Autophagy accompanying the developmental process of male germline stem cells.

Germline stem cells are a crucial type of stem cell that can stably pass on genetic information to the next generation, providing the necessary foundation for the reproduction and survival of organisms. Male mammalian germline stem cells are unique cell types that include primordial germ cells and spermatogonial stem cells. They can differentiate into germ cells, such as sperm and eggs, thereby facilitating offspring reproduction. In addition, they continuously generate stem cells through self-renewal mechanisms to support the normal function of the reproductive system. Autophagy involves the use of lysosomes to degrade proteins and organelles that are regulated by relevant genes. This process plays an important role in maintaining the homeostasis of germline stem cells and the synthesis, degradation, and recycling of germline stem cell products. Recently, the developmental regulatory mechanism of germline stem cells has been further elucidated, and autophagy has been shown to be involved in the regulation of self-renewal and differentiation of germline stem cells. In this review, we introduce autophagy accompanying the development of germline stem cells, focusing on the autophagy process accompanying the development of male spermatogonial stem cells and the roles of related genes and proteins. We also briefly outline the effects of autophagy dysfunction on germline stem cells and reproduction.

Boron/nitrogen-trapping and regulative electronic states around Ru nanoparticles towards bifunctional hydrogen production.

Developing a straightforward and general strategy to regulate the surface microenvironment of a carbon matrix enriched with N/B motifs for efficient atomic utilization and electronic state of metal sites in bifunctional hydrogen production via ammonia-borane hydrolysis (ABH) and water electrolysis is a persistent challenge. Herein, we present a simple, green, and universal approach to fabricate B/N co-doped porous carbons using ammonia-borane (AB) as a triple functional agent, eliminating the need for hazardous and explosive functional agents and complicated procedures. The pyrolysis of AB induces the regulation of the surface microenvironment of the carbon matrix, leading to the formation of abundant surface functional groups, defects, and pore structures. This regulation enhances the efficiency of atom utilization and the electronic state of the active component, resulting in improved bifunctional hydrogen evolution. Among the catalysts, B/N co-doped vulcan carbon (Ru/BNC) with 2.1 wt% Ru loading demonstrates the highest performance in catalytic hydrogen production from ABH, achieving an ultrahigh turnover frequency of 1854 min-1 (depending on the dispersion of Ru). Furthermore, this catalyst shows remarkable electrochemical activity for hydrogen evolution in alkaline water electrolysis with a low overpotential of 31 mV at 10 mA cm-2. The present study provides a simple, green, and universal method to regulate the surface microenvironment of various carbons with B/N modulators, thereby adjusting the atomic utilization and electronic state of active metals for enhanced bifunctional hydrogen evolution.

Aptamer-Based DNA Allosteric Switch for Regulation of Protein Activity.

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation and is deemed the second secret of life. Given the limited understanding of the structure of natural allosteric molecules, the development of artificial allosteric molecules brings a huge opportunity to transform the allosteric mechanism into practical applications. In this study, the concept of bionics is introduced into the design of artificial allosteric molecules and an allosteric DNA switch with an activity site and an allosteric site based on two aptamers for selective inhibition of thrombin activity. Compared with the single aptamer, the allosteric switch possesses a significantly enhanced inhibition ability, which can be precisely regulated by converting the switch states. Moreover, the dynamic allosteric switch is further subjected to the control of the DNA threshold circuit for realizing automatic concentration determination and activity inhibition of thrombin. These compelling results confirm that this allosteric switch equipped with self-sensing and information-processing modules puts a new slant on the research of allosteric mechanisms and further application of allosteric tactics in chemical and biomedical fields.

6-Thioguanine inhibits severe fever with thrombocytopenia syndrome virus through suppression of EGR1.

