Challenges and Opportunities of Transition Metal Oxides as Electrocatalysts.

As a sustainable energy technology, electrocatalytic energy conversion and storage has become increasingly prominent. The oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), nitrogen reduction reaction (NRR), and carbon dioxide reduction reaction (CO2 RR) are the key steps in the industrial applications of energy conversion and storage. Compared to the widely used precious metal catalysts, less-noble transition metal oxides (TMOs) and TMO-like materials have attracted broad attention as electrocatalysts in the above reactions. In this concept, we summarize the challenges and opportunities of some typical TMOs in electrocatalysis, and modification strategies of TMOs as electrocatalysts are discussed.

Predicting incidence of hepatitis E using machine learning in Jiangsu Province, China.

Hepatitis E is an increasingly serious worldwide public health problem that has attracted extensive attention. It is necessary to accurately predict the incidence of hepatitis E to better plan ahead for future medical care. In this study, we developed a Bi-LSTM model that incorporated meteorological factors to predict the prevalence of hepatitis E. The hepatitis E data used in this study are collected from January 2005 to March 2017 by Jiangsu Provincial Center for Disease Control and Prevention. ARIMA, GBDT, SVM, LSTM and Bi-LSTM models are adopted in this study. The data from January 2009 to September 2014 are used as the training set to fit models, and data from October 2014 to March 2017 are used as the testing set to evaluate the predicting accuracy of different models. Selecting models and evaluating the effectiveness of the models are based on mean absolute per cent error (MAPE), root mean square error (RMSE) and mean absolute error (MAE). A total of 44 923 cases of hepatitis E are detected in Jiangsu Province from January 2005 to March 2017. The average monthly incidence rate is 0.35 per 100 000 persons in Jiangsu Province. Incorporating meteorological factors of temperature, water vapour pressure, and rainfall as a combination into the Bi-LSTM Model achieved the state-of-the-art performance in predicting the monthly incidence of hepatitis E, in which RMSE is 0.044, MAPE is 11.88%, and MAE is 0.0377. The Bi-LSTM model with the meteorological factors of temperature, water vapour pressure, and rainfall can fully extract the linear and non-linear information in the hepatitis E incidence data, and has significantly improved the interpretability, learning ability, generalisability and prediction accuracy.

Shrimp-shell derived carbon nanodots as carbon and nitrogen sources to fabricate three-dimensional N-doped porous carbon electrocatalysts for the oxygen reduction reaction.

Development of cheap, abundant and metal-free N-doped carbon materials as high efficiency oxygen reduction electrocatalysts is crucial for their practical applications in future fuel cell devices. Here, three-dimensional (3D) N-doped porous carbon (NPC) materials have been successfully developed by a simple template-assisted (e.g., SiO2 spheres) high temperature pyrolysis approach using shrimp-shell derived N-doped carbon nanodots (N-CNs) as carbon and nitrogen sources obtained through a facile hydrothermal method. The shrimp-shell derived N-CNs with a product yield of ∼ 5% possess rich surface O- and N-containing functional groups and small nanodot sizes of 1.5-5.0 nm, which are mixed with surface acidification treated SiO2 spheres with an average diameter of ∼ 200 nm in aqueous solution to form a N-CNs@SiO2 composite subjected to a thermal evaporation treatment. The resultant N-CNs@SiO2 composite is further thermally treated in a N2 atmosphere at different pyrolysis temperatures, followed by acid etching, to obtain 3D N-doped porous carbon (NPC) materials. As electrocatalysts for oxygen reduction reaction (ORR) in alkaline media, the experimental results demonstrate that 3D NPC obtained at 800 °C (NPC-800) with a surface area of 360.2 m(2) g(-1) exhibits the best ORR catalytic activity with an onset potential of -0.06 V, a half wave potential of -0.21 V and a large limiting current density of 5.3 mA cm(-2) (at -0.4 V, vs. Ag/AgCl) among all NPC materials investigated, comparable to that of the commercial Pt/C catalyst with an onset potential of -0.03 V, a half wave potential of -0.17 V and a limiting current density of 5.5 mA cm(-2) at -0.4 V. Such a 3D porous carbon ORR electrocatalyst also displays superior durability and high methanol tolerance in alkaline media, apparently better than the commercial Pt/C catalyst. The findings of this work would be valuable for the development of low-cost and abundant N-doped carbon materials from biomass as high performance metal-free electrocatalysts.

