Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Gold (III) cyclometalated based amphiphiles in aqueous media have been revealed with excellent supramolecular transformations to external stimuli to open new pathways for soft functional material fabrications. Herein, we report a new chiral cyclometalated gold (III) amphiphile (GA) assembling into lamellar nanostructures in aqueous media confirmed with transmission electron microscopy (TEM). Counterion exchange with D-, L-, or racemic-camphorsulfonates features the significant supramolecular helicity enhancements, enabling transformations of GA from lamellar structure to vesicles and to nanotubes with multi-equivalents of counterion. The limited cytotoxicity of GA in aqueous media exhibits good biocompatibility.

Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Invited for this month's cover are the collaborating groups of Prof. Man-Kin Wong and Dr. Franco King-Chi Leung from The Hong Kong Polytechnic University. The cover picture illustrates chiral gold (III) amphiphiles assemble into tubular supramolecular structures in aqueous media through counterion controlled pathway. The nanostructures were further demonstrated with good cytocompatibility in aqueous media. More information can be found in the Research Article by Man-Kin Wong, Franco King-Chi Leung, and co-workers.

Effect of prehabilitation-related DIETary protein intake on Quality of Recovery after elective cardiac surgery (DIETQoR) study: protocol of a randomised controlled trial.

INTRODUCTION: Protein malnutrition is associated with higher risks of postoperative complications, mortality, prolonged postoperative stays in hospital, slower physical and mental recovery after surgery and lower subsequent health-related quality of life. To reduce the risk of postoperative morbidity and mortality, nutritional prehabilitation programmes have been developed recently to build up patient's nutritional reserve to withstand the stress of surgery. The intervention involves nutritional screening and counselling, and increasing dietary protein intake in protein-malnourished patients in the several weeks before surgery. However, there are few well-conducted preoperative studies to examine the effect of increasing dietary protein intake on the quality of recovery of malnourished patients after elective cardiac surgery. METHOD AND ANALYSIS: This randomised controlled trial of malnourished patients undergoing major elective cardiac surgery will compare the quality of postoperative recovery in patients with or without nutritional prehabilitation. One hundred and thirty-two patients will be randomised to receive nutritional prehabilitation (target-adjusted whey protein powder supplementation and an individualised 1 hour session/week counselling by a dietician 1 month before operation date) or standard care (no nutritional prehabilitation). Primary outcomes will be the quality of recovery after surgery (15-item Quality of Recovery) on the third postoperative day. Secondary outcomes will include days (alive and) at home within 30 days, changes in the WHO Disability Assessment Schedule 2.0, changes in health-related quality of life (EQ-5D) and Cardiac Postoperative Morbidity Survey. An outcomes assessor will be blinded to the treatment allocation. Appropriate univariate analyses, generalised estimating equations and multiple regressions will be performed for intention-to-treat and per-protocol analyses. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No.: 2021.703 T). The findings will be presented at scientific meetings, peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2200057463.

Development and Recent Advances in Lysine and N-Terminal Bioconjugation for Peptides and Proteins.

The demand for creation of protein diversity and regulation of protein function through native protein modification and post-translational modification has ignited the development of selective chemical modification methods for peptides and proteins. Chemical bioconjugation offers selective functionalization providing bioconjugates with desired properties and functions for diverse applications in chemical biology, medicine, and biomaterials. The amino group existing at the lysine residue and N-terminus of peptides and proteins has been extensively studied in bioconjugation because of its good nucleophilicity and high surface exposure. Herein, we review the development of chemical methods for modification of the amino groups on lysine residue and N-terminus featuring excellent selectivity, mild reaction conditions, short reaction time, high conversion, biocompatibility, and preservation of protein integrity. This review is organized based on the chemoselectivity and site-selectivity of the chemical bioconjugation reagents to the amino acid residues aiming to provide guidance for the selection of appropriate bioconjugation methods.

Isoindolium-Based Allenes: Reactivity Studies and Applications in Fluorescence Temperature Sensing and Cysteine Bioconjugation.

The reaction of a series of electron-deficient isoindolium-based allenes with sulfhydryl compounds has been studied, leading to the formation of isoindolium-based vinyl sulfides. The vinyl sulfides generated could be readily converted into the corresponding indanones and amines upon heating at 30-70 °C with good yields up to 61 %. The thermal cleavage reaction of vinyl sulfides was further studied for developing temperature-sensitive systems. Notably, a novel FRET-based fluorescent temperature sensor was designed and synthesized for temperature sensing at 50 °C, giving a 6.5-fold blue fluorescence enhancement. Moreover, chemoselective bioconjugation of cysteine-containing peptides with the isoindolium-based allenes for the construction of multifunctional peptide bioconjugates was investigated. Thermal cleavage of isoindoliums on the modified peptides at 35-70 °C gave indanone bioconjugates with up to >99 % conversion. These results indicated the biocompatibility of this novel temperature-sensitive reaction.

Perspective of smokers and healthcare professionals toward real-time video counseling smoking cessation program in general out-patient clinics in Hong Kong: a qualitative study.

OBJECTIVE: This study aimed to explore the perceptions and experiences of individuals that currently smoke and healthcare professionals on using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong. DESIGN: This was a qualitative study using face-to-face semi-structured interviews based on the extended technology acceptance model. All interviews were audiotaped and transcribed verbatim. Two investigators coded the transcripts independently. Thematic analysis was adopted. PARTICIPANTS: Individuals that currently smoke and healthcare professionals who had experience using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong were recruited. Purposive sampling was adopted. 18 participants were interviewed to reach data saturation. MAIN OUTCOME MEASURES: Themes that emerged from thematic analysis of data were the main outcome measures. The emerged themes were refined and verified via inductive and then deductive processes until data saturation was reached. RESULTS: Two core themes, which were in coherence with the extended technology acceptance model, namely (i) perceived ease of use and (ii) perceived usefulness, were identified. Under perceived ease of use, we identified 2 subthemes: (i) convenience and (ii) measures to facilitate the use of real-time video counseling. Three subthemes were identified under perceived usefulness: (i) empathy and rapport, (ii) measures for pandemics, and (iii) service outcome. CONCLUSION: Our study provided a culture-specific perspective of users towards real-time video counseling. It identified users' opinions on the easiness and usefulness of the service. Those could provide clues for future improvement and development of using real-time video counseling in healthcare services.

Effect of a patient education video and prehabilitation on the quality of preoperative person-centred coordinated care experience: protocol for a randomised controlled trial.

INTRODUCTION: Multimodal prehabilitation, an emerging field within the Perioperative Medicine specialty, requires close multidisciplinary team coordination. The goal is to optimise the patient's health status in the 4-8 weeks before elective surgery to withstand surgical stress. Most patients are unfamiliar with the concept of prehabilitation but are interested in participating in such a programme after explanation. The objective of this randomised controlled trial is to evaluate the effect of prehabilitation (patient education video and multimodal prehabilitation) on the preoperative patient-centred coordinated care experience. METHOD AND ANALYSIS: One hundred patients undergoing major elective surgery (cardiac, colorectal, hepatobiliary-pancreatic and urology) will be recruited into a two-group, parallel, superiority, single-blinded randomised controlled trial. Patients will be randomised to receive either preoperative patient education comprising of a video and prehabilitation programme with standard care (intervention) or standard care (control). The primary outcome measure will be the quality of preoperative patient care experience using the 11-item Chinese version of the Person-Centred Coordinated Care Experience Questionnaire (P3CEQ) before surgery. Secondary outcomes will include the change in Hospital Anxiety and Depression Scale (HADS) score from trial enrolment to before surgery, Quality of Recovery Score (QoR-15) on third day after surgery and Days Alive and At Home within 30 days after surgery (DAH30). Intention-to-treat and per-protocol analyses will be performed. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No. 2021.518-T). The findings will be presented at scientific meetings, in peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2100053637.

