Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism.

Physical separation between the mammalian immune system and commensal bacteria is necessary to limit chronic inflammation. However, selective species of commensal bacteria can reside within intestinal lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid-tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulated their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal lymphoid tissues and induced multiple members of the IL-10 cytokine family, including dendritic-cell-derived IL-10 and group 3 innate lymphoid cell (ILC3)-derived IL-22. Notably, IL-10 limited the development of pro-inflammatory Th17 cell responses, and IL-22 production enhanced LRC colonization in the steady state. Furthermore, LRC colonization protected mice from lethal intestinal damage in an IL-10-IL-10R-dependent manner. Collectively, our data reveal a unique host-commensal-bacteria dialog whereby selective subsets of commensal bacteria interact with dendritic cells to facilitate tissue-specific responses that are mutually beneficial for both the host and the microbe.

Size-Controlled Synthesis of Gold Nanoparticles Tethering Antimicrobial Peptides with Potent Broad-Spectrum Antimicrobial and Antibiofilm Activities.

New antimicrobials are urgently needed to combat the rising global health concern of antibiotic resistance. Antimicrobial peptides (AMPs) are one of the leading candidates as new antimicrobials since they target bacterial membranes and are therefore less prone to bacterial resistance. However, poor enzymatic stability, high production costs, and toxicity are drawbacks that limit their clinical use. Conjugation of AMPs to gold nanoparticles (NPs) may help to improve enzymatic stability and, thus, their overall antimicrobial efficiency. We did a one-pot synthesis of size-controlled (10 nm) gold NPs selectively conjugated to lipopeptides and determined their antibacterial activity. The conjugates exhibited potent (0.13-1.25 µM) antimicrobial activity against clinical isolates, including Gram-positive methicillin-resistant Staphylococcus aureus (S. aureus) ATCC33593, Gram-negative Escherichia coli (E. coli) CTX-M-14, multidrug-resistant Pseudomonas aeruginosa LESB58 and Acinetobacter baumannii ATCC19606, and showed promising activity (90% inhibition of initial biofilms and 80% reduction of preformed biofilms) against S. aureus and E. coli DH5α biofilms at low micromolar concentrations. The conjugates were stable in rat serum and not toxic to representative mammalian cell lines in vitro (≤64 µM) and in vivo (≤100 µM).

Rational design of self-assembling ultrashort peptides for the shape- and size-tunable synthesis of metal nanostructures.

Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self-assembled to form stabilised three-dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81-AuNPs, whereas hexagonal nanoparticles were observed for TOH_1N-AuNPs and PentaOH-AuNPs in their respective hydrogel networks. The PentaOH-AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH_1N-AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials.

Homo and Hetero-Branched Lipopeptide Dendrimers: Synthesis and Antimicrobial Activity.

Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2, 3-triazole click chemistry. Antimicrobial studies against drug resistant clinical isolates of Escherichia coli (ESBL E. coli Ctx-M14), Pseudomonas aeruginosa (P. aeruginosa Q502), and Methicillin resistant Staphylococcus aureus (MRSA ATCC 33593), as well as clinically isolated Acinetobacter baumannii (A. baumannii ATCC 19606), and P. aeruginosa (ATCC 27853), revealed that the dendrimeric peptides have antimicrobial activity in the low micromolar range (0.5 -- 4 µM) which was 10 times more potent than the monomer peptides. Under high salt concentrations (150 mM NaCl, 2 mM MgCl2, and 2.5 mM CaCl2) the di-branched lipopeptides retained their antimicrobial activity while the monomer peptides were not active (>100 µM). The di-branched triazole click lipopeptide, Peptide 12, was membrane lytic, showed faster killing kinetics, and exhibited antibiofilm activity against A. baumannii and MRSA and eradicated > 85 % preformed biofilms at low micromolar concentrations. The di-branched analogues were > 30-fold potent than the monomers against Candida albicans. Peptide 12 was not haemolytic (HC10 = 932.12 µM) and showed up to 40-fold higher selectivity against bacteria and fungi than the monomer peptide. Peptide 12 exhibited strong proteolytic stability (>80 % not degraded) in rat serum over 24 h whereas > 95 % of the thiol-maleimide analogue (Peptide 10) was degraded. The tetra-branched peptides showed comparable antibacterial potency to the di-branched analogues. These findings indicate that dual branching using triazole click chemistry is a promising strategy to improve the antimicrobial activity and proteolytic stability of battacin based lipopeptides. The information gathered can be used to build effective antimicrobial dendrimeric peptides as new peptide antibiotics.

