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Suspended sediment and salinity stresses may escalate under climate change in inshore turbid habitats. We test whether fertilization and embryonic development of Acropora tumida and Platygyra carnosa are less prone to both stressors in turbid coral habitats compared to thresholds reported in literature for species found in clear water reefs. Under optimal sperm concentration (10 6 sperm mL -1 ), fertilization of A. tumida declined by 50 % when exposed to combined sediment (92 mg L -1 ) and salinity stresses. However, these stressors had no significant impact on P. carnosa. We found ∼20- and ∼ 7-fold increases in abnormal embryos for A. tumida and P. carnosa, respectively, under combined stressors. Furthermore, silicon-rich terrestrial-originated sediment caused 50 % larval mortality for A. tumida at a lower concentration of 53 mg L -1 . We showed that climate change-related salinity and sediment stresses may hinder coral reproduction and challenge coral recovery, questioning the coral survival in nearshore turbid habitats., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fluoroquinolones (FQs) are widely prescribed antibiotics that are commonly detected in aquatic environments, but the persistence, fates, and ecotoxicities of new generation FQs have yet to be fully investigated. We investigated the direct and indirect (hydroxyl radical (·OH), singlet oxygen (O21), and excited stated of organic matter ( 3 CDOM * )) photodegradation of three 3rd generation FQs, moxifloxacin (MOX), gatifloxacin (GAT), and sparfloxacin (SPAR). The photodegradation rates and photolytic quantum yields (Φ FQ ) of the FQs depended on their dissociation species at different pH in a range of 1×10 -4 to 1×10 -3 M mol-photon -1 . Unlike MOX and GAT whose zwitterions had the highest Φ FQ , the anionic form of SPAR had the highest Φ FQ . The k ·OH,FQ values were in the order of: k ·OH,SPAR > k ·OH,GAT ≈ k ·OH,MOX with the 10 10 M -1 s -1 order of magnitude. The k O21,FQ values were in the order of: k O21,SPAR (∼10 8 M -1 s -1 ) > k O21,MOX (∼10 7 M -1 s -1 ) > >> k O21,GAT (insignificant). Higher k LC*3,FQ values were observed for MOX (10 9 to 10 10 M -1 s -1 ) compared to GAT and SPAR (10 8 to 10 9 M -1 s -1 ). The zwitterions had the highest reactivities with ·OH and the lowest reactivities with O21 and 3 CDOM * . Reactions with ·OH enhanced the formation of transformation products (TPs) from decarboxylation and sidechain oxidation pathways, whereas reactions with O21 and 3 CDOM * enhanced the formation of TPs from sidechain oxidation pathways. Some of the TPs were predicted to exhibit aquatic ecotoxicity and environmental persistence. The half-lives of the FQs were estimated to be 0.42 to 0.67 h for MOX and SPAR, and 4.6 to 4.9 h for GAT. Their half-lives and main photochemical fates depended on the surface water pH and water column depth. These results highlight the key roles that photodegradation plays in removing new generation FQs from aquatic environments, though this might lead to the formation of TPs that are harmful to aquatic ecosystems., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Theodora Nah reports financial support was provided by City University of Hong Kong State Key Laboratory of Marine Pollution. Theodora Nah reports financial support was provided by Guangdong Basic and Applied Basic Research Fund Committee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents., Methods: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively., Results: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2) + CD4 + , SNM-specific IL-2 + CD8 + , S-specific IL-2 + CD8 + , N-specific IL-2 + CD4 + , N-specific IL-2 + CD8 + and M-specific IL-2 + CD4 + responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2 + CD4 + , interferon-γ + CD8 + and IL-2 + CD8 + responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions., Conclusion: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines., (© 2023. The Author(s).)

