of coronary computed tomography angiography (CCTA) images and is being stimulated by the field of deep learning. However, the complex structures with tiny and narrow branches of the coronary artery bring it a great challenge. Coupled with the medical image limitations of low resolution and poor contrast, fragmentations of segmented vessels frequently occur in the prediction. Therefore, a geometry-based cascaded segmentation method is proposed for the coronary artery, which has the following innovations: 1) Integrating geometric deformation networks, we design a cascaded network for segmenting the coronary artery and vectorizing results. The generated meshes of the coronary artery are continuous and accurate for twisted and sophisticated coronary artery structures, without fragmentations. 2) Different from mesh annotations generated by the traditional marching cube method from voxel-based labels, a finer vectorized mesh of the coronary artery is reconstructed with the regularized morphology. The novel mesh annotation benefits the geometry-based segmentation network, avoiding bifurcation adhesion and point cloud dispersion in intricate branches. 3) A dataset named CCA-200 is collected, consisting of 200 CCTA images with coronary artery disease. The ground truths of 200 cases are coronary internal diameter annotations by professional radiologists. Extensive experiments verify our method on our collected dataset CCA-200 and public ASOCA dataset, with a Dice of 0.778 on CCA-200 and 0.895 on ASOCA, showing superior results. Especially, our geometry-based model generates an accurate, intact and smooth coronary artery, devoid of any fragmentations of segmented vessels.

The natural compound sinometumine E derived from Corydalis decumbens promotes angiogenesis by regulating HIF-1/ VEGF pathway in vivo and in vitro.

The rhizome of Corydalis decumbens is a traditional Chinese medicine commonly utilized in the clinical treatment of acute ischemic stroke. Numerous phytochemical and biological investigations have demonstrated that protoberberine alkaloids from C. decumbens exhibit diverse pharmaceutical activities against various diseases. Sinometumine E (SE), a protoberberine alkaloid isolated from C. decumbens for the first time, is characterized by a complex 6/6/6/6/6/6 hexacyclic skeleton. In the current study, we investigated the protective effects of SE on endothelial cell injury and its angiogenesis effects in zebrafish. The results suggested that SE showed significant anti-ischemic effects on OGD/R-induced HBEC-5i and HUVECs cell ischemia/reperfusion injury model. Furthermore, it promoted angiogenesis in PTK787-induced, MPTP-induced, and atorvastatin-induced vessel injury models of zebrafish, while also suppressing hypoxia-induced locomotor impairment in zebrafish. Transcriptome sequencing analysis provided a sign that SE likely to promotes angiogenesis through the HIF-1/VEGF signaling pathway to exert anti-ischemic effects. Consistently, SE modulated several genes related to HIF-1/VEGF signal pathway, such as hif-1, vegf, vegfr-2, pi3k, erk, akt and plcγ. Molecular docking analysis revealed that VEGFR-2 exhibited high binding affinity with SE, and western blot analysis confirmed that SE treatment enhanced the expression of VEGFR-2. In conclusion, our study profiled the angiogenic activities of SE in vitro and in vivo. The key targets and related pathways involved in anti-ischemic effects of SE, shedding light on the pharmacodynamic components and mechanisms of Corydalis decumbens, and provides valuable insights for identifying effective substances for the treatment of ischemic stroke.

Pancreatic STAT5 activation promotes KrasG12D-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

Sagittal slope angle of lateral atlantoaxial articulation is associated with the severity of basilar invagination with atlantoaxial dislocation and predicts reduction degree after surgery.

OBJECTIVE: To investigate (1) lateral atlantoaxial articulation (LAA) morphology in patients with basilar invagination (BI) with atlantoaxial dislocation (AAD) and healthy individuals and its relationship with the severity of dislocation and (2) the effect of the LAA morphology on reduction degree (RD) after surgery. METHODS: In this retrospective propensity score matching case-control study, imaging and baseline data of 62 patients with BI and AAD from 2011 to 2022 were collected. Six hundred thirteen  participants without occipitocervical junctional deformity served as controls. Logistic regression and receiver operating characteristic (ROC) curve were used for analysis. RESULTS: The age, BMI and sex did not differ significantly between the two groups after propensity score matching. Sagittal slope angle (SSA) and coronal slope angle (CSA) was lower and greater, respectively, in the patient group than in the control group. A negative SSA value usually indicates anteverted LAA. Regression analysis revealed a significant negative correlation between SSA and severity of dislocation. However, no relationship was found between CSA and the severity of dislocation. The multivariate logistic regression analysis revealed that minimum-SSA emerged as an independent predictor of satisfactory reduction (RD ≥ 90%). The ROC curve demonstrated an area under the curve of 0.844, with a cut-off value set at -40.2. CONCLUSION: SSA in patients group was significantly smaller and more asymmetric than that in the control group. Dislocation severity was related to SSA but not to CSA. Minimum-SSA can be used as a predictor of horizontal RD after surgery.

Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.

Chemical structure and immunomodulatory activity of a polysaccharide from Saposhnikoviae Radix.

