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This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P

Abstract Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage‐associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti‐inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis‐associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time‐polymerase chain reaction (qRT‐PCR), immunofluorescent staining, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS‐induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5‐lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro‐inflammatory factors, that is, interleukin‐6 and tumor necrosis factor‐α (IL‐6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5‐mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Effects of pre-treatment (either pre-deformation or composed of pre-aging and pre-deformation prior to aging) on the dislocation morphologies and subsequent precipitation, corrosion behaviors, and mechanical properties of a novel Al-8.26Zn-1.95Mg-1.89Cu-0.08Sc-0.17Zr (wt.%) alloy were investigated. Pre-existing Al3(Sc, Zr) dispersoids can pin dislocations induced by pre-deformation before aging to form dislocation cells and cell walls. As a result, bimodal microstructures are formed during the subsequent aging process, with coarse precipitates dispersed along dislocation walls and fine precipitates inside dislocation cells. Meanwhile, dislocations pinned by Al3(Sc, Zr) dispersoids nearby grain boundaries inhibit the diffusion of solutes towards grain boundaries, which can modify grain boundary features by decreasing the potential difference between grain boundaries and grain interiors, and reducing precipitation-free zone width and grain boundary precipitate size. In particular, pre-aging prior to pre-deformation makes the dislocation distribution more uniform, which increases the volume fraction of nanoprecipitates without significant coarsening and further improves the grain boundary characteristics. Compared with the traditional T74 treated sample, these multiple microstructures significantly enhance the corrosion resistance of the alloy with less strength degradation. This study offers novel insights into the strengthening and corrosion mechanisms of pre-treated Al–Zn–Mg–Cu alloys with Zr and Sc microalloying.

Introduction: Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysis: In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.

【Objective】The aim of this study was to elucidate the effect of associated chives on bacterial wilt and microecological characteristics of tomato rhizosphere, and to reveal the mechanism of reducing incidence of tomato bacterial wilt.【Method】Two treatments of tomato monoculture and tomatoes with chives were set for field experiments, and rhizosphere soils of diseased tomatoes in tomato monoculture treatment (QK), healthy tomatoes in tomato monoculture treatment (NBS) and tomatoes with chives treatment (BS) were collected. And the effects of companion chives on the micro-ecological characteristics of tomato rhizosphere were investigated by using 16S rDNA high-throughput sequencing and liquid chromatography-mass spectrometry.【Result】The results of field experiments showed that the average disease incidence of tomato bacterial wilt were 50.48% in tomato monoculture treatment and 31.43% in companion chives treatment. The control effect of companion chives on tomato bacterial wilt was 37.74%. According to the resulyts of 16S rDNA high-throughput sequencing, the relative abundance and diversity of bacterial communities in the rhizosphere soils of BS and NBS were significantly higher than those of QK. Compared with QK, the relative abundance of Ralstonia in the rhizosphere soils of BS and NBS was significantly lower than that of QK, and the relative abundance of Bacillus was higher than that of QK. Moreover, compared with NBS, the relative abundance of Ralstonia in the rhizosphere soil of BS was reduced, and the relative abundance of Bacillus was significantly enhanced. A total of 586 metabolites in tomato rhizosphere soil were identified by using LC-MS, including 320 positive ion mode metabolites and 266 negative ion mode metabolites. The functions of metabolites were annotated to metabolic pathways such as metabolism, genetic information processing and environmental information processing. Compared with NBS, the contents of valine, L-asparagine and citric acid in BS rhizosphere soil were significantly lower than those in NBS, and the contents of L-lysine, glutamic acid, D-glutamine and isoleucine in rhizosphere soil of BS were also lower than those of NBS, though, the difference was not significant.【Conclusion】The companion chives significantly reduced the disease incidence of tomato bacterial wilt in the field, and changed the bacterial community structure and metabolite contents in tomato rhizosphere soil.

Abstract Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Apricot fruit is highly susceptible to infection by pathogenic fungi. In this study, the pathogenic fungi in the diseased parts of the fruits of ‘Golden Sun’ and ‘Red almond’ apricot (Prunus armeniaca L.) during postharvest storage were isolated and purified, and the purified strains were inoculated back to the healthy fruits of corresponding varieties, showing the same disease symptoms as the diseased fruits. Five fungi isolates were identified based on morphological characteristics and internal transcribed spacer (ITS) sequence analysis combined with construction of phylogenetic tree. Three isolates from ‘Golden Sun’ apricot were identified as Diaporthe eres (325#), Botryosphaeria dothidea (327#) and Aureobasidium pullulans (328#). Two isolates from ‘Red almond’ apricot were identified as Botrytis elliptica (326#) and Botrytis cinerea (331#). D. eres, B. dothidea, A. pullulans and B. elliptica were pathogenic fungi that had not been reported in the literature on apricot fruits, whereas B. cinerea had not been reported on the infection of ‘Red almond’ apricot. The present results provided references for the biological control measures of apricot fruits.

Microbial communities during winemaking are diverse and change throughout the fermentation process. Microorganisms not only drive alcohol fermentation, flavor and aroma, but also enhance wine functional components such as extraction of polyphenols from the berries, production of γ-aminobutyric acid, hydroxytyrosol and melatonin. Polyphenols such as resveratrol, catechin and quercetin determine the functional quality of the wine. Moderate wine consumption, particularly red wine has been associated with functional benefits to human health, which includes anti-inflammation, promoting healthy aging, prevention of cardiovascular diseases, cancers, type 2 diabetes and metabolic syndrome. Indeed, the management of microbiota allows the production of wine with distinct features and functional components that benefits human health. This review scrutinizes the possible contributions of wine microbiota to the production of wine with enhanced functional components and highlights the contributions of Saccharomyces and non-Saccharomyces yeasts and bacteria to enhance wine functional components during winemaking. Thus, contributing to the dissemination of the benefits of light to moderate wine intake to human health.

Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1β, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role and mechanism of HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover the beneficial effects of HT and its detailed mechanism in UC. Experimental colitis was induced by 2.5% dextran sodium sulfate (DSS) for seven days. HT ameliorated DSS-induced colitis in mice, showing marked improvement in weight loss, colon length, colonic pathological severity, and the levels of TNFα and IL6 in serum. A combination of informatics, network pharmacology, and molecular docking identified eight key targets and multi-pathways influenced by HT in UC. As a highlight, the experimental validation demonstrated that PTGS2, a marker of ferroptosis, along with other indicators of ferroptosis (such as ACSL4, Gpx4, and lipid peroxidation), were regulated by HT in vivo and in vitro. Additionally, the supplement of HT increased the diversity of gut microbiota, decreased the relative abundance of Proteobacteria and Gammaproteobacteria, and restored beneficial bacteria (Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001). In conclusion, HT is an effective nutritional supplement against experimental colitis by suppressing ferroptosis and modulating gut microbiota.

ABSTRACTFerroptosis is a distinctive form of iron-dependent necrotic cell death, characterized by excessive lipid peroxidation on cellular membranes and compromised cellular antioxidant defenses. Multiple metabolic pathways, including iron and lipid metabolism, as well as antioxidant systems, contribute to the execution of ferroptosis. The gut microbiota exerts regulatory effects on ferroptosis through its microbial composition, biological functions, and metabolites. Notably, most pathogenic bacteria tend to promote ferroptosis, thereby inducing or exacerbating diseases, while most probiotics have been shown to protect against cell death. Given microbiota colonization in the gut, an intimate association is found between intestinal diseases and microbiota. This review consolidates the essential aspects of ferroptotic processes, emphasizing key molecules and delineating the intricate interplay between gut microbiota and ferroptosis. Moreover, this review underscores the potential utility of gut microbiota modulation in regulating ferroptosis for the treatment of intestinal diseases.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L−1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L−1), phycoerythrin (102.95 mg L−1), and polysaccharide (1.42 g L−1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

BackgroundAdherent–invasive E. coli (AIEC) LF82 is capable of adhering to and invading intestinal epithelial cells, as well as replicating within macrophages without inducing host cell death.MethodsWe compared the transcriptomics of LF82 at pH=7.5 and pH=5.8 by RNA-sequencing, and qRT-PCR verified differentially expressed genes (DEGs). The deletion mutants of DEGs in the treatment group (pH=5.8) compared to the control group (pH=7.5) were constructed by λ recombinant. The replication differences between the mutants and WT infected Raw 264.7 at 24 h.p.i were analyzed by combining LB solid plate count and confocal observation. NH4Cl and chloroquine diphosphate (CQ) were used for acid neutralization to study the effect of pH on the replication of LF82 in macrophages. Na2NO3 was added to RPMI 1640 to study the effect of nitrate on the replication of LF82 in macrophages. 0.3% solid LB was used for flagellar motility assay and Hela was used to study flagellar gene deletion mutants and WT adhesion and invasion ability.ResultsIn this study, we found that infection with LF82 results in acidification of macrophages. Subsequent experiments demonstrated that an intracellular acidic environment is necessary for LF82 replication. Transcriptome and phenotypic analysis showed that high expression of acid shock genes and acid fitness genes promotes LF82 replication in macrophages. Further, we found that the replication of LF82 in macrophages was increased under nitrate treatment, and nitrogen metabolism genes of LF82 were upregulated in acid treatment. The replication in macrophages of ΔnarK, ΔnarXL, ΔnarP, and Δhmp were decreased. In addition, we found that the expression of flagellar genes was downregulated in acidic pH and after LF82 invading macrophages. Motility assay shows that the movement of LF82 on an acidic semisolid agar plate was limited. Further results showed that ΔfliC and ΔfliD decreased in motility, adhesion ability, and invasion of host cells, but no significant effect on replication in macrophages was observed.ConclusionIn this study, we simulated the acidic environment in macrophages, combined with transcriptome technology, and explained from the genetic level that LF82 promotes replication by activating its acid shock and fitness system, enhancing nitrate utilization, and inhibiting flagellar function.

The genetic basis of spider major ampullate (Ma) gland silk production remains unknown. Hu et al. unveil a molecular atlas of this gland for the golden orb-weaving spider combining genome assembly and multiomics, revealing the single-cell spatial architecture of silk production in the Ma gland.

PURPOSEEarly monitoring and intervention for patients with novel coronavirus disease-2019 (COVID-19) will benefit both patients and the medical system. Chest computed tomography (CT) radiomics provide more information regarding the prognosis of COVID-19.METHODSA total of 833 quantitative features of 157 COVID-19 patients in the hospital were extracted. By filtering unstable features using the least absolute shrinkage and selection operator algorithm, a radiomic signature was built to predict the prognosis of COVID-19 pneumonia. The main outcomes were the area under the curve (AUC) of the prediction models for death, clinical stage, and complications. Internal validation was performed using the bootstrapping validation technique.RESULTSThe AUC of each model demonstrated good predictive accuracy [death, 0.846; stage, 0.918; complication, 0.919; acute respiratory distress syndrome (ARDS), 0.852]. After finding the optimal cut-off for each outcome, the respective accuracy, sensitivity, and specificity were 0.854, 0.700, and 0.864 for the prediction of the death of COVID-19 patients; 0.814, 0.949, and 0.732 for the prediction of a higher stage of COVID-19; 0.846, 0.920, and 0.832 for the prediction of complications of COVID-19 patients; and 0.814, 0.818, and 0.814 for ARDS of COVID-19 patients. The AUCs after bootstrapping were 0.846 [95% confidence interval (CI): 0.844–0.848] for the death prediction model, 0.919 (95% CI: 0.917–0.922) for the stage prediction model, 0.919 (95% CI: 0.916–0.921) for the complication prediction model, and 0.853 (95% CI: 0.852–0.0.855) for the ARDS prediction model in the internal validation. Based on the decision curve analysis, the radiomics nomogram was clinically significant and useful.CONCLUSIONThe radiomic signature from the chest CT was significantly associated with the prognosis of COVID-19. A radiomic signature model achieved maximum accuracy in the prognosis prediction. Although our results provide vital insights into the prognosis of COVID-19, they need to be verified by large samples in multiple centers.

Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, causes diarrheal illness and gastrointestinal diseases. S. Typhimurium survives and replicates in phagocytic and non-phagocytic cells for acute or chronic infections. In these cells, S. Typhimurium resides within Salmonella-containing vacuoles (SCVs), in which the phosphate (Pi) concentration is low. S. Typhimurium senses low Pi and expresses virulence factors to modify host cells. However, the mechanism by which host cells reduce the Pi concentration in SCVs is not clear. In this study, we show that through the TLR4-MyD88-NF-κB signaling pathway, S. Typhimurium upregulates PIT1, which in turn transports Pi from SCVs into the cytosol and results in Pi starvation in SCVs. Immunofluorescence and western blotting analysis reveal that after the internalization of S. Typhimurium, PIT1 is located on SCV membranes. Silencing or overexpressing PIT1 inhibits or promotes Pi starvation, Salmonella pathogenicity island-2 (SPI-2) gene expression, and replication in SCVs. The S. Typhimurium ΔmsbB mutant or silenced TLR4-MyD88-NF-κB pathway suppresses the expression of the SPI-2 genes and promotes the fusion of SCVs with lysosomes. Our results illustrate that S. Typhimurium exploits the host innate immune responses as signals to promote intracellular replication, and they provide new insights for the development of broad-spectrum therapeutics to combat bacterial infections.

Mega land reclamation projects have been carried out on the coral reefs in the South China Sea. Coral sand was used as a backfill material through hydraulic filling, with fill heights ranging from 6 to 10 m. To enhance foundation stability, vibro-flotation and impact rolling have been employed. However, the uneven distribution of coral sand, irregular particle shape, lower single-particle strength, and paucity of engineering cases for reference have posed challenges in evaluating the effectiveness of these foundation treatments. In this study, the effectiveness of vibro-flotation and impact rolling on the densification and bearing capacity of coral sand foundations has been investigated. In situ tests, including the plate load test, California Bearing Ratio (CBR) test, density measurements, dynamic penetration test (DPT), and settlement monitoring, were conducted at four distinct zones: an untreated zone, a vibro-flotation zone at a 5 m depth, a vibro-flotation zone at a 10 m depth, and an impact rolling zone. The findings suggest that coral sand exhibits promising characteristics for foundation construction. Seepage and self-weight consolidation following land reclamation formation significantly enhance the compaction degree of the coral sand foundation, thereby meeting the requirements for areas with lower bearing capacity demands. Both vibro-flotation and impact rolling techniques could significantly enhance the foundation-bearing capacity, with marginal differences between them. Since the machinery is simple and construction speed is quick, the impact rolling method is considered to be the most efficient for the treatment of coral sand foundation. The DPT results suggest that the reinforcement effect of both vibro-flotation and impact rolling on the deep foundation is not as substantial as the surface layers. This study provides valuable insights into optimizing foundation treatments for land reclamation projects on the coral reefs.

ABSTRACTAdherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn’s disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

ABSTRACTMitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells’ mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

Abstract Objective This study explored the feasibility of mesoplasty with end-to-side anastomosis in the treatment of different apple-peel mesenteric defects with high jejunal atresia. Methods A retrospective analysis was performed on 42 premature infants admitted to the hospital between 2014 and 2021. Prenatal ultrasound scans revealed bowel dilatation. The patients experienced vomiting after birth and produced white or no meconium. Plain radiography showed double or triple bubble signs and the patients underwent emergency laparotomy. High jejunal atresia with different apple-peel atresia appearance was discovered intraoperatively, involving mobilization of the ileocecal region. Patients received end-to-side anastomosis between the enlarged blind pouch and atretic bowel, as well as mesoplasty. A jejunal feeding tube was placed trans-nasally. Patients were discharged after achieving full enteral feeding. We also reviewed the literature on the subject. Results Three patients died and 39 survived. The discharged patients were followed up for 12 months, and none showed post-operative complications such as intestinal obstruction, malnutrition, or chronic diarrhea. All surviving patients reached the expected height and weight for children of the same age. Conclusion For cases of high jejunal atresia with apple-peel intestinal atresia, mesoplasty may be a good option to avoid postoperative volvulus.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy. First-line treatments for CIDP include corticosteroids, intravenous immunoglobulin, and plasma exchange. However, the application is always limited by high costs, effectiveness, and adverse events. This study investigated a new potentially effective and safe therapeutic treatment to alleviate CIDP symptoms and improve the quality of life. In the present case, a 47-year-old rural woman presented with weakness and numbness of progressive extremities. She was diagnosed with CIDP based on abnormal cerebrospinal fluid and electromyography. The patient was treated with intravenous dexamethasone for 1 week and with Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions for 90 days. Surprisingly, after the treatment, the weakness and numbness were eliminated, and the quality of life improved. The varying INCAT, MRC, and BI scores also reflected the treatment effects. After 8 months of discharge, the symptoms did not relapse during the follow-up. We also searched “traditional Chinese medicine (TCM)” and “CIDP” in PubMed, EMBASE, the Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases, Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database. Finally, only ten studies were included in the literature review. Three studies were randomized controlled trials, and seven were case reports or case series. There were 419 CIDP patients, but all study sites were in China. Nine TCM formulas involving 44 herbs were reported, with Huang Qi (Astragalus membranaceus) being the most important herb. In conclusion, the case and literature demonstrated that TCM treatment might be a more effective, low-cost, and safe option for treating CIDP. Although these preliminary findings are promising, a larger sample size and higher-quality randomized clinical trials are urgently required to confirm our findings.

