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1.
J Am Coll Surg ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655173

RESUMO

BACKGROUND: Supermicrosurgical lymphaticovenous anastomosis (LVA) alleviates lymphedema by draining stagnant lymph from the lymphatic vessels into the venous system. Nevertheless, LVA is believed to be unsuitable for treating moderate-to-severe lymphedema presenting diffuse-pattern dermal backflow (DB). DB is considered to be the sign of superficial lymphatic functional failure that renders LVA ineffective. Based on a current algorithm, a more invasive vascularized lymph node flap transfer is recommended instead of LVA. This retrospective study aimed to further investigate and possibly challenge this concept. METHODS: One-hundred patients with unilateral lymphedematous lower limbs who underwent LVA were included. Patients were divided into Group I (10 patients with mild lymphedema) and Group II (90 patients with moderate-to-severe lymphedema). Demographic data and intraoperative findings were recorded. The post-LVA volume reductions by magnetic resonance volumetry were recorded and analyzed. RESULTS: Preoperatively, significant differences were found in body mass index (20.6 vs. 26.0, p = 0.004) and the volume gained in the lymphedematous limb (396.8 mL vs. 1056.8 mL, p = 0.005) between Groups I and II. Postoperatively, a significant median post-LVA volume reduction (-282.0 mL vs. -763.5 mL, p = 0.022) was found in Group II. However, there were no differences in the percentage of post-LVA volume reduction (-43.8% vs. -36.4%, p=0.793) in Groups I and II. CONCLUSION: The use of supermicrosurgical LVA is as effective at treating moderate-to-severe lymphedema as milder lymphedema. The indication for LVA should be broadened to include such cases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31658507

RESUMO

BACKGROUND: Parasympathetic nerve hypersensitivity contributes to the severity of allergic rhinitis (AR), but the precise mechanism underlying neuroimmune regulation in patients with AR remains unclear. This study investigated the effect of cholinergic nerve inhibition on AR CD4+ T-helper (Th)2-cell polarization and the underlying regulatory mechanism in vitro. METHODS: An in-vitro neuroimmune coculture model of D-U87 cells and CD4+ T cells was established. D-U87 cells with cholinergic neuron characteristics were used as cholinergic neuron models. CD4+ T cells were derived from peripheral blood monocytes from AR patients (n = 60) and control subjects (n = 40). Th1- and Th2-cell percentages were measured by flow cytometry. Proteins involved in related signaling pathways were analyzed by protein chip assay and Western blotting. RESULTS: The Th2-cell percentage among CD4+ T cells from AR patients was significantly increased after coculture with D-U87 cells and was decreased by ipratropium bromide (IB) treatment. In contrast, the Th1-cell percentage among control CD4+ T cells was significantly increased after coculture with D-U87 cells, but was unaltered by IB treatment. Furthermore, phosphorylated Akt (p-Akt) protein levels increased in CD4+ T cells from both controls and AR patients after coculture with D-U87 cells and decreased after IB treatment. However, higher p-Akt levels were observed in cells from AR patients than in cells from control subjects. Moreover, Akt inhibition decreased Th2-cell percentage in AR patients. CONCLUSION: In-vitro cholinergic nerve inhibition with IB decreased AR CD4+ T-cell polarization into Th2 cells partially through an Akt-dependent mechanism.

3.
Cell Rep ; 29(5): 1336-1350.e4, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665644

RESUMO

Bacteriophages provide excellent tools for diagnostics, remediation, and targeted microbiome manipulation, yet isolating viruses with suitable host specificity remains challenging. Using Listeria phage PSA, we present a synthetic biology blueprint for host-range engineering through targeted modification of serovar-specific receptor binding proteins (RBPs). We identify Gp15 as the PSA RBP and construct a synthetic phage library featuring sequence-randomized RBPs, from which host range mutants are isolated and subsequently integrated into a synthetic, polyvalent phage with extended host range. To enable rational design of chimeric RBPs, we determine the crystal structure of the Gp15 receptor-binding carboxyl terminus at 1.7-Å resolution and employ bioinformatics to identify compatible, prophage-encoded RBPs targeting different Listeria serovars. Structure-guided design enables exchange of heterologous RBP head, neck, or shoulder domains to generate chimeric phages with predictable and extended host ranges. These strategies will facilitate the development of phage biologics based on standardized virus scaffolds with tunable host specificities.

