Clinical Efficacy of Transcatheter Arterial Chemoembolization Combined With Percutaneous Microwave Coagulation Therapy for Advanced Hepatocellular Carcinoma.

Background: The aim of the study was to explore the clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave coagulation therapy (PMCT) for advanced hepatocellular carcinoma (HCC). Methods: Eighty-three advanced HCC patients were divided into the experimental group (TACE + PMCT, 57 cases) and the control group (TACE alone, 26 cases). They received TACE treatment first, and computed tomography (CT) or hepatic artery angiography was performed 3 - 4 weeks after each treatment. Based on the comprehensive evaluation of iodine oil deficiency, fistula recanalization, residual lesions, and lesion progression, TACE or PMCT treatment was selectively performed, and three consecutive treatments were considered as one treatment cycle. Results: The experimental group had a response rate (RR) of 49.1%, and the control group had a RR of 38.4%. The reduction rate of alpha-fetoprotein (AFP) in the experimental group was significantly higher than the control group (P < 0.05). The cumulative survival rates in the experimental at 1-, 1.5-, and 2-year post-treatment were higher than the control group. The cumulative recurrence and metastasis rates in the experimental at 1.5-, and 2-year post-treatment were significantly lower than those in the control group (P < 0.05). In addition, there were no significant differences in treatment-related complications in the two groups. Conclusions: The combined treatment of TACE and PMCT for advanced HCC is a safe, feasible, and effective treatment method, prolonging the survival time, and reducing the recurrence and metastasis rate, without increased toxic and side effects.

Comparison of engineered nanoparticle transport in columns of three different lengths: Transport experiments and multi-observation point modeling.

This study focuses on the effectiveness of commonly-used 15 cm column lengths for investigating nanoparticle transport in porous media. Experimental tests examined the transport and retention behaviors of two types of nanoparticles, graphene oxide (GO) and titanium dioxide (TiO2) nanoparticles, in saturated sand columns of different lengths (15, 30 and 45 cm), while considering key environmental factors like ionic strength (IS, 1-50 mM), flow rate (1-3 mL min-1), and grain size (150-850 µm). In the 15 cm columns, both GO and TiO2 transport decreased with higher IS and lower flow rate; grain size affected GO and TiO2 differently. Smaller grain size increased GO retention in the sand columns through straining, thus weakening GO mobility, whereas increased fluid shear force suppressed the ripening of TiO2, enhancing its migration. Similar environmental effects were noted in longer columns (30 and 45 cm), but fitted transport parameters (Smax and k) and predicted long-term mobility (Lmax) indicated that 15 cm columns might underestimate nanoparticle mobility. Blocking and ripening models based on single and multiple observation points to simulate nanoparticle transport and retention showed that predictions aligned well with experimental data. These results indicate that using combinations of columns of different lengths to achieve multiple observation points improves model prediction accuracy; in single-column experiments, the 45 cm and 30 cm columns respectively better predict the mobility range of GO and TiO2 compared to 15 cm columns.

Engineering Yarrowia lipolytica for sustainable Cis-13, 16-docosadienoic acid production.

Cis-13, 16-docosadienoic acid (DDA) is an omega-6 polyunsaturated fatty acid with great potential for application in medicine and health. Using microbial cell factories for DDA production is considered a viable alternative to extracting DDA from plant seeds. In this study, using Yarrowia lipolytica Po1f (Δku70) as a chassis, firstly, the adaptation of three elongases in Po1f (Δku70) were explored. Secondly, the DDA biosynthetic pathway was redesigned, resulting in a DDA content of 0.046 % of total fatty acids (TFAs). Thirdly, through the "push-pull" strategy, the DDA content increased to 0.078 % of TFAs. By enhancing the supply of acetyl-CoA, the DDA production in the engineered strain YL-7 reached 0.391 % of the TFAs (3.19 mg/L). Through optimizing the fermentation conditions, the DDA titer of YL-7 reached 29.34 mg/L. This research achieves the sustainable biological production of DDA in Y. lipolytica.

WY-14643, a novel antiplatelet and antithrombotic agent targeting the GPIbα receptor.

