PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion.

BACKGROUND: For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. AIM: To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. METHODS: A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. RESULTS: Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. CONCLUSION: Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.

Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1 ), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1 ) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1 , which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

One-pot Twostep Chemobiocatalytic Synthesis of a Furan Amino Acid from 5-Hydroxymethylfurfural.

Recently, catalytic valorization of biomass-derived furans has received growing interest. 5-Aminomethyl-2-furancarboxylic acid (AMFC), a furan amino acid, holds great promise in the aeras of polymer and pharmaceutical, but its synthesis remains limited. In this work, we report a chemobiocatalytic route toward AMFC by combining laccase-TEMPO system and recombinant Escherichia coli (named E. coli_TAF) harboring ω-transaminase (TA), L-alanine dehydrogenase (L-AlaDH) and formate dehydrogenase (FDH), starting from 5-hydroxymethylfurfural (HMF). In the cascade, HMF is oxidized into 5-formyl-2-furancarboxylic acid (FFCA) by laccase-TEMPO system, and then the resulting intermediate is converted into AMFC by E. coli_TAF via transamination with cheap ammonium formate instead of costly organic amine donors, theoretically generating H2O and CO2 as by-products. The tandem process was run in a one-pot twostep manner, affording AMFC with approximately 81 % yield, together with 10 % 2,5-furandicarboxylic acid (FDCA) as by-product. In addition, the scale-up production of AMFC was demonstrated, with 0.41 g/L h productivity and 8.6 g/L titer. This work may pave the way for green manufacturing of the furan-containing amino acid.

BLK positively regulates TLR/IL-1R signaling by catalyzing TOLLIP phosphorylation.

TLR/IL-1R signaling plays a critical role in sensing various harmful foreign pathogens and mounting efficient innate and adaptive immune responses, and it is tightly controlled by intracellular regulators at multiple levels. In particular, TOLLIP forms a constitutive complex with IRAK1 and sequesters it in the cytosol to maintain the kinase in an inactive conformation under unstimulated conditions. However, the underlying mechanisms by which IRAK1 dissociates from TOLLIP to activate TLR/IL-1R signaling remain obscure. Herein, we show that BLK positively regulates TLR/IL-1R-mediated inflammatory response. BLK-deficient mice produce less inflammatory cytokines and are more resistant to death upon IL-1ß challenge. Mechanistically, BLK is preassociated with IL1R1 and IL1RAcP in resting cells. IL-1ß stimulation induces heterodimerization of IL1R1 and IL1RAcP, which further triggers BLK autophosphorylation at Y309. Activated BLK directly phosphorylates TOLLIP at Y76/86/152 and further promotes TOLLIP dissociation from IRAK1, thereby facilitating TLR/IL-1R-mediated signal transduction. Overall, these findings highlight the importance of BLK as an active regulatory component in TLR/IL-1R signaling.

Application of contrast-enhanced ultrasound in renal space-occupying lesion puncture biopsy.

OBJECTIVE: The purpose of this study was to investigate the utility of contrast-enhanced ultrasound (CEUS) in percutaneous renal space-occupying lesion puncture biopsy. METHODS: Ultrasound (US)-guided percutaneous needle biopsies were performed on 55 patients with renal space-occupying lesions, and the results were analyzed retrospectively. The US group included 36 patients receiving conventional US, and the contrast-enhanced ultrasound (CEUS) group included 22 patients, including 19 patients receiving CEUS directly and 3 patients receiving additional enhanced ultrasound due to the first conventional ultrasound puncture failure. The relevant data were subjected to statistical analysis. RESULTS: The results of this study showed that the successful rate of obtaining effective tissue (100% vs. 75%) and the puncture accuracy (100% vs. 88.89%) in CEUS group were significantly higher than those in US group (P < 0.05). CEUS-guided puncture biopsy of renal mass, especially in the case of urothelial carcinoma of the renal pelvis, outperforms conventional ultrasound, and the difference was statistically significant (P < 0.05). CONCLUSION: Percutaneous renal space-occupying lesion puncture biopsies aided by CEUS yield more effective tissue and improved puncture accuracy.

