The AP2/ERF transcription factor MdDREB2A regulates nitrogen utilisation and sucrose transport under drought stress.

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.

Efficacy and safety of third-line or later-line targeted treatment for patients with metastatic colorectal cancer: a meta-analysis.

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.

Altered cognition and anxiety in adolescent offspring whose mothers underwent different-pattern maternal sleep deprivation, and cognition link to hippocampal expressions of Bdnf and Syt-1.

Background: Inadequate sleep during pregnancy negatively affects the neural development of offspring. Previous studies have focused on the continuous sleep deprivation (CSD) paradigm, but the sleep pattern during late pregnancy is usually fragmented. Objective: To compare the effects of CSD and fragmented sleep deprivation (FSD) in late pregnancy on emotion, cognition, and expression of synaptic plasticity-related proteins in offspring mice. Methods: Pregnant CD-1 mice were either subjected to 3/6 h of CSD/FSD during gestation days 15-21, while those in the control group were left untreated. After delivery, the offspring were divided into five groups, i.e., control (CON), short or long CSD (CSD3h, CSD6h), and short or long FSD (FSD3h, FSD6h). When the offspring were 2 months old, the anxiety-like behavior level was tested using the open field (OF) and elevated plus maze (EPM) test, and spatial learning and memory were evaluated using the Morris water maze (MWM) test. The expression of hippocampal of brain-derived neurotrophic factor (Bdnf) and synaptotagmin-1 (Syt-1) was determined using RT-PCR and western blotting. Results: The CSD6h, FSD3h, and FSD6h had longer latency, fewer center times in the OF test, less open arms time and fewer numbers of entries in the open arms of the EPM, longer learning distance swam and lower memory percentage of distance swam in the target quadrant in the MWM test, and decreased BDNF and increased Syt-1 mRNA and protein levels in the hippocampus. Compared to the CSD6h, the FSD3h and FSD6h had longer distance swam, a lower percentage of distance swam in the target quadrant, decreased BDNF, and increased Syt-1 mRNA and protein levels in the hippocampus. Conclusion: The results suggested that maternal sleep deprivation during late pregnancy impairs emotion and cognition in offspring, and FSD worsened the cognitive performance to a higher extent than CSD. The observed cognitive impairment could be associated with the expression of altered hippocampal of Bdnf and Syt-1 genes.

Environmental enrichment improves declined cognition induced by prenatal inflammatory exposure in aged CD-1 mice: Role of NGPF2 and PSD-95.

Introduction: Research suggests that prenatal inflammatory exposure could accelerate age-related cognitive decline that may be resulted from neuroinflammation and synaptic dysfunction during aging. Environmental enrichment (EE) may mitigate the cognitive and synaptic deficits. Neurite growth-promoting factor 2 (NGPF2) and postsynaptic density protein 95 (PSD-95) play critical roles in neuroinflammation and synaptic function, respectively. Methods: We examined whether this adversity and EE exposure can cause alterations in Ngpf2 and Psd-95 expression. In this study, CD-1 mice received intraperitoneal injection of lipopolysaccharide (50 µg/kg) or normal saline from gestational days 15-17. After weaning, half of the male offspring under each treatment were exposed to EE. The Morris water maze was used to assess spatial learning and memory at 3 and 15 months of age, whereas quantitative real-time polymerase chain reaction and Western blotting were used to measure hippocampal mRNA and protein levels of NGPF2 and PSD-95, respectively. Meanwhile, serum levels of IL-6, IL-1ß, and TNF-α were determined by enzyme-linked immunosorbent assay. Results: The results showed that aged mice exhibited poor spatial learning and memory ability, elevated NGPF2 mRNA and protein levels, and decreased PSD-95 mRNA and protein levels relative to their young counterparts during natural aging. Embryonic inflammatory exposure accelerated age-related changes in spatial cognition, and in Ngpf2 and Psd-95 expression. Additionally, the levels of Ngpf2 and Psd-95 products were significantly positively and negatively correlated with cognitive dysfunction, respectively, particularly in prenatal inflammation-exposed aged mice. Changes in serum levels of IL-6, IL-1ß, and TNF-α reflective of systemic inflammation and their correlation with cognitive decline during accelerated aging were similar to those of hippocampal NGPF2. EE exposure could partially restore the accelerated decline in age-related cognitive function and in Psd-95 expression, especially in aged mice. Discussion: Overall, the aggravated cognitive disabilities in aged mice may be related to the alterations in Ngpf2 and Psd-95 expression and in systemic state of inflammation due to prenatal inflammatory exposure, and long-term EE exposure may ameliorate this cognitive impairment by upregulating Psd-95 expression.

