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Abstract Background Magnetotactic bacteria (MTB) are a unique group of microorganisms that sense and navigate through the geomagnetic field by biomineralizing magnetic nanoparticles. MTB from the phylum Nitrospirota (previously known as Nitrospirae) thrive in diverse aquatic ecosystems. They are of great interest due to their production of hundreds of magnetite (Fe3O4) magnetosome nanoparticles per cell, which far exceeds that of other MTB. The morphological, phylogenetic, and genomic diversity of Nitrospirota MTB have been extensively studied. However, the metabolism and ecophysiology of Nitrospirota MTB are largely unknown due to the lack of cultivation techniques. Methods Here, we established a method to link the morphological, genomic, and metabolic investigations of an uncultured Nitrospirota MTB population (named LHC-1) at the single-cell level using nanoscale secondary-ion mass spectrometry (NanoSIMS) in combination with rRNA-based in situ hybridization and target-specific mini-metagenomics. Results We magnetically separated LHC-1 from a freshwater lake and reconstructed the draft genome of LHC-1 using genome-resolved mini-metagenomics. We found that 10 LHC-1 cells were sufficient as a template to obtain a high-quality draft genome. Genomic analysis revealed that LHC-1 has the potential for CO2 fixation and NO3 − reduction, which was further characterized at the single-cell level by combining stable-isotope incubations and NanoSIMS analyses over time. Additionally, the NanoSIMS results revealed specific element distributions in LHC-1, and that the heterogeneity of CO2 and NO3 − metabolisms among different LHC-1 cells increased with incubation time. Conclusions To our knowledge, this study provides the first metabolic measurements of individual Nitrospirota MTB cells to decipher their ecophysiological traits. The procedure constructed in this study provides a promising strategy to simultaneously investigate the morphology, genome, and ecophysiology of uncultured microbes in natural environments. Video Abstract

Contamination of soils with antimony (Sb) is becoming increasingly severe and widespread, and the associated ecological risks cannot be ignored. To evaluate how different Sb forms affected the earthworm Eisenia fetida in soil, the biomarker response index (BRI), effect addition index (EAI), and microbial diversity were characterized after single and joint application of Sb(III) and Sb(V). The results showed that Sb(III) was better enriched by earthworms than Sb(V). The metallothionein (MT) content in earthworms increased under Sb stress, and the superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) activities also showed an increasing trend, suggesting waken-up antioxidant capacity. Severe alterations for health status were observed under combined treatment. Additionally, the EAI indicated that Sb(III) and Sb(V) had synergistic and antagonistic effects at low and high concentrations, respectively. The bacterial populations in the drilosphere (gut and burrow lining) appeared to be more susceptible to Sb contamination than in the non-drilosphere, their specific microecology may be an important factor in soil Sb migration and transformation. The abundance of Actinobacteria exhibited a significant decrease with increasing concentrations of single Sb(III) and Sb(V), while the abundance of Bacteroidia increased. The correlation heatmap showed that Sphingobacterium faecium was highly tolerant to Sb. These results provide not only an important basis for the ecological risk assessment of Sb in the soil environment but also new insights into the altered drilosphere bacterial communities under Sb stress.

Antimony (Sb) poses a significant ecological threat. This study combines biochemical, pathological, transcriptome, and metabolome analyses to assess the short-term (14-day) toxic impact of two Sb levels (25 mg/kg and 125 mg/kg) on earthworms (Eisenia fetida). Higher Sb concentration caused severe intestinal damage, elevated metallothionein (MT) levels, and reduced antioxidant capacity. Metabolome analysis identifies 404 and 1698 significantly differential metabolites in the two groups. Metabolites such as S(-)-cathinone, N-phenyl-1-naphthylamine, serotonin, 4-hydroxymandelonitrile, and 5-fluoropentylindole contributed to the metabolic responses to Sb stress. Transcriptome analysis shows increased chitin synthesis as a protective response, impacting amino sugar and nucleotide sugar metabolism for cell wall synthesis and damage repair. Integrated analysis indicated that 5 metabolite-gene pairs were found in two Sb levels and 11 enriched pathways were related to signal transduction, carbohydrate metabolism, immune system, amino acid metabolism, digestive system, and nervous system. Therefore, the integration of multiomics approaches enhanced our comprehension of the molecular mechanisms underlying the toxicity of Sb in E. fetida.

Abstract GBA1 variants are important risk factors for Parkinson’s disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. Although the coding region of the GBA1 gene in the Chinese population has been analyzed, the sample sizes were not adequate. In this study, we aimed to investigate GBA1 variants in a large Chinese cohort of patients with PD and healthy control and explore the associated clinical characteristics. GBA1 variants in 4034 patients and 2931 control participants were investigated using whole-exome and whole-genome sequencing. The clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze GBA1 variants and the clinical symptoms of different groups. We identified 104 variants, including 8 novel variants, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the control (1.81%) (P

Abstract Background The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development. Methods Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non‐targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways. Results In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma‐glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid‐like molecules. The most obvious age‐related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L‐cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway. Conclusion This study revealed many age‐related metabolite alterations in the feline plasma. These age‐varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5′ untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain. Results In this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC) 98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients. Conclusions Our study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.

Abstract Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.

Cordycepin (with a molecular formula of C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.

Parkinson’s disease (PD) is a well-known neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, and oxidative stress and neuroinflammation are also associated with the pathogenesis of PD. Mitochonic acid 5 (MA-5), an analogue of indole-3-acetic acid, exerts key protective roles in inhibiting apoptosis, oxidative stress and neuroinflammation in multiple diseases. However, whether MA-5 can be beneficial for PD remains unclear. Hence, the aim of this study was to investigate the neuroprotective role of MA-5 in PD. In the current study, MPTP-challenged mice were treated as the in vivo model, and the effect of MA-5 on the motor function, neuronal survival, oxidative stress, neuroinflammation and the underlying mechanisms involved with AMPK and autophagy were determined. We revealed that MA-5 obviously up-regulated the phosphorylation of AMPK and promoted the autophagy (indicated by the increased LC3II/LC3I, parkin, pink and decreased p62) in substantia nigra (SN), ameliorated the motor deficits, up-regulated the expression of TH, suppressed the inflammation (indicated by the decreased protein levels of interleukin (IL)-1b, IL-6, tumour necrosis factor a) in SN in MPTP-induced mice. However, these patterns were reversed after the treatment of Compound C, an inhibitor of AMPK; also, after the application of CSA, an inhibitor of autophagy, MA-5 cannot play against the neurotoxicity of MPTP in mice. These combined results suggest that MA-5 can protect against MPTP-induced neurotoxicity to ameliorate the impaired motor function, which may be modulated via activation of AMPK-induced autophagy.