BACKGROUND AND PURPOSE: Hypolipidemia and platelet activation play key roles in atherosclerotic diseases. Pirinixic acid (WY-14643) was originally developed as a lipid-lowering drug. Here we focused on its antiplatelet and antithrombotic abilities and the underlying mechanism. EXPERIMENTAL APPROACH: The effects of WY-14643 on platelet aggregation was measured using a lumi-aggregometer. Clot retraction and spreading on fibrinogen were also assayed. PPARα-/- platelets were used to identify the target of WY-14643. The interaction between WY-14643 and glycoprotein Ibα (GPIbα) was detected using cellular thermal shift assay (CETSA), surface plasmon resonance (SPR) spectroscopy and molecular docking. GPIbα downstream signaling was examined by Western blot. The antithrombotic effect was investigated using mouse mesenteric arteriole thrombosis model. Mouse tail bleeding model was used to study its effect on bleeding side effects. KEY RESULTS: WY-14643 concentration-dependently inhibits human washed platelet aggregation, clot retraction, and spreading. Significantly, WY-14643 inhibits thrombin-induced activation of human washed platelets with an IC50 of 7.026 µM. The antiplatelet effect of WY-14643 is mainly dependent of GPIbα. CESTA, SPR and molecular docking results indicate that WY-14643 directly interacts with GPIbα and acts as a GPIbα antagonist. WY-14643 also inhibits phosphorylation of PLCγ2, Akt, p38, and Erk1/2 induced by thrombin. Noteworthily, 20 mg/kg oral administration of WY-14643 inhibits FeCl3-induced thrombosis of mesenteric arteries in mice similarly to clopidogrel without increasing bleeding. CONCLUSION AND IMPLICATIONS: WY-14643 is not only a PPARα agonist with lipid-lowering effect, but also an antiplatelet agent as a GPIbα antagonist. It may have more significant therapeutic advantages than current antiplatelet agents for the treatment of atherosclerotic thrombosis, which have lipid-lowering effects without bleeding side effects.

Constructing polynomial libraries for reservoir computing in nonlinear dynamical system forecasting.

Reservoir computing is an effective model for learning and predicting nonlinear and chaotic dynamical systems; however, there remains a challenge in achieving a more dependable evolution for such systems. Based on the foundation of Koopman operator theory, considering the effectiveness of the sparse identification of nonlinear dynamics algorithm to construct candidate nonlinear libraries in the application of nonlinear data, an alternative reservoir computing method is proposed, which creates the linear Hilbert space of the nonlinear system by including nonlinear terms in the optimization process of reservoir computing, allowing for the application of linear optimization. We introduce an implementation that incorporates a polynomial transformation of arbitrary order when fitting the readout matrix. Constructing polynomial libraries with reservoir-state vectors as elements enhances the nonlinear representation of reservoir states and more easily captures the complexity of nonlinear systems. The Lorenz-63 system, the Lorenz-96 system, and the Kuramoto-Sivashinsky equation are used to validate the effectiveness of constructing polynomial libraries for reservoir states in the field of state-evolution prediction of nonlinear and chaotic dynamical systems. This study not only promotes the theoretical study of reservoir computing, but also provides a theoretical and practical method for the prediction of nonlinear and chaotic dynamical system evolution.

GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

Inflammasome-Independent Mechanism of NLRP3 Is Critical for Platelet GPIb-IX Function and Thrombosis.

