A systematic review of microbial markers for risk prediction of colorectal neoplasia.

BACKGROUND: Substantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance. METHODS: A comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed. RESULTS: Forty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9-485 cases) and lack of independent external validation (76.7%). CONCLUSIONS: This review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.

Maternal postpartum feeding anxiety was associated with infant feeding practices: results from the mother-infant cohort study of China.

BACKGROUND: Maternal feeding anxiety (FA) was prevalent during puerperium and might affect infant feeding practices. This study was aimed to investigate the FA status in Chinese postpartum women and its relationship with infant feeding practices (FPs). METHODS: Participants were from the Mother-Infant Cohort Study of China, in which the dietary and feeding practices, physical and psychiatric health for both mothers and infants were followed up from childbirth to next 2 years. In this study the maternal feeding anxiety (FA) status at 0-3 months postpartum was assessed by Li's Self-rating Feeding Anxiety Scale (SFAS). Infant feeding practices (FPs) at 0-3 months, including breastfeeding-related behaviors, responsive feeding and infant food refusal were investigated by self-designed questionnaire. RESULTS: In total 456 mothers the average feeding anxiety scores (FAS) was 41.02 ± 8.02 (mean ± SD), and maternal FA prevalence were 61.4% (FAS>38) with severe FA being 8.6% (FAS>52) at 0-3 months postpartum. The FAS was related with infant FPs, and lower maternal FAS was significantly related with infant colostrum feeding (40.86 ± 8.02 vs 44.74 ± 11.33, P < 0.05), but higher FAS was related with bottle feeding (41.95 ± 8.28 vs 39.69 ± 7.92, P < 0.05). The mothers with severe feeding anxiety (FAS > 53) were more likely to feed infants with bottle (ORs, 95%CI: 2.41, 1.11 ~ 5.19). There were not significant association between FAS and exclusive breastfeeding and responsive feeding practices (P > 0.05). The higher FAS was associated with infant food refusal behaviors, the maternal scores whose infant "never", "rarely", "sometimes" and "often" spat out food when feeding were 39.86 ± 8.02, 41.47 ± 8.18, 41.36 ± 7.44 and 42.14 ± 12.03 increasingly (P > 0.05), and the FA prevalence was significantly different among groups (P < 0.05). The infants whose mother was identified as feeding anxiety were more likely to refuse opening the mouth when feeding (P < 0.05). Multivariate analysis indicated maternal FAS was positively related to infant bottle feeding (ßi = 2.487, P < 0.05) and outdoor sunshine exposure practice (ßi = 1.787, P < 0.05), and negatively related to household income level (ßi = - 0.118, P < 0.05). CONCLUSIONS: Maternal postpartum feeding anxiety was associated with some infant feeding practices, including bottle feeding and infant food refusal behaviors.

The effects of TPL-PEI-CyD on suppressing performance of MCF-7 stem cells.

Triptolide, an ingredient of Tripterygium wilfordii, has been demonstrated to possess many biological activities such as immunomodulatory, antitumor activity in experiment. The purpose of this study was to survey the toxicity of TPL-PEI-CyD on renal cells and its effects on breast carcinoma stem cells. The cytotoxicity of TPL-PEI-CyD and TPL on HK-2 was comparatively assessed by CCK-8. After incubation and culturing with TGF-ß1, the MCF-7 cells were assessed by flow cytometry for the proportion of CD44+> CD24- cells; then the CD44>+> CD24- cells were sorted by immunomagnetic beads as MCF-7 stem cells. To assess the effect of TPL-PEI-CyD on MCF-7 stem cells, Western Blot was used to detect the expression of Oct-4 and ALDHl in MCF-7 stem cells after being dosed with TPL- PEI-CyD. Results showed that, compared with TPL, the toxicity of TPL-PEI-CyD on HK-2 cells was significantly reduced (P<0.05). Breast carcinoma stem cells can be enriched by TGF-ß1 and isolated from MCF-7 cells by immunomagnetic sorting. TPL- PEI-CyD can even more significantly suppress the expression of Oct-4 and ALDHA1 in MCF-7 stem cells than TPL (P<0.05). In conclusion, after coupling TPL and PEI-CyD, TPL-PEI-CyD showed characteristics of effective suppression to breast carcinoma stem cell and decrease of cytotoxicity. It presented the unique effect of traditional Chinese medicine as an efficient and low toxic drug carrier complex for breast carcinoma treatment.

Tricin, a flavonoid monomer in monocot lignification.

