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Author(s): Hongjiang Wu 1, Eric S. H. Lau 1, Aimin Yang 1,2, Xinge Zhang 1, Baoqi Fan 1, Ronald C. W. Ma 1,2,3, Alice P. S. Kong 1,2,3, Elaine Chow [...], Background The prevalence of type 2 diabetes has increased in both young and old people. We examined age-specific associations and population attributable fractions (PAFs) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes. Methods and findings We analysed data from 360,202 Chinese with type 2 diabetes who participated in a territory-wide diabetes complication screening programme in Hong Kong between January 2000 and December 2019. We compared the hazard ratios and PAFs of eight risk factors, including three major comorbidities (cardiovascular disease [CVD], chronic kidney disease [CKD], all-site cancer) and five modifiable risk factors (suboptimal HbA1c, suboptimal blood pressure, suboptimal low-density lipoprotein cholesterol, smoking, and suboptimal weight), for mortality across four age groups (18 to 54, 55 to 64, 65 to 74, and [greater than or equal to]75 years). During a median 6.0 years of follow-up, 44,396 people died, with cancer, CVD, and pneumonia being the leading causes of death. Despite a higher absolute mortality risk in older people (crude all-cause mortality rate: 59.7 versus 596.2 per 10,000 person-years in people aged 18 to 54 years versus those aged [greater than or equal to]75 years), the relative risk of all-cause and cause-specific mortality associated with most risk factors was higher in younger than older people, after mutually adjusting for the eight risk factors and other potential confounders including sex, diabetes duration, lipid profile, and medication use. The eight risk factors explained a larger proportion of mortality events in the youngest (PAF: 51.6%, 95% confidence interval [CI] [39.1%, 64.0%], p < 0.001) than the oldest (PAF: 35.3%, 95% CI [27.2%, 43.4%], p < 0.001) age group. Suboptimal blood pressure (PAF: 16.9%, 95% CI [14.7%, 19.1%], p < 0.001) was the leading attributable risk factor for all-cause mortality in the youngest age group, while CKD (PAF: 15.2%, 95% CI [14.0%, 16.4%], p < 0.001) and CVD (PAF: 9.2%, 95% CI [8.3%, 10.1%], p < 0.001) were the leading attributable risk factors in the oldest age group. The analysis was restricted to Chinese, which might affect the generalisability to the global population with differences in risk profiles. Furthermore, PAFs were estimated under the assumption of a causal relationship between risk factors and mortality. However, reliable causality was difficult to establish in the observational study. Conclusions Major comorbidities and modifiable risk factors were associated with a greater relative risk for mortality in younger than older people with type 2 diabetes and their associations with population mortality burden varied substantially by age. These findings highlight the importance of early control of blood pressure, which could reduce premature mortality in young people with type 2 diabetes and prevent the onset of later CKD and related mortality at older ages.

Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes. [ABSTRACT FROM AUTHOR]

Many annotated long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs), some of which have been demonstrated to encode small proteins or micropeptides with fundamental biological importance. However, functions of lncRNAs-encoded small proteins or micropeptides in viral pathogenesis remain largely unexplored. Here, we identified a 110-amino acid small protein as a key regulator of influenza A virus (IAV) replication. This small protein that we call PESP was encoded by the putative lncRNA PCBP1-AS1. It was observed that both PCBP1-AS1 and PESP were significantly upregulated by IAV infection. Furthermore, they were markedly induced by treatment with either type I or type III interferon. Overexpression of either PCBP1-AS1 or PESP alone significantly enhanced IAV replication. In contrast, shRNA-mediated knockdown of PCBP1-AS1 or CRISPR/Cas9-mediated knockout of PESP markedly inhibited the viral production. Moreover, the targeted deletion or mutation of the sORF within the PCBP1-AS1 transcript, which resulted in the disruption of PESP expression, significantly diminished the capacity of PCBP1-AS1 to enhance IAV replication, underscoring the indispensable role of PESP in the facilitation of IAV replication by PCBP1-AS1. Interestingly, overexpression of PESP enhanced the IAV-induced autophagy by increasing the expression of ATG7, an essential autophagy effector enzyme. We also found that the 7–22 amino acids at the N-terminus of PESP were crucial for its functionality in modulating ATG7 expression and action as an enhancer of IAV replication. Additionally, HSP90AA1, a protein identified previously as a facilitator of autophagy, was found to interact with PESP, resulting in the stabilization of PESP and consequently an increase in the production of IAV. These data reveal a critical lncRNA-encoded small protein that is induced and exploited by IAV during its infection, and provide a significant insight into IAV-host interaction network. Author summary: Emerging evidence has shown that some lncRNAs encode biologically active small proteins or micropeptides involved in diverse cellular processes. Here, we identified a previously unrecognized small protein derived from the lncRNA PCBP1-AS1 and established a role for this protein in influenza A virus (IAV) infection. We named it as PCBP1-AS1-encoded small protein (PESP) and found it to be crucially implicated in replication of IAV. Expression of both PESP and PCBP1-AS1 were significantly increased in response to IAV infection or upon interferon treatment. By overexpressing PESP, we observed a substantial enhancement in IAV replication, which was counteracted by reducing PESP level. We further demonstrated that PESP coding sequences were essential for PCBP1-AS1 to facilitate IAV replication, as evidenced by significantly reduced functionality of PCBP1-AS1 with deletion of the sequences. Intriguingly, PESP appeared to promote viral replication by modulating autophagy. This was achieved by significant upregulation of ATG7, a key enzyme in autophagy. Additionally, we revealed that interaction of PESP with HSP90AA1, a protein known to support autophagy, contributed to the protein's stability of PESP and consequently to increased IAV replication. This study sheds light on the intricate interplay between host factors and viral pathogens, offering potential targets for antiviral strategies. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To determine the population health burden attributable to the development of diabetes among women with a history of gestational diabetes mellitus (GDM). Materials and Methods: We conducted a retrospective analysis of women with a history of GDM attending the Hong Kong Hospital Authority between 2000 and 2019. The time‐varying population attributable fraction was calculated. Results: A total of 76,181 women with a history of gestational diabetes mellitus were included, 6,606 of them developed diabetes during a median follow‐up of 8.6 years. The respective hazard ratios (95% confidence interval) among women with GDM who developed diabetes vs those with GDM only were 2.8 (2.2, 3.7) for cardiovascular disease (CVD), 4.8 (3.0, 7.7) for end‐stage kidney disease (ESKD), 2.2 (1.9, 2.6) for infection‐related hospitalization, and 1.8 (1.3, 2.4) for all‐cause mortality. The development of diabetes was associated with 1.3 (0.8, 1.7), 0.6 (0.3, 0.8), 3.2 (2.4, 4.0), and 0.5 (0.2, 0.9) additional incident cases per 1,000 person‐years, accounting for 24.0% (13.2%, 35.9%), 42.0% (22.5%, 58.8%), 10.8% (7.1%, 14.9%), and 6.0% (−3.1%, 16.1%) of absolute number of CVD, ESKD, infection‐related hospitalization, and all‐cause mortality over 20 years after GDM, respectively. Conclusions: Diabetes is a significant contributor to the population health burden of some clinical outcomes in women with a history of gestational diabetes mellitus, but other risk factors need to be considered. [ABSTRACT FROM AUTHOR]

Author(s): Xinge Zhang 1, Hongjiang Wu 1, Baoqi Fan 1, Mai Shi 1, Eric S. H. Lau 1, Aimin Yang 1, Elaine Chow 1, Alice P. S. Kong 1,2,3, Juliana [...], Background Little is known about the lifetime risk of progression to diabetes in the Asian population. We determined remaining lifetime risk of diabetes and life years spent with diabetes in Chinese people with normoglycemia and prediabetes. Methods and findings Using territory-wide diabetes surveillance data curated from electronic medical records of Hong Kong Hospital Authority (HA), we conducted a population-based cohort study in 2,608,973 individuals followed from 2001 to 2019. Prediabetes and diabetes were identified based on laboratory measurements, diagnostic codes, and medication records. Remaining lifetime risk and life years spent with diabetes were estimated using Monte Carlo simulations with state transition probabilities based on a Markov chain model. Validations were performed using several sensitivity analyses and modified survival analysis. External replication was performed using the China Health and Retirement Longitudinal Survey (CHARLS) cohort (2010 to 2015). The expected remaining lifetime risk of developing diabetes was 88.0 (95% confidence intervals: 87.2, 88.7)% for people with prediabetes and 65.9 (65.8, 65.9)% for people with normoglycemia at age 20 years. A 20-year-old person with prediabetes would live with diabetes for 32.5 (32.0, 33.1) years or 51.6 (50.8, 52.3)% of remaining life years, whereas a person with normoglycemia at 20 years would live 12.7 (12.7, 12.7) years with diabetes or 18.4 (18.4, 18.5)% of remaining life years. Women had a higher expected remaining lifetime risk and longer life years with diabetes compared to men. Results are subjected to possible selection bias as only people who undertook routine or opportunistic screening were included. Conclusions These findings suggest that Hong Kong, an economically developed city in Asia, is confronted with huge challenge of high lifetime risk of diabetes and long life years spent with diabetes, especially in people with prediabetes. Effective public health policies and targeted interventions for preventing progression to diabetes are urgently needed.

The hypothesis that brain activity may differ during varied types of video game play was investigated in two studies of event-related potentials exhibited by children age 7 to 12 when processing game-based stimuli requiring correct/incorrect responses or choices between two imaginative alternative responses. The first study had 22 children of families from the university community and the second (replication) study had 22 children from a diverse group of community families. These participants also were interviewed regarding the children's video game habits. In Study 1, mean amplitude of P300 in the two conditions showed significant differences at P100 and N200 locations. Study 2 results showed greater N200 and P300 positive amplitude in the choice condition at Pz. Both studies found significant frontal lobe interaction for younger children in mixed conditions, suggesting they put more attention resources into the mixed task. Implications of video game play effects on brain development during the elementary years are discussed.

This study examined the independent associations between psychosocial factors, perceived neighborhood characteristics, and physical activity (PA) in Chinese adolescents. A cross-sectional study using a convenience sample was conducted in fall 2019 at a high school in Wuhan, China. Sociodemographic data, body weight, height, psychosocial factors, perceptions of neighborhood environment, and PA were collected using questionnaires. Hierarchical linear regression analyses were performed in 4 steps, where step 1 included demographic covariates, step 2 added psychosocial factors into the model, step 3 added perceived neighborhood environmental factors, and step 4 added interaction terms between significant psychosocial and environmental factors. A total of 4027 adolescents were included in analysis. The results of the third model indicated that friends' support (b = 4.58), friends' norms (b = 7.16), barriers to PA (b = −10.19), autonomous motivation (b = 4.75), self-efficacy (b = 8.86), the presence of shops/stores nearby (b = 5.79), and the availability of PA resources (b = 6.02) were significant predictors (P <.05) of moderate to vigorous PA. None of the interaction terms were significant in the fourth model. Our results suggest that interventions targeting the PA of Chinese adolescents should take into account the attitudes toward PA, perceived barriers to PA, controlled motivation, perceptions of neighborhood PA resource availability, and perceived neighborhood safety to maximize effectiveness. [ABSTRACT FROM AUTHOR]

In this paper, 5083 aluminum alloy and T2 copper were selected for the friction stir lap welding test. The effect of intermetallic compounds on the microstructure and properties of Al/Cu dissimilar metal lap joints was studied. The results showed that the circulating Al/Cu composite structure was formed on the advancing side of the lap joint, and the Al/Cu staggered hook-like structure and copper-rich region were generated on the retreating side. There was no typical 'onion ring' structure in the joint. Element diffusion occurred at the interface of the joint, forming a thin and uniform interfacial layer of Al/Cu intermetallic compounds, thus achieving a well-metallurgical bond at the Al/Cu interface. There were the intermetallic compounds Al2Cu and Al4Cu9, without AlCu, in the lap joint. In addition, dynamic recrystallization occurred in the nugget zone, and higher dislocation density and dislocation entanglement were generated, which enhanced the deformation resistance in the nugget zone and increased the joint strength. The tensile test showed that the ductile–brittle mixed fracture occurred in the heat-affected zone on the advancing side of the aluminum plate, and the fracture had necking. The failure load of the lap joint was 4350 ± 30 N, about 80% of the aluminum base metal. The elongation of the Al/Cu dissimilar lap joint tensile specimen was 2.5%. [ABSTRACT FROM AUTHOR]

Three kinds of surfacing layers of the austenitic steel, niobium alloyed steel and hypereutectic high chromium alloyed cast iron were prepared on 1045 steel substrate by arc surfacing process with self-shielding flux-cored wires. The bonding strength between surfacing layers and the substrate was tested by pull-lift test method. The experimental results show that the bonding strength between austenitic steel surfacing layer and the substrate is the highest up to 549.1 MPa, and the fracture location is near the fusion line with quasi-cleavage fracture characteristic. The bonding strength between the surfacing layer of niobium alloyed steel and the substrate is 314.4 MPa and the fracture mainly occurred at the bottom of the surfacing layer, which also presents quasi-cleavage characteristic. While the bonding strength between hypereutectic high chromium alloyed cast iron surfacing layer and the substrate is as low as 170.7 MPa and the specimen ruptures along the fusion line with brittle fracture characteristic. The bonding properties between surfacing layers and the substrate are directly related to the compositions and microstructures near the fusion line.

Microorganism adhesion and the resulting contamination of the biomaterial is one of the major causes of biomedical device failure. Stimuli-responsive materials based on dynamically regulating interactions with reversible characteristics of on–off states have attracted increasing attention. Here, a facile self-assembled biomaterial nanocoating constructed using acidity- and photoregulated spiropyran-modified nanoparticles was developed for reversibly regulating bacteria or mammalian cell adhesion-and-detachment. The coating was formed by coating a solution of spiropyran-conjugated nanoparticles around the surface of a silica gel followed by curing and drying at 60 °C for 30 min. Importantly, efficient adhesion-and-detachment of bacteria or cells could be controlled even after 8 cycles owing to the excellent acidity- and light-switched ability. Collectively, this well-defined self-assembled nanocoating as a dynamical and reversible agent provides promising insight for the development of biomedical devices, especially for biomaterial medical coatings. [ABSTRACT FROM AUTHOR]

Dental caries is a common disease caused by plaque biofilms, which are important pathogenic factors in many diseases. When hosts are overexposed to dietary sugars, pathogens such as Streptococcus mutans (S. mutans) and other cariogenic bacteria, metabolically assemble an extracellular matrix rich in exopolysaccharides to form a disease‐causing biofilm, in which the microenvironment is characterized by regional hypoxia, low pH, and nutritional deprivation. Current antimicrobials with inadequate penetration and a lack of pathogens targeting the biofilm do not degrade the protective matrix within the biofilm. In this study, a guanidine and galactose decorated nanophotosensitizer with oxygen self‐sufficient capability, p(GF/GEF)‐I, is developed to enhance the permeability of biofilms by positively charging the particle surface and easily binding to the bacteria within the membrane through electrostatic interactions. 90% of the biofilm on enamel surface is eliminated after treatment with p(GF/GEF)‐I under laser irradiation. Notably, the nanophotosensitizer inhibits the recolonization of dental biofilms by S. mutans, preventing secondary infections. Furthermore, dental caries in a rodent model are reduced with exposure to nanophotosensitizer. p(GF/GEF)‐I is a significantly higher efficacy without damaging the surrounding soft tissue. With further development and optimization, p(GF/GEF)‐I shows significant potential as a phototherapeutic agent for the treatment of biofilm‐induced diseases. [ABSTRACT FROM AUTHOR]

Chemoresistance to cisplatin (DDP) therapy is a major obstacle that needs to be overcome in treating lung cancer patients. Xanthatin has been reported to exhibit an antitumor effect on various cancers, but the function of xanthatin in DDP‐resistance lung cancer remains unclear. The study aimed to explore the effect and mechanisms of xanthatin on proliferation, apoptosis, and migration in DDP‐resistance lung cancer cells. In the present study, xanthatin suppresses the expression of glucose transporter 1 (GLUT1), attenuates the pentose phosphate pathway (PPP), and causes ROS accumulation and apoptosis, thereby mitigating the antioxidative capacity in DDP‐resistance cells. Previous studies have shown that GLUT1 is associated with resistance to platinum drugs. We found that GLUT1 was significantly increased in the DDP‐resistant lung cancer cell line compared to the parental cell line, and xanthatin significantly downregulated GLUT1 expression in DDP‐resistant lung cancer cells. Notably, overexpression of GLUT1 significantly reduced the production of ROS and increased cellular NADPH/NADP+ and GSH/GSSG ratios. Thus, these results suggest that xanthatin induces DDP‐resistance lung cancer cells apoptosis through regulation of GLUT1‐mediated ROS accumulation. These findings might provide a possible strategy for the clinical treatment of DDP‐resistant lung cancer. [ABSTRACT FROM AUTHOR]