Prenatal exposure to inflammation increases anxiety-like behaviors in F1 and F2 generations: possible links to decreased FABP7 in hippocampus.

Anxiety disorder has a high prevalence, and the risk of anxiety increases with age. Prenatal inflammation during key developmental timepoints can result in long-term changes in anxiety phenotype, even over a lifetime and across generations. However, whether maternal inflammation exposure during late gestation has intergenerational transmission effects on age-related anxiety-like behaviors and the possible underlying mechanisms are largely unknown. Fatty acid binding protein 7 (FABP7) is critical in hippocampal neurogenesis and is closely related to neuropsychiatric diseases, including anxiety disorder. The current study investigated the effects of maternal (F0 generation) lipopolysaccharide administration (50 µg/kg, i.p.) during late gestation on anxiety-like behaviors and FABP7 expression in F1 and F2 offspring, as well as the potential sex-specificity of intergenerational effects. Anxiety-like behaviors were evaluated using open field (OF), elevated plus maze, and black-white alley (BWA) tests at 3 and 13 months of age. The protein and messenger RNA levels of FABP7 in the hippocampus were measured using Western blot and real-time quantitative polymerase chain reaction (PCR), respectively. Overall, gestational LPS exposure in the F0 generation increased anxiety levels and decreased FABP7 expression levels in the F1 generation, which carried over to the F2 generation, and the intergenerational effects were mainly transferred via the maternal lineage. Moreover, hippocampal FABP7 expression was significantly correlated with performance in the battery of anxiety tests. The present study suggested that prenatal inflammation could increase age-related anxiety-like behaviors both in F1 and F2 offspring, and these effects possibly link to the FABP7 expression.

Multiphonon processes of the inelastic electron transfer in olfaction.

Inelastic electron transfer, regarded as one of the potential mechanisms to explain odorant recognition in atomic-scale processes, is still a matter of intense debate. Here, we study multiphonon processes of electron transfer using the Markvart model and calculate their lifetimes with the values of key parameters widely adopted in olfactory systems. We find that these multiphonon processes are as quick as the single phonon process, which suggests that contributions from different phonon modes of an odorant molecule should be included for electron transfer in olfaction. Meanwhile, the temperature dependence of electron transfer could be analyzed effectively based on the reorganization energy which is expanded into the linewidth of multiphonon processes. Our theoretical results not only enrich the knowledge of the mechanism of olfaction recognition, but also provide insights into quantum processes in biological systems.

Complete Genome Sequence of the Biocontrol Agent Pseudomonas chlororaphis subsp. aureofaciens SPS-41.

Pseudomonas chlororaphis subsp. aureofaciens SPS-41 is a plant growth-promoting rhizobacterium with biocontrol potential that was isolated from the rhizosphere of sweet potato in Xuzhou, Jiangsu Province, China. Our previous study demonstrated that volatile organic compounds (VOCs) produced by SPS-41 inhibited black spot disease fungi Ceratocystis fimbriata in postharvest sweet potatoes and a variety of other plant pathogens, and the VOCs also displayed strong nematocidal activity. In order to further explore the application potential of this strain, we here report the complete genome sequence of strain SPS-41. The genome consists of one chromosome (6,757,898 bp) with a G+C content 63.10%, which contains 5,951 coding genes, 67 transfer RNA genes, 16 ribosome RNA genes, and 85 other non-coding RNA genes. No plasmid was detected. The information of the genome will provide resources for studying the biocontrol mechanism of this strain.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Circular RNA in gastric cancer.

Gastric cancer (GC) is a common malignancy and is the third leading cause of cancer-related death. At present, there is no simple and effective screening method for early-stage GC, and the treatment results and prognosis are poor. With the continuous improvement of molecular biology techniques, research on circular RNA (circRNA) has gradually expanded over time. Much data supports the role of circRNA in tumorigenesis. Moreover, due to its structural specificity and biological stability, circRNA is anticipated to be a potential biomarker for tumor diagnosis. Studies have confirmed that circRNA can participate in the proliferation, invasion, metastasis, and apoptosis of GC. These findings will lead to novel directions for the diagnosis and treatment of GC. This article reviews the structure and function of circRNA, summarizes the current studies on circRNA, and discusses the potential diagnostic value of circRNA in GC.