A new polysaccharide, named SP40015A01, was obtained from Saposhnikoviae Radix by water extraction, isolation and purification. SP40015A01 (9.7 × 105 Da) is composed of Rhamnose (Rha), Galacturonic acid (GalA), Galactose (Gal), and Arabinose (Ara) with the proportion of 1.6:85.6:5.8:7.6. The backbone of SP40015A01 is composed of 3-α-GalAp, 2-α-GalAp, 2,3-ß-GalAp and 2,3-ß-Galp, and branched at C3 of 2,3-ß-GalAp, C3 of 2,3-ß-Galp. Zebrafish experiments were used to explore the immunomodulatory activity of SP40015A01. Results showed that SP40015A01 could significantly improve the neutrophils density of immunocompromised zebrafish and reduce the content of nitric oxide (NO) and interleukin-1ß (IL-1ß). This study demonstrated that SP40015A01 has significant immunomodulatory activity, which can improve the neutrophils density and reduce inflammatory factor content, suggesting SP40015A01 may be a potential immunomodulator in Saposhnikoviae Radix (SR) for treatment of hypoimmunity related disease. This study supplemented the research on the polysaccharide components in traditional Chinese medicine and provided a scientific explanation for the development and clinical applications of SR.

Glutathione-responsive CD-MOFs co-loading honokiol and indocyanine green biomimetic active targeting to enhance photochemotherapy for breast cancer.

Breast cancer has now replaced lung cancer as the most prevalent malignant tumor worldwide, posing a serious health risk to women. We have recently designed a promising option strategy for the treatment of breast cancer. In this work, cyclodextrin metal-organic frameworks with high drug-carrying properties were endo-crosslinked by 3,3'dithiodipropionyl chloride to form cubic phase gel nanoparticles, which were drug-loaded and then coated by MCF-7 cell membranes. After intravenous injection, this multifunctional nanomedicine achieved dramatically homologous targeting co-delivery of honokiol and indocyanine green to the breast tumor. Further, the disulfide bonds in the nanostructures achieved glutathione-responsive drug release, induced tumor cells to produce reactive oxygen species and promoted apoptosis, resulting in tumor necrosis, and at the same time, inhibited Ki67 protein expression, which enhanced photochemotherapy, and resulted in a 94.08 % in vivo tumor suppression rate in transplanted tumor-bearing mice. Thereby, this nanomimetic co-delivery system may have a place in breast cancer therapy due to its simple fabrication process, excellent biocompatibility, efficient targeted delivery of insoluble drugs, and enhanced photochemotherapy.

Preparation of a novel foamed concrete modified with carbon fiber and graphite: Mechanical, electro-magnetic and microstructural characteristics based on X-CT.

In this paper, foam concrete is modified using graphite and carbon fiber as absorbents. The mechanical properties are analyzed in conjunction with hydration products, pore size distribution based on XCT test. Additionally, the resistivity, complex permittivity and complex permeability are tested. The results demonstrate that carbon fiber enhances the proportion of pores with diameters less than 200 µm in foam concrete, thereby significantly enhancing its flexural strength. Furthermore, incorporating graphite helps offset the initial retardation of sulfoaluminate cement hydration induced by carbon fibers, leading to an increase in the average pore size and a reduction in compressive strength. The incorporation of carbon fibers at a concentration of 0.6 wt% achieves the percolation threshold, akin to scenarios with singular fiber incorporation. Exceeding 2 wt% graphite content results in negligible influence on the conductivity. The synergistic integration of graphite and carbon fibers significantly improves the electromagnetic wave absorption performance of the composite. At a thickness of 6 mm, the material exhibits an effective bandwidth where the reflection loss is less than -10 dB, extending up to 2.5 GHz, which constitutes 52.08 % of the tested frequency spectrum.

Evaluation of plasma-derived extracellular vesicles miRNAs and their connection with hippocampal mRNAs in alcohol use disorder.

Alcohol use disorder (AUD) is a common mental illness with high morbidity and disability. The discovery of laboratory biomarkers has progressed slowly, resulting in suboptimal diagnosis and treatment of AUD. This study aimed to identify promising biomarkers, as well as the potential miRNA-mRNA networks associated with AUD pathogenesis. RNA sequencing was performed on plasma-derived small extracellular vesicles (sEVs) from AUD patients and healthy controls (HCs) to harvest miRNAs expression profiles. Machine learning (ML) models were built to screen characteristic miRNAs, whose target mRNAs were analyzed using TargetScan, miRanda and miRDB databases. Gene Expression Omnibus (GEO) datasets (GSE181804 and GSE180722) providing postmortem hippocampal gene expression profiles of AUD subjects were mined. A total of 247 differentially expressed (DE) plasma-derived sEVs miRNAs and 122 DE hippocampal mRNAs were obtained. Then, 22 overlapping sEVs miRNAs with high importance scores were gained by intersecting 5 ML models. As a result, we established a putative sEVs miRNA-hippocampal mRNA network that can effectively distinguish AUD patients from HCs. In conclusion, we proposed 5 AUD-representative sEVs miRNAs (hsa-miR-144-5p, hsa-miR-182-5p, hsa-miR-142-5p, hsa-miR-7-5p, and hsa-miR-15b-5p) that may participate in the pathogenesis of AUD by modulating downstream target hippocampal genes. These findings may provide novel insights into the diagnosis and treatment of AUD.

Estrogen-related receptor, a molecular target against lepidoptera pests.

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.