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus, recently being officially renamed as Dabie bandavirus, and a causative agent for an emerging infectious disease associated with high fatality. Effective therapeutics and vaccines are lacking and disease pathogenesis is yet to be fully elucidated. In our effort to identify new SFTSV inhibitory molecules, 6-Thioguanine (6-TG) was found to potently inhibit SFTSV infection. 6-TG has been widely used as therapeutic agent since the approval of the Food and Drug Administration in the 1960s. In the current study, we showed that 6-TG was a potent inhibitor of SFTSV infection with 50% effective concentrations (EC50) of 3.465 µM in VeroE6 cells, and 1.848 µM in HUVEC cells. The selectivity index (SI) was >57 in VeroE6 cells and >108 in HUVEC cells, respectively. The SFTSV RNA transcription, protein synthesis, and progeny virions were reduced in a dose dependent manner by the presence of 6-TG in the in vitro infection assay. Further study on the mechanism of the anti-SFTSV activity showed that 6-TG downregulated the production of early growth response gene-1 (EGR1). Using gene silencing and overexpression, we further confirmed that EGR1 was a host restriction factor against SFTSV. Meanwhile, treatment of infected experimental animals with 6-TG inhibited SFTSV infection and alleviated multi-organ dysfunction. In conclusion, we have identified 6-TG as an effective inhibitor of SFTSV replication via the inhibition of EGR1 expression. Further studies are needed to evaluate of 6-TG as a potential therapeutic for treating SFTS.

Deforestation in Latin America in the 2000s predominantly occurred outside of typical mature forests.

The role of tropical forests in the global carbon budget remains controversial, as carbon emissions from deforestation are highly uncertain. This high uncertainty arises from the use of either fixed forest carbon stock density or maps generated from satellite-based optical reflectance with limited sensitivity to biomass to generate accurate estimates of emissions from deforestation. New space missions aiming to accurately map the carbon stock density rely on direct measurements of the spatial structures of forests using lidar and radar. We found that lost forests are special cases, and their spatial structures can be directly measured by combining archived data acquired before and after deforestation by space missions principally aimed at measuring topography. Thus, using biomass mapping, we obtained new estimates of carbon loss from deforestation ahead of forthcoming space missions. Here, using a high-resolution map of forest loss and the synergy of radar and lidar to estimate the aboveground biomass density of forests, we found that deforestation in the 2000s in Latin America, one of the severely deforested regions, mainly occurred in forests with a significantly lower carbon stock density than typical mature forests. Deforestation areas with carbon stock densities lower than 20.0, 50.0, and 100.0 Mg C/ha accounted for 42.1%, 62.0%, and 83.3% of the entire deforested area, respectively. The average carbon stock density of lost forests was only 49.13 Mg C/ha, which challenges the current knowledge on the carbon stock density of lost forests (with a default value 100 Mg C/ha according to the Intergovernmental Panel on Climate Change Tier 1 estimates, or approximately 112 Mg C/ha used in other studies). This is demonstrated over both the entire region and the footprints of the spaceborne lidar. Consequently, our estimate of carbon loss from deforestation in Latin America in the 2000s was 253.0 ± 21.5 Tg C/year, which was considerably less than existing remote-sensing-based estimates, namely 400-600 Tg C/year. This indicates that forests in Latin America were most likely not a net carbon source in the 2000s compared to established carbon sinks. In previous studies, considerable effort has been devoted to rectify the underestimation of carbon sinks; thus, the overestimation of carbon emissions should be given sufficient consideration in global carbon budgets. Our results also provide solid evidence for the necessity of renewing knowledge on the role of tropical forests in the global carbon budget in the future using observations from new space missions.

Folate supports IL-25-induced tuft cell expansion following enteroviral infections.

Intestinal tuft cells, a kind of epithelial immune cells, rapidly expand in response to pathogenic infections, which is associated with infection-induced interleukin 25 (IL-25) upregulation. However, the metabolic mechanism of IL-25-induced tuft cell expansion is largely unknown. Folate metabolism provides essential purine and methyl substrates for cell proliferation and differentiation. Thus, we aim to investigate the roles of folate metabolism playing in IL-25-induced tuft cell expansion by enteroviral infection and recombinant murine IL-25 (rmIL-25) protein-stimulated mouse models. At present, enteroviruses, such as EV71, CVA16, CVB3, and CVB4, upregulated IL-25 expression and induced tuft cell expansion in the intestinal tissues of mice. However, EV71 did not induce intestinal tuft cell expansion in IL-25-/- mice. Interestingly, compared to the mock group, folate was enriched in the intestinal tissues of both the EV71-infected group and the rmIL-25 protein-stimulated group. Moreover, folate metabolism supported IL-25-induced tuft cell expansion since both folate-depletion and anti-folate MTX-treated mice had a disrupted tuft cell expansion in response to rmIL-25 protein stimulation. In summary, our data suggested that folate metabolism supported intestinal tuft cell expansion in response to enterovirus-induced IL-25 expression, which provided a new insight into the mechanisms of tuft cell expansion from the perspective of folate metabolism.

Spatiotemporal control of DNAzyme activity for fluorescent imaging of telomerase RNA in living cells.

BACKGROUND: Human telomerase is a ribonucleoprotein complex that includes proteins and human telomerase RNA (hTR). Emerging evidence suggested that the expression level of hTR was high related with the development of tumor, so it is important to accurately detect the content of hTR. Optical control of DNAzyme activity shows a promising strategy for precise biosensing, biomedical imaging and modulation of biological processes. Although DNAzyme-based sensors can be controlled spatiotemporally by light, its application in the detection of hTR in living cells is still rare. Therefore, designing DNAzyme activity spatiotemporal controllable sensors for hTR detection is highly needed. RESULTS: We developed a UV light-activated DNAzyme-based nanoprobe for spatially accurate imaging of intracellular hTR. The proposed nanoprobe was named MDPH, which composed of an 8-17 DNAzyme (D) inactivated by a protector strand (P), a substrate strand (H), and MnO2 nanosheets. The MnO2 nanosheets can enhance the cellular uptake of DNA strands, so that MDPH probe can enter cells autonomously through endocytosis. Under the high concentration of GSH in cancer cells, MnO2 nanosheets can self-generate cofactors to maintain the catalytic activity of DNAzyme. When exposing UV light and in presence of target hTR, DNAzyme could cleave substrate H, resulting in the recovery of fluorescence of the system. The cells imaging results show that MDPH probe could be spatiotemporally controlled to image endogenous hTR in cancer cells. SIGNIFICANCE: With this design, telomerase RNA-specific fluorescent imaging was achieved by MDPH probe in both cancer and normal cells. Our probe made a promising new platform for spatiotemporal controllable intracellular hTR monitoring. This current method can be applied to monitor a variety of other biomarkers in living cells and perform medical diagnosis, so it may has broad applications in the field of medicine.

Study on the formation pathways of characteristic volatiles in preserved egg yolk caused by lipid species during pickling.

The formation of volatiles in high-fat foods is strongly influenced by the composition and structure of lipids. The relationship between key variable lipid species and characteristic volatiles were performed by lipidomics and flavoromics to resolve the pathways of volatiles in preserved egg yolk (PEY) during pickling. The results showed that the formation of nonanal and benzaldehyde at early stage possibly derived from oleic acid sited at Sn-1 in TG(18:1_18:2_20:4), Sn-2 in PE(22:6_18:1), and linoleic acid bonded at Sn-2 in TG(18:1_18:2_20:4), respectively. 1-octen-3-ol may be formed from linoleic acid located at Sn-2 in TG(18:1_18:2_20:4) and arachidonic acid sited at Sn-3 in TG(18:1_18:2_20:4). Indole was formed through TGs(16:0_16:1_20:1;16:1_18:1_22:1;23:0_18:1_18:1) at the later stage, and acetophenone through TGs(14:0_20:0_20:4;14:0_15:0_18:1; 16:0_16:0_22:6), PCs(24:0_18:1;O-18:1_18:2), PEs(P-18:1_20:4;P-18:1_22:6) and SPH(d18:0) during whole process of pickling. Our study provides a deep and precise insight for the formation pathways of characteristic volatiles in PEY through lipids degradation during pickling at the molecular level.

RNA-Seq transcriptomic analysis reveals gene expression profiles of acetic acid bacteria under high-acidity submerged industrial fermentation process.

