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Background: Increasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals., Methods: Data from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals., Results: A total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds., Conclusion: In conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear., Results: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism., Conclusions: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments., (© 2024. The Author(s).)

Background: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040., Methods: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends., Results: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI., Conclusion: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options., (© 2024. The Author(s).)

Despite that extensive efforts have been dedicated to the search for advanced catalysts to boost the electrocatalytic nitrobenzene reduction reaction (eNBRR), its progress is severely hampered by the limited understanding of the relationship between catalyst structure and its catalytic performance. Herein, this review aims to bridge such a gap by first analyzing the eNBRR pathway to present the main influential factors, such as electrolyte feature, applied potential, and catalyst structure. Then, the recent advancements in catalyst design for eNBRR are comprehensively summarized, particularly about the impacts of chemical composition, morphology, and crystal facets on regulating the local microenvironment, electron and mass transport for boosting catalytic performance. Finally, the future research of eNBRR is also proposed from the perspectives of performance enhancement, expansion of product scope, in-depth understanding of the reaction mechanism, and acceleration of the industrialization process through the integration of upstream and downstream technologies., (© 2023 Wiley‐VCH GmbH.)

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., Competing Interests: None.

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels., Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations., Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate., Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East., Funding: None., Competing Interests: No competing interests declared., (© 2024 The Author(s).)

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., (© 2024. The Author(s).)

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO 2 , this study demonstrates how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO 2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO 2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO 2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO 2 reduction reaction (eCO 2 RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol g -1 h -1 ) and durability (≈48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO 2 RR for Ag nanoparticles and lattice-confined eCO 2 RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration., (© 2024 Wiley‐VCH GmbH.)

This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN., Competing Interests: Declaration of competing interest The authors have disclosed no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest No competing interests declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

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.

Nitrate electroreduction reaction (eNO 3 - RR) to ammonia (NH 3 ) provides a promising strategy for nitrogen utilization, while achieving high selectivity and durability at an industrial scale has remained challenging. Herein, we demonstrated that the performance of eNO 3 - RR could be significantly boosted by introducing two-dimensional Cu plates as electrocatalysts and eliminating the general carrier gas to construct a steady fluid field. The developed eNO 3 - RR setup provided superior NH 3 Faradaic efficiency (FE) of 99 %, exceptional long-term electrolysis for 120 h at 200 mA cm -2 , and a record-high yield rate of 3.14 mmol cm -2  h -1 . Furthermore, the proposed strategy was successfully extended to the Zn-nitrate battery system, providing a power density of 12.09 mW cm -2 and NH 3 FE of 85.4 %, outperforming the state-of-the-art eNO 3 - RR catalysts. Coupled with the COMSOL multiphysics simulations and in situ infrared spectroscopy, the main contributor for the high-efficiency NH 3 production could be the steady fluid field to timely rejuvenate the electrocatalyst surface during the electrocatalysis., (© 2024 Wiley‐VCH GmbH.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (©Cheng-hao Yang, Xin-yu Li, Jia-jie Lv, Meng-jie Hou, Ru-hong Zhang, Hong Guo, Chu Feng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.03.2024.)

