[Effects of oral exposure to iron oxide nanoparticles on reproductive system of male rats].

OBJECTIVE: To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. METHODS: Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. RESULTS: Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P<0.01). The activity of ACP in medium and high dose groups increased(P<0.05), and the activity of γ-GT decreased(P<0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P>0.05). The level of GSH in medium dose group was increased(P<0.05), and the content of MDA in medium and high dose groups was increased(P<0.01). There was no significant difference in SOD activity among the groups(P>0.05). CONCLUSION: Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.

The lead-free perovskite-based heterojunction C2N/CsGeI3: an exploration for superior visible-light absorption.

Halide perovskites have distinguished themselves among the numerous optoelectronic materials due to their versatile processing technology and exceptional optical response. Unfortunately, their stability and toxicity from heavy metals severely hamper their development, in addition to the challenge of further improving photovoltaic performance. Hence, a lead-free perovskite-based heterojunction, C2N/CsGeI3, is investigated using a hybrid density functional, including electron structures, charge density differences, optical properties and more. The study reveals the presence of a built-in electric field directed from the CsGeI3 to the C2N layer. Moreover, based on the work function, it is confirmed that the electrons are transferred in a Z-scheme mechanism after the CsGeI3 contacts with the C2N layer. Under light irradiation, the construction of the C2N/CsGeI3 heterojunction significantly enhances optical absorption within the range of visible-light wavelengths. Additionally, the impact of interfacial strain on the C2N/CsGeI3 is explored and discussed. These findings not only suggest that the C2N/CsGeI3 heterojunction holds promise for photovoltaic applications but also provide a theoretical insight into lead-free perovskite-based functional materials.

Polyphenol-mediated defect patching of graphene oxide membranes for sulfonamide contaminants removal and fouling control.

Graphene oxide (GO)-based laminar membranes are promising candidates for next-generation nanofiltration membranes because of their theoretically frictionless nanochannels. However, nonuniform stacking during the filtration process and the inherent swelling of GO nanosheets generate horizontal and vertical defects, leading to a low selectivity and susceptibility to pore blockage. Herein, both types of defects are simultaneously patching by utilizing tannic acid and FeⅢ. Tannic acid first partially reduced the upper GO framework, and then coordinated with FeⅢ to form a metal-polyphenol network covering horizontal defects. Due to the enhanced steric hindrance, the resulting membrane exhibited a two-fold increase in sulfonamide contaminants exclusion compared to the pristine GO membrane. A non-significant reduction in permeance was observed. In terms of fouling control, shielding defects significantly alleviated the irreversible pore blockage of the membrane. Additionally, the hydrophilic metal-polyphenol network weakened the adhesion force between the membrane and foulants, thereby improving the reversibility of fouling in the cleaning stage. This work opens up a new way to develop GO-based membranes with enhanced separation performance and antifouling ability.

All-trans retinoic acid alleviates collagen-induced arthritis and promotes intestinal homeostasis.

All-trans retinoic acid (ATRA) has emerged as a promising adjunctive treatment for rheumatoid arthritis. However, the mechanism by which ATRA mitigates arthritis remains unclear. In this study, we aimed to explore ATRA alleviation of arthritis and the role of ATRA in regulating intestinal homeostasis. Thus, we established a collagen-induced arthritis (CIA) model in Wistar rats. After 6 weeks of ATRA treatment, the arthritis index of CIA rats decreased, synovial inflammation was alleviated, and the disruption of Th17/Treg differentiation in peripheral blood was reversed. Additionally, the Th17/Treg ratio in the mesenteric lymph nodes decreased and the expression of Foxp3 mRNA increased and that of IL-17 mRNA decreased in the colon and ileum. Microscopically, we observed reduced intestinal inflammation. Transmission electron microscopy revealed that ATRA could repair tight junctions, which was accompanied by an increase in the expression of Claudin-1, Occludin and ZO-1. Moreover, ATRA regulated the composition of the gut microbiota, as was characterized based on the reduced abundance of Desulfobacterota and the increased abundance of Lactobacillus. In conclusion, ATRA demonstrates the potential to alleviate arthritis in CIA rats, which might be correlated with modulating the gut microbiota and regulating the intestinal immune response. Our findings provide novel insights into ATRA-mediated alleviation of arthritis.