A Novel 0.1 mm 3D Laser Imaging Technology for Pavement Safety Measurement.

Traditionally, pavement safety performance in terms of texture, friction, and hydroplaning speed are measured separately via different devices with various limitations. This study explores the feasibility of using a novel 0.1 mm 3D Safety Sensor for pavement safety evaluation in a non-contact and continuous manner with a single hardware sensor. The 0.1 mm 3D images were collected for pavement safety measurement from 12 asphalt concrete (AC) and Portland cement concrete (PCC) field sites with various texture characteristics. The results indicate that the Safety Sensor was able to measure pavement texture data as traditional devices do with better repeatability. Moreover, pavement friction numbers can be estimated using 0.1 mm 3D data via the proposed 3D texture parameters with good accuracy using an artificial neural network, especially for asphalt pavement. Lastly, a case study of pavement hydroplaning speed prediction was performed using the Safety Sensor. The results demonstrate the potential of using ultra high-resolution 3D imaging to measure pavement safety, including texture, friction, and hydroplaning, in a non-contact, continuous, and accurate manner.

Bioactive Components and Anticancer Activities of Spray-Dried New Zealand Tamarillo Powder.

Tamarillo fruit contains many phytochemicals that have beneficial therapeutic and nutritional properties. Spray-drying is widely used to preserve fruit puree in powder form. However, to obtain high-quality fruit powder, the optimisation of spray-drying conditions is necessary, as a high drying temperature can damage sensitive bioactive compounds. This study investigated the effects of spray-drying on the microstructure, polyphenolics, total flavonoids, total carotenoids, antioxidant activity, and anticancer capacity of tamarillo powder. Response surface methodology (RSM) was used to optimise the spray-drying process to produce tamarillo powder. The independent variables were inlet drying temperature (120-160 °C), flow rate (1-5 g/mL), and maltodextrin concentration (0-10%). These variables influenced the microstructural attributes, bioactive components, and cytotoxicity of the spray-dried tamarillo powder. The increase in polyphenols and antioxidant activities were favoured under high-temperature spray drying conditions and a low carrier concentration. The optimised spray-drying conditions for producing tamarillo powder with high antioxidant and anticancer activities, high yield, and stable bioactive compounds were found to be at 146.8 °C inlet temperature, and a flow rate of 1.76 g/mL.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms.

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.

Battacin-Inspired Ultrashort Peptides: Nanostructure Analysis and Antimicrobial Activity.

Peptides can serve as versatile therapeutics with a highly modular structure and tunable biophysical properties. In particular, the efficacy of peptide antibiotics against drug-resistant pathogens is of great promise, as few new classes of antibiotics are being developed to overcome the ever-increasing bacterial resistance to contemporary drugs. This work reports biophysical and antimicrobial studies of a designed library of ultrashort peptides that self-assemble into hydrogels at concentrations as low as 0.5% w/v in buffered saline, as confirmed by rheology. The hydrogels are constituted by ß-sheet-rich nanofibril networks, as determined by biophysical techniques including spectroscopy (attenuated total reflectance Fourier transform infrared spectroscopy and Congo red binding assay), short- and wide-angle X-ray scattering, and electron microscopy. Both peptide solutions and self-assembled hydrogels show potent antimicrobial activity against S. aureus and Pseudomonas aeruginosa by membrane lysis. These peptides also displayed selectivity toward bacterial cells over human dermal fibroblasts in vitro, as determined from Live/Dead, scanning electron microscopy, and coculture assays. This work reports an antimicrobial self-assembling motif of only three residues comprising an aromatically acylated cationic d-Dab/Lys amino acid, a second cationic residue, and naphthylalanine that heavily influences the self-assembly of these peptides into hydrogels. The variations in the antimicrobial activity and self-assembly properties between analogues may have implications in future studies on the correlation between self-assembly and biological activity in ultrashort peptides.

S1 Sacrectomy for Re-recurrent Rectal Cancer: Our Experience with Reconstruction Using an Expandable Vertebral Body Replacement Device.