Magnetotactic bacteria use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Here, Wan et al. identify two proteins involved in magnetosome positioning in Magnetospirillum magneticum, homologs of which are widespread among magnetotactic bacteria.

Skin aging is a complex process involving intricate genetic and environmental factors. In this study, we performed a comprehensive analysis of the transcriptional regulatory landscape of skin aging in canines. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify aging-related gene modules. We subsequently validated the expression changes of these module genes in single-cell RNA sequencing (scRNA-seq) data of human aging skin. Notably, basal cell (BC), spinous cell (SC), mitotic cell (MC), and fibroblast (FB) were identified as the cell types with the most significant gene expression changes during aging. By integrating GENIE3 and RcisTarget, we constructed gene regulation networks (GRNs) for aging-related modules and identified core transcription factors (TFs) by intersecting significantly enriched TFs within the GRNs with hub TFs from WGCNA analysis, revealing key regulators of skin aging. Furthermore, we demonstrated the conserved role of CTCF and RAD21 in skin aging using an H2O2-stimulated cell aging model in HaCaT cells. Our findings provide new insights into the transcriptional regulatory landscape of skin aging and unveil potential targets for future intervention strategies against age-related skin disorders in both canines and humans.

Under the combined action of soil evaporation and vegetation transpiration, the law of soil water dissipation at different depths of vegetated slopes is unknown and the related influencing factors are unclear. In this paper, six large-scale slope models were constructed for long-term dynamic monitoring of soil water. The effects of slope ratio and vegetation on the dynamic changes in soil water at different depths were analyzed. Pearson correlation analysis was used to analyze the relationship between slope conditions, meteorological factors, and soil water dissipation. The results show that under the condition of natural evaporation, slope ratio has little effect on the dynamic change in soil water in bare slopes. However, the greater the slope ratio of vegetated slopes, the faster the soil water decreases in the 40 cm depth range. Additionally, soil water dissipation follows a logarithmic functional relationship with evaporation time in both bare and vegetated slopes. The correlation between slope conditions and soil water dissipation is stronger than that of meteorological factors. The research results can provide some theoretical support for exploring the hydrological effects of vegetated slopes.

This study investigated naturally-restored plant communities on wind farm slopes and analyzed the effects of various habitat factors on the plant diversity. The findings provide a technical support for the ecological restoration of mountainous slopes.Twenty-one slopes on five wind farms were selected and the characteristics of the habitat, including slope position, slope aspect, slope gradient, altitude, years since restoration, and plant communities, were recorded. The species richness of the plant communities and the vegetation diversity indexes of these wind farms were measured and calculated, including the Shannon-Wiener diversity index (H′), Pielou’s species evenness index (J), and Margalef’s richness index (R). The key factors influencing plant diversity were identified using a stepwise regression analysis. A total of 36 families, 54 genera, and 57 species of plants were identified in this study with the Gramineae, Compositae, Rosaceae, Liliaceae, and Juglandaceae families the mostly predominant. Cynodon dactylon, Rubus lambertianus Ser., and Lindera glauca were the dominant species of herbs, shrubs, and trees, respectively. The highest number of species were found on lower slopes, slopes with semi-sunny aspects, slopes with gradients 30–50°, elevation below 500 m, and on slopes with at least five years since restoration. The plant diversity H′ and R tended to be higher on lower slopes than on upper slopes, and higher on slopes with semi-shady aspects than on slopes with semi-sunny aspects (P

Vegetation slope protection plays an important role in improving the slope stability and protecting the environment. In this study, the mechanical properties of root–soil composites in different growth periods and their effects on slope stability were investigated. First, the shear strength of undisturbed root–soil composites associated with Cynodon dactylon (C.d), Magnolia multiflora (M.m) and grass and shrub mixture (G.s) were measured by large direct shear tests. Then, the effects of plant reinforcement in different growth periods on slope stability were analyzed using ABAQUS. The results show that the shear strength of the root–soil composites were significantly higher than that of the unreinforced soil. The root–soil composites met the Mohr–Coulomb criterion. The shear strength of the three root–soil composites increased first and then decreased during the vegetation growth period. The calculation results show that the factor of safety (FS) of the bare slope was 1.482. The FS values of the C.d, M.m, and G.s slopes were 1.601, 1.658 and 1.715, which increased by 8%, 11.9% and 15.7% compared to the bare soil slopes. Therefore, vegetation could significantly improve slope stability, especially the grass–shrub mixture model. This could provide a rational basis for designing and constructing plant slope protection.

