Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens In Vivo Using Positron Emission Tomography.

Understanding how the host immune system engages complex pathogens is essential to developing therapeutic strategies to overcome their virulence. While granzymes are well understood to trigger apoptosis in infected host cells or bacteria, less is known about how the immune system mobilizes individual granzyme species in vivo to combat diverse pathogens. Toward the goal of studying individual granzyme function directly in vivo, we previously developed a new class of radiopharmaceuticals termed "restricted interaction peptides (RIPs)" that detect biochemically active endoproteases using positron emission tomography (PET). In this study, we showed that secreted granzyme B proteolysis in response to diverse viral and bacterial pathogens could be imaged with [64Cu]Cu-GRIP B, a RIP that specifically targets granzyme B. Wild-type or germline granzyme B knockout mice were instilled intranasally with the A/PR/8/34 H1N1 influenza A strain to generate pneumonia, and granzyme B production within the lungs was measured using [64Cu]Cu-GRIP B PET/CT. Murine myositis models of acute bacterial (E. coli, P. aeruginosa, K. pneumoniae, and L. monocytogenes) infection were also developed and imaged using [64Cu]Cu-GRIP B. In all cases, the mice were studied in vivo using mPET/CT and ex vivo via tissue-harvesting, gamma counting, and immunohistochemistry. [64Cu]Cu-GRIP B uptake was significantly higher in the lungs of wild-type mice that received A/PR/8/34 H1N1 influenza A strain compared to mice that received sham or granzyme B knockout mice that received either treatment. In wild-type mice, [64Cu]Cu-GRIP B uptake was significantly higher in the infected triceps muscle versus normal muscle and the contralateral triceps inoculated with heat killed bacteria. In granzyme B knockout mice, [64Cu]Cu-GRIP B uptake above the background was not observed in the infected triceps muscle. Interestingly, live L. monocytogenes did not induce detectable granzyme B on PET, despite prior in vitro data, suggesting a role for granzyme B in suppressing their pathogenicity. In summary, these data show that the granzyme response elicited by diverse human pathogens can be imaged using PET. These results and data generated via additional RIPs specific for other granzyme proteases will allow for a deeper mechanistic study analysis of their complex in vivo biology.

Metabolic surgery results in greater metabolic benefits in patients who achieve healthy weight.

BACKGROUND: A percentage of total weight loss (%TWL) >20% as the expected weight loss target after metabolic surgery might be insufficient to produce adequate metabolic benefits. OBJECTIVES: This study identified the optimal weight loss target to achieve substantial benefits from metabolic surgery. SETTING: University-affiliated tertiary care center. METHODS: In this retrospective study, participants were categorized into healthy weight (18.5 kg/m2 ≤ body mass index [BMI] < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and obesity groups (BMI ≥28 kg/m2) according to their BMI 1 year after metabolic surgery. The weight loss and remission of obesity-related comorbidities were evaluated. Ordinal logistic regression analysis was used to identify predictors for achieving healthy weight 1 year postoperatively. RESULTS: Overall, 125 patients (112 sleeve gastrectomies, 13 Roux-en-Y gastric bypasses) were recruited in this study. Forty-two participants achieved healthy weight, 38 were overweight, and 45 had obesity. Type 2 diabetes mellitus and obstructive sleep apnea were relieved in all groups. Individuals who achieved healthy weight showed more improvements in nonalcoholic fatty liver disease, hypertension, and hyperuricemia than those who did not. Preoperative BMI was an independent predictor for the BMI achieved postoperatively, and the optimal cut-off point for achieving healthy weight was 34.9 kg/m2. CONCLUSIONS: Healthy weight was a more stringent target for patients who underwent metabolic surgery than the %TWL. Populations with a preoperative BMI of <34.9 kg/m2 were prone to realize the goal. Additional weight loss interventions could be considered for those with higher preoperative BMIs and enforced within 1 year postoperatively.

Cytotoxic and Antifungal Staurosporine Derivatives from Marine-Derived Actinomycete Streptomyces sp. ZS-A121.

A novel staurosporine derivate, streptomholyrine A (1), along with 6 known compounds were identified from the rice-based solid fermentation of marine-derived Streptomyces sp. ZS-A121. The planar structure and absolute configuration of streptomholyrine A were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, chemical transformation, ECD and NMR calculations. Screening of all these compounds revealed their cytotoxic activity against HCT-116 cell lines, with IC50 values ranging from 0.012 to 11.67 µM, except for the known 1H-indole-3-hydroxyacetyl, which showed no inhibition activity. Furthermore, streptomholyrine A, along with two known staurosporine derivatives, k252d and staurosporine, exhibited activities against Candida albicans, with MICs of 12.5, 25.0 and 50.0 µg/ml, respectively.

Multi-behavioral recommendation model based on dual neural networks and contrast learning.

In order to capture the complex dependencies between users and items in a recommender system and to alleviate the smoothing problem caused by the aggregation of multi-layer neighborhood information, a multi-behavior recommendation model (DNCLR) based on dual neural networks and contrast learning is proposed. In this paper, the complex dependencies between behaviors are divided into feature correlation and temporal correlation. First, we set up a personalized behavior vector for users and use a graph-convolution network to learn the features of users and items under different behaviors, and we then combine the features of self-attention mechanism to learn the correlation between behaviors. The multi-behavior interaction sequence of the user is input into the recurrent neural network, and the temporal correlation between the behaviors is captured by combining the attention mechanism. The contrast learning is introduced based on the double neural network. In the graph convolution network layer, the distances between users and similar users and between users and their preference items are shortened, and the distance between users and their short-term preference is shortened in the circular neural network layer. Finally, the personalized behavior vector is integrated into the prediction layer to obtain more accurate user, behavior and item characteristics. Compared with the sub-optimal model, the HR@10 on Yelp, ML20M and Tmall real datasets are improved by 2.5%, 0.3% and 4%, respectively. The experimental results show that the proposed model can effectively improve the recommendation accuracy compared with the existing methods.

Recommendation model based on intention decomposition and heterogeneous information fusion.

In order to solve the problem of timeliness of user and item interaction intention and the noise caused by heterogeneous information fusion, a recommendation model based on intention decomposition and heterogeneous information fusion (IDHIF) is proposed. First, the intention of the recently interacting items and the users of the recently interacting candidate items is decomposed, and the short feature representation of users and items is mined through long-short term memory and attention mechanism. Then, based on the method of heterogeneous information fusion, the interactive features of users and items are mined on the user-item interaction graph, the social features of users are mined on the social graph, and the content features of the item are mined on the knowledge graph. Different feature vectors are projected into the same feature space through heterogeneous information fusion, and the long feature representation of users and items is obtained through splicing and multi-layer perceptron. The final representation of users and items is obtained by combining short feature representation and long feature representation. Compared with the baseline model, the AUC on the Last.FM and Movielens-1M datasets increased by 1.83 and 4.03 percentage points, respectively, the F1 increased by 1.28 and 1.58 percentage points, and the Recall@20 increased by 3.96 and 2.90 percentage points. The model proposed in this paper can better model the features of users and items, thus enriching the vector representation of users and items, and improving the recommendation efficiency.

A Social Recommendation Model Based on Basic Spatial Mapping and Bilateral Generative Adversarial Networks.

Social recommender systems are expected to improve recommendation quality by incorporating social information when there is little user-item interaction data. Therefore, how to effectively fuse interaction information and social information becomes a hot research topic in social recommendation, and how to mine and exploit the heterogeneous information in the interaction and social space becomes the key to improving recommendation performance. In this paper, we propose a social recommendation model based on basic spatial mapping and bilateral generative adversarial networks (MBSGAN). First, we propose to map the base space to the interaction and social space, respectively, in order to overcome the issue of heterogeneous information fusion in two spaces. Then, we construct bilateral generative adversarial networks in both interaction space and social space. Specifically, two generators are used to select candidate samples that are most similar to user feature vectors, and two discriminators are adopted to distinguish candidate samples from high-quality positive and negative examples obtained from popularity sampling, so as to learn complex information in the two spaces. Finally, the effectiveness of the proposed MBSGAN model is verified by comparing it with both eight social recommendation models and six models based on generative adversarial networks on four public datasets, Douban, FilmTrust, Ciao, and Epinions.

Recommendation model based on generative adversarial network and social reconstruction.

Social relations can effectively alleviate the data sparsity problem in recommendation, but how to make effective use of social relations is a difficulty. However, the existing social recommendation models have two deficiencies. First, these models assume that social relations are applicable to various interaction scenarios, which does not match the reality. Second, it is believed that close friends in social space also have similar interests in interactive space and then indiscriminately adopt friends' opinions. To solve the above problems, this paper proposes a recommendation model based on generative adversarial network and social reconstruction (SRGAN). We propose a new adversarial framework to learn interactive data distribution. On the one hand, the generator selects friends who are similar to the user's personal preferences and considers the influence of friends on users from multiple angles to get their opinions. On the other hand, friends' opinions and users' personal preferences are distinguished by the discriminator. Then, the social reconstruction module is introduced to reconstruct the social network and constantly optimize the social relations of users, so that the social neighborhood can assist the recommendation effectively. Finally, the validity of our model is verified by experimental comparison with multiple social recommendation models on four datasets.

Analysis of the effect of metal ions on the ability of Xylanase to hydrolyze wheat bran by molecular dynamics simulations.

Introduction: Wheat bran is the main by-product of wheat processing, containing about 30% pentosan and 0.4%-0.7% ferulic acid. Wheat bran is the main raw material used to prepare feruloyl oligosaccharides by hydrolysis of Xylanase, we discovered that the ability of Xylanase to hydrolyze wheat bran could be affected in the presence of different metal ions. Methods: In the present study, we have probed the effects of different metal ions on the hydrolysis activity of Xylanase on wheat bran and tried to analyze the effect of Mn2+ and Xylanase by molecular dynamic (MD) simulation. Results: Our results suggested that Mn2+ had improved the Xylanase hydrolyzing wheat bran to obtain feruloyl oligosaccharides. Particularly when the concentration of Mn2+ reached 4 mmol/L, the optimal product has been obtained 2.8 times higher to compare with no addition. Through the MD simulation analysis, our results reveal that Mn2+ can induce structural change in the active site, which enlarges the substrate binding pocket. The simulation results also revealed that the addition of Mn2+ resulted in a low RMSD value compared with the absence of Mn2+ and helped stabilize the complex. Conclusion: Mn2+ could increase the enzymatic activity of Xylanase in the hydrolysis of feruloyl oligosaccharides in wheat bran. The finding could have significant implications for the preparation of feruloyl oligosaccharides from wheat bran.

Chronic intermittent hypoxia contributes to non-alcoholic steatohepatitis progression in patients with obesity.

BACKGROUND AND PURPOSE: The association between the severity of obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in patients with obesity remains unclear. We conducted this study to determine the effects of OSA on the severity of NAFLD in individuals with obesity and its link to the development of non-alcoholic steatohepatitis (NASH). METHODS: Patients were subjected to standard polysomnography up to 1 week before undergoing bariatric surgery, during which liver biopsy specimens were obtained. The apnea-hypopnea index (AHI) obtained by polysomnography was used to determine the severity of OSA. RESULTS: In total, 183 patients with obesity and biopsy-confirmed NAFLD were included; 49 (27%) had NASH. Patients with NASH had higher AHIs (p = 0.014) and oxygen desaturation indices (p = 0.031), more frequent OSA (p = 0.001), and lower minimum oxygen saturation (p = 0.035). The severity of OSA was directly correlated with the NAFLD activity score (p < 0.001), NASH activity grade (p < 0.001), semi-quantitative indices of lobular inflammation (p = 0.001), and hepatocyte ballooning (p = 0.006). The odds ratios (95% confidence intervals) for NASH and severe NASH (activity grade ≥ 3) associated with moderate-to-severe OSA were 3.85 (1.35-10.94; p < 0.05) and 5.02 (1.66-15.18; p < 0.01), respectively, after adjusting for sex, age, body mass index, waist circumference, insulin resistance values, and metabolic syndrome. CONCLUSIONS: Chronic intermittent hypoxia caused by OSA may aggravate NAFLD and lead to a higher risk of NASH in patients with obesity.

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi-Window Release during Bone Reconstruction.

Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft. Local recurrence remains an important and devastating problem, therefore, a system capable of locally delivering chemotherapeutics will present unique advantages. In this work, a refillable chemotherapeutic (doxorubicin, DOX) delivery platform comprised of PMMA bone cement and insoluble γ-cyclodextrin (γ-CD) polymeric microparticles is developed and explored towards application as a temporary adjuvant chemotherapeutic spacer. The system is characterized for porosity, mechanical strength, DOX filling and refilling capacity, elution kinetics, and cytotoxicity. Since residual chemotherapeutics can adversely impact bone healing, it is important that virtually all DOX be released from material. Composites containing 15 wt% γ-CD microparticles demonstrate 100% DOX release within 100 days, whereas only 6% DOX is liberated from PMMA with free DOX over same period. Refillable properties of PMMA composite system may find utility for customizing dosing regimens. Findings suggest that PMMA composites can have potential as chemotherapeutic delivery platforms to assist in bone reconstruction.

Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients.

PURPOSE: We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic. PATIENTS AND METHODS: Seventy-eight non-diabetic patients were randomly selected and beinaglutide or metformin was administered for 12 weeks. The primary endpoints were changes in body weight and the proportions of patients who lost≥5 and≥10% of their baseline body weights. RESULTS: A total of 64 patients completed the study; patients in the beinaglutide group exhibited more bodyweight loss than those in the metformin group [(9.5±0.8%; 9.1±0.9 kg) and (5.1±0.9%; 4.5±0.8 kg), respectively, corresponding to a difference of approximately 4.5 kg (95% confidence interval, 2.2-6.9 kg; P<0.01)]. In the beinaglutide group, 90.6 and 40.6% of the patients lost≥5 and≥10% of their body weight, respectively, whereas, in the metformin group, these rates were 46.9 and 12.5%, respectively (P<0.01 and P<0.05). Weight loss following beinaglutide treatment mainly resulted from the loss of fat mass. Compared to metformin, beinaglutide induced a greater decrease in the body mass index, weight circumference, percent body fat, and body fat mass (total, trunk, limb, android, and gynoid). Additionally, beinaglutide decreased serum insulin levels and ameliorated insulin resistance. CONCLUSIONS: Beinaglutide is more efficient than metformin at reducing weight and fat mass in patients who are overweight/obese and non-diabetic. Beinaglutide may be a useful therapeutic option for overweight/obesity control in the Chinese population.

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo.

While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to in vivo orthopedic implant-associated infection models, the properties (e.g., degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant in vivo models. The antimicrobial materials are then incorporated into in vivo implant models to evaluate the efficacy of using the material to prevent or treat implant-associated infections. Recent technological advances such as 3D-printing, bacterial genomic sequencing, and real-time in vivo imaging of infection and inflammation have contributed to the development of preclinical implant-associated infection models that more effectively recapitulate the clinical presentation of infections and improve the evaluation of antimicrobial materials. This Review highlights the advantages and limitations of antimicrobial materials used in conjunction with orthopedic implants for the prevention and treatment of orthopedic implant-associated infections and discusses how these materials are evaluated in preclinical in vivo models. This analysis serves as a resource for biomaterial researchers in the selection of an appropriate orthopedic implant-associated infection preclinical model to evaluate novel antimicrobial materials.

[Consecutive 4-year Elevated Atmospheric CO2 on Shaped Microbial Communities in the Rhizosphere Soil of Robinia pseudoacacia L. Seedlings Grown in Pb-contaminated Soils].