A low-cost cementite (Fe3C) nanocrystal@N-doped graphitic carbon electrocatalyst for efficient oxygen reduction.

In this work, chitosan whiskers (CWs) were first extracted using low-cost and earth-abundant crab shells as materials by a series of chemical processes, and then assembled into chitosan whisker microspheres (CWMs) via a simple photochemical polymerization approach. Subsequently, a cementite (Fe3C) nanocrystal@N-doped graphitic carbon (Fe3C@NGC) nanocomposite was successfully fabricated by high temperature pyrolysis of CWMs adsorbed with ferric acetylacetonate (Fe(acac)3) at 900 °C. It was found that a suitable growth atmosphere generated inside CWMs during high temperature pyrolysis is critically important to form Fe3C nanocrystal cores, concurrently accompanying a structural transformation from chitosan whiskers to mesoporous graphitic carbon shells with natural nitrogen (N) doping properties, resulting in the formation of a core-shell structure Fe3C@NGC nanocomposite. The resulting samples were evaluated as electrocatalysts for oxygen reduction reaction (ORR). In comparison with sole N-doped graphitic carbon without Fe3C nanocrystals obtained by direct pyrolysis of chitosan whisker microspheres at 900 °C (CWMs-900), Fe3C@NGC showed significantly improved ORR catalytic activity. The tolerance to fuel cell molecules (e.g., methanol) and the durability of Fe3C@NGC are obviously superior to commercial Pt/C catalysts in alkaline media. The high ORR performance of Fe3C@NGC could be due to its large surface area (313.7 m(2) g(-1)), a synergistic role of Fe3C nanocrystals, N doping in graphitic carbon creating more catalytic active sites, and a porous structure of the nanocomposite facilitating mass transfer to efficiently improve the utilization of these catalytic active sites.

Introducing phosphorus atoms into MoS2 nanosheets through a vapor-phase hydrothermal process for the hydrogen evolution reaction.

Molybdenum disulfide (MoS2)-based electrocatalysts have been considered as promising alternatives to platinum for use in the hydrogen evolution reaction (HER). Developing MoS2 electrocatalysts with more active sites has been recognized as an efficient way to enhance the HER activity. Moreover, phase transition and heteroatom doping show great influence on the HER performance. In this work, we develop a vapor-phase hydrothermal (VPH) approach to introduce phosphorus (P) atoms into a MoS2 nanosheet array on carbon fiber cloth, which presents enhanced HER activity compared with MoS2 without P-doping. The improved performance is due to the synergistic effects of the new active sites formed by the P dopants and the sulfur (S) vacancies in the MoS2 nanosheets generated by the doping of P atoms, which increases the number of active sites. In general, the obtained P-doped MoS2/CFC exhibits a lower onset potential of 80 mV and an overpotential of 162 mV at 10 mA cm-2 than MoS2 without P-doping in 0.5 M H2SO4, accompanied by extremely large cathodic current density and excellent stability. This strategy may open up opportunities for heteroatom doping of electrocatalysts for various applications and provide a new method for material synthesis.

Detecting and Grounding Multi-Modal Media Manipulation and Beyond.

