Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Methods: Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Results: Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; ß-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and ß-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Conclusion: Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Microbiota from Preterm Infants Who Develop Necrotizing Enterocolitis Drives the Neurodevelopment Impairment in a Humanized Mouse Model.

Necrotizing enterocolitis (NEC) is the leading basis for gastrointestinal morbidity and poses a significant risk for neurodevelopmental impairment (NDI) in preterm infants. Aberrant bacterial colonization preceding NEC contributes to the pathogenesis of NEC, and we have demonstrated that immature microbiota in preterm infants negatively impacts neurodevelopment and neurological outcomes. In this study, we tested the hypothesis that microbial communities before the onset of NEC drive NDI. Using our humanized gnotobiotic model in which human infant microbial samples were gavaged to pregnant germ-free C57BL/6J dams, we compared the effects of the microbiota from preterm infants who went on to develop NEC (MNEC) to the microbiota from healthy term infants (MTERM) on brain development and neurological outcomes in offspring mice. Immunohistochemical studies demonstrated that MNEC mice had significantly decreased occludin and ZO-1 expression compared to MTERM mice and increased ileal inflammation marked by the increased nuclear phospho-p65 of NFκB expression, revealing that microbial communities from patients who developed NEC had a negative effect on ileal barrier development and homeostasis. In open field and elevated plus maze tests, MNEC mice had worse mobility and were more anxious than MTERM mice. In cued fear conditioning tests, MNEC mice had worse contextual memory than MTERM mice. MRI revealed that MNEC mice had decreased myelination in major white and grey matter structures and lower fractional anisotropy values in white matter areas, demonstrating delayed brain maturation and organization. MNEC also altered the metabolic profiles, especially carnitine, phosphocholine, and bile acid analogs in the brain. Our data demonstrated numerous significant differences in gut maturity, brain metabolic profiles, brain maturation and organization, and behaviors between MTERM and MNEC mice. Our study suggests that the microbiome before the onset of NEC has negative impacts on brain development and neurological outcomes and can be a prospective target to improve long-term developmental outcomes.

The Impact of Maternal Probiotics on Intestinal Vitamin D Receptor Expression in Early Life.

Vitamin D signaling via the Vitamin D Receptor (VDR) has been shown to protect against intestinal inflammation. Previous studies have also reported the mutual interactions of intestinal VDR and the microbiome, indicating a potential role of probiotics in modulating VDR expression. In preterm infants, although probiotics have been shown to reduce the incidence of necrotizing enterocolitis (NEC), they are not currently recommended by the FDA due to potential risks in this population. No previous studies have delved into the effect of maternally administered probiotics on intestinal VDR expression in early life. Using an infancy mouse model, we found that young mice exposed to maternally administered probiotics (SPF/LB) maintained higher colonic VDR expression than our unexposed mice (SPF) in the face of a systemic inflammatory stimulus. These findings indicate a potential role for microbiome-modulating therapies in preventing diseases such as NEC through the enhancement of VDR signaling.

Serum from acupuncture-treated asthmatic rats regulates p38-MAPK activation in airway smooth muscle cells.

OBJECTIVES: This study aimed to investigate the regulation function of acupuncture on airway smooth muscle cells (ASMCs) of asthmatic rats. METHODS: Male Sprague-Dawley rats were challenged using inhalational Ovalbumin (OVA) to establish an asthma model. The acupuncture points (GV14 for Dazhui, bilateral BL12 for Fengmen, and bilateral BL13 for Feishu) were stimulated for asthma relief. The ASMCs isolated from asthmatic rats were incubated in medium containing the serum obtained from asthmatic rats treated with acupuncture. The expression levels of p38 MAPK and p-p38 MAPK were determined by immunocytochemical and western blot. RESULTS: ASMCs were successfully isolated and cultured. The 20% acupuncture treatment of asthmatic rat serum had the least effect on the proliferation ability of asthmatic ASMCs. The serum from asthmatic rats treated with acupuncture could decrease the expression of p-p38 MAPK in asthmatic rat ASMCs. CONCLUSIONS: The serum from acupuncture-treated asthmatic rats has an effect on treating asthma in rats, and the mechanism of action may be by regulating the p38 pathway.

Limosilactobacillus reuteri normalizes blood-brain barrier dysfunction and neurodevelopment deficits associated with prenatal exposure to lipopolysaccharide.