Root exudates-driven rhizosphere recruitment of the plant growth-promoting rhizobacterium Bacillus flexus KLBMP 4941 and its growth-promoting effect on the coastal halophyte Limonium sinense under salt stress.

Halophytes play an important role in the bioremediation of saline soils. Increased evidence has revealed that plant growth-promoting rhizobacteria (PGPR) have colonized the halophytic rhizosphere, and they have evolved the capacity to reduce salt stress damage to the host. However, the mechanism by which halophytes attract and recruit beneficial PGPR has rarely been reported. This study reports the interaction between the halophyte Limonium sinense and its rhizosphere PGPR strain Bacillus flexus KLBMP 4941, as well as the mechanism by which KLBMP 4941 promotes host plant growth under salt stress. After salt stress treatment, we collected the root exudates (REs) of L. sinense and found that the REs could promote the growth and chemotaxis of the bacterium KLBMP 4941. In addition, the components of the REs under salt stress were analyzed, and some organic acids (2-methylbutyric acid, stearic acid, palmitic acid, palmitoleic acid, and oleic acid) were detected as the major components. Further assessment showed that each of these components had positive effects on the growth, motility, chemotaxis, and root colonization of strain KLBMP 4941. Further pot experiments revealed the potential PGP mechanisms induced by strain KLBMP 4941 on the host plant under salt stress. Inoculation with KLBMP 4941 promoted the accumulation of chlorophyll to enhance photosynthesis, increased osmotic regulator contents, enhanced flavonoid and antioxidant enzymes, and regulated Na+/K+ homeostasis to help the host ameliorate salinity stress damage. Our findings indicate that the halophyte L. sinense can attract and recruit beneficial rhizosphere bacteria by REs under salt stress, and the recruited B. flexus KLBMP 4941 elicited PGP effects under salinity stress through complex plant physiological regulatory mechanisms. This study provides a foundation for the enhancement of the rhizosphere colonization ability of the PGP strain KLBMP 4941, which shows potential applications in phytoremediation of saline soils.

Fermentation conditions optimization, purification, and antioxidant activity of exopolysaccharides obtained from the plant growth-promoting endophytic actinobacterium Glutamicibacter halophytocola KLBMP 5180.

In this study, an endophytic actinobacterium Glutamicibacter halophytocola KLBMP 5180, was investigated for the production and antioxidant activity of exopolysaccharides (EPSs). First, the suitable fermentation time, temperature, inoculation volume, pH value, and the carbon and nitrogen sources for EPSs production were obtained using the one variable at a time method (OVAT). Then, a central composition design was used for fermentation conditions optimization to obtain the maximum EPS yield. The optimal medium and condition were as follows: 100 mL broth in 250 mL Erlenmeyer flasks, including 3.65 g/L maltose, 9.88 g/L malt extract, 3.40 g/L yeast extract, 1.41 g/L MnCl2, pH 7.5, culture temperature 28 °C, and 200 rpm for 7 days, which increased the yield of EPSs to 2.89 g/L. Two purified EPSs, 5180EPS-1 (MW 58.9 kDa) and 5180EPS-2 (10.5 kDa), comprising rhamnose, galacturonic acid, glucose, glucuronic acid, xylose, and arabinose, were obtained for chemical analysis and antioxidant evaluation. The scavenging ability and reducing power of the superoxide anion and hydroxyl radicals demonstrated the moderate in vitro antioxidant activities of the two EPSs, thus indicating their potential to be a new source of natural antioxidants. However, further structure elucidation and functional studies need to be continued.

[Molecular regulation mechanism of Myomaker and Myomerger in myoblast fusion].

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.

Influence of long-term temperature stress on respiration frequency, Na+/K+-ATPase activity, and lipid metabolism in common carp (Cyprinus carpio).

