Large-pore covalent organic framework as solid phase extraction absorbentforefficientdetermination of polypeptide antibiotics in animal-derived foods.

The precise determination of polypeptide antibiotics (PPTs) in foods has been always challenging because of the interference of various endogenous peptides in complex matrix. Herin, a novel large-pore covalent organic framework (TABPT-SPDA-COF) with accessible pore size of 7.9 nm was synthesized as a solid phase extraction (SPE) absorbent for efficiently enriching four PPTs existed in foods originating from animals. The parameters of SPE process were systematically optimized. Subsequently, four PPTs were determined by UHPLC-MS/MS. Under the optimal conditions, TABPT-SPDA-COF shows outstanding enrichment capacity for PPTs in contrast to commercial absorbents ascribed to size selectivity and multiple interaction effects. The method exhibits excellent linear range (0.005-100 ng mL-1), satisfactory limits of detection (0.1 pg mL-1) as well as relative recoveries (86.2-116 %). This work offers a practicable platform to monitor trace PPTs from complex animal-derived foodstuffs.

The burden of non-alcoholic fatty liver disease among working-age people in the Western Pacific Region, 1990-2019: an age-period-cohort analysis of the Global Burden of Disease study.

BACKGROUND: The growing prevalence of non-alcoholic fatty liver disease (NAFLD) in younger populations, particularly those of working age (15-64 years), has become a public health concern. Being diagnosed at a younger age implies a greater likelihood of accruing disability-adjusted life years (DALYs) later in life due to potential progression to conditions such as cirrhosis or hepatocellular carcinoma. This study aims to analyze NAFLD prevalence trends over three decades globally, regionally, and nationally, with a focus on age, period, and birth cohort associations. METHODS: Global, regional, and country time trends in the prevalence of NAFLD among working-age people from 1990 to 2019: Age-period-cohort analysis based on Global Burden of Disease Study 2019 estimates and 95% uncertainty interval (UI) of NAFLD prevalence in the working age population was extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. Age-period-cohort models were used to estimate the prevalence within each age group from 1990 to 2019 (local drift, % per year), fitted longitudinal age-specific rates adjusted for period bias (age effect), and period/cohort relative risk (period/cohort effect). RESULTS: The global age-standardized prevalence (ASPR) of NAFLD increased significantly from 1990 (14,477.6 per 100 000) to 2019 (19,837.6 per 100 000). In the Western Pacific, there were 42,903.8 NAFLD cases in 2019, 54.15% higher than in 1990. The ASPR also increased significantly in the region over the past three decades. At the national level, Palau had the highest ASPR while Brunei Darussalam had the lowest. Age-period-cohort analysis showed that in the Western Pacific, unlike globally, the risk of NAFLD declined after age 60-64 years. Relative to 1980-1989, incidence and DALY risks decreased but prevalence increased in subsequent birth cohorts. Future predictions indicate an upward trend in NAFLD burden, especially among women and medium (SDI) regions like China. CONCLUSION: Non-alcoholic fatty liver disease imparts an immense health burden that continues to grow globally and in the Asia Pacific region. Our work highlights working age adults as an at-risk group and calls attention to socioeconomic gradients within Western Pacific countries. Upward future projections demonstrate that NAFLD prevention is an urgent priority.

New labdane diterpenoids from Alpinia galanga: A new type of GLP-1 secretagogues targeting the PKA-CREB and PI3K-Akt signaling axes.

Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.0%-413.8% at 50 µM. A mechanistic study manifested that the most effective compound 12 upregulated the mRNA expression of Gcg and Pcsk1, and the protein phosphorylation of PKA, CREB, and GSK3ß, but was inactive on GPBAR and GPR119 receptors. Network pharmacology analysis indicated that the PI3K-Akt pathway was involved in the GLP-1 stimulation of 12, which was highly associated with AKT1, CASP3, PPARG, and ICAM1 proteins. This study suggests that A. galanga is rich in diverse labdane diterpenoids with GLP-1 promoting effects, representing a new type of antidiabetic candidates from natural sources.

Effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery: A systematic review and trial sequential analysis of randomized controlled trials.