The fish gill is the first tissue that is exposed to the external media and undergoes continuous osmotic challenges. Recently, our group published an article entitled "Integrated Omics Approaches Revealed the Osmotic Stress-Responsive Genes and Microbiota in Gill of Marine Medaka" in the journal mSystems (e0004722, 2022), and suggested the possible host-bacterium interaction in the fish gill during osmotic stress. The previous study was performed by the progressive fresh water transfer (i.e., seawater to fresh water transfer via 50% seawater (FW)). Our group hypothesized that osmotic gradient could be a factor that determines the microbiota communities in the gill. The current 16S rRNA metagenomic sequencing study found that the direct transfer (i.e., seawater to fresh water (FWd)) could result in different gill microbiota communities in the same fresh water endpoints. Pseduomonas was the dominant bacteria (more than 55%) in the FWd gill. The Kyoto Encyclopedia of Genes and Genomes and MetaCyc analysis further suggested that the FWd group had enhanced osmosensing pathways, such as the ATP-binding cassette transporters, taurine degradation, and energy-related tricarboxylic acid metabolism compared to the FW group.

Aquatic fishes face osmotic stress continuously, and the gill is the first tissue that senses and responds to the external osmotic challenges. However, the understandings of how the gill microbiota could respond to osmotic stress and their potential host-bacterium relationships are limited. The objectives of the current study are to identify the hypotonic responsive genes in the gill cells and profile the gill microbiota communities after fresh water transfer experiment via transcriptome sequencing and 16S rRNA gene sequencing. Transcriptome sequencing identified 1,034 differentially expressed genes (DEGs), such as aquaporin and sodium potassium chloride cotransporter, after the fresh water transfer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further highlighted the steroid biosynthesis and glycosaminoglycan biosynthesis pathways in the gill. Moreover, the 16S rRNA gene sequencing identified Vibrio as the dominant bacterium in the seawater, which changed to Pseudomonas and Cetobacterium after the fresh water transfer. The alpha diversity analysis suggested that the gill bacterial diversity was lower in the fresh water transferred group. The KEGG and MetaCyc analysis further predicted the alteration of the glycosaminoglycan and chitin metabolisms in the gill bacteria. Collectively, the common glycosaminoglycan and chitin pathways in both the gill cells and gill microbiota suggest the host-bacterium interaction in gill facilitates the fresh water acclimation. IMPORTANCE This is the first study using the transcriptome and 16S rRNA gene sequencing to report the hypotonic responsive genes in gill cells and the compositions of gill microbiota in marine medaka. The overlapped glycosaminoglycan- and chitin-related pathways suggest host-bacterium interaction in fish gill during osmotic stress.