Temperature is a key factor that influences fish metabolism. Therefore, it is important to understand how temperature variation affects lipid metabolism and energy consumption in fish. We determined respiration frequency, Na+/K+-ATPase activity, and lipid metabolism in common carp (Cyprinus carpio) after 18 days of temperature stress (5 °C and 30 °C, with 17 °C as the control). We found that respiratory frequency was positively correlated with water temperature (p < 0.01), whereas red blood cell count and mean corpuscular hemoglobin content and concentration were negatively correlated with temperature. In liver and heart, triglyceride (TG) levels were lower in both stress groups (5 °C and 30 °C) than in the control (17 °C) (p < 0.01), and highest in muscle from the high temperature stress group (p < 0.01). The non-esterified fatty acid concentration was negatively correlated with TG levels. In brain, lipoprotein lipase (LPL) activity decreased with increasing temperature and hepatic lipase (HL) activity was lower in both stress groups than in the control (p < 0.01). In muscle, the activity of LPL and HL was lowest in the high temperature stress group, resulting in a significant increase in TG levels. Na+/K+-ATPase activity in heart was lower in both stress groups than in the control (p < 0.01). The expression of LPL mRNA in heart increased with increasing temperature (p < 0.01), whereas LPL mRNA expression in brain and liver increased in both stress groups (p < 0.01). Our results show that temperature can significantly affect lipid metabolism in common carp, and that different tissues respond differently to changes in temperature.

Accelerated Deficits of Spatial Learning and Memory Resulting From Prenatal Inflammatory Insult Are Correlated With Abnormal Phosphorylation and Methylation of Histone 3 in CD-1 Mice.

Gestational infection causes various neurological deficits in offspring, such as age-related spatial learning and memory (SLM) decline. How inflammation causes age-related SLM dysfunction remains unknown. Previous research has indicated that histone modifications, such as phosphorylation of H3S10 (H3S10p) and trimethylation of H3K9 (H3K9me3) may be involved. In our study, pregnant mice received an intraperitoneal injection of lipopolysaccharide (LPS, 50 or 25 µg/kg) or normal saline during gestational days 15-17. After normal parturition, the offspring were randomly separated into 1-, 6-, 12-, 18-, and 22-month-old groups. SLM performance was assessed using a radial six-arm water maze (RAWM). The hippocampal levels of H3S10p and H3K9me3 were detected using an immunohistochemical method. The results indicated that the offspring had significantly impaired SLM, with decreased H3S10p and increased H3K9me3 levels from 12 months onward. Maternal LPS exposure during late gestation significantly and dose-dependently exacerbated the age-related impairment of SLM, with the decrease in H3S10p and increase in H3K9me3 beginning at 12 months in the offspring. The histone modifications (H3S10p and H3K9me3) were significantly correlated with impairment of SLM. Our findings suggest that prenatal exposure to inflammation could exacerbate age-related impairments of SLM and changes in histone modifications in CD-1 mice from 12 months onward, and SLM impairment might be linked to decreased H3S10p and increased H3K9me3.

Efficacy of neuromuscular electrical stimulation on Wilson's disease patients with dysphagia.

[Purpose] Dysphagia is a neurological symptom that is observed in more than half of patients with Wilson's disease. It is often associated with aspiration pneumonia, dehydration, and malnutrition, resulting in drastic reduction of the quality of life. Neuromuscular electrical stimulation could be an adjunct therapy for dysphagia treatment. However, there is limited data about the application of NMES for dysphagia in Wilson's disease. Thus, we explored the potential application of NMES for dysphagia treatment in Wilson's disease. [Participants and Methods] Sixty Wilson's disease patients who suffered from dysphagia were randomized into two groups. Swallowing function training was taught to the control group (n=30) while Neuromuscular electrical stimulation therapy was given to treatment group (n=30). Eight weeks post treatment, using the water swallow test and the Standardized Swallowing Assessment, the swallowing function was determined. [Results] None of the patients experienced discomfort before, during or after the intervention. After 8 weeks of therapy, when compared to the control, an increased improvement in swallowing function was noted for the treatment group. [Conclusion] Neuromuscular electrical stimulation treatment can improve swallowing function in Wilson's disease patients afflicted with dysphagia. Therefore, it has the potential to be a form of therapy in clinical practice.

COX-2 inhibition by celecoxib in epithelial ovarian cancer attenuates E-cadherin suppression through reduced Snail nuclear translocation.