The purpose of this study was to explore whether dietary live microbe intake is associated with various cognitive domains using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. And the specific relationship between low, medium and high dietary live microbe intake groups and cognitive ability of the elderly. Dietary live microbe intake was calculated from 24-h diet recall interviews. Cognitive function was assessed using the number symbol substitution test (DSST, which measures processing speed), the animal fluency test (AFT, which measures executive function), the Alzheimer's Registry sub-test (CERAD, which measures memory), and the Composite Z-score, which adds the Z-values of individual tests. Multiple linear regression models and restricted cubic bar graphs were used to investigate the relationship between live microbe intake and cognitive performance. A total of 2,450 participants aged 60 or older were included. Live microbe intake was positively correlated with cognitive ability on the whole. Specifically, when the intake of low, medium and high live microbe was > 2640 g, > 39 g and > 0 g respectively, the CERAD, DSST, AFT and compositive-Z score of the subjects increased with the increase of microbial intake (P < 0.05). In American adults age 60 or older, higher intakes of live microbes were associated with better cognitive performance, especially after a certain amount was reached., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC., Patients and Methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety., Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group., Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975., (Copyright © 2023 X. Yan, M. Ye, Q. Zou, P. Chen, Z. He, B. Wu, D. He, C. He, X. Xue, Z. Ji, H. Chen, S. Zhang, Y. Liu, X. Zhang, C. Fu, D. Xu, M. Qiu, J. Lv, J. Huang, X. Ren, Y. Cheng, W. Qin, X. Zhang, F. Zhou, L. Ma, J. Guo, D. Ding, S. Wei, Y. He, H. Guo, B. Shi, L. Liu, F. Liu, Z. Hu, X. Jin, L. Yang, S. Zhu, J. Liu, Y. Huang, T. Xu, B. Liu, T. Sun, Z. Wang, H. Jiang, D. Yu, A. Zhou, J. Jiang, G. Luan, C. Jin, J. Xu, J. Hu, Y. H, Jun, W. Zhai, X. Sheng, Shanghai Junshi Biosciences Co. LTD, Shanghai Junshi Biosciences Co. LTD., a. Published by Elsevier Ltd.. All rights reserved.)

Rational design and exploration of oxygen evolution reaction (OER) electrocatalysts with exceptional performance are crucial for the advancement of the hydrogen energy economy. In this study, vanadium/cobalt (V/Co) dual-doped nickel sulfide (Ni 3 S 2 ) nanowires were synthesized on a nickel foam (NF) substrate to overcome the sluggish kinetics typically associated with OER. The resulting catalyst exhibited outstanding electrocatalytic activity towards OER in a 1.0 M KOH electrolyte, with a minimal overpotential of 155 and 263 mV, the current densities of 10 and 100 mA cm -2 can be achieved effortlessly. Importantly, this catalyst demonstrated remarkable stability over extended periods, maintaining its performance for 25 h under constant current density, 55 h under continuously varying current density, and even after undergoing 2000 cycles of cyclic voltammetry (CV), which had surpassed those of most non-noble metal electrocatalysts. The X-ray photoelectron spectroscopy and density functional theory analyses confirmed that the co-doping of Co and V redistributed the electron of Ni, leading to improvements in the d-band center, structural characteristics, and free energy landscapes of adsorbed intermediates. This work presents a novel strategy, based on the connection between electronic structure and catalytic properties, in the design of double-doped catalysts for efficient OER., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aims to delineate the burden of congenital birth defects (CBDs) in children under 14 years of age from 1990 to 2019, using an age-period-cohort framework to analyse data from the Global Burden of Disease Study (GBD)., Methods: Data on prevalence cases, age-standardised prevalence rates (ASPRs), death cases, and age-standardised death rates (ASDRs) of congenital birth defects (CBDs) from 1990 to 2019 were obtained from GBD 2019. Using this data set, we conducted an age-period-cohort (APC) analysis to examine patterns and trends in mortality, prevalence, and disability-adjusted life years (DALYs) associated with CBDs, while exploring correlations with age, time periods, and generational birth cohorts. Furthermore, to quantify the temporal trends, we calculated the estimated annual percentage changes (EAPCs) for these parameters., Results: The global prevalence of CBDs decreased from 1404.22 to 1301.66 per 100 000 with an EAPC of -0.18% from 1990 to 2019. CBD mortality decreased by 42.52% between 1990 and 2019, with the global age-standardised death rate declining from 49.72 to 25.58 per 100 000. The age-standardised DALY rate decreased from 4529.16 to 2393.61 per 100 000. Prevalence declined most notably among older children. The risk of CBDs reached its lowest during adolescence (10-14 years) across all regions. The most recent period (2015-2019) showed a reduced risk of prevalence compared to 2000-2004. Earlier birth cohorts displayed declining tendencies followed by slight increases in risk., Conclusions: This study demonstrates encouraging global reductions in the burden of CBDs among children over the past three decades. Prevalence, mortality, and DALYs attributable to CBDs have exhibited downward trajectories, although regional disparities remain. APC analysis provides valuable insights to inform prevention and management strategies for pediatric CBDs., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests, (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance., Methods and Results: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE -/- ) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE -/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis., Conclusions: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases., Competing Interests: Disclosures None.

