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Ocean winds in the Baltic Sea are expected to power many wind farms in the coming years. This study examines satellite Synthetic Aperture Radar (SAR) images from Envisat ASAR for mapping wind resources with high spatial resolution. Around 900 collocated pairs of wind speed from SAR wind maps and from 10 meteorological masts, established specifically for wind energy in the study area, are compared. The statistical results comparing in situ wind speed and SAR-based wind speed show a root mean square error of 1.17 m s−1, bias of −0.25 m s−1, standard deviation of 1.88 m s−1 and correlation coefficient of R2 0.783. Wind directions from a global atmospheric model, interpolated in time and space, are used as input to the geophysical model function CMOD-5 for SAR wind retrieval. Wind directions compared to mast observations show a root mean square error of 6.29° with a bias of 7.75°, standard deviation of 20.11° and R2 of 0.950. The scale and shape parameters, A and k, respectively, from the Weibull probability density function are compared at only one available mast and the results deviate ~2% for A but ~16% for k. Maps of A and k, and wind power density based on more than 1000 satellite images show wind power density values to range from 300 to 800 W m−2 for the 14 existing and 42 planned wind farms.

Abstract Introduction Dental caries is one of the most prevalent chronic diseases of childhood. Early childhood caries (ECC), defined as onset of dental caries before 6 years of age, is preventable and reversible in the early stages with proper interventions. The purpose of the study is to assess the clinical effectiveness and cost-effectiveness of technology-enabled anticipatory guidance and peer support in empowering parents to establish good diets, feeding and oral hygiene practices to prevent ECC. Methods and analysis Mother-child dyads will be recruited from pre-natal clinics and post-natal wards of a tertiary care hospital in Singapore. The control group will receive conventional oral health education materials while the intervention group will join four rounds of online parent empowerment sessions focusing on anticipatory guidance and peer-support. Mothers will complete a questionnaire and food frequency checklist when their child turns 12, 24 and 36 months; each child will undergo an oral examination at the age of 24 and 36 months. Chi-square tests and two-sample t-tests, or their non-parametric equivalents will be used to compare proportions of children with caries by decayed, missing and filled teeth (dmft) and decayed, missing and filled surfaces (dmfs) scores between groups. Effect sizes and their confidence intervals will be calculated along with number needed to treat. Multivariable analyses will be carried out to assess the effect of the intervention on primary outcomes (caries incidence at 24 and 36 months) and secondary outcomes (including parental efficacy, child’s oral health behaviours and oral hygiene status, quality of life). Cost-effectiveness analyses will also be carried out. Ethics and dissemination The study was approved by Domain Specific Review Board (DSRB 2024/00244). Results will be published in international peer-reviewed journals. Trial registration number The trial was retrospectively registered on ClinicialTrials.gov (NCT06558955) around the time of the commencement of patient recruitment, but prior to the commencement of any intervention.

Abstract Background Fetal growth monitoring is important for twin pregnancies. However, there has been no clinically validated tool for monitoring fetal growth of twin pregnancies in China. This study aims to develop and validate a chorionicity-specific growth chart of ultrasound estimated fetal weight (EFW) for Chinese twin pregnancies. Methods This retrospective cohort study included all twin pregnancies who delivered two live fetuses with gestational age ≥ 34 weeks without severe obstetric complications at a tertiary hospital from January 2007 to March 2021. The participants were divided into a development set (delivered in or before December 2017) and a validation set (delivered in or after January 2018). Chorionicity-specific growth charts were created using the generalized additive models for location, scale, and shape (GAMLSS) based on the development set. The fetuses from the validation set were classified into three groups based on the last EFW: small-for-gestational-age (SGA) indicated by both the newly established twin charts and the Hadlock singleton chart currently used for twin pregnancies in China, suspected SGA indicated by only the singleton chart, and no SGA indicated by either chart. The incidence of neonatal outcomes among the three groups was then compared accordingly, including intensive care unit (NICU) stay length, respiratory diseases, and neurological disorders. Results The development set included 883 twin pregnancies and a total of 6374 EFW measurements between 16 and 38 weeks of gestation, and the validation set included 801 twin pregnancies and 7630 EFW measurements. In the development set, monochorionic diamniotic (MCDA) twins had a significantly lower EFW compared to dichorionic diamniotic (DCDA) twins beginning at 26 weeks, with the difference gradually increasing thereafter, supporting the establishment of chorionicity-specific growth charts. Of the 1,602 twin neonates in the validation set, 103 (6.4%) were classified into the SGA group, 164 (10.2%) into the suspected SGA group, and 1335 (83.3%) into the no SGA group. The incidence of respiratory diseases and neurological disorders was comparable between the suspected SGA group and the no SGA group, but apparently higher in the SGA group. Meanwhile, NICU stay lengths were consistently longer for twins in the SGA group compared to the no SGA group (difference: 0.57, 95% CI: 0.31–0.83), with no significant differences observed between the suspected SGA and no SGA groups. Conclusions The fetal growth trajectories differed by chorionicity, with a lower EFW for MCDA twins beginning at 26 weeks. The establishment of chorionicity-specific growth chart could reduce overdiagnosis of SGA and improve fetal growth monitoring of twin pregnancies.

Objective: Protein tyrosine phosphatase non-receptor type 6 (PTPN6) is a cytoplasmic phosphatase that acts as a key regulatory protein in cell signaling to control inflammation and cell death. In order to investigate the role of PTPN6 in hematologic tumor myelodysplastic syndrome (MDS), this study infected SKM-1 cell line (MDS cell line) with packaged H_PTPN6-shRNA lentivirus to obtain H_PTPN6-shRNA SKM-1 stable strain. The effect of PTPN6 knockdown on apoptosis, erythroid differentiation, and inflammations in SKM-1 cell line was examined. Methods: The stable knockdown SKM-1 cell line was validated using qPCR and Western blot assays. The proliferation activity, apoptosi, erythroid differentiation, and inflammatory cytokines in SKM-1 cells were assessed before and after transfection. Results: qPCR confirmed that the expression level of H_PTPN6-shRNA in SKM-1 cells was significantly reduced, and Western blot showed that the protein expression level of H_PTPN6-shRNA in SKM-1 cells was also significantly reduced. The CCK-8 cell viability assay confirmed that stable gene knockdown did not affect cell viability. Flow cytometry revealed that the apoptosis rate of cells in the PTPN6 knockdown group was 0.8%, lower than the 2.7% observed in the empty plasmid group; the expression rate of the erythroid differentiation marker CD235a was 13.2%, lower than the 25.0% observed in the empty plasmid group. The expression levels of the proinflammatory factors IL-6 and IL-8 increased, and the expression levels of the inhibitor factor IL-4 decreased. Conclusions: The PTPN6 gene was successfully knocked down using lentivirus-mediated transduction, and the constructed cell line was validated using PCR and Western blot. The CCK-8 cell viability assay confirmed that stable gene knockdown did not affect cell proliferation viability. Flow cytometry analysis of apoptosis and erythroid differentiation indicated that PTPN6 knockdown inhibits apoptosis and erythroid differentiation in SKM-1 cells and also alters the level of inflammations in the bone marrow microenvironment. It suggests that the PTPN6 gene acts as a tumor suppressor in myelodysplastic syndrome cells, influencing hematopoietic cell apoptosis, erythroid differentiation, and inflammations. This provides a reliable experimental basis for further in-depth studies on the mechanism of PTPN6 in MDS and related pharmacological research.

Abstract Background Despite coalition resection being the preferred treatment for talocalcaneal coalition (TCC), postoperative complications, suboptimal functional recovery, and recurrence risks remain challenges. Although current TCC classification systems guide personalized surgical plans, the impact of middle and posterior facet coalitions on TCC resection surgery’s effectiveness is still poorly understood. Therefore, this study aims to compare the clinical outcomes of TCC patients with and without involvement of the subtalar joint’s (STJ) middle and posterior facets undergoing coalition resection to explore the potential impact of these coalitions on surgical outcomes. Methods We conducted a retrospective study on 115 patients who underwent coalition resection surgery due to symptomatic TCC between November 2009 and February 2023. According to preoperative CT scan results, patients were divided into an isolated posterior facet coalition (P-type) group and a middle-posterior facet coalition (MP-type) group. Demographic characteristics (including age, sex, body mass index (BMI), follow-up time, and medical history duration), pre-and postoperative assessments (including Visual Analog Scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Pain Interference (PI) and Physical Function (PF) scores from the Patient-Reported Outcomes Measurement Information System (PROMIS)), as well as postoperative self-assessment of efficacy (excellent, good, fair, poor) and hindfoot stiffness, were compared between the two groups. Postoperatively, TCC recurrence was evaluated through imaging follow-up examinations. Results 69 patients meeting the inclusion criteria were included, with 30 patients in the P-type group and 39 in the MP-type group. There were no statistically significant differences between the two groups in demographic characteristics (P

