Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer's disease.

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD-associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD-associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy.

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.

Identification and validation of a metabolism-related gene signature for predicting the prognosis of paediatric medulloblastoma.

Medulloblastoma (MB) is a malignant brain tumour that is highly common in children and has a tendency to spread to the brain and spinal cord. MB is thought to be a metabolically driven brain tumour. Understanding tumour cell metabolic patterns and characteristics can provide a promising foundation for understanding MB pathogenesis and developing treatments. Here, by analysing RNA-seq data of MB samples from the Gene Expression Omnibus (GEO) database, 12 differentially expressed metabolic-related genes (DE-MRGs) were chosen for the construction of a predictive risk score model for MB. This model demonstrated outstanding accuracy in predicting the outcomes of MB patients and served as a standalone predictor. An evaluation of functional enrichment revealed that the risk score showed enrichment in pathways related to cancer promotion and the immune response. In addition, a high risk score was an independent poor prognostic factor for MB in patients with different ages, sexes, metastasis stages and subgroups (SHH and Group 4). Consistently, the metabolic enzyme ornithine decarboxylase (ODC1) was upregulated in MB patients with poor survival time. Inhibition of ODC1 in primary and metastatic MB cell lines decreased cell proliferation, migration and invasion but increased immune infiltration. This study could aid in identifying metabolic targets for MB as well as optimizing risk stratification systems and individual treatment plans for MB patients via the use of a metabolism-related gene prognostic risk score signature.

Identification of pine wood nematode (Bursaphelenchus xylophilus) loading response genes in Japanese pine sawyer (Monochamus alternatus) through comparative genomics and transcriptomics.

BACKGROUND: Pine wood nematode (PWN; Bursaphelenchus xylophilus) is the causative agent of pine wilt disease (PWD), which is considered the most dangerous biohazard to conifer trees globally. The transmission of PWN relies on insect vectors, particularly the Japanese pine sawyer (JPS; Monochamus alternatus). However, the molecular mechanism underlying PWN-JPS assembly remains largely unknown. RESULTS: Here, we found that both geographical and gender could significantly affect the PCA (PWN carrying amount) of JPS; thus, JPS transcriptomes from diverse locations and genders were explored regard to PWN loading. Due to the shortage of genomes, we developed a full-length reference transcriptome for analyzing next-generation sequencing data. A comparative genomic study was performed, and 11 248 potential PWN-carrying associate genes (ß) were nominated in JPS by using the reported genomes of PWN and non-PWN carrier insect species. Then, 151 differentially expressed transcripts (DETs), 28 of them overlapped with ß, correlated with the PCA of JPS were nominated by RNA-Seq, and found that fatty acid ß-oxidation might be the key factor that affected the PCA of JPS. Furthermore, JPS fatty acid ß-oxidation rates were experimentally decreased using the inhibitor Etomoxir, leading to an increased PCA of JPS. Meanwhile, silencing MaCPT1 in JPS by RNA interference led to a decreased fatty acid ß-oxidation rate and increased PCA of JPS. CONCLUSIONS: In conclusion, MaCPT1 was able to decrease the PWN-JPS assembly formation through the fatty acid ß-oxidation of JPS. These results provide new insights for exploring the impact of PWN invasion on JPS. © 2024 Society of Chemical Industry.

A scenario-based web app to facilitate patient education in lung tumor patients undergoing video-assisted thoracoscopic surgery: Development and usability testing.

Background: Patient education (PE) is essential for improving patients' knowledge, anxiety, and satisfaction, and supporting their postoperative recovery. However, the advantages of video-assisted thoracoscopic surgery (VATS)-smaller incisions and faster recovery-can result in shorter hospital stays, making PE more challenging to implement effectively. Multimedia PE can potentially enhance PE, but its effectiveness for patients undergoing VATS is unclear. Objective: This study developed a scenario-based PE web app for lung tumor patients undergoing VATS (SPE-VATS) to facilitate the PE process and evaluated its usability through a clinical trial. Methods: The SPE-VATS provided the experimental group (EG: 32 participants) with interactive scenario, query guidance, diagnostic analysis, experience sharing, and active reminder, while the control group (CG: 32 participants) used pamphlets and videos. The usability of SPE-VATS in terms of postoperative anxiety reduction and patient satisfaction with the app was evaluated using self-reported questionnaires based on the state-trait anxiety inventory, technology acceptance model, system usability scale, and task load index. Results: There was no statistically significant difference in postoperative anxiety reduction between the EG and CG, possibly because 90% of the participants underwent a low-risk surgical type, and VATS is known to be advantageous in alleviating surgical anxiety. However, females and higher educated EG participants showed a non-significant but favorable reduction than their CG counterparts. Moreover, the EG was highly satisfied with the app (rated 4.2 to 4.4 out of 5.0), with no significant gender and education level difference. They particularly valued the interactive scenario, experience sharing, and diagnostic analysis features of SPE-VATS. Conclusions: The SPE-VATS demonstrated its usability and high patient satisfaction, particularly for female and higher educated patients. Low-risk patient predominance and VATS's advantages may explain non-significant postoperative anxiety reduction, warranting further studies on high-risk patients to evaluate the impact of SPE-VATS on clinical practice.