Asthma is a common chronic respiratory disease, with onset usually occurring during childhood or adolescence. The aim of this study was to estimate the dynamic changes in the burden of asthma disease among adolescents (aged 15-39 years). Between 1990 and 2019, our comprehensive analysis spanned 204 nations and territories to ascertain the global prevalence of asthma. This extensive evaluation meticulously quantified the disease's burden by examining a range of critical metrics-including mortality rates, prevalence figures, and disability-adjusted life-years (DALYs)-across diverse demographics. Our investigation systematically segmented the data by age, gender, and year, as well as by geographical regions and the Socio-demographic Index (SDI), offering an in-depth perspective on the multifaceted impact of asthma worldwide. From 1990 to 2019, there was a global increase in the incidence cases of asthma among young adults, with the number rising from 6487957.18 (95 %UI: 4578735.08-8736387.55) to 7604488.39 (95 % UI:5428024.98-10177808.25). The prevalence rate of asthma among young adults exhibited a decline from 580.09 per 1,00,000 (95 %UI:481.37-757.28) to 504.28 per 1,00,000 (95 %UI:400.64-633.26). It is also noteworthy that the incidence rates in the remaining SDI regions, although lower, also showed varying degrees of increase in 2015. The age-standardized disease burden rate for asthma among young adults has exhibited a decline over the course of the previous three decades. Nevertheless, regions characterized by lower SDI demonstrate elevated age-standardized mortality rates for asthma, thereby warranting focused attention and prioritized allocation of medical resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The value-added chemicals, monoxide, methane, ethylene, ethanol, ethane, and so on, can be efficiently generated through the electrochemical CO 2 reduction reaction (eCO 2 RR) when equipped with suitable catalysts. Among them, ethylene is particularly important as a chemical feedstock for petrochemical manufacture. However, despite its high Faradaic efficiency achievable at relatively low current densities, the substantial enhancement of ethylene selectivity and stability at industrial current densities poses a formidable challenge. To facilitate the industrial implementation of eCO 2 RR for ethylene production, it is imperative to identify key strategies and potential solutions through comprehending the recent advancements, remaining challenges, and future directions. Herein, the latest and innovative catalyst design strategies of eCO 2 RR to ethylene are summarized and discussed, starting with the properties of catalysts such as morphology, crystalline, oxidation state, defect, composition, and surface engineering. The review subsequently outlines the related important state-of-the-art technologies that are essential in driving forward eCO 2 RR to ethylene into practical applications, such as CO 2 capture, product separation, and downstream reactions. Finally, a greenhouse model that integrates CO 2 capture, conversion, storage, and utilization is proposed to present an ideal perspective direction of eCO 2 RR to ethylene., (© 2023 Wiley-VCH GmbH.)

Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study. In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: In recent years, headache disorders have garnered significant attention as a pressing global health issue. This concern is especially pronounced in low- to middle-income countries and exhibits a notable increase in prevalence among adolescents and young adults. Such a surge in these disorders has invariably diminished the quality of life for affected individuals. Despite its global impact, comprehensive studies exploring the ramifications of headache disorders in the younger population remain scant. Our study endeavored to quantify the global prevalence of headache disorders in individuals between the ages of 15 and 39, over a three-decade span from 1990 to 2019., Methods: Our study, conducted from 1990 to 2019, evaluated the impact of headache disorders, specifically migraines and tension-type headaches (TTH), in 204 different countries and territories. This comprehensive assessment included a detailed analysis of incidence rates, prevalence, and disability-adjusted life-years (DALYs) across various demographics such as age, gender, year, geographical location, and Socio-demographic Index (SDI)., Results: In 2019, there were an estimated 581,761,847.2 migraine cases globally (95% UI: 488,309,998.1 to 696,291,713.7), marking a 16% increase from 1990. Concurrently, TTH cases numbered at 964,808,567.1 (95% UI: 809,582,531.8 to 1,155,235,337.2), reflecting a 37% rise since 1990. South Asia reported the highest migraine prevalence with 154,490,169.8 cases (95% UI: 130,296,054.6 to 182,464,065.6). High SDI regions exhibited the most substantial migraine prevalence rates both in 1990 (22,429 per 100,000 population) and 2019 (22,606 per 100,000 population). Among the five SDI classifications, the middle SDI region recorded the highest tally of TTH cases in both 1990 (210,136,691.6 cases) and 2019 (287,577,250 cases). Over the past 30 years, East Asia experienced the most pronounced surge in the number of migraine cases. On the whole, there was a discernible positive correlation between the disease burden of migraine and TTH and the SDI., Conclusion: Migraine and TTH represent formidable challenges in global health. The intensity of their impact exhibits marked disparities across nations and is distinctly elevated among women, individuals within the 30-39 age bracket, and populations characterized by a high SDI. The results of our research emphasize the imperative of assimilating migraine and TTH management into contemporary healthcare paradigms. Such strategic integration holds the potential to amplify public cognizance regarding pertinent risk factors and the spectrum of therapeutic interventions at hand., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Introduction: Efficiently recognizing emotions is a critical pursuit in brain-computer interface (BCI), as it has many applications for intelligent healthcare services. In this work, an innovative approach inspired by the genetic code in bioinformatics, which utilizes brain rhythm code features consisting of δ, θ, α, β, or γ, is proposed for electroencephalography (EEG)-based emotion recognition., Methods: These features are first extracted from the sequencing technique. After evaluating them using four conventional machine learning classifiers, an optimal channel-specific feature that produces the highest accuracy in each emotional case is identified, so emotion recognition through minimal data is realized. By doing so, the complexity of emotion recognition can be significantly reduced, making it more achievable for practical hardware setups., Results: The best classification accuracies achieved for the DEAP and MAHNOB datasets range from 83-92%, and for the SEED dataset, it is 78%. The experimental results are impressive, considering the minimal data employed. Further investigation of the optimal features shows that their representative channels are primarily on the frontal region, and associated rhythmic characteristics are typical of multiple kinds. Additionally, individual differences are found, as the optimal feature varies with subjects., Discussion: Compared to previous studies, this work provides insights into designing portable devices, as only one electrode is appropriate to generate satisfactory performances. Consequently, it would advance the understanding of brain rhythms, which offers an innovative solution for classifying EEG signals in diverse BCI applications, including emotion recognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Lin, Che, Lv, Chen, Wang, Zeng, Ren, Zhao and Lu.)

Background: Volatile organic compounds (VOCs) are a large group of chemicals widely used in People's Daily life. There is increasing evidence of the cumulative toxicity of VOCs. However, the association between VOCs and the risk of COPD has not been reported., Objective: We comprehensively evaluated the association between VOCs and COPD., Methods: Our study included a total of 1,477 subjects from the National Health and Nutrition Examination Survey, including VOCs, COPD, and other variables in the average US population. Multiple regression models and smooth-curve fitting (penalty splines) were constructed to examine potential associations, and stratified analyses were used to identify high-risk groups., Results: We found a positive association between blood benzene and blood o-xylene concentrations and COPD risk and identified a concentration relationship between the two. That is, when the blood benzene and O-xylene concentrations reached 0.28 ng/mL and 0.08 ng/mL, respectively, the risk of COPD was the highest. In addition, we found that gender, age, and MET influence the relationship, especially in women, young people, and people with low MET., Significance: This study revealed that blood benzene and blood o-xylene were independently and positively correlated with COPD risk, suggesting that long-term exposure to benzene and O-xylene may cause pulmonary diseases, and providing a new standard of related blood VOCs concentration for the prevention of COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Li, Shen, You, Wen, Wang and Yang.)

Macathioureas A-D (1-4), four new thiourea derivatives with a carbamothioylpyrrolidine-2-carboxamide framework, were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were identified based on extensive spectroscopic data, including 1D NMR, 2D NMR, and HRESIMS techniques. Their absolute configurations were assigned as 7S by the comparison of the experimental and predicted electronic circular dichroism (ECD) spectra. All the thiourea analogues were tested for their cytotoxicities against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40 μM., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2023. Published by Elsevier B.V.)

An electrochemical approach for ammonia production is successfully developed by coupling the anodic dinitrogen oxidation reaction (NOR) and cathodic hydrogen evolution reaction (HER) within a well-designed membraneless flow electrolyzer. The obtained reactor shows the preferential yield of ammonia over nitrogen oxides on the vanadium nitride catalyst surface. At an applied oxidation potential of 2.25 V versus the reversible hydrogen electrode (vs RHE), a promoted ammonia production rate and Faradaic efficiency (FE) were obtained with 9.9 mmol g -1 h -1 (0.029 mmol cm -2 h -1 ) and 4.8%, respectively. Besides, the negative affection of ammonia contamination is efficiently alleviated. Density functional theory calculations revealed that the thermodynamic energy needed to produce ammonia (-0.63 eV) is far lower than that of producing nitrogen oxide (0.96 eV) from hydrogenated nitrogen oxides [∗N 2 OH] splitting, confirming the coupling of NOR and HER., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Sun, Liu, Shi, Lv and Peng.)

Bivalve mollusks can accumulate diarrheic shellfish poisoning (DSP) toxins through filter-feeding, but they exhibit some resistance to the toxins. Previous studies have suggested that the ABC transporters may have an important role in the resistance to DSP toxins, but comprehensive studies are lacking. In this study, we comprehensively analyzed the distribution of ABC transporters in the mussel Perna viridis, and observed responses of ABCB and ABCC transporters to the DSP toxins-producing dinoflagellate Prorocentrum lima. Total 39 members of ABC transporters were identified in P. viridis, including 3 full PvABCBs, 3 half PvABCBs, and 7 PvABCCs transporters. We found that PvABCBs and PvABCCs subfamilies were expressed in hemocytes, gills and digestive gland with some difference, especially in hemocytes. After exposure to P. lima, PvABCBs and PvABCCs displayed different expression changes in different tissues. The short-term (3 h) exposure to P. lima induced the transcription of PvABCB1&#95;like1, PvABCB6, PvABCC1, PvABCC1&#95;like and PvABCC1/3, and the longer-term (96 h) exposure increased the transcription of PvABCB1, PvABCB1&#95;like, PvABCB10, PvABCC1 and PvABCC1&#95;like1 in gills and PvABCC10 in digestive gland. These results suggest that different types of PvABCBs and PvABCCs in P. viridis may contribute to the detoxification of DSP toxins in different tissues at different time after exposure to DSP toxins. Our finding provides new evidence for further understanding the role of ABC transporters in the tolerance of mussel to DSP toxins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Brucellosis is a common zoonotic infectious disease worldwide that can affect almost all organs in the human body. Osteonecrosis of the femoral head has numerous possible causes. Patients usually experience movement disorders, severe pain, and an extremely high disability rate. We herein describe a 32-year-old male farmer living in Shanxi, China who accidentally injured his right hip while working. After 1 month of rest, the pain in the right hip was relieved, and the patient began to walk again. However, after 2 months of walking, he developed aggravated pain and claudication in the right lower limb. Examination revealed shortening of the right lower limb. We carried out a comprehensive and systematic examination and performed total hip arthroplasty. Hip trauma with Brucella infection may progress to osteonecrosis of the femoral head in a short period of time without typical symptoms of Brucella infection. Systematic examination and treatment should be performed at an early stage to prevent the eventual deterioration of the disease and serious complications that are difficult to treat.

A novel fluorescent compound, named C-TPA, based on coumarin (acceptor) and triphenylamine (donor) was facilely designed and fabricated through a one-step Suzuki coupling reaction. As a donor group, triphenylamine can efficiently enhance the fluorescence intensity and photostability of coumarin, and thus improve the detection efficiency. C-TPA-S was obtained from C-TPA treated with Lawesson's reagent and C-TPA-S can be used for the turn-on detection of hypochlorite through oxidative desulfurization with a low detection limit of 0.12 μM. Moreover, the intramolecular charge transfer process between the donor and acceptor group endows C-TPA with solvatochromism property and makes C-TPA a good candidate for polarity detection. The C-TPA with bright green fluorescence was highly efficient for imaging the microenvironment of polarity both in living cells and tissues with high selectivity and photostability, which can be applied in the diagnosis for the cancer cells., (Copyright © 2022. Published by Elsevier B.V.)