Tricin was recently discovered in lignin preparations from wheat (Triticum aestivum) straw and subsequently in all monocot samples examined. To provide proof that tricin is involved in lignification and establish the mechanism by which it incorporates into the lignin polymer, the 4'-O-ß-coupling products of tricin with the monolignols (p-coumaryl, coniferyl, and sinapyl alcohols) were synthesized along with the trimer that would result from its 4'-O-ß-coupling with sinapyl alcohol and then coniferyl alcohol. Tricin was also found to cross couple with monolignols to form tricin-(4'-O-ß)-linked dimers in biomimetic oxidations using peroxidase/hydrogen peroxide or silver (I) oxide. Nuclear magnetic resonance characterization of gel permeation chromatography-fractionated acetylated maize (Zea mays) lignin revealed that the tricin moieties are found in even the highest molecular weight fractions, ether linked to lignin units, demonstrating that tricin is indeed incorporated into the lignin polymer. These findings suggest that tricin is fully compatible with lignification reactions, is an authentic lignin monomer, and, because it can only start a lignin chain, functions as a nucleation site for lignification in monocots. This initiation role helps resolve a long-standing dilemma that monocot lignin chains do not appear to be initiated by monolignol homodehydrodimerization as they are in dicots that have similar syringyl-guaiacyl compositions. The term flavonolignin is recommended for the racemic oligomers and polymers of monolignols that start from tricin (or incorporate other flavonoids) in the cell wall, in analogy with the existing term flavonolignan that is used for the low-molecular mass compounds composed of flavonoid and lignan moieties.

[Role of Pediatric Critical Illness Score in evaluating severity and prognosis of severe hand-foot-mouth disease].

OBJECTIVE: To investigate the role of Pediatric Critical Illness Score (PCIS) in evaluating the prognosis and severity of severe hand-foot-mouth disease (HFMD). METHODS: This study included 424 children with severe HFMD, consisting of 390 survivors and 34 deceased patients. Related physiological parameters and clinical data were collected for calculating PCIS scores. The area under receiver operating characteristic curve (AUC) was employed to assess the performance of PCIS in evaluating the complications and outcomes. RESULTS: The median of PCIS scores for survivors was higher than that for deceased patients (P<0.01). Of the 424 children with severe HFMD, only 26 (6.1%) had critical illness according to the severity assessment using PCIS. The AUC (95%CI) of PCIS was 0.74 (0.66, 0.82) in predicting pulmonary edema, 0.82 (0.74, 0.90) in predicting pulmonary hemorrhage, and 0.83 (0.75, 0.92) in predicting death. CONCLUSIONS: PCIS can predict the complications and prognosis in children with severe HFMD. However, the existing scoring system of PCIS cannot fully assess the severity of HFMD.

Development of a clickable designer monolignol for interrogation of lignification in plant cell walls.

Lignin is an abundant and essential polymer in land plants. It is a prime factor in the recalcitrance of lignocellulosic biomass to agricultural and industrial end-uses such as forage, pulp and papermaking, and biofuels. To better understand lignification at the molecular level, we are developing a lignin spectroscopic and imaging toolbox on one "negligible" auxiliary. Toward that end, we describe the design, synthesis, and characterization of a new designer monolignol, 3-O-propargylcaffeyl alcohol, which contains a bioorthogonal alkynyl functional group at the 3-O-position. Importantly, our data indicate that this monolignol does not alter the fidelity of lignification. We demonstrate that the designer monolignol provides a platform for multiple spectroscopic and imaging approaches to reveal temporal and spatial details of lignification, the knowledge of which is critical to reap the potential of energy-rich renewable plant biomass for sustainable liquid fuels and other diverse economic applications.

Stretchable Iontronic Tactile Sensing Fabric.

The iontronic tactile sensing modality has garnered significant attention due to its exceptional sensitivity, immunity to noise, and versatility in materials. Recently, various formats of iontronic tactile sensors have been developed, including droplets, polymer films, paper, ionic gels, and fabrics. However, the stretchability of the current iontronic pressure sensing fabric is inadequate, hindered by the limited stretchiness of the ionic functional fabric. Incorporating a stretchable tactile sensing implement could enhance the wear comfortability by preventing relative movement and ensuring intimate contact between the sensor and the skin. The research focuses on the development of a stretchable iontronic pressure sensing (SIPS) fabric for monitoring diverse aspects of body health and movement in wearable applications. The tactile sensing structure is generated at the iontronic interface between highly stretchable ionic and conductive fabrics. In particular, the ionic fabric is prepared by coating a layer of polyurethane/ionic liquid gel onto a Spandex fabric. To showcase its remarkable sensitivity, stretchability, and ability to detect diverse body information, several application scenarios have been demonstrated including an elastic wristband for precise pulse wave detection, a flexible belt with multitactile sensing channels for respiration and motion tracking purposes, and a stretchable fabric cuff equipped with a high-resolution sensing array comprising 32 × 32 units for accurate gesture recognition.

