Inositol-requiring enzyme 1α and c-Jun N-terminal kinase axis activation contributes to intracellular lipid accumulation in calf hepatocytes.

During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content <1%) and 10 cows with fatty liver (hepatic TG content >5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and ß-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30-40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

Targeting PHB2-mediated mitophagy alleviates nonesterified fatty acid-induced mitochondrial dysfunction in bovine mammary epithelial cells.

Mitochondrial dysfunction has been reported to occur in the mammary gland of dairy cows suffering from ketosis. Prohibitin 2 (PHB2) plays a crucial role in regulating mitophagy, which clears impaired mitochondria to maintain normal mitochondrial function. Therefore, the current study aimed to investigate how PHB2 mediates mitophagy, thereby influencing mitochondrial function in the immortalized bovine mammary epithelial cell line (MAC-T cells). First, mammary gland tissue and blood samples were collected from healthy cows (n = 15, BHB <0.6 mM) and cows with clinical ketosis (n = 15, BHB >3.0 mM). Compared with healthy cows, cows with clinical ketosis exhibited lower DMI, milk production, milk protein, milk lactose, and serum glucose. In contrast, milk fat, serum nonesterified fatty acids (NEFA) and BHB were greater in cows with clinical ketosis. The protein abundance of PHB2, peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α), mitofusin 2 (MFN2) in whole cell lysates (WCL), as well as PHB2, sequestosome-1 (SQSTM1, also called p62), microtubule-associated protein 1 light chain 3-II (MAP1LC3-II, also called LC3-II), and ubiquitinated proteins in mitochondrial fraction were significantly lower in cows with clinical ketosis. The ATP content of mammary gland tissue in cows with clinical ketosis was lower than that of healthy cows. Second, MAC-T were cultured and treated with NEFA (0, 0.3, 0.6, 1.2 mM). The MAC-T treated with 1.2 mM NEFA displayed decreased protein abundance of PHB2, PGC-1α, and MFN2 in WCL, as well as protein abundance of PHB2, p62, LC3-II, and ubiquitinated proteins in mitochondrial fraction. The content of ATP and JC-1 aggregates in 1.2 mM NEFA group were lower than in the 0 mM NEFA group. Additionally, 1.2 mM NEFA disrupted the fusion between mitochondria and lysosomes. The MAC-T were then pretreated with 100 nM rapamycin, followed by treatment with or without NEFA. Rapamycin alleviated impaired mitophagy and mitochondria dysfunction induced by 1.2 mM NEFA. Third, MAC-T were transfected with small interfering RNA to silence PHB2 or a plasmid for overexpression of PHB2, followed by treatment with or without NEFA. The silencing of PHB2 aggravated 1.2 mM NEFA-induced impaired mitophagy and mitochondrial dysfunction, whereas the overexpression of PHB2 alleviated these effects. Overall, this study provides evidence that PHB2, in regulation of mitophagy, is a mechanism for bovine mammary epithelial cells to counteract NEFA-induced mitochondrial dysfunction.

[Distribution characteristics of 46 elements in drinking water in Ankang area in 2020].

OBJECTIVE: To understand the distribution characteristics of 46 elements in drinking water in Ankang area of Shanxi Province. METHODS: A total of 46 elements in drinking water samples collected in Ankang area during dry and wet seasons in 2020 were determined by inductively coupled plasma mass spectrometry(ICP-MS). According to the "drinking water hygiene standards"(GB 5749-2022) and "food safety national standards". the 46 elements were classified As general chemical indexes(Al, Mn, Fe, Cu, Zn), toxicological indexes(Cr, As, Cd, Hg, Pb, Ba, B, Mo, Ni, Sb, Be, Ag, Tl), new reference indexes(U, V), and major elements(K, Ca, N) A, Mg), trace elements(Li, Co, Se, Sr, Sn) and rare earth elements(Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Th) were analyzed and described. RESULTS: The maximum values of Al and Fe in drinking water in Ankang area were 1.21 and 0.98 mg/L, exceeding the limits of 0.2 and 0.3 mg/L. In dry season, the median content of Fe in drinking water of different water sources was higher in groundwater than in surface water. The Al and Fe of surface water were higher than that of groundwater in wet season. The toxicological indexes all met the standard requirements, and there was no significant difference among districts and counties. The median content of Na in drinking water of different water sources was higher in groundwater than in surface water, while Mg, K and Ca were higher in surface water than in groundwater. The maximum value of the newly added reference index U was 0.015 mg/L lower than the limit standard 0.03 mg/L, and the maximum value of V was 0.019 mg/L higher than the limit standard 0.01 mg/L, but the median of both indexes were low. The median content of Li in drinking water of different water sources was that surface water was higher than groundwater, while Se and Sr were higher in groundwater than surface water. The maximum content of Se was 0.016 mg/L in Ziyang County, and Sr content was generally higher. The content of rare earth elements was low, mostly below the detection. CONCLUSION: The drinking water quality in Ankang area is excellent and rich in strontium. However, the general chemical indexes Al, Fe and the newly added appendix index V in some sampling points exceed the limit standard, so supervision and monitoring should be strengthened.