4.
Neuroimage ; : 116287, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655111

RESUMO

Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been inconsistent and the mechanisms underlying rumination remain elusive. Functional brain imaging studies have identified areas in the default mode network (DMN) that appear to be critically involved in ruminative processes. However, a meta-analysis to synthesize the findings of brain regions underlying rumination is currently lacking. Here, we conducted a meta-analysis consisting of experimental tasks that investigate rumination by using Signed Differential Mapping of 14 fMRI studies comprising 286 healthy participants. Furthermore, rather than treat the DMN as a unitary network, we examined the contribution of three DMN subsystems to rumination. Results confirm the suspected association between rumination and DMN activation, specifically implicating the DMN core regions and the dorsal medial prefrontal cortex subsystem. Based on these findings, we suggest a hypothesis of how DMN regions support rumination and present the implications of this model for treating major depressive disorder characterized by rumination.

5.
Nat Commun ; 10(1): 4283, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570766

RESUMO

The foodborne pathogen Listeria monocytogenes (Lm) is a highly heterogeneous species and currently comprises of 4 evolutionarily distinct lineages. Here, we characterize isolates from severe ovine listeriosis outbreaks that represent a hybrid sub-lineage of the major lineage II (HSL-II) and serotype 4h. HSL-II isolates are highly virulent and exhibit higher organ colonization capacities than well-characterized hypervirulent strains of Lm in an orogastric mouse infection model. The isolates harbour both the Lm Pathogenicity Island (LIPI)-1 and a truncated LIPI-2 locus, encoding sphingomyelinase (SmcL), a virulence factor required for invasion and bacterial translocation from the gut, and other non-contiguous chromosomal segments from another pathogenic species, L. ivanovii. HSL-II isolates exhibit a unique wall teichoic acid (WTA) structure essential for resistance to antimicrobial peptides, bacterial invasion and virulence. The discovery of isolates harbouring pan-species virulence genes of the genus Listeria warrants global efforts to identify further hypervirulent lineages of Lm.

6.
J Immunol Res ; 2019: 8656282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583260

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating cancer types despite the improvement of modern medicine. In our present study, we found that dickkopf-related protein 2 (DKK2) shares a higher expression in PDAC compared with adjacent pancreas tissue in tissue microarray. In addition, an elevated expression of DKK2 predicts poorer prognosis of patients and positively correlated with poor tumor differentiation. Multivariate Cox regression analysis was also performed and confirmed that the expression of DKK2 is an independent prognostic factor in PDAC. A high expression of DKK2 correlates with cell migration and epithelial mesenchymal transition based on gene set enrichment analysis (GSEA) while knockdown of DKK2 in PDAC cells resulted in impaired cellular migration. Furthermore, GSEA predicts negative correlation between tumor immunity invasion and DKK2 expression. We then confirmed these results and demonstrated that a higher expression of DKK2 imparts the recruitment of CD8+ T cells. Our work suggested that DKK2 imparts tumor immune evasion and is associated with poor prognosis in pancreatic ductal adenocarcinoma.

7.
PLoS Pathog ; 15(10): e1008032, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31589660

RESUMO

The intracellular pathogen Listeria monocytogenes is distinguished by its ability to invade and replicate within mammalian cells. Remarkably, of the 15 serovars within the genus, strains belonging to serovar 4b cause the majority of listeriosis clinical cases and outbreaks. The Listeria O-antigens are defined by subtle structural differences amongst the peptidoglycan-associated wall-teichoic acids (WTAs), and their specific glycosylation patterns. Here, we outline the genetic determinants required for WTA decoration in serovar 4b L. monocytogenes, and demonstrate the exact nature of the 4b-specific antigen. We show that challenge by bacteriophages selects for surviving clones that feature mutations in genes involved in teichoic acid glycosylation, leading to a loss of galactose from both wall teichoic acid and lipoteichoic acid molecules, and a switch from serovar 4b to 4d. Surprisingly, loss of this galactose decoration not only prevents phage adsorption, but leads to a complete loss of surface-associated Internalin B (InlB),the inability to form actin tails, and a virulence attenuation in vivo. We show that InlB specifically recognizes and attaches to galactosylated teichoic acid polymers, and is secreted upon loss of this modification, leading to a drastically reduced cellular invasiveness. Consequently, these phage-insensitive bacteria are unable to interact with cMet and gC1q-R host cell receptors, which normally trigger cellular uptake upon interaction with InlB. Collectively, we provide detailed mechanistic insight into the dual role of a surface antigen crucial for both phage adsorption and cellular invasiveness, demonstrating a trade-off between phage resistance and virulence in this opportunistic pathogen.

