Cross-sectional associations between multiple plasma heavy metals and lung function among elderly Chinese.

Environmental exposure to heavy metals may adversely affect lung function particularly in the elderly. However, limited data are available directly evaluating the relationship of heavy metal exposures with lung function in Chinese elderly. We aimed to investigate the associations between plasma metals and lung function among Chinese elderly residents.

Genetic evidence for the effects of glucokinase activation on frailty-related outcomes: A Mendelian randomisation study.

Aims: We aimed to use the Mendelian randomisation (MR) design to investigate the potential causal effects of glucokinase (GK) activation on frailty-related outcomes and to explore the potential mediating effects of metabolic and inflammatory biomarkers.

Materials And Methods: Seventeen independent single-nucleotide polymorphisms (SNPs) located within the GCK gene and significantly correlated with the glycated haemoglobin (HbA) level were used as genetic proxies for the effect of GK activation. We employed two-sample MR analysis to assess the relationship between genetically proxied GK activation and multifactorial frailty-related outcomes (frailty index, grip strength, walking pace, appendicular lean mass [ALM] and telomere length) We also explored the potential mediating effects using two-step MR.

Short- and long-term comparative effectiveness of nirmatrelvir/ritonavir and molnupiravir in asthma patients: a cohort study.

Background: Few studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.

Methods: This is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication.

Phase separation of p62: roles and regulations in autophagy.

The phase separation of the cargo receptor sequestome-1/p62 (SQSTM1/p62) is a critical mechanism for assembling signaling complexes in autophagy. During this process, p62 undergoes phase separation upon binding to polyubiquitin chains, concentrating ubiquitinated substrates within p62 droplets. These droplets further gather membrane sources and core autophagy machineries to facilitate autophagosome formation.

Development and Validation of the Patient-Level Chinese Diabetes Outcome Model on Long-term Complications in Type 2 Diabetes: An Application of the Hong Kong Diabetes Register.

Objective: Patient-level simulation models, mainly developed in Western populations, capture complex interactions between risk factors and complications to predict the long-term effectiveness and cost-effectiveness of novel treatments and identify high-risk subgroups for personalized care. However, incidence of outcomes varies significantly by ethnicity and region. We used high-quality, patient-level register data to develop the Chinese Diabetes Outcomes Model (CDOM) for predicting incident and recurrent events in type 2 diabetes (T2D).

Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID-19 outcomes among outpatients: a target trial emulation investigation.

Limited studies compared the effectiveness of nirmatrelvir/ritonavir and molnupiravir against a control group on post-COVID-19 conditions. Our study examined the association of nirmatrelvir/ritonavir and molnupiravir with post-acute mortality and hospitalizations among outpatients using real-world outpatient records of COVID-19 designated clinics in Hong Kong. This is an observational study using a target trial emulation framework, involving nirmatrelvir-ritonavir versus no antiviral treatment (Trial 1) and molnupiravir versus no antiviral treatment (Trial 2).

Predictive factors influencing hypothyroidism following the radioactive iodine treatment of Graves' disease in different periods.

In China, due to the risks of hypothyroidism after radioiodine treatment, radioiodine is not commonly used as a first-line treatment. In this study, factors influencing the development of hypothyroidism after I therapy for Graves' hyperthyroidism were evaluated. This was a retrospective study with a 12-month follow-up.

Synthesis and structural modification of the natural product Ivesinol to discover novel autophagy activators.

Autophagy is a lysosome-dependent cellular degradation pathway that responds to a variety of environmental and cellular stresses, which is defective in aging and age-related diseases, therefore, targeting autophagy with small-molecule activators has potential therapeutic benefits. In this study, we successfully completed the first total synthesis of Ivesinol, an identified antibacterial natural product, and efficiently constructed a library of its analogs. To measure the effect of Ivesinol analogs on autophagic activity, we performed cell imaging-based screening approach, and observed that several Ivesinol analogs exhibited potent autophagy-regulating activity.

Temporal incremental healthcare costs associated with complications in Hong Kong Chinese patients with type 2 diabetes: A prospective study in Joint Asia diabetes evaluation (JADE) Register (2007-2019).

Objective: We examined incremental healthcare costs (inpatient and outpatient) related to complications in Chinese patients with type 2 diabetes (T2D) during the year of occurrence and post-event years, utilizing the Joint Asia Diabetes Evaluation (JADE) Register cohort of Hong Kong Chinese patients with T2D between 2007 and 2019.

Research Design And Methods: 19,440 patients with T2D underwent structured evaluation utilizing the JADE platform with clinical outcomes data retrieved from territory-wide electronic medical records including inpatient, outpatient and emergency care. Two-part model was adopted to account for skewed healthcare costs distribution.