Acetic acid bacteria (AAB) are Gram-negative obligate aerobics in Acetobacteraceae family. Producing acetic acid and brewing vinegars are one of the most important industrial applications of AAB, attributed to their outstanding ability to tolerate the corresponding stresses. Several unique acid resistance (AR) mechanisms in AAB have been revealed previously. However, their overall AR strategies are still less-comprehensively clarified. Consequently, omics analysis was widely performed for a better understanding of this field. Among them, transcriptome has recently obtained more and more attention. However, most currently reported transcriptomic studies were conducted under lab conditions and even in low-acidity environment, which may be unable to completely reflect the conditions that AAB confront under industrialized vinegar-brewing processes. In this study, we performed an RNA-Seq transcriptomic analysis concerning AAB's AR mechanisms during a continuous and periodical industrial submerged vinegar fermentation process, where a single AAB strain performed the fermentation and the acetic acid concentration fluctuated between ~8% and ~12%, the highest acidity as far we know for transcriptomic studies. Samples were directly taken from the initial (CK), mid, and final stages of the same period of the on-going fermentation. 16S rRNA sequence analysis indicated the participation of Komagataeibacter europaeus in the fermentation. Transcriptomic results demonstrated that more genes were downregulated than upregulated at both mid and final stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrich analysis reflected that the upregulated genes mainly carried out tricarboxylic acid cycle and oxidative phosphorylation processes, probably implying a considerable role of acetic acid overoxidation in AR during fermentation. Besides, upregulation of riboflavin biosynthesis pathway and two NAD+-dependent succinate-semialdehyde dehydrogenase-coding genes suggested a critical role of succinate oxidation in AR. Meanwhile, downregulated genes were mainly ribosomal protein-coding ones, reflecting that the adverse impact on ribosomes initiates at the transcription level. However, it is ambiguous whether the downregulation is good for stress responding or it actually reflects the stress. Furthermore, we also assumed that the fermentation stages may have a greater effect on gene expression than acidity. Additionally, it is possible that some physiological alterations would affect the AR to a larger extent than changes in gene expression, which suggests the combination of molecular biology and physiology research will provide deeper insight into the AR mechanisms in AAB.

The Pretreatment of Xiaoqinglong Decoction Alleviates Inflammation and Oxidative Damage and Up-Regulates Angiotensin-Converting Enzyme 2 in Lipopolysaccharide-Induced Septic Acute Lung Injury Rats.

Xiaoqinglong decoction (XQLD), a classic prescription of Traditional Chinese Medicine, has already been used clinically to cure acute lung injury (ALI), but its mechanism remains unclear. This subject aimed to explore the preventive role of XQLD in septic ALI rats besides its effects on angiotensin-converting enzyme (ACE)2 and its downstream factors. After, respectively, administrated with different concentrations of XQLD (6.25 g/kg/d, 12.5 g/kg/d, 25 g/kg/d) for 5 days and dexamethasone (DEX, 1 mg/kg) for 0.5 h, the rat models of ALI were established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. All rats were evaluated by lung function test, arterial blood gas analysis, morphological observation, lung wet/dry (W/D) ratio, and the lung injury score. The levels of malonaldehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and angiotensin (Ang) (1-7) in the lung were measured through biochemical and ELISA kits. The expressions of angiotensin-converting enzyme (ACE)2, mitochondrial assembly receptor (MasR), and nuclear factor (NF)-κB in lung tissue were detected by qRT-PCR and western blotting. Positive reaction cells of MasR were observed by immunohistochemistry. The results show that XQLD significantly ameliorated septic lung injury including edema and hemorrhage, as well as improved pulmonary function and arterial blood gas. Furthermore, XQLD markedly decreased the levels of IL-1ß, TNF-α, MDA, and NF-κB while increased the levels of SOD, Ang (1-7), ACE2, and MasR in septic ALI rats. Pearson correlation showed that the expressions of ACE2 were inversely related to IL-1ß, TNF-α, MDA, and NF-κB and positively correlated with SOD contents. Our data indicated that XQLD pretreatment alleviated inflammation and oxidative damage in septic ALI rats, which might be related to the up-regulation of ACE2-Ang (1-7)-MasR axis and inhibition of the NF-κB pathway.

Oxidative Fermentation of Acetic Acid Bacteria and Its Products.