8.
Microvasc Res ; 128: 103930, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31639383

RESUMO

The integrity of structure and function of blood-brain barrier (BBB) plays a central role in maintaining the homeostasis of the central nervous system. Patients with severe cerebrovascular stenosis often undergo cerebrovascular bypass surgery. However, the sharply increased fluid shear stress (FSS) after cerebrovascular bypass disrupts the physiological function of brain microvascular endothelial cells (BMECs) at the lesion site, damaging BBB and inducing intracerebral hemorrhage eventually. At present, there are great interests in cerebral vascular flow regulating the structure and function of BBB under physiological and pathological conditions, and most of studies have highlighted the importance of BMECs in BBB. Understanding of how FSS regulating BBB can promote the development of new protective and restorative cerebral vascular interventional therapy.

9.
Rev Sci Instrum ; 90(9): 093301, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31575235

RESUMO

A low-energy, compact, and superconducting electron beam ion trap (the Shanghai-Wuhan EBIT or SW-EBIT) for extraction of highly charged ions is presented. The magnetic field in the central drift tube of the SW-EBIT is approximately 0.21 T produced by a pair of high-temperature superconducting coils. The electron-beam energy of the SW-EBIT is in the range of 30-4000 eV, and the maximum electron-beam current is up to 9 mA. Acting as a source of highly charged ions, the ion-beam optics for extraction is integrated, including an ion extractor and an einzel lens. A Wien filter is then used to measure the charge-state distribution of the extracted ions. In this work, the tungsten ions below the charge state of 15 have been produced, extracted, and analyzed. The charge-state distributions and spectra in the range of 530-580 nm of tungsten ions have been measured simultaneously with the electron-beam energy of 279 eV and 300 eV, which preliminarily indicates that the 549.9 nm line comes from W14+.

10.
Nanoscale ; 11(41): 18923-18945, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31532436

RESUMO

The human body is a "delicate machine" full of sensors such as the fingers, nose, and mouth. In addition, numerous physiological signals are being created every moment, which can reflect the condition of the body. The quality and the quantity of the physiological signals are important for diagnoses and the execution of therapies. Due to the incompact interface between the sensors and the skin, the signals obtained by commercial rigid sensors do not bond well with the body; this decreases the quality of the signal. To increase the quantity of the data, it is important to detect physiological signals in real time during daily life. In recent years, there has been an obvious trend of applying graphene devices with excellent performance (flexibility, biocompatibility, and electronic characters) in wearable systems. In this review, we will first provide an introduction about the different methods of synthesis of graphene, and then techniques for graphene patterning will be outlined. Moreover, wearable graphene sensors to detect mechanical, electrophysiological, fluid, and gas signals will be introduced. Finally, the challenges and prospects of wearable graphene devices will be discussed. Wearable graphene sensors can improve the quality and quantity of the physiological signals and have great potential for health-care and telemedicine in the future.

11.
Mol Genet Genomic Med ; 7(11): e604, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31487119

RESUMO

BACKGROUND: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population. METHODS: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay. RESULTS: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H. CONCLUSION: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

12.
Ther Apher Dial ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31381247

RESUMO

Blood pressure variability is an independent predictor of adverse clinical events in hemodialysis patients. Volume overload is one of the most important factors affecting blood pressure homeostasis. In the present study, we explored the effects of dry weight reduction on home blood pressure variability in volume overload hemodialysis patients. Hemodialysis patients with volume overload had their dry weight gradually decreased under the guidance of bioimpedance methods, which was represented by calf-bioimpedance ratio (Calf-BR). Home blood pressure was measured on waking up and at bedtime for 1 week at baseline and at the end of the two-month study. Coefficient of variation was used to define home blood pressure variability. Thirty-eight hemodialysis patients had their dry weight significantly decreased from 60.7 ± 11.3 to 59.6 ± 10.7 kg (P = 0.003) accompanied with a significant reduction in calf-BR (0.828 ± 0.023 vs. 0.786 ± 0.020, P<0.001). The systolic and diastolic blood pressure decreased significantly. Moreover, the whole-day, morning, and evening systolic blood pressure variability gradually and significantly decreased by the end of the study (5.6 ± 2.1% versus 4.0 ± 1.7%, P<0.001; 7.7 ± 3.5% vs. 6.3 ± 2.7%, P = 0.005; 7.5 ± 2.8% vs. 5.9 ± 2.3%, P = 0.002, respectively). Diastolic blood pressure variability parameters were unchanged. The interdialytic weight gain and the incidence of adverse events were similar throughout the study period. Gradual dry weight reduction by bioimpedance methods improved home blood pressure variability in hemodialysis patients with chronic fluid overload.

13.
Angew Chem Int Ed Engl ; 58(44): 15904-15909, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31398275

RESUMO

Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic-peptide ligands for therapeutic targets, phage-displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage-display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded Nϵ -acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine-AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4- to 6-fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.

14.
Kidney Int ; 96(5): 1105-1120, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31405732

RESUMO

Inflammation and tubular cell death are the hallmarks of acute kidney injury. However, the precise mechanism underlying these effects has not been fully elucidated. Here we tested whether caspase-11, an inflammatory member of the caspase family, was increased in cisplatin or ischemia-reperfusion-induced acute kidney injury. Caspase-11 knockout mice after cisplatin treatment exhibited attenuated deterioration of renal functional, reduced tubular damage, reduced macrophage and neutrophil infiltration, and decreased urinary IL-18 excretion. Mechanistically, the upregulation of caspase-11 by either cisplatin or ischemia-reperfusion cleaved gasdermin D (GSDMD) into GSDMD-N, which translocated onto the plasma membrane, thus triggering cell pyroptosis and facilitated IL-18 release in primary cultured renal tubular cells. These results were further confirmed in GSDMD knockout mice that cisplatin-induced renal morphological and functional deterioration as well as urinary IL-18 excretion were alleviated. Furthermore, deficiency of GSDMD significantly suppressed cisplatin-induced IL-18 release but not the transcription and maturation level of IL-18 in tubular cells. Thus, our study indicates that caspase-11/GSDMD dependent tubule cell pyroptosis plays a significant role in initiating tubular cell damage, urinary IL-18 excretion and renal functional deterioration in acute kidney injury.

15.
ACS Appl Mater Interfaces ; 11(38): 34939-34947, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31465194

RESUMO

Garnet-type solid electrolytes are suitable for solid-state batteries with a lithium metal anode, but it is challenging to fabricate garnet-based lithium metal batteries with a long cycle life at high rates. This study demonstrates that a mosaic Li7Sn3/LiF interface layer formed in situ on the surface of garnet-type Li6.75La3Zr1.75Ta0.25O12 (LLZT) through the reaction between a SnF2 coating layer and a lithium metal enables stable, high-rate cycling for LLZT-based batteries. The interface layer possesses a nanomosaic structure of Li7Sn3 nanoparticles and surrounding LiF, enabling fast lithium-ion conduction. Meanwhile, ion insulating Li2CO3 on the surface of LLZT pellets is completely removed by SnF2 during the formation of the interface layer, which reduces the ion diffusion barrier from LLZT to the lithium anode. Benefiting from the advantageous interface layer, LiFePO4∥SnF2-LLZT∥Li cells show superior cycle performance over 200 cycles at 1 C (272 µA cm-2) with a capacity of 140.6 mAh g-1 (94.6% retention) at 30 °C. Even at 2 C, a capacity of 102.9 mAh g-1 remains after 200 cycles. This work provides an optimal interfacial structure to enhance lithium-ion migration between garnet electrolytes and a lithium metal and paves the way for developing high-performance solid-state batteries.

16.
Sci Rep ; 9(1): 11883, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417156

RESUMO

Post-translational regulation plays a central role in the circadian clock mechanism. However, nucleocytoplasmic translocation of core clock proteins, a key step in circadian timekeeping, is not fully understood. Earlier we found that the NRON scaffolding complex regulates nuclear translocation of NFAT and its signaling. Here, we show that components of the NRON complex also regulate the circadian clock. In peripheral cell clock models, genetic perturbation of the NRON complex affects PER and CRY protein nuclear translocation, dampens amplitude, and alters period length. Further, we show small molecules targeting the NFAT pathway alter nuclear translocation of PER and CRY proteins and impact circadian rhythms in peripheral cells and tissue explants of the master clock in the suprachiasmatic nucleus. Taken together, these studies highlight a key role for the NRON complex in regulating PER/CRY subcellular localization and circadian timekeeping.

18.
Medicine (Baltimore) ; 98(34): e16862, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441860

RESUMO

This study aimed to investigate the effect of auxiliary Kirschner wire (K-wire) technique in the closed reduction of children with Gartland type III supracondylar humerus fractures by comparing with manual reduction alone.Retrospective analysis was performed on the clinical data of 68 cases of supracondylar humerus fractures. Thirty-six patients received closed reduction and percutaneous fixation with auxiliary K-wire technique (group A). Thirty-two patients received conventional manual reduction and percutaneous pin fixation (Group B).In group A, the average operation time was 20.5 ±â€Š8.5 minutes, the average frequency of intraoperative radiographic observations was 4.3 ±â€Š1.1, the average fracture healing time was 6.2 ±â€Š1.8 weeks, and the complication rate was 3/36, 8.3%. The mean operation time was 36.1 ±â€Š10.2 minutes, the average frequency of intraoperative radiography was 8.9 + 1.7 times, the average fracture healing time was (6.1 ±â€Š1.6) weeks, and the complication rate was 2/32, 6.3%. The operation time in group A was significantly shorter than that in group B. The difference between the 2 groups was statistically significant (P = .012). The frequency of radiography in group A was significantly less than that in group B (P = .001).Compared with manual reduction, auxiliary K-wire technology can significantly shorten the operation time, reduce the radiant quantity of the surgeon, improve the efficiency of closed reduction of children with Gartland type III supracondylar humerus fractures, and reduce the risk of developing postoperative complications. And meanwhile, there is no significant effect on the imaging and functional outcomes of affected extremities, which is worthy of respect.


Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Fraturas do Úmero/classificação , Fraturas do Úmero/diagnóstico por imagem , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
19.
IEEE Int Conf Rehabil Robot ; 2019: 611-617, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31374698

RESUMO

In physical rehabilitation, exoskeleton assistive devices aim to restore lost motor functions of a patient suffering from neuromuscular or musculoskeletal disorders. These assistive devices are classified as operating in one of two modes: (1) passive mode, in which the exoskeleton passively moves its joints through the full range (or a subset) of the patient's motion during engagement, or (2) assist-as-needed (AAN) mode, in which the exoskeleton provides assistance to the joints of the patient, either by initiating the movements or assisting the patient's movements to complete the task at hand. Achieving high physical human-robot interaction (pHRI) transparency is an open problem for multiple degrees-of-freedom (DOFs) redundant exoskeletons. Using the EXO-UL8 exoskeleton, this study compares two multi-joint admittance control schemes (hyper parameter-based, and Kalman Filter-based) with comfort optimization to improve human-exoskeleton transparency. The control schemes were tested by three healthy subjects who completed reaching tasks while assisted by the exoskeleton. Kinematic information in both joint and task space, as well as force-and torque-based power exchange between the human arm and exoskeleton, are collected and analyzed. The results show that the preliminary Kalman Filter-based control scheme matches the performance of the existing hyper parameter-based scheme, highlighting the potential of the Kalman Filter-based approach for additional performance.

20.
Science ; 365(6453): 578-582, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395780

RESUMO

Dielectric capacitors with ultrahigh power densities are fundamental energy storage components in electrical and electronic systems. However, a long-standing challenge is improving their energy densities. We report dielectrics with ultrahigh energy densities designed with polymorphic nanodomains. Guided by phase-field simulations, we conceived and synthesized lead-free BiFeO3-BaTiO3-SrTiO3 solid-solution films to realize the coexistence of rhombohedral and tetragonal nanodomains embedded in a cubic matrix. We obtained minimized hysteresis while maintaining high polarization and achieved a high energy density of 112 joules per cubic centimeter with a high energy efficiency of ~80%. This approach should be generalizable for designing high-performance dielectrics and other functional materials that benefit from nanoscale domain structure manipulation.

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