Effects of food-grade iron(III) oxide nanoparticles on cecal digesta- and mucosa-associated microbiota and short-chain fatty acids in rats.

Although iron(III) oxide nanoparticles (IONPs) are widely used in diverse applications ranging from food to biomedicine, the effects of IONPs on different locations of gut microbiota and short-chain fatty acids (SCFAs) are unclear. So, a subacute repeated oral toxicity study on Sprague Dawley (SD) rats was performed, administering low (50 mg/kg·bw), medium (100 mg/kg·bw), and high (200 mg/kg·bw) doses of IONPs. In this study, we found that a high dose of IONPs increased animal weight, and 16S rRNA sequencing revealed that IONPs caused intestinal flora disorders in both the cecal digesta- and mucosa-associated microbiota. However, only high-dose IONP exposure changed the abundance and composition of the mucosa-associated microbiota. IONPs increased the relative abundances of Firmicutes, Ruminococcaceae_UCG-014, Ruminiclostridium_9, Romboutsia, and Bilophila and decreased the relative abundance of Bifidobacterium, and many of these microorganisms are associated with weight gain, obesity, inflammation, diabetes, and mucosal damage. Functional analysis showed that changes in the gut microbiota induced by a high dose of IONPs were mainly related to metabolism, infection, immune, and endocrine disease functions. IONPs significantly elevated the levels of valeric, isobutyric, and isovaleric acid, promoting the absorption of iron. This is the first description of intestinal microbiota dysbiosis in SD rats caused by IONPs, and the effects and mechanisms of action of IONPs on intestinal and host health need to be further studied and confirmed.

Nitrogen removal capability and mechanism of a novel heterotrophic nitrifying-aerobic denitrifying strain H1 as a potential candidate in mariculture wastewater treatment.

The nitrogen removal performance and mechanisms of Bacillus subtilis H1 isolated from a mariculture environment were investigated. Strain H1 efficiently removed NH4+-N, NO2--N, and NO3--N in simulated wastewater with removal efficiencies of 85.61%, 90.58%, and 57.82%, respectively. Strain H1 also efficiently degraded mixed nitrogen (NH4+-N mixed with NO2--N and/or NO3--N) and had removal efficiencies ranging from 82.39 to 89.54%. Nitrogen balance analysis revealed that inorganic nitrogen was degraded by heterotrophic nitrification-aerobic denitrification (HN-AD) and assimilation. 15N isotope tracing indicated that N2O was the product of the HN-AD process, while N2 as the final product was only detected during the reduction of 15NO2--N. The nitrogen assimilation and dissimilation pathways by strain H1 were further clarified using complete genome sequencing, nitrification inhibitor addition, and enzymatic activity measurement, and the ammonium oxidation process was speculated as NH4+ → NH2OH → NO → N2O. These results showed the application prospect of B. subtilis H1 in treating mariculture wastewater.

Nitrogen removal capability and mechanism of a novel heterotrophic nitrification-aerobic denitrification bacterium Halomonas sp. DN3.

Recently, the functional microorganisms capable of eliminating nitrogenous waste have been applied in mariculture systems. As a potential candidate for treating mariculture wastewater, strain DN3 eliminated 100% of ammonia and nitrate and 96.61%-100% of nitrite within 72 h, when single nitrogen sources at concentrations of 0-50 mg/L. Strain DN3 also exhibited the efficient removal performance of mixed-form nitrogen (ammonia, nitrate, and nitrite) at salinity 30 ‰, C/N ratio 20, and 180 rpm. The nitrogen assimilation pathway dominated inorganic nitrogen metabolism, with less nitrogen (14.23%-25.02% of TN) lost into the air via nitrification and denitrification, based on nitrogen balance analysis. Moreover, the bacterial nitrification pathway was explored by enzymatic assays and inhibition assays. These complex nitrogen assimilation and dissimilation processes were further revealed by bacterial genome analysis. These results provide important insight into nitrogen metabolism of Halomonas sp. and theoretical support for treating mariculture wastewater with strain DN3.