Acetic acid bacteria (AAB) are a group of Gram-negative, strictly aerobic bacteria, including 19 reported genera until 2021, which are widely found on the surface of flowers and fruits, or in traditionally fermented products. Many AAB strains have the great abilities to incompletely oxidize a large variety of carbohydrates, alcohols and related compounds to the corresponding products mainly including acetic acid, gluconic acid, gulonic acid, galactonic acid, sorbose, dihydroxyacetone and miglitol via the membrane-binding dehydrogenases, which is termed as AAB oxidative fermentation (AOF). Up to now, at least 86 AOF products have been reported in the literatures, but no any monograph or review of them has been published. In this review, at first, we briefly introduce the classification progress of AAB due to the rapid changes of AAB classification in recent years, then systematically describe the enzymes involved in AOF and classify the AOF products. Finally, we summarize the application of molecular biology technologies in AOF researches.

O-GlcNAcase inhibitor has protective effects in intracerebral hemorrhage by suppressing the inflammatory response.

BACKGROUND: Intracerebral hemorrhage (ICH) is aggravated by immune cells that participate in the inflammatory response from the blood-brain barrier (BBB). O-Glycosylation has been reported to regulate the inflammatory response in the central nervous system but its cerebral protective effects remain unknown. Therefore, this study was carried out to investigate the protective effects of O-GlcNAcylation in a murine model of ICH and the possible mechanisms involved. METHODS: The effects of O-GlcNAcylation on hematoma and edema formation were tested using pathological and dry/wet weight methods, whereas its effects on neural function were determined using neurologic tests. The effect of O-GlcNAcylation on BBB integrity was determined by Evans blue dye extrusion. Flow cytometry was used to quantify the immune cells in the central nervous system. Immunofluorescence was used to detect the protective effect of O-GlcNAcylation in ICH. RESULTS: The hematoma volume was significantly lower in the prevention and treatment groups than in the control group after ICH induction, indicating that O-GlcNAcylation had reduced the formation of cerebral hematoma in ICH. In the prevention and treatment groups, the modified neurological severity score, corner turn test and rotating rod test results were improved and the BBB integrity was better than that in the control group. O-GlcNAcylation also regulated the microglia, neutrophils and other central nervous system immune cells after ICH, effectively reducing the inflammatory response. CONCLUSIONS: O-GlcNAcylation played an important role in suppressing the inflammatory response, enhancing the BBB integrity and reducing edema after ICH.

Sustainable one-pot construction of oxygen-rich nitrogen-doped carbon nanosheets stabilized ultrafine Rh nanoparticles for efficient ammonia borane hydrolysis.

Heteroatom-doped porous carbons that possess large surface areas and well-defined porosity show great promise in heterogeneous catalysis, whereas their syntheses inevitably require complicated steps, hazardous activation and functional reagents, and an inert gas atmosphere. Herein, a one-pot synthetic strategy to oxygen-rich porous nitrogen-doped carbon (OPNC) is developed through pyrolysis of ethylenediamine tetra-acetic acid tetra-sodium in air without any activation and functionalization agents. The as-prepared OPNC with more surface oxygenated groups and mesopores not only benefits synthesis of well-dispersed ultrafine Rh nanoparticles (NPs) with abundant accessible active sites, but also facilitates the diffusion of reactants and avoids mass transfer limitations, thereby considerably contributes to a high performance toward AB hydrolysis. Specifically, the optimal Rh/OPNC exhibits a high activity toward AB hydrolysis with a turnover frequency (TOF) of 433 min-1. The kinetic isotope studies indicate that the cleavage of OH bond in H2O molecules is the rate-determining step (RDS). The Rh/OPNC can be reused for five repetitive cycles with approximately 62% remained activity of the first cycle. The catalytic activity of Rh/OPNC can be further improved with a very high TOF of 1201 min-1 in alkaline solution. This study proposes a simple and sustainable pathway to synthesize efficient catalyst support for depositing metal NPs toward AB hydrolysis.

Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke.