Prediction Model of Lean Coal Adsorption of Power Plant Flue Gas.

To minimize errors in calculating coal flue gas adsorption capacity due to gas compressibility and to preclude prediction inaccuracies in abandoned mine flue gas storage capacity for power plants, it is imperative to account for the influence of compression factor calculation accuracy while selecting the optimal theoretical adsorption model. In this paper, the flue gas adsorption experiment of a power plant with coal samples gradually pressurized to close to 5 MPa at two different temperatures is carried out, and the temperature and pressure data obtained from the experiment are substituted into five different compression factor calculation methods to calculate different absolute adsorption amounts. The calculated adsorption capacities were fitted into six theoretical adsorption models to establish a predictive model suitable for estimating the coal adsorption capacity in power plant flue gas. Results reveal significant disparities in the absolute adsorption capacity determined by different compression factors, with an error range of 0.001278-7.8262 (cm3/kg). The Redlich-Kwong equation of state emerged as the most suitable for the flue gas of the selected experimental coal sample and the chosen composition ratio among the five compression factors. Among the six theoretical adsorption models, the Brunauer-Emmett-Teller model with three parameters demonstrated the highest suitability for predicting the adsorption capacity of coal samples in power plant smoke, achieving a fitting accuracy as high as 0.9922 at 49.7 °C.

Imaging predictors of hemorrhagic progression of a contusion after traumatic brain injury: a systematic review and meta-analysis.

The hemorrhagic progression of a contusion (HPC) after Traumatic brain injury (TBI) is one of the important causes of death in trauma patients. The purpose of this meta-analysis was to evaluate the predictive effect of imaging features of Computed tomography (CT) on HPC after TBI. A comprehensive systematic search was performed using PubMed, EMBASE, and WEB OF SCIENCE databases to identify all relevant literature. A total of 8 studies involving 2543 patients were included in this meta-analysis. Meta-analysis showed that subarachnoid hemorrhage (OR 3.28; 95% CI 2.57-4.20), subdural hemorrhage (OR 4.35; 95% CI 3.29-5.75), epidural hemorrhage (OR 1.47;95% CI 1.15-1.89), contrast extravasation (OR 11.81; 95% CI 4.86-28.71) had a predictive effect on the occurrence of HPC. Skull fracture (OR 1.64; 95% CI 0.84-3.19) showed no statistical significance, and midline displacement > 5 mm (OR 4.66; 95% CI 1.87-11.62) showed high heterogeneity. The results of this meta-analysis showed that some imaging features were effective predictors of HPC after TBI. Well-designed prospective studies are needed to more accurately assess the effective predictors of HPC after TBI.

Identification of the HLA-A*11:463 allele in a Chinese patient and his father.

HLA-A*11:463 has one nucleotide change from HLA-A*11:01:01:01 at nucleotide 508 changing Lysine (146) to Glutamine.

Comprehensive phytohormone metabolomic and transcriptomic analysis of tobacco (Nicotiana tabacum) infected by tomato spotted wilt virus (TSWV).

Tomato spotted wilt virus (TSWV) is ranked among the top 10 most destructive viruses globally. It results in abnormal leaf growth, stunting, and even death, significantly affecting crop yield and quality. Phytohormones play a crucial role in regulating plant-virus interactions. However, there is still limited research on the effect of TSWV on phytohormone levels, particularly growth hormones and genes involved in the phytohormone pathway. In our study, we combined phytohormone metabolomics and transcriptomics to examine the impact of TSWV infection on phytohormone content and gene expression profile. Metabolomic results showed that 41 metabolites, including major phytohormones and their precursors and derivatives were significantly altered after 14 days of TSWV inoculation tobacco plants cvK326, with 31 being significantly increased and 10 significantly reduced. Specifically, the levels of abscisic acid (ABA) and jasmonoyl-isoleucine (JA-Ile) were significantly reduced. The levels of indole-3-acetic acid (IAA) have remained unchanged. However, the levels of cytokinin isopentenyladenine (iP) and salicylic acid (SA) significantly increased. The transcriptome analysis revealed 2,746 genes with significant changes in expression. Out of these, 1,072 genes were significantly downregulated, while 1,674 genes were significantly upregulated. Among them, genes involved in ABA synthesis and signaling pathways, such as 9-cis-epoxycarotenoid dioxygenase (NCED), protein phosphatase 2C (PP2C), serine/threonine-protein kinase (SnRK2), and abscisic acid responsive element binding factor (ABF), exhibited significant downregulation. Additionally, expression of the lipoxygenase gene LOX, Jasmonate ZIM domain-containing protein gene JAZ, and transcription factor gene MYC were significantly down-regulated. In the cytokinin pathway, while there were no significant changes in the expression of the cytokinin synthesis genes, a significant downregulation of transcriptionally active factor type-B response regulators (type-B RRs) was observed. In terms of SA synthesis and signaling pathways, the isochorismate synthase gene ICS1 and the pathogenesis-related gene PR1 were significantly upregulated. These results can strengthen the theoretical foundation for understanding the interaction between TSWV and tobacco and provide new insights for the future prevention and control of TSWV.