Elevated atmospheric CO2 could affect the speciation of heavy metals in rhizosphere soils by changing root exudates, thereby influencing soil microecosystem in the rhizosphere. Therefore, understanding the function of heavy metals in soils on rhizospheric ecology under elevated atmospheric CO2 scenarios is highly important. Here, we investigated the combined effects of a four-year period of elevated air CO2 concentrations[(700±27) µmol·L-1] and Pb-contamination (15.6 mg·kg-1 and 515.6 mg·kg-1) on the soil rhizopheric microbial community of Robinia pseudoacacia L. seedlings. Significant (P<0.05) effects of CO2, Pb, and their interaction on bacterial richness and fungal diversity were observed. Relative to Pb exposure alone, elevated CO2 significantly increased pH, total C, total N, and water-soluble organic carbon, and the C/N ratio under Pb exposure (P<0.05) and significantly decreased total and soluble Pb content (P<0.05). The richness and diversity of bacteria increased (P<0.05), fungal richness decreased (P<0.05), and microbial diversity increased (P<0.05) under the combined treatments relative to Pb contamination alone. The changes in the relative abundance of the top two dominant bacterial and fungal genera were not significant; however, differences in the relative abundances of other groups, such as Anaerolineaceae, Solirubrobacterales, Eurotiomycetes, Aspergillus, and Trichocomaceae, were significant between the different treatments. According to a redundancy analysis, total C and soluble Pb had a significant influence (P<0.05) on the dominant bacterial genera, and total C affected (P<0.05) the dominant genera in the fungal community. These results suggest that the responses of soil environmental factors to the combination of elevated atmospheric CO2 and Pb could shape soil microbial community structure in the rhizosphere of R. pseudoacacia seedlings.

Are Chinese Patients with Type 2 Diabetes and a Body Mass Index of 27.5-32.5 kg/m2 Suitable for Metabolic Surgery? A One-Year Post-Surgery Study.

INTRODUCTION: The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m2. METHODS: A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m2 and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m2 and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated. RESULTS: Of patients with BMI 27.5-32.5 kg/m2 undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m2 receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m2 who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events. CONCLUSION: A BMI cutoff of 27.5 kg/m2 for metabolic surgery may be suitable for Chinese patients with T2DM.

Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue.

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections. Previous work demonstrated efficacy of incorporating insoluble cyclodextrin (CD) microparticles into PMMA to improve antibiotic release and allow for post-implantation drug refilling to occur in a tissue-mimicking model. To simulate how antibiotic refilling may be possible in more physiologically relevant models, this work investigated development of bone and muscle refilling models. The bone refilling model involved embedding PMMA-CD into rabbit femur and administering antibiotic via intraosseous infusion. Muscle tissue refilling model involved implanting PMMA-CD beads in bovine muscle tissue and administering antibiotic via tissue injection. Duration of antimicrobial activity of refilled PMMA-CD was evaluated. PMMA-CD composite in bone and muscle tissue models was capable of being refilled with antibiotics and resulted in prolonged antimicrobial activity. PMMA-CD provided sustained and on-demand antimicrobial activity without removal of implant if infection develops. Intraosseous infusion appeared to be a viable technique to enable refilling of PMMA-CD after implantation in bone, reporting for the first time the ability to refill PMMA in bone.

The combined effects of elevated atmospheric CO2 and cadmium exposure on flavonoids in the leaves of Robinia pseudoacacia L. seedlings.

Flavonoids participate in several plant processes such as growth and physiological protection in adverse environments. In this study, we investigated the combined effects of eCO2 and cadmium (Cd)-contaminated soils on the total flavonoid and monomer contents in the leaves of Robinia pseudoacacia L. seedlings. Elevated CO2, Cd, and eCO2+ Cd increased the total flavonoids in the leaves relative to the control, and eCO2 mostly increased (p < 0.05) the total flavonoid content under Cd exposure. Elevated CO2 increased (p < 0.05) robinin, rutin, and acacetin contents in the leaves of 45-day seedlings and decreased (p < 0.05) the content of robinin and acacetin at 90 and 135 d under Cd exposure except for robinin at day 45 under Cd1 and acacetin on day 135 under Cd1. Quercetin content decreased (p < 0.05) under the combined conditions relative to Cd alone. Kaempferol in the leaves was only detected under eCO2 on day 135. The responses of total chlorophyll, total soluble sugars, starch, C, N, S, and the C/N ratio in the leaves to eCO2 significantly affected the synthesis of total flavonoids and monomers under Cd exposure. Overall, rutin was more sensitive to eCO2+ Cd than the other flavonoids. Cadmium, CO2, and time had significant interactive effects on the synthesis of flavonoids in the leaves of R. pseudoacacia L. seedlings. Elevated CO2 may improve the protection and defense system of seedlings grown in Cd-contaminated soils by promoting the synthesis of total flavonoids, although robinin, rutin, quercetin, and acacetin yields may reduce with time. Additionally, increased Cd in the leaves suggested that eCO2 could improve the phytoremediation of Cd-contaminated soils.