Brief pup separation during lactation confers resilience in behavioural deficits induced by chronic restraint stress in postpartum C57BL/6J dams.

BACKGROUND: The postpartum period is a complex time for females that affects health recovery. Stress during this period is one of the main risk factors for depression. Therefore, preventing stress-induced depression in the postpartum period is of great importance. Pup separation (PS) is a natural paradigm of postpartum care; however, the effect of different PS protocols during lactation on stress-induced depressive behaviours in dams is unknown. METHODS: Lactating C57BL/6J mice were subjected to no pup separation (NPS), brief PS (15 min/day, PS15) or long PS (180 min/day, PS180) from postpartum day 1 to postpartum day 21 and were then subjected to chronic restraint stress (CRS) for 21 days. Behavioural tests, specifically the open field test (OFT), elevated plus maze (EPM) test and tail suspension test (TST), were performed. The expression of mRNA and protein in the hippocampus and microbiota composition were also assessed. RESULTS: We observed CRS-induced anxiety- and depression-like behaviours in NPS dams. In addition, in NPS dams, microglial activation and the levels of NOD-like receptor pyrin domain containing 3, caspase-1 and interleukin-1ß were increased, whereas expression levels of collapsing response mediator protein 2 (CRMP2) and α-tubulin were decreased. However, immobility time in the TST was lower in PS15+CRS dams than in NPS+CRS dams, and time spent in the centre during the OFT and in the open arms during the EPM test was higher in PS15+CRS dams, indicating resilience. Expression of hippocampal biomarkers of neuroinflammation was inhibited and levels of CRMP2-mediated neuroplasticity were increased in PS15+CRS dams. Notably, we observed taxonomic changes in the cecal microbiota across different PS groups, as well as relationships between gut microbiota composition and some biomarkers of hippocampal neuroinflammation and neuroplasticity. LIMITATIONS: The sample size for gut microbiota analysis in this study was small. CONCLUSION: Collectively, the results of this study confirm that brief PS confers stress resilience in CRS-induced behavioural deficits and reverses hippocampal neuroinflammation-neuroplasticity injury and gut microbiota imbalance.

A low-cost and hand-hold PCR microdevice based on water-cooling technology.

Polymerase chain reaction (PCR) has become a powerful tool for detecting various diseases due to its high sensitivity and specificity. However, the long thermocycling time and the bulky system have limited the application of PCR devices in Point-of-care testing. Herein, we have proposed an efficient, low-cost, and hand-hold PCR microdevice, mainly including a control module based on water-cooling technology and an amplification module fabricated by 3D printing. The whole device is tiny and can be easily hand-held with a size of about 110 mm × 100 mm × 40 mm and a weight of about 300 g at a low cost of about $170.83. Based on the water-cooling technology, the device can efficiently perform 30 thermal cycles within 46 min at a heating/cooling rate of 4.0/8.1 ℃/s. To test our instrument, plasmid DNA dilutions were amplified with this device; the results demonstrate successful nucleic acid amplification of the plasmid DNA and exhibit the promise of this device for Point-of-care testing.

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms.

Backgrounds: The neural circuit mechanisms underlying depression remain unclear. Recently optogenetics has gradually gained recognition as a novel technique to regulate the activity of neurons with light stimulation. Scientists are now transferring their focus to the function of brain regions and neural circuits in the pathogenic progress of depression. Deciphering the circuitry mechanism of depressive-like behaviors may help us better understand the symptomatology of depression. However, few studies have summarized current progress on optogenetic researches into the neural circuit mechanisms of depressive-like behaviors. Aims: This review aimed to introduce fundamental characteristics and methodologies of optogenetics, as well as how this technique achieves specific neuronal control with spatial and temporal accuracy. We mainly summarized recent progress in neural circuit discoveries in depressive-like behaviors using optogenetics and exhibited the potential of optogenetics as a tool to investigate the mechanism and possible optimization underlying antidepressant treatment such as ketamine and deep brain stimulation. Methods: A systematic review of the literature published in English mainly from 2010 to the present in databases was performed. The selected literature is then categorized and summarized according to their neural circuits and depressive-like behaviors. Conclusions: Many important discoveries have been made utilizing optogenetics. These findings support optogenetics as a powerful and potential tool for studying depression. And our comprehension to the etiology of depression and other psychiatric disorders will also be more thorough with this rapidly developing technique in the near future.

Swimming exercise reverses chronic unpredictable mild stress-induced depression-like behaviors and alleviates neuroinflammation and collapsing response mediator protein-2-mediated neuroplasticity injury in adult male mice.

OBJECTIVE: Impaired neuroplasticity and neuroinflammation are vital in the mechanisms of depression. Exercise alleviates depressive symptoms and ameliorates body functions. Swimming is one of the most common exercises; however, whether swimming alters depressive behaviors and the underlying mechanism has not been fully elucidated. METHODS: Male C57/BL6J mice were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks and then were subjected to a 5-week swimming program. Behavioral test, including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM) test, and tail suspension test (TST), was conducted to assess the anxiety-like and depressive behaviors. Western blotting and immunofluorescence staining were carried out after tissue collection. RESULTS: This study showed that CUMS-induced depressive behaviors but swimming exercise increased sucrose preference in SPT, increased time and velocity in the center on OFT, decreased time in the closed arm, increased time in the open arm in EPM, and decreased immobility time in TST. We further found swimming exercise increased hippocampal collapsing response mediator protein-2 (CRMP2) expression and decreased p-CRMP2 expression in CUMS mice. CUMS inhibited the levels of α-tubulin and CRMP2, and the expression of ionized calcium-binding adaptor molecule 1 and caspase-1, whereas swimming reversed them in CUMS-exercised mice. CONCLUSION: Our study confirmed that swimming exercise reverses CUMS-induced depressive behaviors, and neuroinflammation and CRMP2-mediated neuroplasticity are involved, which may provide a new insight into the antidepression therapy of exercise.

Evaluation of Potential Probiotic Properties of a Strain of Lactobacillus plantarum for Shrimp Farming: From Beneficial Functions to Safety Assessment.

In recent years the safety of probiotics has received increasing attention due to the possible transfer and spread of virulence factors (VFs) and antibiotic resistance genes (ARGs) among microorganisms. The safety of a strain of Lactobacillus plantarum named W2 was evaluated in phenotype and genotype in the present study. Its probiotic properties were also evaluated both in vivo and in vitro, including adherence properties, antibacterial properties and beneficial effects on the growth and immunity of Pacific white shrimp, Penaeus vannamei. Hemolysis tests, antibiotic resistance tests and whole genome sequence analysis showed that W2 had no significant virulence effects and did not carry high virulence factors. W2 was found to be sensitive to chloramphenicol, clindamycin, gentamicin, kanamycin and tetracycline, and to be resistant to ampicillin and erythromycin. Most ARGs have no transfer risk and a few have transfer risk but no significant enrichment in human-associated environments. The autoaggregation of W2 was 82.6% and the hydrophobicity was 81.0%. Coaggregation rate with Vibrio parahaemolyticus (24.9%) was significantly higher than Vibrio's autoaggregation rate (17.8%). This suggested that W2 had adhesion potential to mucosal/intestinal surfaces and was able to attenuate the adherence of V. parahaemolyticus. In addition, several adhesion-related protein genes, including 1 S-layer protein, 1 collagen-binding protein and 9 mucus-binding proteins were identified in the W2 genome. W2 had efficiently antagonistic activity against 7 aquatic pathogenic strains. Antagonistic components analysis indicated that active antibacterial substances might be organic acids. W2 can significantly promote the growth of shrimp when supplemented with 1 × 1010 cfu/kg live cells. Levels of 7 serological immune indicators and expression levels of 12 hepatopancreatic immune-related genes were up-regulated, and the mortality of shrimp exposed to V. parahaemolyticus was significantly reduced. Based on the above, L. plantarum W2 can be applied safely as a potential probiotic to enhance the growth performance, immunity capacity and disease resistance of P. vannamei.

Swimming Exercise Modulates Gut Microbiota in CUMS-Induced Depressed Mice.