Parkinson’s disease (PD) is a neurodegenerative disorder that frequently occurs in the older population. Previous epidemiological studies have suggested an association between PD and autoimmune diseases (AIDs). However, some studies have shown conflicting results. This study aimed to summarize existing epidemiological studies on the association between PD with AIDs and to conduct a meta-analysis of combinable results. Four electronic databases (PubMed, Embase, Web of Science Core Collection, and MEDLINE) were searched from each database’s inception date until December 12, 2022. All studies that explored the relationship between PD and AIDs were included for quantitative analysis and qualitative review. The pooled relative risk with 95% confidence intervals (CIs) was calculated using a random or fixed effects model. A total of 46 observational studies involving 873,643 patients and 13,402,821 controls were included; ultimately, 38 studies were included in the meta-analysis. The risk of PD combined with AIDs was significantly higher (odds ratio [OR]=1.55, 95% CI: 1.33–1.81), and subgroup analysis found no significant differences in risk by study type, gender, age, and race. Regarding the AID types, the results showed an increased risk of PD combined with bullous pemphigoid (OR=2.67, 95% CI: 2.15–3.31), inflammatory bowel disease (OR=1.30, 95% CI: 1.18–1.45), Crohn’s disease (OR=1.30, 95% CI: 1.20–1.42), ulcerative colitis (OR=1.31, 95% CI: 1.14–1.50), Sjögren’s syndrome (OR=1.61, 95% CI: 1.24–2.09), and Graves’ disease (OR=1.45, 95% CI: 1.24–1.70) than controls. However, there appeared to be no significant association between PD and systemic lupus erythematosus (OR=0.82, 95% CI: 0.66–1.03), multiple sclerosis (OR=2.02, 95% CI: 0.87–4.70), rheumatoid arthritis (OR=0.79, 95% CI: 0.61–1.03), or celiac disease (OR=1.16, 95% CI: 0.79–1.69). This study supports the existence of a strong link between AIDs and PD. When PD and AIDs are identified, clinicians need to be aware of the possibility of coexistence. However, there are some limitations of this study, such as the apparent heterogeneity of some of the results and the fact that most of the included study types were retrospective. Therefore, future larger prospective cohort studies are needed to further explore the interaction between PD and AIDs.Systematic review registrationINPLASY, identifier INPLASY202280088.

IntroductionThe primo vascular system (PVS), an intensive network structure, has been claimed to be representative of the acupuncture meridian. Here, we explored the role of the PVS in local enteritis and its modification by acupuncture.MethodsChronic cecitis in rabbits was induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS). The PVS on the cecum was visualized with trypan blue staining, and collected with the help of microsurgical forceps under an optical stereomicroscope.ResultsThe increased primo vessels (PVs) and primo nodes (PNs) of the PVS on the surface of the cecum were induced by local inflammation, which was positively correlated with the inflammatory cells in the cecal mucosa. Tandem mass tag (TMT) based proteomic analysis revealed that 110 differentiated proteins of the PVS existed between TNBS-treated and control rabbits; 65 proteins were upregulated, while 45 proteins were downregulated. These proteins were mainly enriched in inflammation- and immunity-related processes, such as inflammatory cell proliferation, antigen presentation, and cell adhesion in the proliferated PVS (data are available via ProteomeXchange with the identifiers PXD034280). Importantly, TNBS-induced cecitis, the proliferated PVS and inflammation response-related proteins (CD40, CD45, HLA-DRA1, LAMP1, JAGN1 and FGL1) in the PVS were alleviated or reversed by repetitive electroacupuncture (EA) stimulations.ConclusionThese results suggest that the proliferated PVS and its active inclusions were related to the inflammatory process, which was modified by EA. Our study provides a new avenue for further exploration of the mechanism by which EA exerts anti-inflammatory effects.

Background and aimsThe metabolomic profile of a biofluid can be affected by age, and thus provides detailed information about the metabolic alterations in biological processes and reflects the in trinsic rule regulating the growth and developmental processes.MethodsTo systemically investigate the characteristics of multiple metabolic profiles associated with canine growth, we analyzed the metabolomics in the plasma and urine samples from 15 young and 15 adult beagle dogs via UHPLC-Q-TOFMS-based metabolomics. Blood routine and serum biochemical analyses were also performed on fasting blood samples.ResultsThe metabolomics results showed remarkable differences in metabolite fingerprints both in plasma and urine between the young and adult groups. The most obvious age-related metabolite alterations include decreased serumlevels of oxoglutaric acid and essential amino acids and derivatives but increased levels of urine levels of O-acetylserine. These changes primarily involved in amino acid metabolism and bile secretion pathways. We also found that the levels of glutamine were consistently higher in both serum and urine of adults, while N-acetylhistamine and uracil concentrations were much lower in the adult group compared to younger ones.ConclusionOur study provides a whole metabolic profile of serum and urine characteristics of young and adult canines, identifying several metabolites that were significantly associated with age change, which provides theoretical support for the nutrition-related research and age-related homeostasis maintenance in dogs.

Summary Med‐ORF10, a single‐domain protein with unknown function encoded by a gene located in a gene cluster responsible for the biosynthesis of a novel antitumour antibiotic medermycin, shares high homology to a group of small proteins widely distributed in many aromatic polyketide antibiotic pathways. This group of proteins contain a nuclear transport factor‐2 (NTF‐2) domain and appear to undergo an evolutionary divergence in their functions. Gene knockout and interspecies complementation suggested that Med‐ORF10 plays a regulatory role in medermycin biosynthetic pathway. Overexpression of med‐ORF10 in its wild‐type strain led to significant increase of medermycin production. It was also shown by qRT‐PCR and Western blot that Med‐ORF10 controls the expression of genes encoding tailoring enzymes involved in medermycin biosynthesis. Transcriptome analysis and qRT‐PCR revealed that Med‐ORF10 has pleiotropic effects on more targets. However, there is no similar conserved domain available in Med‐ORF10 compared to those of mechanistically known regulatory proteins; meanwhile, no direct interaction between Med‐ORF10 and its target promoter DNA was detected via gel shift assay. All these studies suggest that Med‐ORF10 regulates medermycin biosynthesis probably via an indirect mode.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Due to asymptomatic patients in the early stage, most patients are diagnosed at an advanced stage and lose the opportunity for radical resection. In addition, for patients who underwent procedures with curative intent for early-stage HCC, up to 70% of patients may have disease recurrence within 5 years. With the advent of an increasing number of systemic therapy medications, we now have more options for the treatment of HCC. However, data from clinical studies show that with different combinations of regimens, the objective response rate is approximately 40%, and most patients will not respond to treatment. In this setting, biomarkers for predicting treatment response are of great significance for precise treatment, reducing drug side effects and saving medical resources. In this review, we summarized the existing and emerging biomarkers in the literature, with special emphasis on the pathways and mechanism underlying the prediction value of those biomarkers for systemic treatment response.

Background and aimsOverweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model.Materials and methodsBeagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays.ResultsTwenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways.ConclusionThe prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.