Misinformation has become a pressing issue. Fake media, in both visual and textual forms, is widespread on the web. While various DeepFake detection and text fake news detection methods have been proposed, they are only designed for single-modality forgery based on binary classification, let alone analyzing and reasoning subtle forgery traces across different modalities. In this paper, we highlight a new research problem for multi-modal fake media, namely Detecting and Grounding Multi-Modal Media Manipulation (DGM 4). DGM 4 aims to not only detect the authenticity of multi-modal media, but also ground the manipulated content (i.e., image bounding boxes and text tokens), which requires deeper reasoning of multi-modal media manipulation. To support a large-scale investigation, we construct the first DGM 4 dataset, where image-text pairs are manipulated by various approaches, with rich annotation of diverse manipulations. Moreover, we propose a novel HierArchical Multi-modal Manipulation rEasoning tRansformer (HAMMER) to fully capture the fine-grained interaction between different modalities. HAMMER performs: 1) manipulation-aware contrastive learning between two uni-modal encoders as shallow manipulation reasoning and 2) modality-aware cross-attention by multi-modal aggregator as deep manipulation reasoning. Dedicated manipulation detection and grounding heads are integrated from shallow to deep levels based on the interacted multi-modal information. To exploit more fine-grained contrastive learning for cross-modal semantic alignment, we further integrate Manipulation-Aware Contrastive Loss with Local View and construct a more advanced model HAMMER++. Finally, we build an extensive benchmark and set up rigorous evaluation metrics for this new research problem. Comprehensive experiments demonstrate the superiority of HAMMER and HAMMER++; several valuable observations are also revealed to facilitate future research in multi-modal media manipulation.

Talk-to-Edit: Fine-Grained 2D and 3D Facial Editing via Dialog.

Facial editing is to manipulate the facial attributes of a given face image. Nowadays, with the development of generative models, users can easily generate 2D and 3D facial images with high fidelity and 3D-aware consistency. However, existing works are incapable of delivering a continuous and fine-grained editing mode (e.g., editing a slightly smiling face to a big laughing one) with natural interactions with users. In this work, we propose Talk-to-Edit, an interactive facial editing framework that performs fine-grained attribute manipulation through dialog between the user and the system. Our key insight is to model a continual "semantic field" in the GAN latent space. 1) Unlike previous works that regard the editing as traversing straight lines in the latent space, here the fine-grained editing is formulated as finding a curving trajectory that respects fine-grained attribute landscape on the semantic field. 2) The curvature at each step is location-specific and determined by the input image as well as the users' language requests. 3) To engage the users in a meaningful dialog, our system generates language feedback by considering both the user request and the current state of the semantic field. We demonstrate the effectiveness of our proposed framework on both 2D and 3D-aware generative models. We term the semantic field for the 3D-aware models as "tri-plane" flow, as it corresponds to the changes not only in the color space but also in the density space. We also contribute CelebA-Dialog, a visual-language facial editing dataset to facilitate large-scale study. Specifically, each image has manually annotated fine-grained attribute annotations as well as template-based textual descriptions in natural language. Extensive quantitative and qualitative experiments demonstrate the superiority of our framework in terms of 1) the smoothness of fine-grained editing, 2) the identity/attribute preservation, and 3) the visual photorealism and dialog fluency. Notably, the user study validates that our overall system is consistently favored by around 80% of the participants.

An important role of interleukin-10 in counteracting excessive immune response in HT-29 cells exposed to Clostridium butyricum.

BACKGROUND: Clostridium butyricum has become increasingly important in preventing and treating intestinal inflammation. In the intestine it may increase the resistance of the gut to pathogen invasion via inducing the secretion of anti-inflammatory cytokines. Interleukin 10 (IL-10) plays a central role in preventing certain inflammatory diseases by down-regulating inflammatory cascades. In a previous study, we observed that the level of IL-10 mRNA was modulated by C. butyricum. The aim of this study was to investigate whether C. butyricum achieves its beneficial effects through IL-10. RESULTS: We treated HT-29 cells with anti-IL-10 (IL-10 antibody) or siIL-10 (IL-10 small interfering RNA) to disrupt IL-10. In both cases, the effects of C. butyricum-induced NF-κB activation and IL-8 expression were enhanced. We also found that neutralization or knockdown of IL-10 could induce apoptosis and necrosis of HT-29 cells treated with C. butyricum compared with control cells. CONCLUSIONS: These findings show that IL-10 serves an important role in C. butyricum-mediated immune protection, and in host recognition of C. butyricum.

Effect of double mutations K214/A-E215/Q of FRATide on GSK3ß: insights from molecular dynamics simulation and normal mode analysis.

