METTL3/IGF2BP1 influences the development of non-small-cell lung cancer by mediating m6A methylation modification of TRPV1.

BACKGROUND: Methyltransferase 3 (METTL3) accelerates N6-methyladenosine (m6A) modifications and affects cancer progression, including non-small-cell lung cancer (NSCLC). In this study, we aimed to explore the regulatory mechanisms of METTL3 underling NSCLC. METHODS: Immunohistochemical assay, quantitative real-time polymerase chain reaction (qRT-PCR) assay, and western blot assay were conducted for gene expression. MTT assay and colony formation assay were performed to explore cell proliferation capacity. Cell apoptosis and THP-1 cell polarization were estimated by flow cytometry analysis. Cell migration and invasion capacities were evaluated by transwell assay. Methylated RNA immunoprecipitation assay, dual-luciferase reporter assay, actinomycin D treatment and RIP assay were performed to analyze the relationships of METTL3, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), and transient receptor potential cation channel subfamily V member 1 (TRPV1). The functions of METTL3 and TRPV1 in vivo were investigated through establishing the murine xenograft model. RESULTS: TRPV1 expression was upregulated in NSCLC and related poor prognosis. TRPV1 silencing inhibited NSCLC cell growth and metastasis, induced NSCLC cell apoptosis, and repressed M2 macrophage polarization. The results showed that METTL3 and IGF2BP1 could regulate TRPV1 expression through m6A methylation modification. Moreover, METTL3 deficiency inhibited NSCLC cell growth, metastasis, and M2 macrophage polarization and facilitated NSCLC cell apoptosis, while TRPV1 overexpression restored the impacts. In addition, METTL3 knockdown restrained tumor growth in vivo via regulating TRPV1 expression. CONCLUSION: METTL3 bound to IGF2BP1 and enhanced IGF2BP1's m6A recognition of TRPV1 mRNA, thereby promoting NSCLC cell growth and metastasis, and inhibiting M2 macrophage polarization.

Reactivity against the BP180 ectodomain in patients with bullous pemphigoid, mucous membrane pemphigoid, multiple sclerosis and Parkinson disease.

The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%-90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti-BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti-NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His-tagged proteins covering the entire BP180 ectodomain (BP180(ec)1-4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A-negative pemphigoid patients.

Alignment Prediction of Air Spring Vibration Isolation System for Marine Shafting Based on Genetic Algorithm-Back Propagation Neural Network.

Shafting alignment plays an important role in the marine propulsion system, which affects the safety and stability of ship operation. Air spring vibration isolation systems (ASVISs) for marine shafting can not only reduce mechanical noise but also help control alignment state by actively adjusting air spring pressures. Alignment prediction is the first and a key step in the alignment control of ASVISs. However, in large-scale ASVISs, due to factors such as strong interference and raft deformation, alignment prediction faces problems such as alignment measurement sensors failure and difficulty in establishing a mathematical model. To address this problem, a data model for predicting alignment state is developed based on a back propagation (BP) neural network, fully taking advantage of its self-learning and self-adaption abilities. The proposed model exploits the collected data in the ASVIS instead of the alignment measurement data to calculate the alignment state, providing another alignment prediction approach. Then, in order to solve the local optimum issue of BP neural network, we introduce the genetic algorithm (GA) to optimize the weights and thresholds of the BP neural network, and an improved GA-BP model is designed. The GA-BP model can leverage the advantages of the global search capability of GA as well as the BP neural network's fast convergence in local search. Finally, we conduct experiments on a real ASVIS and evaluate the prediction models using different criteria. The experimental results show that the proposed prediction model with the GA-BP neural network can accurately predict the alignment state, with a mean-square error (MSE) of 0.0114. And compared to the BP neural network, the GA-BP neural network reduces the MSE by approximately 74%.

Live Cell Protein Imaging of Tandem Complemented-GFP11-Tagged Coiled-Coil Domain-Containing Protein-124 Identifies this Factor in G3BP1-Induced Stress-Granules.