Identification of grass-specific enzyme that acylates monolignols with p-coumarate.

Lignin is a major component of plant cell walls that is essential to their function. However, the strong bonds that bind the various subunits of lignin, and its cross-linking with other plant cell wall polymers, make it one of the most important factors in the recalcitrance of plant cell walls against polysaccharide utilization. Plants make lignin from a variety of monolignols including p-coumaryl, coniferyl, and sinapyl alcohols to produce the three primary lignin units: p-hydroxyphenyl, guaiacyl, and syringyl, respectively, when incorporated into the lignin polymer. In grasses, these monolignols can be enzymatically preacylated by p-coumarates prior to their incorporation into lignin, and these monolignol conjugates can also be "monomer" precursors of lignin. Although monolignol p-coumarate-derived units may comprise up to 40% of the lignin in some grass tissues, the p-coumarate moiety from such conjugates does not enter into the radical coupling (polymerization) reactions of lignification. With a greater understanding of monolignol p-coumarate conjugates, grass lignins could be engineered to contain fewer pendent p-coumarate groups and more monolignol conjugates that improve lignin cleavage. We have cloned and expressed an enzyme from rice that has p-coumarate monolignol transferase activity and determined its kinetic parameters.

Microfluidic-based in vitro thrombosis model for studying microplastics toxicity.

The potential impact of microplastics (MPs) on health has caused great concern, and a toxicology platform that realistically reproduces the system behaviour is urgently needed to further explore and validate MP-related health issues. Herein, we introduce an optically assisted thrombus platform to reveal the interaction of MPs with the vascular system. The risk of accumulation has also been evaluated using a mouse model, and the effect of MPs on the properties of the thrombus are validated via in vitro experiments. The microfluidic system is endothelialized, and the regional tissue injury-induced thrombosis is then realized through optical irradiation. Whole blood is perfused with MPs, and the invasion process visualized and recorded. The mouse model shows a cumulative risk in the blood with continuous exposure to MPs (P-value < 0.0001). The on-chip results show that MP invasion leads to decreased binding of fibrin to platelets (P-value < 0.0001), which is consistent with the results of the in vitro experiments, and shows a high risk of thrombus shedding in real blood flow compared with normal thrombus. This work provides a new method to further reveal MP-related health risks.

Release of methylene blue from graphene oxide-coated electrospun nanofibrous scaffolds to modulate functions of neural progenitor cells.

Transplantation of neural progenitor cells (NPCs) can repair the damaged neurons and therefore holds significant promise as a new treatment strategy for Alzheimer's disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a useful approach for AD therapy. In our study, the functional scaffolds were obtained by fabrication of a poly(lactic-co-glycolic acid) (PLGA) nanofibrous mat by the electrospinning technique, followed by coating of a layer of graphene oxide (GO) and then physisorption of methylene blue (MB) under mild conditions. The precoating of GO on the nanofibrous scaffolds allows efficient loading and release of MB from the substrate for regulating the functions of NPCs. The NPCs cultured on the scaffolds remained in the quiescence phase due to the activation of autophagy signaling pathway by MB. Moreover, the MB-loaded nanofibrous scaffolds diminish tau phosphorylation and protect NPCs from apoptosis. Definitely, more work, especially the in vivo experiment, is highly desired to demonstrate the feasibility of the current strategy for AD treatment. STATEMENT OF SIGNIFICANCE: Transplantation of neural progenitor cells (NPCs) can repair the damaged neurons and hold significant promise as a new treatment strategy for Alzheimer's disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a novel and useful approach for AD therapy. In this work, we have developed a GO and MB sequentially coated PLGA nanofibrous mat as a new scaffold for NPC transplantation and tauopathy inhibition. The coating of GO that we have demonstrated significantly enhanced the loading and release of MB on the scaffolds. Furthermore, NPCs cultured on the nanofibrous scaffolds entered quiescence phase through the activation of autophagy signaling pathway, leading to improved performance of NPCs to cope with stressors of disease. More importantly, the release of MB from the scaffolds leads to attenuation of tauopathy and protection of NPCs, which may represent a novel, versatile, and effective therapeutic approach for AD and other neurodegenerative diseases.