Background: Egg allergy is one of the most common food allergies in childhood with increasing prevalence in Hong Kong. While ample studies were published on its optimal diagnosis, there was limited data on predictors for the natural history of egg allergy in Asian populations., Objective: This study aimed to characterize the clinical course and outcome of children with egg allergy and identify its prognostic factors., Methods: All Chinese children with immediate-type egg allergy being followed since ≥3 years old in allergy clinic of our university-affiliated teaching hospital were reviewed to determine if they outgrew egg allergy at the latest follow-up. The predictive values of clinical and atopic factors for resolution of egg allergy were analyzed on Kaplan-Meier curves, and factors independently associated with persistent egg allergy was analyzed by logistic regression., Results: Seventy-six patients with median (interquartile range) age 8.9 years (6.3-13.0 years) were recruited. They initially presented with egg-allergic reactions at 1.0 years (0.7-1.7 years). Fifty-four children (71%) were able to tolerate egg at a median of 36 months from initial reaction. Patients with concomitant peanut allergy and those with initial reaction at ≥1 year old were more likely to have persistent egg allergy ( p = 0.015 and p = 0.027 respectively). Skin prick test wheal ≥6 mm to egg yolk and egg white individually as well as to both egg yolk and egg white were predictors for egg allergy persistence (respective, p < 0.001, p = 0.001, and p = 0.001 by log-rank tests). Logistic regression showed that initial SPT ≥ 6 mm to egg yolk was the only independent predictor for persistent egg allergy (B = 2.59 ± 0.98, p = 0.008)., Conclusion: Most Chinese children with immediate-type egg allergy can tolerate egg in long run. SPT wheal size to egg, concomitant peanut allergy and initial presentation after infancy may predict egg allergy persistence., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2021. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Objective: Cleft lip (CL) is a common congenital anomaly that can be syndromic or non-syndromic. It can be triggered by the mutation of gene or environmental factors. The incidence of CL is about 1 out of 700 live births. Facial development is a complex process, and there is no existing therapy to prevent the disease development. One of the characteristics in this facial malformation is the increased presence of reactive oxygen species (ROS). In this study, we hypothesize that the antioxidant glutathione (GSH) could help to attenuate the oxidative stress in this disease., Methods: Bioinformatics network pharmacology was applied to determine pharmacological targets and molecular mechanisms of GSH treatment for CL. Moreover, RNA-sequencing of the POLR1C knockdown osteoblast CL model was applied to validate the in silico data of using GSH in CL., Results: Twenty-two core targets of GSH and CL were identified via various bioinformatics tools. The GO and KEGG analysis indicated that GSH could modulate two major families (matrix metalloproteinase and integrins), which are related to extracellular matrix modification and composition for facial development in CL. The findings from POLR1C knockdown model further supported the rescue response of GSH in CL., Conclusions: The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: High tibial osteotomy (HTO) is a treatment of choice for active adult with knee osteoarthritis. With advancement in CT imaging with three-dimensional (3D) model reconstruction, virtual planning and 3D printing, patient-specific instrumentation (PSI) in form of cutting jigs is employed to improve surgical accuracy and outcome of HTO. The aim of this randomised controlled trial (RCT) is to explore the surgical outcomes of HTO for the treatment of medial compartment knee osteoarthritis with or without a 3D printed patient-specific jig., Methods and Analysis: A double-blind RCT will be conducted with patients and outcome assessors blinded to treatment allocation. This meant that neither the patients nor the outcome assessors would know the actual treatment allocated during the trial. Thirty-six patients with symptomatic medial compartment knee osteoarthritis fulfilling our inclusion criteria will be invited to participate the study. Participants will be randomly allocated to one of two groups (1:1 ratio): operation with 3D printed patient-specific jig or operation without jig. Measurements will be taken before surgery (baseline) and at postoperatively (6, 12 and 24 months). The primary outcome includes radiological accuracy of osteotomy. Secondary outcomes include a change in knee function from baseline to postoperatively as measured by three questionnaires: Knee Society Scores (Knee Scores and Functional Scores), Oxford Knee Scores and pain visual analogue scale (VAS) score., Ethics and Dissemination: Ethical approval has been obtained from the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (CREC no. 2019.050), in accordance with the Declaration of Helsinki. The results will be presented at international scientific meetings and through publications in peer-reviewed journals., Trial Registration Number: NCT04000672; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Limited studies have examined the relationship between axial rotational alignment and functional outcome in mobile-bearing UKA. The aims of this study was to determine the correlation between component axial rotational alignment and functional outcomes, and to recommend a safety range for component rotation for Oxford UKA., Methods: A retrospective study of 83 Oxford UKA was performed in 67 patients. Postoperative CT scans and clinical assessments were performed at a mean follow up of 21 months. Functional outcomes were measured by the OKS, modified KSS and KFS scores. A moving threshold analysis was performed to evaluate the relationship between different rotational alignment cut-off values and functional outcome scores., Results: The mean femoral and tibial components were positioned with a mean of 4.8° and 7.5° external rotation (ER), respectively. Increasing tibial external rotation was negatively correlated with clinical outcome scores while increasing femoral component rotation did not correlate with clinical outcomes. Better functional scores were observed at mean femoral and tibial rotation angles between 2-6° ER (1.2-6.6°) and 1-8° ER (0.5-8.8°), respectively; with the highest OKS, KSS and FKS observed at 3-4° ER for femoral component, and 4-5° ER for tibial component., Conclusion: Femoral component axial rotation between 2°- 6° ER, and tibial component axial rotation between 1° and 8° ER correlated with significantly better functional scores. Surgeons should be especially aware of the relatively high variability in tibial component rotation and its implications of functional outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Monitoring population dynamics in co-culture is necessary in engineering microbial consortia involved in distributed metabolic processes or biosensing applications. However, it remains difficult to measure strain-specific growth dynamics in high-throughput formats. This is especially vexing in plate-based functional screens leveraging whole-cell biosensors to detect specific metabolic signals. Here, we develop an experimental high-throughput co-culture system to measure and model the relationship between fluorescence and cell abundance, combining chassis-independent recombinase-assisted genome engineering (CRAGE) and whole-cell biosensing with a P emrR -green fluorescent protein (GFP) monoaromatic reporter used in plate-based functional screening. CRAGE was used to construct Escherichia coli EPI300 strains constitutively expressing red fluorescent protein (RFP) and the relationship between RFP expression and optical density (OD 600 ) was determined throughout the EPI300 growth cycle. A linear equation describing the increase of normalized RFP fluorescence during deceleration phase was derived and used to predict biosensor strain dynamics in co-culture. Measured and predicted values were compared using flow cytometric detection methods. Induction of the biosensor lead to increased GFP fluorescence normalized to biosensor cell abundance, as expected, but a significant decrease in relative abundance of the biosensor strain in co-culture and a decrease in bulk GFP fluorescence. Taken together, these results highlight sensitivity of population dynamics to variations in metabolic activity in co-culture and the potential effect of these dynamics on the performance of functional screens in plate-based formats. The engineered strains and model used to evaluate these dynamics provide a framework for optimizing growth of synthetic co-cultures used in screening, testing and pathway engineering applications., (© The Author(s) 2020. Published by Oxford University Press.)

Alteration of the gut microbiota plays an important role in animal health and metabolic diseases. However, little is known with respect to the influence of environmental osmolality on the gut microbial community. The aim of the current study was to determine whether the reduction in salinity affects the gut microbiota and identify its potential role in salinity acclimation. Using Oryzias melastigma as a model organism to perform progressive hypotonic transfer experiments, we evaluated three conditions: seawater control (SW), SW to 50% sea water transfer (SFW) and SW to SFW to freshwater transfer (FW). Our results showed that the SFW and FW transfer groups contained higher operational taxonomic unit microbiota diversities. The dominant bacteria in all conditions constituted the phylum Proteobacteria, with the majority in the SW and SFW transfer gut comprising Vibrio at the genus level, whereas this population was replaced by Pseudomonas in the FW transfer gut. Furthermore, our data revealed that the FW transfer gut microbiota exhibited a reduced renin-angiotensin system, which is important in SW acclimation. In addition, induced detoxification and immune mechanisms were found in the FW transfer gut microbiota. The shift of the bacteria community in different osmolality environments indicated possible roles of bacteria in facilitating host acclimation., (© 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: One factor in the long-term survivorship of unicompartmental knee arthroplasty is the accuracy of implantation. In addition to implant designs, the instrumentation has also evolved in the last three decades to improve the reproducibility of implant placement. There have been limited studies comparing mobile bearing unicompartmental knee arthroplasty with contemporary instrumentation and fixed bearing unicompartmental knee arthroplasty with conventional instrumentation. This study aims to determine whether the Microplasty instrumentation in Oxford unicompartmental knee arthroplasty allows the surgeon to implant the components more precisely and accurately., Methods: A total of 150 patients (194 knees) were included between April 2013 and June 2019. Coronal and sagittal alignment of the tibial and femoral components was measured on postoperative radiographs. Component axial rotational alignment was measured on postoperative computer tomography. The knee rotation angle was the difference between the femoral and tibial axial rotation. A rotational mismatch was defined as a knee rotation angle of > 10°. Statistical analysis was performed using Student t test and Mann-Whitney nonparametric test. A p value < 0.05 was considered statistically significant in each analysis., Results: Between April 2013 to June 2019, 112 patients (150 knees) received Oxford unicompartmental knee arthroplasty, one patient (2 knees) had Journey unicompartmental knee arthroplasty, and 37 patients (42 knees) received Zimmer unicompartmental knee arthroplasty. All femoral components in the Oxford group were implanted within the reference range, compared with 36.6% in the fixed bearing group (p < 0.001). 88.3% of Oxford knees had tibial component falling within the reference range, whereas 56.1% of knees in the fixed bearing group fell within the reference range (p < 0.001). 97.5% of Oxford knees had tibial slope that fell within reference range, whereas 53.7% fell within range for fixed bearing group (p < 0.001). Femorotibial rotational mismatch of more than 10° was noted in 13.8% in Oxford group and 20.5% in fixed bearing group (p = 0.04)., Conclusion: In conclusion, Microplasty instrumentation for Oxford mobile bearing unicompartmental knee arthroplasty is more accurate and precise compared to conventional fixed bearing unicompartmental knee arthroplasty in sagittal, coronal, and axial alignment. Prospective studies with long-term follow-up are warranted to investigate the clinical implications.