Maternal immune activation (MIA) derived from late gestational infection such as seen in chorioamnionitis poses a significantly increased risk for neurodevelopmental deficits in the offspring. Manipulating early microbiota through maternal probiotic supplementation has been shown to be an effective means to improve outcomes; however, the mechanisms remain unclear. In this study, we demonstrated that MIA modeled by exposing pregnant dams to lipopolysaccharide (LPS) induced an underdevelopment of the blood vessels, an increase in permeability and astrogliosis of the blood-brain barrier (BBB) at prewean age. The BBB developmental and functional deficits early in life impaired spatial learning later in life. Maternal Limosilactobacillus reuteri (L. reuteri) supplementation starting at birth rescued the BBB underdevelopment and dysfunction-associated cognitive function. Maternal L. reuteri-mediated alterations in ß-diversity of the microbial community and metabolic responses in the offspring provide mechanisms and potential targets for promoting BBB integrity and long-term neurodevelopmental outcomes.

Early preterm infant microbiome impacts adult learning.

Interventions to mitigate long-term neurodevelopmental deficits such as memory and learning impairment in preterm infants are warranted. Manipulation of the gut microbiome affects host behaviors. In this study we determined whether early maturation of the infant microbiome is associated with neurodevelopment outcomes. Germ free mice colonized at birth with human preterm infant microbiomes from infants of advancing post menstrual age (PMA) demonstrated an increase in bacterial diversity and a shift in dominance of taxa mimicking the human preterm microbiome development pattern. These characteristics along with changes in a number of metabolites as the microbiome matured influenced associative learning and memory but not locomotor ability, anxiety-like behaviors, or social interaction in adult mice. As a regulator of learning and memory, brain glial cell-derived neurotrophic factor increased with advancing PMA and was also associated with better performance in associative learning and memory in adult mice. We conclude that maturation of the microbiome in early life of preterm infants primes adult associative memory and learning ability. Our findings suggest a critical window of early intervention to affect maturation of the preterm infant microbiome and ultimately improve neurodevelopmental outcomes.

A General Synthesis of Mesoporous Hollow Carbon Spheres with Extraordinary Sodium Storage Kinetics by Engineering Solvation Structure.

Porous and hollow carbon materials have great superiority and prospects in electrochemical energy applications, especially for surface charge storage due to the high active surface. Herein, a general strategy is developed to synthesize mesoporous hollow carbon spheres (MHCS) with controllable texture and compositions by the synergistic effect of dopamine polymerization and metal catalysis (Cu, Bi, Zn). Mesoporous MHCS-Cu and MHCS-Bi are regular spheres, while mesoporous MHCS-Zn possesses an inward concave texture, and simultaneously has a very high surface area of 1675.5 m2 g-1 and lower oxygen content through the catalytic deoxygenation effect. MHCS-Zn displays an exceptional sodium storage kinetics and excellent long cycling life with 171.9 mAh g-1 after 2500 cycles at 5 A g-1 in compatible ether-based electrolytes. Such electrolyte enables enhanced solvated Na+ transport kinetics with appropriate electrostatic interactions at the surface of carbon anode as revealed by molecular dynamics simulations and molecular surface electrostatic potential calculations. Such an anode also displays basically constant capacity working at 0 °C, and still delivers 140 mAh g-1 at 3 A g-1 under -20 °C. Moreover, MHCS-Zn anode is coupled with Na3 V2 (PO4 )3 cathode to construct a hybrid capacitor, which exhibits a high energy density of 145 Wh Kg-1 at a very high power of 8009 W kg-1 .

Necrotizing enterocolitis intestinal barrier function protection by antenatal dexamethasone and surfactant-D in a rat model.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality. METHODS: Pregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults. RESULTS: Antenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro. CONCLUSIONS: Antenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins. IMPACT: Antenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC. A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions. We describe the intestinal SP-D-an overlooked role of antenatal dexamethasone in neonatal NEC?

Maternal administration of probiotics promotes gut development in mouse offsprings.

Necrotizing enterocolitis is the most common gastrointestinal disorder in premature neonates. This disease is characterized by massive epithelial necrosis, gut barrier dysfunction and improper mucosal defense development. Studies have shown that probiotic administration can decrease NEC incidence and mortality. The proposed mechanisms of probiotics for the prevention of NEC are: promotion of intestinal development; improved barrier function through decreased apoptosis and improved mucin production; decreased expression of proinflammatory cytokines IL6, IL8, and TNFα, and modulation of microbiota dysbiosis in preterm infants. However, reported sepsis in the immunocompromised preterm host has deterred routine prophylactic administration of probiotics in the neonatal intensive care unit. We hypothesize that maternal administration of probiotics to pregnant mouse dams can recapitulate the beneficial effects observed in neonates fed with probiotics directly. We exposed pregnant mice to the probiotics and monitored the changes in the developing intestines of the offspring. Pregnant mice were fed daily with the probiotics Lactobacillus acidophilus and Bifidobacterium infantis (LB) from embryonic day15 to 2-week-old postnatally. Intraperitoneal administration of IL-1ß in the pups was used to model proinflammatory insults. Sera were collected at 2 weeks of age and evaluated for inflammatory cytokines by enzyme-linked-immunosorbent-assay and gut permeability by Fluorescein isothiocyanate-dextran tracer assay. Ileal tissues were collected for the evaluation of apoptosis and proliferation of the intestinal epithelium; as well as mucin and tight junction integrity at mucosal surface by immunofluorescent staining. We find that maternal LB exposure facilitated intestinal epithelial cell differentiation, prevented loss of mucin and preserved the intestinal integrity and barrier function and decreased serum levels of IL-1ß, TNF-α and IL-6 in the preweaned offsprings. in LB exposed pups. We demonstrate that maternal probiotic supplementation promotes gut maturation in developing offspring. This is potentially a safe alternative therapy to induce intestinal maturation and prevent prematurity-associated neonatal disorders.

Maternal administration of probiotics promotes brain development and protects offspring's brain from postnatal inflammatory insults in C57/BL6J mice.

Neonatal morbidities are associated with long term neurological deficits in life and have also been associated with dysbiosis. We tested whether optimizing the neonate's microbiome through maternal probiotic supplementation can improve offspring's neurodevelopmental outcomes. Maternal LB supplementation, carried out by giving Lactobacillus acidophilus and Bifidobacterium infantis (LB) to pregnant C57/BL6J mice daily from E16 to weaning, significantly suppressed postnatal peripheral proinflammatory insult-induced systemic inflammation and normalized compromised blood-brain barrier permeability and tight junction protein expression in the offspring at pre-weaned age. Maternal LB exposure also regulated markers associated with leukocyte transendothelial migration, extracellular matrix injury and neuroinflammation. The suppressed neuroinflammation by maternal LB supplementation was associated with reduced astrocyte/microglia activation and downregulation of the transcriptional regulators CEBPD and IκBα. Furthermore, maternal LB supplementation promoted neuronal and oligodendrocyte progenitor cell development. Our study demonstrates the efficacy of maternal LB supplementation in modulating systemic and central nervous system inflammation as well as promoting neural/oligodendrocyte progenitor development in the offspring. This evidence suggests that maternal probiotic supplementation may be a safe and effective strategy to improve neurological outcomes in the offspring.

Impact of Developmental Age, Necrotizing Enterocolitis Associated Stress, and Oral Therapeutic Intervention on Mucus Barrier Properties.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.

Seasonal prediction of Indian wintertime aerosol pollution using the ocean memory effect.

As China makes every effort to control air pollution, India emerges as the world's most polluted country, receiving worldwide attention with frequent winter (boreal) haze extremes. In this study, we found that the interannual variability of wintertime aerosol pollution over northern India is regulated mainly by a combination of El Niño and the Antarctic Oscillation (AAO). Both El Niño sea surface temperature (SST) anomalies and AAO-induced Indian Ocean Meridional Dipole SST anomalies can persist from autumn to winter, offering prospects for a prewinter forecast of wintertime aerosol pollution over northern India. We constructed a multivariable regression model incorporating El Niño and AAO indices for autumn to predict wintertime AOD. The prediction exhibits a high degree of consistency with observation, with a correlation coefficient of 0.78 (P < 0.01). This statistical model could allow the Indian government to forecast aerosol pollution conditions in winter and accordingly improve plans for pollution control.