Structural features of alternative lignin monomers associated with improved digestibility of artificially lignified maize cell walls.

Plant biologists are seeking new approaches for modifying lignin to improve the digestion and utilization of structural polysaccharides in crop cultivars for the production of biofuels, biochemicals, and livestock. To identify promising targets for lignin bioengineering, we artificially lignified maize (Zea mays L.) cell walls with normal monolignols plus 21 structurally diverse alternative monomers to assess their suitability for lignification and for improving fiber digestibility. Lignin formation and structure were assessed by mass balance, Klason lignin, acetyl bromide lignin, gel-state 2D-NMR and thioacidolysis procedures, and digestibility was evaluated with rumen microflora and from glucose production by fungal enzymes following mild acid or base pretreatments. Highly acidic or hydrophilic monomers proved unsuitable for lignin modification because they severely depressed cell wall lignification. By contrast, monomers designed to moderately alter hydrophobicity or introduce cleavable acetal, amide, or ester functionalities into the polymer often readily formed lignin, but most failed to improve digestibility, even after chemical pretreatment. Fortunately, several types of phenylpropanoid derivatives containing multiple ester-linked catechol or pyrogallol units were identified as desirable genetic engineering targets because they readily formed wall-bound polymers and improved digestibility, presumably by blocking cross-linking of lignin to structural polysaccharides and promoting lignin fragmentation during mild acidic and especially alkaline pretreatment.

Cyclic RGD functionalized liposomes encapsulating urokinase for thrombolysis.

Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase, a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy. STATEMENT OF SIGNIFICANCE: In this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis.

Nanosystem composed with MSNs, gadolinium, liposome and cytotoxic peptides for tumor theranostics.

A dual-functional delivery system, based on mesoporous silica nanoparticles (MSNs) with the integration of Magnetic Resonance (MR) imaging and therapeutic peptide delivery, is reported in this paper. A lipid bilayer is attached onto the surface of the nanoparticles, following the doping of Gadolinium (Gd), a paramagnetic lanthanide ion. The liposome-coated GdMSNs exhibit improved colloidal stability, better biocompatibility and more efficient cellular uptake. The Gd renders the nano carrier a potential T1 contrast agent, confirmed by the MR imaging. A pro-apoptotic peptide, KLA (HGGKLAKLAKKLAKLAK), is encapsulated into the GdMSNs-LP and enters into the cells successfully to induce mitochondrial swelling and apoptosis, while it is nontoxic outside the cells. The synthesis procedure is convenient and free of toxic organic reagents. The nanosystem we construct may contribute to a promising theranostic platform for therapeutic peptide delivery in cancer treatment.

Prognostic Value of B-Type Natriuretic Peptide, Leukocytosis, and Hyperglycemia in Children with Severe Hand, Foot, and Mouth Disease.

OBJECTIVE: Our goal is to determine the prognostic value of serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP), leukocytosis, and hyperglycemia in patients with severe hand, foot, and mouth disease (HFMD). DESIGN: This is a prospective cohort study conducted from March 2011 through October 2012 at Hunan Children's Hospital. SETTING: Hunan Children's Hospital, a large children's teaching hospital with 1,500-beds located in the Changsha region of Hunan Province in China. PATIENTS: 295 children who were presented with clinical manifestation of severe HFMD, and required hospitalization. INTERVENTIONS: Standard supportive treatment for HFMD as recommended by the national guidelines. MEASUREMENTS: Admission blood samples were analyzed for NT-proBNP, leukocyte count, and serum glucose. Independent prognostic value of NT-proBNP for predicting mortality was evaluated using the Cox proportional hazard model adjusting for various covariates. MAIN RESULTS: Area under the curve of receiver operating characteristic (AUROC) analysis suggested that a serum concentration of NT-proBNP concentration more than 1,500 pg/mL is an optimal cutoff point. Twenty-four patients (8.1%) had an NT-proBNP more than 1,500 pg/mL, and a 3-day mortality of 46% (11/24). Adjusted for tachycardia, tachypnea, hypertension, hyperglycemia, leukocytosis, and conscious disturbance on presentation, elevated NT-proBNP was associated with a 22.5-fold (95% confidence interval, 3.56-142.66) increased risk of 3-day mortality. We have further improved the specificity and AUROC values by the HFMD laboratory score, which combines NT-proBNP, leukocytosis, and hyperglycemia. CONCLUSIONS: Routine admission surveillance for NT-proBNP is useful for identifying patients with HFMD at risk for mortality. Further studies are needed to determine whether early intervention in patients with highly elevated NT-proBNP can improve outcome.