Fluorogenic Protein Labeling by Generation of Fluorescent Quinoliziniums Using [Cp*RhCl2]2.

Fluorogenic labeling has received considerable attention as a result of the high demand in chemical biology and synthetic biology applications. Herein, we develop a new strategy for fluorescent turn-on ligation targeting alkyne- and quinoline-linked peptides and proteins (λem of 515 nm and up to ΦF of 0.20) using the [Cp*RhCl2]2 catalyst. The good conversion, high flexibility, broad utility, ease of use, and mild reaction conditions are great advantages to extend the rhodium-mediated turn-on fluorogenic bioconjugation for further applications.

Functionalized quinolizinium-based fluorescent reagents for modification of cysteine-containing peptides and proteins.

A series of quinolizinium-based fluorescent reagents were prepared by visible light-mediated gold-catalyzed cis-difunctionalization between quinolinium diazonium salts and electron-deficient alkyne-linked phenylethynyl trimethylsilanes. The electron-deficient alkynyl group of the quinolizinium-based fluorescent reagents underwent nucleophilic addition reaction with the sulfhydryl group on cysteine-containing peptides and proteins. The quinolizinium-based fluorescent reagents were found to function as highly selective reagents for the modification of cysteine-containing peptides and proteins with good to excellent conversions (up to 99%). Moreover, the modified BCArg mutants bearing cationic quinolizinium compounds 1b, 1d, 1e and 1h exhibit comparable activity in enzymatic and cytotoxicity assays to the unmodified one.

Quinolizinium-based fluorescent probes for formaldehyde detection in aqueous solution, serum, and test strip via 2-aza-Cope rearrangement.

Formaldehyde is an abundant contaminant in food and environments causing various diseases. Thus, the development of fast, simple, and selective formaldehyde detection is of great interest. Herein, novel quinolizinium-based fluorescent probes were designed based on a 2-aza-Cope rearrangement reaction and showed high selectivity to formaldehyde by fluorescence emission shift. We successfully reduced the detection time by increasing the bulkiness of the homoallylic moiety. The probes were applied to detect formaldehyde in aqueous solution, serum, and paper format.

Visible light photocatalytic one pot synthesis of Z-arylvinyl halides from E-arylvinyl acids with N-halosuccinimide.

An efficient visible light photocatalytic strategy to synthesize thermodynamically less stable Z-arylvinyl halides (with up to >99/1 Z/E ratio and 86% yield) was developed. The reaction combined base-mediated halodecarboxylation of E-arylvinyl acids with N-halosuccinimide and visible light Ir-photocatalyzed isomerization of E-arylvinyl halides in a one pot sequential catalytic process.

Synthesis of 1H-isoindoliums by electrophile-mediated cascade cyclization/iodination of propargylamine-based 1,6-diynes.

A highly regio- and chemoselective synthesis of 1H-isoindoliums through a facile and novel cascade cyclization reaction of propargylamine-based 1,6-diynes under mild conditions has been developed. Different functional groups were compatible under the optimized reaction conditions, giving the corresponding products in up to 94% yields. Upon treatment with a base, the alkyne moiety of 1H-isoindoliums could be further transformed to allenes in excellent yields.

Integrated Mass Spectrometry Reveals Celastrol As a Novel Catechol-O-methyltransferase Inhibitor.

Natural product celastrol is known to have various biological activities, yet its molecular targets that correspond to many activities remain unclear. Here, we used multiple mass-spectrometry-based approaches to identify catechol-O-methyltransferase (COMT) as a major binding target of celastrol and characterized their interaction comprehensively. Celastrol was found to inhibit the enzymatic activity of COMT and increased the dopamine level in neuroendocrine chromaffin cells significantly. Our study not only revealed a novel binding target of celastrol but also provided a new scaffold and cysteine hot spot for developing new generation COMT inhibitors in combating neurological disorders.