Background: Gills of euryhaline fishes possess great physiological and structural plasticity to adapt to large changes in external osmolality and to participate in ion uptake/excretion, which is essential for the re-establishment of fluid and electrolyte homeostasis. The osmoregulatory plasticity of gills provides an excellent model to study the role of microRNAs (miRs) in adaptive osmotic responses. The present study is to characterize an ex-vivo gill filament culture and using omics approach, to decipher the interaction between tonicity-responsive miRs and gene targets, in orchestrating the osmotic stress-induced responses., Results: Ex-vivo gill filament culture was exposed to Leibovitz's L-15 medium (300 mOsmol l - 1 ) or the medium with an adjusted osmolality of 600 mOsmol l - 1 for 4, 8 and 24 h. Hypertonic responsive genes, including osmotic stress transcriptional factor, Na + /Cl - -taurine transporter, Na + /H + exchange regulatory cofactor, cystic fibrosis transmembrane regulator, inward rectifying K + channel, Na + /K + -ATPase, and calcium-transporting ATPase were significantly upregulated, while the hypo-osmotic gene, V-type proton ATPase was downregulated. The data illustrated that the ex-vivo gill filament culture exhibited distinctive responses to hyperosmotic challenge. In the hyperosmotic treatment, four key factors (i.e. drosha RNase III endonuclease, exportin-5, dicer ribonuclease III and argonaute-2) involved in miR biogenesis were dysregulated (P < 0.05). Transcriptome and miR-sequencing of gill filament samples at 4 and 8 h were conducted and two downregulated miRs, miR-29b-3p and miR-200b-3p were identified. An inhibition of miR-29b-3p and miR-200b-3p in primary gill cell culture led to an upregulation of 100 and 93 gene transcripts, respectively. Commonly upregulated gene transcripts from the hyperosmotic experiments and miR-inhibition studies, were overlaid, in which two miR-29b-3p target-genes [Krueppel-like factor 4 (klf4), Homeobox protein Meis2] and one miR-200b-3p target-gene (slc17a5) were identified. Integrated miR-mRNA-omics analysis revealed the specific binding of miR-29b-3p on Klf4 and miR-200b-3p on slc17a5. The target-genes are known to regulate differentiation of gill ionocytes and cellular osmolality., Conclusions: In this study, we have characterized the hypo-osmoregulatory responses and unraveled the modulation of miR-biogenesis factors/the dysregulation of miRs, using ex-vivo gill filament culture. MicroRNA-messenger RNA interactome analysis of miR-29b-3p and miR-200b-3p revealed the gene targets are essential for osmotic stress responses.

Two experiments are reported on the steering of a tracked vehicle through straight-line courses and corners to determine the relationships between movement time and control accuracy with the geometry of the course, such as the vehicle width, the track width and the type of corner. For straight line tracking, Drury's law in which movement time (MT) is linear with the tracking task difficulty measure [A/(W - d)] is found to hold, where A is the distance traveled, 'W' is the track width and 'd' is the vehicle width. Performance in three types of corners (right angle, cut angle and circular) varied little, with the most important factor being the clearance (W - d) available to the operator. Collisions with boundary walls were also highly related to this factor. The reported research has strong relevance to the training of operators for urban search and rescue robots. Practitioner summary: Data for steering a real vehicle in a simulated environment of straight paths and different corner geometries showed that Drury's law holds for straight line tracking and the clearance between the widths of vehicle and track is important in steering corners. Data show clear need for training of USAR (Urban Search and Rescue) operators.

The 33rd Asia-Pacific Academy of Ophthalmology (APAO) Congress was held on Feb 8-11, 2018 in Hong Kong. This report summarized the highlights of the neuro-ophthalmology program of the Congress, including the scientific symposia (invited and submitted) and the social activities.

Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.

Treacher Collins syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects. Recently, the authors' group unfolded the pathogenesis of polr1c Type 3 TCS by using the zebrafish model. Facial development depends on the neural crest cells, in which polr1c plays a role in regulating their expression. In this study, the authors aimed to identify the functional time window of polr1c in TCS by the use of photo-morpholino to restore the polr1c expression at different time points. Results suggested that the restoration of polr1c at 8 hours after fertilization could rescue the TCS facial malformation phenotype by correcting the neural crest cell expression, reducing the cell death, and normalizing the p53 mRNA expression level in the rescued morphants. However, such recovery could not be reproduced if the polr1c is restored after 30 hours after fertilization., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Rationale, Aims and Objectives: Timely detection and management of acutely deteriorating patients can save lives. Tuen Mun Hospital (TMH), a 1800-bed acute tertiary hospital serving more than 1.06 million populations in Hong Kong, is exploring to quantitatively monitor serious clinical deterioration (SCD) and uses it to guide patient care improvement initiatives., Methods: Literature review on definition and measurement of SCD was conducted. Monthly SCD rates of TMH were first calculated according to the published methodology and benchmarked against those of international centres. A refined composite clinical indicator good for local use was compiled. In the second phase, p-control charts of SCD have been plotted based on cumulative data., Results: TMH's performance was comparable with that of international centres. SCD on p-control charts has been plotting since January 2013. There were peaks in all 4 SCD rates during the winter surge period in 2013-2014. In the third phase, multiple measures have been taking to reduce the SCD rates including targeting the 3 main factors of winter surge situation. We are delighted to observe that the pattern did not repeat in the rate of cardiac arrest without do not attempt cardiopulmonary resuscitation (DNACPR) and rate of death without DNACPR in the same period in 2014-2015., Conclusions: SCD becomes a clinical governance tool to monitor the performance of clinical teams in treating acutely deteriorating patients in TMH. Any abnormal patterns or indications of special cause variations in the control charts would alert leaders to look for root causes of special cause variations and manage accordingly. We hope that this project will extend to corporate level and become a sustainable clinical indicator to guide audits, quality improvement initiatives and strategic planning., (© 2016 John Wiley & Sons, Ltd.)

Fungi are a valuable source of enzymatic diversity and therapeutic natural products including antibiotics. Here we engineer the baker's yeast Saccharomyces cerevisiae to produce and secrete the antibiotic penicillin, a beta-lactam nonribosomal peptide, by taking genes from a filamentous fungus and directing their efficient expression and subcellular localization. Using synthetic biology tools combined with long-read DNA sequencing, we optimize productivity by 50-fold to produce bioactive yields that allow spent S. cerevisiae growth media to have antibacterial action against Streptococcus bacteria. This work demonstrates that S. cerevisiae can be engineered to perform the complex biosynthesis of multicellular fungi, opening up the possibility of using yeast to accelerate rational engineering of nonribosomal peptide antibiotics.

Triclosan (TCS) is an active antimicrobial ingredient used in many household products, such as skin creams and toothpaste. It is produced in high volumes, and humans are directly exposed to it and dispose it on a daily basis. TCS has been found to contaminate water worldwide. This study aimed to understand the potential developmental and metabolic abnormalities caused by TCS exposure by using zebrafish as the experimental model. Four developmental stages (70-85% epiboly, 10-12 somite, prim-5, and 5dpf) were selected to perform in situ hybridization staining to investigate the effects of TCS on dorsal ventral patterning, segmentation, brain development, and organ formation. Results showed, in terms of developmental toxicology, that neither phenotypic nor molecular changes were found after 5 days of 250μg/L TCS exposure. However, such dosage of TCS exposure resulted in lipid droplet accumulation in the yolk sac, which might due to the deregulated mRNA expression level of beta-oxidation transcripts. This study showed that 250μg/L TCS exposure does not affect normal embryogenesis or organogenesis; however, there are concerns regarding possible impairment of lipid metabolism., (Copyright © 2016 Elsevier B.V. All rights reserved.)