[Chronic sleep deprivation exacerbates cognitive and pathological impairments in APP/PS1/tau triple transgenic Alzheimer's disease model mice].

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid ß (Aß) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aß deposition and the excessive activation of microglia in the hippocampus.

Robust Radiation Sources Localization Based on the Peak Suppressed Particle Filter for Mixed Multi-Modal Environments.

This paper addresses a detection problem where sparse measurements are utilized to estimate the source parameters in a mixed multi-modal radiation field. As the limitation of dimensional scalability and the unimodal characteristic, most existing algorithms fail to detect the multi-point sources gathered in narrow regions, especially with no prior knowledge about intensity and source number. The proposed Peak Suppressed Particle Filter (PSPF) method utilizes a hybrid scheme of multi-layer particle filter, mean-shift clustering technique and peak suppression correction to solve the major challenges faced by current existing algorithms. Firstly, the algorithm realizes sequential estimation of multi-point sources in a cross-mixed radiation field by using particle filtering and suppressing intensity peak value, while existing algorithms could just identify single point or spatially separated point sources. Secondly, the number of radioactive sources could be determined in a non-parametric manner as the fact that invalid particle swarms would disperse automatically. In contrast, existing algorithms either require prior information or rely on expensive statistic estimation and comparison. Additionally, to improve the prediction stability and convergent performance, distance correction module and configuration maintenance machine are developed to sustain the multimodal prediction stability. Finally, simulations and physical experiments are carried out in aspects such as different noise level, non-parametric property, processing time and large-scale estimation, to validate the effectiveness and robustness of the PSPF algorithm.

[Evaluation for heavy metal pollution of soil and herb from main producing area of Phellodendron amurense in China].

In order to evaluate the heavy metal potential pollution of soil and medicinal materials in main producing area of Phellodendron amurense, we collected 32 soil samples and 32 herb samples from northeast and north of China covering four provinces. In this study, the detection of heavy metal contents was conducted by ICP emission spectroscopy and atomic fluorescence spectrometry. The results showed that the soil from all areas of Ph amurense generally reached the national standard. As, Hg, Cr, Cd, Pb and Cu content of herb samples met the requirtment of the national standard except Hg content exceeding standard slight in a few samples. The reason of excessive Hg was the ability of Hg accumulation in Ph. amurense and atmospheric environment was polluted. So, national standard and Good Agricultural Practice (GAP) must be carried out severely in Ph. amurense resources production.

Composite control of anti-drone platform for stable tracking under disturbance.

First, focused on the complex problem that a U-shaped tracking frame is unreachable to obtain the pointing angles of an unmanned aerial vehicle target, a novel coordinate transformation method is proposed in this paper. The fixed transformation relationship between the intermediate links is deduced by establishing a unified coordinate system, simplifying the algorithm conversion process, and saving computing resources and time. Furthermore, the accuracy of the proposed method has been verified in both aspects of theory and experiment. Then, in order to achieve smooth motion performance between target pointing strategy and stable tracking strategy, a mode switching method based on hysteresis intervals is developed. Compared with the traditional single-point threshold method, the switching method overcomes the high frequency jitter problem. The experimental results validate the consistency between practical effects and theoretical expectations. Finally, to improve the disturbance rejection performance of the platform, a composite control method integrating the information from the gyroscope and circular grating is proposed. The corresponding control scheme and the compensation principle are conceived and explained. The experimental results show the anti-interference performance of the proposed composite control method is five times that of the closed-loop method based on the gyroscope speed signal and two times that of the disturbance observer control method.