BACKGROUND: We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA). METHODS: From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours). RESULTS: Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73 h, I2 = 22%, P < 0.01), the time to first flatus (MD -7.03 h, I2 = 25%, P < 0.01), the time to start of sips of water (MD -12.02 h, I2 = 0%, P < 0.01), and the time to start of liquid diet (MD -12.97 h, I2 = 0%, P < 0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81 h, I2 = 31%, P = 0.02) and the time to first flatus (MD -10.81 h, I2 = 0%, P < 0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus. CONCLUSIONS: Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future.

Global Burden of Stroke Attributable to Low Physical Activity/High Body Mass Index Among People Aged 55 Years and Older.

BACKGROUND: This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study. METHODS: We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year. RESULTS: Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden. CONCLUSIONS: Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.

Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

Preliminary outcomes of endovascular treatment of moyamoya disease.

PURPOSE: This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty. MATERIALS AND METHODS: We recruited 12 patients (8 women and 4 men) with occlusion and stenosis of intracranial arteries in the context of moyamoya disease who underwent endovascular stent angioplasty. Clinical data, baseline conditions, lesion location, treatment outcomes, periprocedural complications, and follow-up outcomes were analysed. RESULTS: The occlusion was located at the M1 segment of the middle cerebral artery in 8 patients, at both the M1 and A2 segments in one patient, and at the C7 segment of the internal carotid artery in 3. Thirteen stents were deployed at the occlusion site, including the low-profile visualized intraluminal support (LVIS) device in 8 patients, an LVIS device and a Solitaire AB stent in one, and a Leo stent in 3, with a success rate of 100% and no intraprocedural complications. Plain CT imaging after stenting revealed leakage of contrast agent, which disappeared on the second day, resulting in no clinical symptoms or neurological sequelae. Follow-up angiography studies were performed in all patients for 6-12 months (mean, 8.8). Slight asymptomatic in-stent stenosis was observed in 2 patients (16.7%), and no neurological deficits were observed in the other patients. All preoperative ischaemic symptoms completely disappeared at follow-up. CONCLUSION: Stent angioplasty is a safe and effective treatment for occlusion and stenosis of intracranial arteries in moyamoya disease.

Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS: Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.

A Cable-Stayed Honeycomb Superstructure to Improve the Stability of Li-Rich Materials via Inhibiting Interlaminar Lattice Strain.

In layered Li-rich materials, over stoichiometric Li forms an ordered occupation of LiTM6 in transition metal (TM) layer, showing a honeycomb superstructure along [001] direction. At the atomic scale, the instability of the superstructure at high voltage is the root cause of problems such as capacity/voltage decay of Li-rich materials. Here a Li-rich material with a high Li/Ni disorder is reported, these interlayer Ni atoms locate above the honeycomb superstructure and share adjacent O coordination with honeycomb TM. These Ni─O bonds act as cable-stayed bridge to the honeycomb plane, and improve the high-voltage stability. The cable-stayed honeycomb superstructure is confirmed by in situ X-ray diffraction to have a unique cell evolution mechanism that it can alleviate interlaminar lattice strain by promoting in-plane expansion along a-axis and inhibiting c-axis stretching. Electrochemical tests also demonstrate significantly improved long cycle performance after 500 cycles (86% for Li-rich/Li half cell and 82% for Li-rich/Si-C full cell) and reduced irreversible oxygen release. This work proves the feasibility of achieving outstanding stability of lithium-rich materials through superstructure regulation and provides new insights for the development of the next-generation high-energy-density cathodes.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.

MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Conservative versus liberal oxygen therapy for intensive care unit patients: meta-analysis of randomized controlled trials.

BACKGROUND: It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. RESULTS: In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. CONCLUSIONS: COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Burden of depression in adolescents in the Western Pacific Region from 1990 to 2019: An age-period-cohort analysis of the Global Burden of Disease study.

