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Abstract The statefinder diagnostic is useful to discriminate dark energy models. In this paper, under the minimum assumption of a spatially flat Friedmann–Lemaître–Robertson–Walker Universe, we reconstruct the statefinder pair $$\{r(z),s(z)\}$$ { r ( z ) , s ( z ) } in addition to the deceleration parameter q(z) via the Gaussian process from the cosmic observational data points which include the recently released Pantheon+ SN Ia samples and the observational Hubble data H(z). The reconstructed evolution trajectories are shown on the $$r-q$$ r - q , $$r-s$$ r - s planes. The reconstructed q(z) is consistent with previous studies. Meanwhile, a novel quantity named suitability is introduced on the $$r-q$$ r - q , $$r-s$$ r - s planes to assess the validation of a dark energy model.

Plastic products are widely used in human daily life, while facilitating human life, plastics have also produced many negative effects due to the lack of effective recovery measures, plastic pollution has become an important environmental issue of global concern. Marine plastics can be degraded into smaller microplastics (MPs) through various ways under the influence of environmental factors. They can be ingested by marine organisms mixed with food sources, and then accumulated in the body, causing serious negative effects on marine lifes and marine ecology. Recently, it has been proved that the Changshan Islands sediments contain a certain amount of MPs, the content reached 133.14 to 499.82 n/kg. Changshan Islands is one of the eight major islands in China. It is located at the confluence of the Yellow Sea and the Bohai Sea, and has a unique geographical location. The fish community between the islands is rich in species, especially in many migratory species, and high in species diversity. The seasonal change of fish species composition and dominant species is obvious. It has been proved MPs can cause a certain degree of harm to marine organisms. Therefore, the distribution of MPs in organisms in the Changshan Islands sea area deserves to be studied. In this study, the MPs in the gastrointestinal tracts and muscles of wild fish were digested and separated after collecting them from the marine culture zone of Changshan Islands. The results showed that MPs were detected existing in the gastrointestinal tracts of all fish, but not in muscle tissues. The reason may be that MPs are too large to be endocytosed by intestinal epithelial cells, and thus can not participate in the blood circulation of fish. The abundance of MPs in the gastrointestinal tracts of seven species of marine wild fish ranged from 0.19 to 3.79 items/individual. The abundance of MPs in Coilia nasus is the highest among all fish, this phenomenon may be related to the living environment and predation habits of C. nasus, which living in the bottom of the sea. The MPs in sediments will undergo a cyclic process of suspension, sedimentation and resuspension under the flow of seawater, thus greatly increasing the exposure and intake risk of MPs by bottom organisms, such as C. nasus. The shape of MPs was dominated by the fiber, and the color was mostly transparent, which size is mainly less than 300 μm. The reason may be that the individual size of fish collected in this survey is small, and larger-sized MPs cannot enter into the gastrointestinal tract of fish through feeding. Large plastics in the environment are broken under the photooxidation, wave action, physical wear and alternating freeze-thaw. The different shapes of MPs detected in this study may be derived from the decomposition of these large plastics. Fibers are the predominant form of MPs encountered in global wildlife studies. It could also be because fibrous MPs are the most abundant in the marine environment. Additionally, MPs Fibers can be bended or intertwined with food, possibly due to long-term accumulation for the slower fibers excretion, increasing the chance of being ingested by organisms. The types of polymers detected were cellophane, cellulose and polyethylene, among which cellophane had the highest content. Cellophane is an organic cellulose-based polymer that has been used in food packaging and cigarette packaging. It is also used as a release agent in the manufacture of glass fiber and rubber products, or as a coating in combination with synthetic polymers. There was no obvious toxic effect on cellulose and cellulite. The polymer hazard index (PHI) is an important criterion for risk assessment of MPs, and is based primarily on the percentage content of a given polymer and the polymer's hazard fraction for ecological and health risk assessment. The potential risk of MPs to humans can be estimated by the polymer hazard index. The higher the polymer hazard index, the higher the ecological risk in the sea area. The toxicity coefficient of polyethylene is 10, the toxicity grade is grade II, the hazard index is low, and it belongs to the low risk polymer. Moreover, people usually discard the gastrointestinal tract of fish before eating, thus the MPs in the fishes of Changshan Islands, and the safety factor of fish products in Changshan Islands is higher. In this study, through the collection of wild fish in Changshan Islands, the MPs in gastrointestinal tract and muscle tissue were extracted, and the abundance and type of MPs were analyzed. The pollution status of MPs in fish in the adjacent waters of Changshan Islands was clarified, which provided basic data for exploring the impact of MPs on the ecological environment safety of Changshan Islands ecosystem. Further research on the distribution of MPs in other wild organisms, such as shellfish, and in other economically viable locations should be considered, which can provide a scientific basis for the analysis of MP pollution levels and the formulation of prevention and control strategies in the marine environment.

Microplastic pollution and excessive discharge of aquaculture tailwater have become important global issues. The use of filamentous algae to remove nitrogen, phosphorus, and microplastics in the same system has not been reported. In this study, we constructed an algal water purification and removal system and investigated its ability to remove microplastics, nitrogen, and phosphorus from the water column. Three kinds of filamentous algae were used, Spirogyra, Enteromorpha, and Cladophora, in microplastic removal experiments in the system; the three species of filamentous algae were the most effective in removing fibrous microplastics (88.50%, 79.50%, 75.50%) and the least effective in removing granular microplastics (67.50%, 53.00%, 55.00%), respectively. Spirogyra removed microplastics better than the other two algae; therefore, it was used for nitrogen and phosphorus removal experiments in the water column. The density of algae per unit area was set to 0 (control), 2, 4, and 6 g/dm2. Spirogyra showed a Total Nitrogen removal rate of 91.88% (4 g/dm2), a Total Phosphorus removal rate of 90.33% (6 g/dm2), and a PO43–-P removal rate of 90.38% (6 g/dm2) after 15 d. The density of 4 g/dm2 showed the highest removal rate, 90.38%. There were no significant differences between the experimental results of the 4 and 6 g/dm2 groups (P > 0.05). The results showed that the system effectively removed fibrous microplastics and absorbed nitrogen and phosphorus from the water body and that an algal density per unit area of 4 g/dm2 was the most suitable for removing nitrogen and phosphorus in this system.