Abstract Background Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1), the ligase of the UFMylation system, has recently been reported to be involved in apoptosis and endoplasmic reticulum stress (ER stress) in a variety of diseases. Premature ovarian failure (POF) is a gynecological disease that severely reduces the fertility of women, especially in female cancer patients receiving chemotherapy drugs. Whether UFL1 is involved in protection against chemotherapy-induced POF and its mechanism remain unclear. Methods In this study, we examined the function of UFL1 in ovarian dysfunction and granulosa cell (GC) apoptosis induced by cisplatin through histological examination and cell viability analysis. We used western blotting, quantitative real-time PCR (qPCR) and immunofluorescence (IF) to detect the expression of UFL1 and the levels of ER stress specific markers. Enzyme linked immunosorbent assays were used to detect the levels of follicle-stimulating hormone (FSH) and estrogen (E2) in ovaries and GCs. In addition, we used infection with lentiviral particle suspensions to knock down and overexpress UFL1 in ovaries and GCs, respectively. Results Our data showed that the expression of UFL1 was reduced in POF model ovaries, accompanied by ER stress. In vitro, cisplatin induced a stress-related increase in UFL1 expression in GCs and enhanced ER stress, which was aggravated by UFL1 knockdown and alleviated by UFL1 overexpression. Furthermore, UFL1 knockdown resulted in a decrease in ovarian follicle number, an increase in atretic follicles, and decreased expression of AMH and FSHR. Conversely, the overexpression of UFL1 reduced cisplatin-induced damage to the ovary in vitro. Conclusions Our research indicated that UFL1 regulates cisplatin-induced ER stress and apoptosis in GCs, and participates in protection against cisplatin-induced POF, providing a potential therapeutic target for the clinical prevention of chemotherapeutic drug-induced POF. Graphical Abstract

Abstract Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti‐oxidative, anti‐apoptotic, and anti‐inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H2O2) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H2O2‐induced damage at 100 μM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD‐like receptor protein‐3‐mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP‐activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo.

Cantharellus cibarius, an ectomycorrhizal fungus belonging to the Basidiomycetes, has significant medicinal and edible value, economic importance, and ecological benefits. However, C. cibarius remains incapable of artificial cultivation, which is thought to be due to the presence of bacteria. Therefore, much research has focused on the relationship between C. cibarius and bacteria, but rare bacteria are frequently overlooked, and symbiotic pattern and assembly mechanism of the bacterial community associated with C. cibarius remain unknown. In this study, the assembly mechanism and driving factors of both abundant and rare bacterial communities of C. cibarius were revealed by the null model. The symbiotic pattern of the bacterial community was examined using a co-occurrence network. Metabolic functions and phenotypes of the abundant and rare bacteria were compared using METAGENassist2, and the impacts of abiotic variables on the diversity of abundant and rare bacteria were examined using partial least squares path modeling. In the fruiting body and mycosphere of C. cibarius, there was a higher proportion of specialist bacteria compared with generalist bacteria. Dispersal limitation dominated the assembly of abundant and rare bacterial communities in the fruiting body and mycosphere. However, pH, 1-octen-3-ol, and total phosphorus of the fruiting body were the main driving factors of bacterial community assembly in the fruiting body, while available nitrogen and total phosphorus of the soil affected the assembly process of the bacterial community in the mycosphere. Furthermore, bacterial co-occurrence patterns in the mycosphere may be more complex compared with those in the fruiting body. Unlike the specific potential functions of abundant bacteria, rare bacteria may provide supplementary or unique metabolic pathways (such as sulfite oxidizer and sulfur reducer) to enhance the ecological function of C. cibarius. Notably, while volatile organic compounds can reduce mycosphere bacterial diversity, they can increase fruiting body bacterial diversity. Findings from this study further, our understanding of C. cibarius-associated microbial ecology.

In order to find out the contamination of mycotoxins in Triticeae crops of Qinghai-Tibet Plateau, a total of 153 Triticeae crop fruits were collected as target samples, and 22 mycotoxins were tested. High detection rate was found in the Alternaria mycotoxins, including tentoxin (TEN), tenuazonic acid (TEA) and alternariol (AOH) toxins. To further clarify the production rules of Alternaria mycotoxins. A number of 9 high yield toxic strains were selected from 65 bacterial strains and the gene sequences of each were determined. The nine selected Alternaria alternate were cultured under specific pH of the culture medium, temperature and ultraviolet (UV) irradiation, and their growth and toxicity were analyzed. The results showed that the toxic capacity of most A. alternate increased with the increase of culture environment temperature and decreased with the increase of UV irradiation. However, the production of some toxins did not meet this principle, or even met the principle of relativity. In the culture experiments, a total of five Alternaria toxins were detected as positive, which were TEN, AOH, alternariol monomethyl ether (AME), TEA, and Alternaria (ALT). The altenusin (ALS) toxin was not detected in the metabolites of the nine Alternaria strains. It indicated that the TEN, AOH, AME, TEA, and ALT toxins should be particularly valued in the future risk assessments. This finding provided comprehensive information of mycotoxins contamination in the Tibetan Plateau Triticeae crops, it pointed out a direction to the Tibetan Plateau food crops’ quality control.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen that causes a variety of diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. Flagellum-dependent motility plays diverse roles in the pathogenesis of EHEC O157:H7, including its migration to an optimal host site, adherence and colonization, survival at the infection site, and post-infection dispersal. However, it is very expensive for cellular economy in terms of the number of genes and the energy required for flagellar biosynthesis and functioning. Furthermore, the flagellar filament bears strong antigenic properties that induce a strong host immune response. Consequently, the flagellar gene expression and biosynthesis are highly regulated to occur at the appropriate time and place by different regulatory influences. The present review focuses on the regulatory mechanisms of EHEC O157:H7 motility and flagellar biosynthesis, especially in terms of flagellar gene regulation by environmental factors, regulatory proteins, and small regulatory RNAs.