Glycogen synthase kinase 3ß (GSK3ß) is a multifunctional serine/threonine protein kinase that is involved in several biological processes including insulin and Wnt signaling pathways. The Wnt signaling via FRAT-mediated displacement of axin inhibits GSK3ß activity toward non-primed substrates without affecting its activity toward primed substrates. Herein, molecular dynamics simulation, molecular mechanics generalized Born/surface area (MM_GBSA) calculation, and normal mode analysis are performed to explore the structural influence of the double mutations K214/A-E215/Q of FRATide on the GSK3ß-FRATide complex. The results reveal that the priming phosphate-binding site, the primed substrate-binding site, the alignment of the critical active site residues in the ATP-binding site, as well as the periodic open-closed conformational change of the ATP-binding site, which are critical for the catalytic activity of GSK3ß, are negligibly influenced in the mutated system compared with the wild-type (WT) system. This indicates that FRATide does not inhibit the GSK3ß activity toward primed substrates. Additionally, MM_GBSA calculation indicates that the less energy-favorable GSK3ß-FRATide complex is observed in the mutant than in the WT complex.

Clostridium butyricum activates TLR2-mediated MyD88-independent signaling pathway in HT-29 cells.

Oral administration of Clostridium butyricum as probiotic is increasingly gaining importance in the treatment of diarrhea and the improvement of animal performance. However, the mechanisms of host cell receptor recognition of C. butyricum and the downstream immune signaling pathways leading to these benefits remain unclear. The objective of this study was to analyze the mechanisms involved in C. butyricum induction of the toll-like receptor (TLR) signaling. Knockdown of myeloid differentiation primary response protein 88 (MyD88) expression using small interfering RNA in this manner did not affect C. butyricum-induced elevated levels of nuclear factor κB (NF-κB), interleukin-8 (IL-8), IL-6, and tumor necrosis factor alpha (TNF-α), suggesting a MyD88-independent route to TLR signaling transduction. However, a significant reduction in the levels of NF-κB, IL-8, IL-6, and TNF-α was evident in the absence of TLR2 expression, implying the need for TLR2 in C. butyricum recognition. Hence, C. butyricum activates TLR2-mediated MyD88-independent signaling pathway in human epithelial cells, which adds to our understanding of the molecular mechanisms of this probiotic action on gut epithelium.

Predicting incidence of hepatitis E for thirteen cities in Jiangsu Province, China.

Hepatitis E has placed a heavy burden on China, especially in Jiangsu Province, so accurately predicting the incidence of hepatitis E benefits to alleviate the medical burden. In this paper, we propose a new attentive bidirectional long short-term memory network (denoted as BiLSTM-Attention) to predict the incidence of hepatitis E for all 13 cities in Jiangsu Province, China. Besides, we also explore the performance of adding meteorological factors and the Baidu (the most widely used Chinese search engine) index as additional training data for the prediction of our BiLSTM-Attention model. SARIMAX, GBDT, LSTM, BiLSTM, and BiLSTM-Attention models are tested in this study, based on the monthly incidence rates of hepatitis E, meteorological factors, and the Baidu index collected from 2011 to 2019 for the 13 cities in Jiangsu province, China. From January 2011 to December 2019, a total of 29,339 cases of hepatitis E were detected in all cities in Jiangsu Province, and the average monthly incidence rate for each city is 0.359 per 100,000 persons. Root mean square error (RMSE) and mean absolute error (MAE) are used for model selection and performance evaluation. The BiLSTM-Attention model considering meteorological factors and the Baidu index has the best performance for hepatitis E prediction in all cities, and it gets at least 10% improvement in RMSE and MAE for all 13 cities in Jiangsu province, which means the model has significantly improved the learning ability, generalizability, and prediction accuracy when comparing with others.

Compound dietary fiber and high-grade protein diet improves glycemic control and ameliorates diabetes and its comorbidities through remodeling the gut microbiota in mice.

Dietary intervention with a low glycemic index and full nutritional support is emerging as an effective strategy for diabetes management. Here, we found that the treatment of a novel compound dietary fiber and high-grade protein diet (CFP) improved glycemic control and insulin resistance in streptozotocin-induced diabetic mice, with a similar effect to liraglutide. In addition, CFP treatment ameliorated diabetes-related metabolic syndromes, such as hyperlipidemia, hepatic lipid accumulation and adipogenesis, systemic inflammation, and diabetes-related kidney damage. These results were greatly associated with enhanced gut barrier function and altered gut microbiota composition and function, especially those bacteria, microbial functions, and metabolites related to amino acid metabolism. Importantly, no adverse effect of CFP was found in our study, and CFP exerted a wider arrange of protection against diabetes than liraglutide. Thereby, fortification with balanced dietary fiber and high-grade protein, like CFP, might be an effective strategy for the management and treatment of diabetes.

