Construction of photofunctional peptide conjugates through selective modification of N-terminal cysteine with cyclometallated iridium(III) 2-formylphenylboronic acid complexes for organelle-specific imaging, enzyme activity sensing and photodynamic therapy.

Luminescent cyclometallated iridium(III) complexes bearing a 2-formylphenylboronic acid moiety were designed; one of the complexes was utilised to modify peptides containing an N-terminal cysteine to afford luminescent conjugates with selective organelle-targeting or furin-responsive properties.

Reproducibility and Relative Validity of a Short Food Frequency Questionnaire for Chinese Older Adults in Hong Kong.

Changes in an individual's digestive system, hormones, senses of smell and taste, and energy requirement accompanying aging could lead to impaired appetite, but older adults may not notice their risk of nutrient deficiency. When assessing the dietary intake of older adults, it was found that they had more difficulties with short-term recall and open-ended recall and would experience greater fatigue and frustration when compared to younger individuals when completing a lengthy questionnaire. There is a need to develop a brief dietary assessment tool to examine the nutritional needs of older adults. In this study, we aimed to assess the diet of Hong Kong older adults using the short FFQ and examine its reproducibility and relative validity as a dietary assessment tool. Dietary data of 198 older adults were collected via FFQs and three-day dietary records. Correlation analyses, cross-tabulation, one-sample t-tests, and linear regression analyses were used to evaluate the relative validity of the short FFQ. In general, the short FFQ was accurate in assessing the intake of phosphorus, water, grains, and wine, as shown by a significant correlation (>0.7) between values reported in the FFQs and dietary records; good agreement (more than 50% of observations belonged to the same quartile) and insignificant differences detected with the one-sample t-tests and linear regression analyses were observed for the above four variables. Additionally, the intake of proteins, carbohydrates, total fat, magnesium, and eggs in terms of the values reported in the FFQs and dietary records showed good agreement.

Mitochondria-targeting biocompatible fluorescent BODIPY probes.

An increase in the mitochondrial membrane potential (MMP) is a characteristic feature of cancer and cardiovascular disease. Therefore, it remains of crucial importance to develop new and improved fluorescent probes that are sensitive to the MMP, to report on mitochondrial health and function. Reported here are the design, synthesis, photophysical properties and biological characterisation of a series of BODIPY dyes, BODIPY-Mito-n, for mitochondria-targeted fluorescence imaging applications. Six BODIPY-Mito-n analogues were synthesised under mild conditions, and displayed excellent fluorescence quantum yields of between 0.59 and 0.72 in aqueous environments at physiological pH (pH = 7.4). The incorporation of poly(ethylene glycol) (PEG) chains to the triarylphosphonium cation moiety significantly improved the biocompatibility of the probes (BODIPY-Mito-6, IC50 > 50 µM). All BODIPY-Mito-n compounds demonstrated a high MMP-sensitive localisation in the mitochondria, with Pearson's correlation coefficients (PCC) of between 0.76 and 0.96. Compounds BODIPY-Mito-2 and BODIPY-Mito-6 revealed the highest sensitivity to the MMP, with a decrease in the emission intensity of 62% and 75%, respectively following MMP depolarisation. It is anticipated that the highest MMP sensitivity and enhanced biocompatibility of BODIPY-Mito-6 could lead to the development of new probes for mitochondrial imaging in the future.

Effect of Intermittent Fasting on Cardiometabolic Health in the Chinese Population: A Meta-Analysis of Randomized Controlled Trials.

The efficacy of intermittent fasting (IF), as an emerging weight management strategy, in improving cardiometabolic health has been evaluated in various populations, but that among Chinese individuals has not been systematically studied. A comprehensive search on multiple databases was performed to identify eligible randomized controlled trials (RCTs) up to October 2022. The primary outcome was post-intervention weight loss, and secondary outcomes included changes in cardiometabolic indicators. Effect estimates were meta-analyzed using a random-effects model. In total, nine RCTs with 899 Chinese participants were included. Time-restricted eating was the most adopted IF protocol in this study (six out of nine), followed by alternate-day fasting. The IF intervention significantly reduced body weight, body mass index, body fat mass, homeostatic model assessment of insulin resistance, low-density lipoprotein cholesterol, and triglycerides when compared with control groups. However, no statistically significant reductions in waist circumference, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, systolic blood pressure, and diastolic blood pressure were found. To sum up, IF can be a weight management strategy and may improve the cardiometabolic health of Chinese adults, but more long-term trials using different IF strategies are required to generate robust evidence of its efficacy.