INTRODUCTION: R0 resection is achieved by high sacrectomy for local recurrence of colorectal cancer, but significant rates of perioperative complications and long-term patient morbidity are associated with this procedure. In this report, we outline our unique experience of using an expandable cage for vertebral body reconstruction following S1 sacrectomy in a 66-year-old patient with re-recurrent rectal cancer. We aim to highlight several key steps, with a view to improving postoperative outcomes. TECHNIQUE: A midline laparotomy was performed with the patient in supine Lloyd-Davies position, demonstrating recurrence of tumor at the S1 vertebral body. Subtotal vertebral body excision of S1 with sparing of the posterior wall and ventral foramina was completed by using an ultrasonic bone aspirator. Reconstruction was performed using an expandable corpectomy spacer system. The system was assembled and expanded in situ to optimally bridge the corpectomy. The device was secured into the L5 and S2 vertebrae by means of angled end plate screws superiorly and inferiorly. Bone grafts were positioned adjacent to the implant after this. RESULTS: Total operating time was 266 minutes with 350 mL of intraoperative blood loss. There were no immediate postoperative complications. The patient did not report any back pain at the time of discharge, and no neurological deficit was reported or identified. Postoperative CT scan showed excellent vertebral alignment and preservation of S1 height. CONCLUSION: We conclude that high sacrectomy with an expandable metal cage is feasible in the context of re-recurrent rectal cancer when consideration is given to the method of osteotomy and vertebral body replacement.

Lane Marking Detection and Reconstruction with Line-Scan Imaging Data.

Abstract: Lane marking detection and localization are crucial for autonomous driving and lane-based pavement surveys. Numerous studies have been done to detect and locate lane markings with the purpose of advanced driver assistance systems, in which image data are usually captured by vision-based cameras. However, a limited number of studies have been done to identify lane markings using high-resolution laser images for road condition evaluation. In this study, the laser images are acquired with a digital highway data vehicle (DHDV). Subsequently, a novel methodology is presented for the automated lane marking identification and reconstruction, and is implemented in four phases: (1) binarization of the laser images with a new threshold method (multi-box segmentation based threshold method); (2) determination of candidate lane markings with closing operations and a marching square algorithm; (3) identification of true lane marking by eliminating false positives (FPs) using a linear support vector machine method; and (4) reconstruction of the damaged and dash lane marking segments to form a continuous lane marking based on the geometry features such as adjacent lane marking location and lane width. Finally, a case study is given to validate effects of the novel methodology. The findings indicate the new strategy is robust in image binarization and lane marking localization. This study would be beneficial in road lane-based pavement condition evaluation such as lane-based rutting measurement and crack classification.

Automatic Groove Measurement and Evaluation with High Resolution Laser Profiling Data.

Grooving is widely used to improve airport runway pavement skid resistance during wet weather. However, runway grooves deteriorate over time due to the combined effects of traffic loading, climate, and weather, which brings about a potential safety risk at the time of the aircraft takeoff and landing. Accordingly, periodic measurement and evaluation of groove performance are critical for runways to maintain adequate skid resistance. Nevertheless, such evaluation is difficult to implement due to the lack of sufficient technologies to identify shallow or worn grooves and slab joints. This paper proposes a new strategy to automatically identify airport runway grooves and slab joints using high resolution laser profiling data. First, K-means clustering based filter and moving window traversal algorithm are developed to locate the deepest point of the potential dips (including noises, true grooves, and slab joints). Subsequently the improved moving average filter and traversal algorithms are used to determine the left and right endpoint positions of each identified dip. Finally, the modified heuristic method is used to separate out slab joints from the identified dips, and then the polynomial support vector machine is introduced to distinguish out noises from the candidate grooves (including noises and true grooves), so that PCC slab-based runway safety evaluation can be performed. The performance of the proposed strategy is compared with that of the other two methods, and findings indicate that the new method is more powerful in runway groove and joint identification, with the F-measure score of 0.98. This study would be beneficial in airport runway groove safety evaluation and the subsequent maintenance and rehabilitation of airport runway.

Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease.

The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.

Basophils promote innate lymphoid cell responses in inflamed skin.

Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4-enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis-like disease. We show that ILC2s express IL-4Rα and proliferate in an IL-4-dependent manner. Additionally, basophil-derived IL-4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation.