Rather than just focusing on the catalyst itself in the electrocatalytic CO 2 reduction reaction (eCO 2 RR), as previously reviewed elsewhere, we herein extend the discussion to the special topic of the microenvironment around the electrocatalytic center and present a comprehensive overview of recent research progress. We categorize the microenvironment based on the components relevant to electrocatalytic active sites, i.e., the catalyst surface, substrate, co-reactants, electrolyte, membrane, and reactor. Supported by most of the reported articles, the relevant factors affecting the catalytic performance of eCO 2 RR are then discussed in detail, and existing challenges and potential solutions are mentioned. Perspectives for the future research on eCO 2 RR, including the integration of different microenvironment factors, the extension to industrial application by coupling with carbon capture and conversion, and separation of products, are also discussed., (© 2022 Wiley-VCH GmbH.)

Acrivastine is a second-generation H1-receptor antagonist, and its structure is sensitive to ultraviolet. Four unknown and one reported degradation products can be detected in the ultraviolet radiation solutions of acrivastine. To improve the quality control of acrivastine, the photodegradation impurities were isolated and structurally elucidated. There are four new impurities (1-3 and 5), and one reported compound (4). The isolation strategy was designed as preparative high-performance liquid chromatography using a reversed phase column with volatile acid addition in the mobile phase, combined with preparative thin-layer chromatography using silica gel with alkaline addition in the mobile phase. Using the developed methods, five impurities (1-5) were efficiently purified after two or three chromatography runs with purities > 95%. The structures of compounds 1-5 are elucidated based on spectroscopy analysis of MS, and nuclear magnetic resonance spectroscopy. Using the impurity standard, the high-performance liquid chromatography method was developed and validated. The method was proved to be sensitive, accurate (Recovery% 96.1-107.7%), linear (0.15-0.75 μg/mL, R 2 > 0.996), robust, and specific, and it was successfully used to determine the degradation impurities of acrivastine and its formulation., (© 2022 Wiley-VCH GmbH.)

Background: Some guidelines for management of Hirschsprung's disease (HSCR, HD) have been developed, but their quality is vague. This study will systematically assess the quality of guidelines and analyze the key recommendations and the best evidence for guidelines., Methods: Applicable guidelines were retrieved using a systematic search of databases. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used to assess the quality of the guidelines. Then, the recommendations and evidence for the included guidelines were extracted and compared., Results: A total of nine guidelines were included in this study, and only one had an overall standardized score of more than 60%, indicating that it is worthy of recommendation. The problems identified included ambiguous and low-quality evidence; obvious distributional heterogeneity among the recommendations; a lack of in-depth discussion on the interpretation of staging, diagnostic methods, conservative treatment, and surgical staging of disease., Conclusion: The quality of guidelines varies widely, and there is a lack of high-quality professional opinions and supporting evidence for the main recommendations. At present, only comprehensive guidelines can be considered high-quality and there is still room for improvement., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs-lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan-Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Wu, Zhang, Kong, Shang, Lv, Li, Lu, Yong, Zhang, Zheng, Li, Chen, Bian and Wei.)

Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC 50 values ranging from 1.96 to 29.15 μM. They also showed moderate anti-inflammatory activities (IC 50  = 6.30-12.05 μM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC 50  = 2.00 μM) and MCF-7 (IC 50  = 3.55 μM) cells, and anti-inflammatory activity (IC 50  = 6.47 μM)., (Copyright © 2022. Published by Elsevier B.V.)

