Ultralong Cycling and Interfacial Regulation of Bilayer Heterogeneous Composite Solid-State Electrolytes in Lithium Metal Batteries.

Under the background of "carbon neutral", lithium-ion batteries (LIB) have been widely used in portable electronic devices and large-scale energy storage systems, but the current commercial electrolyte is mainly liquid organic compounds, which have serious safety risks. In this paper, a bilayer heterogeneous composite solid-state electrolyte (PLPE) was constructed with the 3D LiX zeolite nanofiber (LiX-NF) layer and in-situ interfacial layer, which greatly extends the life span of lithium metal batteries (LMB). LiX-NF not only offers a continuous fast path for Li+, but also zeolite's Lewis acid-base interaction can immobilize large anions, which significantly improves the electrochemical performance of the electrolyte. In addition, the in-situ interfacial layer at the electrode-electrolyte interface can effectively facilitate the uniform deposition of Li+ and inhibit the growth of lithium dendrites. As a result, the Li/Li battery assembled with PLPE can be stably cycled for more than 2500 h at 0.1 mA cm-2. Meanwhile, the initial discharge capacity of the LiFePO4/PLPE/Li battery can be 162.43 mAh g-1 at 0.5 C, and the capacity retention rate is 82.74% after 500 cycles. These results emphasize that this bilayer heterogeneous composite solid-state electrolyte has distinct properties and shows excellent potential for application in LMB.

Discovery of Novel 1-Phenylpiperidine Urea-Containing Derivatives Inhibiting ß-Catenin/BCL9 Interaction and Exerting Antitumor Efficacy through the Activation of Antigen Presentation of cDC1 Cells.

Aberrant activation of the Wnt/ß-catenin signaling is associated with tumor development, and blocking ß-catenin/BCL9 is a novel strategy for oncogenic Wnt/ß-catenin signaling. Herein, we presented two novel ß-catenin variations and exposed conformational dynamics in several ß-catenin crystal structures at the BCL9 binding site. Furthermore, we identified a class of novel urea-containing compounds targeting ß-catenin/BCL9 interaction. Notably, the binding modalities of inhibitors were greatly affected by the conformational dynamics of ß-catenin. Among them, 28 had a strong affinity for ß-catenin (Kd = 82 nM), the most potent inhibitor reported. In addition, 13 and 35 not only activate T cells but also promote the antigen presentation of cDC1, showing robust antitumor efficacy in the CT26 model. Collectively, our study demonstrated a series of potent small-molecule inhibitors targeting ß-catenin/BCL9, which can enhance antigen presentation and activate cDC1 cells, delivering a potential strategy for boosting innate and adaptive immunity to overcome immunotherapy resistance.

LiF/Li3N-Rich Electrode-Electrolyte Interfaces Enabled by Multi-Functional Electrolyte Additive to Achieve High-Performance Li/LiNi0.8Co0.1Mn0.1O2 Batteries.

LiPF6-based carbonate electrolytes have been extensively employed in commercial Li-ion batteries, but they face numerous interfacial stability challenges while applicating in high-energy-density lithium-metal batteries (LMBs). Herein, this work proposes N-succinimidyl trifluoroacetate (NST) as a multifunctional electrolyte additive to address these challenges. NST additive could optimize Li+ solvation structure and eliminate HF/H2O in the electrolyte, and preferentially be decomposed on the Ni-rich cathode (LiNi0.8Co0.1Mn0.1O2, NCM811) to generate LiF/Li3N-rich cathode-electrolyte interphase (CEI) with high conductivity. The synergistic effect reduces the electrolyte decomposition and inhibits the transition metal (TM) dissolution. Meanwhile, NST promotes the creation of solid electrolyte interphase (SEI) rich in inorganics on the Li metal anode (LMA), which restrains the growth of Li dendrites, minimizes parasitic reactions, and fosters rapid Li+ transport. As a result, compared with the reference, the Li/LiNi0.8Co0.1Mn0.1O2 cell with 1.0 wt.% NST exhibits higher capacity retention after 200 cycles at 1C (86.4% vs. 64.8%) and better rate performance, even at 9C. In the presence of NST, the Li/Li symmetrical cell shows a super-stable cyclic performance beyond 500 h at 0.5 mA cm-2/0.5 mAh cm-2. These unique features of NST are a promising solution for addressing the interfacial deterioration issue of high-capacity Ni-rich cathodes paired with LMA.

Family-based genetic analysis in schizophrenia by whole-exome sequence to identify rare pathogenic variants.

Schizophrenia (SCZ) is influenced by a combination of genetic and environmental factors. Although several studies have been conducted to identify the causative loci and genes, few of these loci or genes can be repeated due to the high phenotypic and genetic heterogeneity of disease, and their mechanisms are not fully understood. There may be some "missing heritability" that has not yet been found. In order to investigate the deleterious heritable mutations, whole-exome sequencing (WES) in pedigrees with SCZ was used in the current work. Two unrelated pedigrees with SCZ were recruited to perform WES. Genetic analysis was next performed to find potential variants in accordance with the prioritized strategy. Followed by genetic analysis to detect candidate variants according to the prioritized strategy. Next, a series of algorithms was used to predict the pathogenicity of variants. Sanger sequencing was finally conducted to verify the co-segregation. Recessive mutations in six genes (TFEB, SNAI2, TFAP2B, PRKDC, ST18 in Pedigree 1 and PKHD1L1 in Pedigree 2) that co-segregated with SCZ in two families were discovered through genetic analysis by WES. Sanger sequencing verified that all of the mutations in the affected siblings were homozygous. These results corroborated the hypothesis that SCZ exhibits strong heterogeneity and complex inheritance patterns. The newly discovered homozygous variations deepen our understanding of the mutation spectrum and offer more proof for the involvement of TFEB, SNAI2, TFAP2B, PRKDC, ST18, and PKHD1L1 in the development of SCZ.

Polydopamine-Induced Metal-Organic Framework Network-Enhanced High-Performance Composite Solid-State Electrolytes for Dendrite-Free Lithium Metal Batteries.

Due to the high safety, flexibility, and excellent compatibility with lithium metals, composite solid-state electrolytes (CSEs) are the best candidates for next-generation lithium metal batteries, and the construction of fast and uniform Li+ transport is a critical part of the development of CSEs. In this paper, a stable three-dimensional metal-organic framework (MOF) network was obtained using polydopamine as a medium, and a high-performance CSE reinforced by the three-dimensional MOF network was constructed, which not only provides a continuous channel for Li+ transport but also restricts large anions and releases more mobile Li+ through a Lewis acid-base interaction. This strategy endows our CSEs with an ionic conductivity (7.1 × 10-4 S cm-1 at 60 °C), a wide electrochemical window (5.0 V), and a higher Li+ transfer number (0.54). At the same time, the lithium symmetric batteries can be stably cycled for 2000 h at 0.1 mA cm-2, exhibiting excellent electrochemical stability. The LiFePO4/Li cells have a high initial discharge specific capacity of 153.9 mAh g-1 at 1C, with a capacity retention of 80% after 915 cycles. This paper proposes an approach for constructing three-dimensional MOF network-enhanced CSEs, which provides insights into the design and development of MOFs for the positive effects of high-performance CSEs.

LiF-Rich Electrode-Electrolyte Interfaces Enabled by Bifunctional Electrolyte Additive to Achieve High-Performance Li/LiNi0.8Co0.1Mn0.1O2 Batteries.

Commercial Li-ion batteries use LiPF6-based carbonate electrolytes extensively, but there are many challenges associated with them, like dendritic Li growth and electrolyte decomposition, while supporting the aggressive chemical and electrochemical reactivity of lithium metal batteries (LMBs). This work proposes 1,1,1,3,3,3-hexafluoroisopropyl methacrylate (HFM) as a multifunctional electrolyte additive, constructing protective solid-/cathode-electrolyte interphases (SEI/CEI) on the surfaces for both lithium metal anode (LMA) and Ni-rich cathode to solve these challenges simultaneously. The highly fluorinated group (-CF3) of the HFM molecule contributes to the construction of SEI/CEI films rich in LiF that offer excellent electronic insulation, high mechanical strength, and surface energy. Accordingly, the HFM-derived LiF-rich interphases can minimize the electrolyte-electrode parasitic reactions and promote uniform Li deposition. Also, the problems of LiNi0.8Co0.1Mn0.1O2 particles' inner microcrack evolution and the growth of dendritic Li are adequately addressed. Consequently, the HFM additive enables a Li/LiNi0.8Co0.1Mn0.1O2 cell with higher capacity retention after 200 cycles at 1 C than the cell with no additive (74.7 vs 52.8%), as well as a better rate performance, especially at 9 C. Furthermore, at 0.5/0.5 mAh cm-2, the Li/Li symmetrical battery displays supersteadfast cyclic performance beyond 500 h when HFM is present. For high-performance LMBs, the HFM additive offers a straightforward, cost-effective route.

Halloysite nanotubes modified poly(vinylidenefluoride-co-hexafluoropropylene)-based polymer-in-salt electrolyte to achieve high-performance Li metal batteries.

Solid-state Li metal batteries (SSLMBs) are one of the most promising energy storage devices, as they offer high energy density and improved safety compared to conventional Li-ion batteries. However, the large-scale application of SSLMBs at room temperature is restricted by the main challenges such as low ionic conductivity and poor cyclic performance. Herein, a composed polymer-in-salt electrolyte (CPISE) is fabricated, which is composed of polyvinylidene vinylidene hexafluoropropene (PVDF-HFP) and high-concentration Li bis(trifluoromethanesulphonyl)imide (LiTFSI), reinforced with natural halloysite nanotubes (HNTs). The High concentration of LiTFSI and introduced HNTs synergized with PVDF-HFP to provide more various Li+ transport pathways. Additionally, the backbones of the uniform dispersion of HNTs in the CPISE effectively boosts the physicochemical nature of the CPISE. As a result, the prepared CPISE achieves excellent mechanical strength, high ionic conductivity (1.23*10-3 S cm-1) and high Li+ transference number (0.57) at room temperature. Consequently, in existence of the CPISE, the Li symmetric cell cycles stably beyond 800 h at 0.15 mA cm-2 and the LiFePO4/Li cell displays impressive cyclic performance with capacity retention of 79% after 1000 cycles at 30 °C. Furthermore, the superiority and the functional mechanism of the CPISE are discovered in detail. This work provides a promising strategy for the development of high-performance SSMLBs at room temperature.

LiF-Rich Interfaces and HF Elimination Achieved by a Multifunctional Additive Enable High-Performance Li/LiNi0.8Co0.1Mn0.1O2 Batteries.

Li-metal batteries (LMBs), especially in combination with high-energy-density Ni-rich materials, exhibit great potential for next-generation rechargeable Li batteries. Nevertheless, poor cathode-/anode-electrolyte interfaces (CEI/SEI) and hydrofluoric acid (HF) attack pose a threat to the electrochemical and safety performances of LMBs due to aggressive chemical and electrochemical reactivities of high-Ni materials, metallic Li, and carbonate-based electrolytes with the LiPF6 salt. Herein, the carbonate electrolyte based on LiPF6 is formulated by a multifunctional electrolyte additive pentafluorophenyl trifluoroacetate (PFTF) to adapt the Li/LiNi0.8Co0.1Mn0.1O2 (NCM811) battery. It is theoretically illustrated and experimentally revealed that HF elimination and the LiF-rich CEI/SEI films are successfully achieved via the chemical and electrochemical reactions of the PFTF additive. Significantly, the LiF-rich SEI film with high electrochemical kinetics facilitates Li homogeneous deposition and prevents dendritic Li from forming and growing. Benefiting from the collaborative protection of PFTF on the interfacial modification and HF capture, the capacity ratio of the Li/NCM811 battery is boosted by 22.4%, and the cycling stability of the symmetrical Li cell is expanded over 500 h. This provided strategy is conducive to the achievement of high-performance LMBs with Ni-rich materials by optimizing the electrolyte formula.

Zeolitic imidazolate framework upgrading polyethylene oxide composite electrolyte for high-energy solid-state lithium batteries.

The energy density of solid-state lithium batteries (SSLBs) has been primarily limited by the low ionic conductivity of solid electrolyte and poor interface compatibility between electrolyte and electrodes. Herein, a multifunctional composite solid polymer electrolyte (CSPE) based on polyethylene oxide (PEO) embedded with zeolitic imidazolate framework-8 deposited on carboxymethyl cellulose (ZIF@CMC) is reported. The ZIF@CMC interpenetrated in PEO matrix creates a continuous Li+ conductive network by combining Zn2+ in ZIF with the unsaturated group in PEO to boost the Li+ transport through the PEO chain segment. On the other hand, Zn2+ can bond with bis(trifluoromethane)sulfonimide (TFSI-) anion, thus promoting the dissolution of lithium salt and releasing more lithium ions. This CSPE demonstrates brilliant electrochemical properties, including a high ionic conductivity of 1.8 × 10-4 S cm-1 at room temperature and a wide electrochemical window of 5 V. The integrated LiFePO4/CSPE/Li batteries using 20 wt.% ZIF-8@CMC show excellent reversible capacity of 145.6 mAh g-1 with a capacity retention of 88.95 % after 200 cycles at a high current density of 0.5C. Our study proposed a novel and effective strategy to construct high-performance solid-state lithium batteries.

Research on multi-Atlas segmentation based on feature clustering / 中华放射肿瘤学杂志

Objective:To study the improvement of normal tissue region of interest (ROI) segmentation based on clustering-based multi-Atlas segmentation method, thereby achieving better delineation of organs at risk.Methods:CT images of 100 patients with cervical cancer who had completed treatment in Zhejiang Cancer Hospital during 2019-2020 were selected as the Atlas database. According to the volume characteristic parameters of the organs at risk (bladder, rectum and outer contour), the Atlas database was divided into several subsets by k-means clustering algorithm. The image to be segmented was matched to the corresponding Atlas library for multi-Atlas segmentation. The dice similarity coefficient (DSC) was used to evaluate the segmentation results.Results:Using 30 patients as the test set, the sub-Atlas generated by different clustering methods were compared for the improvement of image segmentation results. Compared with general multi-Atlas segmentation methods, clustering-based multi-Atlas segmentation method significantly improve the segmentation accuracy for the bladder (DSC=0.83±0.09 vs. 0.69±0.15, P<0.001) and the rectum (0.7±0.07 vs. 0.56±0.16, P<0.001), but no statistical significance was observed for left and right femoral head (0.92±0.04, 0.91±0.02) and bone marrow (0.91±0.06). The average segmentation time of clustering-based multi-Atlas segmentation method was shorter than that of the general multi-Atlas segmentation method (2.7 min vs. 6.3 min). Conclusion:The clustering-based multi-Atlas segmentation method can not only reduce the number of Atlas images registered with the image to be segmented, but also can be expected to improve the segmentation effect and obtain higher accuracy.

Incidence of chronic obstructive pulmonary disease and risk factors in the Suzhou cohort / 中华流行病学杂志

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa.

Antibiotic-resistant Pseudomonas aeruginosa is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography-mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant P. aeruginosa strains that originated from P. aeruginosa ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16CIP, PA-R64CIP, and PA-R128CIP, respectively) higher than the original value, compared to CIP-sensitive P. aeruginosa (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128CIP and clinically multidrug-resistant P. aeruginosa strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant P. aeruginosa strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of P. aeruginosa and provide a target pathway for combating CIP-resistant P. aeruginosa.

Molecular mechanism underlying vascular development in the brain / 解剖学报

As the pipelines of nutrient and oxygen in the brain, cerebral vessels play an important role in the development and normal function of the brain. The development of the cerebrovascular system is divided into two processes, primitive vasculogenesis and angiogenesis. In this review, we summarize the roles, regulation mechanisms, as well as the interactions of the essential signaling molecules, such as the family members of vascular endothelial growth factor（VEGF）, neuropillin, Wnt, Notch, Hedgehog, in the vessel development, aiming to provide a reference for the basic and clinical investigation and the prevention and treatment of vascular diseases. Reset.

The Interventions to enhance the Well-being of Children at early education in China: The Mediating Moderating Approach / Intervenciones para mejorar el bienestar de los niños en la educación temprana en China: el enfoque moderador de la mediación

This research effort depicts the well-being of children in China who have experienced devastating developments in their immediate environment and are indulged in negative emotions which result in negative psychological and behavioral consequences. The study focuses on the interventions taken into consideration in prior literature to address the problem of the ‘left-behind children’. The current research paper seeks to assess the well-being of children influenced by important factors that shape the behavior at early schooling. Tolerance, respect and moral identity are found to be crucial factors that influence individual behavioral outcomes; therefore, the current study empirically investigates the impact of these behavioral interventions. The study reports mixed results as two direct hypotheses’ i.e., moral identity to well-being and tolerance-respect to well-being are observed to be insignificant, however the remaining direct, moderating, and mediating relationship are found to be statistically significant. The implications, limitations and future directions of the current research study are highlighted in the concluding sections of the study.(AU)

Dibenzocyclooctadiene lignans from Artemisia sieversiana and their anti-inflammatory activities.

Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D-E (1-2), as well as eight known ones (3-10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and electronic circular dichroism (ECD) experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory activities on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activities with their IC50 values of 47.7 and 21.9 µM, compared to a positive control quercetin with the IC50 value of 16.0 µM.

Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma.

Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.

Neurotensin 1 receptor in the prelimbic cortex regulates anxiety-like behavior in rats.

The central neurotensin system has been implicated in reward, memory processes, also in the regulation of anxiety. However, the neural substrates where neurotensin acts to regulate anxiety have not been fully identified. The prelimbic region of medial prefrontal cortex (PrL) holds a key position in the modulation of anxiety-related behaviors and expresses neurotensin 1 receptor (NTS1). This study investigated the effects of activation or blockade of NTS1 in the PrL on anxiety-like behaviors of rats. Our results demonstrated that infusion of a selective NTS1 agonist or neurotensin into the PrL produced anxiogenic-like effects. Administration of a NTS1 antagonist into the PrL did not affect anxiety-like behaviors of normal rats, but attenuated anxiogenic effects induced by restraint stress. Moreover, we employed molecular approaches to downregulate the expression of NTS1 in the PrL, and found that downregulation of NTS1 in the PrL induced anxiolytic effects in restraint stress rats, also confirming the pharmacological results. Together, these findings suggest that NTS1 in the PrL is actively involved in the regulation of anxiety.

Glucose-Potentiated Amikacin Killing of Cefoperazone/Sulbactam Resistant Pseudomonas aeruginosa.

Multidrug-resistant Pseudomonas aeruginosa has become one of global threat pathogens for human health due to insensitivity to antibiotics. Recently developed reprogramming metabolomics can identify biomarkers, and then, the biomarkers were used to revert the insensitivity and elevate antibiotic-mediated killing. Here, the methodology was used to study cefoperazone/sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF) and identified reduced glycolysis and pyruvate cycle, a recent clarified cycle providing respiratory energy in bacteria, as the most key enriched pathways and the depressed glucose as one of the most crucial biomarkers. Further experiments showed that the depression of glucose was attributed to reduction of glucose transport. However, exogenous glucose reverted the reduction to elevate intracellular glucose via activating glucose transport. The elevated glucose fluxed to the glycolysis, pyruvate cycle, and electron transport chain to promote downstream proton motive force (PMF). Consistently, exogenous glucose did not promote SCF-mediated elimination but potentiated aminoglycosides-mediated killing since aminoglycosides uptake is PMF-dependent, where amikacin was the best one. The glucose-potentiated amikacin-mediated killing was effective to both lab-evolved PA-RSCF and clinical multidrug-resistant P. aeruginosa. These results reveal the depressed glucose uptake causes the reduced intracellular glucose and expand the application of metabolome-reprogramming on selecting conventional antibiotics to achieve the best killing efficacy.

Effect of Different Extracts of Thlaspi Herba on Gut Microbiota of Hyperuricemia Mice / 中国实验方剂学杂志

Objective:To explore the effect of different extracts of Thlaspi Herba on the gut microbiota of hyperuricemia mice， and to reveal the substance basis and mechanism of its hypouricemic activity. Method:Eighty-eight male Kunming mice were divided into 11 groups， including blank group， model group， allopurinol group， high and low dose groups of petroleum ether extract， high and low dose groups of ethyl acetate extract， high and low dose groups of <italic>n</italic>-butanol extract， high and low dose groups of total flavonoids extract. Mice in the blank group were given 0.5% sodium carboxymethylcellulose by gavage， and the other groups were given oteracil potassium （500 mg·kg^-1） by gavage to duplicate the hyperuricemia model. After modeling for several hours， the blank group and the model group were given distilled water by gavage， while mice in the allopurinol group were given allopurinol suspension （50 mg·kg^-1）， and mice in each treatment group were given high and low doses of corresponding extract （5， 2.5 g·kg^-1）. The serum uric acid （SUA） level and xanthine oxidase （XOD） activity were measured after 14 days. Fresh feces were collected for 16S rDNA sequencing. Result:Compared with the blank group， SUA level and XOD activity of model group were significantly increased （<italic>P</italic><0.05）. Compared with the model group， SUA level and XOD activity of the allopurinol group were significantly decreased （<italic>P</italic><0.01）. After intervention， SUA level were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， except for high dose and low dose groups of petroleum ether extract and low dose group of total flavonoids extract， XOD activity was significantly inhibited in low dose group of petroleum ether extract， high dose group of total flavonoids extract， and high and low dose groups of <italic>n</italic>-butanol extract （<italic>P</italic><0.05， <italic>P</italic><0.01）. The high dose group of total flavonoids extract was the most significant. The results of flora sequencing showed that <italic>α</italic> diversity and abundance of the model group changed significantly， and Bacteroidetes， Firmicutes and Lactobacillaceae were significantly correlated with XOD activity. After intervention， the operational taxonomic unit （OTU）， ACE， Chao1 and Shannon indexes of the high and low dose groups of total flavonoids extract were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Relative abundance of Bacteroidetes in low dose group of ethyl acetate extract， high dose group of total flavonoids extract， and high and low dose groups of <italic>n</italic>-butanol extract was significantly decreased （<italic>P</italic><0.01）， and the relative abundance of Firmicutes was significantly increased （<italic>P</italic><0.01）. The relative abundance of Lactobacillaceae in low dose group of <italic>n</italic>-butanol extract and high dose group of total flavonoids extract was significantly increased （<italic>P</italic><0.01）. Conclusion:The effective part of Thlaspi Herba for reducing uric acid is mainly flavonoids， the improvement of SUA level and XOD activity by affecting gut microbiota such as Lactobacillaceae， Bacteroidetes and Firmicutes， may be one of its mechanisms.