Coiled-coil domain-containing 124 protein is a multifunctional RNA-binding factor, and it was previously reported to interact with various biomolecular complexes localized at diverse subcellular locations, such as the ribosome, centrosome, midbody, and nucleoli. We aimed to better characterize the subcellular CCDC124 translocation by labelling this protein with a fluorescent tag, followed by laser scanning confocal microscopy methods. As traditional GFP-tagging of small proteins such as CCDC124 often faces limitations like potential structural perturbations of labeled proteins, and interference of the fluorescent-tag with their endogenous cellular functions, we aimed to label CCDC124 with the smallest possible split-GFP associated protein-tagging system (GFP11/GFP1-10) for better characterization of its subcellular localizations and its translocation dynamics. By recombinant DNA techniques we generated CCDC124-constructs labelled with either single of four tandem copies of GFP11 (GFP11 × 1::CCDC124, GFP11 × 4::CCDC124, or CCDC124::GFP11 × 4). We then cotransfected U2OS cells with these split-GFP constructs (GFP11 × 1(or X4)::CCDC124/GFP1-10) and analyzed subcellular localization of CCDC124 protein by laser scanning confocal microscopy. Tagging CCDC124 with four tandem copies of a 16-amino acid short GFP-derived peptide-tag (GFP11 × 4::CCDC124) allowed better characterization of the subcellular localization of CCDC124 protein in our model human bone osteosarcoma (U2OS) cells. Thus, by this novel methodology we successfully identified GFP11 × 4::CCDC124 molecules in G3BP1-overexpression induced stress-granules by live cell protein imaging for the first time. Our findings propose CCDC124 as a novel component of the stress granule which is a membraneless organelle involved in translational shut-down in response to cellular stress.

Cumulative Dose from Recurrent CT Scans: Exploring the DNA Damage Response in Human Non-Transformed Cells.

Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number.

Prediction of frequency response of sub-frame bushing and study of high-order fractional derivative viscoelastic model.

This paper presents experimental and dynamic modeling research on the rubber bushings of the rear sub-frame. The Particle Swarm Optimization algorithm was utilized to optimize a Backpropagation (BP) neural network, which was separately trained and tested across two frequency ranges: 1-40 Hz and 41-50 Hz, using wideband frequency sweep dynamic stiffness test data. The testing errors at amplitudes of 0.2 mm, 0.3 mm, and 0.5 mm were found to be 1.03%, 3.05%, and 1.96%, respectively. Subsequently, the trained neural network was employed to predict data within the frequency range of 51-70 Hz. To incorporate the predicted data into simulation software, a dynamic model of the rubber bushing was established, encompassing elastic, friction, and viscoelastic elements. Additionally, a novel model, integrating high-order fractional derivatives, was proposed based on the frequency-dependent model for the viscoelastic element. An enhanced Particle Swarm Optimization algorithm was introduced to identify the model's parameters using the predicted data. In comparison to the frequency-dependent model, the new model exhibited lower fitting errors at various amplitudes, with reductions of 3.84%, 3.61%, and 5.49%, respectively. This research establishes a solid foundation for subsequent vehicle dynamic modeling and simulation.

Comparison of long-term clinical outcomes of bioabsorbable polymer versus durable polymer drug-eluting stents: a systematic review and meta-analysis.

BACKGROUND: One million individuals in the USA die from acute myocardial infarction (MI), which currently affects 3 million people globally. The available data about the early and late outcomes of both biodegradable polymer drug-eluting stents (BP-DES) and durable polymer drug-eluting stents exhibit inconsistency. We performed a meta-analysis comparing the safety and efficacy of BP-DES with DP-DES. METHODS: PubMed, Google Scholar, EMBASE, Cochrane, Ovid Medline, and Clinical Trials.gov databases were used to find out studies comparing BP-DES to DP-DES. All the analyses used the random-effects model. RESULTS: A total of 18 studies were incorporated in this meta-analysis that involved 28,874 patients, out of which 11,997 received the BP Stent, and the rest of 16,578 received the DP stent. Thorough analyses revealed that the risk of all-cause death was significantly higher in the BP-DES group (5.4% vs 2.7%) (RR 1.22, p 0.02) for two years or less than two-year follow-up. For studies with more than two years of follow-up, all-cause death was 9.07% (599/6603) in BP-DES and 9.47% (531/5602) in the DP-DES group but failed to achieve statistically significant levels (RR 0.97, p 0.58). CONCLUSIONS: The study revealed no clinically significant (P value was > 0.05) differences in all-cause death, cardiac death, target lesion revascularization (TLR), late stent thrombosis, device-oriented composite endpoint/target lesion failure (DOCE/TLF), myocardial infarction (MI), target vessel MI, target vessel revascularization (TVR), target vessel infarction (TVI) between BP-DES and DP-DES for more than two years of follow-up. Additionally, all-cause death was only outcomes which found to have a statistically significant difference for less than two years of follow-up, while remaining were statistically non-significant.

LncRNA SNHG5/IGF2BP1/Occludin axis regulates Nd2O3 induced blood-testis barrier disruption.

Neodymium oxide (Nd2O3) is a rare earth element that can lead to various type of tissue and organ damage with prolonged exposure. The long noncoding RNA small nucleolar ribonucleic acid host gene 5 (lncRNA SNHG5) plays a role in disease progressiong. However, its connection with Nd2O3 induced reproductive harm in males has not been thoroughly investigated. Our research discovered that exposure to Nd2O3 increases the expression of SNHG5 in the testes of mice, which in turn binds directly to and reduces in the protein levels of insulin like growth factor 2 mRNA-binding protein 1 (IGF2BP1) both in vivo and in vitro. This process disrupts the cytoskeleton of blood-testis barrier(BTB) by impacting the stability of the tight junction protein Occludin (Ocln) mRNA structure and the permeability of the BTB. In summary, our study elucidates the regulatory mechanism of SNHG5/IGF2BP1/Occludin axis in Nd2O3-induced BTB injury, providing valuable insights for the treatment of male infertility.

Pharmacokinetics, Safety, Tolerability, and Immunogenicity of BP02 (Trastuzumab Biosimilar) Compared to EU- and US-Approved Trastuzumab in Healthy Adult Male Volunteers: A Phase 1, Randomized, Double-Blind Study.

INTRODUCTION: This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab). METHODS: In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria. RESULTS: Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies. CONCLUSION: This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab. TRIAL REGISTRATION: ANZCTR number: ACTRN12621000573853.

Identification of key biomarkers for early warning of diabetic retinopathy using BP neural network algorithm and hierarchical clustering analysis.

Diabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence. In this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through back propagation neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease. The key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation. The key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.

Prevalence and risk factors for atypical femoral fracture among Lebanese patients with hip and shaft fractures.

This retrospective study investigates the prevalence of atypical femoral fractures (AFFs) among patients admitted with hip and shaft fractures at a tertiary referral center in Beirut, Lebanon. We analyzed electronic medical records and radiology studies of patients aged above 40 admitted with hip and shaft fractures between January 2006 and December 2019. Fractures were confirmed by ICD9 or ICD10 codes. All cases were reviewed by radiologists, and AFFs were identified according to the 2013 revised ASBMR criteria. We identified 1366 hip and shaft fracture patients, of which 14 female patients had 19 AFFs. This represents a prevalence of 1.0% among all hip and shaft fractures patients and 1.7% among all female hip and shaft fracture patients. Bilateral AFFs were found in 5 of the 14 patients. Patients with AFF tended to be younger, with a mean age of 74.3 (±8.6) yr compared to 78.0 (±10.6) for patients with non-AFF fractures. A total of 36% of AFF patients had a prior history of non-traumatic fracture at first admission. A high percentage of patients with AFFs reported intake of proton pump inhibitors (42.9%) and glucocorticoids (21.4%). Bisphosphonate exposure was noted in 64.3% of AFF patients. None of the AFF patients were active smokers or consumed alcohol regularly. BMD assessments were available for 7 AFF patients, indicating osteoporosis in 4 and osteopenia in 3 cases. Hip axis length measurements showed no significant difference between AFF patients (N = 7) and sex and age-matched controls (N = 21). The study underlines the prevalence and characteristics of AFFs in Lebanon, which is consistent with the numbers reported in the literature (0.32%-5%). A larger prospective study that includes hospitals across the nation is needed to gain a more comprehensive view of the prevalence of AFFs in the Lebanese population.

Mmu_circ_0005373 and hsa_circ_0136255 participate in the pulmonary fibrosis of systemic sclerosis.

The pathogenesis of SSc pulmonary fibrosis is complex and prognosis is poor. In order to find biomarkers to provide assistance in the diagnosis and treatment of systemic sclerosis (SSc), this study explored the role of SSc-related differentially expressed circRNAs in the fibrosis process. This study explored whether circular RNA (circRNA) mediated the mTOR signaling pathway by interacting with the eukaryotic translation initiation factor eIF4E-binding protein 1 (4E-BP1), participated in a competing endogenous RNA (ceRNA) network, and regulated the mechanism of pulmonary fibrosis in systemic sclerosis (SSc). The results showed that the expression of mmu_circ_0005373 was reduced, and mmu_circ_0005373 may regulate the mTOR signaling pathway by inhibiting the interacting with 4E-BP1 protein in the lung of SSc mice, and promote fibrosis in SSc. Hsa_circ_0136255, which is homologous to mmu_circ_0005373, is also reduced in SSc peripheral blood mononuclear cells, and predicted to interact with 4E-BP1 protein. Hsa_circ_0136255/hsa-miR-330-3p/TNFAIP3 ceRNA network had biological significance in SSc, and correlated with clinical data, including high-resolution CT, average expiratory flow at 25% vital capacity, neutrophil count, lymphocyte percentage, standard deviation of red blood cell distribution width, coefficient of variation of red blood cell distribution width, platelet distribution width, glutamic transaminase, γ-glutamyl transpeptidase, lymphocyte percentage, basophils percentage, red blood cell, plateletcrit, cholinesterase, and mean corpuscular hemoglobin concentration. Hsa_circ_0136255, hsa-miR-330-3p, and TNFAIP3 may be used as biomarkers for clinical diagnosis and treatment of SSc.

IGF2BP3 participates in the pathogenesis of recurrent spontaneous abortion by regulating ferroptosis.

The aberrant invasive capability of trophoblast cells is widely acknowledged as a primary mechanism underlying RSA. Recently, IGF2BP3 has been implicated in various cancers due to its influence on cellular invasion and migration. However, whether IGF2BP3 involve in the occurrence of RSA and the specific functions it assumes in the development of RSA remain elusive. In our study, we firstly collected villous tissues from RSA and those with normal pregnancies individuals to performed Protein sequencing and then detected the expression of IGF2BP3 through Western blot, qRT-PCR and immunohistochemistry. Secondly, we analyzed the single-cell data (GSE214607) to assess the expression of IGF2BP3 in invasive EVT trophoblasts. Thirdly, we utilized lentivirus technology to establish HTR-8/SVneo cell lines with stable IGF2BP3 knockdown and RNA-seq analysis was employed to investigate the GO functional pathway enrichment of IGF2BP3. Meanwhile, the effect of IGF2BP3 knockdown on trophoblast cells apoptosis, migration, and ferroptosis was evaluated through functional experiments. Additionally, LPS-induced abortion animal model was constructed to evaluate IGF2BP3 expression in placental tissues. A significant downregulation of IGF2BP3 was observed in the villous tissues of RSA patient, a finding corroborated by subsequent single cell sequencing results. Furthermore, it suggested that IGF2BP3 may be involved in the migration and apoptotic processes of trophoblast cells. Mechanistic research indicated that IGF2BP3 knockdown could compromise GPX4 mRNA stability, leading to the promotion of ferroptosis. Finally, our investigation observed the down-regulation of IGF2BP3 expression in placental villous tissues of an LPS-induced abortion animal model. Our findings revealed that IGF2BP3 was downregulated in the villous tissues of RSA patients. Mechanically, down-regulation of IGF2BP3 may induce RSA by promoting GPX4-mediated ferroptosis and inhibiting trophoblast invasion and migration. Our study may provide new targets and research directions for the pathogenesis of RSA.

High Muscle Expression of IGF2BP1 Gene Promotes Proliferation and Differentiation of Chicken Primary Myoblasts: Results of Transcriptome Analysis.

Muscle development is a multifaceted process influenced by numerous genes and regulatory networks. Currently, the regulatory network of chicken muscle development remains incompletely elucidated, and its molecular genetic mechanisms require further investigation. The Longsheng-Feng chicken, one of the elite local breeds in Guangxi, serves as an excellent resource for the selection and breeding of high-quality broiler chickens. In this study, we conducted transcriptome sequencing of the pectoral muscles of Longsheng-Feng chickens and AA broiler chickens with different growth rates. Through comprehensive bioinformatics analysis, we identified differentially expressed genes that affect muscle growth and showed that IGF2BP1 is a key participant in chicken muscle development. Subsequently, we employed QRT-PCR, EdU staining, and flow cytometry to further investigate the role of IGF2BP1 in the proliferation and differentiation of chicken myogenic cells. We identified 1143 differentially expressed genes, among which IGF2BP1 is intimately related to the muscle development process and is highly expressed in muscle tissues. Overexpression of IGF2BP1 significantly promotes the proliferation and differentiation of chicken primary myoblasts, while knockdown of IGF2BP1 significantly inhibits these processes. In summary, these results provide valuable preliminary insights into the regulatory roles of IGF2BP1 in chicken growth and development.

Aberrant expression of LGALS3BP drives an unfavorable prognosis and more aggressive in HCC via regulating PI3K/AKT signaling.

Lectin galactoside-binding soluble 3-binding protein (LGALS3BP) is associated with cancer metastasis and is a promising prognostic marker in neoplasms. In hepatocellular carcinoma (HCC), the prognostic impact and pro-metastatic function of LGALS3BP remain unclear. This study evaluated the endogenous LGALS3BP expression in HCC tissue and its association with prognosis. LGALS3BP protein levels were significantly elevated in clinical HCC tissues and cell lines. Increased LGALS3BP expression was closely associated with disease progression in HCC patients, and they also exhibited an unfavorable prognosis. Furthermore, the knockdown of LGALS3BP inhibited the growth, migration, and invasion of HCC cells in vitro. In mice xenografts, silencing LGALS3BP significantly inhibited tumor cell growth in vivo. Mechanically, upon LGALS3BP depletion, the tumor-suppressive function was dependent on inactivating Phosphatidylinositol 3-kinase (PI3K)/V-akt murine thymoma viral oncogene homolog (AKT) signaling pathway. Collectively, these findings suggest that LGALS3BP employs a pro-tumorigenic function in HCC and may be a promising HCC prognostic marker.

Mercury concentrations in Seaside Sparrows and Marsh Rice Rats differ across the Mississippi River Estuary.

Mercury (Hg) concentrations and their associated toxicological effects in terrestrial ecosystems of the Gulf of Mexico are largely unknown. Compounding this uncertainty, a large input of organic matter from the 2010 Deepwater Horizon oil spill may have altered Hg cycling and bioaccumulation dynamics. To test this idea, we quantified blood concentrations of total mercury (THg) in Seaside Sparrows (Ammospiza maritima) and Marsh Rice Rats (Oryzomys palustris) in marshes west and east of the Mississippi River in 2015 and 2016. We also tested for a difference in THg concentrations between oiled and non-oiled sites. To address the potential confounding effect of diet variation on Hg transfer, we used stable nitrogen (δ15N) and carbon (δ13C) isotope values as proxies of trophic position and the source of primary production, respectively. Our results revealed that five to six years after the spill, THg concentrations were not higher in sites oiled by the spill compared to non-oiled sites. In both species, THg was higher at sites east of the Mississippi River compared to control and oiled sites, located west. In Seaside Sparrows but not in Marsh Rice Rats, THg increased with δ15N values, suggesting Hg trophic biomagnification. Overall, even in sites with the most elevated THg, concentrations were generally low. In Seaside Sparrows, THg concentrations were also lower than previously reported in this and other closely related passerines, with only 7% of tested birds exceeding the lowest observed effect concentration associated with toxic effects across bird species (0.2 µg/g ww). The factors associated with geographic heterogeneity in Hg exposure remain uncertain. Clarification could inform risk assessment and future restoration and management actions in a region facing vast anthropogenic changes.

Masked phenomenon: renal and cardiovascular complications; review and updates.

BACKGROUND: In the in-clinic blood pressure (BP) recording setting, a sizable number of individuals with normal BP and approximately 30% of patients with chronic renal disease (CKD) exhibit elevated outpatient BP records. These individuals are known as masked hypertension (MHTN), and when they are on antihypertensive medications, but their BP is not controlled, they are called masked uncontrolled hypertension (MUHTN). The masked phenomenon (MP) (MHTN and MUHTN) increases susceptibility to end-organ damage (a two-fold greater risk for cardiovascular events and kidney dysfunction). The potential extension of the observed benefits of MP therapy, including a reduction in end-organ damage, remains questionable. AIM AND METHODS: This review aims to study the diagnostic methodology, epidemiology, pathophysiology, and significance of MP management in end-organs, especially the kidneys, cardiovascular system, and outcomes. To achieve the purposes of this non-systematic comprehensive review, PubMed, Google, and Google Scholar were searched using keywords, texts, and phrases such as masked phenomenon, CKD and HTN, HTN types, HTN definition, CKD progression, masked HTN, MHTN, masked uncontrolled HTN, CKD onset, and cardiovascular system and MHTN. We restricted the search process to the last ten years to search for the latest updates. CONCLUSION: MHTN is a variant of HTN that can be missed if medical professionals are unaware of it. Early detection by ambulatory or home BP recording in susceptible individuals reduces end-organ damage and progresses to sustained HTN. Adherence to the available recommendations when dealing with masked phenomena is justifiable; however, further studies and recommendation updates are required.

Blood pressure tells us how much force the heart exerts on the blood vessels as it pumps blood. Normal blood pressure should be 120/80 mmHg, which generally decreases when a person is sleeping or sitting. High blood pressure or hypertension occurs when the blood pressure is too high. Hidden or masked hypertension (MH) is a type of high blood pressure. Masked hypertension was described as having high blood pressure readings even though the doctor's office or in-clinic showed normal blood pressure readings.This review aimed to teach people about various kinds of high blood pressure, focusing on hidden (masked) hypertension and how to recognise it, as well as its consequences, treatment, and new information.

CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription.

BACKGROUND: Recurrent or metastatic cervical cancer have an extremely low 5-year survival rates about 17% due to limited therapeutic options. CDYL plays a critical role in multiple cancer development, as an oncogene or tumor suppressor in a context-dependent manner. However, the role of CDYL in cervical carcinogenesis has not yet been explored. METHODS: CDYL expression was examined in cervical cancer and cell lines. The effect of CDYL/IRF2BP2/PD-L1 axis on malignant phenotypes of cervical cancer cells were tested with gain-of-function experiments. A mouse model of cervical cancer was developed to validate the in vitro results. RESULTS: Clinical data analysis revealed that CDYL was downregulated and associated with a poor prognosis in cervical cancer patients. CDYL overexpression suppressed cervical cancer cells proliferation and invasion in vitro and vivo assays and enhanced the immune response by decreasing PD-L1 expression and reversing the tumor immunosuppressing microenvironment. Mechanistically, CDYL inhibited the PD-L1 expression through transcriptionally suppressing IRF2BP2 in cervical cancer cells. CONCLUSIONS: Taken together, our findings established the crucial role of CDYL in cervical carcinogenesis and sensitivity for immune checkpoint blockade therapy, and supported the hypothesis that CDYL could be a potential novel immunotherapy response predictive biomarker for cervical cancer patients.

Novel strategy for optimizing of corn starch-based ink food 3D printing process: Printability prediction based on BP-ANN model.

Although starch has been intensively studied as a raw material for 3D printing, the relationship between several important process parameters in the preparation of starch gels and the printing results is unclear. In this study, the relationship between different processing conditions and the gel printing performance of corn starch was evaluated by printing tests, rheological tests and low-field nuclear magnetic resonance (LF-NMR) tests, and a back-propagation artificial neural network (BP-ANN) model for predicting gel printing performance was developed. The results revealed that starch gels exhibited favorable printing performance when the gelatinization temperature ranged from 75 °C to 85 °C, and the starch content was maintained between 15 % and 20 %. The R2adj of the BP-ANN models were all reached 0.894, which indicated good predictive ability. The results of the study not only provide theoretical support for the application of corn starch gels in 3D food printing, but also present a novel approach for predicting the printing performance of related materials. This method contributes to the optimization of printing parameters, thereby enhancing printing efficiency and quality.

The changes prediction on terrestrial water storage in typical regions of China based on neural networks and satellite gravity data.

Accurate prediction of regional terrestrial water storage change (TWSA) is of great significance for water resources planning and management, and early warning of extreme climate disasters. Aiming at the problem that the conventional methods on prediction of TWSA time series are difficult to be accurate, the six typical regions are selected in China as examples, including the upper reaches of the Yangtze River (UYR), the southwest region (SWR), the Liaohe River Basin (LRB), the North China Plain (NCP), the Qinghai-Tibet Plateau (QTP), and the Pearl River Basin (PRB). The mascon product from GRACE/GRACE-FO provided by CSR is used to extract TWSA time series in six typical areas. The improved Back Propagation (BP) neural network, Long Short-Term Memory (LSTM) neural network and the latest Bidirectional LSTM (BiLSTM-attention) neural network model based on attention mechanism are proposed to predict and analyze the regional TWSA. In the experiment, the selection of the optimal model parameters such as the number of hidden layer nodes and the number of hidden units of the neural network model is tested and analyzed in detail. Meanwhile, the model prediction results are compared with the traditional least squares method and random forest (RF) prediction method. The root mean square error (RMSE), determination coefficient (R2), Nash-Sutcliffe efficiency coefficient (NSE) and mean absolute percentage error (MAPE) were used to evaluate the accuracy of the predicted results. The results show that the improved BP, LSTM and Bi-LSTM-attention neural network models all achieve higher prediction accuracy in UYR and SWR areas. RMSE is less than 2.641 cm, R2 is as high as 0.8 or more, NSE is above 0.6, and MAPE is within 0.1. Compared with the least square method, the RMSE of the predicted results from three neural network decreased by 0.998 cm, 0.700 cm and 0.7563 on average, and the R2 increased by 81.75%, 69.89% and 72% on average. Compared with RFML method, the RMSE from three neural network is reduced by 0.601 cm, 0.316 cm and 0.360, and R2 is increased by 38.20%, 24.60% and 27.06% on average. NSE and RMSE are improved to varying degrees in the above regions. It shows that the improved BP, LSTM and BiLSTM-attention model used can effectively predict TWSA. The research methods and results in this paper can provide important reference for the rational utilization of regional water resources and disaster risk assessment.