ABSTRACT Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies.IMPORTANCESepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.

Paralytic shellfish toxins (PSTs) are some of the most harmful algal neurotoxins in the world. They easily accumulate in bivalve shellfish and are transmitted through the food chain, causing symptoms such as nausea and vomiting, muscle paralysis, dyspnea and even asphyxiation in consumers, leading to food poisoning in humans. Therefore, a widely accepted limit standard of 800 μg STXeq/kg has been established as a safe limit for PSTs. PSTs are produced by some microalgae, among which Alexandrium tamarense is one of the predominant toxic algae found along the coast of China. It was found that the detection rate and over-standard rate of Chlamys farreri in bivalve shellfish sold in China are relatively high. PSTs are mainly stored in visceral masses and are characterized by their fast accumulation and slow metabolism.PSTs are neurotoxins that exert their toxic effects by blocking sodium channels and inhibiting nerve conduction. Studies have shown that PSTs can cause stress responses in bivalves, including production of a large amount of reactive oxygen species (ROS), antioxidant stress (including enzymatic and non-enzymatic defense), imbalance of intracellular redox homeostasis, and cell damage (i.e., lipid peroxidation). As one of the main products of lipid peroxidation, the content of malondialdehyde (MDA) can directly reflect tissue and cell membrane damage caused by PSTs. In addition, superoxide dismutase (SOD) and peroxidase (POD) are often used as indicators to evaluate the level of antioxidation, and glutathione peroxidase (GSH-Px) plays a key role in antioxidant defense. The changes in lipid peroxidation and antioxidant enzymes are commonly used in existing studies to reflect the injury and degree of stress in organisms. Some studies have also shown that PSTs can cause tissue damage and induce abnormal gene expression in C. farreri, but research on the changes of gene expression and regulatory mechanism of PST-induced tissue damage in C. farreri is still lacking. This information is important for establishing and perfecting food safety risk assessment technology.In this study, C. farreri was exposed to a strain of A. tamarense (AT5-3). We measured the toxin accumulation, oxidative stress kinase activity, and its transcriptional regulation in the visceral mass of C. farreri in control and experimental groups. Further, the ultrastructure of the visceral mass in the control group and the experimental group was observed to explore the initial stress response mechanism of C. farreri exposed to PSTs.The 2-year-old scallop C. farreri was selected as the experimental animal. AT5-3 was cultured in L1 medium at temperatures of (20±1) ℃, light intensity of 54 μ/Em2·s, and a light-dark ratio of 12 h: 12 h in the laboratory, and Chlorella vulgaris was cultured simultaneously. The experimental group was fed with algal solution in the exponential growth period and the cell density was 4×104–4.2×104 cells/mL. The control group was fed with the same amount of C. vulgaris. The experiment lasted 20 days, of which the first six (days 0–6) were the exposure stage and the remaining 14 days (days 7–20) were the metabolic stage. During the exposure stage, C. farreri were fed regularly with the AT5-3 strain in exponential growth period twice a day with a feeding dose of 8×106 cells/items/day. The same amount of C. vulgaris was fed in the metabolic stage.The results of toxin accumulation showed that paralytic shellfish toxins could accumulate rapidly in the visceral mass of C. farreri, but the metabolic rate was slow. The toxin content was highest on day 6 of the experiment, and the maximum accumulated content was approximately 15 times higher than the limit standard. The toxin residue reached its highest level (62.4%) on 20th day of the experiment.The results of enzyme activity tests showed that the stress due to MDA, GSH-Px, and POD in the visceral mass was significantly increase (P < 0.05), and the SOD activity was significantly inhibited (P < 0.05) after a brief increase. The results also showed that PSTs could induce lipid peroxidation in C. farreri, and POD, SOD, and GSH-Px were significantly stressed to eliminate the adverse effects of PSTs.The pathological changes in the visceral mass were observed under a transmission electron microscope and included vacuolation, chromatin aggregation, and nucleoplasmic pyknosis. Tissue damage worsened as the exposure time increased and although the toxin content in C. farreri decreased after the exposure period, the tissue damage was further aggravated. The results of transcriptome analysis showed that 933 differentially expressed genes (DEGs) were screened from the visceral mass of C. farreri after PST exposure. The results of KEGG and GO annotations showed that DEGs were mainly annotated in amino acid metabolism, energy metabolism, and other metabolic processes. Weighted gene co-expression network analysis showed that apoptosis and the glutathione metabolic detoxification pathway were significantly up-regulated, mapping ALOX5, AfGST-σ11, caspase-8 and Bax4 key transcription factors. In the experimental group, the expression of ALOX5 and AfGST-σ11 increased significantly when the accumulation rate was highest (P < 0.05). The expression of caspase-8 and Bax4 was highest when toxin accumulation was high, which was significantly higher than that in the control group (P < 0.05).In summary, PSTs can cause lipid peroxidation stress and cell damage to C. farreri. In addition to antioxidant stress, C. farreri can activate characteristic apoptosis and resist PSTs toxicity by glutathione detoxification metabolism. However, this effect is limited and the persistent damage caused by high residual PSTs cannot be eliminated. This study provides a basis for further study on the potential toxicity of PSTs to the scallop C. farreri and its immunomolecular mechanisms.

Excessive fat deposition due to impaired fat metabolism in chickens is a major problem in the poultry industry. Nutritional interventions are effective solutions, but current options are limited. A safe phytochemical, rutin, has shown positive effects in animals, but its effect on lipid metabolism in poultry remains unknown. Hence, this study is to investigate the effects of rutin on egg quality, serum biochemistry, fat deposition, lipid peroxidation and hepatic lipid metabolism in post-peak laying hens. A total of 360 Taihang laying hens (49-week-old) were randomly divided into five groups and fed a basal diet (control group, 0%) and a basal diet supplemented with 300 (0.03%), 600 (0.06%), 900 (0.09%), and 1,200 (0.12%) mg rutin/kg feed, respectively. The results showed that eggshell strength was significantly (p

Summary: Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood. CpsA, protein of Mycobacterium marinum and Mycobacterium tuberculosis, plays a key role in maintaining bacterial virulence and inhibiting host cell LC3-associated phagocytosis. By utilizing CpsA full deletion mutant studies, we re-verified its essential role in infection-induced pathology and revealed its new role in type I IFN expression. CpsA deficiency hindered IFN production in infected macrophages in vitro as well as zebrafish and mice in vivo. This effect was linked to the cGAS-TBK1-IRF3 pathway, as evidenced by decreased TBK1 and IRF3 phosphorylation in CpsA-deficient bacterial strain-infected macrophages. Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology.

As the world embraces the digital economy and enters an information society, data has emerged as a critical production factor.The collection, processing, and storage of data have become increasingly prevalent.Distributed storage systems, known for their efficiency, are widely used in various data fields.However, as the scale of data storage continues to expand, distributed storage faces more significant security risks, such as information leakage and data destruction.These challenges drive the need for innovative advancements in big data distributed storage security technology and foster the integration of domestic cryptographic technology with computing storage technology.This work focused on addressing security issues, particularly information leakage, in distributed storage nodes.A dynamic and reconfigurable encryption storage solution was proposed, which considered the requirements for encryption performance and flexibility.A high-performance reconfigurable cryptographic module was designed based on the bio mapping framework.Based on this module, multiple storage pools equipped with different cryptographic algorithms were constructed to facilitate high-performance encryption and decryption operations on hard disk data.The scheme also enabled dynamic switching of cryptographic algorithms within the storage pools.A cryptographic protocol with remote online loading functions for cryptographic algorithms and keys was developed to meet the unified management and convenient security update requirements of reconfigurable cryptographic modules in various storage nodes.Furthermore, the scheme implemented fine-grained data encryption protection and logical security isolation functions based on cryptographic reconstruction technology.Experimental results demonstrate that the performance loss of this scheme for encryption protection and security isolation of stored data is approximately 10%.It provides a technical approach for distributed storage systems to meet the cryptographic application technology requirements outlined in GB/T 39786-2021 “Information Security Technology-Basic Requirements for Cryptography Applications” Level 3 and above in terms of device and computing security, application and data security.

To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARα) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( ± clofibrate) × 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-14C] palmitic acid (1 mM) as a substrate (0.265 μCi/μmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 μM) or acetoacetate-CoA deacylase (iodoacetamide, 50 μM). Without clofibrate stimulation, 14C accumulation in CO2 was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased 14C-ASP (P

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection.

Paralytic shellfish toxins (PSTs) are phycotoxins widely distributed worldwide and pose serious marine ecosystems and human health threats. In China's Yellow Sea and the Bohai Sea, Alexandrium spp. has been certified as the major causative dinoflagellate of PSTs, especially in Qinhuangdao, Hebei Province where several poisoning events have been reported, with tens of consumers suffering and some even dying. In terms of these events, mussels contaminated with PSTs were the major cause of consumer poisoning. Therefore, it is vital to reveal the risk of PSTs in these shellfish, which requires scientific opinions on the formation of terminal components of PSTs in mussels. Generally, mussels are not sensitive to PSTs, resulting in the high accumulation of PSTs in their tissues. The PSTs distribute, bio-transfer, and metabolism, and the terminal metabolites pose a risk to consumers. From 2016 to the present, several serious events have occurred in Qinhuangdao caused by PSTs contamination in mussels, which resulted in poisoning by tens of consumers and a huge loss of regional economy. This study exposed purple mussel Mytilus galloprovincialis, the key cultured species of bivalves in Qinhuangdao, to Alexandrium catenella (GY-H25), the predominant producer of PSTs in this area. The accumulation and biotransformation process of PSTs in visceral mass and edible tissue and the accumulation metabolism kinetics were analyzed under exposure to different cell densities by liquid chromatography-tandem mass spectrometry. Our results showed that the growth and toxin production of GY-H25 was stable. The main components of PSTs were N-sulfocarbamoylgonyautoxin (C1 and C2), with the highest algal cell density of 3.5×107 cells/L and the highest production capacity of 2.96 pg STXeq/cell. Toxin-producing algae with the highest production of PSTs per unit volume and algal cell density (22 days) were selected for the exposure experiment. After exposure, the mussel accumulated a high content of PSTs in both visceral mass and edible tissue, with a similar trend in both exposure densities. The whole exposure experiment could be divided into four periods: 0~2 days as the initial exposure period (period Ⅰ); 2~7 days as the period of rapid accumulation (period Ⅱ); 7~12 days as the period of rapid metabolism (period Ⅲ); 12~30 days as the stable period (period Ⅳ). However, the level of PSTs in the visceral mass of mussels in both exposure groups exceeded the maximum residue limit (MRL) of EU (800 μg STX EQ/kg) at the end of the experiment, while that of PSTs in edible flesh was below the MRL. Comparatively, the highest concentration of PSTs in the visceral mass reached 6815.36 μg/kg in the high exposure group, which was 2.61 times that of the low exposure group, with an average accumulation rate of 17.89%, which was significantly higher than that of the low exposure group (13.06%). The results showed that the accumulation of PSTs in the visceral mass and edible tissue of Mytilus galloprovincialis was harmful to its tissues and organs. The toxin excretion rates of the high-and low-concentration groups of PSTs were 74.39 % and 59.15 %, respectively, after 23 days. The average daily elimination rate was 14.4 %, the metabolism rate of Mytilus edulis slowed down in the stable period (period Ⅳ), and some toxins remained in the visceral mass after 23 days of metabolism, which easily formed long-term toxin retention and threatened human life safety. In addition, PSTs in Mytilus galloprovincialis showed a strong biotransformation ability, mainly occurring among C1, C2, and GTX5. According to this research, the transformation pathway from C2 to GTX5 was the main pathway for GTX5 formation during rapid metabolism and stable periods. At the same time, the transformation of C1 to GTX5 was higher than that of C2 to C1, leading to a reduction in the overall proportion of C1. According to the comprehensive evaluation of the metabolic products and toxic equivalence factor (TEF) of GST components in mussels, the metabolic transformation of PSTs in mussels will further promote the formation and proportion of highly toxic GTX5, which will increase the terminal toxicity of PSTs in mussels and may also pose a higher risk to consumers. In this study, compared with the natural conditions, the concentration of toxic algae was far below the harmful algal bloom exposure. The total accumulation of toxins was far lower than the total accumulation of toxins in mussels exposed to harmful algal blooms. Even so, the total amount of residual toxins in the mussel viscera of the high concentration group was still enough to threaten human life safety at the end of the experiment. It was found that the toxin content in the visceral tissue tended to be stable over 12 to 30 days without an obvious downward trend. Even the toxin content increases due to the toxin transformation phenomenon, which means the difficulty in predicting the time required for PSTs in the visceral mass reduced to below the MRLs. Therefore, this study contributes to the scientific assessment of PSTs risk in mussels and provides a basis for establishing regional PSTs monitoring programs.

