Nestin+ Mesenchymal Stromal Cells Fibrotic Transition Mediated by CD169+ Macrophages in Bone Marrow Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-ß1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-ß/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development.

CRY1 is involved in the take-off behaviour of migratory Cnaphalocrocis medinalis individuals.

BACKGROUND: Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. RESULTS: The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light-sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. CONCLUSIONS: This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.

Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture.

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease.

Lipid nanoparticles (LNPs) represent the forefront of mRNA delivery platforms, yet achieving precise delivery to specific cells remains a challenge. The current targeting strategies complicate the formulation and impede the regulatory approval process. Here, through a straightforward regulation of helper lipids within LNPs, we introduce an engineered LNP designed for targeted delivery of mRNA into hepatocytes for metabolic dysfunction-associated fatty liver disease (MAFLD) treatment. The optimized LNP, supplied with POPC as the helper lipid, exhibits a 2.49-fold increase in mRNA transfection efficiency in hepatocytes compared to that of FDA-approved LNPs. CTP:phosphocholine cytidylyltransferase α mRNA is selected for delivery to hepatocytes through the optimized LNP system for self-calibration of phosphatidylcholine levels to prevent lipid droplet expansion in MAFLD. This strategy effectively regulates lipid homeostasis, while demonstrating proven biosafety. Our results present a mRNA therapy for MAFLD and open a new avenue for discovering potent lipids enabling mRNA delivery to specific cells.

Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy.

Proximal tubular uptake of aristolochic acid (AA) forms aristolactam (AL)-DNA adducts, which cause a p53/p21-mediated DNA damage response and acute tubular injury. Recurrent AA exposure causes kidney function loss and fibrosis in humans (Balkan endemic nephropathy) and mice and is a model of (acute kidney injury) AKI to chronic kidney disease (CKD) transition. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. C57BL/6J mice (15-wk-old) were administered vehicle or AA every 3 days for 3 wk (10 and 3 mg/kg ip in females and males, respectively). Dapagliflozin (dapa, 0.01 g/kg diet) or vehicle was initiated 7 days prior to AA injections. All dapa effects were sex independent, including a robust glycosuria. Dapa lowered urinary kidney-injury molecule 1 (KIM-1) and albumin (both normalized to creatinine) after the last AA injection and kidney mRNA expression of early DNA damage response markers (p53 and p21) 3 wk later at the study end. Dapa also attenuated AA-induced increases in plasma creatinine as well as AA-induced up-regulation of renal pro-senescence, pro-inflammatory and pro-fibrotic genes, and kidney collagen staining. When assessed 1 day after a single AA injection, dapa pretreatment attenuated AL-DNA adduct formation by 10 and 20% in kidney and liver, respectively, associated with reduced p21 expression. Initiating dapa application after the last AA injection also improved kidney outcome but in a less robust manner. In conclusion, the first evidence is presented that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.NEW & NOTEWORTHY Recurrent exposure to aristolochic acid (AA) causes kidney function loss and fibrosis in mice and in humans, e.g., in the form of the endemic Balkan nephropathy. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. Here we provide the first evidence in a murine model that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

Rational Design of Conjugated Acetylenic Polymers Enables a Two-Electron Water Oxidation Pathway for Enhanced Photosynthetic Hydrogen Peroxide Generation.

Herein, the design of conjugated acetylenic polymers (CAPs) featuring diverse spatial arrangements and intramolecular spacers of diacetylene moieties (─C≡C─C≡C─) for photocatalytic hydrogen peroxide (H2 O2 ) production from water and O2 , without the need for sacrificial agents, is presented. It is shown that the linear configuration of diacetylene moieties within conjugated acetylenic polymers (CAPs) induces a pronounced polarization of electron distribution, which imparts enhanced charge-carrier mobility when compared to CAPs' networks featuring cross-linked arrangements. Moreover, optimizing the intramolecular spacer between diacetylene moieties within the linear structure leads to the exceptional modulation of the band structures, specifically resulting in a downshifted valence band (VB) and rendering the two-electron water oxidation pathway thermodynamically feasible for H2 O2 production. Consequently, the optimized CAPs with a linear configuration (LCAP-2), featuring spatially separated reduction centers (benzene rings) and oxidation centers (diacetylene moieties), exhibit a remarkable H2 O2 yield rate of 920.1 µmol g-1 h-1 , superior than that of the linear LCAP-1 (593.2 µmol g-1 h-1 ) and the cross-linked CCAP (433.4 µmol g-1 h-1 ). The apparent quantum efficiency (AQE) and solar-to-chemical energy conversion (SCC) efficiency of LCAP-2 are calculated to be 9.1% (λ = 420 nm) and 0.59%, respectively, surpassing the performance of most previously reported conjugated polymers.

Band Structure Engineering Promotes Anionic Redox Reversibility of Cobalt-Free Li-Rich Layered Oxides Cathodes.