Summary: Electrophoretic mobility shift assay (EMSA) is a classical and popular approach for DNA/RNA protein-binding affinity detection in vitro. This protocol describes a competitive EMSA assay using digoxigenin (DIG)-labeled probe, which solves the safety issues and limitations attributed to the short lifespan of the 32P-radiolabeled DNA probe. We detail steps for DNA probe preparation, protein-DNA mixture coincubation, EMSA, and competitive EMSA process. We optimize the standard DIG-ddUTP-labeling EMSA protocol to high sensitivity with reproducible results.For complete details on the use and execution of this protocol, please refer to Feng et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Due to their unique biochemical and spectroscopic properties, both heme and phycocyanobilin are widely applied in the medical and food industries. Synechocystis sp. PCC 6803 contains both heme and phycocyanin, and is capable of synthesizing phycocyanin using heme as a precursor. The aim of this study was to uncover viable metabolic targets in the porphyrin pathway from Synechocystis sp. PCC 6803 to promote the accumulation of heme and phycocyanin in the recombinant strains of microalgae. A total of 10 genes related to heme synthesis pathway derived from Synechococcus elongatus PCC 7942 and 12 genes related to endogenous heme synthesis were individually overexpressed in strain PCC 6803. The growth rate and pigment content (heme, phycocyanin, chlorophyll a and carotenoids) of 22 recombinant algal strains were characterized. Quantitative real-time PCR technology was used to investigate the molecular mechanisms underlying the changes in physiological indicators in the recombinant algal strains. Among the 22 mutant strains, the mutant overexpressing the haemoglobin gene (glbN) of strain PCC 6803 had the highest heme content, which was 2.5 times higher than the wild type; the mutant overexpressing the gene of strain PCC 7942 (hemF) had the highest phycocyanin content, which was 4.57 times higher than the wild type. Overall, the results suggest that genes in the porphyrin pathway could significantly affect the heme and phycocyanin content in strain PCC 6803. Our study provides novel crucial targets for promoting the accumulation of heme and phycocyanin in cyanobacteria.

This study aimed to investigate the effects of dietary supplementation of the new single-cell protein Clostridium autoethanogenum protein (CAP) on growth performance, plasma biochemical indexes, liver histology, lipid metabolism, and gut microbiota in Cobb broilers. According to the randomized block experimental design, 960 Cobb broilers (1d old) were divided into six treatments with eight replicates of 20 birds each. Six isonitrogenous and isoenergetic diets were formulated with different contents of CAP (0, 1, 2, 3, 4, and 5%) to replace soybean meal (SBM). The results showed that the addition of CAP did not influence liver health when it exceeded 2%. The protein metabolism markers and feed conversion rate increased (P < 0.05), significantly improving the growth performance. When the content of CAP was greater than 4%, it could promote lipolysis without affecting lipogenesis, decreasing the abdominal fat rate. There was no significant difference in MDA between these groups (P = 0.948). The increase of SOD and GSH-Px indicated the enhancement of antioxidant response. Alpha diversity did not significantly differ between groups (P > 0.05). Inclusion of 4% or less CAP led to the increase in beneficial microbiota, the concentration of short-chain fatty acids (SCFAs) such as acetic acid, propionic acid, and butyric acid (P < 0.05), and the concentration of primary bile acids such as cholic acid and goose deoxycholic acid (P < 0.05). While the concentration of secondary bile acids such as taurocholic acid and taurine goose deoxycholic acid was decreased (P < 0.05). These results illustrated that the CAP had a high potential for application in poultry nutrition. In terms of improving growth performance and antioxidant capacity and reducing fat deposition rate, 4% CAP content is recommended.

IntroductionAs a pigment protein, phycocyanin has been widely used in the fields of food, nutraceutical and biotechnology due to its excellent biological activities of antioxidant. So far, Arthrospira has been generally considered as a great species for phycocyanin production.MethodsIn this study, independent and interactive effect of three factors, NaCl, Bainengsi (BS) and Bainengtai (BT) on microalgae growth and phycocyanin production were explored by response surface methodology (RSM). Using Box-Behnken design (BBD) method, the well-fitting quadratic models were established based on experimental results.ResultsMoreover, the maximum phycocyanin concentration reached 704.66 mg L-1 at the optimal condition (185 mM NaCl, 200 mg L-1 BS, and 20 mg L-1 BT), while the maximum phycocyanin content of 19.03% was obtained at another optimal condition (136 mM NaCl, 200 mg L-1 BS, and 50 mg L-1 BT). Compared to control, the concentration and content of phycocyanin were increased by 22.98% and 16.73%, respectively.DiscussionOverall, this study demonstrated that addition of exogenous substances (BS, BT) into culture medium optimized by RSM was an effective approach to increase phycocyanin production, which paved a potential way to realizing high efficient production of algal biomass and bioactive substances.