BACKGROUND: It is important to predict poststroke cognitive outcome to guide individualized treatment and prevention strategy. We aimed to evaluate the predictive value of the combination of a serum biomarker for axonal damage (neurofilament light chain [NfL]) and neuroimaging markers (volume of infarction and white matter hyperintensities [WMH]) for neuronal abnormality in poststroke cognitive outcome. METHODS: A total of 1028 patients were screened; among them, 144 patients with acute ischemic stroke (stroke group) and 30 patients without stroke (control group) were enrolled. Serum NfL levels of samples obtained from both groups were measured through single molecule array assay. Neuroimaging markers of neuroaxonal injury, including infarct volume and WMH in the stroke group were quantified on magnetic resonance images using an in-house MATLAB code (MATLAB 2017; MathWorks). The primary outcome was the functional independence measure (FIM) cognitive subscores on discharge. We assessed the association of serum NfL levels and neuroimaging markers with cognitive outcome. The prognosis value of the combination of serum NfL levels and imaging markers for predicting FIM cognitive subscores on discharge was calculated using the area under curve (AUC) of the receiver operating characteristic. RESULTS: Serum NfL levels of the stroke group were 9-fold higher than those of the control group (1449.7 vs 157.2 pg/mL, n = 144/30, P < .001). There was a correlation of serum NfL levels with infarct volume (r = 0.530, P < .001) and functional outcome, including FIM cognitive subscores (r = -0.387, P < .001) and FIM motor subscores on admission (r = -0.306, P < .001), but not with WMH volume after adjusting for infarct volume (r = -0.196, P = .245). Serum NfL levels on admission independently predicted poststroke FIM cognitive subscores on discharge (AUC = 0.672, P < .001). The predictive value for poststroke cognitive outcome was improved by combining serum NfL levels with infarct and WMH volume (AUC = 0.760, P < .001). CONCLUSION: The combination of serum NfL levels with volume of infarct and WMH shows an improved predictive value for cognitive function during acute rehabilitation phase after stroke, providing a promising panel of biomarkers for prognosis and guidance of treatment.

Improvement on storage stability of iron-fortified soybean powder by microencapsulation.

Full-fat soybean powder was a more difficult-to-fortify food vehicle than cereal flour and powdered milk products because of a large quantity of unsaturated fatty acids, particularly when iron was necessary to be fortified. Minimizing oxidation of lipids was extremely valuable in the fortified-food industry. However, very limited data were available on the effect of microencapsulation of iron compounds on lipid oxidation in full-fat soybean powder. In our study, ferric pyrophosphate (FP) was microencapsulated by the emulsifying-gelation technique and its effect on the storage stability of Yingyangbao (YYB) was evaluated. The results showed that microencapsulated FP (MFP) was regularly spherical and uniformly distributed. MFP could significantly (P < 0.05) decrease the sensory score of rancid odor for YYB. The formation of lipid oxidation products such as carbonyl compounds, malondialdehyde, pentanal, and hexanal in YYB during the accelerated test was significantly retarded, improving oxidative stability and delaying the sensory deterioration. The E-nose analysis showed that YYB with MFP had significantly (P < 0.05) lower levels of response values on the specific sensors than YYB containing FP with or without ascorbyl palmitate. MFP could significantly (P < 0.05) improve the sensory and oxidative stability of iron-fortified full-fat soybean powder such as YYB.

Impact of Serum Calcium Levels on Alzheimer's Disease: A Mendelian Randomization Study.

BACKGROUND: Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk. OBJECTIVE: To develop effective therapies, we should establish the causal link between serum calcium levels and AD. METHODS: Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate. RESULTS: IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude. CONCLUSION: In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.

Involvement of CX3CL1/CX3CR1 in depression and cognitive impairment induced by chronic unpredictable stress and relevant underlying mechanism.

Studies have suggested that heightened neuroinflammation contributes to the pathogenesis of depressive disorder. A major participant in neuroinflammation is microglia, and fractalkine signaling (which comprises the chemokine CX3CL1, mainly expressed by neurons, and its receptor CX3CR1, almost exclusively present on microglia in healthy brains) has been reported to critically regulate microglial activity. The aim of this study was to investigate whether CX3CR1 deficiency was associated with a different outcome following chronic unpredictable stress (CUS) and the possible mechanism. Wild-type (WT) and CX3CR1-deficient (CX3CR1-/-) mice were subjected to CUS for 3 weeks. CX3CR1-/- mice displayed a better performance through sucrose preference test, open field test and forced swim test, which demonstrated that CX3CR1 deficiency alleviated depressive-like disturbances, such as anhedonia, anxiety or hopelessness. Nevertheless, CX3CR1-/- mice also showed less severe cognitive impairment from the results of Morris Water Maze and Novel object recognition. Long-term potentiation was recorded to test the synaptic plasticity and its result was consistent with that of cognitive ability tests. Both results of real time-PCR and immunofluorescence staining demonstrated that CX3CR1 deficiency facilitated the alternative activation of microglia, thus attenuated the release of inflammatory cytokines, which was verified by ELISA and flow cytometry. Maybe due to the mitigated neuroinflammation, CX3CR1-deficient mice showed higher resilience to CUS-induced blood brain barrier hyperpermeability and loss of dendrite spine (as showed by Golgi and DiI staining) than WT group. All of above results indicated that hampering neuron-microglia communication via CX3CR1-CX3CL1 pathway attenuated the effects of CUS on depressive-like disturbances and cognitive impairment.