Li-rich layered oxides cathodes (LLOs) have prevailed as the promising high-energy-density cathode materials due to their distinctive anionic redox chemistry. However, uncontrollable anionic redox process usually leads to structural deterioration and electrochemical degradation. Herein, a Mo/Cl co-doping strategy is proposed to regulate the relative position of energy band for modulating the anionic redox chemistry and strengthening the structural stability of Co-free Li1.16Mn0.56Ni0.28O2 cathodes. The incorporation of Mo with high d state orbit and Cl with low electronegativity can narrow the band energy gap between bonding and antibonding bands via increasing the filled lower-Hubbard band (LHB) and decreasing the non-bonding O 2p energy bands, promoting the anionic redox reversibility. In addition, strong covalent Mo─O and Mn─Cl bonding further increases the covalency of Mn─O band to further stabilize the O2 n- species and enhance the reversible distortion of MnO6 octahedron. The strengthening electronic conductivity, together with the epitaxial structure Li2MoO4 facilitates the fast Li+ kinetics. As a result, the dual doping material exhibits enhanced anionic redox reversibility and suppressed oxygen release with increased cyclic stability and excellent rate performance. This strategy provides some guidance to design high-energy-density LLOs with desirable anionic redox reversibility and stable crystal structure via band structure engineering.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

Genotypic and phenotypic characteristics of sodium channel-associated epilepsy in Chinese population.

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

Natural variation and artificial selection at the BnaC2.MYB28 locus modulate Brassica napus seed glucosinolate.

The degradation products of glucosinolates (GSLs) greatly lower the nutritional value of rapeseed (Brassica napus) meal; thus, reduction of seed GSL content (SGC) has become an important objective of rapeseed breeding. In our previous study, we finely mapped a major QTL (qGSL-C2) for SGC to a 49-kb collinear region on B. rapa chromosome A2. Here, we experimentally validated that BnaC2.MYB28, encoding an R2R3-MYB transcription factor, is the causal gene of qGSL-C2. BnaC2.MYB28 is a nucleus-localized protein mainly expressed in vegetative tissues. Knockout of BnaC2.MYB28 in the high-SGC parent G120 reduced SGC to a value lower than that in the low-SGC parent ZY50, while overexpression of BnaC2.MYB28 in both parental lines (G120 and ZY50) led to extremely high SGC, indicating that BnaC2.MYB28 acts as a positive regulator of SGC in both parents. Molecular characterization revealed that BnaC2.MYB28 forms a homodimer and specifically interacts with BnaMYC3. Moreover, BnaC2.MYB28 can directly activate the expression of GSL biosynthesis genes. Differential expression abundance resulting from the polymorphic promoter sequences, in combination with the different capability in activating downstream genes involved in aliphatic GSL biosynthesis, caused the functional divergence of BnaC2.MYB28 in SGC regulation between the parents. Natural variation of BnaC2.MYB28 was highly associated with SGC in natural germplasm and has undergone artificial selection in modern low-GSL breeding. This study provides important insights into the core function of BnaC2.MYB28 in regulating SGC and a promising strategy for manipulating SGC in rapeseed.

Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos.

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.

Progress on Copper-Based Anode Materials for Sodium-Ion Batteries.

Fossil fuels have clearly failed to meet people's growing energy needs due to their limited reserves, potential pollution of the environment, and high costs. The development of cleaner, renewable energy sources as well as secondary batteries for energy storage is imminent, in a modern society where energy demand is soaring. Sodium-ion batteries (SIBs) have become the focus of large-scale energy storage systems as a promising alternative to lithium-ion batteries. The development of SIBs relies on the construction of high performance electrode materials. The design of low cost and high performance anode materials is a key link in this regard. Copper-based anodes are characterized by high theoretical capacity, abundant reserves, low cost and environmental friendliness. A variety of copper-based anode materials, which include cobalt oxides, sulfides, selenides and phosphides, have been synthesized and evaluated in the scientific literature for sodium storage. In detail, the preparation methods, response mechanisms, strengths and weaknesses, the relationship between morphology structure and electrochemical performance are discussed, as well as highlighting strategies to improve the electrochemical performance of copper-based anode materials. Finally, we offer our perspective on the challenges and potential for the development of copper-based anodes as a means of developing practical and high performing SIBs.

Hypothalamic Gene Expression in a Rat Model of Chronic Unpredictable Mild Stress Treated with Electroacupuncture.

Depression is characterized by the loss of pleasure and a depressed mood, and it is a common mental disorder in the twenty-first century. Multiple gene imbalances, which are considered pathological factors in depression, were detected in the brain. Electroacupuncture is an effective therapeutic approach for depression that has minimal side effects. As a crucial structure in the hypothalamus-pituitary-adrenal, the hypothalamus plays a key role in depression. Our study focused on the transcriptome level in the hypothalamus of depressive rats. After chronic unpredictable mild stress, the rats exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT, increased time in the central area of the OFT and increased immobility in the FST. Moreover, electroacupuncture alleviated depressive behaviors. Because of the importance of the hypothalamus in depression, we next detected gene expression in the hypothalamus. A total of 510 genes (125 upregulated genes and 385 downregulated genes) were detected in the hypothalamus of depressive rats. 15 of the 125 upregulated genes and 63 of the 385 downregulated genes could be altered by electroacupuncture, which suggests the antidepressant effect of electroacupuncture. Our study also provided the evidence that regulation of transcriptome in the hypothalamus might be a potential mechanism of electroacupuncture treatment.