ObjectiveTo investigate the association between diffusion tensor imaging (DTI) findings and domain-specific cognitive impairment in cerebral small vessel disease (CSVD).MethodsDatabases such as PubMed, Excerpta Medical Database (EMBASE), Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang, Chinese Biomedical Literature Database (SinoMed), and Chongqing Chinese Science and Technology Periodical Database (VIP) were comprehensively retrieved for studies that reported correlation coefficients between cognition and DTI values. Random effects models and meta-regression were applied to account for heterogeneity among study results. Subgroup and publication bias analyses were performed using Stata software.ResultsSeventy-seven studies involving 6,558 participants were included in our meta-analysis. The diagnosis classification included CSVD, white matter hyperintensities (WMH), subcortical ischemic vascular disease, cerebral microbleeding, cerebral amyloid angiopathy (CAA), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Fabry disease. The pooled estimates showed that the fractional anisotropy (FA)-overall exhibited a moderate correlation with general cognition, executive function, attention, construction, and motor performance (r = 0.451, 0.339, 0.410, and 0.319), and the mean diffusitivity/apparent diffusion coefficient (MD/ADC)-overall was moderately associated with general cognition, executive function, and memory (r = −0.388, −0.332, and −0.303, respectively; ps < 0.05). Moreover, FA in cingulate gyrus (CG), cerebral peduncle (CP), corona radiata (CR), external capsule (EC), frontal lobe (FL), fornix (FOR), internal capsule (IC), and thalamic radiation (TR) was strongly correlated with general cognition (r = 0.591, 0.584, 0.543, 0.662, 0.614, 0.543, 0.597, and 0.571), and a strong correlation was found between MD/ADC and CG (r = −0.526), normal-appearing white matter (NAWM; r = −0.546), and whole brain white matter (WBWM; r = −0.505). FA in fronto-occipital fasciculus (FOF) (r = 0.523) and FL (r = 0.509) was strongly associated with executive function. Only MD/ADC of the corpus callosum (CC) was strongly associated with memory (r = −0.730). Besides, FA in CG (r = 0.532), CC (r = 0.538), and FL (r = 0.732) was strongly related to the attention domain. Finally, we found that the sample size, etiology, magnetic resonance imaging (MRI) magnet strength, study type, and study quality contributed to interstudy heterogeneity.ConclusionLower FA or higher MD/ADC values were related to more severe cognitive impairment. General cognition and executive function domains attracted the greatest interest. The FL was commonly examined and strongly associated with general cognition, executive function, and attention. The CC was strongly associated with memory and attention. The CG was strongly related to general cognition and attention. The CR, IC, and TR were also strongly related to general cognition. Indeed, these results should be validated in high-quality prospective studies with larger sample sizes.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021226133.

Spinal infection is a rarely occurred pathology, whose diagnosis remains a major challenge due to the low sensitivity of culturing techniques. Metagenomic next-generation sequencing (mNGS) is a novel approach to identify the pathogenic organisms in infectious diseases. In this study, mNGS technology was adopted for pathogenic detection in spinal infection from the tissue and pus samples. Additionally, the diagnostic performance of mNGS for spinal infection was evaluated, by comparing it with that of the conventional microbial culture, with the histopathological results as the gold standard. Overall, 56 samples from 38 patients were enrolled for mNGS testing, and 69 samples were included for microbial culture. 30 patients (78.95%) were identified to be positive by the mNGS method, which was higher than that of microbial culture (17, 44.74%). The sensitivity and specificity of mNGS with pus samples were 84.2% and 100.0%, respectively, which outperformed those of microbial culture (42.1% and 100.0%). The pathogen identification results were applied to medication guidance, and all 38 patients experienced favorable outcomes at three months, followed-up post-treatment, without any adverse effects. These findings proved that mNGS was superior to microbial culture in pathogenic identification of the spinal infection, thereby showing great promise in guiding drug administration and improving clinical outcomes.

Introduction: Stroke is the first leading cause of mortality and disability worldwide, and post-stroke spasticity (PSS) is the common complication of stroke. Sangdantongluo Granule (Z20210481000), a modern patent Chinese medicine, is widely used in clinical practice to treat PSS. Whereas, there is limited evidence of effectiveness for Sangdantongluo Granule to treat PSS. This study will evaluate the clinical efficacy and safety of Sangdantongluo granule in the treatment of PSS. Methods: and Analysis This multicenter, randomized, double-blind and placebo-controlled study will recruit 132 participants in China who develops PSS 15 days–90 days after stroke. Participants will be randomly assigned in an equal ratio to receive either Sangdantongluo granule or placebo for 2 months twice a day orally. The primary measure is the Modified Ashworth Scale (MAS), Secondary outcome measures include Composite Spasticity Scale (CSS), Simplified Fugl-Meyer Motor Scale (S-FM), National Institute of Health stroke scale (NIHSS), Modified Rankin Scale (mRS), Modified Barther Index (MBI), and Surface electromyography. Adverse events will be supervised throughout the trial. SPSS V. 26.0 statistical software will be used for statistical analysis. Enrolment will be started in April 2022. Ethics and dissemination: The trial and protocol were approved by the Ethics Committee of Hunan Academy of Chinese Medicine Affiliated Hospital (No. [202102]20). We will report the results of this trial in a peer-reviewed journal. Trial registration: ClinicalTrials.gov ChiCTR2100044544. Registered on 23 March 2021.

Purpose: To investigate the impact of different baseline characteristics on the efficacy of immune checkpoint inhibitors (ICIs) for advanced lung cancer.Methods: In order to identify eligible randomized controlled trials (RCTs), a systematic search was conducted in PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases. The primary outcomes were hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). To explore the potential interaction during the administration of ICI, patients were stratified by baseline characteristics.Results: The meta-analysis included 24 RCTs. ① Compared with non-ICI therapy, patients with lung cancer benefitted more from immunotherapy (HR, 0.78; p < 0.0001). ② Patients without liver metastases could get more survival benefits than those with liver metastases (HR, 1.20; p = 0.0139). Similar outcomes were also observed in the following subgroups: small-cell lung cancer (HR, 1.20; p = 0.0433), subsequent line (HR, 1.40; p = 0.0147), and ICI monotherapy (HR, 1.40; p = 0.0147). ③ Subgroup analysis showed that tumor type affected the efficacy of immunotherapy in patients with brain metastases (HR, 0.72 vs. 1.41; interaction, p < 0.01). Among patients with smoking history (HR, 0.87 vs. 1.23; interaction, p = 0.05) and brain metastases (HR, 0.69 vs. 1.21; interaction, p = 0.05), the type of therapy (i.e., monotherapy or combination therapy) had potential influences on the efficacy of immunotherapy.Conclusion: Some critical baseline characteristics could indicate the efficacy of ICI therapy. Liver metastasis status could predict the efficacy of ICI therapy for lung cancer. Compared with small-cell lung cancer, patients with brain metastases might have durable OS in non-small-cell lung cancer. The smoking history or brain metastasis status of patients could indicate the potential clinical benefits of monotherapy or combination therapy.