BACKGROUND: Depression is a highly prevalent and disabling mental health condition among adolescents. The epidemiology of depression in adolescents has been changing over time, reflecting changes in risk factors as well as disease concepts and diagnosis. However, few studies have characterized the longitudinal epidemiology of depression in adolescents. Understanding trends of disease burden provides key insights to improve resource allocation and design targeted interventions for this vulnerable population. The Western Pacific Region (WPR) is home to over 1.3 billion people with tremendous diversity in culture and socioeconomic development. The epidemiology of adolescent depression in WPR remains largely unknown. In this study, we aimed to estimate trends of disease burden attributable to depressive disorders among adolescents aged 10-24 years in WPR countries between 1990 and 2019, and to investigate period and cohort effects using the Global Burden of Disease (GBD) study database. METHODS: The study utilized data from the Global Burden of Disease, Injuries, and Risk Factors Study 2019, concentrating on adolescents aged 10 to 24 years with depression. We conducted an in-depth analysis of depression, including its age-standardized prevalence, incidence, and Disability-Adjusted Life Years (DALYs), across diverse demographics such as regions, ages, genders, and socio-demographic indexes, spanning from 1990 to 2019. RESULTS: The analysis found decreasing trends in the prevalence, incidence, and DALYs of adolescent depression in the WPR between 1990-2019, although some countries like Australia and Malaysia showed increases. Specifically, the prevalence of adolescent depression in the region decreased from 9,347,861.6 cases in 1990 to 5,551,341.1 cases in 2019. The incidence rate declined from 2,508.6 per 100,000 adolescents in 1990 to 1,947.9 per 100,000 in 2019. DALYs decreased from 371.9 per 100,000 in 1990 to ASR 299.7 per 100,000 in 2019. CONCLUSION: This study found an overall decreasing trend in adolescent depression burden in the Western Pacific Region between 1990 and 2019, with heterogeneity across countries. For 30 years, the 20-24 age group accounted for the majority of depression among adolescents Widening inequality in depression burden requires policy attention. Further analysis of risk factors contributing to epidemiological trends is warranted to inform prevention strategies targeting adolescent mental health in the region.

Neuropilin-1-Targeted Nanomedicine for Spatiotemporal Tumor Suppression through Photodynamic Vascular Damage and Antiangiogenesis.

Antiangiogenic therapy is an effective way to disrupt nutrient supply and starve tumors, but it is restricted by poor efficacy and negative feedback-induced tumor relapse. In this study, a neuropilin-1 (NRP-1)-targeted nanomedicine (designated as FPPT@Axi) is reported for spatiotemporal tumor suppression by combining photodynamic therapy (PDT) with antiangiogenesis. In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K(PpIX)-PEG8-TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi). Importantly, the NRP-1-mediated targeting property enables FPPT@Axi to selectively concentrate at vascular endothelial and breast cancer cells, facilitating the production of reactive oxygen species (ROS) in situ for specific vascular disruption and enhanced cell apoptosis under light stimulation. Moreover, the codelivered Axi can further inhibit vascular endothelial growth factor receptor (VEGFR) to impair the negative feedback of PDT-induced tumor neovascularization. Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.

Global, regional and national burdens of depression in adolescents and young adults aged 10-24 years, from 1990 to 2019: findings from the 2019 Global Burden of Disease study.

BACKGROUND: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time. AIMS: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years. METHOD: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019. RESULTS: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males. CONCLUSIONS: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

Global, regional and national epidemiology of allergic disorders in children from 1990 to 2019: findings from the Global Burden of Disease study 2019.

OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.

Development of a novel bioartificial cornea using 3D bioprinting based on electrospun micro-nanofibrous decellularized extracellular matrix.

Corneal damage contributes to blindness in millions of people. Simulating natural corneas with artificial corneas is challenging due to material and manufacturing limitations, including poor mechanical properties, complex manufacturing processes, and ocular histocompatibility. In this study, electrospun micro-nanofibrous decellularized extracellular matrix (dECM) is combined with digital light processing 3D bioprinting and validated as a bioartificial cornea for the first time. Electrospinning gives the material a controllable shape, and the electrospun micro-nanofibrous dECM, with preserved inherent biochemical components, can better mimic the natural ECM native microenvironment. An efficient platform can be developed for creating novel structural materials, when combined with intelligent manufacturing. Artificial biological corneas developed using this method showed five-fold improvements in mechanical properties (248.5 ± 35.67 kPa vs. 56.91 ± 3.68 kPa,p< 0.001), superior guidance for cell organization and adhesion, and better maintenance of the cellular phenotype of keratocytes. In animal studies,in vivotransplantation of this artificial cornea showed better regeneration, which accelerated corneal epithelialization and maintained corneal transparency. This method has potential for biomedical applications, and bioartificial corneas manufactured by this method have ideal properties as an alternative to lamellar keratoplasty, with promise for clinical transformation.

Temporal Trends of Asthma Among Children in the Western Pacific Region From 1990 to 2045: Longitudinal Observational Study.

BACKGROUND: Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE: This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS: The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS: Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS: The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.