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Abstract Mounting evidence suggests that the gut-heart axis is critical in the pathogenesis of cardiovascular diseases. The gut serves as the primary pathway through which Coxsackievirus B3 (CVB3) infects its host, leading to acute viral myocarditis (AVMC). However, little is known about the role of gut microflora and its metabolites in the development of AVMC. The AVMC model was established by intraperitoneal injection of CVB3 in mice. Then, 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) untargeted metabolomics profiling were performed to analyze the microflora composition and metabolic profile of colonic contents. Compared to the Control mice, the AVMC mice displayed a significant reduction in gut microflora richness and diversity, as revealed by an increased abundance of Proteobacteria and a decreased abundance of Cyanobacteria and Desulfobacterota. LEfSe analysis indicated that the main genera differing between the two groups were Escherichia-Shigella, Lactobacillus, Clostridium_sensu_stricto_1, Prevotellaceae_UCG-001, and Odoribacter. Based on the criterion of OPLS-DA VIP ≥ 1.0 and p-value 0.80 and p

Abstract Background Pseudomyxoma peritonei (PMP) is a rare malignant peritoneal tumor that readily recurs and metastasizes. Studies have shown that cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and prognosis. Objective In this study, our aim was to isolate CSCs from various tissues of PMP patients and compare their proliferation, migration, and anti-inflammatory abilities. Methods We identified CSCs subsets with markers CD133+, CD166+, and CD133+/CD166+ at the gene level using single-cell mRNA sequencing (scRNA-seq). Appendiceal CSCs (AC), peritoneal CSCs (PC), and mucous CSCs (MC) were obtained using MACSQuant Tyto sorting technology and FlowSight imaging flow cytometry. The cells were cultured and markers were identified. Finally, the functional phenotypes of the three cell types were compared. Results CSCs content was highest in the appendiceal tumor tissue and lowest in the mucous tissue. The cell viability rate of the sorted CSCs was above 98%, and the positive rate of CD133+ and CD166+ was 70–80%, and CD133+/CD166+ was about 30%. Among the three types of CSCs, MC had the highest proliferation ability, and TNF-α has the greatest inhibitory effect on AC migration. Conclusion AC in patients was more inert and anti-inflammatory, whereas abdominal cavity MC and PC were more active. This study revealed the biological characteristics of CSCs in different tumor tissues of patients with PMP, providing a reference for future targeted CSCs therapy.

Abstract Touch displays are ubiquitous in modern technologies. However, current protective methods for emerging flexible displays against static, scratches, bending, and smudge rely on multilayer materials that impede progress towards flexible, lightweight, and multifunctional designs. Developing a single coating layer integrating all these functions remains challenging yet highly anticipated. Herein, we introduce an organic–inorganic covalent–ionic hybrid network that leverages the reorganizing interaction between siloxanes (i.e., trifluoropropyl–funtionalized polyhedral oligomeric silsesquioxane and cyclotrisiloxane) and fluoride ions. This nanoscale organic–inorganic covalent–ionic hybridized crosslinked network, combined with a low surface energy trifluoropropyl group, offers a monolithic layer coating with excellent optical, antistatic, anti–smudge properties, flexibility, scratch resistance, and recyclability. Compared with existing protective materials, this all–in–one coating demonstrates comprehensive multifunctionality and closed–loop recyclability, making it ideal for future flexible displays and contributing to ecological sustainability in consumer electronics.

The present study focuses on investigating the low cycle fatigue (LCF) behavior and cyclic deformation mechanism of Ti–6Al–4V-0.55Fe alloy under strain and stress control. Based on the results of this alloy under strain amplitudes and the corresponding stress amplitudes, the effect of tension-compression asymmetry (TCA) on fatigue behavior and microstructure evolution was systematically discussed with transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). The results show that under strain control, TCA has little effect on LCF behavior due to the negligible compressive mean stress. And the deformation mechanism is mainly determined by planar slip. While under stress control, the accumulation of significant unidirectional ratcheting strain caused by TCA is observed, resulting in extra heterogeneous plastic deformation and more fatigue damage, responsible for the reduction in fatigue life. However, under low stress amplitude (≤690 MPa), no ratcheting behavior occurs due to the constant strain amplitude (0.56%), which reduces the driving force of crack nucleation and prolongs fatigue life, compared with that under low strain amplitude (0.6%).

Abstract This paper discusses the seismic performance of five reduced-scale shear walls, including one cast-in-place (CIP) concrete shear wall, two precast concrete (PC) shear walls with overlapping U-bar loop connections, and two PC shear walls with modified form-overlapping U-bar loop connections combined with extruded sleeve connections. A quasi-static test was conducted to evaluate the reliability of the overlapping U-bar loop connections and the modified form by comparing the corresponding mechanical parameters of PC specimens with those of the CIP specimen. Moreover, the differences in seismic performance between the CIP specimen and PC specimens with different connection methods were also analyzed in terms of damage process, hysteretic loops and skeleton curves, load carrying capacity, ductility, equivalent stiffness, and energy dissipation. The experimental findings indicated that the mechanical performances of PC specimens with the modified connection form outperformed those of PC specimens with pure overlapping U-bar loop connections, closely resembling the properties of cast-in-place specimens; the failure mode of PC specimens was consistent with that of the CIP specimen; the generation, distribution and development of cracks in PC specimens were also similar to those in the CIP specimen. Furthermore, although the load-bearing capacity and peak displacement of PC specimens were lower than those of the CIP specimen due to the failure of the post-casted concrete strength to meet the requirements, the ductility, equivalent stiffness, and energy dissipation of PC specimens with the modified connection form closely matched that of the CIP specimen.

Accurate origin–destination (OD) demand prediction is crucial for the efficient operation and management of urban rail transit (URT) systems, particularly during a pandemic. However, this task faces several limitations, including real-time availability, sparsity, and high-dimensionality issues, and the impact of the pandemic. Consequently, this study proposes a unified framework called the physics-guided adaptive graph spatial–temporal attention network (PAG-STAN) for metro OD demand prediction under pandemic conditions. Specifically, PAG-STAN introduces a real-time OD estimation module to estimate real-time complete OD demand matrices. Subsequently, a novel dynamic OD demand matrix compression module is proposed to generate dense real-time OD demand matrices. Thereafter, PAG-STAN leverages various heterogeneous data to learn the evolutionary trend of future OD ridership during the pandemic. Finally, a masked physics-guided loss function (MPG-loss function) incorporates the physical quantity information between the OD demand and inbound flow into the loss function to enhance model interpretability. PAG-STAN demonstrated favorable performance on two real-world metro OD demand datasets under the pandemic and conventional scenarios, highlighting its robustness and sensitivity for metro OD demand prediction. A series of ablation studies were conducted to verify the indispensability of each module in PAG-STAN.

Abstract Topological photonics attract significant interests due to their intriguing fundamental physics and potential applications. Researchers are actively exploring various artificial platforms to realize novel topological phenomena, which provides promising pathways for the development of robust photonic devices. Among these platforms, femtosecond laser direct-written photonic waveguides show unique ability to visualize intricate light dynamics in 2 + 1 dimensions, which rendering them ideal tools for investigating topological photonics. By integrating topological concepts into these waveguides, researchers not only deepen their understanding of topological physics but also provide potential methodology for developing advanced topological photonic integrated devices. In this review, we discuss recent experimental implementations of different topological phases within femtosecond laser direct-written photonic waveguides, as well as the fascinating physical phenomena induced by the interplay of topology with non-Hermiticity, nonlinearity and quantum physics are also introduced. The exploration of topological waveguide arrays shows great promise in advancing the field of topological photonics, providing a solid foundation for further research and innovation in this rapidly developing domain.

Abstract Background Methylation-related signatures play crucial roles in tumorigenesis and progression. However, their roles in the immune response in primary glioblastoma (GBM) remains unclear. Methods We analyzed the differential expression of specific members of T cell exhaustion-related pathways in GBM from the perspective of T cell exhaustion. We further screened for significantly negatively correlated methylation sites as candidate methylation markers for T cell exhaustion. Using consensus clustering, we divided the samples into two categories with significant differences in overall survival (OS). We then performed univariate and multivariate Cox regression analyses to construct the T Cell Exhaustion Methylation (TEXM) signature. Finally, we confirmed that this signature served as an independent prognostic factor, and further characterized it in terms of drug resistance and immunotherapy. Results We identified 95 significantly differentially expressed T cell exhaustion-related genes and 51 methylation markers associated with T cell exhaustion. The cancer samples were classified according to methylation site markers, thus indicating two subtypes with significant differences in OS: subtype A and subtype B. Tumor scores, stromal scores, tumor purity, and ESTIMATE scores all showed significant differences between subtypes (P

Abstract Letermovir (LTV) prophylaxis is effective in reducing the incidence of clinically significant cytomegalovirus (CMV) infection (cs CMVi) after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Since our centre began administering LTV prophylaxis in June 2022, we have observed a certain increase in the incidence of Epstein–Barr virus (EBV) reactivation after haploidentical HSCT. We retrospectively analysed 230 consecutive patients who underwent haploidentical HSCT with rabbit anti-thymocyte globulin (ATG) from October 2022 to June 2023. The LTV group included 133 patients who received LTV prophylaxis, and the control group included 97 patients who did not receive LTV prophylaxis. At 1 year after HSCT, EBV reactivation was observed in 36 patients (27%) in the LTV group and 13 patients (13%) in the control group (p = 0.012). All patients with EBV reactivation had EBV-DNAemia, and one patient in each group developed EBV-associated posttransplantation lymphoproliferative disorder (PTLD). The proportion of patients with low EBV-DNA loads (> 5 × 102 to

Abstract Objective To investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management. Methods A retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People’s Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software. Results Of the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes. Conclusion Most BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.

Abstract Aims A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta‐analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies. Methods and results According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta‐analyses. Data were extracted and curated for Bayesian network meta‐analysis. The primary outcome was the change in the 6‐min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (−77.76 m, 95% CI: −102.04 to −54.34 m), Macitentan (−65.32 m, 95% CI: −95.34 to −36.1 m), Bosentan (−64.5 m, 95% CI: −94.7 to −35.07 m), Iloprost (−62.66 m, 95% CI: −99.48 to −27.13 m), Oxygen (−62.42 m, 95% CI: −100.01 to −25.78 m), Treprostinil (−62.01 m, 95% CI: −89.04 to −35.61 m), Riociguat (−60.59 m, 95% CI: −86.11 to −35.98 m), Selexipag (−47.2 m, 95% CI: −85.61 to −10.19 m), Sildenafil (−44.92 m, 95% CI: −74.43 to −16.15 m), or Sitaxsentan (−39.53 m, 95% CI: −78.99 to −0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re‐hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions. Conclusions Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual‐drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

Abstract Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained‐release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady‐state trough concentrations (Ctrough) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20–50 kg. As a result, the PK characteristics of VPA were described using a one‐compartment model with first‐order absorption. The absorption rate constant (ka) was set at 2.64 and 0.46 h−1 for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target Ctrough, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.

Abstract Background Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. Methods A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. Results Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. Conclusion Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

Abstract Previous findings have reported the association between frailty and chronic kidney disease. However, the causality remains ambiguous. This study aimed to determine whether frailty index is causally associated with chronic kidney disease. We obtained the frailty genome-wide association study (GWAS) data and chronic kidney disease GWAS data from the FinnGen R5 (total n = 216,743; case = 3902, control = 212,841) as the exposure and outcome, respectively. A two-sample Mendelian randomization (MR) analysis was primarily conducted using the inverse-variance weighted (IVW), weighted median and MR-Egger regression analyses. Multivariable MR analysis (MVMR) was conducted for additional adjustment. In the two-sample Mendelian randomization analyses, a total of 14 single nucleotide polymorphisms (SNPs) were recognized as effective instrumental variables. The IVW method showed evidence to support a causal association between frailty index and chronic kidney disease (beta = 1.270; 95% CI 0.608 to 1.931; P

Abstract Background The causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations. Methods All genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran’s Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method. Results Genetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 ∼ 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 ∼ 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 ∼ 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 ∼ 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 ∼ 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 ∼ 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 ∼ 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 ∼ 1.545) and the risk of IPF persisted even after adjusting for smoking. Conclusions Increased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.

Abstract In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority 3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Magnetorheological finishing (MRF) is one of the candidate technologies for the efficient polishing of single crystal silicon carbide (SiC). It is of great importance to improve the efficiency of MRF and reduce the costs by improving the catalytic activity and corrosion resistance of iron-based magnetic particles while maintaining the magnetic properties. In this work, α-Fe2O3 and TiH2 powders were used as raw materials, and Fe–Ti–O composite powders for MRF were prepared by three processes: ball milling + reduction (R1), ball milling + calcination (R2) and ball milling + calcination + reduction (R3). The effects of TiH2 content (5 wt%-15 wt%) on the phase composition, microstructure, catalytic activity and corrosion resistance of the composite powders were investigated. The results demonstrated that submicron α-Fe2O3/TiH2 mixed powders with uniform composition were obtained by ball milling. Compared to the powders prepared by the R1 and R2 routes, the Fe–Ti–O composite powders prepared by the R3 were composed of Fe2TiO4 particles (500–800 nm) and iron-rich particles (30–200 nm). The iron-rich particles were uniformly distributed on the surface of the agglomerated Fe2TiO4 spheres, forming a unique ''Ferrero'' structure. When the TiH2 content was 15 wt%, the Fe–Ti–O composite powders exhibited the required saturation magnetization (Ms) for MRF (61.0 emu/g), the highest catalytic activity and the best corrosion resistance.

Primary malignant melanoma of the esophagus (PMME) is an extremely rare esophageal malignancy that is often misdiagnosed or overlooked due to its atypical symptoms. We report a case of a 75-year-old male patient who presented with progressive dysphagia. Endoscopic examination revealed a black mass located 25 cm from the incisors. Further imaging studies, including computed tomography (CT) and emission computed tomography (ECT), showed significant thickening of the mid-esophageal wall with localized soft tissue mass formation and heterogeneous enhancement on contrast scans. Multiple lymph nodes around the lesion were visible, leading to an initial misdiagnosis of esophageal cancer. Additionally, metabolic abnormalities in the left scapula suggested possible bone metastasis of the tumor. The final pathological diagnosis was esophageal melanoma. After thorough evaluation of the patient's medical history and additional relevant tests, the primary origin was considered. Diagnosing primary malignant melanoma of the esophagus is a challenging task. This case, through the combination of endoscopic examination, imaging, and pathology, illustrates the characteristics of PMME, providing important insights for clinicians and emphasizing the necessity of comprehensive early evaluation to improve diagnostic accuracy and treatment outcomes.

The amount of data collected from underwater explosion tests is enormous, which is mixed with a large amount of useless data. To protect the data from the effects of the explosion, it is crucial to prioritize the recognition and storage of key data during the test. In response to this, a key signal recognition model that combined feature extraction methods with deep learning models was proposed to improve the accuracy of key signal recognition. Firstly, different preprocessing methods for removing trend components from underwater explosion acceleration signals were studied. Existing test results demonstrated that wavelet packet decomposition, empirical mode decomposition, and high-pass filtering could significantly enhance the model’s recognition performance. Secondly, to make the extracted features more conducive to distinguishing between explosion and non-explosion segments, a feature extraction method based on the inter-class variance ratio for underwater explosion acceleration signals was proposed. According to the actual measured underwater explosion acceleration signal data, it was found that compared to Log Mel features, the proposed features improved classification accuracy by approximately 4.92% using the K-means method. Finally, the ECAPA-TDNN model incorporating the SE-Res2Block module was introduced, ensuring better recognition accuracy. With the proposed features as input, the recognition accuracy reached 99.31%.

Abstract Introduction ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. Methods From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P

Abstract Objective This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Abstract Historians and paleoclimatologists have long studied the connection between ecoclimatic changes and empire growth, transformation, and decline, but striking cases remain rare. Here, we introduce a tree-ring chronology from southern China to reconstruct changes in April-to-November water balance of the middle reaches of the Yangtze River over the last 464 years. The reconstruction supports a quantitative assessment of the spatiotemporal structure of the late Ming megadrought and potential effects on subsequent dynastic transitions. Our results indicate that the late Ming megadrought from 1625 – 1644 CE occurred in both the northern and southern parts of the East Asian monsoon region in China. However, variations in the onset, duration, and magnitude of this event differ between regions. The combination of factors such as Pacific sea surface temperature anomalies, weakened solar activity, and large-scale volcanic eruptions may have contributed to the occurrence of the late Ming megadrought. These factors are also identified as key drivers of interannual to decadal fluctuations in drought in the middle reaches of the Yangtze River. Our reconstruction provides an historical context for the development of adaptive measures to mitigate future drought impacts in the region.