This study proposed a gait recognition method based on the deep neural network of surface electromyography (sEMG) signals to improve the stability and accuracy of gait recognition using sEMG signals of the lower limbs. First, we determined the parameters of time domain features, including the mean of absolute value, root mean square, waveform length, the number of zero-crossing points of the sEMG signals after noise elimination, and the frequency domain features, including mean power frequency and median frequency. Second, the time domain feature and frequency domain feature were combined into a multi-feature combination. Then, the classifier was trained and used for gait recognition. Finally, in terms of the recognition rate, the classifier was compared with the support vector machine (SVM) and extreme learning machine (ELM). The results showed the method of deep neural network (DNN) had a better recognition rate than that of SVM and ELM. The experimental results of the participants indicated that the average recognition rate obtained with the method of DNN exceeded 95%. On the other hand, from the statistical results of standard deviation, the difference between subjects ranged from 0.46 to 0.94%, which also proved the robustness and stability of the proposed method.

Medicinal plants are inhabited by diverse microbes in every compartment, and which play an essential role in host growth and development, nutrient absorption, synthesis of secondary metabolites, and resistance to biological and abiotic stress. However, the ecological processes that manage microbiota assembly and the phenotypic and metabolic characteristics of the core microbiota of Eucommia ulmoides remain poorly explored. Here, we systematically evaluated the effects of genotypes, compartment niches, and environmental conditions (climate, soil nutrition, and secondary metabolites) on the assembly of rhizosphere soil and bark associated bacterial communities. In addition, phenotypic and metabolic characteristics of E. ulmoides core microbiota, and their relationship with dominant taxa, rare taxa, and pharmacologically active compounds were deciphered. Results suggested that microbiota assembly along the two compartments were predominantly shaped by the environment (especially pH, relative humidity, and geniposide acid) and not by host genotype or compartment niche. There were 690 shared genera in the rhizosphere soil and bark, and the bark microbiota was mainly derived from rhizosphere soil. Core microbiota of E. ulmoides was a highly interactive “hub” microbes connecting dominant and rare taxa, and its phenotypic characteristics had a selective effect on compartment niches. Metabolic functions of the core microbiota included ammonia oxidation, nitrogen fixation, and polyhydroxybutyrate storage, which are closely related to plant growth or metabolism. Moreover, some core taxa were also significantly correlated with three active compounds. These findings provide an important scientific basis for sustainable agricultural management based on the precise regulation of the rhizosphere soil and bark microbiota of E. ulmoides.

Diffusion tensor imaging (DTI) is a relatively novel magnetic resonance-based imaging methodology that can provide valuable insight into the microstructure of white matter tracts of the brain. In this paper, we evaluated the reliability and reproducibility of deriving a semi-automated pseudo-atlas DTI tractography method vs. standard atlas-based analysis alternatives, for use in clinical cohorts with neurodegeneration and ventriculomegaly. We showed that the semi-automated pseudo-atlas DTI tractography method was reliable and reproducible across different cohorts, generating 97.7% of all tracts. However, DTI metrics obtained from both methods were significantly different across the majority of cohorts and white matter tracts (p < 0.001). Despite this, we showed that both methods produced patterns of white matter injury that are consistent with findings reported in the literature and with DTI profiles generated from these methodologies. Scatter plots comparing DTI metrics obtained from each methodology showed that the pseudo-atlas method produced metrics that implied a more preserved neural structure compared to its counterpart. When comparing DTI metrics against a measure of ventriculomegaly (i.e., Evans’ Index), we showed that the standard atlas-based method was able to detect decreasing white matter integrity with increasing ventriculomegaly, while in contrast, metrics obtained using the pseudo-atlas method were sensitive for stretch or compression in the posterior limb of the internal capsule. Additionally, both methods were able to show an increase in white matter disruption with increasing ventriculomegaly, with the pseudo-atlas method showing less variability and more specificity to changes in white matter tracts near to the ventricles. In this study, we found that there was no true gold-standard for DTI methodologies or atlases. Whilst there was no congruence between absolute values from DTI metrics, differing DTI methodologies were still valid but must be appreciated to be variably sensitive to different changes within white matter injury occurring concurrently. By combining both atlas and pseudo-atlas based methodologies with DTI profiles, it was possible to navigate past such challenges to describe white matter injury changes in the context of confounders, such as neurodegenerative disease and ventricular enlargement, with transparency and consistency.

Summary: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important extracellular human pathogen. The initial adherence of EHEC to host cells is a major cue for transcriptional induction of the locus of enterocyte effacement (LEE) genes to promote colonization and pathogenesis, but the mechanism through which this adherence is sensed and the LEE is induced remains largely elusive. Here, we report a complete signal transduction pathway for this virulence activation process. In this pathway, the outer-membrane lipoprotein NlpE senses a mechanical cue generated from initial host adherence and activates the BaeSR two-component regulatory system; the response regulator BaeR then directly activates the expression of airA located on O-island-134 and encoding a LEE transcriptional activator. Disruption of this pathway severely attenuates EHEC O157:H7 virulence both in vitro and in vivo. This study provides further insights into the evolution of EHEC pathogenesis and the host-pathogen interaction.

The effect of Cu and Fe sheets on the thermocatalytic oxidation of synthetic hydrocarbon lubricating oils at high temperatures were investigated using various analytic techniques. The fast oxidation rate, low thermal stability, more composition and high relative content of compounds was observed by adding Fe sheets compared to Cu sheets, whereas the high oxidation rate of Cu-bearing oil was observed in the initial heating. With increasing temperature from 230 to 300 °C, the acid number and viscosity of Fe-bearing oil was higher and lower, respectively, than Cu-bearing oil. The oxidation mechanism was attributed to electron transfer and chain reactions of free radical.

ABSTRACT Hepatitis D is the most severe form of human viral hepatitis and currently lacks an efficient therapy. Dendritic cell-derived exosomes (Dexs) have been found to induce immune responses capable of eliminating viruses. However, the therapeutic potential of antigen-loaded exosomes in hepatitis D is still unknown. Recently, we designed exosomes loaded with ubiquitinated hepatitis delta virus (HDV) small delta antigen (Ub-S-HDAg) and then treated mice bearing replicating HDV with these exosomes to explore their antiviral effect and mechanism. Mature dendritic cell-derived exosomes (mDexs) were loaded with Ub-S-HDAg and their antivirus function was evaluated in mice with HDV viremia. Furthermore, the proportion of CD8+ cells, the ratio of Th1/Th2 cells, the postimmunization levels of cytokines were explored, and the Janus kinases (JAK)/signal transducer and activator of transcription (STAT) pathway was evaluated with a JAK2 inhibitor AG490. In Ub-S-HDAg-Dexs group, the HDV RNA viral load was significantly decreased compared with other groups by CD8+ cell enrichment and an increase Th1/Th2 cell ratio. Furthermore, lymphocyte infiltration was increased, while the HDAg level was decreased in mouse liver tissue. However, there were no significant differences in HBV surface antigen (HBsAg), alanine aminotransferase (ALT), or aspartate aminotransferase (AST) levels among the groups. Moreover, p-JAK2, p-STAT1, p-STAT4, STAT1, and STAT4 expression was increased in Ub-S-HDAg-Dexs group. In conclusion, Ub-S-HDAg-Dexs might be a potential immunotherapeutic agent for eradicating HDV by inducing specific cellular immune response via the JAK/STAT pathway. IMPORTANCE Hepatitis D is the most severe viral hepatitis with accelerating the process of liver cirrhosis and increasing the risk of hepatocellular carcinoma. However, there are no effective antiviral drugs. Exosomes derived from mature dendritic cells are used not only as immunomodulators, but also as biological carriers to deliver antigens to induce robust immune response. Based on these properties, exosomes could be used as a biological immunotherapy by enhancing adaptive immune response to inhibit hepatitis D virus replication. Our research may provide a new therapeutic strategy to eradicate HDV in the future.

Abstract Background Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai. Method This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically. Results Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P

Background: Exercise is considered as an important intervention for treatment and prevention of several diseases, such as osteoarthritis, obesity, hypertension, and Alzheimer's disease. This review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise brought. Methods: PubMed was utilized as the data source. To collect research articles, we used the following terms to create the search: (exercise [Title] OR physical activity [Title] OR training [Title]) AND (rats [Title/Abstract] OR rat [Title/Abstract] OR rattus [Title/Abstract]). To best cover targeted studies, publication dates were limited to “within 11 years.” The exercise intervention methods used for different diseases were sorted according to the mode, frequency, and intensity of exercise. Results: The collected articles were categorized into studies related to 6 systems or disease types: motor system (17 articles), metabolic system (110 articles), cardiocerebral vascular system (171 articles), nervous system (71 articles), urinary system (2 articles), and cancer (21 articles). Our review found that, for different diseases, exercise intervention mostly had a positive effect. However, the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the disease. Conclusion: As a model animal, rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on diseases. This review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.

Abstract It is widely accepted that both particle shape and mineralogy could have a great effect on the particle strength. However, due to the complexity of nature grains, it is difficult to distinguish the influence of particle shape from mineralogy. This paper shows measurements of the particle shape and mineralogy of carbonate sand, completely decomposed granite, Leighton Buzzard sand and pumice sand. The particle shape of carbonate sand and completely decomposed granite is similar, but the mineral of carbonate sand is carbon dioxide while the mineral of completely decomposed granite is mica and feldspar. It is found that the single particle strength of completely decomposed granite is higher than that of carbonate sand, and the particle breakage caused by one-dimensional compressing tests of completely decomposed granite is higher than that of carbonate sand. The mineralogy of both completely decomposed granite and Leighton Buzzard sand are quartz, but completely decomposed granite is more heterogeneous, result in the single particle strength of completely decomposed granite is much lower than that of Leighton Buzzard sand. It is also found the particle breakage from the one-dimensional compression test for completely decomposed is larger than Leighton Buzzard sand. It should be noted that carbonate sand is stronger than completely decomposed granite after quantitatively analysis the particle shape, particle breakage and compressibility behavior although carbonate sand has extremely irregular shape such as a branch shape, and also several pores. On the other hand, although Leighton Buzzard sand, completely decomposed granite and also pumice sand to some extent have composition of silica, the crystal of those three is completely different, result in the strength or compressibility are quite different. It seems that particle shape is not a major factor to affect strength or compressibility, but the mineralogy could be a major factor.

Abstract Background Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. Methods Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients’ age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. Results 181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). Conclusions The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

ER stress and activation of the unfolded protein response in the periphery as well as the central nervous system have been linked to various metabolic abnormalities. Chemically lowering protein kinase R–like ER kinase (PERK) activity within the hypothalamus leads to decreased food intake and body weight. However, the cell populations required in this response remain undefined. In the current study, we investigated the effects of proopiomelanocortin-specific (POMC-specific) PERK deficiency on energy balance and glucose metabolism. Male mice deficient for PERK in POMC neurons exhibited improvements in energy balance on a high-fat diet, showing decreased food intake and body weight, independent of changes in glucose and insulin tolerances. The plant-based inhibitor of PERK, celastrol, increases leptin sensitivity, resulting in decreased food intake and body weight in a murine model of diet-induced obesity (DIO). Our data extend these observations by demonstrating that celastrol-induced improvements in leptin sensitivity and energy balance were attenuated in mice with PERK deficiency in POMC neurons. Altogether, these data suggest that POMC-specific PERK deficiency in male mice confers protection against DIO, possibly providing a new therapeutic target for the treatment of diabetes and metabolic syndrome.