Green tea has significant protective activity on nerve cells, but the mechanism of action is unclear. Epigallocatechin gallate (EGCG) and N-ethyl-L-glutamine (L-theanine) are the representative functional components of green tea (Camellia sinensis). In this study, an AD model of Aβ25–35-induced differentiated neural cell line PC12 cells was established to study the synergistic effect of EGCG and L-theanine in protecting neural cells. The results showed that under Aβ25–35 stress conditions, mitochondria and axons degenerated, and the expression of cyclins was up-regulated, showing the gene and protein characteristics of cellular hyperfunction. EGCG + L-theanine inhibited inflammation and aggregate formation pathways, significantly increased the percentage of G0/G1 in the cell cycle, downregulated the expression of proteins such as p-mTOR, Cyclin D1, and Cyclin B1, upregulated the expression of GAP43, Klotho, p-AMPK, and other proteins, promoted mitochondrial activity and energy metabolism, and had repair and regeneration effects on differentiated nerve cells. The synergistic mechanism study showed that under the premise that EGCG inhibits amyloid stress and inflammation and promotes metabolism, L-theanine could play a nourish nerve effect. EGCG + L-theanine keeps differentiated nerve cells in a quiescent state, which is beneficial to the repair and regeneration of nerve cells. In addition, EGCG + L-theanine maintains the high-fidelity structure of cellular proteins. This study revealed for the first time that the synergistic effect of EGCG with L-theanine may be an effective way to promote nerve cell repair and regeneration and slow down the progression of AD. Our findings provide a new scientific basis for the relationship between tea drinking and brain protection.

Canine models are increasingly being used in metabolic studies due to their physiological similarity with humans. The present study aimed to identify changes in metabolic pathways and biomarkers with potential clinical utility in a canine model of obesity and metabolic disorders induced by a high-fat diet (HFD). Eighteen male beagles were included in this study, 9 of which were fed a HFD for 24 weeks, and the remaining 9 were fed normal chow (NC) during the same period. Plasma and urine samples were collected at weeks 12 and 24 for untargeted metabolomic analysis. Dogs fed a HFD showed a gradual body weight increase during the feeding period and had hyperlipidemia, increased leukocyte counts, and impaired insulin sensitivity at week 24. Plasma and urine metabonomics analysis displayed clear separations between the HFD-fed and NC-fed dogs. A total of 263 plasma metabolites varied between the two groups, including stearidonic acid, linolenic acid, carnitine, long-chain ceramide, 3-methylxanthine, and theophylline, which are mainly engaged in fatty acid metabolism, sphingolipid metabolism, and caffeine metabolism. A total of 132 urine metabolites related to HFD-induced obesity and metabolic disorders were identified, including 3-methylxanthine, theophylline, pyridoxal 5’-phosphate, and harmine, which participate in pathways such as caffeine metabolism and vitamin digestion and absorption. Eight metabolites with increased abundance (e.g., 3-methylxanthine, theophylline, and harmine) and 4 metabolites with decreased abundance (e.g., trigonelline) in both the plasma and urine of the HFD-fed dogs were identified. In conclusion, the metabolomic analysis revealed molecular events underlying a canine HFD model and identified several metabolites as potential targets for the prevention and treatment of obesity-related metabolic disorders.

PurposeThe aim of this study was to investigate changes in the retinal and choroidal thickness between high myopic amblyopia (HMA), low myopia (LM), moderate myopia (MM), high myopia (HM), and normal group (NG) using a spectral-domain optical coherence tomography (SD-OCT).Materials and MethodsA total of 75 Chinese children (128 eyes; mean age 10.5 years) were recruited. Retinal thickness (RT) and choroidal thickness (CT) were measured at different locations including subfoveal (SF), and at 0.5 mm/1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to the fovea in superior, nasal, inferior, and temporal sectors using enhanced depth imaging (EDI) system of SD-OCT. Axial length (AL), best-corrected visual acuity (BCVA), and refraction errors were also collected.ResultsNo significant differences were found in subfoveal retinal thickness (SFRT). Moreover, a significantly thinner subfoveal choroidal thickness (SFCT) was found in HMA compared to NG, LM, and MM, but not compared to HM. RT at 0.5 mm to fovea, HMA was significantly thinner compared to LM and MM in the three sectors (superior, inferior, and temporal). Nevertheless, no significant differences were found compared to NG and HM. CT at 0.5 mm to fovea, HMA was the significantly thinnest in all four sectors compared to NG, LM, and MM. RT at 1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to fovea, HMA was thinner compared to NG, LM, and MM. CT at 1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to fovea, HMA was thinner compared to NG, LM, and MM. At the superior and inferior sectors, HMA showed to be statistically thinner compared with HM. Moreover, SFCT in the HMA, HM, and NG were negatively correlated with AL.ConclusionsThinner retina and choroidal tissue appear to be related to HMA, and thus can be used as useful parameters for discovering the underlying mechanisms of the disease.

Abstract Cerebral ischemia reperfusion (CIR) is one of the highly lethal diseases in the world. MicroRNA‐370 (miR‐370) exerts multiple functions in different diseases. However, further research is needed to investigate the potential role of miR‐370 in CIR injury. The in vivo middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen‐glucose deprivation/reoxygenation (OGD/R) SH‐SY5Y cell model were successfully established to mimic CIR injury. The infarct sizes of brain tissues from rats were evaluated. The relationship between miR‐370 and silencing information regulatory protein 6 (SIRT6) was confirmed by luciferase activity assay. The cell viability and apoptosis were determined by CCK‐8 assay and terminal‐deoxynucleoitidyl transferase mediated nick end labeling staining. In this study, miR‐370 was upregulated in brain tissues of MCAO rats and knockdown of miR‐370 decreased cerebral infarction volume of MCAO rats and it alleviated CIR injury in vivo. The in vitro experiments indicated that knockdown of miR‐370 promoted cell viability and alleviated OGD/R‐induced SH‐SY5Y cell apoptosis. Additionally, the TargetScan predicted that SIRT6 was a target of miR‐370 and confirmed by luciferase activity assay. Moreover, miR‐370 inhibited SIRT6 expression and regulated Nrf2/ARE signal pathway, whereas overexpression of SIRT6 partly reversed the effect of miR‐370 on OGD/R‐induced SH‐SY5Y cell injury. Thus, we could conclude that miR‐370 accelerated CIR injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway, which might provide novel therapeutic targets for CIR injury treatment.