Elevated cyclooxygenase-2 (COX-2) closely associates with tumor progression and distant metastasis in various human cancers. However, the role of COX-2 in epithelial ovarian cancer (EOC), and its mechanistic details, remain poorly understood. In the present study, we tested hypothesis that COX-2 induces loss of expression of E-cadherin, with resulting promotion of cancer cells' invasiveness in ovarian cancer. First, we observed an inverse relationship between COX-2 and E-cadherin expression as COX-2 was enhanced but E-cadherin was decreased in surgically-resected specimens of EOC. Depletion of COX-2, by celecoxib treatment, resulted in attenuated nuclear translocation of Snail, and, in turn, significantly increased E-cadherin in EOC cell line SKOV3, which was established to be due to the reduced binding of Snail onto E-cadherin promoter. Such COX-2 inhibition resulted in reduced invasion of EOC cells, similar to what was achieved through Snail silencing in SKOV as well as ES-2 EOC cells. These results suggest that COX-2-Snail signaling plays a critical role in regulation of E-cadherin and might provide insights into mechanisms for paracrine inflammation-mediated aggressiveness in EOC.

Research progress in sRNAs and functional proteins in epididymosomes.

The semen quality is a basic and the most important indicator of male reproductive health. Mammalian spermatozoa undergo a series of complex structural and functional changes in the epididymis to mature and achieve fertilization capacity. Sperm cell maturation is mediated by a complex physiological process, which is synergistically regulated by a large number of transcription factors, hormones and other signaling molecules. In recent years, there is increasing evidence supporting the notion that functional proteins and sRNA (small RNAs) in epididymosomes participate in sperm maturation and fertilization process. In this review, we summarize the biological roles of functional proteins and two major sRNAs (tRNAs and miRNAs) in sperm maturation in epididymosomes, and provide some theoretical guidance and new ideas for treatments of low fertility, infertility and other reproductive diseases in men.

Accelerated reduction of serum thyroxine and hippocampal histone acetylation links to exacerbation of spatial memory impairment in aged CD-1 mice pubertally exposed to bisphenol-a.

Age-related cognitive decline has been associated with changes in endogenous hormones and epigenetic modification of chromatin, including histone acetylation. Developmental exposure to endocrine disrupting chemicals, such as bisphenol-A (BPA) that produces endocrine disruption and epigenetic changes, may be a risk factor for accelerating cognitive deficits during aging. Thus, we exposed CD-1 mice to BPA (0, 1, and 100 mg/l BPA in the drinking water) orally during puberty (from postnatal days 28 to 56) and investigated whether pubertal BPA exposure exacerbates the age-related impairment of spatial cognition in old age (18 months old) and whether serum sex and thyroid hormones or hippocampal histone acetylation (H3K9ac and H4K8ac) are associated with cognitive effects. A young control group (6 months old) was added to analyze the age effect. Results showed untreated aged mice had marked decline of spatial learning and memory in the novel location recognition and radial six-arm water maze tasks, with decreased levels of these hormones and hippocampal H3K9ac and H4K8ac compared to young controls. The BPA treatment exacerbated age-related spatial cognitive impairment and accelerated the reduction of free thyroxine (FT4), H3K9ac, and H4K8ac, and the 100 mg/l BPA group showed more significant impact. Additionally, correlation analyses revealed that lower levels of FT4, H3K9ac, and H4K8ac were accompanied by decreased spatial memory abilities. We concluded that accelerated reduction of serum FT4 and hippocampal H3K9ac and H4K8ac might be linked to exacerbation of age-related spatial cognitive impairment due to pubertal BPA exposure.

Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol.

Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p < .05), whereas the CDD patients performed poorly in all the assessed memory types (p < .05). In addition, the CID patients had higher levels (mean difference [95% CI]) of corticotrophin-releasing hormone, cortisol (31.98 [23.97, 39.98] µg/l), total triiodothyronine (667.58 [505.71, 829.45] µg/l), and total thyroxine (41.49 [33.23, 49.74] µg/l) (p < .05), and lower levels of thyrotropin-releasing hormone (-35.93 [-38.83, -33.02] ng/l), gonadotropin-releasing hormone (-4.50 [-5.02, -3.98] ng/l) (p < .05), and adrenocorticotropic hormone compared to the CDD patients. After controlling for confounding variables, the partial correlation analysis revealed that the levels of cortisol positively correlated with the errors in object working memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels.

Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice.

Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-ß, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-ß42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.

Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25µg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude.