A review regarding the article 'Electrocardiographic abnormalities in patients with metabolic dysfunction-associated Steatotic liver disease: A systematic review and meta-analysis.'

Metabolic-dysfunction-associated Steatotic liver disease (MASLD) is a high-risk condition for both liver fibrosis and cardiovascular disease (CVD). Therefore, therapeutic strategies to prevent both liver fibrosis and atherosclerotic CVD are required for the treatment of MASLD. Metabolic dysfunction-associated steatohepatitis (MASH) is the more severe form of MASLD, is defined histologically by the presence of lobular inflammation and hepatocyte ballooning and is associated with a greater risk of fibrosis progression. While CVD is the leading cause of mortality in patients with MASLD, those with more severe liver fibrosis are at increased risk of liver-related mortality, with the risk increasing exponentially with fibrosis stage. MASH has been found in 63% of patients with MASLD undergoing liver biopsy in an Asian multi-center cohort. Multiple complex pathways are involved in the association between MASLD and CVD. The visceral accumulation of fat around the liver and other organs, including the pericardium, leads to the release of fat-derived metabolites with the activation of several inflammatory pathways Cardiac rhythm abnormalities are prevalent in MASLD, such as prolongation of the QT interval, ventricular arrhythmias, and atrial fibrillation. Therapeutic interventions that improve cardiometabolic risk factors may be beneficial for an improvement in MASLD. The effects of such therapeutic interventions on lipid, lipoprotein and apoprotein accumulation in the liver and on hepatic steatosis and fibrosis still remain unelucidated. Which lipid factor is crucial for developing MASLD also remains largely unknown.

How Labor Costs Affect Innovation Output in Pharmaceutical Companies: Evidence from China.

Existing literature generally suggests that rising labor costs lead to the substitution of capital for labor, prompting firms to save on labor costs through technological upgrades. However, as a typical human capital-intensive industry, the pharmaceutical sector finds it challenging to replace labor with capital through the introduction of advanced equipment. Therefore, compared to other industries, the pharmaceutical sector faces greater adverse impacts. Research on how pharmaceutical R&D behavior is influenced by labor costs is scarce. This paper analyzes the triple effects of rising labor costs on corporate innovation from the perspectives of human capital, physical capital, and financial capital. Based on empirical research using data from Chinese listed companies, we found that an increase in labor costs promotes innovation output in the pharmaceutical sector, but this effect is more pronounced in other sectors. Financing constraints play a negative role on corporate innovation in the pharmaceutical sector, while it is not significant in the other sectors. Factor substitution play a positive effect on corporate innovation in the other sectors, which is invalid in the pharmaceutical sector. This research contributes to a deeper understanding of the unique mechanisms by which labor costs impact innovation activities in the pharmaceutical industry.

Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.

Following infection, influenza viruses strive to establish a new host cellular environment optimized for efficient viral replication and propagation. Influenza viruses use or hijack numerous host factors and machinery not only to fulfill their own replication process but also to constantly evade the host's antiviral and immune response. For this purpose, influenza viruses appear to have formulated diverse strategies to manipulate the host proteins or signaling pathways. One of the most effective tactics is to specifically induce the degradation of the cellular proteins that are detrimental to the virus life cycle. Here, we summarize the cellular factors that are deemed to have been purposefully degraded by influenza virus infection. The focus is laid on the mechanisms for the protein ubiquitination and degradation in association with facilitated viral amplification. The fate of influenza viral infection of hosts is heavily reliant on the outcomes of the interplay between the virus and the host antiviral immunity. Understanding the processes of how influenza viruses instigate the protein destruction pathways could provide a foundation for the development of advanced therapeutics to target host proteins and conquer influenza.

Fracture resistance of partial and complete coverage veneers and ceramic crowns for maxillary central incisors.

STATEMENT OF PROBLEM: Minimally invasive treatments have gained popularity in recent years. However, research comparing the fracture resistance of lithium disilicate partial coverage veneer restorations with that of ceramic crowns is lacking. PURPOSE: The purpose of this in vitro study was to evaluate and compare the fracture resistance of lithium disilicate restorations fabricated for preparations of various designs. The designs included veneer preparations with finish lines in the upper, middle, and lower third of the facial surface and ceramic crown preparations with margins in the lower third of the facial surface. All restorations were designed and fabricated using a chairside digital workflow. MATERIAL AND METHODS: Four maxillary right central incisor typodont teeth were prepared for partial coverage veneer preparation with the margin in the upper middle third of the facial surface (PU1/3); partial coverage veneer preparation with margin in lower middle third of the facial surface (PL1/3); complete coverage veneer preparation (CV) with margin in the cervical region; and ceramic crown (CC) preparation. Each preparation was scanned, and 15 casts were 3D printed from each scan. A total of 60 lithium disilicate restorations were fabricated (n=15 per group) using a chairside computer-aided design and computer-aided manufacturing (CAD-CAM) system (Primescan and MCXL). The different restorations were cemented to the 3D printed testing dies with a photopolymerizable resin cement. The specimens were artificially aged with 10 000 thermal cycles between 5 and 55 °C with a dwell time of 30 seconds and were loaded to failure using a universal testing machine. The maximum load to fracture was analyzed using a 1-way ANOVA and post hoc Tukey honestly significant difference (HSD) test (α=.05). Additionally, the fracture patterns of the specimens were evaluated with a stereomicroscope for descriptive purposes. RESULTS: The mean fracture resistance of the chairside CAD-CAM lithium disilicate veneers and ceramic crowns was statistically different depending on the design of the restoration (P<.05). Group CC demonstrated the highest fracture resistance values (1440.66 N), followed by CV (929.8 N) and PU1/3 (756.13 N). The lowest value was for PL1/3 (532.4 N). CONCLUSIONS: The fracture resistance measured for the maxillary central incisor partial coverage veneers with margins in the middle third of the facial surface appear capable of resisting average occlusal forces. However, these veneers demonstrated lower fracture resistance values when compared with complete coverage veneers. Further, lithium disilicate crowns demonstrated higher fracture resistance than veneers, irrespective of their design.

Temporal dynamics of spatial attentional biases toward weight-related words among females with weight dissatisfaction.

Attentional bias toward weight-related stimuli plays a crucial role in the development and maintenance of body image disturbances. However, the temporal dynamics of attentional biases responsible for the previously reported behavioral effects caused by the task-irrelevant but spatial-relevant weight-related stimuli presented in the peripheral visual field among females with high weight dissatisfaction (HWD) remain unclear. The present study combined the modified dot-probe task and event-related potentials to explore the temporal dynamics of spatial attentional biases toward weight-related words among females with HWD. The results showed significantly larger N2pc amplitudes were elicited by fat-related and thin-related words than neutral words only in the HWD group. Moreover, only fat-related words elicited a significant PD for the HWD group, and the PD amplitudes were larger in the HWD group than in the control group. These findings revealed that weight-related words initially captured spatial allocation among females with HWD, and then fat-related words were actively suppressed after the initial capturing.

Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function.

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. METHODS: We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied. RESULTS: Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes. CONCLUSIONS: Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.

Gaps between current practice in perinatal depression screening and guideline recommendations: a systematic review.

OBJECTIVE: Screening for perinatal depression is recommended by many guidelines to reduce the disease burden, but current implementation practices require clarification. METHOD: Fifteen databases were searched for observational studies using a pre-tested search strategy. In addition, the websites of academic organizations were searched for guidelines, recommendations, and reports. Literature published between January 1, 2010, and December 19, 2021, in either English or Chinese, was included. The standard form of the Joanna Briggs Institute (JBI) was used to assess risk of bias of the included studies. RESULTS: The data analysis covered 103 studies, 21 guidelines, 11 recommendations, five position statements, three reports, two committee opinions, three consensuses, one consultation, and one policy statement. All but one guideline recommended that mothers be routinely screened for perinatal depression at least once during the perinatal period. In addition, 39 documents recommended that perinatal mothers at risk of perinatal depression be provided with or referred to counseling services. In original studies, however, only 8.7% of the original studies conducted routine screenings, and only one-third offered referral services after the screening process. The EPDS emerged as the most frequently used screening tool to measure perinatal depression. 32% (n = 33) of studies reported the technology used for screening. The most commonly used method was face-to-face interviews (n = 22). Screening personnel the agents conducting the screening comprised researchers (n = 26), nurses (n = 15), doctors (n = 11). CONCLUSIONS: A significant disparity was observed between the recommendations and implementation of perinatal depression screening, highlighting the need to integrate routine screening and referral processes into maternal care services.