Heparinase (HPA) is a β-D glucuronidase that belongs to the endoglycosidase enzyme family, and plays an important role in numerous pathological and physiological processes, including inflammation, angiogenesis and tumor metastasis. When the expression of HPA is abnormally high, the side chain of heparin sulfate proteoglycans degrades, destroying the cell barrier and leading to the occurrence and development of inflammation, with systemic inflammation occurring in severe cases. Sepsis is a major cause of mortality in critically ill patients. In sepsis, the gastrointestinal tract is the first and most frequently involved target organ, which often leads to gastrointestinal dysfunction. HPA overexpression has been determined to accelerate sepsis progression and gastrointestinal dysfunction; thus, it was hypothesized that HPA may play an important role and may serve as an index for the diagnosis of gastrointestinal dysfunction in sepsis. HPA inhibitors may therefore become applicable as targeted drugs for the treatment of gastrointestinal dysfunction in patients with sepsis. The present review mainly discussed the role of HPA in gastrointestinal dysfunction of sepsis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Chen et al.)

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: This study aimed to investigate the clinical, histological, immunohistochemical and chromosomal features of primary cutaneous adenoid cystic carcinoma (PCACC)., Methods and Results: We retrospectively analysed 13 cases identified on their clinicopathological features and performed fluorescence in-situ hybridisation (FISH) on six available cases. Head and neck (46.2%) were most commonly involved. The median age was 53 years, with a male predilection. Histologically, tumours were classified as grades 1 (eight), 2 (four) and 3 with high-grade transformation (HGT) (one). The HGT component was demonstrated as poorly differentiated carcinoma with multifocal necrosis and myoepithelial differentiation. Patients with one of the following factors: longest diameter of the lesion (≥ 1 cm), involvement of subcutaneous fat tissue and widely infiltrative border had a relatively higher rate of local recurrence, distant metastasis and death. Five of six cases were confirmed to have MYB translocation, while nuclear staining for MYB proto-oncogene, transcription factor (MYB) protein was found in four cases. During the follow-up (median = 64 months), two patients experienced local recurrences. One patient, who was classified as grade III PCACC with HGT, developed multiple metastases and died of disease. Another patient was alive with multiple metastases., Conclusions: This is the largest single-institution study, to our knowledge, of PCACC in an Asian population. We describe the first case of scalp PCACC with HGT, which is the only death case in our series. PCACC tends to recur locally and has metastatic potential. PCACC with HGT has a poor prognosis., (© 2021 John Wiley & Sons Ltd.)

Diarrheic shellfish poisoning (DSP) toxins are widely distributed over the world, causing diarrhea, vomiting, and even tumor in human. However, bivalves, the main carrier of the DSP toxins, have some tolerant mechanisms to DSP toxins, though it remains unclear. In this study, we scrutinized the role of Jun N-terminal kinases (JNK) in tolerance of DSP toxins and the relationship between JNK, apoptosis and nuclear factor E2-related factor/antioxidant response element (Nrf2/ARE) pathways. We found that the phosphorylated level of JNK protein was significantly increased both in hemocytes (6 h) and gills (3 h) of the mussel Perna viridis after short-term exposure to DSP toxins-producing dinoflagellate Prorocentrum lima. Exposure of P. lima induced oxidative stress in mussels. Hemocytes and gills displayed different sensitivities to the cytotoxicity of DSP toxins. Exposure of P. lima activated caspase-3 and induced apoptosis in gills but did not induce caspase-3 and apoptosis in hemocytes. The short-term exposure of P. lima could activate Nrf2/ARE signaling pathway in hemocytes (6 h), while longer-term exposure could induce glutathione reductase (GR) expression in hemocytes (96 h) and glutathione-S-transferases (GST) in gills (96 h). Based on the phylogenetic tree of Nrf2, Nrf2 in P. viridis was closely related to that in other mussels, especially Mytilus coruscus, but far from that in Mus musculus. The most likely phosphorylated site of Nrf2 in the mussels P. viridis is threonine 504 for JNK, which is different from that in M. musculus. Taken all together, the tolerant mechanism of P. viridis to DSP toxins might be involved in JNK and Nrf2/ARE signaling pathways, and JNK play a key role in the mechanism. Our findings provide a new clue to further understand tolerant mechanisms of bivalves to DSP toxins., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Red deer ( Cervus elaphus ) blood is widely used as a health product. Mixed culture fermentation improves the flavor and bioavailability of deer blood (DB), and both DB and its enzymatic hydrolysates exhibit anti-fatigue activities in vivo. To elucidate the bioactive ingredients, enzymatic hydrolysates were fractioned into different peptide groups using reversed phase resin chromatography, and then evaluated using an exhaustive swimming mice model to assess swimming time and biochemical parameters. The structures of the bioactive peptides were elucidated by high performance liquid chromatography with tandem mass detection. Thirty-one compounds were identified as glutamine or branched-chain amino acids containing short peptides, of which Val-Ala-Asn, Val-Val-Ser-Ala, Leu(Ile)-Leu(Ile)-Val-Thr, Pro-His-Pro-Thr-Thr, Glu-Val-Ala-Phe and Val-Leu(Ile)-Asp-Ala-Phe are new peptides. The fractions containing glutamine or valine short peptides, Ala-Gln, Val-Gln, Val-Val-Ser-Ala, Val-Leu(Ile)-Ser improved exercise endurance by increasing hepatic glycogen (HG) storage. The peptides group containing Leu(Ile)-Leu(Ile), Asp-Gln, Phe- Leu(Ile), Val-Val-Tyr-Pro contributed to decreased muscle lactic acid (MLA)accumulation and to an increase in HG. The anti-fatigue activities of DB hydrolysates were attributed to the synergistic effects of different types of peptides.