Isolation and characterization of a relatively broad-spectrum phage against Escherichia coli.

Multiple pathogenic types or serotypes restrict treatment for colibacillosis. In addition, rising antibiotic resistance has heightened public awareness to prevent and control pathogenic Escherichia coli. The bacteriophage is a viable technique to treat colibacillosis as an alternative to antibiotics. In this study, PH444, a relatively broad-spectrum obligate lytic phage, was screened from 48 Shiga toxin-producing Escherichia coli (STEC) phages isolated from farm manure samples and sewage samples in order to conduct genome-wide analysis, biological characterization, and a bacterial challenge experiment in milk. The results demonstrated that PH444 was a T7-like phage with a double-stranded DNA of 115,111 bp that belongs to the Kuravirus and was stable at temperatures between 4 and 50 °C and a pH range of 3 to 11. After adding PH444, the bacterial load in milk could be reduced from 3 × 103 PFU/ mL to zero within 1 h. In consideration of the biological properties of phage PH444, it was, therefore, demonstrated that PH444 has the potential to be used in phage biocontrol.

An Atomistic Level Investigation of the PFDTES-Graphene Interfacial Shear Strength and the Stick-Slip Mechanism.

1H,1H,2H,2H-Perfluorodecyltriethoxysilane (PFDTES) is the most widely used coating material with low surface energy and has the potential to be used as a dust-mitigating coating material during lunar landing missions. Graphene can be added to the PFDTES matrix to improve its mechanical properties. In this study, molecular dynamics simulations were performed to investigate the interfacial shear strength and friction mechanism between the PFDTES matrix and graphene. A systematic molecular dynamics (MD) simulation has been performed to calculate the interfacial shear strength of the PFDTES-graphene interface with considering the effect of graphene sliding velocity and vacancy defect density. For a pristine graphene layer with a size of 10 nm × 10 nm, the interfacial force between graphene and the PFDTES matrix is around 3 nN. Like other polymeric materials, the interfacial shear force exhibited stick-slip behavior under loading. The interfacial shear force will start to increase after the graphene starts sliding against the PFDTES matrix and reaches a stable plateau in a very short distance. It has been found that the influence of the interfacial shear strength from the sliding velocity of graphene is minimal. However, a significant increase in the interfacial shear strength has been observed after the graphene defect density increased; i.e., the magnitude of the shear force increased from 3 nN to around 14 nN after the defect density increased from 0% for pristine graphene to 40%. It has been found that vacancy defects will increase the fluctuation in the interfacial shear force, and it is due to not only the increased roughness near defects but also the stretched bonds in graphene under loading according to the distribution of the bond length. This study concluded that interfacial stick-slip behavior also exists in the PFDTES-graphene interface, and vacancy defects will have a significant improvement in the interfacial shear strength.

vB_EcoM-P896 coliphage isolated from duck sewage can lyse both intestinal pathogenic Escherichia coli and extraintestinal pathogenic E. coli.

Pathogenic Escherichia coli strains cause diseases in both humans and animals. The limiting factors to prevent as well as control infections from pathogenic E. coli strains are their pathotypes, serotypes, and drug resistance. Herein, a bacteriophage (vB_EcoM-P896) has been isolated from duck sewage. Furthermore, aside from targeting intestinal pathogenic E. coli strains like enteropathogenic E. coli, Shiga toxin-producing E. coli, entero-invasive E. coli, and enteroaggregative E. coli, vB_EcoM-P896 can cause lysis in extraintestinal pathogenic E. coli strains such as avian pathogenic E. coli. Stability analysis revealed that vB_EcoM-P896 was stable under the following conditions: temperature, 4℃-50℃; pH, 3-11. The sequencing of the vB_EcoM-P896 genome was conducted utilizing an HiSeq system (Illumina, San Diego, CA) and subjected to de novo assembling with the aid of Spades 3.11.1. The characteristics of the DNA genome were as follows: size, 170,656 bp; GC content, 40.4%; the number of putative coding regions, 294. Transmission electron microscopy analysis of morphology and genome analysis revealed that the phage vB_EcoM-P896 belonged to the order Caudovirales and the family Myoviridae. The pan-genome analysis of vB_EcoM-P896 was divided into two levels. The first level involved the analysis of 91 strains of muscle tail phages, which were mainly divided into 5 groups. The second level involved the analysis of 24 strains of myophage with high homology. Of the 1480 gene clusters, 23 were shared core genes. Neighbor-joining phylogenetic trees were constructed using the Poisson model with MEGA6.0 based on the conserved sequences of phage proteins, the amino acid sequence of the terminase large subunit, and tail fibrin. Further analysis revealed that vB_EcoM-P896 was a typical T4-like potent phage with potential clinical applications.