Role of bridging water molecules in GSK3ß-inhibitor complexes: insights from QM/MM, MD, and molecular docking studies.

The role of water molecules is increasingly gaining interest in drug design, and several studies have highlighted their paramount contributions to the specificity and the affinity of ligand binding. In this study, we employ the two-layer ONIOM-based quantum mechanics/molecular mechanics (QM/MM) calculations, molecular dynamics (MD) simulations, and molecular docking studies to investigate the effect of bridging water molecules at the GSK3ß-inhibitors interfaces. The results obtained from the ONIOM geometry optimization and AIM analysis corroborated the presence of bridging water molecules that form hydrogen bonds with protein side chain of Thr138 and/or backbone of Gln185, and mediate interactions with inhibitors in the 10 selected GSK3ß-inhibitor complexes. Subsequently, MD simulations carried out on a representative system of 1R0E demonstrated that the bridging water molecule is stable at the GSK3ß-inhibitor interface and appears to contribute to the stability of the protein-inhibitor interactions. Furthermore, molecular docking studies of GSK3ß-inhibitor complexes indicated that the inhibitors can increase binding affinities and the better docked conformation of inhibitors can be obtained by inclusion of the bridging water molecules, especially for the flexible inhibitors, in docking experiments into individual protein conformations. Our results elucidate the importance of bridging water molecules at the GSK3ß-inhibitor interfaces and suggest that they might prove useful in rational drug design.

FeCl3-promoted alkylation of indoles by enamides.

An efficient iron-promoted alkylation of indoles with enamides has been accomplished under mild reaction conditions. The reaction proceeded with remarkable regioselectivity leading exclusively to substitution by indoles at α-position of enamides.

Molecular modeling and molecular dynamics simulation studies of the GSK3ß/ATP/substrate complex: understanding the unique P+4 primed phosphorylation specificity for GSK3ß substrates.

Substrate specificity of protein kinases is of fundamental importance for the integrity and fidelity of signaling pathways. Glycogen synthase kinase 3ß (GSK3ß) has a unique substrate specificity that prefers phosphorylation of its substrates at the P+4 serine before it can further phosphorylate the substrate at the P0 serine in the canonical motif SXXXS(p), where S(p) is the primed phosphorylation site. The detailed phosphorylation mechanism, however, is not clearly understood. In this study, a three-dimensional (3D) model of the ternary complex of GSK3ß, ATP, and the phosphorylated glycogen synthase (pGS), termed GSK3ß/ATP/pGS, is constructed using a hierarchical approach and by integrating molecular modeling and molecular dynamics (MD) simulations. Based on the 3D model, the substrate primed phosphorylation mechanism is investigated via two 12 ns comparative MD simulations of the GSK3ß/ATP/pGS and GSK3ß/ATP/GS systems, which differ in the phosphate group bound to the P+4 serine of GS. In agreement with structural analysis, computed binding free energies reveal that the binding of pGS to GSK3ß is favored in the prephosphorylated state compared with the GS native state. More importantly, comparison with the system simulated without primed phosphorylation in the GSK3ß/ATP/GS complex shows that for an optimal phosphorylation reaction to occur, the pGS priming phosphate in the GSK3ß/ATP/pGS system optimizes the proper orientation of the GSK3ß N- and C-terminal domains and clamps the P0 serine of pGS in the appropriate configuration for interaction with the ATP γ-phosphate within the catalytic groove.

Dissection of the difference between the group I metal ions in inhibiting GSK3ß: a computational study.