Abstract Pyroptosis, a typical inflammatory cell death mode, has been increasingly demonstrated to have therapeutic value in inflammatory diseases such as sepsis. However, the mechanisms and therapeutic targets of sepsis remain elusive. Here, we reported that REGγ inhibition promoted pyroptosis by regulating members of the gasdermin family in macrophages. Mechanistically, REGγ directly degraded Bim, a factor of the Bcl-2 family that can inhibit the cleavage of GSDMD/E, ultimately preventing the occurrence of pyroptosis. Furthermore, cecal ligation and puncture (CLP)-induced sepsis model mice showed downregulation of REGγ at both the RNA and protein levels. Gasdermin-mediated pyroptosis was augmented in REGγ-knockout mice, and these mice exhibited more severe sepsis-related tissue injury. More importantly, we found that REGγ expression was downregulated in clinical sepsis samples, such as those from patients with Pseudomonas aeruginosa (PA) infection. Finally, PA-infected mice showed decreased REGγ levels in the lung. In summary, our study reveals that the REGγ-Bim-GSDMD/E pathway is a novel regulatory mechanism of pyroptosis in sepsis-related tissue injury.

Abstract Purpose The characteristic of RENT3B in cancer remains ambiguous. We aimed to study the relationship between RENT3B and immune infiltration in liver hepatocellular carcinoma (LIHC) and lung squamous cell carcinoma (LUSC). Patients and methods We investigated the expression levels of RENT3B using ONCOMINE and TIMER databases, and assessed the interrelationship between RENT3B expression and survival using PrognoScan, GEPIA, and Kaplan–Meier plotter. Additionally, we examined the association between RENT3B and immune cells in the tumor microenvironment (TME), as well as markers of immune cells, using TIMER. Subsequently, we performed prognostic analysis based on the expression level of RENT3B within specific immune cell subgroups. Furthermore, we evaluated the promoter methylation profile of RENT3B between tumor and normal tissues in LIHC and LUSC using the DNMIVD database. Results RENT3B exhibited increased levels in both in LIHC and LUSC. High RENT3B expression was associated with unfavorable prognosis in LIHC, whereas it indicated a beneficial prognosis in LUSC. In LIHC, the expression of RENT3B positively correlated with immune infiltration levels of B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. However, in LUSC, the expression of RENT3B showed a negative correlation with immune infiltration levels of B cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. RENT3B exhibited positive correlations with 42 immune markers in LIHC, while it displayed negative associations with 10 immune markers in LUSC. Despite variations in immune cell enrichment and reduction subgroups, high RENT3B expression consistently indicated poor prognosis in LIHC, whereas it remained favorable in LUSC. Additionally, there were no significant differences observed in RENT3B promoter methylation between tumor and normal tissues in both LIHC and LUSC. Conclusion RENT3B can affect the overall tumor prognosis and is associated with immune infiltration, especially in LIHC and LUSC. Consequently, RENT3B can become a prognostic biomarker for LIHC and LUSC.

Abstract Background Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Objectives: Thoracic spinal tuberculosis (TB) is still common, and surgical treatment can rapidly relieve pain, correct deformity, reduce bone loss and prevent further damage to neurological function. We have practiced an efficient and safe surgical method. Methods: From January 2013 to April 2021, 38 patients with thoracic spinal TB were included in our study. Debridement and bone grafting were performed via the lateral extracavitary approach, combined with two different fixation methods. Data from these cases were analyzed retrospectively. Results: For all cases, the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) of all the patients decreased to normal levels at the last follow-up. The average visual analog scale (VAS) score was 7.5 ± 1.6 preoperatively and 0.6 ± 0.8 at the last follow-up, showing a significant reduction. The average angle of kyphosis correction was 6.3 ± 4.7°, and the loss of correction was 1.4 ± 1.6°. Neurological function was significantly improved in all cases according to the American Spinal Injury Association (ASIA) classification. Solid fusion was observed in all cases at the last follow-up. Conclusions: Debridement and bone graft fusion via the lateral extracavitary approach combined with two fixation methods can be very effective in the treatment of thoracic spinal TB.

To investigate the impacts of glycation modification on the structure and flavor of fish viscera-derived protein hydrolysates, channel catfish viscera was utilized and hydrolyzed by Flavourzyme, followed by glycation with glucosamine, xylose, ribose and glucose, respectively. The structural characteristics, taste and odor of glycated products were evaluated. The results revealed that glycation led to an increase in peptides (5 kDa). UV and fluorescence spectra indicated a gradual rise in absorbance and fluorescence intensity. Glucosamine-induced glycation significantly mitigated bitterness, while enhancing saltiness and umami. GC–MS/MS analysis revealed that glycation led to reduced undesirable odor, and formation of aromatic compounds. LC-MS/MS identified Arg and Lys as the main modification sites. Interestingly, aldehydes were found to modify peptides via carbonyl-amine reaction, leading to decreased fishy odor. The present study contributes to flavor improvement of fish viscera-derived peptides through glycation and high-value utilization of fish viscera.

Background This research investigates the metabolic profiles of follicular fluid (FF) samples from patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilisation and aims to identify diagnostic and therapeutic biomarkers for PCOS through lipidomic analysis.Methods We performed non-targeted lipid analysis of FF samples from women with PCOS (n = 6) and normal controls (n = 6) using ultra-high-performance liquid chromatography–tandem mass spectrometry. Differential lipids between the two groups were screened using multidimensional statistical analysis, followed by fold change analysis and t-tests to identify potential PCOS biomarkers.Results Multivariate statistical analysis revealed significant differences in FF lipid levels between the PCOS and control groups. Five different lipids were selected as standards, with p

BackgroundCombining genetic risk factors and plasma fatty acids (FAs) can be used as an effective method of precision medicine to prevent hypertension risk.MethodsA total of 195,250 participants in the UK Biobank cohort were included in this study from 2006–2010. Polygenic risk scores (PRSs) were calculated for hypertension using single-nucleotide polymorphisms (SNPs). Concentrations of plasma FAs, including polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs), were tested by nuclear magnetic resonance. The Cox model was used to test for the main effects of PRS, different plasma FAs and their joint effects on hypertension. Relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP) were used to test the additive interaction.ResultsPlasma PUFAs, n-3 PUFAs, MUFAs and SFAs were related to the risk of hypertension (PUFAs: HR, 0.878; 95% CI, 0.868–0.888; MUFAs: HR, 1.13; 95% CI, 1.123–1.150; SFAs: HR, 1.086; 95% CI, 1.074–1.098; n-3 PUFAs: HR, 0.984; 95% CI, 0.973–0.995). Moreover, an additive interaction was found between PRS and plasma FAs, which could contribute to an approximately 10–18% risk of hypertension, and the associations between high plasma MUFAs and a high PRS of hypertension were the strongest positive [RERI: 0.178 (95% CI: 0.062, 0.294), AP: 0.079 (95% CI: 0.027, 0.130)].ConclusionIncreased plasma MUFAs or SFAs and decreased plasma PUFAs or n-3 PUFAs were associated with hypertension risk, especially among people at high genetic risk.

Abstract Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles’ pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles’ pore closure and that clathrin around Ω-profiles’ base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles’ base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin’s well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents’ function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin’s pivotal role in pore constriction/closure.

The deep coaxial borehole heat exchanger (DCBHE) is a highly promising technology which has garnered significant attention. However, there has been a notable scarcity of studies focusing on the physical and mathematical models essential for accurately describing the heat transfer processes involving the DCBHE, well, and rock. This study addresses this gap by employing an improved numerical heat transfer method through programming to conduct an in-depth analysis of the heat transfer performance. The model is solved using the finite volume method (FVM) and validated using experimental data from an existing literature. The simplified effect of pipes and filling material on the heat transfer performance of the DCBHE are analyzed. Furthermore, the characteristics of outlet temperature, heat extraction power, change rate, reduction degree of DCBHE with different operation modes are also analyzed, considering both the heat extraction of one season and 20 years. The results indicate that the simplification of the outer pipe and filling material as thermal resistances is unreasonable while the simplification of inner pipe is acceptable. The maximum outlet water temperature decreases year by year, as the rock-soil temperature fails to recover to its initial level. The water outlet temperature decreases with the run stop ratio while the heat extraction increases. Moreover, the operation mode of 2:2 is recommended both in one heat extraction season and 20 years operation.

Abstract Background Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. Results In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. Conclusions These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.

Abstract Background Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. Results By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. Conclusions Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal–fetal interface formation.

Abstract Background Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance. Methods To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites. Results Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers. Conclusions Our study underscores the critical role of phospholipid metabolism in the brain’s metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

Abstract Background Klippel–Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of two or more cervical vertebrae during early prenatal development. This fusion results from a failure of segmentation during the first trimester. Although six genes have previously been associated with KFS, they account for only a small proportion of cases. Among the distinct subtypes of KFS, “sandwich fusion” involving concurrent fusion of C0-1 and C2-3 vertebrae is particularly noteworthy due to its heightened risk for atlantoaxial dislocation. In this study, we aimed to investigate novel candidate mutations in patients with “sandwich fusion.” Methods We collected and analyzed clinical data from 21 patients diagnosed with “sandwich fusion.” Whole-exome sequencing (WES) was performed, followed by rigorous bioinformatics analyses. Our focus was on the six known KFS-related genes (GDF3, GDF6, MEOX1, PAX1, RIPPLY2, and MYO18). Suspicious mutations were subsequently validated through in vitro experiments. Results Our investigation revealed two novel exonic mutations in the FGFR2 gene, which had not previously been associated with KFS. Notably, the c.1750A > G variant in Exon 13 of FGFR2 was situated within the tyrosine kinase domain of the protein, in close proximity to several established post-translational modification sites. In vitro experiments demonstrated that this certain mutation significantly impacted the function of FGFR2. Furthermore, we identified four heterozygous candidate variants in two genes (PAX1 and MYO18B) in two patients, with three of these variants predicted to have potential clinical significance directly linked to KFS. Conclusions This study encompassed the largest cohort of patients with the unique “sandwich fusion” subtype of KFS and employed WES to explore candidate mutations associated with this condition. Our findings unveiled novel variants in PAX1, MYO18B, and FGFR2 as potential risk mutations specific to this subtype of KFS.

The freshwater lakes in the middle and lower reaches of the Yangtze River (MLYR) have been affected by a multitude of factors, including climate change and human activities, and are currently facing a range of aquatic ecological environment problems. In order to establish restoration goals and paths, it is essential to have a scientific understanding of the historical process and pattern of long-term degradation of the lake ecological environment. This study focused on Shengjin Lake, a representative Yangtze River-connected lake in MLYR. Based on the analysis results of cellulose carbon isotopes (δ13Ccellulose) in modern aquatic macrophytes, the response characteristics of aquatic macrophytes δ13Ccellulose to lake environment evolution were revealed by high-resolution multi-proxy (δ13Ccellulose of plant residues and geochemistry indices) analysis of a sediment core. The study also reconstructed the ecological environment evolution process of Shengjin Lake over the past two hundred years. The primary research findings are as follows: Firstly, the results of the modern process survey demonstrated that the δ13Ccellulose of different modern species exhibited considerable variation. The submerged plants exhibited an enrichment of 13C, while the emergent plants exhibited an enrichment of 12C. Secondly, a comprehensive modern process investigation, coupled with palaeo-limnological records and literature data, led to the conclusion that the large plant residues of sediments were primarily derived from submerged plants. Concurrently, statistical analysis indicated that the content of total organic carbon in lakes was the primary factor influencing the changes in sediment δ13Ccellulose. The composition of δ13Ccellulose may be indicative of changes in lake primary productivity. Finally, the paleo-limnological record revealed that the ecological environment of Shengjin Lake has undergone significant changes over the past two hundred years. In particular, since the 1970 s, the δ13Ccellulose has been significantly enriched by 12C, and the geochemical indexes of elements have shown an increasing trend (p

Neurodegenerative diseases including glaucoma affect insulin signaling, and insulin treatment has been shown to reverse the neurodegenerative loss of dendritic complexity in retinal ganglion cells. Therefore, strategies for enhancing or maintaining insulin signaling are worth pursuing to establish new therapies for these diseases. In the present study, we generated constitutively active insulin receptor (F-iIR) and insulin-like growth factor-1 receptor (F-iIGF1R) using a system that forces membrane localization of the intracellular domains of these receptors by farnesylation. Immunohistochemistry and Western blot analysis revealed that F-iIR and F-iIGF1R caused the activation of ERK and AKT in the absence of ligands in vitro. Our results suggest that in vivo effects of F-iIR and F-iIGF1R on the progression of neurodegenerative diseases should be investigated in the future.

We study the possible effect of climate change on the extreme wind over northern Europe using data from 18 models of the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6) and the high-emission Shared Socioeconomic Pathway 5-8.5 (SSP585) scenario. We use the spectral correction method to correct the 6-hourly wind speeds and calculate the 50-year wind at an equivalent temporal resolution of 10 min, consistent with the International Electrotechnical Commission (IEC) standard. We obtain the possible effect of climate change through the comparison of the extreme wind parameters, including the 50-year wind and the 95%-percentile of the wind speed, and the change in turbine class at 50 m, 100 m and 200 m, between a near future period (2020–2049) and the historic period (1980–2009). The analysis shows an overall increase in the extreme winds in the North Sea and the southern Baltic Sea, but a decrease over the Scandinavian Peninsula and most of the Baltic Sea. However, the suggested change is not significant enough to conclude whether higher or lower classes of turbines will be needed in this area in the future.

ObjectivesQuantitatively assess the severity and predict the mortality of interstitial lung disease (ILD) associated with Rheumatoid arthritis (RA) was a challenge for clinicians. This study aimed to construct a radiomics nomogram based on chest computed tomography (CT) imaging by using the ILD-GAP (gender, age, and pulmonary physiology) index system for clinical management.MethodsChest CT images of patients with RA-ILD were retrospectively analyzed and staged using the ILD-GAP index system. The balanced dataset was then divided into training and testing cohorts at a 7:3 ratio. A clinical factor model was created using demographic and serum analysis data, and a radiomics signature was developed from radiomics features extracted from the CT images. Combined with the radiomics signature and independent clinical factors, a nomogram model was established based on the Rad-score and clinical factors. The model capabilities were measured by operating characteristic curves, calibration curves and decision curves analyses.ResultsA total of 177 patients were divided into two groups (Group I, n = 107; Group II, n = 63). Krebs von den Lungen-6, and nineteen radiomics features were used to build the nomogram, which showed favorable calibration and discrimination in the training cohort [AUC, 0.948 (95% CI: 0.910–0.986)] and the testing validation cohort [AUC, 0.923 (95% CI: 0.853–0.993)]. Decision curve analysis demonstrated that the nomogram performed well in terms of clinical usefulness.ConclusionThe CT-based radiomics nomogram model achieved favorable efficacy in predicting low-risk RA-ILD patients.

Abstract Background The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next‐generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. Methods Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. Results Twenty‐four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN‐positive tumors showed higher mutant allele tumor heterogeneity (p

Abstract This paper investigates Regional Integrated Energy Systems (RIES), emphasizing the connection of diverse energy supply subsystems to address varied user needs and enhance operational efficiency. A novel low-carbon economic dispatch method, utilizing the multi-objective chaotic artificial hummingbird algorithm, is introduced. The method not only optimizes economic and environmental benefits but also aligns with "carbon peak and carbon neutrality" objectives. The study begins by presenting a comprehensive low-carbon economic dispatch model, followed by the proposal of the multi-objective chaotic artificial hummingbird algorithm, crucial for deriving the Pareto frontier of the low-carbon economic dispatch model. Additionally, we introduce a TOPSIS approach based on combined subjective and objective weights, this approach harnesses the objective data from the Pareto solution set deftly, curbs the subjective biases of dispatchers effectively and facilitates the selection of an optimal system operation plan from the Pareto frontier. Finally, the simulation results highlight the outstanding performance of our method in terms of optimization outcomes, convergence efficiency, and solution diversity. Noteworthy among these results is an 8.8% decrease in system operational economic costs and a 14.2% reduction in carbon emissions.

Abstract Background Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit–harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals. Methods We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for

Mirror therapy is proposed to enhance post-stroke awareness of the affected limb and mental ability, but convincing evidence on the perceptuo-motor processes is insufficient. In this study, we aimed to investigate the longitudinal effect of mirror therapy on limb perception and early motor processes in stroke patients using the hand mental rotation (HMR) task with both behavioral and electrophysiological evidence. Fifty stroke patients were randomly assigned to a mirror therapy group (MG, N =25) or a conventional treatment group (CG, N =25). Before and after 4-week intervention, the HMR task was performed, and its behavioral performance and EEG characteristics were measured and correlated with clinical outcomes. Behavioral analysis showed that enhanced accuracy of the HMR task, correlating with greater improvement in upper extremity motor function, was only observed in the MG. The ERD/ERS and brain network analysis revealed significant group differences in brain activation and local network metrics in the ipsilesional hemisphere during the preparation and execution of mental rotation while processing the affected hand stimuli. Specifically, the MG showed enhanced ipsilesional parietal ERD in the $\alpha $ (8-13 Hz) and $\beta 1$ (13-20 Hz) bands, along with increased ipsilesional centroparietal nodal strength and betweenness centrality, which were cross-correlated. The results indicate the potential of long-term mirror therapy for promoting perceptuo-motor processes, facilitating visuospatial perception, and improving motor preparation and mental ability of the affected limb, thereby contributing to post-stroke recovery.

Abstract Background Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. Methods A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. Results (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC 1.02 mmol/L and LDL 1.25 mmol/L and LDL 1.10 mmol/L and LDL

This article presents comprehensive validation of specific sea state parameters (SSPs) and synthetic aperture radar (SAR)-derived wind speeds (${{u}_{\text{SAR}}}$). The article introduces a novel approach to retrieving roughness length (${{z}_0}$) based on wave steepness, following the retrieval of the short wavelengths necessary to estimate ${{z}_0}$. The SAR onboard the Sentinel-1 (S1) satellite that was used specifically in the interferometric wide swath mode (IW) data. The data were processed using the extended version of CWAVE (CWAVE_EX) algorithm for SSPs and CMOD5 for ${{u}_{\text{SAR}}}$. CWAVE_EX was developed especially for coastal waters; the processing chain includes steps for SAR image denoising and eliminating image artifacts. SAR S-1 data inherently exhibit a substantial azimuthal cutoff length due to the data's high satellite altitude and SAR IW resolution. That complicates the retrieving of short wavelengths prevalent in coastal zones and needed to retrieve ${{z}_0}$. The article focuses on the coastal seas of the USA, benefiting from the presence of an extensive network of ocean buoys for validation purposes. The complete SAR S1 A/B archive from 2014 to 2022 was first processed to retrieve SSPs and ${{u}_{\text{SAR}}}$. The validation for significant wave height (${{H}_s}$), second moment wave period (${{T}_{m2}}$), and ${{u}_{\text{SAR}}}$ was performed using in-situ measurements with about 6000 collocations. ${{H}_s}$ and ${{T}_{m2}}$ were compared against the corresponding parameters from hindcast spectral numerical model data with about 380 000 collocations. The comparisons between the retrieved ${{H}_s}$ and ${{T}_{m2}}$ against the in-situ observations and hindcast wave model data yielded a root mean square error (RMSE) of 0.46–0.50 m and 0.9–1.1 s. The RMSE of ${{u}_{\text{SAR}}}$ against in-situ observation was about 2 m/s with a bias of 0.78 m/s. The estimated ${{z}_0}$ values from satellite-driven wave parameters were highly correlated with the ${{z}_0}$ estimated from the in-situ observations, with an RMSE of 0.04 × 10−3 m and a bias of −0.01 × 10−3 m. The article highlights the possibility of using SAR remote sensing data for global mapping of ${{z}_0}$, including coastal effects of local variability in sea state and wind field gustiness.

In this study, we propose a novel approach to achieve an ultra-narrow bandwidth and high transmittance filter in the visible range. By employing TiO2 as the waveguide layer material, the coupling energy in the waveguide layer is enhanced, leading to a reduction in the full width half maximum (FWHM). Additionally, a double-layer dielectric film structure composed of SiO2 and Al2O3 is employed on the Ag grating to suppress random scattering leakage in the short wavelength range, resulting in reduced sidebands and improved transmittance of the resonant peak. To minimize wave loss between the metal grating and the waveguide layer, a SiO2 dielectric layer is introduced. By adjusting the metal grating period, the resonance peak position can be shifted across the entire visible range. The proposed approach offers a metal grating-based guided-mode resonance (GMR) transmissive filter with low sidebands, high transmittance, ultra-narrow bandwidth, and tunability in the entire visible range. Experimental validation of the proposed design is conducted, and the results demonstrate the effectiveness of this approach in achieving superior filter performance in the visible spectral range.

Introduction Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC).Methods and analysis This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual’s relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100β, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC.Ethics and dissemination This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300078564).

Abstract A forward‐bias bipolar membrane (BPM) provides an alkaline cathode condition, which can be beneficial to some electrochemical reactions, such as the CO2 reduction reaction (CO2RR), but the water association (WA) in forward‐bias BPM is not well understood at all. In this study, BPMs are designed with different interfacial polymeric catalysts to investigate the WA reaction under forward‐bias for electrochemical applications. An enhanced current density is observed with added polymeric catalysts (−OH, −O−, −N−, and graphene oxide) compared to the blank control. Temperature‐dependent measurements indicated that the WA in BPM is not kinetically controlled. The in‐plane and through‐plane ions diffusion is investigated, which showed that the WA in BPM is limited mostly by the transport of OH− and, to a lesser degree, H+ at the interface. Molecular dynamic studies presented that the migration rate of OH− at the interface is approximately one order of magnitude lower than that of H+, indicating that the WA is mainly governed by the transport of OH−. Finally, a forward‐bias CO2RR electrolyzer is demonstrated with an Faradaic effeiciency CO (FECO) of 92.2 ± 2.7%. This work provides important fundamental insights into the WA reaction that would enable the use of forward‐bias BPM electrolyzers in future electrochemical applications.

Summary: Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

Soil enzymes play important roles in soil C and nutrient cycling. However, the effects of N addition on soil enzyme kinetics and the underlying mechanisms remain unclear. Thus, we aimed to determine the effects of short-term N addition on the soil properties, microbial properties, maximum reaction rate (Vm, which is attained at saturating substrate concentrations), and Michaelis constant (Km, where a high Km indicates low substrate affinity) of microbial C- (β-1,4-glucosidase and cellobiohydrolase), N- (β-1,4-N-acetylglucosaminidase and L-leucine aminopeptidase), and P-degrading (acid phosphatase and alkaline phosphatase) enzymes in subtropical coniferous (Pinus taiwanensis) and broadleaf (Castanopsis faberi) forests. In the broadleaf forest, N addition increased the Vm and substrate-binding affinities (decline in Km) of C- and P-degrading enzymes by triggering a P deficiency response in microorganisms (i.e., increased microbial biomass N:P ratio). These findings indicate that the soil enzyme kinetics followed the optimal foraging strategy in response to N addition. Moreover, N addition reduced the proportion of complex organic molecules in dissolved organic matter (DOM; e.g., reduced abundance of humic-like fluorophores and humification index), suggesting that N addition increased soil DOM quality and thus increased the affinities of C-degrading enzymes. N addition increased the abundance of Acidobacteria and Chloroflexi but reduced the abundance of Proteobacteria and Rhizobiales, indicating a shift in microbial community toward efficient P acquisition. N addition affected bacterial composition and thus indirectly influenced N- and P-degrading enzymes. In the coniferous forest, N addition significantly increased the Vm of C-degrading enzymes but did not change other enzyme kinetics, which could be partly attributed to the unchanged N availability and microbial properties. Collectively, our findings provide insights into the relationship between enzyme kinetics, DOM quality, and microbial properties, which are important for predicting soil nutrient cycling and parameterizing models of C cycling under N deposition.

IntroductionSoil salinization poses a significant environmental challenge affecting plant growth and agricultural sustainability. This study explores the potential of salt-tolerant endophytes to mitigate the adverse effects of soil salinization, emphasizing their impact on the development and resistance of Arachis hypogaea L. (peanuts).MethodsThe diversity of culturable plant endophytic bacteria associated with Miscanthus lutarioriparius was investigated. The study focused on the effects of Bacillus tequilensis, Staphylococcus epidermidis, and Bacillus siamensis on the development and germination of A. hypogaea seeds in pots subjected to high NaCl concentrations (200 mM L−1).ResultsUnder elevated NaCl concentrations, the inoculation of endophytes significantly (p

Objective: The aim of this study is to investigate the correlation between periodontal disease and chronic obstructive pulmonary disease (COPD) from the perspective of gene regulation, as well as the inflammatory pathways involved. Methods: Forty C57BL/6 mice were randomly divided into four groups: control group, chronic periodontitis (CP) group, COPD group, and CP&COPD group. Lung tissue samples were selected for messenger ribonucleic acid (mRNA) sequencing analysis, and differential genes were screened out. Gene enrichment analysis was carried out, and then crosstalk gene enrichment analysis was conducted to explore the pathogenesis related to periodontal disease and COPD. Results: Results of enrichment analysis showed that the differentially expressed genes (DEGs) in the CP group were concentrated in response to bacterial origin molecules. The DEGs in the COPD group gene were enriched in positive regulation of B cell activation. The DEGs in the CP&COPD group were concentrated in neutrophil extravasation and neutrophil migration. The mice in the three experimental groups had 19 crosstalk genes, five of which were key genes. Conclusions: Lcn2, S100a8, S100a9, Irg1, Clec4d are potential crossover genes of periodontal disease and COPD. Lcn2, S100a8, S100a9 are correlated with neutrophils in both diseases. Irg1 and Clec4d may bind to receptors on the surface of lymphocytes to produce cytokines and activate inflammatory pathways, this requires further research.