Background: Gut microbiota is associated with anxiety and depression, while exercise has been proved to alleviate depressive symptoms. However, the interaction of exercise, depression, and gut microbiota remains unclear. Methods: Male C57/BL6J mice were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks and then were subjected to a 5-week swimming program. Behavioral tests, including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM) test, and tail suspension test (TST), were conducted to assess the anxiety-like and depressive behaviors. Gut microbiota analysis was carried out after sample collection. Results: This study showed that CUMS induced depressive behaviors, but swimming exercise increased sucrose preference rate in the SPT, increased time in the center and number of rearing in the OFT, decreased time in the closed arm and increased time in the open arm in EPM, and decreased immobility time in the TST. Firmicutes were the predominant phylum in the gut microbiome, followed by the phyla Bacteroidetes and Proteobacteria. We further found that CUMS and swimming influenced the relative abundance of the genus Desulfovibrio, genus Streptococcus, genus p-75-a5. Among the metabolic pathways, aromatic biogenic amine degradation (PWY-7431), mono-trans and polycis decaprenyl phosphate biosynthesis (PWY-6383), chlorosalicylate degradation (PWY-6107), mycothiol biosynthesis (PWY1G-0), mycolyl-arabinogalactan-peptidoglycan complex biosynthesis (PWY-6397), toluene degradation I (aerobic) (via o-cresol) (PWY-5180), toluene degradation II (aerobic) (via 4-methylcatechol) (PWY-5182), and starch degradation III (PWY-6731) may be related to the mechanism of anti-depression effect. Conclusion: Swimming exercise reverses CUMS-induced depressive behaviors, and the alteration of gut microbiota composition and regulation of microbiota metabolic pathways are involved.

The Effects and Mechanisms of Exercise on the Treatment of Depression.

Background: It is necessary to seek alternative therapies for depression, because side effects of medications lead to poor adherence and some patients do not achieve a clinical treatment effect. Recently the role of exercise as a low-cost and easy-to-use treatment for depression has gained attention with a number of studies showing that exercise is effective at reducing depressive symptoms and improving body functions such as cardiorespiratory system and cognitive function. Because of the heterogeneity of exercise therapy programs, there is no standardized and unified program. Few studies have summarized the specific properties of exercise programs (type, intensity, duration, and frequency) and clinical prescriptions for exercise are not mentioned in most articles. Aims: This study aimed to investigate the feasibility and efficacy of exercise therapy for patients with depression, in order to appraise the evidence and outline accepted guidelines to direct individualized treatment plans for patients with depression based on their individual situations. Methods: A systematic review of English language literature including papers published from 2010 to present in PubMed was performed. Given the feasibility of prescribing exercise therapy for patients with depression, nearly 3 years of clinical studies on the treatments of depressive symptoms with exercise were first reviewed, comparing the exercise programs utilized. Conclusions: Exercise has therapeutic effects on depression in all age groups (mostly 18-65 years old), as a single therapy, an adjuvant therapy, or a combination therapy, and the benefits of exercise therapy are comparable to traditional treatments for depression. Moderate intensity exercise is enough to reduce depressive symptoms, but higher-dose exercise is better for overall functioning. Exercise therapy has become more widely used because of its benefits to the cardiovascular system, emotional state, and systemic functions. Recommendations: Aerobic exercise/mind-body exercise (3-5 sessions per week with moderate intensity lasting for 4-16 weeks) is recommended. Individualized protocols in the form of group exercise with supervision are effective at increasing adherence to treatment.

Swimming exercise reduces the vulnerability to stress and contributes to the AKT/GSK3ß/CRMP2 pathway and microtubule dynamics mediated protective effects on neuroplasticity in male C57BL/6 mice.