Glycogen synthase kinase 3ß (GSK3ß) is a serine/threonine kinase that requires two cofactor Mg(2+) ions for catalysis in regulating many important cellular signals. Experimentally, Li(+) is a competitive inhibitor of GSK3ß relative to Mg(2+), while this mechanism is not experienced with other group I metal ions. Herein, we use native Mg(2)(2+)-Mg(1)(2+) GSK3ß and its Mg(2)(2+)-M(1)(+) (M = Li, Na, K, and Rb) derivatives to investigate the effect of metal ion substitution on the mechanism of inhibition through two-layer ONIOM-based quantum mechanics/molecular mechanics (QM/MM) calculations and molecular dynamics (MD) simulations. The results of ONIOM calculations elucidate that the interaction of Na(+), K(+), and Rb(+) with ATP is weaker compared to that of Mg(2+) and Li(+) with ATP, and the critical triphosphate moiety of ATP undergoes a large conformational change in the Na(+), K(+), and Rb(+) substituted systems. As a result, the three metal ions (Na(+), K(+), and Rb(+)) are not stable and depart from the active site, while Mg(2+) and Li(+) can stabilize in the active site, evident in MD simulations. Comparisons of Mg(2)(2+)-Mg(1)(2+) and Mg(2)(2+)-Li(1)(+) systems reveal that the inline phosphor-transfer of ATP and the two conserved hydrogen bonds between Lys85 and ATP, together with the electrostatic potential at the Li(1)(+) site, are disrupted in the Mg(2)(2+)-Li(1)(+) system. These computational results highlight the possible mechanism why Li(+) inhibits GSK3ß.

Review of prophylactic swallowing interventions for head and neck cancer.

BACKGROUND: Head and neck cancer treatment destroys nerves and/or organs associated with swallowing. Previous studies have investigated the efficacy of exercises for muscles used in swallowing before treatment in reducing disuse atrophy and delaying the occurrence of muscle fibrosis. However, the rehabilitation effects of training and the optimal intervention strategy are unknown. OBJECTIVES: To establish evidence for the efficacy of prophylactic swallowing interventions in reducing aspiration and restoring oral intake in patients with head and neck cancer with dysphagia. METHODS: We searched electronic databases (PubMed, Embase, Cochrane and MEDLINE) for studies published up to June 2021 reporting outcomes following prophylactic swallowing interventions in patients with head and neck cancer with dysphagia and the related influencing factors. The methodological quality of the literature was assessed using the Joanna Briggs Institute appraisal tools. RESULTS: The search identified 1468 articles, and 13 studies were eventually included. Four categories involving 12 different swallowing interventions were classified. Regarding the descriptive analysis of the rehabilitation effects across all studies, in terms of oropharyngeal safety, five studies showed that swallowing interventions reduced the risk of aspiration, penetration or residue. In terms of oral intake and tube feeding dependence, four studies demonstrated reduced time to return to oral intake in the intervention group compared with the control group. In terms of intervention adherence, three studies showed that speech-language pathologist- and nurse-supervised training was a potential promoter of adherence, and five studies showed that the negative factors affecting adherence included pain, fatigue, forgetting, smoking, decreased exercise motivation, side effects of radiotherapy and distance to the rehabilitation site. CONCLUSIONS: Preventive swallowing interventions may be effective at reducing aspiration, improving swallowing function, and restoring oral intake. However, due to the lack of standardization and consistency of interventions and measurement results, which prevented the production of a best practice guide, future rigorous methodological trials will be needed to determine the most effective interventions for maximizing exercise adherence over the long term.

Dietary supplementation with Bacillus subtilis promotes growth performance of broilers by altering the dominant microbial community.

The purpose of this study was to investigate the effects of Bacillus subtilis on growth performance, intestinal morphology, and cecal microbial composition of broilers. A total of 270 healthy one-day-old Arbor Acres male broiler chicks were randomly divided into 3 dietary treatment groups, with 6 replicates per group and 15 chickens per replicate. The dietary treatment groups were as follows: 1) basal diet, negative control group; 2) basal diet +250 g/t of zinc bacitracin, positive control group; and 3) basal diet +750 g/t of B. subtilis, B. subtilis group. Results of this experiment showed that compared with the negative control group, body weight at 42 d, average daily gain and European Production Efficiency Factor over the 42 d phase in the B. subtilis group and positive control group were significantly increased (P < 0.05); feed conversion rates in the B. subtilis group and positive control group were significantly decreased (P < 0.05); and average daily feed intake and mortality were not significantly different (P > 0.05). The villus height to crypt depth ratio in the ileum of the B. subtilis group was significantly higher (P < 0.05) than that of the negative control group. The results of cecal microflora at genus level were as follows. As compared with the negative control group, the abundance of Blautia, Faecalibacterium, Flavonifractor, and Hydrogenoanaerobacterium of the B. subtilis group and positive control group was significantly higher (P < 0.05), whereas the abundance of Odoribacter was significantly lower (P < 0.05). Moreover, abundance of the genera Romboutsia in the B. subtilis group was higher (P < 0.05) than that in the positive control group. The abundance of Flavonifractor, Erysipelatoclostridium, and Hydrogenoanaerobacterium were positively correlated with body weight and average daily gain by Spearman correlation analysis. In conclusion, dietary supplementation with B. subtilis improved growth performance of broilers which may be related to the increased abundance of Blautia, Faecalibacterium, Flavonifractor, Hydrogenoanaerobacterium, and Romboutsia, along with the decreased abundance of Odoribacter. In addition, the effect of B. subtilis was superior to zinc bacitracin in improving intestinal microbial composition of broilers. Therefore, B. subtilis may act as an effective antibiotic substitute in broilers.

Efficacy and safety of combined nonpharmacological interventions for repeated procedural pain in preterm neonates: A systematic review of randomized controlled trials.

INTRODUCTION: Premature infants undergo numerous painful procedures during hospitalization. Some trials have examined the effectiveness and safety of combined nonpharmacological interventions in which two or more non-pharmacological interventions are used simultaneously or continuously to relieve repeated procedural pain via multisensory stimulation in preterm neonates. However, a systematic review of this topic has not yet been carried out. OBJECTIVE: To review the evidence on the efficacy and safety of combined nonpharmacological interventions for repeated procedural pain in preterm neonates. METHOD: Eight databases were searched using keywords to identify peer-reviewed journal articles in English or Chinese. Randomized controlled trials (RCTs) focusing on combined nonpharmacological interventions for repeated procedural pain in preterm neonates published from database inception until May 2019 were included. RESULTS: Eight RCTs were retrieved that included ten different combined nonpharmacological interventions. Different study designs were used in the included trials, which did not allow us to carry out a meta-analysis. The findings from the included articles were categorized in terms of efficacy and safety. With respect to efficacy, 1. two trials reported that combined nonpharmacological interventions were more effective than usual care during painful procedures; 2. three trials reported that combined nonpharmacological interventions were more effective than single nonpharmacological interventions; 3. three trials reported the effects of different combinations of nonpharmacological interventions and found that their effect depends on intervention type rather than number of interventions. Only four trials reported on safety, and they found that combined nonpharmacological interventions were safe for repeated procedural pain in preterm neonates. CONCLUSION: According to the literature, combined nonpharmacological interventions may be effective and safe for repeated procedural pain in premature infants. However, due to the diversity of interventions included in this systematic review, the evidence is not strong enough to produce a best practice guideline. Further research is needed with larger sample sizes and less heterogeneity to adequately explore the efficacy and safety of combined nonpharmacological interventions for repeated procedural pain in premature infants.

Single-step purification of dracorhodin from dragon's blood resin of Daemonorops draco using high-speed counter-current chromatography combined with pH modulation.

Dracorhodin is a major constituent found in "Dragon's blood" resin of Daemonorops draco Willd. Blume. This natural flavylium compound is a potent pharmaceutical substance due to its biological and pharmacological activities such as antimicrobial, antiviral, antitumor and cytotoxic activity. An effective high-speed counter-current chromatography method was successfully established for the isolation and purification of dracorhodin directly from extract of D. draco by using a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (2:3:2:3 v/v). Under the optimal conditions, 6.6 mg dracorhodin was obtained from 100 mg crude resin. The isolated fraction of counter-current chromatography was determined by HPLC, NMR, UV/visible and ESI/MS combined with pH modulation, since dracorhodin is unstable in solution which exists in different forms depending on pH values. The data were compared with those of the reference substance, and the literatures as well. The purity of dracorhodin was over 98% based on the HPLC result.