PAK4 Regulates Actin and Microtubule Dynamics during Meiotic Maturation in Mouse Oocyte.

Meiotic maturation of oocyte is an important process for successful fertilization, in which cytoskeletal integrality takes a significant role. The p-21 activated kinases (PAKs) belong to serine/threonine kinases that affect wide range of processes that are crucial for cell motility, survival, cell cycle, and proliferation. In this study, we used a highly selective inhibitor of PAK4, PF-3758309, to investigate the functions of PAK4 during meiotic maturation of mouse oocytes. We found that PAK4 inhibition resulted in meiotic arrest by inducing abnormal microfilament and microtubule dynamics. PAK4 inhibition impaired the microtubule stability and led to the defective kinetochore-microtubule (K-M) attachment which inevitably resulted in aneuploidy. Also, PAK4 inhibition induced abnormal acentriolar centrosome assembly during meiotic maturation. In conclusion, all these combined results suggest that PAK4 is necessary for the oocyte meiosis maturation as a regulator of cytoskeleton.

Melatonin protects against Fenoxaprop-ethyl exposure-induced meiotic defects in mouse oocytes.

Prolonged exposure of Fenoxaprop-ethyl (FE), a post-emergence herbicide, can cause serious damage to animals through food chain. Melatonin is synthesized by the pineal gland in mammals and believed to protect cells from oxidative stress damage. In this study, we aimed to investigate the effects of FE on mouse oocyte meiosis maturation and the protective roles of melatonin on FE-exposed oocytes by in vitro maturation model. FE exposure significantly caused defects of the first polar body extrusion, which could be protected by co-culture with melatonin. Furthermore, we examined the meiotic maturation details by performing the sperm binding, actin and tubulin immunofluorescence, ROS and apoptosis detection, and histone methylation assay. Our data showed that FE exposure to oocytes led to disrupted actin filament dynamics, mis-organized spindle, and reduced the sperm binding capacity. In addition, FE-exposure increased oxidative stress level and induced oocyte apoptosis. We also found that FE exposure resulted in histone methylation changes. Treatment with melatonin could significantly improve these phenotypes in oocytes exposed to FE. In conclusion, FE exposure can cause meiotic defects by disrupting the cytoskeletal integrality and inducing excessive ROS accumulation to initiate apoptosis in oocytes, while melatonin can reduce all these damages, suggesting that melatonin has protective effects on oocytes exposed to FE during meiotic maturation.

Structural and biochemical properties of silver carp surimi as affected by comminution method.

Effects of two typical comminution methods (shearing and blending) on structural and biochemical properties of silver carp surimi were comparatively investigated. Surimi myofibrils in striated appearance were progressively disrupted within 15 min of blending. The myofibrils were completely disintegrated after shearing for 5 min. Surface hydrophobicity of surimi increased and then gradually decreased (p < 0.05) under shearing, while it continuously increased (p < 0.05) under blending. As shearing time was extended, α-helical structure decreased and ß-sheet structure increased simultaneously; surface active sulfhydryl content (SH) increased and then decreased (p < 0.05); and intensity of myosin heavy chain (MHC) was gradually reduced. However, secondary structure, MHC intensity and SH were slightly changed as blending time extended. Ca2+-ATPase activities increased and then declined (p < 0.05) with transition times at 1 min and 5 min under shearing and blending, respectively. Results indicated that shearing disrupted the ultrastructure and changed biochemical properties of surimi more pronouncedly than blending.