Osthole Activates the Cholinergic Anti-Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses.

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.

Non-invasive prediction of the chronic degree of lupus nephropathy based on ultrasound radiomics.

OBJECTIVE: Through machine learning (ML) analysis of the radiomics features of ultrasound extracted from patients with lupus nephritis (LN), this attempt was made to non-invasively predict the chronicity index (CI)of LN. METHODS: A retrospective collection of 136 patients with LN who had renal biopsy was retrospectively collected, and the patients were randomly divided into training set and validation set according to 7:3. Radiomics features are extracted from ultrasound images, independent factors are obtained by using LASSO dimensionality reduction, and then seven ML models were used to establish predictive models. At the same time, a clinical model and an US model were established. The diagnostic efficacy of the model is evaluated by analysis of the receiver operating characteristics (ROC) curve, accuracy, specificity, and sensitivity. The performance of the seven machine learning models was compared with each other and with clinical and US models. RESULTS: A total of 1314 radiomics features are extracted from ultrasound images, and 5 features are finally screened out by LASSO for model construction, and the average ROC of the seven ML is 0.683, among which the Xgboost model performed the best, and the AUC in the test set is 0.826 (95% CI: 0.681-0.936). For the same test set, the AUC of clinical model constructed based on eGFR is 0.560 (95% CI: 0.357-0.761), and the AUC of US model constructed based on Ultrasound parameters is 0.679 (95% CI: 0.489-0.853). The Xgboost model is significantly more efficient than the clinical and US models. CONCLUSION: ML model based on ultrasound radiomics features can accurately predict the chronic degree of LN, which can provide a valuable reference for clinicians in the treatment strategy of LN patients.

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.

Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6-endo-dig cyclization and trichloromethylation of N3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-b]quinazolinone was prepared over five steps. The present method features broad substrate scope, good functional group tolerance, new dearomatization of pyridine rings, and chloroform as the trichloromethylation reagent.

Establishment of a mandible defect model in rabbits infected with multiple bacteria and bioinformatics analysis.

Objective: A model of chronic infectious mandibular defect (IMD) caused by mixed infection with Staphylococcus aureus and Pseudomonas aeruginosa was established to explore the occurrence and development of IMD and identify key genes by transcriptome sequencing and bioinformatics analysis. Methods: S. aureus and P. aeruginosa were diluted to 3 × 108 CFU/mL, and 6 × 3 × 3 mm defects lateral to the Mandibular Symphysis were induced in 28 New Zealand rabbits. Sodium Morrhuate (0.5%) and 50 µL bacterial solution were injected in turn. The modeling was completed after the bone wax closed; the effects were evaluated through postoperative observations, imaging and histological analyses. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein‒protein interaction (PPI) network analyses were performed to investigate the function of the differentially expressed genes (DEGs). Results: All rabbits showed characteristics of infection. The bacterial cultures were positive, and polymerase chain reaction (PCR) was used to identify S. aureus and P. aeruginosa. Cone beam CT and histological analyses showed inflammatory cell infiltration, pus formation in the medullary cavity, increased osteoclast activity in the defect area, and blurring at the edge of the bone defect. Bioinformatics analysis showed 1,804 DEGs, 743 were upregulated and 1,061 were downregulated. GO and KEGG analyses showed that the DEGs were enriched in immunity and osteogenesis inhibition, and the core genes identified by the PPI network were enriched in the Hedgehog pathway, which plays a role in inflammation and tissue repair; the MEF2 transcription factor family was predicted by IRegulon. Conclusion: By direct injection of bacterial solution into the rabbit mandible defect area, the rabbit chronic IMD model was successfully established. Based on the bioinformatics analysis, we speculate that the Hedgehog pathway and the MEF2 transcription factor family may be potential intervention targets for repairing IMD.

