Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal ...microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The violation of Leggett–Garg inequalities tested the quantumness of neutrino oscillations (NOs) across macroscopic distances. The quantumness can be quantified by using the tools of the quantum ...resource theories. Recently, a new genuine tripartite entanglement measure (Xie et al. in Phys Rev Lett 127:040403, 2021), concurrence fill, is defined as the square root of the area of the concurrence triangle satisfying all genuine multipartite entanglement conditions. It has several advantages compared to other existing tripartite measures. Here, we focus on using concurrence fill to quantify the tripartite entanglement in three-flavor NOs. Concurrence fill can reach its maximum 0.89 for the experimentally-observed electron antineutrino oscillations, but it cannot for the muon antineutrino oscillations. In both cases, we compare its performance with other three tripartite entanglement measures, including the generalized geometric measure (GGM), the three-
π
entanglement, and the genuinely multipartite concurrence (GMC), in the neutrino propagation, and accordingly show that concurrence fill contains the most quantum resource. Furthermore, concurrence fill and the three-
π
entanglement are always smooth, while GGM and GMC measures have several sharp peaks. The genuine tripartite quantification of the quantumness of three-flavor NOs represents the first step towards the further potential application of neutrinos on quantum information processing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A metal‐free trimolecular 2+2+2 cycloaddition of internal ynamides and nitriles for de novo synthesis of fully substituted pyridines is disclosed. With the versatile Brønsted acid catalyst HNTf2, the ...mild intermolecular cyclotrimerization process proceeds with complementary chemoselectivity and excellent regioselectivity.
Triple two: A metal‐free 2+2+2 cycloaddition of internal ynamides and nitriles was developed for the de novo synthesis of fully substituted pyridines. In contrast to metal catalysis, the versatile Brønsted acid HNTf2 smoothly catalyzes the mild intermolecular cyclotrimerization of a range of ynamides and unactivated nitriles with complementary chemoselectivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for ...antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix4arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems.
Here we report a light‐induced FeCl3‐catalyzed approach for benzyl C−H chlorination with remarkable regioselectivity, which enables alkylbenzenes to be converted into versatile benzyl chlorides under ...mild conditions using trifluoromethanesulfonyl chloride (TfCl) as the chlorine source. DFT calculations show that the dynamics preference of benzylic α−C−H chlorination is more pronounced by employing TfCl.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Due to the persistence of metals in the ecosystem and their threat to all living organisms, effects of heavy metal on soil microbial communities were widely studied. However, little was known about ...the interactions among microorganisms in heavy metal-contaminated soils. In the present study, microbial communities in Non (CON), moderately (CL) and severely (CH) contaminated soils were investigated through high-throughput Illumina sequencing of 16s rRNA gene amplicons, and networks were constructed to show the interactions among microbes. Results showed that the microbial community composition was significantly, while the microbial diversity was not significantly affected by heavy metal contamination. Bacteria showed various response to heavy metals. Bacteria that positively correlated with Cd, e.g. Acidobacteria_Gp and Proteobacteria_thiobacillus, had more links between nodes and more positive interactions among microbes in CL- and CH-networks, while bacteria that negatively correlated with Cd, e.g. Longilinea, Gp2 and Gp4 had fewer network links and more negative interactions in CL and CH-networks. Unlike bacteria, members of the archaeal domain, i.e. phyla Crenarchaeota and Euryarchaeota, class Thermoprotei and order Thermoplasmatales showed only positive correlation with Cd and had more network interactions in CH-networks. The present study indicated that (i) the microbial community composition, as well as network interactions was shift to strengthen adaptability of microorganisms to heavy metal contamination, (ii) archaea were resistant to heavy metal contamination and may contribute to the adaption to heavy metals. It was proposed that the contribution might be achieved either by improving environment conditions or by cooperative interactions.
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•Heavy metals were the most important factor affecting microbes.•Microbial interactions were changed in response to heavy metal contamination.•Bacteria showed diverse changes in response to heavy metal contamination.•Archaea were tolerant to heavy metals.•Microbes adapt to heavy metal contamination through their interactions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In Buckdahn, Djehiche, Li, and Peng (2009), the authors obtained mean-field Backward Stochastic Differential Equations (BSDEs) in a natural way as a limit of some highly dimensional system of forward ...and backward SDEs, corresponding to a great number of “particles” (or “agents”). The objective of the present paper is to deepen the investigation of such mean-field BSDEs by studying their stochastic maximum principle. This paper studies the stochastic maximum principle (SMP) for mean-field controls, which is different from the classical ones. This paper deduces an SMP in integral form, and it also gets, under additional assumptions, necessary conditions as well as sufficient conditions for the optimality of a control. As an application, this paper studies a linear quadratic stochastic control problem of mean-field type.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Dielectric elastomer actuators (DEAs) with large electrically-actuated strain can build light-weight and flexible non-magnetic motors. However, dielectric elastomers commonly used in the ...field of soft actuation suffer from high stiffness, low strength, and high driving field, severely limiting the DEA’s actuating performance. Here we design a new polyacrylate dielectric elastomer with optimized crosslinking network by rationally employing the difunctional macromolecular crosslinking agent. The proposed elastomer simultaneously possesses desirable modulus (~0.073 MPa), high toughness (elongation ~2400%), low mechanical loss (tan
δ
m
= 0.21@1 Hz, 20 °C), and satisfactory dielectric properties (
$${\varepsilon }_{{{\rm{r}}}$$
ε
r
= 5.75, tan
δ
e
= 0.0019 @1 kHz), and accordingly, large actuation strain (118% @ 70 MV m
−1
), high energy density (0.24 MJ m
−3
@ 70 MV m
−1
), and rapid response (bandwidth above 100 Hz). Compared with VHB
TM
4910, the non-magnetic motor made of our elastomer presents 15 times higher rotation speed. These findings offer a strategy to fabricate high-performance dielectric elastomers for soft actuators.
Background
The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota ...dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown.
Methods
A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions
via
16S RNA gene sequencing.
Results
Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA
DRB1*08:03
than did the controls (21.2% vs. 9.0%,
P
=0.0001). HLA-
DRB1*03:01
,
DRB1*07:01
,
DRB1*14:05
, and
DRB1*14:54
frequencies were also increased but did not reach significance after Bonferroni’s correction. Conversely, the
DQB1*03:01
frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%,
P
=0.0010). The patients’ gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA
DRB1
high-risk alleles) than in FHRAC-negative patients (
P
<0.05). Of the top 10 microbial genera,
Lachnospiraceae_incertae_sedis
was higher in the FHRAC-positive patients than in the FHRAC-negative patients (
P
<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients.
DQB1*03:01
-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of
Veillonella
were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative.
Conclusion
The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.
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