Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Solvent Effects on the 1 H-NMR Chemical Shifts of Imidazolium-Based Ionic Liquids.

The 1 H nuclear magnetic resonance (1 H-NMR) spectrum is a useful tool for characterizing the hydrogen bonding (H-bonding) interactions in ionic liquids (ILs). As the main hydrogen bond (H-bond) donor of imidazolium-based ILs, the chemical shift (δH2 ) of the proton in the 2-position of the imidazolium ring (H2) exhibits significant and complex solvents, concentrations and anions dependence. In the present work, based on the dielectric constants (ϵ) and Kamlet-Taft (KT) parameters of solvents, we identified that the δH2 are dominated by the solvents polarity and the competitive H-bonding interactions between cations and anions or solvents. Besides, the solvents effects on δH2 are understood by the structure of ILs in solvents: 1) In diluted solutions of inoizable solvents, ILs exist as free ions and the cations will form H-bond with solvents, resulting in δH2 being independent with anions but positively correlated with ßS . 2) In diluted solutions of non-ionzable solvents, ILs exist as contact ion-pairs (CIPs) and H2 will form H-bond with anions. Since non-ionizable solvents hardly influence the H-bonding interactions between H2 and anions, the δH2 are not related to ßS but positively correlated with ßIL .

Triad3A involved in the regulation of endotoxin tolerance and mycobactericidal activity through the NFκB-nitric oxide pathway.

INTRODUCTION: Sepsis is characterized by an endotoxin tolerance phenotype that occurs in the stage of infection. Persistent bacterial infection can lead to immune cell exhaustion. Triad3A, an E3 ubiquitin ligase, negatively regulates its activation by TLR4. However, the effect of Triad3A on endotoxin tolerance and bactericidal ability in the state of endotoxin tolerance remains unclear. METHODS: Using single dose LPS and repeated LPS stimulated macrophage cell lines at indicated times, we investigated miR-191, Tirad3A, TRAF3, TLR4, p-P65, TNF-α, IL-1ß, and iNOS expression, the effect of miR-191 on Triad3A and TRAF3, gene loss-of-function analyses, the effect of Triad3A on TLR4, p-P65, cytokine, and mycobactericidal activity in endotoxin tolerant cells infected with Mycobacterium marinum. RESULTS: Here we found that Triad3A is involved in regulating endotoxin tolerance. Our result also displayed that miR-191 expression is downregulated in macrophages in the state of endotoxin tolerance. miR-191 can directly bind to Triad3A and TRAF3. Additionally, knockdown of Triad3A can reverse the effect of decreasing TNF-α and IL-1ß in endotoxin tolerant macrophages. Furthermore, we demonstrated that the TLR4-NF-κB-NO pathway was associated with Triad3A and responsible for the killing of intracellular mycobacteria in a tuberculosis sepsis model. CONCLUSIONS: These results provide new insight into the mechanisms of Triad3A induced tolerogenic phenotype in macrophages, which can help the better comprehension of the pathogenesis involved in septic shock with infection of Mycobacterium tuberculosis, and suggest that Triad3A may be a potential drug target for the treatment of severe septic tuberculosis.

Microstructure and Mechanical Properties of High-Specific-Strength (TiVCrZr)100-xWx (x = 5, 10, 15 and 20) Refractory High-Entropy Alloys.

With the increasing demand for high-specific-strength materials for high-temperature applications, particularly in the aerospace field, novel (TiVCrZr)100-xWx (x = 5, 10, 15 and 20) refractory high-entropy alloys (RHEAs) were developed. The phase formation, microstructure, and mechanical properties were studied. The (TiVCrZr)100-xWx RHEAs exhibit a relatively high specific strength and low density compared with the W-containing RHEAs and most of the W-free RHEAs. In (TiVCrZr)100-xWx RHEAs, Laves, BCC and Ti-rich phases are formed, where the Laves phase is the major phase, and the volume fraction of the BCC phase increases with increasing W content. (TiVCrZr)100-xWx RHEAs exhibit dendrite structures, where W is enriched in the dendrite region, and increasing W-rich precipitations corresponding to the BCC phase are observed. The improvement of the strength and hardness of RHEAs is mainly attributed to the evolution of the microstructure and corresponding strengthening effect of W. The empirical parameters and calculated phase diagram were investigated, which further explain and verify the formation and variation of phases. The present findings give more insights into the formation of multi phases in (TiVCrZr)100-xWx RHEAs, and explore their application potential in the aerospace industry and nuclear reactors due to their high specific strength and low-activation constituent elements.

On the WEDM of WNbMoTaZrx (x = 0.5, 1) Refractory High Entropy Alloys.