Tandem Nitrate-to-Ammonia Conversion on Atomically Precise Silver Nanocluster/MXene Electrocatalyst.

Electrocatalytic reduction of nitrate (NO3 RR) to synthesize ammonia (NH3 ) provides a competitive manner for carbon neutrality and decentralized NH3 synthesis. Atomically precise nanoclusters, as an advantageous platform for investigating the NO3 RR mechanisms and actual active sites, remain largely underexplored due to the poor stability. Herein, we report a (NH4 )9 [Ag9 (mba)9 ] nanoclusters (Ag9 NCs) loaded on Ti3 C2 MXene (Ag9 /MXene) for highly efficient NO3 RR performance towards ambient NH3 synthesis with improved stability in neutral medium. The composite structure of MXene and Ag9 NCs enables a tandem catalysis process for nitrate reduction, significantly increasing the selectivity and FE of NH3 . Besides, compared with individual Ag9 NCs, Ag9 /MXene has better stability with the current density performed no decay after 108 hours of reaction. This work provides a strategy for improving the catalytic activity and stability of atomically precise metal NCs, expanding the mechanism research and application of metal NCs.

20(S)-Ginsenoside Rg2 amino acid derivatives for anti hemorrhagic shock: Synthesis, characterization and evaluation.

The purpose of this study is to screen a novel Rg2 derivative for anti hemorrhagic shock. Eight Rg2 amino acid ester derivatives were designed and synthesized, and their effects on hypoxia and shock were studied. Among them, the derivative 1 (D1) exhibited excellent anti hypoxia by promoting survival rate of H9c2 cells damaged by hypoxia. D1 improved physiological indicators of the rats in hemorrhagic shock, such as blood pressure, heart rate, lactate, acid-base balance, and alleviate oxidative stress and inflammatory damage. Its latent mechanisms were explored by a method of plasma metabolomics based on UPLC-QTOF-MS. As a result, a total of 16 biomarkers were identified involving 6 metabolic pathways. The results of this study contained that the derivative 1 could be considered as potent drug candidates for anti shock and deserved further research and development.

Abatement of environmental pollution by research on electrical resistivity and conductivity mechanism of poplar dust.

Under conventional processing conditions, the resistivity of wood dust is in the range of insulating materials, which can induce a dust cloud explosion when there are static sparks. This paper took the fast-growing poplar wood commonly used in Chinese wood processing and studied the effects of moisture content, temperature, and particle size on the electrical resistivity value of sanded wood dust. Orthogonal analysis was conducted on the influencing factors. The results showed that the influence of moisture content on electrical resistivity was the most significant factor, followed by temperature and particle size. Further experiments have shown that when the moisture content increased from 6% to 32%, the resistivity decreased from 109 Ω cm to 105 Ω cm, which reached the suitable resistivity range of static discharge method. The ion concentration of wood dust extracted in cold water and hot water and the resistivity of poplar dust residue after extraction were determined. Nine metal ions (a total of 105.02 mol/g) were detected in cold-water extract, and the concentrations of K+, Na+, Mg2+ and Ca2+ accounted for 99.8%. The original poplar dust and the extracted poplar dust were measured and analyzed. The changes in water-soluble ion content, functional groups, crystallinity, and complexes of the wood dust before and after ion dissolution, jointly led to changes in the electrical resistivity of the wood dust (a difference of 2-4 orders of magnitude). It was verified that the way wood dust conducts electricity is through ion conduction. There were more abundant capillary system structures between poplar dust particles, allowing water-soluble ions to move more freely with water channels. The larger specific surface area and higher temperature also promoted the dissolution of water-soluble ions, which affected the electrical resistivity.

NRF1 promotes primordial germ cell development, proliferation and survival.

Primordial germ cells (PGCs) are the germline precursors that give rise to oocytes and sperm, ensuring the continuation of life. While the PGC specification is extensively studied, it remains elusive how the PGC population is sustained and expanded after they migrate to embryonic gonads before birth. This study demonstrates that NRF1, a known regulator for mitochondrial metabolism, plays critical roles in post-migrating PGC development. We show that NRF1 protein level gradually increases in post-migrating PGCs during embryonic development. Conditional Nrf1 knockout from embryonic germ cells leads to impaired PGC proliferation and survival. In addition, NRF1 may also actively drive PGC derivation from pluripotent stem cells. Using whole genome transcriptome profiling and ChIP-seq analyses, we further reveal that NRF1 directly regulates key signalling molecules in PGC formation, transcription factors in proliferation and cell cycle and enzymes in mitochondrial metabolism. Overall, our findings highlight an essential requirement of NRF1 in regulating a broad transcriptional network to support post-migrating PGC development both in vitro and in vivo.