Mussel-Inspired Anisotropic Nanocellulose and Silver Nanoparticle Composite with Improved Mechanical Properties, Electrical Conductivity and Antibacterial Activity

Materials for wearable devices, tissue engineering and bio-sensing applications require both antibacterial activity to prevent bacterial infection and biofilm formation, and electrical conductivity to electric signals inside and outside of the human body. Recently, cellulose nanofibers have been utilized for various applications but cellulose itself has neither antibacterial activity nor conductivity. Here, an antibacterial and electrically conductive composite was formed by generating catechol mediated silver nanoparticles (AgNPs) on the surface of cellulose nanofibers. The chemically immobilized catechol moiety on the nanofibrous cellulose network reduced Ag+ to form AgNPs on the cellulose nanofiber. The AgNPs cellulose composite showed excellent antibacterial efficacy against both Gram-positive and Gram-negative bacteria. In addition, the catechol conjugation and the addition of AgNP induced anisotropic self-alignment of the cellulose nanofibers which enhances electrical and mechanical properties of the composite. Therefore, the composite containing AgNPs and anisotropic aligned the cellulose nanofiber may be useful for biomedical applications.open11128sciescopu

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Chiral nematic self-assembly of minimally surface damaged chitin nanofibrils and its load bearing functions

Chitin is one of the most abundant biomaterials in nature, with 1010 tons produced annually as hierarchically organized nanofibril fillers to reinforce the exoskeletons of arthropods. This green and cheap biomaterial has attracted great attention due to its potential application to reinforce biomedical materials. Despite that, its practical use is limited since the extraction of chitin nanofibrils requires surface modification involving harsh chemical treatments, leading to difficulties in reproducing their natural prototypal hierarchical structure, i.e. chiral nematic phase. Here, we develop a chemical etching-free approach using calcium ions, called "natural way", to disintegrate the chitin nanofibrils while keeping the essential moiety for the self-assembly, ultimately resulting in the reproduction of chitin's natural chiral structure in a polymeric matrix. This chiral chitin nanostructure exceptionally toughens the composite. Our resultant chiral nematic phase of chitin materials can contribute to the understanding and use of the reinforcing strategy in nature.open119sciescopu

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

Phase I-II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury

published_or_final_versionCreative Commons: Attribution 3.0 Hong Kong Licens

Do Patient Expectations Represent a More Important Clinical Difference? A Study of Surgical Outcomes in the Cervical Spine

Objective This study aims to compare the impact of achieving an MCID or meeting preoperative expectations on patient satisfaction following cervical spine procedures. Methods A surgical database was retrospectively reviewed for cervical spine surgery patients from 2016 to 2020. Inclusion criteria were primary or revision, single- or multilevel cervical disc arthroplasty or anterior cervical discectomy and fusions (ACDF). Visual analogue scale (VAS) neck and arm pain was assessed preoperatively and postoperatively (6-week, 12-weeks, 6-months, 1-year). Preoperative patient expectation and postoperative satisfaction were recorded. MCID achievement was determined using previously established values. Expectations met and MCID achievement were compared as possible predictors of satisfaction. Results One hundred and six cervical spine patients were included. Both meeting expectations and achieving MCID were significant predictors of satisfaction for arm pain at 6-weeks and 12-weeks (all p≤0.007). Achieving MCID significantly predicted satisfaction for neck pain at all timepoints (all p≤0.007) and meeting expectations predicted satisfaction for neck pain at 6-weeks, 12-weeks, and 1-year (all p≤0.003). Comparison of coefficients revealed no significant difference in effect size between meeting expectations and achievement of MCID as predictors of patient satisfaction (all p>0.050). Conclusion MCID achievement and meeting expectations were significant predictors of satisfaction for neck pain and short-term arm pain. Both measures may be similarly useful for interpretation of patient outcomes and the optimal choice of metric may depend on practice-specific factors

Lateral Lumbar Interbody Fusion in the Outpatient Setting with Multimodal Analgesic Protocol: Clinical Case Series

Objective Minimally invasive techniques and multimodal analgesia protocols have made spine surgery in the outpatient setting increasingly feasible. A number of spinal procedures have been documented in the outpatient setting, though the feasibility of lateral lumbar interbody fusion (LLIF) on an ambulatory basis has not been thoroughly assessed. To present a clinical case series of patients undergoing LLIF in the outpatient setting. Methods A prospectively maintained surgical database was retrospectively reviewed to identify patients undergoing outpatient spine procedures with an enhanced multimodal analgesia protocol from October 2016 to February 2021. Patient demographics, medical and spinal diagnoses, procedural characteristics, operative duration, estimated blood loss (EBL), postoperative length of stay (LOS), postoperative pain scores, postoperative narcotic consumption, and incidence of any intra- or postoperative complications were collected. The state’s prescription monitoring program was queried to assess rates of filling narcotic prescriptions >6 weeks following surgery. Results A total of 24 LLIF patients were included. Mean postoperative pain score was 5.8, and mean postoperative narcotic consumption was 26.8 oral morphine equivalents. All patients were discharged on the same day of surgery. No postoperative complications were observed. After the 6-week postoperative timepoint, 16.7% of patients filled a prescription for tramadol, 8.3% for hydrocodone, 4.2% for hydromorphone, 4.2% for cyclobenzaprine, and 4.2% for alprazolam. Conclusion This clinical case series demonstrates that LLIF can be both safe and feasible in the outpatient setting, with minimal narcotic medication dependence in the postoperative period

Lipopolysaccharides Impair Insulin Gene Expression in Isolated Islets of Langerhans via Toll-Like Receptor-4 and NF-κB Signalling

BACKGROUND:Type 2 diabetes is characterized by pancreatic β-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that the signalling cascade activated by lipopolysaccharides (LPS) binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets. METHODOLOGY/PRINCIPAL FINDINGS:A 24-h exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of pancreas-duodenum homebox-1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Accordingly, LPS exposure also decreased glucose-induced insulin secretion. LPS repression of insulin, PDX-1 and MafA expression, as well as its inhibition of insulin secretion, were not observed in islets from TLR4-deficient mice. LPS inhibition of β-cell gene expression in rat islets was prevented by inhibition of the NF-κB pathway, but not the p38 mitogen-activated protein kinase (p38 MAPK) pathway. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that LPS inhibit β-cell gene expression in a TLR4-dependent manner and via NF-κB signaling in pancreatic islets, suggesting a novel mechanism by which the gut microbiota might affect pancreatic β-cell function

The Road Less Traveled: Regulation of Leukocyte Migration Across Vascular and Lymphatic Endothelium by Galectins

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function