Abstract Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Abstract Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 μC/cm2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials.

Abstract In the realm of multiferroicity in 2D magnets, whether magnetic and polar skyrmions can coexist within a single topological entity has emerged as an important question. Here, we study Janus 2D magnets CrInX 3 (X=Se, Te) for a comprehensive investigation of the magnetic ground state, magnetic excited state, and corresponding ferroelectric polarization by first-principles electronic structure calculations and Monte Carlo simulations. Specifically, we have thoroughly elucidated the magnetic exchange mechanisms, and have fully exemplified the magnetic field dependence of the magnon spectrum. More importantly, our study reveals a previously unrecognized, remarkably large spin-spiral-induced ferroelectric polarization (up to 194.9 μC/m2) in both compounds. We propose an approach to identify polar skyrmions within magnetic skyrmions, based on the observed direct correlation between spin texture and polarization density. Elucidating this correlation not only deepens our understanding of magnetic skyrmions but also paves the way for innovative research in the realm of multiferroic skyrmions.

Abstract The study of rock burst tendency of rock masses with different sizes plays a key role in the prevention of rock burst. Through theoretical analysis, it is proposed that uniaxial compressive strength and deformation modulus ratio are the key mechanical parameters affecting rock burst occurrence. In order to find out the size effect of uniaxial compressive strength and deformation modulus ratio, theoretical analysis and uniaxial compression experiment are carried out on rock samples with different heights, different cross-sectional areas and different volumes. The results show that the smaller the uniaxial compressive strength is, the larger the deformation modulus ratio is, and the more likely rock burst are to occur. On the contrary, rock burst is still not easy to generate. The uniaxial compressive strength of rock samples with different heights, different cross-sectional areas and different volumes increases with the increase of rock sample size. The deformation modulus ratio of rock samples with different heights and different volumes shows an upward trend on the whole, while that of rock samples with different cross-sectional areas shows a downward trend on the whole. The fracture forms of rock are analyzed using the energy conversion law in the process of deformation and failure for three kinds of rock with different shapes and sizes.

Abstract Background Quantitative transport mapping (QTM) of blood velocity, based on the transport equation has been demonstrated higher accuracy and sensitivity of perfusion quantification than the traditional Kety’s method-based cerebral blood flow (CBF). This study aimed to investigate the associations between QTM velocity and cognitive function in Alzheimer’s disease (AD) using multiple post-labeling delay arterial spin labeling (ASL) MRI. Methods A total of 128 subjects (21 normal controls (NC), 80 patients with mild cognitive impairment (MCI), and 27 AD) were recruited prospectively. All participants underwent MRI examination and neuropsychological evaluation. QTM velocity and traditional CBF maps were computed from multiple delay ASL. Regional quantitative perfusion measurements were performed and compared to study group differences. We tested the hypothesis that cognition declines with reduced cerebral blood perfusion with consideration of age and gender effects. Results In cortical gray matter (GM) and the hippocampus, QTM velocity and CBF showed decreased values in the AD group compared to NC and MCI groups; QTM velocity, but not CBF, showed a significant difference between MCI and NC groups. QTM velocity and CBF showed values decreasing with age; QTM velocity, but not CBF, showed a significant gender difference between male and female. QTM velocity and CBF in the hippocampus were positively correlated with cognition, including global cognition, memory, executive function, and language function. Conclusion This study demonstrated an increased sensitivity of QTM velocity as compared with the traditional Kety’s method-based CBF. Specifically, we observed only in QTM velocity, reduced perfusion velocity in GM and the hippocampus in MCI compared with NC. Both QTM velocity and CBF demonstrated a reduction in AD vs. controls. Decreased QTM velocity and CBF in the hippocampus were correlated with poor cognitive measures. These findings suggest QTM velocity as potential biomarker for early AD blood perfusion alterations and it could provide an avenue for early intervention of AD.

Abstract We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications.

Abstract SAR202 bacteria in the Chloroflexota phylum are abundant and widely distributed in the ocean. Their genome coding capacities indicate their potential roles in degrading complex and recalcitrant organic compounds in the ocean. However, our understanding of their genomic diversity, vertical distribution, and depth-related metabolisms is still limited by the number of assembled SAR202 genomes. In this study, we apply deep metagenomic sequencing (180 Gb per sample) to investigate microbial communities collected from six representative depths at the Bermuda Atlantic Time Series (BATS) station. We obtain 173 SAR202 metagenome-assembled genomes (MAGs). Intriguingly, 154 new species and 104 new genera are found based on these 173 SAR202 genomes. We add 12 new subgroups to the current SAR202 lineages. The vertical distribution of 20 SAR202 subgroups shows their niche partitioning in the euphotic, mesopelagic, and bathypelagic oceans, respectively. Deep-ocean SAR202 bacteria contain more genes and exhibit more metabolic potential for degrading complex organic substrates than those from the euphotic zone. With deep metagenomic sequencing, we uncover many new lineages of SAR202 bacteria and their potential functions which greatly deepen our understanding of their diversity, vertical profile, and contribution to the ocean’s carbon cycling, especially in the deep ocean.

Abstract The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Introduction In this study, we investigated the effect of depression on the interaction between lung disease and cardiovascular health (CVH). Methods Utilising data from the National Health and Nutrition Examination Survey (2013–2018), we employed multivariate regression and bootstrap mediation analysis to explore the relationships among lung diseases, depression, and CVH scores. Results Complex and significant associations were identified among lung diseases, depression, and CVH scores, with depression mediating 9.42% of the effect on CVH, especially for chronic bronchitis patients. Conclusions Depression significantly mediated the relationship between lung disease and reduced CVH scores, highlighting the importance of mental health management in lung disease patients.

Abstract Over the past two decades, more frequent and intense climate events have seriously threatened the operation of water transfer projects in the Pacific Rim region. However, the role of climatic change in driving runoff variations in the water source areas of these projects is unclear. We used tree-ring data to reconstruct changes in the runoff of the Hanjiang River since 1580 CE representing an important water source area for China’s south-north water transfer project. Comparisons with hydroclimatic reconstructions for the southwestern United States and central Chile indicated that the Pacific Rim region has experienced multiple coinciding droughts related to ENSO activity. Climate simulations indicate an increased likelihood of drought occurrence in the Pacific Rim region in the coming decades. The combination of warming-induced drought stresses with dynamic El Niño (warming ENSO) patterns is a thread to urban agglomerations and agricultural regions that rely on water transfer projects along the Pacific Rim.

This review evaluated research results on polyvinyl alcohol fiber cement-stabilized macadam (PVA-FCSM) to further improve the long-term durability of road structures and promote its in-depth study and high-quality application. The suitable PVA fiber technical indexes for ordinary cement-stabilized macadam (CSM) were recommended. The difference in the mechanical properties between CSM and PVA-FCSM was described. The extent to which PVA fibers enhance the durability of CSM were clarified. Additionally, the mechanism of enhancement of CSM by PVA fibers was revealed. Finally, the performance of each type of fiber cement-stabilized macadam (FCSM) was compared and evaluated. The results indicated that the suggested PVA fiber length and content for CSM were 12–30 mm and 0.6–1.2 kg/m3, respectively. At different ages, the mean degree of improvement in the unconfined compressive strength was 14%, 20%, and 14%, that in the compressive resilience modulus was 8%, 11%, and 6%, and that in the splitting strength was 29%, 15%, and 22%, respectively. At different ages, the mean degree of decreased in the dry shrinkage coefficient was 21%, 16%, and 15% and that in the temperature shrinkage coefficient (20 °C–30 °C) was 23%, 23%, and 18%, respectively. The coefficients increased with extended curing age. Moreover, at the same stress level, PVA-FCSM has a higher fatigue life compared to CSM. The bridging effect, high strength, and high modulus of PVA fiber enhance the strength and anti-cracking of CSM. The recommended fiber type for CSM is PVA fiber.

Abstract Background The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed amygdalin content of P. sibirica is an interesting question. Mandelonitrile is known as one key intermediate of amygdalin metabolism, but which mandelonitrile lyase (MDL) family member essential for its dissociation destined to low amygdalin accumulation in P. sibirica seeds still remains enigmatic. An integration of our recent 454 RNA-seq data, amygdalin and mandelonitrile content detection, qRT-PCR analysis and function determination is described as a critical attempt to determine key MDL and to highlight its function in governing mandelonitrile catabolism with low amygdalin accumulation in Prunus sibirica seeds for better developing edible oil and biodiesel in China. Results To identify key MDL and to unravel its function in governing seed mandelonitrile catabolism with low amygdalin accumulation in P. sibirica. Global identification of mandelonitrile catabolism-associated MDLs, integrated with the across-accessions/developing stages association of accumulative amount of amygdalin and mandelonitrile with transcriptional level of MDLs was performed on P. sibirica seeds of 5 accessions to determine crucial MDL2 for seed mandelonitrile catabolism of P. sibirica. MDL2 gene was cloned from the seeds of P. sibirica, and yeast eukaryotic expression revealed an ability of MDL2 to specifically catalyze the dissociation of mandelonitrile with the ideal values of K m (0.22 mM) and V max (178.57 U/mg). A combination of overexpression and mutation was conducted in Arabidopsis. Overexpression of PsMDL2 decreased seed mandelonitrile content with an increase of oil accumulation, upregulated transcript of mandelonitrile metabolic enzymes and oil synthesis enzymes (involving FA biosynthesis and TAG assembly), but exhibited an opposite situation in mdl2 mutant, revealing a role of PsMDL2-mediated regulation in seed amygdalin and oil biosynthesis. The PsMDL2 gene has shown as key molecular target for bioengineering high seed oil production with low amygdalin in oilseed plants. Conclusions This work presents the first integrated assay of genome-wide identification of mandelonitrile catabolism-related MDLs and the comparative association of transcriptional level of MDLs with accumulative amount of amygdalin and mandelonitrile in the seeds across different germplasms and developmental periods of P. sibirica to determine MDL2 for mandelonitrile dissociation, and an effective combination of PsMDL2 expression and mutation, oil and mandelonitrile content detection and qRT-PCR assay was performed to unravel a mechanism of PsMDL2 for controlling amygdalin and oil production in P. sibirica seeds. These findings could offer new bioengineering strategy for high oil production with low amygdalin in oil plants.

Abstract Background IDH1-wildtype glioblastoma multiforme (IDHwt-GBM) is a highly heterogeneous and aggressive brain tumour characterised by a dismal prognosis and significant challenges in accurately predicting patient outcomes. To address these issues and personalise treatment approaches, we aimed to develop and validate robust multiomics molecular subtypes of IDHwt-GBM. Through this, we sought to uncover the distinct molecular signatures underlying these subtypes, paving the way for improved diagnosis and targeted therapy for this challenging disease. Methods To identify stable molecular subtypes among 184 IDHwt-GBM patients from TCGA, we used the consensus clustering method to consolidate the results from ten advanced multiomics clustering approaches based on mRNA, lncRNA, and mutation data. We developed subtype prediction models using the PAM and machine learning algorithms based on mRNA and MRI data for enhanced clinical utility. These models were validated in five independent datasets, and an online interactive system was created. We conducted a comprehensive assessment of the clinical impact, drug treatment response, and molecular associations of the IDHwt-GBM subtypes. Results In the TCGA cohort, two molecular subtypes, class 1 and class 2, were identified through multiomics clustering of IDHwt-GBM patients. There was a significant difference in survival between Class 1 and Class 2 patients, with a hazard ratio (HR) of 1.68 [1.15–2.47]. This difference was validated in other datasets (CGGA: HR = 1.75[1.04, 2.94]; CPTAC: HR = 1.79[1.09–2.91]; GALSS: HR = 1.66[1.09–2.54]; UCSF: HR = 1.33[1.00–1.77]; UPENN HR = 1.29[1.04–1.58]). Additionally, class 2 was more sensitive to treatment with radiotherapy combined with temozolomide, and this sensitivity was validated in the GLASS cohort. Correspondingly, class 2 and class 1 exhibited significant differences in mutation patterns, enriched pathways, programmed cell death (PCD), and the tumour immune microenvironment. Class 2 had more mutation signatures associated with defective DNA mismatch repair (P = 0.0021). Enriched pathways of differentially expressed genes in class 1 and class 2 (P-adjust

Abstract To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4’s inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.

Abstract Background Education is urgently needed to equip medical students with knowledge, values and skills to promote planetary health. However, the current literature offers little insight into evidence-based approaches and best practices. In response to this pressing need, a novel serious game was introduced into the medical curriculum at Erasmus Medical Center in 2023. The aim of this study was to evaluate the knowledge and attitudes of medical students after they had played a serious game that addresses climate change and health. Methods In accordance with a mixed-methods design, quantitative data were collected using pre- and post-intervention surveys. Differences were assessed using the Wilcoxon signed rank test. Focus group discussions were held after the game and thematically analysed. Results One hundred forty-five students (38.6% of the entire cohort) played the game, of which 59 students completed the pre- and post-intervention surveys. After the game, self-reported knowledge increased. Regarding objective knowledge, an increase in the proportion of students who answered one of the two questions correctly was observed, while the proportion of correct responses decreased for the other question. Student’s responses to two out of five attitude questions were significantly more positive. The proportion of students who recognized the importance of climate change education, to inform patients and society about the health impacts of climate change, increased. Moreover, survey results indicated a significant increase in climate worry subsequent to the game. Eleven students participated in the focus group discussions. Thematic analysis highlighted participants’ reflections on the roles and responsibilities in climate change and health, along with their realisation of the tools for action that climate and health co-benefits provide. Another significant aspect was the importance participants placed on learning alongside peers with diverse attitudes. Additionally, participants appreciated the tangible overview of climate change and health provided by the serious game. Conclusions Our novel serious game addressed an important gap in the medical curriculum. The game can enable medical students to cultivate the necessary knowledge and attitudes to promote health in times of a climate crisis. The accompanying climate worry needs attention through the empowerment of students’ agency to foster change.

Abstract Background The Triglyceride glucose (TyG) index-related indicators improve risk stratification by identifying individuals prone to atherosclerosis early in life. This study aimed to examine the relation between TyG-waist circumference-to-height ratio (TyG-WHtR) and coronary heart disease. Methods Data from four National Health and Nutrition Examination Surveys (NHANES) cycles between 2011 and 2018 were used for a cross-sectional study. The association between TyG-WHtR and coronary heart disease risk was examined using a multifactorial logistic regression model, and corresponding subgroup analyses were performed. Nonlinear correlations were analyzed using smooth curve fitting and threshold effects analysis. When nonlinear connections were discovered, appropriate inflection points were investigated using recursive methods. Results TyG-WHtR and coronary heart disease were significantly positively correlated in the multifactorial logistic regression analysis. Subgroup analyses and interaction tests revealed that gender, age, smoking status, and cancer were not significantly associated with this correlation (P for interaction > 0.05). Furthermore, utilizing threshold effect analysis and smooth curve fitting, a nonlinear connection with an inflection point of 0.36 was observed between TyG-WHtR and coronary heart disease. Conclusions According to this study, the American population is far more likely to have coronary heart disease if they have higher TyG-WHtR levels.

IntroductionMulti-layer aggregation is key to the success of out-of-distribution (OOD) detection in deep neural networks. Moreover, in real-time systems, the efficiency of OOD detection is equally important as its effectiveness.MethodsWe propose a novel early stopping OOD detection framework for deep neural networks. By attaching multiple OOD detectors to the intermediate layers, this framework can detect OODs early to save computational cost. Additionally, through a layer-adaptive scoring function, it can adaptively select the optimal layer for each OOD based on its complexity, thereby improving OOD detection accuracy.ResultsExtensive experiments demonstrate that our proposed framework is robust against OODs of varying complexity. Adopting the early stopping strategy can increase OOD detection efficiency by up to 99.1% while maintaining superior accuracy.DiscussionOODs of varying complexity are better detected at different layers. Leveraging the intrinsic characteristics of inputs encoded in the intermediate latent space is important for achieving high OOD detection accuracy. Our proposed framework, incorporating early stopping, significantly enhances OOD detection efficiency without compromising accuracy, making it practical for real-time applications.

IntroductionThis study presented an end-to-end 3D deep learning model for the automatic segmentation of brain tumors.MethodsThe MRI data used in this study were obtained from a cohort of 630 GBM patients from the University of Pennsylvania Health System (UPENN-GBM). Data augmentation techniques such as flip and rotations were employed to further increase the sample size of the training set. The segmentation performance of models was evaluated by recall, precision, dice score, Lesion False Positive Rate (LFPR), Average Volume Difference (AVD) and Average Symmetric Surface Distance (ASSD).ResultsWhen applying FLAIR, T1, ceT1, and T2 MRI modalities, FusionNet-A and FusionNet-C the best-performing model overall, with FusionNet-A particularly excelling in the enhancing tumor areas, while FusionNet-C demonstrates strong performance in the necrotic core and peritumoral edema regions. FusionNet-A excels in the enhancing tumor areas across all metrics (0.75 for recall, 0.83 for precision and 0.74 for dice scores) and also performs well in the peritumoral edema regions (0.77 for recall, 0.77 for precision and 0.75 for dice scores). Combinations including FLAIR and ceT1 tend to have better segmentation performance, especially for necrotic core regions. Using only FLAIR achieves a recall of 0.73 for peritumoral edema regions. Visualization results also indicate that our model generally achieves segmentation results similar to the ground truth.DiscussionFusionNet combines the benefits of U-Net and SegNet, outperforming the tumor segmentation performance of both. Although our model effectively segments brain tumors with competitive accuracy, we plan to extend the framework to achieve even better segmentation performance.

Development of functional recovery therapies is critical to reduce the global impact of stroke as the leading cause of long-term disability. Our previous studies found that acute-phase protein orosomucoid (ORM) could provide an up to 6 h therapeutic time window to reduce infarct volume in acute ischemic stroke by improving endothelial function. However, its role in neurons and functional recovery post-stroke remains largely unknown. Here, we showed that exogenous ORM administration with initial injection at 0.5 h (early) or 12 h (delayed) post-MCAO daily for consecutive 7 days significantly decreased infarct area, improved motor and cognitive functional recovery, and promoted mitochondrial biogenesis after MCAO. While neuron-specific knockout of ORM2, a dominant subtype of ORM in the brain, produced opposite effects which could be rescued by exogenous ORM. In vitro, exogenous ORM protected SH-SY5Y cells from OGD-induced damage and promoted mitochondrial biogenesis, while endogenous ORM2 deficiency worsened these processes. Mechanistically, inactivation of CCR5 or AMPK eliminated the protective effects of ORM on neuronal damage and mitochondrial biogenesis. Taken together, our findings demonstrate that ORM, mainly ORM2, is an endogenous regulator of neuronal mitochondrial biogenesis by activating CCR5/AMPK signaling pathway, and might act as a potential therapeutic target for the functional recovery post-stroke.

While the development of wind energy presents great potential and opportunities, the high level of uncertainty inherent in wind farms also poses considerable challenges for operators, especially when it comes to participating in the energy market. The intermittent and unpredictable fluctuation characteristics of wind power generation may cause significant deviations in the frequency and voltage of the grid, which pose a certain threat to the stability of the grid and power quality and need to be mitigated by advanced energy storage solutions. Salt caverns, these geological structures deep in underground space, are widely used in oil and gas storage, compressed air energy storage(CAES), and other projects around the world. In the operation of underground salt caverns as storage, there is no effective technical means to monitor the deformation of deep caverns in real-time. Therefore, developing a high-precision real-time prediction method for cavern volume deformation is of great significance for the safety assessment during the underground salt cavern operation. In this context, this paper proposes a comprehensive technical approach to meet the needs of real-time monitoring of the cavern status, including volume changes, in the intelligent construction of underground salt cavern facilities in China. Firstly, through the shut-in pressure test of the brine well, the volume shrinkage of the cavern during the monitoring period is obtained, and the creep parameters of the salt rock strata in the regional salt mine are inversely derived. Secondly, for a typical cavern in operation in this region, the creep deformation is predicted using numerical simulation methods. By analyzing the cavern volume deformation under different pressures, an empirical equation for cavern volume deformation is established. Finally, by combining the volume changes obtained from sonar tests conducted during the operation of the cavern, the accuracy of the simulated results and the theoretical model derived from the inverted creep parameters is verified. The real-time analysis method for cavern volume deformation developed from this research will be applied to the intelligent construction of underground salt cavern facilities, ensuring safe and controllable operation management of the storage facilities.

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.

BackgroundRheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate the potential role and molecular mechanism of N6-methyladenosine (m6A) methylation regulators in the pathogenesis of RA.MethodsIn this study, we employed bioinformatics tools to elucidate the association between RA and m6A modifications, aiming to identify potential biological markers. We extracted datasets GSE12021, GSE55235, and GSE55457 from the Gene Expression Omnibus (GEO) database for comprehensive analysis. Utilizing differential expression analysis, protein-protein interaction (PPI) analysis, and single-cell sequencing techniques, we identified pivotal hub genes implicated in the pathogenesis of RA. Subsequently, we assessed the correlation between these hub genes and the pathogenesis of RA using Gene Set Enrichment Analysis (GSEA). Both in vivo and in vitro experiments were performed to confirm the expression and functional roles of the identified key hub gene in RA.ResultsDifferential expression analysis, PPI analysis, and single-cell analysis identified three key hub genes (YTHDC1, YTHDC2, and YTHDF2) associated with RA. GSEA results further revealed that these genes are enriched in pathways associated with inflammatory responses. Subsequent correlation analysis demonstrated a significant negative correlation between YTHDC1 expression and CD8+ T cell levels. Notably, the gene and protein expression levels of YTHDC1 and YTHDF2 were significantly reduced in the synovial tissue of RA patients. Furthermore, silencing YTHDC1 in fibroblast-like synoviocytes (FLSs) significantly inhibited their migration, invasion, proliferation, and induced apoptosis.ConclusionYTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs.

Non-stimulant atomoxetine is recognized in various current clinical guidelines as an important alternative to stimulants for the pharmacological treatment of attention deficit/hyperactivity disorder (ADHD) in children. While its efficacy and tolerability for core symptoms are established, there is considerable inter-individual variability in response and exposure, highlighting the need for personalized dosing. In this review, we evaluated existing studies and summarized comprehensive evidence supporting the clinical implementation of therapeutic drug monitoring (TDM) and personalized dosing of atomoxetine, organized around a series of logically structured questions. Although there are notable gaps in achieving personalized dosing across multiple critical elements, the available evidence is helpful to endorse personalized dose adjustments based on TDM and CYP2D6 genotyping “whenever possible.” We advocate for ongoing improvement and enhancement in clinical practice. Future advancements will rely on a deeper understanding of ADHD, facilitating more precise diagnoses and personalized treatment strategies.

Abstract Plasmonic nanoparticles enable manipulation and enhancement of light fields at deep subwavelength scales, leading to structures and devices for diverse applications in optics. Despite hybrid plasmonic materials display remarkable optical properties due to interactions between components in nanoproximity, scalable production of plasmonic nanostructures within a single‐crystalline matrix to achieve an ideal plasmon–crystal interface remains challenging. Here, a novel approach is presented to realize efficient manipulation of in‐lattice plasmonic nanoparticles. Employing ultrafast‐laser‐driven plasmonic nanolithography, metallic nanoparticles with controllable morphology are precisely defined in the crystalline lattice of yttrium aluminum garnet (YAG) crystal. Through direct ion implantation, hybrid plasmonic material composed of nanoparticles embedded in a sub‐surface amorphous YAG layer is created. Subsequently, femtosecond laser pulses guide formation and reshaping of plasmonic nanoparticles from the amorphous layer into the single‐crystalline matrix along direction of light propagation, facilitated by a plasmon‐mediated evolution of laser energy deposition. By tailoring resonance modes and optimizing the coupling between structured particle assemblies, a range of applications including polarization‐dependent absorption and nonlinearity, controllable photoluminescence, and structural color generation is demonstrated. This research introduces a new approach for fabricating advanced optical materials featuring in‐lattice plasmonic nanostructures, paving the way for the development of diverse functional photonic devices.

Abstract Reprogramming tumor‐associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF‐κB p65, MAPK p38 and JNK by glycolysis‐mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti‐PD‐L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

PurposeCurrently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction.MethodsFinite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice.ResultsTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo.ConclusionTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM.

ABSTRACT: A suspected outbreak of duck astrovirus (DAstV) disease occurred in a large Muscovy duck farm in Guangdong Province, China, in June 2022, which severely affected the production performance and health of Muscovy ducks. This study aimed to investigate the prevalence of DAstV disease in Southeast China. Herein, we employed semi-nested PCR ethodto screen 5203 swab and liver samples from 11 Muscovy duck farms in 5 provinces of China for the presence of DAstV. Among them, 1356 samples (26.06%, 1356/5203) tested positive for DAstV, out of which 11 DAstV strains were isolated after 10 generations of blind transmission through Leghorn male hepatoma (LMH) cells and performed their whole-genome sequencing. The alignment results showed that the 11 DAstV isolates exhibited relatively low homology (15.4%–75%) with the astrovirus isolates from other species published in GenBank, whereas their homology (nucleotide: 90.4%–99.99%; amino acid: 94%–99.8%) with the DAstV type 1 (DAstV-1) reference strain was higher, indicating considerable homology. The results indicated that DAstV-1 was the main pathogenic factor. Herein, we successfully recreated the clinical symptoms of natural infection in 28-day-old specific-pathogen-free (SPF) ducks using the DAstV-1-GDB-2022 strain. The primary clinical manifestations included liver enlargement, hemorrhaging, and disruptions in liver function. Additionally, we confirmed the cross-species transmission potential of DAstV-1, marking the first occurrence of clinical symptoms of DAstV in 28-day-old SPF chickens. Our findings provide new perspectives on the epidemiology and pathogenicity of DAstV-1 and may help in advancing the development of DAstV vaccines.

An increasing population, climate change, and diminishing natural resources present severe threats to global food security, with traditional breeding and genetic engineering methods often falling short in addressing these rapidly evolving challenges. CRISPR/Cas systems have emerged as revolutionary tools for precise genetic modifications in crops, offering significant advancements in resilience, yield, and nutritional value, particularly in staple crops like rice and maize. This review highlights the transformative potential of CRISPR/Cas technology, emphasizing recent innovations such as prime and base editing, and the development of novel CRISPR-associated proteins, which have significantly improved the specificity, efficiency, and scope of genome editing in agriculture. These advancements enable targeted genetic modifications that enhance tolerance to abiotic stresses as well as biotic stresses. Additionally, CRISPR/Cas plays a crucial role in improving crop yield and quality by enhancing photosynthetic efficiency, nutrient uptake, and resistance to lodging, while also improving taste, texture, shelf life, and nutritional content through biofortification. Despite challenges such as off-target effects, the need for more efficient delivery methods, and ethical and regulatory concerns, the review underscores the importance of CRISPR/Cas in addressing global food security and sustainability challenges. It calls for continued research and integration of CRISPR with other emerging technologies like nanotechnology, synthetic biology, and machine learning to fully realize its potential in developing resilient, productive, and sustainable agricultural systems.