INTRODUCTION: Platelets link thrombosis and inflammation, but how platelets handle the endogenous intraplatelet inflammatory machinery is less well understood. NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) is the central component of the interleukin (IL)-1-producing inflammasome. Elucidating the cell type-specific mechanism of NLRP3 in platelets may improve our understanding of thrombotic diseases. METHODS: Ferric chloride-induced mesenteric arteriole thrombosis models, tail bleeding models, and microfluidic whole-blood perfusion were used to study thrombosis and hemostasis. Additionally, we utilized aggregometry, flow cytometry, immunoprecipitation, and western blotting to investigate glycoprotein (GP)Ib-IX-mediated platelet function and signaling. RESULTS: NLRP3-/- mice exhibited severely impaired thrombosis and hemostasis, whereas apoptosis-associated speck-like protein containing a CARD (ASC)-/-, caspase-1-/-, and Nlrp3 A350V/+ CrePF4 mice did not exhibit such changes. NLRP3-/- platelets exhibited reduced adhesion to injured vessel walls and collagen and impaired von Willebrand factor (vWF)-dependent translocation and rolling behavior. NLRP3 deficiency decreased botrocetin-induced platelet aggregation and the phosphorylation of key signaling molecules in the GPIb-IX pathway. Mechanistically, decreased cAMP/PKA activity led to reduced phosphorylation of NLRP3, thereby enabling the interaction between NLRP3 and filamin A. This interaction accelerated the dissociation of filamin A from GPIbα, which allowed a 14-3-3ζ-dependent increase in GPIb-IX affinity to vWF. Finally, platelet NLRP3 was found to largely regulate thrombotic disease models, such as models of stroke and deep vein thrombosis. CONCLUSION: NLRP3 promoted the function of the major platelet adhesion receptor GPIb-IX without involving NLRP3 inflammasome assembly or IL-1ß production.

Pararhizobium qamdonense sp. nov., Isolated from an Alpine Soil in Tibet and the Reclassification of Rhizobium gei Shi et al. 2016 as Pararhizobium gei comb. nov.

A novel Gram-stain-negative, aerobic, rod-shaped bacterium named T808T was isolated from an alpine soil in Qamdo, Tibet, PR China. Strain T808T grew at 5-30℃, pH 5.0-9.0 (optimum, 25℃ and pH 7.0-8.0) with 0-2% (w/v) NaCl (optimum, 0%). The 16S rRNA gene sequences of strain T808T showed the highest similarity with Pararhizobium herbae CCBAU83011T (98.8%), followed by Pararhizobium polonicum F5.1T (98.7%), Pararhizobium giardinii H152T (98.5%), Rhizobium gei ZFJT-2 T (98.4%), and Pararhizobium antarcticum NAQVI59T (97.5%). The highest digital DNA-DNA hybridization (dDDH), core-proteome average amino acid identity (cpAAI) and average nucleotide identity (ANI) values between strain T808T and related strains were estimated as 28.0%, 92.1% and 84.4%, respectively. Phylogenetic analysis based on 16S rRNA, core-proteome and whole-genome indicated that strain T808T belonged to the genus Pararhizobium. The genome size was 6.24 Mbp with genomic DNA G + C content of 60.1%. The major cellular fatty acids were Summed feature 8 (C18:1 ω7c or C18:1 ω6c), C16:0 and C19:0 cyclo ω8c. The polar lipids were diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl choline and unidentified aminophospholipid. The isoprenoid quinone were ubiquinone-10 and ubiquinone-9. Based on phenotypic, phylogenetic, and genotypic data, strain T808T is considered to represent a novel species of the genus Pararhizobium, for which the name Pararhizobium qamdonense sp. nov. is proposed. The type strain is T808T (= JCM 36247 T = CICC 25216 T). According to phylogenetic coherence based on 16S rRNA, core-proteome and whole-genome, it is also proposed that the type strain Rhizobium gei Shi et al. 2016 should be reclassified as Pararhizobium gei comb. nov., the type strain is ZFJT-2 T (= CCTCC AB 2013015 T = KCTC 32301 T = LMG 27603 T).

Reprogramming the fatty acid metabolism of Yarrowia lipolytica to produce the customized omega-6 polyunsaturated fatty acids.

Omega-6 polyunsaturated fatty acids (ω6-PUFAs), such as γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), are indispensable nutrients for human health. Harnessing the lipogenesis pathway of Yarrowia lipolytica creates a potential platform for producing customized ω6-PUFAs. This study explored the optimal biosynthetic pathways for customized production of ω6-PUFAs in Y. lipolytica via either the Δ6 pathway from Mortierella alpina or the Δ8 pathway from Isochrysis galbana. Subsequently, the proportion of ω6-PUFAs in total fatty acids (TFAs) was effectively increased by bolstering the provision of precursors for fatty acid biosynthesis and carriers for fatty acid desaturation, as well as preventing fatty acid degradation. Finally, the proportions of GLA, DGLA and ARA synthesized by customized strains accounted for 22.58%, 46.65% and 11.30% of TFAs, and the corresponding titers reached 386.59, 832.00 and 191.76 mg/L in shake-flask fermentation, respectively. This work provides valuable insights into the production of functional ω6-PUFAs.

Efficient production of cordycepin by engineered Yarrowia lipolytica from agro-industrial residues.

Cordycepin, a nucleoside compound with a variety of biological activities, has been extensively applied in the nutraceutical and pharmaceutical industries. The advancement of microbial cell factories using agro-industrial residues provides a sustainable pathway for cordycepin biosynthesis. Herein, the cordycepin production was enhanced by the modification of glycolysis and pentose phosphate pathway in engineered Yarrowia lipolytica. Then, cordycepin production based on economical and renewable substrates (sugarcane molasses, waste spent yeast, and diammonium hydrogen phosphate) was analyzed. Furthermore, the effects of C/N molar ratio and initial pH on cordycepin production were evaluated. Results indicated that the maximum cordycepin productivity of 656.27 mg/L/d (72 h) and cordycepin titer was 2286.04 mg/L (120 h) by engineered Y. lipolytica in the optimized medium, respectively. The cordycepin productivity in the optimized medium was increased by 28.81% compared with the original medium. This research establishes a promising way for efficient cordycepin production from agro-industrial residues.

A Small RNA, SaaS, Promotes Salmonella Pathogenicity by Regulating Invasion, Intracellular Growth, and Virulence Factors.

Salmonella enterica serovar Enteritidis is a common foodborne pathogen that infects both humans and animals. The S. Enteritidis virulence regulation network remains largely incomplete, and knowledge regarding the specific virulence phenotype of small RNAs (sRNAs) is limited. Here, we investigated the role of a previously identified sRNA, Salmonella adhesive-associated sRNA (SaaS), in the virulence phenotype of S. Enteritidis by constructing mutant (ΔsaaS) and complemented (ΔsaaS/psaaS) strains. SaaS did not affect S. Enteritidis; it was activated in the simulated intestinal environment (SIE), regulating the expression of virulence target genes. We discovered that it directly binds ssaV mRNA. Caco-2 and RAW 264.7 cell assays revealed that SaaS promoted S. Enteritidis invasion and damage to epithelial cells while suppressing macrophage overgrowth and destruction. Furthermore, a BALB/c mouse model demonstrated that the deletion of SaaS significantly reduced mortality and attenuated the deterioration of pathophysiology, bacterial dissemination into systemic circulation, and systemic inflammation. Our findings indicate that SaaS is required for S. Enteritidis virulence and further highlight its biological role in bacterial pathogenesis. IMPORTANCE Salmonella is a zoonotic pathogen with high virulence worldwide, and sRNAs have recently been discovered to play important roles. We explored the biological characteristics of the sRNA SaaS and developed two cell infection models and a mouse infection model. SaaS is an SIE-responsive sRNA that regulates the expression of virulence-targeted genes. Additionally, it differentially mediates invasion and intracellular growth for survival and infection of the epithelium and macrophages. We further found that SaaS enhanced bacterial virulence by promoting lethality, colonization, and inflammatory response. These findings provide a better understanding of the critical role of sRNA in bacterial virulence.

Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization.

The amyloid precursor protein (APP) is critical for the pathogenesis of Alzheimer's disease (AD). The AD patients usually have lower pain sensitivity in addition to cognitive impairments. However, considerably less is known as yet about the role of APP and its two mammalian homologues, amyloid precursor-like protein 1 and 2 (APLP1, APLP2), in spinal processing of nociceptive information. Here we found that all APP family members were present in spinal cord dorsal horn of adult male C57BL/6J mice. Peripheral nerve injury specifically reduced the expression of spinal APLP2 that correlated with neuropathic mechanical allodynia. The loss of APLP2 was confined to inhibitory GABAergic interneurons. Targeted knockdown of APLP2 in GABAergic interneurons of GAD2-Cre mice evoked pain hypersensitivity by means of microglia activation. Our data showed that GABAergic terminals expressed APLP2, a putative cell adhesion protein that interacted with microglia-specific integrin molecule CD11b. Knocking down APLP2 in GAD2-positive neurons to disrupt the trans-cellular interaction led to microglia-dependent pain sensitization. Our data thus revealed an important role of APLP2 for GABAergic interneurons to control microglial activity and pain sensitivity.

Value of Three-dimensional Quantitative Coronary Angiography and μ Quantitative Flow Ratio Methods on the Perfusion Disorder Evaluation of Side Branch in Patience With Side Branch Occlusion:Influencing Factors and Establishment of a Risk Prediction Model / 中国循环杂志

Objectives:The risk factors affecting the blood perfusion of side branch(SB)in coronary bifurcation lesions were explored by the three-dimensional quantitative coronary angiography(3D-QCA)and the Murray's law based quantitative flow ratio(μQFR),and a risk prediction model affecting SB perfusion disorders was established to provide reference for the percutaneous coronary intervention(PCI)strategies of bifurcation lesions. Methods:From October 2022 to April 2023,393 bifurcation lesions were evaluated by coronary angiography in Hunan Provincial People's Hospital.The general clinical evaluation index of the patient,the anatomical index of coronary bifurcation lesion,and the μQFR representing branch perfusion in bifurcation lesion were collected.All samples were randomly divided into training set and test set at the 8:2 ratio.Univariate logistic regression was used to determine filter variables,and the influencing factors of branch perfusion in bifurcated lesions were evaluated by multivariate logistic regression analysis.A risk prediction model was established,and the accuracy of the model was further verified in the test set. Results:The maximum area stenosis rate,maximum lumen diameter stenosis rate of the bifurcation nucleus,ostia diameter stenosis rate,as well as the branch maximum diameter stenosis rate,and length of the bifurcation lesion are independent predictors of SB perfusion disorders(SB μQFR<0.8),P<0.05.A SB perfusion disorder risk prediction model was established based on the above five independent risk factors.The area under the ROC curve of the model was 0.926(95%CI:0.896-0.958),the sensitivity was 0.864(95%CI:0.818-0.910),and the specificity was 0.850(95%CI:0.780-0.920).This model was applied to the test set,the results showed that the area under the ROC curve of this model was 0.897(95%CI:0.817-0.976),the sensitivity was 0.870(95%CI:0.756-0.936),and the specificity was 0.923(95%CI:0.759-0.986). Conclusions:The blood perfusion of branches in coronary bifurcation lesions is mainly related to multiple anatomical factors of the main branch and SB.Among them,the maximum area stenosis rate,maximum lumen diameter stenosis rate of the bifurcation nucleus,ostia diameter stenosis rate,branch maximum diameter stenosis rate and length of the bifurcation lesion are independent predictors of perfusion disorders in the SB.Future studies are needed to validate the clinical value of the established risk prediction model of the SB perfusion disorders in daily clinical practice.

Acinetobacter tibetensis sp. nov., Isolated from a Soil Under a Greenhouse in Tibet.

A Gram-stain-negative, light yellow, aerobic, non-motile, short rod-shaped bacterium named strain Y-23T with iprodione-degrading capability was isolated from a soil under a greenhouse in Tibet, PR China. Strain Y-23T grew at 4-37 â„ƒ and pH 5.0-9.0 (optimum, 25 â„ƒ and pH 7.0) with 0-3% (w/v) NaCl (optimum, 0%). Phylogenetic analysis based on 16S rRNA gene and chromosome genome indicated that strain Y-23T formed a stable evolutionary branch with Acinetobacter tandoii DSM 14970T. The 16S rRNA gene similarity, digital DNA-DNA hybridization and average nucleotide identity values between strain Y-23T and Acinetobacter tandoii DSM 14970T were 98.31%, 43.2% and 91.2%, respectively. The genome size was 3.39 Mbp with a genomic DNA G+C content of 40.59 mol%. The predominant fatty acids were C18:1 ω9c, Summed feature 3 (C16:1 ω7c/C16:1 ω6c), C12:0, C12:0 3-OH and C16:0. The polar lipids were diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl choline, unidentified phospholipid, four unidentified aminophospholipids and two unidentified lipids. The isoprenoid quinone was Q-8 (19.43%) and Q-9 (80.57%). Based on phenotypic, phylogenetic, and genotypic data, strain Y-23T is considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacter tibetensis sp. nov. is proposed. The type strain is Y-23T (= CICC 25150T = JCM 35630T).

High-level de novo biosynthesis of cordycepin by systems metabolic engineering in Yarrowia lipolytica.

Cordycepin is a nucleoside antibiotic with various biological activities, which has wide applications in the area of cosmetic and medicine industries. However, the current production of cordycepin is costly and time-consuming. To construct the promising cell factory for high-level cordycepin production, firstly, the design and construction of cordycepin biosynthetic pathway were performed in Yarrowia lipolytica. Secondly, the adaptivity between cordycepin biosynthetic pathway and Y. lipolytica was enhanced by enzyme fusion and integration site engineering. Then, the production of cordycepin was improved by the enhancement of adenosine supply. Furthermore, through modular engineering, the production of cordycepin was achieved at 3588.59 mg/L from glucose. Finally, 3249.58 mg/L cordycepin with a yield of 76.46 mg/g total sugar was produced by the engineered strain from the mixtures of glucose and molasses. This research is the first report on the de novo high-level production of cordycepin in the engineered Y. lipolytica.

Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a protein tyrosine phosphatase that negatively regulates T-cell signaling. However, whether it is expressed and functions in platelets remains unknown. Here we investigated the expression and role of PTPN22 in platelet function. We reported PTPN22 expression in both human and mouse platelets. Using PTPN22-/- mice, we showed that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation without affecting venous thrombosis and the coagulation factors VIII and IX. Consistently, PTPN22-deficient platelets exhibited enhanced platelet aggregation, granule secretion, calcium mobilization, lamellipodia formation, spreading, and clot retraction. Quantitative phosphoproteomic analysis revealed the significant difference of phosphodiesterase 5A (PDE5A) phosphorylation in PTPN22-deficient platelets compared with wild-type platelets after collagen-related peptide stimulation, which was confirmed by increased PDE5A phosphorylation (Ser92) in collagen-related peptide-treated PTPN22-deficient platelets, concomitant with reduced level and vasodilator-stimulated phosphoprotein phosphorylation (Ser157/239). In addition, PTPN22 interacted with phosphorylated PDE5A (Ser92) and dephosphorylated it in activated platelets. Moreover, purified PTPN22 but not the mutant form (C227S) possesses intrinsic serine phosphatase activity. Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction, and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

Neorhizobium xiangyangii sp. nov., isolated from a highland barley cultivation soil in Qamdo, Tibet.

A novel Gram-negative, aerobic, rod-shaped and non-nitrogen fixing bacterium named T786T was isolated from a highland barley cultivation soil in Qamdo, Tibet Autonomous Region, PR China. Strain T786T grew at 5-30 â„ƒ and pH 6.0-10.0 (optimum, 20-25 â„ƒ and pH 7.0-8.0) with 0-4% (w/v) NaCl (optimum, 0%). The 16S rRNA gene sequences of strain T786T showed the highest similarity to Neorhizobium vignae CCBAU 05176T (98.7%), followed by Neorhizobium alkalisoli CCBAU 01393T (98.5%), Neorhizobium tomejilense T17_20T (98.4%), Neorhizobium huautlense S02T (98.4%), and Neorhizobium galegae ATCC 43677T (98.0%). Phylogenetic analysis based on 16S rRNA genes indicated that strain T786T was a new member of the genus Neorhizobium. The digital DNA-DNA hybridization and average nucleotide identity values between strain T786T and related strains were estimated as 20.2-20.6% and 76.6-80.0%, respectively. The genomic DNA G + C content based on the draft genome sequence was 60.2%. The major cellular fatty acids were Summed feature 8 (C18:1 ω7c or C18:1 ω6c), C16:0 and Summed feature 3 (C16:1 ω7c or C16:1 ω6c). The polar lipids were diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl methyl ethanolamine, unidentified phospholipid and unidentified lipids (1-4). The isoprenoid quinone was ubiquinone-10. The DAP and sugar components of cell wall were meso-DAP and ribose, glucose, respectively. Based on phenotypic, phylogenetic, and genotypic data, for which the name Neorhizobium xiangyangii sp. nov. is proposed. The type strain is T786T (= JCM 35100T = CICC 25102T).

The Function Improved of the Newly Designed Magnetic-End Ureteric Stenting Retrieval Device: A Clinical Prospective Randomized and Control Trial in a Multicenter Study.

Objective: To demonstrate the advantage of our newly designed magnetic ureteric stenting retrieval device over traditional nonmagnetic ureteric stents and other retrieval devices without cystoscopy intervention on clinical application and cost-related outcomes. Patients and Methods. A total of 333 patients were recruited into two study groups: magnetic-end ureteral stent (Group A) and conventional ureteral stent (Group B). The effects were evaluated by Ureteral Stent Symptom Questionnaire (USSQ) scores, complications of the indwelling stent, visual analog scale (VAS) pain scores at stent removal, and cost-analysis outcomes between the magnetic ureteric stenting retrieval device and traditional double-J ureteral stent (DJUS) removed by cystoscopy. Results: The VAS of the pain score of patients undergoing magnetic stent removal with the retrieval device was 2 ± 0.97, whereas that of patients undergoing conventional ureteral stent removal with cystoscopy was 5.76 ± 1.53 (p < 0.001). The removal of magnetic stents by a retrieval device proved to be less painful than cystoscopy-mediated stent removal (p < 0.001). Obviously, the total cost for the magnetic stent removal was much lower than the conventional ureteral stent removal, although the magnetic stent costs more than the conventional ureteral stent. The improved magnetic stent used in our study showed a remarkable cost saving of 705/111 USD Chinese Yuan (CNY) per patient when compared with the conventional ureteral stent. Conclusion: We reported the integrated design features of the improved magnetic stent in the world, which was granted a patent in China. USSQ scores and rate of complications in the magnetic stent were as equally acceptable as a conventional stent. Furthermore, successful stent insertion rate reached 100% by both the antegrade and retrograde approaches, and no failure case of magnetic stent removal was reported in our study.

Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice.

Casitas B-lineage lymphoma b (Cbl-b) is one of the E3 ubiquitin ligases that ubiquitinate Tropomyosin-related kinase A (TrkA), a key nerve growth factor receptor involved in the pathological pain. Here we found that Cbl-b was abundant in dorsal root ganglion (DRG) neurons of mice and co-localized with TrkA. Ubiquitination of TrkA by Cbl-b exerted a tonic negative control over the protein level of TrkA. Knockdown of Cbl-b caused TrkA accumulation in DRGs and evoked mechanical and heat hypersensitivity in intact mice. Our data showed that knee osteoarthritis induced by destabilization of the medial meniscus (DMM) led to the dissociation of Cbl-b with TrkA in DRG neurons, which impaired the ability of Cbl-b to ubiquitinate TrkA and served as an important mechanism to cause TrkA-dependent pain sensitization. Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia. Viral delivery of Cbl-b through intra-articular route generated a similar analgesic action. These data suggested that ubiquitination of TrkA by Cbl-b might represent an effective way to treat the osteoarthritic pain.

Roles of Gut Microbiota in Pathogenesis of Alzheimer's Disease and Therapeutic Effects of Chinese Medicine.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive impairment. The pathogenesis of AD is complex, and its susceptibility and development process are affected by age, genetic and epigenetic factors. Recent studies confirmed that gut microbiota (GM) might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflflammatory and immune processes. CM formula, herbs, and monomer enjoy unique advantages to treat and prevent AD. Hence, the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD. Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed. The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.