Taking advantage of the interaction between the sulfoxide and heme cofactor to develop indoleamine 2, 3-dioxygenase 1 inhibitors.

Taking advantage of key interactions between sulfoxide and heme cofactor, we used the sulfoxide as the anchor functional group to develop two series of indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors: 2-benzylsulfinylbenzoxazoles (series 1) and 2-phenylsulfinylbenzoxazoles (series 2). In vitro enzymatic screening shows that both series can inhibit the activity of IDO1 in low micromolar (series 1) or nanomolar (series 2) levels. They also show inhibitory selectivity between IDO1 and tryptophan 2, 3-dioxygenase 2. Interestingly, although series 1 is less potent IDO1 inhibitors of these two series, it exhibited stronger inhibitory activity toward kynurenine production in interferon-γ stimulated BxPC-3 cells. Enzyme kinetics and binding studies demonstrated that 2-sulfinylbenzoxazoles are non-competitive inhibitors of tryptophan, and they interact with the ferrous form of heme. These results demonstrated 2-sulfinylbenzoxazoles as type II IDO1 inhibitors. Furthermore, molecular docking studies supports the sulfoxide being of the key functional group that interacts with the heme cofactor. Compound 22 (series 1) can inhibit NO production in a concentration dependent manner in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and can relieve pulmonary edema and lung injury in LPS induced mouse acute lung injury models.

Inflammatory lung injury is associated with endothelial cell mitochondrial fission and requires the nitration of RhoA and cytoskeletal remodeling.

Higher levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a TLR4 agonist, are associated with poor clinical outcomes in sepsis-induced acute lung injury (ALI). Little is known regarding the mechanisms by which eNAMPT is involved in ALI. Our recent work has identified a crucial role for mitochondrial dysfunction in ALI. Thus, this study aimed to determine if eNAMPT-mediated inflammatory injury is associated with the loss of mitochondrial function. Our data show that eNAMPT disrupted mitochondrial bioenergetics. This was associated with cytoskeleton remodeling and the loss of endothelial barrier integrity. These changes were associated with enhanced mitochondrial fission and blocked when Rho-kinase (ROCK) was inhibited. The increases in mitochondrial fission were also associated with the nitration-mediated activation of the small GTPase activator of ROCK, RhoA. Blocking RhoA nitration decreased eNAMPT-mediated mitochondrial fission and endothelial barrier dysfunction. The increase in fission was linked to a RhoA-ROCK mediated increase in Drp1 (dynamin-related protein 1) at serine(S)616. Another TLR4 agonist, lipopolysaccharide (LPS), also increased mitochondrial fission in a Drp1 and RhoA-ROCK-dependent manner. To validate our findings in vivo, we challenged C57BL/6 mice with eNAMPT in the presence and absence of the Drp1 inhibitor, Mdivi-1. Mdivi-1 treatment protected against eNAMPT-induced lung inflammation, edema, and lung injury. These studies demonstrate that mitochondrial fission-dependent disruption of mitochondrial function is essential in TLR4-mediated inflammatory lung injury and identify a key role for RhoA-ROCK signaling. Reducing mitochondrial fission could be a potential therapeutic strategy to improve ARDS outcomes.

The complete chloroplast genome sequence of leibnitzia anandria (linnaeus) turczaninow.

Leibnitzia anandria is a perennial herbaceous plant with medicinal properties, and the entire plant can be used in traditional medicine. Leibnitzia anandria was once classified under the genus Gerbera Cass., but was reclassified under Leibnitzia Cass. recently. In this study, using the GeneLab M sequencing technology of the Genemind platform, we have sequenced, assembled, and analyzed the complete chloroplast genome of Leibnitzia anandria for the first time. The genome is 154168 bp in length, consisting of a large single-copy region(LSC, 80166 bp), a small single-copy region(SSC, 18202 bp), and a pair of inverted repeat sequences(IR, 27900 bp). We have predicted and annotated a total of 133 genes, including 88 protein-coding genes, 37 tRNA-coding genes, and 8 rRNA-coding genes. The results of the phylogenetic analysis indicate that Leibnitzia anandria and Leibnitzia nepalensis, as well as the closely related Gerbera plant, clustered into a separate clade, rather than grouping together with the other plants belonging to the tribe Mutisieae. This study provides new information for the phylogeny research of Leibnitzia anandria, contributing to a better understanding of its taxonomy and evolution.

The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

OBJECTIVE: The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. METHODS: A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. CONCLUSIONS: This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Deciphering the Prognostic Efficacy of MRI Radiomics in Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis.

This meta-analysis investigates the prognostic value of MRI-based radiomics in nasopharyngeal carcinoma treatment outcomes, specifically focusing on overall survival (OS) variability. The study protocol was registered with INPLASY (INPLASY202420101). Initially, a systematic review identified 15 relevant studies involving 6243 patients through a comprehensive search across PubMed, Embase, and Web of Science, adhering to PRISMA guidelines. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPS) tool and the Radiomics Quality Score (RQS), highlighting a low risk of bias in most domains. Our analysis revealed a significant average concordance index (c-index) of 72% across studies, indicating the potential of radiomics in clinical prognostication. However, moderate heterogeneity was observed, particularly in OS predictions. Subgroup analyses and meta-regression identified validation methods and radiomics software as significant heterogeneity moderators. Notably, the number of features in the prognosis model correlated positively with its performance. These findings suggest radiomics' promising role in enhancing cancer treatment strategies, though the observed heterogeneity and potential biases call for cautious interpretation and standardization in future research.

Corrigendum: Establishment of noncycloplegic methods for screening myopia and pre-myopia in preschool children.

[This corrects the article DOI: 10.3389/fmed.2023.1291387.].

Association between lipoprotein(a) plasma levels and diabetic nephropathy in Han Chinese patients with type 2 diabetes mellitus.

The goal of this study was to evaluate the relationship between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy (DN) among Han Chinese individuals with type 2 diabetes mellitus (T2DM). This retrospective analysis comprised a consecutive case series of 767 grown-up patients with T2DM (199 among them with DN) hospitalized in the Department of Endocrinology at the The First Affiliated Hospital of Anhui Medical University from February 20220 to February 2021. Clinical data and other laboratory measurements, such as glycated hemoglobin (HbA1c), were extracted from medical records and compared among groups. Clinical characteristics according to Lp(a) quartiles were also studied. Univariate and multivariate regression analysis were used to examine the relationship between serum Lp(a) and DN. Patients with DN had a longer disease duration, higher HbA1c, higher level of Lp(a), and were more likely to have diabetic retinopathy (DR) than those without DN (P < 0.005 for each). With regard to the Lp(a) quartile group, patients with a higher Lp(a) concentration were more likely to have DN and have higher level of HbA1c during the study (P for trend < 0.005 for each). After adjusting for several confounding factors, the development of DN was significantly associated with the serum Lp(a) level (P = 0.026, comparing the 4th vs 1st quartile of Lp(a)) according to multivariate regression analysis. The receiver operating characteristic (ROC) curves for DN development using serum Lp(a) showed that the area under the receiver operating characteristic curves (AUC) was 0.590 (P < 0.001). Findings from this study demonstrated that the DN was independently associated with the serum Lp(a) level in patients with T2DM in this retrospective study.

Heterogeneity of macrophage activation syndrome and treatment progression.

Macrophage activation syndrome (MAS) is a rare complication of autoimmune inflammatory rheumatic diseases (AIIRD) characterized by a progressive and life-threatening condition with features including cytokine storm and hemophagocytosis. Predisposing factors are typically associated with microbial infections, genetic factors (distinct from typical genetically related hemophagocytic lymphohistiocytosis (HLH)), and inappropriate immune system overactivation. Clinical features include unremitting fever, generalized rash, hepatosplenomegaly, lymphadenopathy, anemia, worsening liver function, and neurological involvement. MAS can occur in various AIIRDs, including but not limited to systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), systemic lupus erythematosus (SLE), Kawasaki disease (KD), juvenile dermatomyositis (JDM), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), etc. Although progress has been made in understanding the pathogenesis and treatment of MAS, it is important to recognize the differences between different diseases and the various treatment options available. This article summarizes the cell types and cytokines involved in MAS-related diseases, the heterogeneity, and treatment options, while also comparing it to genetically related HLH.

Efficacy of endovascular therapy for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Background: Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy, particularly intra-arterial vasodilator infusion (IAVI), has emerged as a potential alternative treatment for CV. Methods: A systematic review and meta-analysis were conducted to compare the efficacy of endovascular therapy with standard treatment in patients with CV following aSAH. The primary outcomes assessed were in-hospital mortality, discharge favorable outcome, and follow-up favorable outcome. Secondary outcomes included major infarction on CT, ICU stay duration, and total hospital stay. Results: Regarding our primary outcomes of interest, patients undergoing intervention exhibited a significantly lower in-hospital mortality compared to the standard treatment group, with the intervention group having only half the mortality risk (RR = 0.49, 95% CI [0.29, 0.83], p = 0.008). However, there were no significant differences between the two groups in terms of discharge favorable outcome (RR = 0.99, 95% CI [0.68, 1.45], p = 0.963) and follow-up favorable outcome (RR = 1.09, 95% CI [0.86, 1.39], p = 0.485). Additionally, there was no significant difference in major infarction rates (RR = 0.79, 95% CI [0.34, 1.84], p = 0.588). It is important to note that patients undergoing endovascular treatment experienced longer stays in the ICU (MD = 6.07, 95% CI [1.03, 11.12], p = 0.018) and extended hospitalization (MD = 5.6, 95% CI [3.63, 7.56], p < 0.001). Subgroup analyses based on the mode of endovascular treatment further supported the benefits of IAVI in lowering in-hospital mortality (RR = 0.5, 95% CI [0.27, 0.91], p = 0.023). Conclusion: Endovascular therapy, particularly IAVI, holds promising potential in reducing in-hospital mortality for patients with CV following aSAH. However, it did not show significant improvement in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate these findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023451741.

Iodine metabolism in urine and breast milk among lactating women with adequate iodine.

BACKGROUND: In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the kidneys and breasts. OBJECTIVE: This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE). METHODS: The 7-day iodine metabolism study was conducted on 41 lactating women with a mean age of 30 years in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined. RESULTS: Iodine metabolism studies were performed for 285 days. The median TII and TIE values were 255 and 263 µg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 µg/d, the BMIER decreased with the increase of the TII (ß, -0.90, 95% CI: -1.08, -0.72). CONCLUSIONS: When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine levels was higher than their BMIE.

DNMT1 regulates human erythropoiesis by modulating cell cycle and endoplasmic reticulum stress in a stage-specific manner.

The dynamic balance of DNA methylation and demethylation is required for erythropoiesis. Our previous transcriptomic analyses revealed that DNA methyltransferase 1 (DNMT1) is abundantly expressed in erythroid cells at all developmental stages. However, the role and molecular mechanisms of DNMT1 in human erythropoiesis remain unknown. Here we found that DNMT1 deficiency led to cell cycle arrest of erythroid progenitors which was partially rescued by treatment with a p21 inhibitor UC2288. Mechanically, this is due to decreased DNA methylation of p21 promoter, leading to upregulation of p21 expression. In contrast, DNMT1 deficiency led to increased apoptosis during terminal stage by inducing endoplasmic reticulum (ER) stress in a p21 independent manner. ER stress was attributed to the upregulation of RPL15 expression due to the decreased DNA methylation at RPL15 promoter. The upregulated RPL15 expression subsequently caused a significant upregulation of core ribosomal proteins (RPs) and thus ultimately activated all branches of unfolded protein response (UPR) leading to the excessive ER stress, suggesting a role of DNMT1 in maintaining protein homeostasis during terminal erythroid differentiation. Furthermore, the increased apoptosis was significantly rescued by the treatment of ER stress inhibitor TUDCA. Our findings demonstrate the stage-specific role of DNMT1 in regulating human erythropoiesis and provide new insights into regulation of human erythropoiesis.