High-stocking density is one of the factors that can easily cause oxidative stress and inflammatory reaction of broilers. Currently, music therapy has been proposed to help animals relieve stress to some extent. However, it is still unclear whether classical music can alleviate stress in broilers at high stocking densities. Hence, this study aimed to investigate the effects of classical music on growth performance, stress level, antioxidant index, immune function and meat quality of broilers under different stocking densities. A total of 540 one-day-old broilers with similar body weight were randomly divided into 6 treatment groups, with 6 replicates per group, which included two feeding environments (with/without classical music) and three stocking densities (15.5, 17.9, and 20.3 birds/m2), thereby making a 2 × 3 factorial arrangement. The results showed as follows: increasing stocking density decreased the average daily feed intake and average daily gain (ADG), increased feed-to-gain ratio (F/G) and mortality of broilers. Moreover, increased density resulted in an increase in serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. Increasing stocking density decreased spleen and bursal indices, serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels. Increasing stocking density elevated serum malondialdehyde (MDA) and decreased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities. Increasing stocking density decreased serum total protein (TP) levels and increased total cholesterol (TC) and glucose (GLU) levels. Additionally, increasing stocking density decreased the cooking liss of pectoralis and increased the L*24h value of pectoralis. Meanwhile, playing classical music for broilers increased their ADG and decreased F/G, and decreased serum CORT, ACTH, GLU content. In addition, the bursa of Fabricius index, serum IgA and IgG contents as well as the a*24h value of pectoralis was increased under the music therapy. In conclusion, high-stocking density (20.3 birds/m2) harmed the growth performance and health of broilers, and the classical music stimulus ameliorated the negative effects to some extent.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a virulent pathogen that causes acute diarrhea in piglets. The virus was first discovered in Guangdong Province, China, in 2017 and has since emerged in Jiangxi, Fujian, and Guangxi Provinces. The outbreak exhibited a localized and sporadic pattern, with no discernable temporal continuity. The virus can infect human progenitor cells and demonstrates considerable potential for cross-species transmission, representing a potential risk for zoonotic transmission. Therefore, continuous surveillance of and comprehensive research on SADS-CoV are imperative. This review provides an overview of the temporal and evolutionary features of SADS-CoV outbreaks, focusing on the structural characteristics of the virus, which serve as the basis for discussing its potential for interspecies transmission. Additionally, the review summarizes virus–host interactions, including the effects on host cells, as well as apoptotic and autophagic behaviors, and discusses prevention and treatment modalities for this viral infection.

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections.

Nuclear factor (NF)-κB plays an important role in the innate immune response by inducing antiviral genes’ expression. However, the herpes simplex virus 1 (HSV-1) virus has developed multiple ways to interfere with NF-κB activity to escape the host antiviral response. Here, we found that HSV-1 envelope glycoprotein L(gL) markedly inhibits interferon (IFN) production and its downstream antiviral genes. Our results showed that ectopic expression of gL inhibited IFN-β promoter activation, and decreased IFN-β production, the expression of IFN-stimulated genes (ISGs), and inhibited immunologic stimulant (poly I:C) induced activation of IFN signaling pathway. Depletion of gL by short interfering RNA (siRNA) significantly upregulated IFN-β and ISG production. Further study showed that the N-terminus of the gL bound to the Rel homology domain (RHD) of the p65 and concealed the nuclear localization signal of p65, thereby impeding the translocation of phosphorylated p65 to the nucleus. In summary, our findings indicated that the N-terminal of HSV-1 gL contributes to immune invasion by inhibiting the nuclear translocation of p65.

The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a significant role in health and disease. In this pathway, cGAS, one of the major cytosolic DNA sensors in mammalian cells, regulates innate immunity and the STING-dependent production of pro-inflammatory cytokines, including type-I interferon. Moreover, the cGAS–STING pathway is integral to other cellular processes, such as cell death, cell senescence, and autophagy. Activation of the cGAS–STING pathway by “self” DNA is also attributed to various infectious diseases and autoimmune or inflammatory conditions. In addition, the cGAS–STING pathway activation functions as a link between innate and adaptive immunity, leading to the inhibition or facilitation of tumorigenesis; therefore, research targeting this pathway can provide novel clues for clinical applications to treat infectious, inflammatory, and autoimmune diseases and even cancer. In this review, we focus on the cGAS–STING pathway and its corresponding cellular and molecular mechanisms in health and disease.

Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.