Seasonal Variations of Arctic Low-Level Clouds and Its Linkage to Sea Ice Seasonal Variations.

Using CALIPSO-CloudSat-Clouds and the Earth's Radiant Energy System-Moderate Resolution Imaging Spectrometer data set, this study documents the seasonal variation of sea ice, cloud, and atmospheric properties in the Arctic (70°N-82°N) for 2007-2010. A surface-type stratification-consisting Permanent Ocean, Land, Permanent Ice, and Transient Sea Ice-is used to investigate the influence of surface type on low-level Arctic cloud liquid water path (LWP) seasonality. The results show significant variations in the Arctic low-level cloud LWP by surface type linked to differences in thermodynamic state. Subdividing the Transient Ice region (seasonal sea ice zone) by melt/freeze season onset dates reveals a complex influence of sea ice variations on low cloud LWP seasonality. We find that lower tropospheric stability is the primary factor affecting the seasonality of cloud LWP. Our results suggest that variations in sea ice melt/freeze onset have a significant influence on the seasonality of low-level cloud LWP by modulating the lower tropospheric thermal structure and not by modifying the surface evaporation rate in late spring and midsummer. We find no significant dependence of the May low-level cloud LWP peak on the melt/freeze onset dates, whereas and September/October low-level cloud LWP maximum shifts later in the season for earlier melt/later freeze onset regions. The Arctic low cloud LWP seasonality is controlled by several surface-atmosphere interaction processes; the importance of each varies seasonally due to the thermodynamic properties of sea ice. Our results demonstrate that when analyzing Arctic cloud-sea ice interactions, a seasonal perspective is critical.

Microbiota influence the development of the brain and behaviors in C57BL/6J mice.

We investigated the contributions of commensal bacteria to brain structural maturation by magnetic resonance imaging and behavioral tests in four and 12 weeks old C57BL/6J specific pathogen free (SPF) and germ free (GF) mice. SPF mice had increased volumes and fractional anisotropy in major gray and white matter areas and higher levels of myelination in total brain, major white and grey matter structures at either four or 12 weeks of age, demonstrating better brain maturation and organization. In open field test, SPF mice had better mobility and were less anxious than GF at four weeks. In Morris water maze, SPF mice demonstrated better spatial and learning memory than GF mice at 12 weeks. In fear conditioning, SPF mice had better contextual memory than GF mice at 12 weeks. In three chamber social test, SPF mice demonstrated better social novelty than GF mice at 12 weeks. Our data demonstrate numerous significant differences in morphological brain organization and behaviors between SPF and GF mice. This suggests that commensal bacteria are necessary for normal morphological development and maturation in the grey and white matter of the brain regions with implications for behavioral outcomes such as locomotion and cognitive functions.

Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice.

Poor growth in the Neonatal Intensive Care Unit is associated with an increased risk for poor neurodevelopmental outcomes for preterm infants, however the mechanism is unclear. The microbiome has increasingly been recognized as a modifiable environmental factor to influence host development. Here we explore the hypothesis that the microbiome influences both growth phenotype and brain development. A germ free mouse transfaunation model was used to examine the effects of preterm infant microbiotas known to induce either high growth or low growth phenotypes on postnatal brain development. The microbiome which induced the low growth phenotype was associated with decreases in the neuronal markers NeuN and neurofilament-L as well as the myelination marker MBP when compared to the microbiome associated with the high growth phenotype. Additionally, poor growth phenotype-associated microbiota was associated with increased neuroinflammation marked by increased Nos1, as well as alteration in IGF-1 pathway including decreased circulating and brain IGF-1, decreased circulating IGFBP3, and increased Igfbp3 brain mRNA expression. This study suggests that growth-associated microbiota can influence early neuron and oligodendrocyte development and that this effect may be mediated by effects on neuroinflammation and circulating IGF-1.

[Acupuncture for TGF-ß1 expression in lung tissues of asthma rats].