Effects of elevated CO2 on arbuscular mycorrhizal fungi associated with Robinia pseudoacacia L. grown in cadmium-contaminated soils.

As symbionts capable of reciprocal rewards, arbuscular mycorrhizal fungi (AMF) can alleviate heavy metal toxicity to host plants and are easily influenced by elevated CO2 (ECO2). Although the individual effects of ECO2 and cadmium (Cd) on AMF have been widely reported, the response of AMF to ECO2 + Cd receives little attention. We evaluated the combined effects of ECO2 and Cd on AMF in the rhizosphere soil and roots of Robinia pseudoacacia L. seedlings. Under ECO2 + Cd relative to Cd, AMF gene copies and richness in rhizosphere soils increased (p < 0.05) and the diversity reduced (p < 0.05) at 4.5 mg Cd kg-1 dry soil; whereas root AMF abundance at 4.5 mg Cd kg-1 dry soil and the diversity and richness reduced (p < 0.05). Elevated CO2 caused obvious differences in the dominant genera abundance between rhizosphere soils and roots upon Cd exposure. Responses of C, water-soluble organic nitrogen (WSON), pH, and diethylene triamine penta-acetic acid (DTPA)-Cd in rhizosphere soils and root N to ECO2 shaped dominant genera in Cd-polluted rhizosphere soils. Levels of DTPA-Cd, WSON, C and pH in rhizosphere soils and C/N ratio, N, and Cd in roots to ECO2 affected (p < 0.05) dominant genera in roots under Cd exposure. AMF richness and diversity were lower in roots than in rhizosphere soils. Elevated CO2 altered AMF communities in rhizosphere soils and roots of R. pseudoacacia seedlings exposed to Cd. AMF associated with R. pseudoacacia may be useful/interesting to be used for improving the phytoremediation of Cd under ECO2.

A consecutive 4-year elevated air temperature shaped soil bacterial community structure and metabolic functional groups in the rhizosphere of black locust seedlings exposed to lead pollution.

Global warming may influence the bioavailability and mobility of heavy metals by stimulating or inhibiting plant growth, thereby influencing rhizosphere soil chemistry and microbial characteristics. Black locust has been widely planted in China as a promising species for afforestation programs, farmland shelterbelt projects, and soil restoration in mined areas because of its rapid growth and adaptability to environmental stressors. Here, we examined soil bacterial community structure and predicted bacterial metabolic function in the rhizosphere of black locust exposed to elevated temperature (+1.99 °C) and Pb for 4 years. Elevated temperature significantly (p < 0.05) reduced total carbon (TC), total nitrogen (TN), and total sulfur (TS) contents in above-ground parts but increased TC and TN contents in roots and seedling height under Pb exposure. Elevated temperature significantly (p < 0.05) increased Pb availability and raised pH, TC, TN, TS and water-soluble organic carbon (WSOC) contents, and the C:H ratio in rhizosphere soils under Pb exposure. The interactive effects between Pb and temperature on pH, TC, TH, TS, WSOC, and the C:H ratio were significant (p < 0.05). Elevated temperature significantly (p < 0.05) reduced the diversity and the richness of bacterial community, altered genus-level bacterial community composition, and improved (p < 0.05) the relative abundances of some bacteria involving in terpenoids and polyketides and xenobiotics biodegradation metabolism under Pb exposure. Canonical correspondence analysis indicated that pH, WSOC, C:N ratio, and soluble Pb were significant (p < 0.05) factors on the relative abundance of bacterial genera, such as Ochrobactrum and Sphingomnas. Overall, long-term elevated temperature resulted in changes in rhizosphere soil characteristics and Pb availability, thus affecting the bacterial community structure and metabolic functional groups. The conclusion helps us understand the response mechanism of soil bacteria in the rhizosphere to heavy metals under global warming scenarios.

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet.

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

Correction: Investigation of a Measles Outbreak in China to Identify Gaps in Vaccination Coverage, Routes of Transmission, and Interventions.

[This corrects the article DOI: 10.1371/journal.pone.0133983.].