Clams are commercially important species and are a vital component of the offshore ecosystem. Investigations on microplastics (MPs) in clams have attracted public attention recently, for its ecological and food safety risks. However, knowledge gaps still exist regarding MPs in commercial clams from the intertidal zone of the South Yellow Sea (SYS), China, an important clam habitat. In this study, to investigate the distribution of MPs in clams of the SYS, four species of clams were collected from nine sites in different tide zones (high, middle, and low tides) in three coastal areas (Nantong, Yancheng and Lianyungang). The abundance and characteristics of MPs, including size, shape, color and composition, were determined using microscope and micro-Fourier transform infrared (FTIR) spectroscopy. Furthermore, to evaluate the MPs purification ability of clams, the abundance of MPs in various tissues was examined by microscopic observation after being purified in filtered seawater for 72 h. The results showed that there were significant differences in the abundance of MPs in clams from different regions, with the most serious pollution in the high-tide zone. Moreover, the lowest MPs abundance was found in Yancheng (5.07 ± 2.73 items/individual, 1.16 ± 0.78 items/g), while Lianyungang was found with the most abundant MPs (7.52 ± 2.68 items/individual, 3.94 ± 3.00 items/g). The size of MPs in Ruditapes philippinarum (1,329.99 μm) was significantly higher than in other species. The MPs in clams were characterized by fiber in shape, black-grey, blue-green and white-transparent in color and rayon in composition. Moreover, it was found that the MPs originally present in various tissues tended to migrate and accumulate into the mantle of the clam during depuration, and after 72 h of depuration, removing the mantle could reduce nearly half amount of microplastics in clams. Overall, our study revealed the microplastic distribution in commercial clams from the intertidal zone of the SYS and provided suggestions for the safety of aquatic production.

Inorganic zinc (Zn) supplements are commonly used in poultry feeds, but their low utilization results in the increase of Zn excretion. Thus, to provide a new perspective for the substitution of inorganic Zn, a novel Zn methionine hydroxy analog chelate (Zn-MHA) was studied in the present study to evaluate its effects on laying performance, serum hormone indexes and reproductive axis-related genes in broilers breeders. A total of 480 Hubbard breeders (56-week-old) were fed a basal diet (containing 27.81 mg Zn/kg) without Zn addition for 2 weeks, and then allocated to 4 groups with 6 replicates (each replicate consisting of 10 cages and 2 breeders per cage) for 10 weeks. Four treatment diets given to broiler breeders included the basal diet added with 25, 50, and 75 mg/kg of Zn-MHA and 100 mg/kg of Zn sulfate (ZnSO4). The laying rate, egg weight and feed conversation ratio increased in the 75 mg/kg Zn-MHA group compared to the ZnSO4 group. The eggshell thickness was not decreased with the addition of 50 mg/kg and 75 mg/kg Zn-MHA in the diet compared to the 100 mg/kg ZnSO4 group. There was a significant improvement in the reproductive performance of breeders in the 75 mg/kg Zn-MHA group, including the fertility and 1-day-old offspring weight. Besides, serum sex hormone levels including FSH and P4 increased significantly in 75 mg/kg Zn-MHA group. No significant effect on the ovarian weight or the number of follicles in broiler breeders was observed by supplementing Zn-MHA. Compared to the 100 mg/kg ZnSO4 group, dietary supplementation with 75 mg/kg of Zn-MHA showed an up-regulation of the FSHR mRNA in the granular layer of follicles. However, dietary supplementation of Zn-MHA had no effects on mRNA expressions of the ovarian LHR and PRLR genes. These findings reinforce the suggestion that Zn-MHA (75 mg/kg) could replace ZnSO4 (100 mg/kg) as a Zn supplement in diet of broiler breeders, which resulted in better laying and reproduction performances by regulating the expression levels of reproductive axis related genes and serum hormone levels.

Bile acids (BAs) have long been known to facilitate digestion, transport, and absorption of lipids in the small intestine as well as regulate host lipid metabolic homeostasis. However, excessive BAs may lead to long-term damage to tissue. Also, it is unknown whether different levels of porcine BAs supplementation could improve performance, host metabolism, intestinal functions in laying hens. Hence, this study was aimed to investigate the potential effects of BAs addition on laying performance, egg quality, blood parameters, organ indexes, and intestinal histopathology of hens in the late phase. A total of 300 58-week-old Hy-line Gray hens were randomly divided into five groups which fed a basal diet (control) or basal diets supplemented with 60, 300, 600, and 3,000 mg/kg BAs for 56 days. Compared with the control group, no significant differences (P > 0.05) were observed in egg production, egg weight, ADFI, and FCR of hens in 60, 300, 600, and 3,000 mg/kg BAs groups. Dietary 60 mg/kg BAs supplementation resulted in a significant increase (P < 0.05) in egg mass. Meanwhile, no significant differences were observed in egg quality, including eggshell strength, eggshell thickness, albumen height, and Haugh unit among any treatment groups (P > 0.05). Dramatically, dietary 3,000 mg/kg BAs supplement decreased yolk color (P < 0.05). There was no significant difference in the blood parameters such as WBC, RBC, HGB, HCT, and PLT among any treatments. However, in 3,000 mg/kg BAs group, ovary coefficient was lower than the control (P < 0.05), and serum urea and creatinine were higher than the control (P < 0.05). Also, kidney and oviduct injury appeared in 3,000 mg/kg BAs group. These results indicated that a porcine BAs concentration of 3,000 mg/kg may cause harmful effects while 600 mg/kg was non-deleterious to laying hens after a daily administration for 56 days, namely that dietary supplement of up to 10 times the recommended dose of BAs was safely tolerated by laying hens.

Abstract Background African swine fever (ASF) leads to high mortality in domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). Currently, no vaccine is commercially available for prevention, and the epidemic is still spreading. Here, we constructed a recombinant pseudorabies virus (PRV) (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) that expresses the CD2v protein of ASFV and evaluated its effectiveness and safety as a vaccine candidate in mice. Methods A homologous recombination fragment containing ASFV CD2v was synthesized and co-transfected into HEK 293 T cells, a knockout vector targeting the PRV TK gene. The transfected cells were infected with PRV-ΔgE/ΔgI, and the recombinant strain (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) was obtained by plaque purification in Vero cells. The expression of ASFV CD2v in the recombinant virus was confirmed by sequencing, Western blotting, and immunofluorescence analysis, and the genetic stability was tested in Vero cells over 20 passages. The virulence, immunogenicity and protective ability of the recombinant virus were further tested in a mouse model. Results The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain is stable in Vero cells, and the processing of CD2v does not depend on ASFV infection. The vaccination of PRV-ΔgE/ΔgI/ΔTK-(CD2v) causes neither pruritus, not a systemic infection and inflammation (with the high expression of interleukin-6 (IL6)). Besides, the virus vaccination can produce anti-CD2v specific antibody and activate a specific cellular immune response, and 100% protect mice from the challenge of the virulent strain (PRV-Fa). The detoxification occurs much earlier upon the recombinant virus vaccination and the amount of detoxification is much lower as well. Conclusions The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain has strong immunogenicity, is safe and effective, and maybe a potential vaccine candidate for the prevention of ASF and Pseudorabies.

Barnacles and bivalves are two well-known sessile invertebrates that play important roles in marine ecosystems. Microplastic (MP) pollution has attracted widespread attention. Barnacles and wild bivalves are smaller than farmed individuals; thus, they may be more sensitive to MPs. However, less is known about the abundance and spatial distribution of MPs in wild bivalves along with the coastal areas of China. This study evaluates MP pollution in the most abundant bivalves and barnacles (Crassostrea gigas, Ostrea cucullata, Mytilus edulis, and Balanus albicostatus) at five stations in the intertidal zone of the Yellow Sea. B. albicostatus was divided into ecotype A and ecotype B. The abundance of MPs in barnacles, wild bivalves barnacles, and wild bivalves varied from 0 to 2.25 items/individual and 0 to 118.21 items/g. O. cucullata and B. albicostatus (ecotype A) had the highest abundance of MPs, with average abundances of 0.56 ± 0.36 items/individual and 21.59 ± 27.26 items/g, respectively. The types of MPs found in bivalves and barnacles include fibers, fragments, films, and microbeads. The most abundant size was less than 1,000 μm, which accounted for 53% of the total MPs. Cellophane (CP), polypropylene (PP), polyethylene (PE), and polyethylene terephthalate (PET) were the main polymer types in bivalves and barnacles. This study suggests that the abundance of MPs in wild bivalves is close to that of farmed bivalves with commercial specifications, despite their smaller size. The MP abundance of barnacles in the Yellow Sea is higher than that in other areas in terms of items per gram. In addition, the ecological type may affect the ability of barnacles to accumulate MPs. Ingestion of MPs by barnacles and wild bivalves should be of concern because they may enter the human body through the food web and may pose a potential threat to human health.

Acute hepatopancreatic necrosis disease (AHPND), formerly called early mortality syndrome (EMS), causes high mortality in cultured penaeid shrimp, particularly Penaeus vannamei and Penaeus monodon. AHPND is mainly caused by Vibrio species carrying the pVA1 plasmid encoding the virulence genes Photorhabdus insect-related (pir) pirVPA and pirVPB. We developed a new molecular assay that combines recombinase polymerase amplification (RPA) and CRISPR/Cas12a technology (RPA-CRISPR/Cas12a) to detect pirVPA and pirVPB, with a fluorescent signal result. The fluorescence RPA-CRISPR/Cas12a assay had a detection limit of 20 copies/μL for pirVPA and pirVPB. To improve usability and visualize RPA-CRISPR/Cas12a assay results, a lateral flow strip readout was added. With the lateral flow strip, the RPA-CRISPR/Cas12a assay had a lower limit of detection of 200 copies/μL (0.3 fmol/L). The lateral flow assay can be completed in 2 h and showed no cross-reactivity with pathogens causing other shrimp diseases. In a field test of 60 shrimp samples, the RPA-CRISPR/Cas12a lateral flow assay showed 92.5% positive predictive agreement and 100% negative predictive agreement. As the new RPA-CRISPR/Cas12a assay is rapid, specific, and does not require complicated experimental equipment, it may have important field applications for detecting AHPND in farmed shrimp.

Oncolytic viruses (OVs) have emerged as effective gene therapy and immunotherapy drugs. As an important gene delivery platform, the integration of exogenous genes into OVs has become a novel path for the advancement of OV therapy, while the herpes simplex virus type 1 (HSV-1) is the most commonly used. However, the current mode of administration of HSV-1 oncolytic virus is mainly based on the tumor in situ injection, which limits the application of such OV drugs to a certain extent. Intravenous administration offers a solution to the systemic distribution of OV drugs but is ambiguous in terms of efficacy and safety. The main reason is the synergistic role of innate and adaptive immunity of the immune system in the response against the HSV-1 oncolytic virus, which is rapidly cleared by the body’s immune system before it reaches the tumor, a process that is accompanied by side effects. This article reviews different administration methods of HSV-1 oncolytic virus in the process of tumor treatment, especially the research progress in intravenous administration. It also discusses immune constraints and solutions of intravenous administration with the intent to provide new insights into HSV-1 delivery for OV therapy.

Because the signal of water pump bearing is seriously disturbed by noise and the fault evolution is complex, it is difficult to describe the performance degradation trend of water pump bearing in a timely and accurate manner using the traditional performance degradation index (PDI). In this paper, a new Cluster Migration Distance (CMD) algorithm is proposed. The extraction of the indicator includes the following four steps: First, the relevant blind separation is used to extract the useful signal of the monitored bearing from the mixed signal; secondly, the impact component is further enhanced by wavelet packet analysis. Then, the redundancy of the original feature vectors is eliminated using our previously proposed KJADE (Kernel Joint Approximate Diagonalization of Eigen-matrices) method. Finally, the newly proposed CMD index is computed as PDI. By calculating the offset trajectory of the feature cluster centroid in the continuous running process of the bearing, CMD can aptly deal with the complex and variable features in the fault evolution process of the water pump bearing. The whole-life monitoring data of a 220 KW water pump system are processed. The results show that the proposed CMD index has better early-warning ability and monotonicity than the traditional kurtosis index.