While swimming exercise has been shown to positively affect the development of the nervous system, it still remains unclear whether it reduces the vulnerability to stress. In this study, male C57BL/6 mice were exposed to swimming training for 5 weeks, and then subjected to chronic unpredictable mild stress (CUMS) for 4 weeks. We found that swimming exercise prevented anxiety-like and depressive phenotypes induced by CUMS, including increased anxiety-like behavior in the open field test (OFT) and elevated plus-maze (EPM) test and increased despair behavior in the tail suspension test (TST). Moreover, the control+stress group showed reduced expression of phosphorylated AKT kinase (p-AKT), phosphorylated glycogen synthase kinase-3ß (p-GSK3ß), and tubulin-tyrosine ligase (Tyr-tubulin) and increased protein expression of phosphorylated collapsin response mediator protein 2 (p-CRMP-2); the control+control, swim+control, and swim+stress groups exhibited higher expression of these proteins than the control+stress group. This study confirmed that swimming exercise could reduce the vulnerability of individuals to stress and that it contributes to the AKT/GSK-3ß/CRMP-2 pathway and microtubule dynamics mediated protective effects on neuroplasticity. The AKT/GSK-3ß/CRMP-2 pathway and microtubule dynamics may be involved in resilience to stress.

Neuroinflammation decreased hippocampal microtubule dynamics in the acute behavioral deficits induced by intracerebroventricular injection of lipopolysaccharide in male adult rats.

Neuroinflammation plays a vital role in the pathology of depression. Microtubule dynamics produces an immediate response to stress, but the effect of microtubule dynamics in the rats with acute behavioral deficits following a central immune challenge remains elusive. Adult male Sprague-Dawley rats were subjected to the intracerebroventricular (icv) injection of lipopolysaccharide (. Behavioral tests, including bodyweight, sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT), were performed to evaluate anxiety-like and depressive-like phenotypes at 24 h after injection, and some neuroinflammation biomarkers and microtubule dynamics in the hippocampus were detected. Lipopolysaccharide decreased the bodyweight, sucrose preference in SPT (depressive-like behavior), spontaneous activity in OFT (anxiety-like behavior) and increased the immobility time in FST (depressive-like behavior). Besides, lipopolysaccharide increased the mRNA levels of hippocampal CD11b and ionized calcium binding adaptor molecule (Iba1), which suggest microglial activation, and also upregulated hippocampal NLR Family Pyrin Domain Containing 3 inflammasome/interleukin-18/nuclear factor kappa-B mRNA. Lipopolysaccharide injection(icv) reduced the ratio of Tyr-/Acet-tubulin, an important marker of microtubule dynamics, in the acute behavioral deficit rats. Specifically, a decrease in Tyr-tubulin and an increase in the expression of Acet-tubulin were observed, indicating weakened microtubule dynamics. Pearson correlation analysis further showed that there was a significant negative correlation between hippocampal microtubule dynamics and neuroinflammatory activity. This study confirmed that hippocampal microtubule dynamics was decreased in the rats with acute behavioral deficits following a central immune challenge.

Brief postpartum separation from offspring promotes resilience to lipopolysaccharide challenge-induced anxiety and depressive-like behaviors and inhibits neuroinflammation in C57BL/6J dams.

Emerging evidence indicates an important role for neuroinflammation in depression. Brief maternal separation promotes resilience to depression in offspring, but relatively little is known about the effects of different durations of postpartum separation (PS) from offspring on anxiety and depressive-like behaviors in dams following immune challenge. Lactating C57BL/6J mice were subjected to no separation (NPS), brief PS (15 min/day, PS15) or prolonged PS (180 min/day, PS180) from postpartum day (PPD) 1 to PPD21 and then injected with lipopolysaccharide (LPS). Behavioral tests, including the open field test (OFT) and forced swimming test (FST), were carried out at 24 h after the injection. LPSresulted in anxiety and depressive-like behaviors in NPS dams and activated ionized calcium-binding adaptor molecule (Iba1), an important biomarker of microglia, in the hippocampus. However, compared with NPS + LPS dams, PS15 + LPS dams spent significantly more time in the center of the OFT (anxiety-like behavior) and exhibited lower immobility time in the FST (depressive-like behavior), which indicated a phenomenon of resilience. Furthermore, the activation of neuroinflammation was inhibited in PS15 dams. Specifically, levels of the Iba1 mRNA and protein were decreased, while the mRNA expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome/interleukin-18 (IL-18)/nuclear factor kappa-B (NF-κB) was decreased in the hippocampus. Furthermore, positive linear correlations were observed between microglial activation and LPS-induced depressive-like behaviors in dams. Collectively, the findings of this study confirm that brief PS from offspring promotes resilience to LPS immune challenge-induced behavioral deficits and inhibits neuroinflammation in dams separated from their offspring during lactation.