Efficacy of extracellular vesicles as a cell-free therapy in colitis: a systematic review and meta-analysis of animal studies.

Background: Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the treatment of inflammatory bowel disease (IBD) has been under intensive focus. Some studies have been conducted in animal models of colitis, while systematic reviews and meta-analyses are lacking. The current study aimed to conduct a systematic review and meta-analysis of studies investigating the efficacy of EVs on IBD. Methods: A systematic retrieval of all studies in PubMed, EMBASE, MEDLINE, Web of Science, and Cochrane Library reported the effects of EVs in the colitis model up to 22 June 2023. The methodological quality was assessed based on SYRCLE's risk of bias (RoB) tool. Disease activity index (DAI), myeloperoxidase activity (MPO), histopathological score (HS), and inflammatory cytokines (TNF-α, NF-κB, IL-1ß, IL-6, and IL-10) were extracted as analysis indicators by Web Plot Digitizer 4.5. A meta-analysis was performed to calculate the standardized mean difference and 95% confidence interval using random-effect models by Review Manager 5.3 and STATA 14.0 software. Results: A total of 21 studies were included in this meta-analysis. Although the heterogeneity between studies and the potential publication bias limits confidence in the extent of the benefit, EV treatment was superior to the control in the colitis evaluation with reduced DAI, HS, MPO activity, and pro-inflammatory cytokines, including TNF-α, NF-κB, IL-1ß, and IL-6, while increasing the content of anti-inflammatory cytokine IL-10 (all p < 0.05). Conclusion: Our meta-analysis results supported the protective effect of EVs on colitis rodent models based on their potential role in IBD therapy and propelling the field toward clinical studies.

Quantitative evaluation of colorectal tumour vasculature using contrast-enhanced ultrasound: Correlation with angiogenesis and prognostic significance.

BACKGROUND: Ultrasound is a vital tool for the diagnosis and management of colorectal cancer (CRC). Contrast-enhanced ultrasound (CEUS) is a non-invasive, safe, and cost-effective method for evaluating tumour blood vessels, that play a crucial role in tumour growth and progression. AIM: To explore CEUS's role in the quantitative evaluation of CRC blood vessels and their correlation with angiogenesis markers and prognosis. METHODS: This study prospectively enrolled 100 patients with CRC confirmed by histopathology. All patients received preoperative CEUS examinations. Quantitative parameters, such as peak intensity (PI), time to peak (TTP), and area under the curve (AUC), were derived from time-intensity curve (TIC) analysis. Tumour tissue samples were obtained during surgery and examined immunohistochemically to assess the expression of angiogenesis markers, including vascular endothelial growth factor (VEGF) and microvessel density (MVD). The correlation between CEUS parameters, angiogenesis markers, and clinicopathological features was evaluated using appropriate statistical tests. RESULTS: Quantitative CEUS parameters (PI, TTP, and AUC) showed significant correlations with VEGF expression (P < 0.001) and MVD (P < 0.001), indicating a strong link between tumour blood vessels and angiogenesis. Increased PI, reduced TTP, and expanded AUC values were significantly related to higher tumour stage (P < 0.001), lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). Furthermore, these parameters were recognized as independent predictors of overall survival and disease-free survival in multivariate analysis (P < 0.001). CONCLUSION: CEUS has a high potential in guiding treatment planning and predicting patient outcomes. However, more comprehensive, multicentre studies are required to validate the clinical utility of CEUS in CRC management.

Liquid Chromatography-Tandem Mass Spectrometry Detection of Human and Veterinary Drugs and Pesticides in Surface Water.

Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C18 column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L-1) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L-1. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L-1. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.

Tyrosine phosphorylation of IRF3 by BLK facilitates its sufficient activation and innate antiviral response.

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.

Etiological Survey and Traceability Analysis of a Foodborne Disease Outbreak of Salmonella Senftenberg in Guizhou Province.

To conduct a study that examined the molecular epidemiology and pathogenesis of Salmonella Senftenberg isolates associated with an outbreak of foodborne disease in Guizhou Province and to provide a reference basis for the traceability of foodborne salmonellosis outbreaks and clinical diagnosis and treatment in the province. Fourteen strains of suspected Salmonella isolated from patient stool and food samples were used for pathogenic identification and serotyping by biochemical and mass spectrometry methods. Fourteen types of antibiotics were tested for drug sensitivity by the microbroth dilution method, and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). After the sequencing data were spliced by SPAdes, the gene protein sequences were compared with the Comprehensive Antibiotic Research Database and Virulence Factor Database, drug resistance and virulence genes were predicted, and whole genome multilocus sequence typing (wgMLST) was performed. The results were compared with those for Salmonella strains of the same serotype from the past 5 years in China detailed on the TraNet website. All 14 strains were identified as Salmonella Senftenberg (with the antigenic formula 1,3,19:g,s,t:-), and in the PFGE cluster tree, the strains were divided into two band types, with a similarity of 88.9%. The 14 strains were sensitive to the 14 antibiotics. WGS analysis showed that the 14 strains carried the same drug resistance and virulence genes and that all strains carried 3 aminoglycoside and lipopeptide drug resistance genes, including 114 virulence genes. The wgMLST results showed that the strains were distributed on the same small branch as those obtained from previous outbreaks of infection in Tianjin and Jilin. Salmonella Senftenberg, which caused the outbreak, carries a variety of virulence genes, which suggests that the strain is highly pathogenic. These pathogenic bacteria may be associated with the Salmonella strain in Tianjin, Jilin, and other places and have caused foodborne disease outbreaks as a result of imported contamination.

Molecular mechanism of tillering response to nitrogen in rice.

Nitrogen (N) fertilizer acts as the main driving force for agricultural productivity improvement. However, overuse of N fertilizer has caused severe effects to environment and ecosystem. Thus, it is pivotal to improve nitrogen use efficiency (NUE) for future sustainable agriculture. Agronomic traits response to N are significant indices for NUE phenotyping. For example, tiller number, grain number per panicle, and grain weight are three major components for cereal yields. Although regulatory mechanisms regarding to these three traits have been largely reported, few is known about how N affects them. Tiller number is one of the most sensitive traits response to N and also plays a key role for N-promoted yield improvement. It is thereby of great significance to dissect the genetic basis underlying tillering response to N. In this review, we summarize the factors contributing to NUE as well as the regulatory mechanisms over rice tillering and emphasize how N affects rice tillering, future research directions are also discussed for further improving NUE.

Immune functions of the Dscam extracellular variable region in Chinese mitten crab.

In arthropods, there is only a single copy of Down Syndrome Cell Adhesion Molecule (Dscam) in the genome, but it can exist as numerous splice variants. There are three hypervariable exons in the extracellular domain and one hypervariable exon in the transmembrane domain. In Chinese mitten crab (Eriocheir sinensis), exons 4, 6 and 14 can produce 25, 34 and 18 alternative splice variants, respectively. In this study, through Illumina sequencing, we identified additional splice variants for exons 6 and 14, hence there may be > 50,000 Dscam protein variants. Sequencing of exons 4, 6 and 14 showed that alternative splicing was altered after bacterial stimulation. Therefore, we expressed and purified the extracellular variable region of Dscam (EsDscam-Ig1-Ig7). Exons 4.3, 6.46 and 14.18, three variable exons of the recombinant protein, were randomly selected. The functions of EsDscam-Ig1-Ig7 in immune defences of E. sinensis were subsequently explored. EsDscam-Ig1-Ig7 was discovered to bind to both Gram-positive Staphylococcus aureus and Gram-negative Vibrio parahaemolyticus, but it did not exhibit antibacterial activity. By promoting hemocyte phagocytosis and bacterial removal, EsDscam-Ig1-Ig7 can also shield the host from bacterial infection. The findings highlight the immunological activities of Dscam alternative splicing and reveal the potential for many more Dscam isoforms than were previously predicted in E. sinensis.