Abstract Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T11) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBS-treated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7–22. Goats of Sham-A, VH or EA group showed higher (P

Cordycepin (known as 3-deoxyadenosine, CRD), a natural product from the valuable traditional Chinese medicine Cordyceps militaris, has been reported to improve cognitive function and modulate neuroprotective effects on the central nervous system (CNS). However, the modulating mechanisms of cordycepin on information processing in hippocampal CA1 pyramidal neurons are not fully understood. To clarify how cordycepin modulates synaptic responses of pyramidal neurons in rat hippocampal CA1 region, we conducted an electrophysiological experiment using whole-cell patch-clamp technique. The spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) and the spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs, respectively) recorded by this technique evaluated pure single or multi-synapse responses and enabled us to accurately quantify how cordycepin influenced the pre and postsynaptic aspects of synaptic transmission. The present results showed that cordycepin significantly decreased the frequency of both glutamatergic and GABAergic postsynaptic currents without affecting the amplitude, while these inhibitory effects were antagonized by the A1 adenosine receptor antagonist (DPCPX), but not the A2A (ZM 241385), A2B (MRS1754) and A3 (MRS1191) adenosine receptor antagonists. Taken together, our results suggested that cordycepin had a clear presynaptic effect on glutamatergic and GABAergic transmission, and provided novel evidence that cordycepin suppresses the synaptic transmission through the activation of A1AR.

AIM: To investigate the retinal thickness, choroidal thickness and optic disc nerve fiber layers thickness in high myopia amblyopia eyes and high myopia eyes with the similar diopter by using enhanced depth imaging optical coherence tomography(EDI-OCT).METHODS:Nineteen Chinese children, 26 eyes were recruited. Those patients were divided into high myopia amblyopia group(11 eyes)and high myopia group(15 eyes). The thickness in the retina and choroid in different regions, as well as the thickness of optic disc nerve fiber layer were measured by EDI-OCT.RESULTS: The retinal thickness at the 1.0mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm to the fovea, in most directions, retinal thicknesses were statistically different between the two groups(PP=0.012). In the optic disc nerve fiber layer, there was no statistical difference between high myopia amblyopia and high myopia(P>0.05).CONCLUSION: In the same diopter range, the retinal thickness around the fovea in the high myopia amblyopia was significantly thinner than high myopia, and the occurrence and development of amblyopia may be involved in its change process.

Aging and lipid metabolism disorders promote the formation and accumulation of amyloid with β-sheet structure, closely related to cardiovascular disease, senile dementia, type 2 diabetes, and other senile degenerative diseases. In this study, five representative teas were selected from each of the six types of tea, and a total of 30 teas were selected to evaluate the inhibitory activities on the formation of aging-related amyloid in vitro. The results showed that the 30 teas had a significant inhibitory effect on the formation activity on aging-related amyloid at the protein level in vitro. Although the content of catechins is relatively low, black tea and dark tea still have significant antioxidant activity and inhibit the formation of amyloid. A high-fat diet established the model of lipid metabolism disorder in premature aging SAMP8 mice, and these mice were gavaged different tea water extracts. The results showed that different tea types have a significant inhibitory effect on the formation of β-amyloid and Aβ42 mediated by age-related lipid metabolism disorders, and the in vivo activity of fully fermented teas was better than that of green tea. The action mechanism was related to antioxidation, anti-inflammatory, and improving lipid metabolism.

Plant parasitic nematodes cause severe damage to crops. Endoparasitic nematophagous fungi (ENF) are a type of important biocontrol fungi, which can cause disease or kill nematodes by producing various spores. As a major ENF, Drechmeria coniospora displays certain potential for controlling plant-parasitic nematodes. In this study, the pathogenicity and secondary metabolites of the endoparasitic fungus D. coniospora YMF1.01759 were investigated. The strain D. coniospora YMF1.01759 had high infection efficiency against nematodes. The process of infecting nematodes by the strain was observed under an electron microscope. Here, 13 metabolites including one new compound 4(S)-butoxy-3-(butoxymethyl)-2-hydroxycyclopent-2-en-1-one (2) were isolated and identified from the fermentation products of D. coniospora YMF1.01759 cultured in a SDAY solid medium. Furthermore, a bioassay showed that 5-hydroxymethylfuran-2-carboxylic acid (1) is toxic to the root knot nematode Meloidogyne incognita and affects the hatching of its egg. Thereby, the nematicidal mortality attained 81.50% at 100 μg/mL for 48 h. Furthermore, egg hatching was inhibited at the tested concentrations, compared with water control eggs. This is the first report on the secondary metabolites of the ENF D. coniospora. The results indicated that D. coniospora could infect nematodes by spores and produce active metabolites to kill nematodes. The biological control potential of D. coniospora against nematodes was expounded further.

Abstract What are the neural mechanisms underlying beauty based on objective parameters and beauty based on subjective social construction? This study scanned participants with fMRI while they performed aesthetic judgments on concrete pictographs and abstract oracle bone scripts. Behavioral results showed both pictographs and oracle bone scripts were judged to be more beautiful when they referred to beautiful objects and positive social meanings, respectively. Imaging results revealed regions associated with perceptual, cognitive, emotional and reward processing were commonly activated both in beautiful judgments of pictographs and oracle bone scripts. Moreover, stronger activations of orbitofrontal cortex (OFC) and motor-related areas were found in beautiful judgments of pictographs, whereas beautiful judgments of oracle bone scripts were associated with putamen activity, implying stronger aesthetic experience and embodied approaching for beauty were elicited by the pictographs. In contrast, only visual processing areas were activated in the judgments of ugly pictographs and negative oracle bone scripts. Results provide evidence that the sense of beauty is triggered by two processes: one based on the objective parameters of stimuli (embodied natural beauty) and the other based on the subjective social construction (social endowed beauty).