Synthesis of new quinolizinium-based fluorescent compounds and studies on their applications in photocatalysis.

Quinoliziniums, cationic aromatic heterocycles bearing a quaternary bridgehead nitrogen, have been widely used as fluorescent dyes, DNA intercalators, ionic liquids etc. A library of new quinolizinium compounds was synthesized from quinolines and internal alkyne substrates in up to 65% isolated yields. Systematic studies of their photophysical properties were conducted. The quinoliziniums have been used in three visible-light-induced photocatalysis reactions with good yields.

Recent Advances in the Development of Chiral Gold Complexes for Catalytic Asymmetric Catalysis.

Asymmetric gold catalysis has been rapidly developed in the past ten years. Breakthroughs have been made by rational design and meticulous selection of chiral ligands. This review summarizes newly developed gold-catalyzed enantioselective organic transformations and recent progress in ligand design (since 2016), organized according to different types of chiral ligands, including bisphosphine ligands, monophosphine ligands, phosphite-derived ligands, and N-heterocyclic carbene ligands for asymmetric gold(I) catalysis as well as heterocyclic carbene ligands and oxazoline ligands for asymmetric gold(III) catalysis.

A highly selective quinolizinium-based fluorescent probe for cysteine detection.

A novel fluorescent quinolizinium-based turn-off probe has been developed for selective detection of cysteine. The probe showed high selectivity and sensitivity towards cysteine over other amino acids including the similarly structured homocysteine and glutathione with a detection limit of 0.18 µM (S/N = 3). It was successfully applied to cysteine detection in living cells with low cytotoxicity and quantitative analysis of spiked mouse serum samples with moderate to good recovery (96-109%).

8-prenylgenistein exerts osteogenic effects via ER α and Wnt-dependent signaling pathway.

8-prenylgenistein (8PG) was previously reported to exert stronger osteogenic activity than genistein, a well-known soy phytoestrogen. However, the molecular mechanism underlying the actions of 8PG on osteoblasts was far from clear. In the present study, the osteogenic effects and mechanisms of 8PG and genistein were studied using human BMSC and murine pre-osteoblast MC3T3-E1 cells. Our results indicated that the stimulatory effects of 8PG and genistein on osteoblast differentiation were abolished by co-incubation with MPP (10-6 M, an ERα antagonist), but not PHTPP (10-6 M, an ERß antagonist). Molecular docking indicated that the binding mode of 8PG toward ERα was similar to that of genistein and therefore could not account for their differential osteogenic actions. In silico target profiling identified the involvement of glycogen synthase kinase-3ß (GSK-3ß), a key mediator of Wnt/ß-catenin pathway, in the actions of 8PG. However, instead of directly inhibiting GSK-3ß enzymatic activities, 8PG and genistein were found to induce GSK-3ß phosphorylation at Serine-9 in osteoblastic MC3T3-E1 cells. 8PG exerted more potent effects than genistein in stimulating expressions of LRP5, ß-catenin, Runx2, osteocalcin, alp, opg, major protein and gene markers involved in Wnt signaling pathway in MC3T3-E1 cells. Moreover, the inhibition of Wnt signaling by DKK1 could be restored by treatment with 8PG and genistein. However, 8PG, but not genistein, stimulated ERα-dependent ß-catenin protein expression in MC3T3-E1 cells. Furthermore, the increase in ALP activity, LRP5 and phospho-Akt/Akt expression by 8PG and genistein were abolished by co-treatment with LY294002 (10-5 M, a PI3K pathway inhibitor). Collectively, our results suggested that the osteogenic activities of 8PG was mediated by GSK-3ß phosphorylation through the induction of Wnt/ß-catenin and ERα-associated PI3K/Akt signaling.

Impact of Motivational Interviewing on Self-Management in Patients With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: The nonpharmacological approach to diabetic control in patients with diabetes focuses on a healthy diet, physical activity, and self-management. Therefore, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns and include brief advice and counseling services. Within this context, motivational interviewing (MI) has proven to be effective in changing health behaviors for specific cases. However, stronger evidence is needed on the effectiveness of MI in treating chronic pathologies such as diabetes. OBJECTIVE: This study will obtain preliminary data on the impact of a nurse-led MI intervention in improving glycemic control, as well as clinical, psychosocial, and self-care outcomes for individuals with type 2 diabetes mellitus when compared with usual care, with the aim of improving diabetic control in patients with diabetes. METHODS: An open, two-arm, parallel, randomized controlled, pilot exploratory trial will be performed. Two government outpatient clinics in the New Territories West Cluster in Hong Kong will be involved. In total, 20 to 25 participants will be invited in each arm. Intervention participants will receive face-to-face MI interventions in addition to their usual care from the clinic. Control participants will only receive usual care. Outcomes are assessed at baseline, 6 months, and 12 months. The primary outcome measure is glycated hemoglobin levels. Secondary outcomes include blood pressure, BMI, hip and waist circumference, fasting blood, and psychosocial and self-care measures. RESULTS: This study is currently underway with funding support from the Hong Kong College of Family Physician Research Seed Fund 2017. CONCLUSIONS: MI skills constitute the main strategies primary care nurses use on their patients. Having economical, simple, effective, and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of MI. It will be performed with strict control over the data collection, ensuring the maintenance of therapeutic integrity. TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics CUHK_CCRB00614; https://tinyurl.com/v9awzk6. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15709.

Selective modification of alkyne-linked peptides and proteins by cyclometalated gold(III) (C

Alkyne is a useful functionality incorporated in proteins for site-selective bioconjugation reactions. Although effective bioconjugation reactions such as copper(I)-catalyzed and/or copper-free 1,3-dipolar cycloadditions of alkynes and azides are the most common approaches, the development of new alkyne-based bioconjugation reactions is still an ongoing interest in chemical biology. In this work, a new approach has been developed for selective modification of alkyne-linked peptides and proteins through the formation of arylacetylenes by a cross-coupling reaction of 6-membered ring cyclometalated gold(III) (C^N) complexes (HC^N = 2-arylpyridines) with terminal alkynes. Screening of the reaction conditions with a series of cyclometalated gold(III) complexes with phenylacetylene gave an excellent yield (up to 82%) by conducting the reaction in slightly alkaline aqueous conditions. The reaction scope was expanded to various alkynes, including alkyne-linked peptides to achieve up to >99% conversion. Using fluorescent dansyl (1l) and BODIPY (1m)-linked gold(III) complexes, alkyne-linked lysozyme has been selectively modified.

N-Terminal selective modification of peptides and proteins using 2-ethynylbenzaldehydes.

Selective modification of the N-terminus of peptides and proteins is a promising strategy for single site modification methods. Here we report N-terminal selective modification of peptides and proteins by using 2-ethynylbenzaldehydes (2-EBA) for the production of well-defined bioconjugates. After reaction screening with a series of 2-EBA, excellent N-terminal selectivity is achieved by the reaction in slightly acidic phosphate-buffered saline using 2-EBA with electron-donating substituents. Selective modification of a library of peptides XSKFR (X = either one of 20 natural amino acids) by 2-ethynyl-4-hydroxy-5-methoxybenzaldehyde (2d) results in good-to-excellent N-terminal selectivity in peptides (up to >99:1). Lysozyme, ribonuclease A and a therapeutic recombinant Bacillus caldovelox arginase mutant (BCArg mutant) are N-terminally modified using alkyne- and fluorescein-linked 2-EBA. Alkyne-linked BCArg mutant is further modified by rhodamine azide via copper(I)-catalyzed [3 + 2] cycloaddition indicating that the reaction has high functional group compatibility. Moreover, the BCArg mutant modified by 2-ethynyl-5-methoxybenzaldehyde (2b) exhibits comparable activity in enzymatic and cytotoxic assays with the unmodified one.