Abstract Coix seed has traditionally been used in traditional Chinese medicine to fortify the spleen and inhibit dampness, and has shown anticancer effects in humans. However, it is not known whether coix seed improves post-weaning growth performance and productivity, and the mechanism of interaction between coix seed and gut microbiota remains unknown. In this study, we established four groups: (i) control, (ii) antibiotic-fed, (iii) coix seed powder-fed, and (iv) coix seed extract-fed. The feeding experiment was conducted for 4 weeks. Coix seed extract significantly increased average weight gain and reduced the feed/meat ratio in weaned pigs, in addition to reducing the pH of their gastric juice. Further assays demonstrated that coix seed promotes an increase in the density and length of the gastrointestinal villi. Next, 16s sequencing of gut microbiota showed that coix seed significantly increased the abundance of phylum Bacteroidetes and genus Lactobacillus (p

As a typical granular bulk medium, problems are common in boulder-cobble mixed grounds, such as easy collapse and instability and difficult effective support for large-section tunnel excavation. Tunnels constructed in BCM grounds are rare still, and there is a big gap between the design and construction of tunnels. Based on the Nianggaicun highway tunnel crossing the BCM grounds, the construction technology of tunnel in BCM grounds is studied by means of literature investigation and field survey. Here are the main conclusions: the overall deformation of surrounding rock is quite small; the pressure distribution of surrounding rock is small and loose pressure is dominant, and the safety reserve of secondary lining is large. The deformation process of surrounding rock concentrates on the construction stage. During the construction process, there are many problems, such as serious overexcavation, difficulty of bolt penetration, and continuous rock fall. In this paper, a three-bench complementary cyclic excavation method is proposed, which replaces the original CD and CRD methods. Meanwhile, the supporting system is optimized. The results show that the disturbance of surrounding rock is reduced, while the safety of construction process and the reliability of structure are increased. The new excavation method and optimized supporting system are expected to fill the gap between design and construction of tunnel in BCM grounds and provide reference for construction of such tunnels in the future.

Spinal muscular atrophy (SMA) is a motor neuron disease caused by insufficient levels of the survival motor neuron (SMN) protein. One of the most prominent pathological characteristics of SMA involves defects of the neuromuscular junction (NMJ), such as denervation and reduced clustering of acetylcholine receptors (AChRs). Recent studies suggest that upregulation of agrin, a crucial NMJ organizer promoting AChR clustering, can improve NMJ innervation and reduce muscle atrophy in the delta7 mouse model of SMA. To test whether the muscle-specific kinase (MuSK), part of the agrin receptor complex, also plays a beneficial role in SMA, we treated the delta7 SMA mice with an agonist antibody to MuSK. MuSK agonist antibody #13, which binds to the NMJ, significantly improved innervation and synaptic efficacy in denervation-vulnerable muscles. MuSK agonist antibody #13 also significantly increased the muscle cross-sectional area and myofiber numbers in these denervation-vulnerable muscles but not in denervation-resistant muscles. Although MuSK agonist antibody #13 did not affect the body weight, our study suggests that preservation of NMJ innervation by the activation of MuSK may serve as a complementary therapy to SMN-enhancing drugs to maximize the therapeutic effectiveness for all types of SMA patients.

The self-rotation of liquid metal droplets (LMDs) has garnered potential for numerous applications, such as chip cooling, fluid mixture, and robotics. However, the controllable self-rotation of LMDs utilizing magnetic fields is still underexplored. Here, we report a novel method to induce self-rotation of LMDs solely utilizing a rotating magnetic field. This is achieved by rotating a pair of permanent magnets around a LMD located at the magnetic field center. The LMD experiences Lorenz force generated by the relative motion between the droplet and the permanent magnets and can be rotated. Remarkably, unlike the actuation induced by electrochemistry, the rotational motion of the droplet induced by magnetic fields avoids the generation of gas bubbles and behaves smoothly and steadily. We investigate the main parameters that affect the self-rotational behaviors of LMDs and validate the theory of this approach. We further demonstrate the ability of accelerating cooling and a mixer enabled by the self-rotation of a LMD. We believe that the presented technique can be conveniently adapted by other systems after necessary modifications and enables new progress in microfluidics, microelectromechanical (MEMS) applications, and micro robotics.

Ulva is the dominant genus in the green tide events and is considered to have efficient CO2 concentrating mechanisms (CCMs). However, little is understood regarding the impacts of ocean acidification on the CCMs of Ulva and the consequences of thalli's acclimation to ocean acidification in terms of responding to environmental factors. Here, we grew a cosmopolitan green alga, Ulva linza at ambient (LC) and elevated (HC) CO2 levels and investigated the alteration of CCMs in U. linza grown at HC and its responses to the changed seawater carbon chemistry and light intensity. The inhibitors experiment for photosynthetic inorganic carbon utilization demonstrated that acidic compartments, extracellular carbonic anhydrase (CA) and intracellular CA worked together in the thalli grown at LC and the acquisition of exogenous carbon source in the thalli could be attributed to the collaboration of acidic compartments and extracellular CA. Contrastingly, when U. linza was grown at HC, extracellular CA was completely inhibited, acidic compartments and intracellular CA were also down-regulated to different extents and thus the acquisition of exogenous carbon source solely relied on acidic compartments. The down-regulated CCMs in U. linza did not affect its responses to changes of seawater carbon chemistry but led to a decrease of net photosynthetic rate when thalli were exposed to increased light intensity. This decrease could be attributed to photodamage caused by the combination of the saved energy due to the down-regulated CCMs and high light intensity. Our findings suggest future ocean acidification might impose depressing effects on green tide events when combined with increased light exposure.

The performance of the ground treatment is always critical for a tunnel excavated in unstable stratum. Laodongnanlu Xiangjiang Tunnel (Changsha, China) across the Xiangjiang River will be constructed in a sandy gravel ground which is characterized by loose structure, extensive porosity, elevated sensitivity, poor stability, and a high groundwater table. Permeation grouting will be employed to improve the bearing capacity and mitigate groundwater movement into the excavation. In order to seek suitable injection parameters and grouting method, a field trial of vertical grouting was conducted in the sandy gravel stratum in river floodplain. A series of tests focusing on grout material, grouting sequence of boreholes, injection pressure, and grouting volume were performed to improve the sandy gravel mass strength and reduce water permeability. The examination of the results obtained during water pressure testing and core drilling on completion of the grouting trial successfully demonstrated that the specified injection criteria had led to an expected effect. Grouting control method of this saturated sandy gravel stratum was concluded after the test, which would contribute to the future pregrouting work during the tunnelling.