Hypothalamic-pituitary-ovary (HPO) axis is a dominant system controlling ovulation during puberty. Electro-acupuncture (EA) has been widely used to cure the reproductive diseases associated with endocrinological disorders. However, whether EA treatment affects HPO axis activity of physiological animals and induces alterations on the hormones in the HPO axis was also unclear. Here, we performed the EA stimuli on bilateral acupoints of Sanyinjiao (SP6) and Zusanli (ST36) on female virgin rats every 3 days and for a total of 5 times. The results showed that GnRH levels in hypothalamus were greatly upregulated in EA-treated rats than untreated animals at day 7 and 13. The serum levels for FSH and LH were severely reduced after EA treatment compared with EA-untreated animals at day 1, while they were greatly increased at day 7 and 13. The serum concentrations of 17β-estradiol were lower in EA-treated rats versus untreated animals at day 7, while they were higher in EA-treated rats than other groups at day 13. However, the progesterone concentrations were lower in EA-treated rats than Control and Sham-EA rats both at day 7 and 13. More importantly, we found that the prostaglandin E2 level in serum was reduced in EA-treated rats versus untreated rats at day 1, while they were upregulated at day 7 and 13. Conversely, the norepinephrine level in serum was increased at day 1, while they were decreased greatly in EA-treated rats versus untreated rats at day 7 and 13. The current results demonstrated that EA could modulate homeostasis of HPO axis in physiologic rats, which would be useful to clarify the mechanisms of EA application on pathological and physiological animals or human.

Background: Electroacupuncture (EA) tolerance, a negative therapeutic effect, is a gradual decline in antinociception because of its repeated or prolonged use. This study aims to explore the role of thymosin beta 4 (Tβ4), having neuro-protection properties, in EA tolerance (EAT).Methods: Rats were treated with EA once daily for eight consecutive days to establish EAT, effect of Tβ4 on the development of EAT was determined through microinjection of Tβ4 antibody and siRNA into the cerebroventricle. The mRNA and protein expression profiles of Tβ4, opioid peptides (enkephalin, dynorphin and endorphin), and anti-opioid peptides (cholecystokinin octapeptide, CCK-8 and orphanin FQ, OFQ), and mu opioid receptor (MOR) and CCK B receptor (CCKBR) in the brain areas (hypothalamus, thalamus, cortex, midbrain and medulla) were characterized after Tβ4 siRNA was administered.Results: Tβ4 levels were increased at day 1, 4, and 8 and negatively correlated with the changes of tail flick latency in all areas. Tβ4 antibody and siRNA postponed EAT. Tβ4 siRNA caused decreased Tβ4 levels in all areas, which resulted in increased enkephalin, dynorphin, endorphin and MOR levels in most measured areas during repeated EA, but unchanged OFQ, CCK-8, and CCKBR levels in most measured areas. Tβ4 levels were negatively correlated with enkephalin, dynorphin, endorphin, or MOR levels in all areas except medulla, while positively correlated with OFQ and CCK-8 levels in some areas.Conclusion: These results confirmed Tβ4 facilitates EAT probably through negatively changing endogenous opioid peptides and their receptors and positively influencing anti-opioid peptides in the central nervous system.

In order to realize the resource utilization of fly ash, a kind of ecological slope protection substrate was prepared by mixing fly ash produced by MSW incineration into slope protection soil. Through the direct shear test and a leaching experiment on ion pollutants, the influence that shear strength of the substrate changed with root content, ash content, and moisture content and the ecological effects of leach liquor were investigated. The results showed the following: (1) When the optimum moisture content is about 24.9%, the shear strength of the substrate is the maximum. (2) Fly ash can improve the shear strength of the soil, which can reach 1.67 times as much as that of plain soil, and the optimum content of fly ash is 5%–6.7%. (3) The root system can increase the cohesion and internal friction angle of the substrate soil but mainly increases the cohesion of the substrate soil. (4) Plants grow taller in ash-mixed soil than in plain soil. (5) When the fly ash content is 20%, the ion concentrations of Cl, Cu, and Zn are the highest: 220.7, 0.153, and 1.526 mg/L, respectively. All of them are lower than the standard limit of class V water and gradually decrease with time. Therefore, the leaching liquid will not cause environmental pollution and meet the ecological requirements.

To investigate dynamic processes of enkephalin (ENK), cholecystokinin octapeptide (CCK-8), orphanin FQ (OFQ) and their receptors (μ opioid receptor, MOR; CCK B type receptor, CCKBR and opioid receptor-like 1 receptor, OPRL1) in the central nerve system (CNS) during electroacupuncture (EA) tolerance, EA of Sixty Hz was used to stimulate goats for 6 h. Pain threshold was measured using potassium iontophoresis. The expression levels of ENK, CCK-8, and OFQ and their receptors were determined with ELISA and qPCR, respectively. The results showed that the change rates of pain threshold in EA-treated goats decreased from 89.9 ± 11.7% at 0.5 h to –11.4 ± 8.9% at 6 h. EA induced the decreased ENK and increased CCK-8 and OFQ in the most measured nuclei. EA caused decreased preproenkephalin mRNAs in ACB, CAU, PVH, and PAG at 4 h, and decreased or unchanged MOR mRNAs at 2–6 h, but increased CCK mRNAs in CAU, PVT, PVH, PAG, and SCD at 4–12 h. Increased prepronociceptin mRNAs and fluctuated CCKBR and OPLR1 mRNAs were found in the most measured nuclei. ENK levels were positively correlated (p < 0.01) with the change rates of pain thresholds in the measured nuclei or areas while CCK-8 levels (or OFQ levels) were negatively correlated (p < 0.01) with the pain thresholds in CAU (or CAU and ACB). These results suggest that the development and recovery of EA tolerance may be associated with the specific expression patterns of opioid peptides, anti-opioid peptides and their receptors in the analgesia-related nuclei or areas.

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral “Sanjinjiao” and “Zusanli” acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.

Positive-sense (+) RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+) RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D) imaging technologies, such as electron tomography (ET) and focused ion beam-scanning electron microscopy (FIB-SEM), has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.