Primary intra-abdominal paraganglioma: A case report.

BACKGROUND: Paragangliomas are rare neuroendocrine tumors. We hereby report a case of a localized paraganglioma found in the abdominal cavity, and review the relevant literature to improve the understanding of this disease. CASE SUMMARY: A 29-year-old Chinese female patient was referred to our hospital due to an abdominal mass found on physical examination. Imaging revealed a mass in the left upper abdomen, suggestive of either a benign stromal tumor or an ectopic accessory spleen. Laparoscopic radical resection was subsequently performed, and histopathological analysis confirmed the diagnosis of a paraganglioma. The patient was followed up 3 months post-operation, and reported good recovery with no metastasis. CONCLUSION: Radical resection can effectively treat intra-abdominal paragangliomas, with few side effects and low recurrence risk. In addition, early and accurate diagnosis and timely intervention are essential for the prognosis of this disease.

Patient-controlled intravenous administration of dexmedetomidine with nalbuphine versus sufentanil for post cesarean delivery analgesia: A retrospective observational study.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 µg/kg/h DEX in combination with 0.03 µg/kg/h SUF in Group I (n = 150) or 0.11 µg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

Caspar negatively regulates anti-bacterial immunity by controlling the nuclear translocation of Relish in Chinese mitten crab (Eriocheir sinensis).

Caspar, a homolog of the Fas-associated factor 1 (FAF1) family, contains an N-terminal ubiquitin interaction domain, a ubiquitin-like self-association domain, and a C-terminal ubiquitin regulatory domain. Caspar has been reported to be involved in the antibacterial immunity of Drosophila, which is unclear whether it is involved in the antibacterial immune process of crustaceans. In this article, we identified a Caspar gene in Eriocheir sinensis and named it EsCaspar. EsCaspar positively respond to bacterial stimulation and downregulate the expression of certain associated antimicrobial peptides by inhibiting the nuclear translocation of EsRelish. Thus, EsCaspar might be a suppressor of the immune deficiency (IMD) pathway that prevents over-activation of the immune system. Indeed, excess EsCaspar protein in crabs reduced resistance to bacterial infection. In conclusion, EsCaspar is a suppressor of the IMD pathway in crabs that plays a negative regulatory role in antimicrobial immunity.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aß neurotoxicity and promotes Aß clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Grain filling leads to backflow of surplus water from the maize grain to the cob and plant via the xylem.

Rapid dehydration of maize grain is one of the main characteristics of cultivar selection for mechanical grain harvest; however, the dominant driving forces and mechanisms of grain dehydration before physiological maturity remain disputable and obscure. This study compared the grain moisture content and dehydration rate of coated treatment (no surface evaporation) and control grains. Meanwhile, the xylem-mobile dye was infused from stem and cob, and its movement was observed in cob, ear-stalk and stem xylem. The development dynamics of husk, grain and cob were analyzed to determine the mechanism of grain dehydration. The results showed that, from grain formation to 5-10 days before physiological maturity, the main driving force of grain dehydration of the early and middle-maturity maize cultivars was filling, followed by surface evaporation. In the dye movement experiment, the movement of the stem-infused xylem-mobile dye through the pedicel xylem was observed during but not after the grain formation period. Moreover, the cob-infused xylem-mobile dye moved to the ear- stalk and the stem via the xylem. There was a significantly positive correlation between grain filling rate and dehydration rate from grain formation to physiological maturity. According to these results, we proposed that in the grain dehydration phase driven by filling, the surplus water in the grain flows back to the cob via the pedicel xylem, of which some flowed back to the plant via the cob and ear- stalk xylem. This provides a new theoretical basis for selecting and breeding maize cultivars suitable for mechanical grain harvesting.