As a potential candidate for the next generation of high-temperature alloys, refractory high entropy alloys (RHEAs) have excellent mechanical properties and thermal stability, especially for high-temperature applications, where the processing of RHEAs plays a critical role in engineering applications. In this work, the wire electrical discharge machining (WEDM) performance of WNbMoTaZrx (x = 0.5, 1) RHEAs was investigated, as compared with tungsten, cemented carbide and industrial pure Zr. The cutting efficiency (CE) of the five materials was significantly dependent on the melting points, while the surface roughness (Ra) was not. For the RHEAs, the CE was significantly affected by the pulse-on time (ON), pulse-off time (OFF) and peak current (IP), while the surface roughness was mainly dependent on the ON and IP. The statistical analyses have shown that the CE data of RHEAs have relatively-smaller Weibull moduli than those for the Ra data, which suggests that the CE of RHEAs can be tuned by optimizing the processing parameters. However, it is challenging to tune the surface roughness of RHEAs by tailoring the processing parameters. Differing from the comparative materials, the WEDMed surfaces of the RHEAs showed dense spherical re-solidified particles at upper recast layers, resulting in larger Ra values. The proportion of the upper recast layers can be estimated by the specific discharge energy (SDE). Following the WEDM, the RHEAs maintained the main BCC1 phase, enriched with the W and Ta elements, while the second BCC2 phase in the Zr1.0 RHEA disappeared. Strategies for achieving a better WEDMed surface quality of RHEAs were also proposed and discussed.

Disrupted Spontaneous Neural Activity and Its Interaction With Pain and Emotion in Temporomandibular Disorders.

Background and Purpose: Temporomandibular disorders (TMD), especially pain-related TMD, are closely related to social and psychological factors. We aimed to measure changes in spontaneous brain activity and its related functional connectivity (FC), as well as FC characteristics within the mood-regulating circuits (MRC) in TMD patients by resting-state functional magnetic resonance imaging (RS-fMRI), and to analyze the relationship between these parameters and emotional symptoms. Materials and Methods: Twenty-one adult TMD patients and thirty demographically matched healthy controls (HCs) underwent clinical scale evaluation and RS-fMRI scanning. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) between the two groups were compared. Regions with abnormal ALFF values were selected as areas of interest (ROIs) to compare the differences of whole-brain seed-based FC between groups. The FCs between regions within MRC were also analyzed and compared. In addition, the relationships between RS-fMRI characteristics and pain and mood were explored by correlation and mediation analyses. Results: Compared with HCs, TMD patients showed increased ALFF in the right parahippocampal gyrus (PHG), the right supplementary motor area, and the bilateral precentral gyrus, with decreased ALFF in the right cerebelum_crus2. Patients showed enhanced right PHG-related FC in the vermis and posterior cingulate cortex, orbitofrontal cortex (OFC)-related FC in the striatal-frontal regions, while decreased dorsolateral prefrontal cortex-related FC in the amygdala. In TMD patients, ALFF values in the right PHG and FC values between the right PHG and the vermis were positively correlated with depressive symptoms. Abnormal FCs in the left striatal-orbitofrontal pathway were correlated with pain and depressive symptoms. More importantly, mediation analysis revealed that chronic pain mediates the relationship between FC of right PHG with vermis and depressive symptoms, and abnormal FC in the left striatal-orbitofrontal pathway can mediate the association between pain and depressive symptoms. Conclusion: TMD patients have dysregulated spontaneous activity and FC in the default mode network, sensorimotor network and pain-related regions, as well as dysfunction of the fronto-striatal-limbic circuits. The development of negative emotions in TMD may be related to the dysfunction of components within the reward system (especially hippocampus complex, OFC, striatum) due to chronic pain.

The relationship between previous pulmonary tuberculosis and risk of lung cancer in the future.

Various investigations have expanded the views that tuberculosis is an important risk factor for lung cancer occurrence. Lung cancer originates from chronic inflammation and infection. It is becoming clearer that Mycobacterium tuberculosis (M.tb) in tuberculosis patients meticulously schemes multiple mechanisms to induce tumor formation and is indispensable to participate in the occurrence of lung cancer. In addition, some additional factors such as age, sex and smoking, accelerate the development of lung cancer after Mycobacterium tuberculosis infection. The clarification of these insights is fostering new diagnoses and therapeutic approaches to prevention of the patients developing from tuberculosis into lung cancer.

Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.

BACKGROUND AND PURPOSE: The appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms. METHODS: Thirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses. RESULTS: Compared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation. CONCLUSION: IBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal-limbic-midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.

Polymer solubility in ionic liquids: dominated by hydrogen bonding.

Polymer solubility in ionic liquids (ILs) cannot be predicted by the solubility parameter approach based on the "like dissolves like" principle. According to the Kamlet-Abraham-Taft (KAT) multi-parameter polarity scale, ILs can be categorized on the basis of hydrogen-bond acidity or basicity ones. The experimental observations, that acidic ILs easily dissolve basic polymers and basic ILs dissolve acidic polymers, reflect the complementary nature of hydrogen-bonding interactions. A quantitative hydrogen-bonding analysis is proposed for predicting the solubility by taking the product of ΔαΔß as an indicator of the competition between cross-association and self-association hydrogen bonding (H-bonding), where Δα is the difference of acidity parameters between the polymer and IL, and Δß is the difference of basicity. This solubility criterion has been validated by the solubility data of 19 polymers (11 acidic and 8 basic) in 11 ILs (7 acidic and 4 basic). These principles based on KAT parameters can be applied to other systems dominated by hydrogen bonding.

Adenosylation reactions catalyzed by the radical S-adenosylmethionine superfamily enzymes.

The radical S-adenosylmethionine (SAM) superfamily enzymes reductively cleave SAM to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical, which in most cases abstracts a hydrogen from the substrate and initiates highly diverse reactions. In rare cases, the dAdo radical can add to a sp2 carbon to result in the production an adenosylated product. These radical SAM-dependent adenosylation reactions are present in natural product biosynthetic pathways and can be achieved by using unnatural substrate analogs containing olefin or aryl moieties. This Opinion provides a focused perspective on this emerging type of biochemistry and discusses its potential use in bioengineering and biocatalysis.

Pyridoxal-5'-phosphate-dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi.

Indolizidine alkaloids such as anticancer drugs vinblastine and vincristine are exceptionally attractive due to their widespread occurrence, prominent bioactivity, complex structure, and sophisticated involvement in the chemical defense for the producing organisms. However, the versatility of the indolizidine alkaloid biosynthesis remains incompletely addressed since the knowledge about such biosynthetic machineries is only limited to several representatives. Herein, we describe the biosynthetic gene cluster (BGC) for the biosynthesis of curvulamine, a skeletally unprecedented antibacterial indolizidine alkaloid from Curvularia sp. IFB-Z10. The molecular architecture of curvulamine results from the functional collaboration of a highly reducing polyketide synthase (CuaA), a pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (CuaB), an NADPH-dependent dehydrogenase (CuaC), and a FAD-dependent monooxygenase (CuaD), with its transportation and abundance regulated by a major facilitator superfamily permease (CuaE) and a Zn(II)Cys6 transcription factor (CuaF), respectively. In contrast to expectations, CuaB is bifunctional and capable of catalyzing the Claisen condensation to form a new C-C bond and the α-hydroxylation of the alanine moiety in exposure to dioxygen. Inspired and guided by the distinct function of CuaB, our genome mining effort discovers bipolamines A-I (bipolamine G is more antibacterial than curvulamine), which represent a collection of previously undescribed polyketide alkaloids from a silent BGC in Bipolaris maydis ATCC48331. The work provides insight into nature's arsenal for the indolizidine-coined skeletal formation and adds evidence in support of the functional versatility of PLP-dependent enzymes in fungi.

Enzyme-catalysed [6+4] cycloadditions in the biosynthesis of natural products.

Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis2 for the formation of six-membered rings and are now well-established in biosynthesis3-6. [6+4] and other 'higher-order' cycloadditions were predicted7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states.

Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi.

Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.

Theoretical study of the local structure and Raman spectra of CaO-SiO2 binary melts.

A procedure for the Raman spectra calculation of vitreous and molten silicates was presented in this paper. It includes molecular dynamics MD simulation for the generation of equilibrium configurations, Wilson's GF matrix method for the calculations of eigenfrequencies and corresponding vectors, electro-optical parameters method (EOPM) for the Raman intensity calculations, and the bond polarizability model (BPM) for the determination of polarizability and polarizability derivative. One of the most important characteristics of this procedure is the achievement of the partial Raman spectra of five tetrahedral units, as well as the total spectral envelope. In this paper, the calculation was carried out for the vitreous and molten calcium silicates with different compositions and at various temperatures. It is worthwhile to note that the calculation is based on statistical configurations distribution in the space and so it is not needed to artificially adjust the full width at half maximum (FWHM) of spectra. It was also tested through the good agreement of the calculated spectra with the experimental, including some regularity of spectral properties. According to the calculation, the symmetrical stretching of whole tetrahedral units, to which the stretching of Si-O(nb) bond gives the main contribution to intensity, is proven to be the dominance in the high-frequency range (800-1200 cm(-1)) and the symmetrical bending of Si-O(b)-Si, to which the stretching of Si-O(b) bond exhibits the main contribution, is the dominance in the medium-frequency range (400-700 cm(-1)). As the first theoretical results, the Raman scattering coefficient of each Q(i) was found little change along with the variation of composition and temperature.

[Raman spectroscopic study of silicon-oxygen tetrahedrons microstructure in x CaSiO3.LiBO2 solid solutions].

Raman spectra of xCaSiO3.LiBO2 (by weight ratio, x = 0, 0.25, 0.33, 0.50) crystals were measured. The microstructure of different silicon-oxygen tetrahedrons and their abundant variations with silica contents were studied. It shows that all the silicon-oxygen tetrahedrons are isolated by Si-Ob-B bondings or free SiO4(4-). No evidence suggests that there exist considerable Si-Ob-Si bondings. The abundance of Q2, Q4 species increases with the increasing silica content, there exists barely Q3 species even at high silica content. And the sum of integrated Raman peaks for all Qi species are linearly correlated with silica concentration in crystal, which offers the possibility to analysis silica in minerals, slags, glasses and soil samples directly.