Background and objective It has been proven that nm23-H1 gene is an important metastatic-suppressed gene of lung cancer. In order to screen the differential expression genes related to nm23-H1, we constructed the suppression subtractive cDNA libraries of human large cell lung cancer line L9981 transfected and untransfected with nm23-H1 gene by suppression subtractive hybridization (SSH) in this study, which lay a solid foundation for further screening and cloning metastatic-related genes of nm23-H1. Methods The forward and reverse suppression subtractive cDNA libraries were constructed in the human large cell lung cancer line L9981 before and after transfection with nm23-H1 gene (L9981 and L9981-nm23-H1) by SSH method. The positive clones were preliminarily screened by blue-white colony, and precisely identified by PCR. Results The suppression subtractive cDNA libraries were successfully constructed in the human large cell lung cancer line L9981 transfected and untransfected with nm23-H1 gene (L9981-nm23-H1 and L9981). After the blue-white screening, about three hundred positive clones in the forward subtracted library and four hundred positive clones in the reverse subtracted library were obtained. Ramdom analysis of 96 clones in each library with colony PCR methods showed that 84 clones in the forward subtracted library and 83 clones in the reverse subtracted library contained (300-750) bp inserts. Conclusion SSH is proved to be an efficient tool for differential expression gene cloning. The forward and reverse suppression subtractive cDNA libraries of human large cell lung cancer line L9981 transfected and untransfected with nm23-H1 gene (L9981-nm23-H1 and L9981) are successfully constructed by SSH and T/A cloning technology. The expression of nm23-H1 gene in the human large cell lung cancer cell lines may affect the differential expression of some metastatic-related genes.

Background and objective Lung cancer is the most dangerous threating tumor to human's health and life. Metastasis is not only the malignant characteristics of lung cancer, but also the chief cause of failure to cure the disease and of high mortality. Ginsenoside Rg3 has been proved to have obvious effect against tumor. The molecular mechanism of Rg3 against lung cancer cell line will be investigated by using two-dimensional gel electrophoresis in this paper. Methods The IC50 of Rg3 against human high-metastatic large cell lung cancer cell line 95D was determined by MTT. Then 95D cells were treated with Rg3 at the concentration of 0.1×IC50 for 72 h. The total proteins of 95D cell line treated with Rg3 and not treated were separated and protein profiles were obtained by using immobilized PH gradient (IPG)-based two-dimensional gel electrophoresis. The differential expression proteins of 95D cell line treated with Rg3 and not treated were analyzed using image analysis software.15 of differentially expressed proteins were further identified using MALDI-TOF MS/MS analysis and LC-MS/MS analysis. Protein identification was performed by searching the protein database. Results The IC50 of Rg3 against 95D cell line was 100 μg/mL. There were 27 differently expressed protein spots through analysis by Image Master Microsoft.15 proteins were identified using mass spectrometry. Chloride intracellular channel protein 1, Ubiquitin-Conjugating Enzyme E2-25 Kda only expressed in control; 14-3-3 protein teta, SKI-interacting protein only expressed in 95D cell line treated by Rg3; Annexin A2, profilin 2 isoform b were down-regulated in 95D cell line treated by Rg3; 14-3-3 protein zeta, Eukaryotic translation initiation factor 4H were up-regulated in 95D cell line treated by Rg3. Conclusion A significantly different expression of proteins were found in 95D cell line treated with Rg3 and those not treated. Most of identified proteins have been reported to be associated with tumor metastasis. The identified proteins will provide the basis for searching potential biomarkers and the molecular mechanism of Rg3 against the metastasis of lung cancer cells.

This paper presents a detailed study on the stochastic stability, jump, and bifurcation of the motion of the composite laminated beams subject to axial load. The largest Lyapunov exponent which determines the almost sure stability of the trivial solution is quantificationally resolved and the results show that the increase of the bandwidth facilitates the almost sure stability of the trivial response. The stochastic jump and bifurcation of the response are numerically calculated through the stationary joint probability and the results reveal that (a) the higher the excitation frequency is, the more probable the jump from the stable stationary nontrivial solution to the stable stationary trivial one is; (b) the most probable motion is around the nontrivial solution when the bandwidth is smaller; (c) the outer flabellate peak decreases, while the central volcano peak increases as the value of the excitation load decreases; and (d) the overall tendency of the response is that the probable motion jumps from the stable stationary nontrivial branch to the stable stationary trivial one as the fiber orientation angle of the first lamina with respect to the x-axis of the beam increases from zero to a smaller angle.

Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

Spinal muscular atrophy (SMA), the top genetic cause of infant mortality, is characterized by motor neuron degeneration. Mechanisms underlying SMA pathogenesis remain largely unknown. Here, we report that the activity of cyclin-dependent kinase 5 (Cdk5) and the conversion of its activating subunit p35 to the more potent activator p25 are significantly up-regulated in mouse models and human induced pluripotent stem cell (iPSC) models of SMA. The increase of Cdk5 activity occurs before the onset of SMA phenotypes, suggesting that it may be an initiator of the disease. Importantly, aberrant Cdk5 activation causes mitochondrial defects and motor neuron degeneration, as the genetic knockout of p35 in an SMA mouse model rescues mitochondrial transport and fragmentation defects, and alleviates SMA phenotypes including motor neuron hyperexcitability, loss of excitatory synapses, neuromuscular junction denervation, and motor neuron degeneration. Inhibition of the Cdk5 signaling pathway reduces the degeneration of motor neurons derived from SMA mice and human SMA iPSCs. Altogether, our studies reveal a critical role for the aberrant activation of Cdk5 in SMA pathogenesis and suggest a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]