AIM: To compare posterior choroidal thickness in high myopia amblyopia eyes at different points to high myopia and normal eyes of Chinese children and investigate the relationships between choroidal thickness, axial length and age.METHODS: Fifty Chinese children(65 eyes)with age 4～15 years(mean 9.91±3.41 years)were recruited. By atropine optometry they were divided into high myopia amblyopia group(24 eyes), high myopia group(19 eyes), and normal group(22 eyes). Choroidal scans were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography(EDI-OCT). Subfoveal choroidal thickness(SFCT), macular thinkness, choroidal thickness and retinal thickness at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0mm superior(S, 12:00 position), temporal(T, 9:00 position), inferior(I, 6:00 position), nasal(N, 3:00 position)were measured. Meanwhile, axial lengths of all eyes were measured by A-Scan. RESULTS: Compared high myopia group and emmetropia group, SFCT and the thickness of choroids on each position were thinnest in high myopic amblyopia group, with statistically significant differences(Pr=-0.531, R2=0.282, F=7.476, P=0.013), with no relative in age(r=-0.292, R2=0.085, F=2.044, P=0.167).CONCLUSION: The choroidal thickness thinning in high myopic amblyopia shows a negative correlation with axial length.

Electroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis.Methods: Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40% ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7, then every 3 days for six times. VH was assessed by visceromotor response (VMR) and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh thoracic vertebra and the brain were collected at day 22. The protein and mRNA levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and qPCR, respectively. The distribution of these substances was observed with immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal motor nucleus of vagi (DMV).Results: Goats administered with TNBS-ethanol solution showed diarrhea, enhanced VMR and pain behavior response, and increased IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG, NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA level of these three substances in the SCDH.Conclusion: EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH axis.

Accurate determination of soil-water characteristic curve (SWCC) is of immense importance for understanding the mechanical behavior of unsaturated soils. Due to the difficulty and long duration of experimental procedures, it is of great significance to estimate the SWCC by indirect methods. To address this issue, in this article an effective fractal method is proposed for predicting the SWCC based on mercury intrusion porosimeter (MIP) data. Only two characteristic parameters, namely the fractal dimension and air-entry value, are needed in the presented approach. Detailed procedures for determining the parameters are clearly elaborated. Due to the influence of sample size difference on the equivalent connected pore size, a sample scale effect coefficient is proposed to predict air-entry values. The concept of “critical pore size„ is introduced to obtain the optimal fractal dimension, which can accurately reflect the fractal behaviour of SWCC samples. By comparisons between predicted and experimental SWCCs, the validation of the proposed method is verified. The comparisons reveal the good agreement between the proposed approach and laboratory experiments.

Background and Aims: Crohn’s Disease (CD), a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24) and Saline (n = 24), respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR) to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD) at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6), and dorsal root ganglia (T11) for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05) VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral hypersensitivity, as well as for establishing the therapeutic protocol for Crohn’s ileitis.

Objective. To investigate VIP effect on the cytotoxicity of NK cell to gastric cancer cells in vitro and the relation between the effect with the NKG2D signal molecules in NK cells. Material and Methods. NK cells were purified from peripheral blood mononuclear cells (PBMC). Before and after NK cells were incubated with VIP or its antagonist (D-p-Cl-Phe6,Leu17)-VIP, we detected the cytotoxicity of NK cells to MKN45 gastric cancer cells by MTT and detected the expressions of NKG2D, DAP10, and NF-κB proteins and mRNAs in NK cells by immunocytochemistry and RT-PCR in those conditions. Then we analyzed the effect of VIP and its antagonist on the cytotocicity of NK cell to gastric cancer cells and on expressions of NKG2D, DAP10, and NF-κB signal molecules in NK cells. Results. VIP could inhibit the cytotoxicity of NK cells to MKN45 cells and could inhibit the expressions of NKG2D, DAP10, and NF-κB in NK cells. However, (D-p-Cl-Phe6, Leu17)-VIP could reverse those effects. Conclusions. The VIP inhibited the cytotoxicity of NK cell to MKN45 cells which might get through inhibiting the expressions of NKG2D signal molecules in NK cells. This may be one mechanism of gastric cancer cells escaping organism immune clearance.

Abstract Background A given movement requires precise coordination of multiple muscles under the control of center nervous system. However, detailed knowledge about the changing characteristics of neuromuscular control for multi-muscle coordination in post-stroke hemiplegic patients during standing is still lacking. This study aimed to investigate the hemiplegia-linked neuromuscular dysfunction during standing from the perspective of multi-muscle dynamical coordination by utilizing a novel network approach – weighted recurrence network (WRN). Methods Ten male hemiplegic patients with first-ever stroke and 10 age-matched healthy male adults were instructed to stand on a platform quietly for 30 s with eyes opened and eyes closed, respectively. The WRN was constructed based on the surface electromyography signals of 16 muscles from trunk, hips, thighs and calves. Relevant topological parameters, including clustering coefficient (C) and average shortest path length (L), were extracted to evaluate the dynamical coordination of multiple muscles. A measure of node centrality in network theory, degree of centrality (DC), was innovatively introduced to assess the contribution of single muscle in the multi-muscle dynamical coordination. The standing-related assessment metric, center of pressure (COP), was provided by the platform directly. Results Results showed that the post-stroke hemiplegic patients stood with remarkably higher similarity of muscle activation and more coupled intermuscular dynamics, characterized by higher C and lower L than the healthy subjects (p

Abstract Background The prevalence of dementia is increasing worldwide and many people with the condition require some level of palliative care. However, the trajectories of function and symptom burden in palliative care services at the end of life remain unclear. This study aimed to describe and compare the longitudinal trajectories of function and symptom burden among patients with dementia between hospital versus palliative community care services in the last two weeks of life. Methods A retrospective cohort study used data from the Australian Palliative Care Outcomes Collaboration. Patients with dementia who died between 1 January 2013 and 31 December 2020 from the Australian Palliative Care Outcomes Collaboration. Four validated clinical instruments were used to collect outcomes on each individual’s function and symptom distress and severity. Multilevel models were used to estimate the differences in clinical trajectories between hospital and community-based palliative care in the last two weeks of life. Results Patients with dementia tended to have low levels of distress for most symptoms but increasing levels of functional impairment. There were no or only marginally significant differences in the symptom trajectories between the community and hospital groups (OR ranged from 0.57 to 1.97). Although clinical trajectories of function were relatively similar between two groups, statistically higher functional indicators were observed for people when admitted to community palliative care services (OR = 0.42 and 2.27, respectively). Conclusions Our findings suggest that community-based palliative care services can be as effective as hospital-based care for many patients with dementia nearing the end of life. With appropriate support for families, community-based care could serve as a viable alternative to hospital-based care for some patients in the final stages of dementia.