Transcriptome Analysis Reveals the Genes Related to Water-Melon Fruit Expansion under Low-Light Stress.

Watermelon is one of people's favorite fruits globally. Fruit size is one of the important characteristics of fruit quality. Low light can seriously affect fruit development, but there have been no reports concerning molecular mechanism analysis in watermelons involved in fruit expansion under low-light stress. To understand this mechanism, the comparative transcriptomic file of watermelon fruit flesh at four different developmental stages under different light levels was studied. The results showed that the fruit size and content of soluble sugar and amino acids at low-light stress significantly decreased compared to the control. In addition, 0-15 DAP was the rapid expansion period of watermelon fruit affected by shading. In total, 8837 differentially expressed genes (DEGs) were identified and 55 DEGs were found to play a role in the four different early fruit development stages. We also found that genes related to oxidation-reduction, secondary metabolites, carbohydrate and amino acid metabolism and transcriptional regulation played a key role in watermelon fruit expansion under low-light stress. This study provides a foundation to investigate the functions of low-light stress-responsive genes and the molecular mechanism of the effects of low-light stress on watermelon fruit expansion.

Effect of Controlling Light on Cashmere Growth and Harmful Gas Parameters in Shanbei White Cashmere Goats.

The quality and yield of cashmere closely affect the economic benefits of cashmere goat farming. Studies have shown that controlling light can have an important impact on cashmere but can also affect the concentration of harmful gases. In order to explore the impact of a short photoperiod on the growth of cashmere and harmful gases in goat houses, 130 female (non-pregnant) Shanbei white cashmere goats, aged 4-5 years with similar body weights, were randomly divided into a control group and a treatment group, with 65 goats in each group. The dietary nutrition levels of the experimental goats were the same, and completely natural light was used in the control group; the light control group received light for 7 h every day (9:30-16:30), and the rest of the time (16:30-9:30 the next day) they did not receive light. The light control treatment was carried out in a control house, and the gas content was analyzed. It was found that a shortened period of light exposure could increase the annual average cashmere production by 34.5%. The content of each gas has a certain functional relationship with the measurement time period, but at the same time, we found that the content of NH3 also changes seasonally. In summary, the use of shortened light periods when raising cashmere goats can significantly increase cashmere production and quality, but at the same time, it will increase the concentration of harmful gases in the goat barn, and ventilation should be increased to ensure the health of the goats and the air quality in the barn.

Selective orexin 1 receptor antagonist SB-334867 aggravated cognitive dysfunction in 3xTg-AD mice.

Cognitive dysfunction is the main clinical manifestation of Alzheimer's disease (AD). Previous research found that elevated orexin level in the cerebrospinal fluid was closely related to the course of AD, and orexin-A treatment could increase amyloid ß protein (Aß) deposition and aggravate spatial memory impairment in APP/PS1 mice. Furthermore, recent research found that dual orexin receptor (OXR) antagonist might affect Aß level and cognitive dysfunction in AD, but the effects of OX1R or OX2R alone is unreported until now. Considering that OX1R is highly expressed in the hippocampus and plays important roles in learning and memory, the effects of OX1R in AD cognitive dysfunction and its possible mechanism should be investigated. In the present study, selective OX1R antagonist SB-334867 was used to block OX1R. Then, different behavioral tests were performed to observe the effects of OX1R blockade on cognitive function of 3xTg-AD mice exhibited both Aß and tau pathology, in vivo electrophysiological recording and western blot were used to investigate the potential mechanism. The results showed that chronic OX1R blockade aggravated the impairments of short-term working memory, long-term spatial memory and synaptic plasticity in 9-month-old female 3xTg-AD mice, increased levels of soluble Aß oligomers and p-tau, and decreased PSD-95 expression in the hippocampus of 3xTg-AD mice. These results indicate that the detrimental effects of SB-334867 on cognitive behaviors in 3xTg-AD mice are closely related to the decrease of PSD-95 and depression of in vivo long-term potentiation (LTP) caused by increased Aß oligomers and p-tau.

Development and Preliminary Application of a Droplet Digital PCR Assay for Quantifying the Oncolytic Herpes Simplex Virus Type 1 in the Clinical-Grade Production.

Oncolytic herpes simplex virus (oHSV) is a type of virus that selectively targets and kills cancer cells, leaving normal cells unharmed. Accurate viral titer is of great importance for the production and application of oHSV products. Droplet digital PCR (ddPCR) is known for having good reproducibility, not requiring a standard curve, not being affected by inhibitors, and being precise even in the detection of low copies. In the present study, we developed a droplet digital PCR assay for the quantification of HSV-1 and applied it in the oHSV production. The established ddPCR showed good specificity, linearity, a low limit of quantification, great reproducibility, and accuracy. The quantification result was well-associated with that of plaque assay and CCID50. Amplification of the purified virus without DNA extraction by ddPCR presented similar results to that from the extracted DNA, confirming the good resistance against PCR inhibitors. With the ddPCR, viral titer could be monitored in real time during the production of oHSV; the optimal harvest time was determined for the best virus yield in each batch. The ddPCR can be used as a useful tool for the quantification of oHSV and greatly facilitate the manufacturing process of oHSV products.

OX40L-Armed Oncolytic Virus Boosts T-cell Response and Remodels Tumor Microenvironment for Pancreatic Cancer Treatment.

Rationale: The resistance of pancreatic ductal adenocarcinoma (PDAC) to immunotherapies is caused by the immunosuppressive tumor microenvironment (TME) and dense extracellular matrix. Currently, the efficacy of an isolated strategy targeting stromal desmoplasia or immune cells has been met with limited success in the treatment of pancreatic cancer. Oncolytic virus (OV) therapy can remodel the TME and damage tumor cells either by directly killing them or by enhancing the anti-tumor immune response, which holds promise for the treatment of PDAC. This study aimed to investigate the therapeutic effect of OX40L-armed OV on PDAC and to elucidate the underlying mechanisms. Methods: Murine OX40L was inserted into herpes simplex virus-1 (HSV-1) to construct OV-mOX40L. Its expression and function were assessed using reporter cells, cytopathic effect, and immunogenic cell death assays. The efficacy of OV-mOX40L was then evaluated in a KPC syngeneic mouse model. Tumor-infiltrating immune and stromal cells were analyzed using flow cytometry and single-cell RNA sequencing to gain insight into the mechanisms of oncolytic virotherapy. Results: OV-mOX40L treatment delayed tumor growth in KPC tumor-bearing C57BL/6 mice. It also boosted the tumor-infiltrating CD4+ T cell response, mitigated cytotoxic T lymphocyte (CTL) exhaustion, and reduced the number of regulatory T cells. The treatment of OV-mOX40L reprogrammed macrophages and neutrophils to a more pro-inflammatory anti-tumor state. In addition, the number of myofibroblastic cancer-associated fibroblasts (CAF) was reduced after treatment. Based on single-cell sequencing analysis, OV-mOX40L, in combination with anti-IL6 and anti-PD-1, significantly extended the lifespan of PDAC mice. Conclusion: OV-mOX40L converted the immunosuppressive tumor immune microenvironment to a more activated state, remodeled the stromal matrix, and enhanced T cell response. OV-mOX40L significantly prolonged the survival of PDAC mice, either as a monotherapy or in combination with synergistic antibodies. Thus, this study provides a multimodal therapeutic strategy for pancreatic cancer treatment.

Dietary Nutritional Level Affects Intestinal Microbiota and Health of Goats.

The intestine is a complex micro-ecosystem, and its stability determines the health of animals. Different dietary nutritional levels affect the intestinal microbiota and health. In this study, the nutritional levels of energy and protein in the diet of goats were changed, and the body weight was measured every 15 days. In the late feeding period, 16 S rRNA sequencing technology was used to detect the content of microorganisms. A meteorological chromatograph was used to detect volatile fatty acids in the cecum and colon of goats. In the feeding stage, reducing the nutritional level of the diet significantly reduced the weight of the lamb (p < 0.05). In the cecum, the abundance of potentially harmful bacteria, such as Sphingomonas, Marvinbryantia, and Eisenbergiella, were significantly enriched in goats fed with the standard nutritional level diets (p < 0.05). Additionally, the contents of acetate (p = 0.037) and total VFAs (p = 0.041) increased. In the colon, the abundance of SCFAs-producing bacteria, such as Ruminococcaceae, Christensenellaceae, and Papillibacter, decreased as the nutritional level in the diet increased (p < 0.05). In conclusion, the increase in nutritional level could affect the growth performance and composition of intestinal microbiota.

A study on the cyclist head kinematic responses in electric-bicycle-to-car accidents using decision-tree model.

Due to the high frequent traffic accidents involving electric bicycles (E-bike), it urgently needs improved protection of cyclists, especially their heads. In this study, by adjusting the initial impact velocities of E-bike and car, initial impact angle between E-bike and car, initial E-bike impact location, and body size of cyclist, 1512 different accident conditions were constructed and simulated using a verified E-bike-to-car impact multi-body model. The cyclist's head kinematic responses including the head relative impact velocity, WAD (Wrap around distance) of head impact location and HIC15 (15 ms Head Injury Criterion) were collected from simulation results to make up a dataset for data mining. The decision tree models of cyclist's head kinematic responses were then created from this dataset and verified accordingly. Based on simulated results obtained from decision tree models, it can be found as follows. 1. In the E-bike-to-car accidents, the average head impact relative velocity and WAD of head impact location are higher than those in the car-to-pedestrian accidents. 2. Increasing the initial impact velocity of car can increase the cyclist's head relative impact velocity, WAD of head impact location, and HIC15. 3. The WAD of cyclist's head impact location is also significantly affected by the initial impact angle between E-bike and car and body size of cyclist: the WAD of head impact location becomes higher with increasing initial impact angle between E-bike and car and body size of cyclist. 4. The effects of initial E-bike impact location on the WAD of cyclist's head impact location is not significant when initial E-bike impact location is concentrated in the region of 0.25 m around the centerline of the car.

MES7 Modulates Seed Germination via Regulating Salicylic Acid Content in Arabidopsis.

Seed germination is an important phase transitional period of angiosperm plants during which seeds are highly sensitive to different environmental conditions. Although seed germination is under the regulation of salicylic acid (SA) and other hormones, the molecular mechanism underlying these regulations remains mysterious. In this study, we determined the expression of SA methyl esterase (MES) family genes during seed germination. We found that MES7 expression decreases significantly in imbibed seeds, and the dysfunction of MES7 decreases SA content. Furthermore, MES7 reduces and promotes seed germination under normal and salt stress conditions, respectively. The application of SA restores the seed germination deficiencies of mes7 mutants under different conditions. Taking together, our observations uncover a MeSA hydrolytic enzyme, MES7, regulates seed germination via altering SA titer under normal and abiotic stress conditions.

Chronic sleep deprivation exacerbates cognitive and synaptic plasticity impairments in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits. Sleep deprivation (SD) could lead to memory deficits, and it was a candidate risk factor for AD. However, the effects of chronic SD on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1 transgenic mice and wild type (WT) littermates were subjected to chronic SD by using the modified multiple platform method (MMPM), with 20 h of SD each day for 21 days. Then, the effects of chronic SD on cognitive functions in APP/PS1 mice were tested by using behavioral tests, the potential mechanisms were investigated by in vivo electrophysiological recording, western blot and immunochemistry. The results showed that chronic SD obviously aggravated the cognitive impairments, exacerbated in vivo hippocampal long-term potentiation (LTP) suppression, reduced the expression level of PSD95, increased amyloid-ß (Aß) protein deposition and overactivated microglia in the hippocampus of APP/PS1 mice. These results indicate that chronic SD exacerbates the cognitive deficits in APP/PS1 mice by accelerating the development of AD pathologies, reducing the expression of PSD95 and aggravating the LTP suppression in hippocampus. At the same time, chronic SD also impaired cognitive functions and synaptic plasticity in WT mice through down-regulating the level of PSD95 and activating microglia. These findings further clarify the electrophysiological and molecular mechanisms of exacerbated cognitive deficits in AD caused by chronic SD.

DEAD-box helicases modulate dicing body formation in Arabidopsis.

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

Genome-wide identification, characterization, and expression analysis of the expansin gene family in watermelon (Citrullus lanatus).