Natural therapeutic agents for neurodegenerative diseases from the shells of Xanthoceras sorbifolium.

Neuroinflammation is linked to neurodegenerative diseases, manifested by the microglial-released over-production of nitric oxide (NO). However, so far there is no effective strategy regarding curing or preventing neurodegenerative diseases. Triterpene saponins from Xanthoceras sorbifolium were proved to be capable of eliciting a protective effect in neurodegenerative diseases. Thus, a systematic chemical study on the 70% ethanol extract of X. sorbifolium was conducted, leading to the identification of 22 compounds, including four previously undescribed triterpenes saponins and 14 known ones, along with four alkaloids. Their structures were elucidated by physicochemical and spectral methods. The in vivo anti-AD effects of 1-18 were predicted with a field-based 3D-QSAR model and anti-neuroinflammatory activities were assayed in BV-2 cells by assessing LPS-induced NO production and examine levels of iNOS, TNF-α, IL-1ß, and IL-6 to support the predicted results. As a result, compounds 14, 16, 19, and 20 could have therapeutic potentials for neurodegenerative diseases due to their potent anti-neuroinflammatory activities.

Long-term maternal separation potentiates depressive-like behaviours and neuroinflammation in adult male C57/BL6J mice.

Early life experience is closely related to depression caused by stress in adulthood. Early life experience, including maternal separation (MS), has been shown to evoke stress sensitivity to depression upon re-exposure to stress in adults. However, MS has also been shown to lead to resilience to stress-induced depression, which is contradictory and rarely studied. To investigate the effects of MS on depression in adults and the related mechanism, male C57/BL6J mouse pups were exposed to different MS procedures from postnatal day (PD)1 to PD21. Body weight (BW) measurements and behavioural tests (the forced swimming test (FST) and open field test (OFT)) were performed on PD41 to explore depressive and anxiety-like behaviours. Then, as adults, the mice were exposed to chronic unpredictable mild stress (CUMS) for 28 days, and then behavioural tasks were recorded. After CUMS exposure, the mice in the MS180 group (which were separated from their mothers for 3 h on PD1-PD21) showed significantly decreased time spent in the centre of the open field and reduced velocity in the OFT, a reduced latency to immobility in the FST, and decreased BW. However, the mice in the MS15 group (which were separated from their mothers for 15 min on PD1-PD21) performed similarly to NSNC mice (which were not separated from their mothers) in the behavioural tests. We further found that the expression of Iba1, a marker of neuroinflammation, was increased in the MS180 group but not in the MS15 group. In addition, our study showed decreased mRNA and protein expression of CRMP2, an important neuroprotective factor, in the MS180 group, but CRMP2 expression was unchanged in the MS15 group. This study confirmed the generation of different behavioural responses to stress exposure in adulthood due to different degrees of MS. Neuroinflammation and neuroprotection are involved, which requires further research.

Chemical constituents from shells of Xanthoceras sorbifolium.

Three undescribed triterpenes and four previously unreported saponins, along with two known ones, were isolated from shells of Xanthoceras sorbifolium (Sapindaceae). Their structures were elucidated by the interpretation of 1D and 2D NMR data. The nitric oxide (NO) assay revealed that 28-O-isobutyryl-21-O-angeloyl-R1-barrigenol and 3-O-ß-D-6-O-methylglucuronopyranosyl-21,22-di-O-angeloyl-R1-barrigenol possessed stronger inhibitory effects on LPS-induced NO overproduction (IC50 = 18.5 ± 1.2 and 28.2 ± 1.8 µM, respectively) than the positive drug minocycline (IC50 = 30.1 ± 1.3 µM) in activated BV2 cells. Western blot, RT-qPCR, and docking experiments further validated that the regulation of iNOS and IL-1ß expressions was involved in the anti-neuroinflammatory effects of these two compounds.