Background: Interleukin 10 receptor alpha subunit (IL10RA) dysfunction is the main cause of very early-onset inflammatory bowel disease (VEO-IBD) in East Asians., Aim: To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations., Methods: From May 2016 to September 2020, four young patients with clinically diagnosed VEO-IBD were recruited. Before hospitalization, using targeted gene panel sequencing and trio-whole-exome sequencing (WES), three patients were found to harbor a IL10RA mutation (c.301C>T, p.R101W in one patient; c.537G>A, p.T179T in two patients), but WES results of the fourth patient were not conclusive. We performed whole-genome sequencing (WGS) on patients A and B and reanalyzed the data from patients C and D. Peripheral blood mononuclear cells (PBMCs) from patient D were isolated and stimulated with lipopolysaccharide (LPS), interleukin 10 (IL-10), and LPS + IL-10. Serum IL-10 levels in four patients and tumor necrosis factor-α (TNF-α) in the cell supernatant were determined by enzyme-linked immunosorbent assay. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and Ser727 in PBMCs was determined by western blot analysis., Results: The four children in our study consisted of two males and two females. The age at disease onset ranged from 18 d to 9 mo. After hospitalization, a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data. Patient D was homozygous for the 333 bp deletion. All four patients had elevated serum IL-10 levels. In vitro , IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-α production induced by LPS. Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS + IL-10 in both healthy subjects and in patient D., Conclusion: WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD, whereas the WES results were inconclusive., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions., Methods: Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated., Results: Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria., Conclusion: The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome., (© 2021 John Wiley & Sons Ltd.)

Objective: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment., Methods: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to ashi point (target skin lesions), Zusanli (ST 36), Xuehai (SP 10) and Qihai (CV 6) for 30 min each time, 3 times a week. The control group was treated with calcipotriol ointment (0.25 g each time, once in the morning and evening) on the target skin lesions. Both groups were treated for 8 weeks. The psoriasis area and severity index (PASI) score before and after treatment, main clinical symptoms of TCM score and dermatology life quality index (DLQI) score before and after treatment and 3 and 6 moths follow-up were observed in the two groups; the clinical efficacy after treatment was evaluated and the recurrence rates of the two groups were followed up for 3 and 6 months after treatment., Results: After treatment, the PASI scores in the both groups were lower than before treatment ( P <0.01). After treatment and 3 and 6 months follow-up, the main clinical symptoms of TCM scores and DLQI scores of the two groups were lower than those before treatment ( P <0.05), and at 3 and 6 months follow-up, those in the observation group were lower than the control group ( P <0.01). There was no statistically significant difference between the observation group and the control group in overall effective rate and target skin lesion effective rate ( P >0.05). At 3 and 6 months follow-up, the overall recurrence rate and target skin lesion recurrence rate in the observation group were lower than those in the control group ( P <0.05)., Conclusion: Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Aims: The blood-brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease., Methods and Results: We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial-specific CD147 knockout mice, we performed RNA-sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD., Conclusions: Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)