Expansins are plant cell-wall loosening proteins involved in cell enlargement, adaptive responses to environmental stimuli, and various developmental processes. Although expansins have been characterized in many plant species, little is reported on this family in watermelon. In this study, 30 expansin genes in the watermelon genome (ClEXPs) were identified. These genes which were divided into four subfamilies (7 ClEXLAs, 2 ClEXLBs, 18 ClEXPAs, and 3 ClEXPBs) are unevenly distribute on 10 of 11 watermelon chromosomes. Chromosome mapping suggested that tandem duplication events may have played important roles in the expanding of watermelon expansins. Gene structure and motif identification revealed that same subfamily and subgroup have conserved gene structure and motif. Detection of cis-acting elements revealed that ClEXPs gene promoter regions were enriched with light-responsive elements, hormone-responsive, environmental stress-related, and development-related elements. Expression patterns of ClEXPs were investigated by qRT-PCR. The results showed that expression patterns of 15 ClEXP genes differed in three tissues. Through our own and public RNA-seq analysis, we found that ClEXPs had different expression patterns in fruit flesh, fruit rind, and seed at various developmental stages, and most of ClEXPs were highly responsive to abiotic and biotic stresses. Remarkably, 7 ClEXPs (ClEXLA1, ClEXLA6, ClEXLB1, ClEXLB2, ClEXPA5, ClEXPA10, and ClEXPA16) exhibited positive response to at least three kinds of stresses, suggesting that they might play important roles in the crosstalk of stress signal pathways. The results of this study provide useful insights for the functional identification of expansin gene family in watermelon.

A study on cyclist head injuries based on an electric-bicycle to car accident reconstruction.

OBJECTIVE: In China, the electric-bicycle (E-bike) has become one of the most common modes of travel. However, the safety of E-bike has not received sufficient attentions, especially in the area of protection of the cyclists' head. METHODS: In this study, an E-bike-to-car accident was reconstructed using MADYMO and LS-DYNA software and head injuries of the cyclist were analyzed. A multi-rigid body model in MADYMO and a head to windshield impact finite element (FE) model using LS-DYNA were separately developed to achieve objectives of the work. RESULTS: Kinematic responses of the cyclist were predicted by the multi-rigid body model to obtain the best reconstructed results compared to those given in the accident report, and the instantaneous linear and angular relative velocities at the onset of contact between the head and windshield, which were used as input loading conditions to the FE model, were obtained. The maximum principal strain (MPS) of skull, and intracranial pressure (ICP), von-Mises stress and MPS (Maximum principal strain) of brain tissue were predicted by the FE model for the head injuries analyses. CONCLUSIONS: The results of accident reconstruction in this study case showed that: (1) The head impact region on the windshield in the E-bike-to-car impact accidents is higher than that in the pedestrian-to-car impact accidents. (2) The skull MPS, ICP, von-Mises stress and MPS of strain can accurately predict the head injury risk, location, etc. (3) The directly impact force caused the skull fracture, and the tensile inertial force torn bridge vein resulting in the subdural hematoma on the opposite side of impact in this accident. (4) The models developed in this study were validated against the reconstructed accident and can be used for further study on head injuries of E-bike's cyclist and helmet design.

AtXRN4 Affects the Turnover of Chosen miRNA*s in Arabidopsis.

Small RNA (sRNA) turnover is a key but poorly understood mechanism that determines the homeostasis of sRNAs. Animal XRN genes contribute the degradation of sRNAs, AtXRN2 and AtXRN3 also contribute the pri-miRNA processing and miRNA loop degradation in plants. However, the possible functions of the plant XRN genes in sRNA degradation are far from known. Here, we find that AtXRN4 contributes the turnover of plant sRNAs in Arabidopsis thaliana mainly by sRNA-seq, qRT-PCR and Northern blot. The mutation of AtXRN4 alters the sRNA profile and the accumulation of 21 nt sRNAs was increased. Some miRNA*s levels are significantly increased in xrn4 mutant plants. However, the accumulation of the primary miRNAs (pri-miRNAs) and miRNA precursors (pre-miRNAs) were generally unchanged in xrn4 mutant plants which indicates that AtXRN4 contributes the degradation of some miRNA*s. Moreover, AtXRN4 interacts with Arabidopsis Argonaute 2 (AtAGO2). This interaction takes place in Processing bodies (P-bodies). Taken together, our observations identified the interaction between XRN4 with AtAGO2 and suggested that plant XRN4 also contributes the turnover of sRNAs.