Helping cancer patients quit smoking by increasing their risk perception: a study protocol of a cluster randomized controlled trial.

BACKGROUND: Despite smoking cessation can largely improve cancer prognosis and quality of life, many patients continued smoking after the diagnosis of cancer. This study aims to test the effectiveness of a smoking cessation intervention using risk communication approach to help cancer patients quit smoking, and to improve their health related quality of life. METHODS: A cluster randomized controlled trial will be employed. Cancer patients who continued smoking after the diagnosis of cancer and have medical follow-up at the out-patient clinics of the five acute hospitals in Hong Kong will be invited to participate. Subjects in the experimental group will receive (1) health warnings of smoking based on a special designed leaflet; and (2) a patient-centred counseling from nurse counselors with emphasis on risk perceptions of smoking to cancer prognosis. Additionally, they will receive two more telephone counseling at 1-week and 1-month. Control group receive standard care and a generic self-help smoking cessation booklet. Outcomes measure include (a) self-reported and the biochemically validated quit rate, (b) patient's smoking reduction by at least 50% compared to baseline, (c) quit attempt(s), (d) change in the intention to quit, (e) change in risk perceptions of smoking, and (f) change in health related quality of life. DISCUSSION: This study will make an important contribution to evidence-based practice by testing the effectiveness of a tailored smoking cessation intervention for cancer patients. The results will support the development of clinical practice guidelines to promote smoking cessation in cancer patients to improve their prognosis and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01685723. Registered 9 November 2012.

Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer's disease.

A series of tacrine-rhein hybrid compounds have been designed and synthesized as novel multifunctional potent ChE inhibitors. Most of the compounds inhibited ChEs in the nanomolar range in vitro effectively. Compound 10b was one of the most potent inhibitors and was 5-fold more active than tacrine toward AChE, and it also showed a moderate BuChE inhibition with an IC50 value of 200 nM. Kinetic and molecular modeling studies of 10b also indicated that it was a mixed-type inhibitor binding simultaneously to the active and peripheral sites of AChE. In inhibition of the AChE-induced Aß aggregation assay, compound 10b (70.2% at 100 µM) showed the greatest inhibitory activity. In addition, 10b showed metal-chelating property and low hepatotoxicity. These results suggested that 10b might be an excellent multifunctional agent for AD treatment.

Text messaging interventions for breastfeeding outcomes: A systematic review and meta-analysis.

BACKGROUND: Given the health benefits of breastfeeding for infants and mothers, breastfeeding has become a significant public health issue. The global growth of mobile phone usage has created new options for breastfeeding promotion, including text messaging. OBJECTIVE: We aimed to evaluate the efficacy of text messaging interventions on breastfeeding outcomes and to identify the efficacy moderators of such interventions. METHODS: Ten electronic databases were searched from the inception of the databases to 5 July 2023. Studies were included if they used randomized controlled trials or quasi-experimental designs to evaluate the effect of text messaging interventions on breastfeeding outcomes. Two reviewers screened the included studies, assessed the risk of bias, and extracted the data. Pooled results were obtained by the random-effects model, and subgroup analyses were conducted on intervention characteristics to identify potential moderators. The protocol of this study was registered on PROSPERO (ID: CRD42022371311). RESULTS: Sixteen studies were included. Text messaging interventions could improve the exclusive breastfeeding rate (at <3 months: OR = 2.04; 95 % CI: 1.60-2.60, P < 0.001; at 3-6 months: OR = 1.66; 95 % CI: 1.18-2.33, P = 0.004; at ≥6 months: OR = 2.13; 95 % CI: 1.47-3.08, P < 0.001), and the breastfeeding self-efficacy (SMD = 0.30, 95 % CI: 0.14-0.45, P < 0.001). Text messaging interventions that covered antenatal and postnatal periods, delivered weekly were most effective in improving the exclusive breastfeeding rate. CONCLUSIONS: Text messaging interventions may improve breastfeeding practice compared with no or general health information. We suggest text messaging conducted from the pre- to postnatal periods in a weekly manner can effectively increase exclusive breastfeeding rates and breastfeeding self-efficacy. Further studies should investigate the relation between new theories (such as the health action process approach and the theory of message-framing) and efficacy of breastfeeding interventions, using text components.

Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Methods: Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. Results: EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. Conclusion: High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.