Diagnostic Accuracy of Waist-to-Height Ratio, Waist Circumference, and Body Mass Index in Identifying Metabolic Syndrome and Its Components in Older Adults: A Systematic Review and Meta-Analysis.

Background: Although numerous studies have indicated the utility of waist-to-height ratio (WHtR) in early screening for individuals with adverse cardiometabolic health, there is controversy on using WHtR as a one-size-fits-all approach, including in older adults. Objectives: Our study aims to identify the pooled diagnostic accuracy of WHtR in screening for metabolic syndrome (MetS) and its components among older adults. Methods: A systematic review of observational studies was performed using 4 databases. A diagnostic meta-analysis with a random effects model was conducted, and the pooled area under the summary receiver operating characteristic curve, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (dOR) of each outcome compared with WHtR, body mass index (BMI), and waist circumference (WC) were calculated, with sex-stratified analysis. Results: A total of 17 studies with 74,520 participants were included. As reflected by the dOR, WHtR (7.65; 95% CI: 6.00, 9.75) performed better than BMI (5.17; 95% CI: 4.75, 5.62) and WC (5.77; 95% CI: 4.60, 7.25) in screening for MetS among older adults and was potentially better among males. For hyperglycemia, hypertension, and dyslipidemia, the performances of WHtR, BMI, and WC were comparable. Conclusion: More studies focusing on older adults are still needed to determine the cutoff values of WHtR to screen for MetS.The search strategy was registered in PROSPERO as CRD42022350379.

Composition of gut microbiota and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to summarize the associations between gut microbiota composition and non-alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α-diversity index and relative abundance of gut microbes. The ß-diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α-diversity indices including Shannon (SMD = -0.36, 95% CI = [-0.53, -0.19], p < 0.001) and Chao 1 (SMD = -0.42, 95% CI = [-0.68, -0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance-based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in ß-diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti-inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.

Bioorthogonal dissociative rhenium(i) photosensitisers for controlled immunogenic cell death induction.

Photosensitisers for photoimmunotherapy with high spatiotemporal controllability are rare. In this work, we designed rhenium(i) polypyridine complexes modified with a tetrazine unit via a bioorthogonally activatable carbamate linker as bioorthogonally dissociative photosensitisers for the controlled induction of immunogenic cell death (ICD). The complexes displayed increased emission intensities and singlet oxygen (1O2) generation efficiencies upon reaction with trans-cyclooct-4-enol (TCO-OH) due to the separation of the quenching tetrazine unit from the rhenium(i) polypyridine core. One of the complexes containing a poly(ethylene glycol) (PEG) group exhibited negligible dark cytotoxicity but showed greatly enhanced (photo)cytotoxic activity towards TCO-OH-pretreated cells upon light irradiation. The reason is that TCO-OH allowed the synergistic release of the more cytotoxic rhenium(i) aminomethylpyridine complex and increased 1O2 generation. Importantly, the treatment induced a cascade of events, including lysosomal dysfunction, autophagy suppression and ICD. To the best of our knowledge, this is the very first example of using bioorthogonal dissociation reactions as a trigger to realise photoinduced ICD, opening up new avenues for the development of innovative photoimmunotherapeutic agents.

Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis.

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

A network meta-analysis of association between cardiometabolic risk factors and COVID-19 outcome severity.

BACKGROUND: Cardiometabolic comorbidities have been associated with a higher risk of COVID-19 severity and mortality, but more investigations are needed to determine which comorbidity is more detrimental. METHODS: Embase, Emcare, and MEDLINE were searched systematically for prospective and retrospective studies assessing the associations of cardiometabolic risk factors and COVID-19 outcomes of hospitalization, severity, and mortality among COVID-19-diagnosed patients. Literature search was performed from first publication to May 19, 2021. Study quality was assessed by the Newcastle-Ottawa Scale. RESULTS: From the literature search, 301 studies suggested that all included cardiometabolic risk factors were associated with a higher risk of COVID-19 hospitalization, severity, and mortality, except that overweight was associated with a decreased risk of mortality (relative risk [RR] 0.88; 95% CI, 0.80-0.98). Patients with diabetes (RR 1.46; 95% CI, 1.45-1.47) were most likely to be hospitalized; patients with heart failure had the highest risk for severe COVID-19 outcomes (RR 1.89; 95% CI, 1.71-2.09); while patients with stroke were most susceptible to overall mortality (RR 1.99; 95% CI, 1.90-2.08). In the network meta-analysis, cerebrovascular disease had the highest impact (RR 1.69; 95% CI, 1.65-1.73) on COVID-19 outcomes compared to other cardiometabolic risk factors. For different combinations of risk factors, cardiovascular disease and diabetes combined (RR 6.98; 95% CI, 5.28-9.22) was more detrimental than others. CONCLUSIONS: Considering the high prevalence of cardiometabolic comorbidities and risk of all severe outcomes, patients with cardiometabolic comorbidities should be prioritized in vaccination and treatment development of COVID-19.

Luminescent iridium(III) porphyrin complexes as near-infrared-emissive biological probes.

We report herein the design, synthesis and characterisation of a series of luminescent iridium(III) porphyrin complexes [Ir(ttp)(CH2CH2OH)] (H2ttp = 5,10,15,20-tetra-4-tolylporphyrin) (1), [Ir(tpp-Ph-NO2)(CO)Cl] (H2tpp-Ph-NO2 = 5-(4-((4-nitrophenoxy)carbonyloxymethyl)phenyl)-10,15,20-triphenylporphyrin) (2), [Ir(tpp-COOMe)(Py)2](Cl) (H2tpp-COOMe = 5-(4-methoxycarbonylphenyl)-10,15,20-triphenylporphyrin; Py = pyridine) (3) and [Ir(tpp-COOH)(Py)2](Cl) (H2tpp-COOH = 5-(4-carboxylphenyl)-10,15,20-triphenylporphyrin) (4). All the complexes displayed long-lived near-infrared (NIR) emission attributed to an excited state of mixed triplet intraligand (3IL) (π → π*) (porphyrin) and triplet metal-to-ligand charge transfer (3MLCT) (dπ(Ir) → π*(porphyrin)) character. The cytotoxicity of the complexes toward HeLa cells was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cationic complexes 3 and 4 exhibited higher cytotoxic activity toward HeLa cells than their neutral counterparts 1 and 2. Cellular uptake studies by inductively coupled plasma-mass spectrometry (ICP-MS) and laser-scanning confocal microscopy (LSCM) indicated that complexes 3 and 4 showed higher cellular uptake efficiencies than complexes 1 and 2 due to their cationic charge, and they were enriched in the perinuclear region of the cells with negligible nuclear uptake. Additionally, the carboxyl complex 4 was used to label a model protein bovine serum albumin (BSA) via an amidation reaction. The resultant luminescent protein conjugate 4-BSA displayed similar photophysical properties and intracellular localisation behaviour to its parent complex. The results of this work will contribute to the development of luminescent iridium(III) porphyrin complexes and related bioconjugates as NIR-emissive probes for bioimaging applications.

Dual-emissive Iridium(III) Complexes as Phosphorescent Probes with Orthogonal Responses to Analyte Binding and Oxygen Quenching.

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual-emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions.

Relative Validity of a Short Food Frequency Questionnaire for Disadvantaged Families in Hong Kong.

Individuals with lower socioeconomic status are more vulnerable in securing good nutritional quality. It was also found that people who had received a lower education level had greater difficulty in completing the conventional dietary assessment such as a food frequency questionnaire (FFQ). Previous studies have demonstrated the validity of a short FFQ in Hong Kong's pregnant women, but its validity among a wider community was still unknown. For the present study, we aimed to validate a short FFQ among disadvantaged communities in Hong Kong. Amongst 103 individuals participating in a dietary intervention programme, their dietary data were collected by FFQs and three-day dietary records. Relative validity was assessed by correlation analysis, cross-tabulation, one-sample t-test, and linear regression. In general, water and total energy intake had significant correlations (0.77 for crude water intake and 0.87 for crude total energy intake) between values reported by FFQ and dietary records, good agreement (both with over 50% of observations falling into the same quartile), and insignificant differences between assessment methods reported by one-sample t-test and linear regression. Meanwhile, several nutrients had good agreement in terms of the values reported by FFQ and dietary records, such as energy from total fat, carbohydrates, total fat, cholesterol, phosphorus, and potassium. The results of this study demonstrated that the short version FFQ could be a convenient assessment tool of multiple dietary behaviors, especially in total energy and water intakes.

Successful delayed treatment of acute glans penis ischaemia after adult circumcision: a case report.

Penile glans ischaemia post-circumcision is very rare. A 20-year-old male presented with glans ischaemia following an elective circumcision and was successfully treated with a combination of subcutaneous injection of low molecular weight heparin 0.5 mg·kg⁻¹ twice-daily, oral Tadalafil 5 mg once-daily for three days and 12 hyperbaric oxygen treatments at 243 kPa (2.4 atmospheres absolute) beginning 48 hours after the onset of ischaemia.