OBJECTIVE: To explore the regulation of acupuncture for transforming growth factor ß1 (TGF-ß1) expression in the lung tissues of bronchial asthmatic rats. METHODS: Forty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a shallow fast acupuncture group, 10 rats in each group. Asthma model was established in the model, acupuncture, and shallow fast acupuncture groups, and no intervention was applied in the blank and model groups. Before atomization excitation, 20 min acupuncture was applied at "Dazhui" (GV 14) "Feishu" (BL 13) "Fengmen" (BL 12) in the acupuncture group. Acupuncture only into skin without needle retained at the above acupoints was used in the shallow fast acupuncture group before atomization excitation from the day of model established. All the treatment was given 7 times, once the other day. The pathological lunge tissues of rats were observed by HE staining; the protein expression of TGF-ß1 in the lung tissues was examined by immunohistochemical staining and immunofluorescence staining. The TGF-ß1 expressions in bronchoalveolar lavage fluid (BALF) and serum were showed by ELISA. RESULTS: There were changes in the lung tissues in the model group, including mucus plug in the bronchial lumen, irregular bronchial epithelium, thick airway smooth muscle, local break, narrow lumen, a large number of inflammatory cell infiltration. The phenomena in the acupuncture group were improved and those in the shallow fast acupuncture group were not apparently changed compared with those in the model group. The IOD value of TGF-ß1 expression in the model group increased compared with that in the blank group (P<0.05); the positive expression in the acupuncture group was lower than those in the model and shallow fast acupuncture groups (both P<0.05). The contents of TGF-ß1 in BALF and serum of the acupuncture group were lower than those in the model and shallow fast acupuncture groups (all P<0.05). CONCLUSIONS: Acupuncture may improve airway inflammatory response and remolding of asthma by inhibiting TGF-ß1 expression.

[Regulation of acupuncture on expression of AKT protein in lung tissues of asthma rats].

OBJECTIVE: To explore the effects of acupuncture on the expression of protein kinase B (PKB/AKT) in lung tissues of asthma rats. METHODS: Forty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a blocker group, 10 rats in each one. The rat model of asthma was established by egg albumin stimulation in the model group, acupuncture group and blocker group. Since the establishment of rat model, the rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14), "Feishu" (BL 13) and "Fengmen" (BL 12) before atomization; the rats in the blocker group were treated with intervention of blocker LY294002, once every two days, for 7 times. There was no treatment in the blank group and model group. HE staining was applied to observe the morphologic changes of lung tissues; the immunohistochemical method was applied to test the protein expression of AKT in lung tissue. RESULTS: HE staining indicated the infiltration and aggregation of a variety of inflammatory cells around airways, as well as bronchial smooth muscle spasm and confined lumen in the model group; in the acupuncture group and blocker group the inflammatory cells were less and confined lumen was relieved. Compared with the blank group, the protein expression of AKT was higher in the model group (P<0.05); compared with the model group, the protein expression of AKT in the acupuncture group and blocker group was reduced (both P<0.05); the differences between the acupuncture group and blank group, blocker group were not significant (both P>0.05). CONCLUSIONS: Acupuncture could reduce the protein expression of AKT in lung tissue in asthma rats, leading to relieved inflammation reaction and airway remodeling.

Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

Crop residue management and fertilization effects on soil organic matter and associated biological properties.

Returning crop residue may result in nutrient reduction in soil in the first few years. A two-year field experiment was conducted to assess whether this negative effect is alleviated by improved crop residue management (CRM). Nine treatments (3 CRM and 3 N fertilizer rates) were used. The CRM treatments were (1) R0: 100 % of the N using mineral fertilizer with no crop residues return; (2) R: crop residue plus mineral fertilizer as for the R0; and (3) Rc: crop residue plus 83 % of the N using mineral and 17 % manure fertilizer. Each CRM received N fertilizer rates at 270, 360, and 450 kg N ha(-1) year(-1). At the end of the experiment, soil NO3-N was reduced by 33 % from the R relative to the R0 treatment, while the Rc treatment resulted in a 21 to 44 % increase in occluded particulate organic C and N, and 80 °C extracted dissolved organic N, 19 to 32 % increase in microbial biomass C and protease activity, and higher monounsaturated phospholipid fatty acid (PLFA):saturated PLFA ratio from stimulating growth of indigenous bacteria when compared with the R treatment. Principal component analysis showed that the Biolog and PLFA profiles in the three CRM treatments were different from each other. Overall, these properties were not influenced by the used N fertilizer rates. Our results indicated that application of 17 % of the total N using manure in a field with crop residues return was effective for improving potential plant N availability and labile soil organic matter, primarily due to a shift in the dominant microorganisms.