Abstract Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents’ health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People’s Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43–4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11–2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Abstract Aim To explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes. Methods Twenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables. Results In the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network. Conclusion Unlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients.

Abstract Extracellular vesicles (EVs), especially those derived from stem cells, have emerged as a novel treatment for promoting wound healing in regenerative medicine. However, the clinical application of mammalian cells-derived EVs is hindered by their high cost and low yields. Inspired by the ability of EVs to mediate interkingdom communication, we explored the therapeutic potential of EVs released by the probiotic strain Lactobacillus rhamnosus GG (LGG) in skin wound healing and elucidated the underlying mechanism involved. Using full-thickness skin wound-healing mouse models, we found that LGG-EVs accelerated wound healing procedures, including increased re-epithelialization and promoted angiogenesis. Using in vitro experiments, we further demonstrated that LGG-EVs boosted the proliferation and migration capacities of both epithelial and endothelial cells, as well as promoted endothelial tube formation. miRNA profiling analysis revealed that miR-21-5p was highly enriched in LGG-EVs and LGG-EV treatment significantly increased miR-21-5p level in recipient cells. Mechanically, LGG-EVs induced regulatory effects via miR-21-5p mediated metabolic signaling rewiring. Our results suggest that EVs derived from LGG could serve as a promising candidate for accelerating wound healing and possibly for treating chronic and impaired healing conditions. Graphical abstract

Abstract In response to the challenge of telomere attrition during DNA replication, cancer cells predominantly employ telomerase or, in 10–15% of cases, the alternative lengthening of telomeres (ALT). The intricate details of ALT, however, remain elusive. In this study, we unveil that the knockdown of lamina-associated polypeptide 2 alpha (LAP2α) in ALT cells results in telomere dysfunction, triggering a notable increase in ALT-associated hallmarks, including high frequencies of PML bodies (APBs), C-rich extrachromosomal circles (C-circles), and telomere sister chromatid exchange (T-SCE). Furthermore, LAP2α emerges as a crucial player in break-induced telomere replication for telomerase-positive cells following telomeric double-strand breaks. Mechanistically, our investigation suggests that LAP2α may influence the regulation of the heterochromatic state of telomeres, thereby affecting telomeric accessibility. In line with our findings, LAP2α expression is markedly reduced in ALT-positive osteosarcoma. And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion. This is evidenced by a significant inhibition of tumor proliferation in ALT-positive patient-derived xenograft (PDX) mouse models. These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.

Abstract Background Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis. Methods In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility. Results Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models. Conclusions These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.

ObjectiveTo detect and analyze the contamination of hygiene indicator bacteria in bulk ready-to-eat foods in various regions of Jilin province, providing a reference for the safety supervision of the bulk ready-to-eat food industry in Jilin province. MethodsFrom 2011 to 2021, 5 664 ready-to-eat food samples were collected from 9 regions in Jilin province, including Baicheng city, Baishan city, Jilin city, Liaoyuan city, Siping city, Songyuan city, Tonghua city, Yanbian Korean Autonomous Prefecture, and Changchun city. Four types of hygiene indicator bacteria, including total bacterial count, coliform bacteria, Escherichia coli, and mold, were detected and analyzed. ResultsThe overall pass rate of total bacterial count was 82.19% (3563/4335), the overall pass rate of coliform bacteria was 63.34% (1617/2553), the overall pass rate of Escherichia coli was 96.5% (1655/1715), and the overall pass rate of mold was 72.07% (240/333). Among the 9 monitored cities, Tonghua city had the lowest pass rate of total bacterial count at 58.53% (367/627), with a mean value of (4.41 ± 1.51) lgCFU/g; Baishan city had the lowest pass rate of coliform bacteria at 43.48% (100/230), with a mean value of (3.47 ± 1.34) lgCFU/g; Tonghua city had the lowest pass rate of Escherichia coli at 92.54% (310/335), with a mean value of (2.11 ± 0.87) lgCFU/g; and Songyuan city had the lowest pass rate of mold at 54.17% (13/24), with a mean value of (2.13 ± 1.04) lgCFU/g. Among different types of foods, salads had the lowest pass rate of total bacterial count at 0, with a mean value of (5.70 ± 0.71) lgCFU/g; Chinese-style cold dishes had the lowest pass rate of coliform bacteria at 15.13% (23/152), with a mean value of (3.49 ± 1.08) lgCFU/g; salads had the lowest pass rate of Escherichia coli at 94.34% (150/159), with a mean value of (1.88 ± 0.61) lgCFU/g; and cakes had the lowest pass rate of mold at 32.26% (10/31), with a mean value of (3.08 ± 1.98) lgCFU/g. Among different sampling locations, small restaurants had the lowest pass rate of total bacterial count at 74.74% (494/661), with a mean value of (4.14 ± 1.35) lgCFU/g; The qualified rates of Escherichia coli and Escherichia coli in department stores are the lowest, at 28.95% (11/38) and 80.00% (4/5), respectively. The average value of Escherichia coli is (4.06 ± 1.21) lgCFU/g, and the number of positive samples for Escherichia coli is 2.04 lgCFU/g; and convenience stores had the lowest pass rate of mold at 53.33% (24/45), with a mean value of (2.41 ± 1.00) lgCFU/g. ConclusionThe contamination levels of hygiene indicator bacteria in bulk ready-to-eat foods that do not undergo a final heating step, such as raw foods, cold dishes, and filled foods, are relatively high in different regions of Jilin province and should be prioritized for prevention. Small and medium-sized restaurants, fast food restaurants, and department stores have higher contamination rates of hygiene indicator bacteria and require focused supervision and management.