A Concerted Enzymatic and Bioorthogonal Approach for Extra- and Intracellular Activation of Environment-Sensitive Ruthenium(II)-Based Imaging Probes and Photosensitizers.

In this article, we report a novel targeting strategy involving the combination of an enzyme-instructed self-assembly (EISA) moiety and a strained cycloalkyne to generate large accumulation of bioorthogonal sites in cancer cells. These bioorthogonal sites can serve as activation triggers in different regions for transition metal-based probes, which are new ruthenium(II) complexes carrying a tetrazine unit for controllable phosphorescence and singlet oxygen generation. Importantly, the environment-sensitive emission of the complexes can be further enhanced in the hydrophobic regions offered by the large supramolecular assemblies, which is highly advantageous to biological imaging. Additionally, the (photo)cytotoxicity of the large supramolecular assemblies containing the complexes was investigated, and the results illustrate that cellular localization (extracellular and intracellular) imposes a profound impact on the efficiencies of photosensitizers.

Trends in elevated waist-to-height ratio and waist circumference in U.S. adults and their associations with cardiometabolic diseases and cancer, 1999-2018.

Introduction: Although waist-to-height ratio (WHtR) has established association with cardiometabolic disease, the trend of changes in elevated WHtR among general population have not been examined adequately. Methods: This study examined the prevalence of elevated WHtR and waist circumference (WC) and their trends over time using Joinpoint regression models among adults who participated in the United States National Health and Nutrition Examination Survey (U.S. NHANES) 1999-2018. We performed weighted logistic regression to identify the association between central obesity subtypes and the prevalence of comorbidities, including diabetes, chronic kidney disease, hypertension, cardiovascular disease, and cancer. Results: The prevalence of elevated WHtR has increased from 74.8% in 1999-2000 to 82.7% in 2017-2018 while elevated WC also increased from 46.9% in 1999-2000 to 60.3% in 2017-2018. Men, older adults, former smokers, and people with lower education levels were more likely to have elevated WHtR. A total of 25.5% of American adults had normal WC but elevated WHtR, and they had a significantly higher chance of suffering from diabetes (odds ratio [OR] = 2.06 [1.66, 2.55]), hypertension (OR = 1.75 [1.58, 1.93]) and CVD (OR = 1.32 [1.11, 1.57]). Discussion: In conclusion, the burden of elevated WHtR and WC have been increasing among U.S. adults throughout the years, and the changes have been more significant across most subgroups. It is also notable that approximately a quarter of the population had normal WC but elevated WHtR, which had increased likelihood of having cardiometabolic diseases, especially diabetes. Future clinical practices should pay more attention to this subgroup of the population with overlooked health risks.

Association of serum uric acid levels with cardiovascular and all-cause mortality in hypertensive patients in China: a cohort study.

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

Pooled prevalence of depressive symptoms among medical students: an individual participant data meta-analysis.

BACKGROUND: The methodological choice of aggregated estimates for meta-analysis may be notable for some common drawbacks, including variations in the cut-off values of depression, and lower statistical power for analyzing the associated factors. The study aimed to refine the precision of previous findings on the prevalence of depressive symptoms among medical students, through gathering individual participant data (IPD) as identified from our previous reviews. MATERIAL AND METHODS: In the present study, we searched MEDLINE, EMBASE, PsycINFO, WanFang, Scielo and LILACS to identify published systematic reviews and meta-analyses up to March 2018, then individual data was requested for further analysis (PROSPERO registration: CRD42018091917). The participants' age, sex, year of study, scores for depressive symptoms, and other predictor variables were requested. To pool the prevalence from the included studies, random-effects model (two-step method) was used. Multiple linear regression was used to examine the associated factors on the depression z-scores (one-step method). RESULTS: Of the 249 studies, the datasets of 34 studies were included. The crude prevalence was 19.4% (95% CI: 18.8%, 19.9%) by one-step method and the pooled prevalence was 18.1% (95% CI: 14.1%, 22.1%) by two-step method. Multiple linear regression revealed that being a female, older age, and senior year of study were significantly associated with the z-score. CONCLUSION: The pooled prevalence of depressive symptoms from the Individual Participant Data (IPD) meta-analysis was lower than the previous meta-analyses using aggregated data. Age, sex, and year of study were significantly associated with the depression z-score. IPD meta-analysis may provide a more accurate estimation of disease burden, and allow verification of associated factors.