The relationship of changes in insulin demand and insulin adequacy over the life course.

Aims/hypothesis: Insulin requirements in the human body undergo continuous changes in response to growth and development. We assessed the life course relationships between insulin demand and insulin adequacy.

Methods: Three independent Chinese cohorts (204 children, aged [mean ± SD] 7.

Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.

Aims/hypothesis: Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes.

Methods: We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong.

Association of nirmatrelvir-ritonavir with post-acute sequelae and mortality among patients who are immunocompromised with COVID-19 in Hong Kong: a retrospective cohort study.

Background: The effect of nirmatrelvir-ritonavir on post-COVID-19 outcomes for individuals who are immunocompromised is understudied. We aimed to examine the association of nirmatrelvir-ritonavir with post-acute sequelae and mortality among patients who are immunocompromised and admitted to hospital with COVID-19.

Methods: We did a retrospective cohort study using territory-wide electronic health records from the Hong Kong Hospital Authority and Hong Kong Department of Health.

COVID-19 vaccination modified the effect of nirmatrelvir-ritonavir on post-acute mortality and rehospitalization: a retrospective cohort study.

While previous research examined coronavirus disease 2019 (COVID-19) antiviral-vaccine interactions through exploratory subgroup analysis, none specifically designed for examining this interaction or its impact on post-acute outcomes. This study examined the interaction between nirmatrelvir-ritonavir and complete COVID-19 vaccination on reducing the risk of post-acute outcomes among COVID-19 patients. We followed COVID-19 patients hospitalized between 11 March 2022 and 10 October 2023, until 31 October 2023 in Hong Kong.

Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations.

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.

Design and Evaluation of Peptide Inhibitors Targeting the Dimerization of SARS-CoV-2 Main Protease.

The severe acute respiratory syndrome virus 2 (SARS-CoV-2) seriously impacted public health. The evolutionarily conserved viral chymotrypsin-like main protease (M) is an important target for anti-SARS-CoV-2 drug development. Previous studies have shown that the eight N-terminal amino acids (N8) of SARS-CoV M are essential for its dimerization, and are used to design inhibitors against SARS-CoV M dimerization.

Cohort profile: the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde, China (Speed-Shunde cohort).

Aims: The objective of this prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde (Speed-Shunde cohort) was to evaluate the incidence of cardiovascular-kidney-metabolic (CKM) syndrome and metabolic-associated multimorbidity, such as diabetes, hypertension, dyslipidaemia, and metabolic dysfunction-associated steatotic liver disease in Shunde, Foshan, Guangdong, China. Additionally, the study sought to identify the potential determinants that may impact the development of these conditions and the potential consequences that may result.

Methods And Results: In the Speed-Shunde cohort, data were gathered via questionnaires, physical measurements, and laboratory analyses encompassing demographic data, behavioural tendencies, anthropometric assessments, controlled attenuation parameters, and liver stiffness measurement utilizing vibration-controlled transient elastography, as well as serum and urine detection (such as oral 75 g glucose tolerance tests, haemoglobin A1c levels, lipid profiles, liver and renal function tests, urinary microalbumin, and creatinine levels).

MiR-183-5p inhibits lung squamous cell carcinoma survival through disrupting hypoxia adaptation mediated by HIF-1α/NDUFA4L2 axis.

Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined.

Textual emotion classification using MPNet and cascading broad learning.

As one of the most important tasks of natural language processing, textual emotion classification (TEC) aims to recognize and detect all emotions contained in texts. However, most existing methods are implemented using deep learning approaches, which may suffer from long training time and low convergence. Motivated by these challenges, in this paper, we provide a new solution for TEC by using cascading broad learning (CBL) and sentence embedding using a masked and permuted pre-trained language model (MPNet), named CBLMP.

Protocol for evaluating S-acylated protein membrane affinity using protein-lipid conjugates.

S-acylation of proteins allows their association with membranes. Here, we present a protocol for establishing a platform for membrane affinity evaluation of S-acylated proteins in vitro. We describe steps for preparing lipid-maleimide compounds, mCherry-p62 recombinant proteins, and total cellular membranes.

Higher risk of incident diabetes among patients with primary hyperparathyroidism.

Objectives: There is relatively scarce data regarding the association between primary hyperparathyroidism (PHPT) and incident diabetes in large population-based longitudinal studies. We aimed to evaluate the risk of incident diabetes in individuals with and without PHPT and investigate the association between serum calcium concentrations and the risk of incident diabetes in patients with PHPT.

Methods: We included 2749 PHPT patients and 13,745 age, sex and index year matched non-PHPT individuals during 2000-2019.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011-2018.

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals.