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Using data collected from more than 5.8 million high school and college graduates ages 18 to 65 years who participated in the American Community Survey between 2009 and 2021, the authors estimate the internal rates of return (IRRs) for individuals with college degrees in 10 broad majors compared with high school graduates. The analysis shows significant differences in the age-earnings trajectories and IRRs across college majors. Furthermore, quantile regression analyses show that IRR is generally higher at the high end of the earnings distribution compared with the low end. Finally, the authors observed a slight decrease in IRR during the study period, which is consistent with the flattening and even decline in college wage premiums following the 2008 Great Recession.

Abstract Purpose An anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital heart disease. Some high-risk anatomical structures are at risk of inducing cardiogenic shock or even sudden death. This article summarizes our surgical experience with AAOCA in paediatric patients. Methods We retrospectively analysed the clinical data of 27 paediatric AAOCA patients admitted to the Department of Cardiothoracic Surgery in our hospital from July 2015 to June 2023 and summarized the surgical treatment experience and follow-up results. Results A total of 27 patients were included in this study, including 14 patients with an anomalous left coronary artery (ALCA) and 13 patients with an anomalous right coronary artery (ARCA). A comparison of clinical data between ALCA and ARCA patients revealed that the preoperative left ventricular ejection fraction (LVEF) in ALCA patients was significantly lower than that in ARCA patients (p

Abstract Background Ulcerative colitis (UC) is a chronic and recurrent digestive tract disease that can lead to significant morbidity and mortality. The pathogenesis of UC is intricately associated with the presence of reactive oxygen species (ROS). Prussian blue (PB), an inorganic nanozyme with potent antioxidant properties, has been extensively applied in the treatment of various inflammatory conditions and tumors. However, despite the explicit antioxidant properties, the underlying molecular mechanism of PB nanozyme in the treatment of UC remains poorly understood. Furthermore, there is a deficiency in antioxidants that possess specific targeting capabilities towards UC lesions. The present study pioneered the fabrication of neutrophil (N)-macrophage (M) hybrid membrane-coated PB (NM-PB) nanozyme for the treatment of UC and investigated its underlying molecular mechanism. Results We have successfully constructed PB, N-PB, M-PB, and NM-PB nanozymes. In both the colitis cell model and UC mouse model, compared with PB, N-PB, and M-PB nanozymes, NM-PB nanozymes exhibited remarkable targeting capabilities, significantly enhancing the localization and uptake of PB nanozymes at the lesion site. NM-PB nanozymes significantly reduced levels of ROS (•OH, •OOH, and H2O2) and decreased the production of proinflammatory cytokines (TNF-α, IL-6, IL-1β). Meanwhile, these nanozymes regulated the expression of intestinal mucosal barrier-related proteins (ZO-1, E-cadherin, and Occludin) and apoptosis-related proteins (Bcl2, Bax). Furthermore, NM-PB nanozymes facilitated the polarization of proinflammatory M1-phenotype macrophage towards an anti-inflammatory M2-phenotype. The mechanistic studies demonstrated that NM-PB nanozymes mitigated the progression of UC by inhibiting the pathway of cytokine-cytokine receptor interaction. Conclusion The NM-PB nanozymes provide a promising and innovative alternative for the treatment of UC, offering enhanced targeting and efficacy through their unique design and mechanism of action. Graphical Abstract

Abstract The incidence of blast injuries has been rising globally, particularly affecting the lungs due to their vulnerability. Primary blast lung injury (PBLI) is associated with high morbidity and mortality rates, while early diagnostic methods are limited. With advancements in medical technology, and portable handheld ultrasound devices, the efficacy of ultrasound in detecting occult lung injuries early remains unclear. This study evaluates the effectiveness of immediate lung ultrasound in diagnosing PBLI. The study involved 25 healthy male Bama mini-pigs subjected to BST-I-type biological shock wave tubes. The pigs were randomly assigned to non-injured and injured groups with driving pressures of 4.0 MPa, 4.5 MPa, and 4.8 MPa. Four PBLI models were created: no injury, minor, moderate, serious and severe. Immediate lung ultrasound following the BLUE-PLUS protocol and arterial blood gas analysis were conducted pre-injury and 0.5 h, 3 h, 6 h, 12 h, and 24 h post-injury, respectively. The study analyzed lung ultrasound score differences and their correlations with lung function parameters, using ROC analysis to determine early diagnostic standards and mortality prediction efficacy. The study found that in cases of moderate and severe PBLI, lung ultrasound scores and AaDO2 significantly increased at 0.5 h post-injury, while PaO2 decreased. There was good consistency between left and right lung ultrasound results at all times. Lung ultrasound scores were significantly correlated with PaO2 and AaDO2 but not with PaCO2. The scores accurately predicted injury severity at various time points within 24 h post-injury, and the 0.5 h lung ultrasound score predicted 24 h mortality with 95.8% efficiency. PBLI exhibits hidden severity, necessitating improved early diagnostics. Immediate lung ultrasound provides effective differentiation for moderate and severe PBLI at multiple time points within 24 h post-injury, is easy to implement, and offers effective mortality risk prediction as early as 0.5 h post-injury. These findings underscore lung ultrasound’s significant clinical application value in pre-hospital early treatment settings for PBLI.

Abstract Background Homozygous familial hypercholesterolaemia (HoFH) increases risk of premature cardiovascular events and cardiac death. In severe cases of HoFH, clinical signs and symptoms cannot be controlled well by non-surgical treatments, liver transplantation (LT) currently represents the viable option. Method To assess the clinical efficacy, prognosis, and optimal timing of LT for HoFH, a retrospective analysis was conducted on the preoperative, surgical conditions, and postoperative follow-up of children who received an LT for HoFH at the Beijing Friendship Hospital over the period from December 2014 to August 2022. Results Xanthoma and decreased activity tolerance were the primary clinical manifestations in the 7 HoFH children initially assessed (one child died suddenly prior to surgery due to cardiac arrest). Accompanying these symptoms were increased blood total cholesterol (TC) and low density lipoprotein (LDL) levels, along with severe cardiovascular diseases. HoFH was confirmed in all cases by genetic and biochemical assays. Initial treatments administered to these patients consisted of low-fat diets and lipid-lowering drugs with poor outcomes. Accordingly, all 6 patients received orthotopic liver transplantations (OLT), with the result that significant postoperative reductions were observed in levels of TC and LDL. The median follow-up of these six cases was 37.41 months (range: 19.40–94.10 months). Regular postoperative follow-ups revealed that all survived and showed significant improvements in their clinical symptoms. Conclusion So far, LT is the only way to heal HoFH. LT before the appearance of obvious cardiovascular atherosclerotic lesions can significantly improve the quality of life and prognosis of patients. At the same time, the blood cholesterol level of patients should be continuously monitored after LT to further control the progression of vascular complications.

The maximum flame propagation speed, the peak pressure and the pressure rise rate of gas explosion were studied under the influence of two factors of ignition energy and gas volume fraction, by using the orthogonal experimental method in a closed pipeline with a length of 35 m and a cross-sectional area of 200 mm×200 mm. The significant impact law of gas-air mixture explosion under different ignition energy and gas volume fraction conditions was obtained. The experimental results show that under the same gas volume fraction, the flame propagation speed of gas explosion gradually increases with the extension of propagation distance from the ignition position, reaching the maximum value near the outlet, and the larger the ignition energy is, the greater the flame propagation speed is; under the same ignition energy, the maximum flame propagation speed first increases and then decreases with the increase of gas volume fraction, reaching its maximum at a gas volume fraction of 9.5%; from the analysis of range and significance effects, gas volume fraction and ignition energy and their interaction have significant effects on the maximum flame propagation speed, and the significant effects are as follows: the gas volume fraction > the ignition energy > their interaction; under the same gas volume fraction, the peak pressure and the pressure rise rate of gas explosion both increase with the increase of ignition energy, the larger the ignition energy, the higher the peak pressure and the pressure rise rate; under the same ignition energy, the peak pressure and the pressure rise rate first increase and then decrease with the increase of gas volume fraction, with the maximum value at a gas volume fraction of 9.5%; in the aspects of range and significance effects, the gas volume fraction and the ignition energy have a significant impact on the peak pressure and the pressure rise rate, the significance effects are as follows: the ignition energy > the gas volume fraction, and the interaction between the two has no significant effect on the peak pressure and the pressure rise rate.

Abstract Climate change, population growth, and agricultural intensification are increasing nitrogen (N) inputs, while driving the loss of inland water bodies that filter excess N. However, the interplay between N inputs and water body dynamics, and its implications for water quality remain poorly understood. Analyzing data from 1995 to 2015 across China, here, we find a 71% reduction in the area of small (

Abstract The discovery of tertiary lymphoid structures (TLS) within tumor tissues provides a promising avenue to promote the efficacy of cancer immunotherapy. Yet, the lack of effective strategies to induce TLS formation poses a substantial obstacle. Thus, the exploration of potential inducers for TLS formation is of great interest but remains challenging. Here, inspired by the mechanism of artificially cultivated pearls, a covalent organic framework (COF) is employed to induce TLS formation. Single-cell sequencing analysis reveals that this is achieved by promotion of cytokine hypersecretion, which facilitates the maturation, proliferation, and migration of T and B cells, critical for triggering TLS formation. Furthermore, the efficacy of COF-mediated phototherapy in inducing TLS formation is validated in both the MC38 and 4MOSC1 female tumor models. Notably, a strong synergistic effect between COF-mediated phototherapy and αCTLA-4 is observed, resulting in the effective eradication of both primary and distant tumors, while also inhibiting tumor recurrence.

Abstract Liquid organic hydrogen carriers (LOHCs) are considered promising carriers for large-scale H2 storage and transportation, among which the toluene-methylcyclohexane cycle has attracted great attention from industry and academia because of the low cost and its compatibility with the current infrastructure facility for the transportation of chemicals. The large-scale deployment of the H2 storage/transportation plants based on the toluene-methylcyclohexane cycle relies on the use of high-performance catalysts, especially for the H2 release process through the dehydrogenation of methylcyclohexane. In this work, we have developed a highly efficient catalyst for MCH dehydrogenation reaction by incorporating subnanometer PtFe clusters with precisely controlled composition and location within a rigid zeolite matrix. The resultant zeolite-encapsulated PtFe clusters exhibit the up-to-date highest reaction rate for dehydrogenation of methylcyclohexane to toluene, very high chemoselectivity to toluene (enabling the production of H2 with purity >99.9%), remarkably high stability (>2000 h) and regenerability over consecutive reaction-regeneration cycles.

Abstract Pectin is a complex plant heteropolysaccharide whose structure and function differ depending on its source. In animal feed, breaking down pectin is essential, as its presence increases feed viscosity and reduces nutrient absorption. Soybean meal, a protein-rich poultry feed ingredient, contains significant amounts of pectin, the structure of which remains unclear. Consequently, the enzyme activities required to degrade soybean meal pectin and how they interact are still open questions. In this study, we produced 15 recombinant fungal carbohydrate-active enzymes (CAZymes) identified from fungal secretomes acting on pectin. After observing that these enzymes were not active on soybean meal pectin when used alone, we developed a semi-miniaturized method to evaluate their effect as multi-activity cocktails. We designed and tested 12 enzyme pools, containing up to 15 different CAZymes, using several hydrolysis markers. Thanks to our multiactivity enzymatic approach combined with a Pearson correlation matrix, we identified 10 fungal CAZymes efficient on soybean meal pectin, 9 of which originate from Talaromyces versatilis. Based on enzyme specificity and linkage analysis, we propose a structural model for soybean meal pectin. Our findings underscore the importance of combining CAZymes to improve the degradation of agricultural co-products.

Abstract Extraskeletal osteosarcoma (ESOS) is a very rare malignant tumor. This study aimed to provide more evidence about the natural history and clinical features of ESOS, and clarify the impact of chemotherapy (CT) and radiotherapy (RT) on patient survival and postoperative recurrence for the sake of gaining a better understanding about the disease. Patient/tumor characteristics, recurrence, treatment, and follow-up durations were collected by searching studies in PubMed, Web of Science, Ovid, Elsevier, SpringerLink, Chinese National Knowledge Infrastructure (CNKI), and WAN FANG Data before June 30, 2023. Data were analyzed by SPSS-26. Altogether 1287 patients diagnosed with ESOS were retrieved from the literature. Of them, follow-up data were available in 981 patients, in whom 78 patients (7.6%) had metastases and 730 patients (74.5%) had localized disease at the time of diagnosis. Of the 730 patients with localized disease, 682 (93.4%) received surgical resection. The 5-year OS in all 981 patients, 78 metastatic patients, and 682 patients with localized disease was 33.40%, 4.9% and 41.1%, respectively. Of the 682 surgical patients, 367 patients underwent surgical resection alone, 170 received surgical resection + CT, 82 patients received surgical resection + RT, and 58 patients received both adjuvants. In addition, 348 (51%) of the 682 patients developed recurrence, including local recurrence (n = 102), metastasis (n = 130), and both (n = 116). Univariate analysis of 5-year PFS and 5-year OS showed that age, tumor size, CT, metastasis, and local recurrence were significant prognostic factors in the 682 patients with localized disease. There was no significant difference in 5-year OS between osteosarcoma-type and soft tissue-type regimens (P = 0.273). Multivariate analysis of 431 patients showed that postoperative recurrence and metastasis were significant prognostic factors for survival, and CT was not a significant prognostic factor, though CT decreased the incidence of local recurrence in ≤ 45-year age group (P = 0.047). RT reduced the incidence of local recurrence in patients ≤ 45years (P = 0.035) and patients with tumors > 5 cm (P = 0.044). So, we recommend that CT should be used for patients aged ≤ 45years, and RT can be used for patients ≤ 45years or those with tumors > 5 cm for the sake of decreasing the incidence of local recurrence, which we believe would indirectly benefit the survival of ESOS patients.

Abstract Owing to their synergistic interactions, dual-atom catalysts (DACs) with well-defined active sites are attracting increasing attention. However, more experimental research and theoretical investigations are needed to further construct explicit dual-atom sites and understand the synergy that facilitates multistep catalytic reactions. Herein, we precisely design a series of asymmetric selenium-based dual-atom catalysts that comprise heteronuclear SeN2–MN2 (M = Fe, Mn, Co, Ni, Cu, Mo, etc.) active sites for the efficient oxygen reduction reaction (ORR). Spectroscopic characterisation and theoretical calculations revealed that heteronuclear selenium atoms can efficiently polarise the charge distribution of other metal atoms through short-range regulation. In addition, compared with the Se or Fe single-atom sites, the SeFe dual-atom sites facilitate a reduction in the conversion energy barrier from *O to *OH via the coadsorption of *O intermediates. Among these designed selenium-based dual-atom catalysts, selenium-iron dual-atom catalysts achieves superior alkaline ORR performance, with a half-wave potential of 0.926 V vs. a reversible hydrogen electrode. In addition, the SeN2–FeN2-based Zn–air battery has a high specific capacity (764.8 mAh g−1) and a maximum power density (287.2 mW cm−2). This work may provide a good perspective for designing heteronuclear DACs to improve ORR efficiency.

Abstract Background The myriad implications of heavy metal pollution on human health have garnered substantial attention within the academic domain. Nevertheless, a notable research gap persists, as there is currently insufficient direct investigation elucidating the intricate interplay between nickel exposure and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods The data utilized in this study was sourced from the National Health and Nutrition Examination Survey 2017–2020. Hepatic steatosis was evaluated utilizing controlled attenuation parameters (CAP), and nickel exposure level was reflected by urinary nickel concentration. To analyze the association between nickel exposure and MASLD, three multiple logistic regression models with weights were developed. Furthermore, a mediation analysis was performed to examine insulin resistance’s potential mediating role. Results There were a total of 1,187 participants in the study, of which 548 (46.17%) had MASLD. MASLD individuals had a significantly higher urinary nickel concentration than non-MASLD individuals (P = 0.008). After accounting for demographic factors, biochemical indicators, and metabolic conditions, the odds ratio (OR) and 95% confidence interval (CI) for MASLD were 2.10 (1.09–4.05) per onefold increase in urinary nickel concentration and 2.61 (1.22–5.55) for the highest tertile versus the lowest tertile. Insulin resistance was found to mediate approximately 73.69% of the total association between nickel exposure and MASLD (P = 0.004). Conclusions Nickel exposure was independently associated with the prevalence of MASLD. Excessive exposure to nickel may promote the occurrence of MASLD by enhancing insulin resistance.

Abstract Long-term potentiation (LTP) and long-term depression (LTD) are widely used to study synaptic plasticity. However, whether proteins regulating LTP and LTD are altered in cognitive disorders and contribute to disease onset remains to be determined. Herein, we induced LTP and LTD in the hippocampal CA3-CA1 Schaffer collateral pathway, respectively, and then performed proteomic analysis of the CA1 region. We identified 20 differentially expressed proteins (DEPs) shared by the LTP and the LTD processes. Among them, we found that HtrA serine peptidase 2 (HTRA2) was mainly expressed in neurons and that HTRA2 levels were increased in both the LTP and the LTD processes in C57BL/6 mice. HTRA2 downregulation impaired synapses and reduced ATP production in cultured primary neurons. Furthermore, adeno-associated virus (AAV)-mediated HTRA2 downregulation in the hippocampus impaired synaptic plasticity and cognitive function in C57BL/6 mice. Moreover, we found that HTRA2 expression decreased in the brains of Alzheimer’s disease patients, frontotemporal lobar degeneration with ubiquitin inclusions patients, and tauopathy model mice. Finally, we showed that lentivirus-mediated HTRA2 overexpression in the hippocampus rescued PP2B reduction, alleviated tau hyperphosphorylation, and partially attenuated synaptic plasticity and cognitive deficits in the PS19 tauopathy model mice. Our study not only indicates that HTRA2 in neurons plays an important role in regulating synaptic plasticity under both physiological and pathological conditions, but also provides a novel, electrophysiology-based strategy to identify proteins regulating synaptic plasticity systematically.

China has committed to achieving carbon neutrality by 2060. It is essential to develop representative CO2 emissions pathways at the provincial level that align with the national target to facilitate effective policy implementation and scientific research. To address inconsistencies between provincial aggregate emissions and national estimates, this study compares the 2021 CO2 emissions estimates of China's provinces from the bottom‒up emissions factor method and the top‒down atmospheric CO2 concentration inversion method. We find that these methods yield comparable results for the emissions from energy combustion and industrial processes at the provincial level. Based on a review of existing research on CO2 pathways for China's provinces, we propose a set of representative pathways for China's provinces. These pathways align with past practices of allocating national emissions intensity reduction targets to provinces and are consistent with the national Tsinghua‒CMA pathway. The proposed pathways require provinces to sequentially peak their emissions by 2030, followed by rapid emissions reduction. Compared to a reference scenario without the carbon neutrality target, these pathways would incur an estimated cumulative GDP loss of about 1% between 2020 and 2060. However, there are notable regional variations, with some regions in the northwest potentially experiencing higher economic growth due to the availability of high-quality low-carbon resources. We recommend that China enhance provincial-level CO2 emissions accounting by cross-validating bottom‒up and top‒down methods. Additionally, careful consideration should be given to aligning provincial targets with national and global commitments when updating pathways toward carbon neutrality.

This study integrates field outcrop profiles, drilling cores, 2D seismic profiles, and 3D seismic data of key areas to analyze the Triassic tectonic-sequence stratigraphy in the Kuqa foreland basin, and investigates the impact of episodic thrust structures on sedimentary evolution and source rock distribution. (1) The Kuqa foreland basin has experienced stages of initial strong, weakened activities, relaxation and inactivity of episodic thrusting, resulting in the identification of 4 second-order sequences (Ehebulake Formation, Karamay Formation, Huangshanjie Formation, Taliqike Formation) and 11 third-order sequences (SQ1–SQ11) in the Triassic strata. Each sequence or secondary sequence displays a “coarse at the bottom and fine at the top” pattern due to the influence of secondary episodic thrust activity. (2) The episodic thrusting is closely linked to regional sequence patterns, deposition and source rock formation and distribution. The sedimentary evolution in the Triassic progresses from fan delta to braided river delta, lake, braided river delta, and meandering river delta, corresponding to the initial strong to the inactivity stages of episodic thrusting. The development stage of thick, coarse-grained sandy conglomerate reservoirs aligns with the strong to weakened thrust activities, while the source rock formation period coincides with the relaxation to inactivity stages. (3) Controlled by the intensity and stages of episodic thrust activity, the nearly EW trending thrust fault significantly thickened the footwall source rock during the Huangshanjie Formation, becoming the development center of Triassic source rock, and experienced multiple overthrust nappes in the soft stratum of the source rock, showing “stacked style” distribution. (4) The deep layers of the Kuqa foreland basin have the foundation and conditions necessary for the formation of substantial gas reservoirs, capable of forming various types of reservoirs such as self-generating and self-storing lithology, lower generating and upper storing fault block-lithology, and stratigraphic unconformity. This area holds significant importance for future gas exploration efforts aimed at enhancing reserves and production capabilities.

Abstract Background The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer’s disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive. Methods CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. Results We find that CD2AP is abundantly expressed in microglia and its levels are elevated in the brain of AD patients and the 5xFAD model mice at pathological stages. We demonstrate that CD2AP haploinsufficiency in microglia significantly attenuates cognitive and synaptic deficits, weakens the response of microglia to Aβ and the formation of disease-associated microglia (DAM), and alleviates synapse loss in 5xFAD mice. We show that CD2AP-deficient microglia exhibit compromised uptake ability. In addition, we find that CD2AP expression is positively correlated with the expression of the complement C1q that is important for synapse phagocytosis and the formation of DAM in response to Aβ deposition. Moreover, we reveal that CD2AP interacts with colony stimulating factor 1 receptor (CSF1R) and regulates CSF1R cell surface levels, which may further affect C1q expression. Conclusions Our results demonstrate that CD2AP regulates microgliosis and identify a protective function of microglial CD2AP deficiency against Aβ deposition, suggesting the importance of detailed investigation of AD-associated genes in different brain cells for thoroughly understanding their exact contribution to AD.

Abstract Range sidelobe modulation is a primary issue that forbids application of inter‐pulse and intra‐coherent processing interval (coherent processing interval) waveform diversity in moving target indication or moving target detection radars. Previous research has adopted mismatched filters (MMFs) to reconstruct identical compressed outputs based on an ideal model. In practice however, echo truncation is inevitable due to transceiver isolation, significantly degrading the effectiveness of MMFs. In this paper, the design of MMFs under an echo‐truncated model to achieve a robust design is considered. Specifically, the authors extract the dominant scattering profile from the close‐range echo and incorporate it into the MMF design model. To judiciously combine the robust design with the ideal one, a segmented pulse compression scheme is proposed. Numerical results indicate that the proposed robust processing scheme can effectively reduce clutter leakage in both truncated and intact scenarios.

Abstract Background Cognitive bias plays a crucial role in the onset and persistence of depression. Research has established a link between personality traits and cognitive bias; however, most of them focused on the general population, overlooking individuals with depression. We aim to explore the relationship between personality and cognitive bias in patients with major depressive disorder (MDD) and compare the results with healthy controls (HCs) to identify potential patterns. Methods The study included 124 patients with MDD and 123 HCs recruited from the Zhumadian Psychiatric Hospital in Henan, China, using the 16 Personality Factor Questionnaire (16 PF) to measure personality traits and the Cognitive Bias Questionnaire (CBQ) to measure cognitive biases. Pearson correlations and hierarchical regression analyses were employed to investigate the correlations and predictive powers. Results Traits related to neuroticism or extraversion were associated with biased responses. After controlling for sociodemographic and clinical information, neuroticism traits were found to have a significant independent effect in the MDD group. Also, the significance of Privateness in the MDD group merits more extensive exploration. Although consistent correlation patterns were found in both groups, neuroticism traits were more significant and independent in predicting biased cognitive processing in the MDD group, indicating the importance of neuroticism in the depressive context. Conclusions The present study provides insights into the connection between personality and cognitive bias from a clinical perspective, potentially enhancing clinical diagnosis and treatment modalities.

Abstract Zn-air batteries (ZABs) present high energy density and high safety but suffer from low oxygen reaction reversibility and dendrite growth at Zn electrode in alkaline electrolytes. Non-alkaline electrolytes have been considered recently for improving the interfacial processes in ZABs. However, the dynamic evolution and reaction mechanisms regulated by electrolytes at both the positive and Zn negative electrodes remain elusive. Herein, using in situ atomic force microscopy, we disclose that thin ZnO2 nanosheets deposit in non-alkaline electrolyte during discharge, followed by the formation of low-modulus products encircled around them. During recharge, the nanosheets are completely decomposed, revealing the favorable reversibility of the O2/ZnO2 chemistry. The circular outlines with low-modulus, composed of C = C and ZnCO3, are left which play a key role in promoting the oxygen reduction reaction (ORR) during the subsequent cycles. In addition, in situ optical microscopy shows that Zn can be uniformly dissolved and deposited in non-alkaline electrolyte, with the formation of homogeneous solid electrolyte interphase. Our work provides straightforward evidence and in-depth understanding of the interfacial reactions at both electrode interfaces in non-alkaline electrolyte, which can inspire strategies of interfacial engineering and material design of advanced ZABs.

Abstract Background Dorper sheep are celebrated for their fast maturation and superior meat quality, with some shedding their wool each spring. Wool shedding occurs naturally due to the hair follicle (HF) cycle, but its regulatory mechanisms remain unclear and need further investigation. Results In this study, shedding and non-shedding sheep were selected from the same Dorper flock. Skin samples were collected in September of the first year and January and March of the following years. RNA sequencing was performed on these samples. Principal component analysis (PCA) was used to assess the results. A total of 2536 differentially expressed genes (DEGs) were identified. Using a clustering heatmap and fuzzy clustering analysis three distinct gene expression patterns were identified: A pattern (high expression in anagen), T1 pattern, and T2 pattern (high expression in telogen). For each pattern, differentially expressed genes (DEGs) were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Combining this with pathway expression analysis, six A-pattern and fourteen T-pattern pathways linked to telogen-anagen transition in the HF cycle were identified. Networks of key pathways were then constructed. Additionally, key genes were identified in the telogen-anagen transition, including one A-pattern gene and seven T-pattern (T1, 1; T2, 6) genes, using the Maximal Clique Centrality (MCC) tool in Cytoscape. Predicted transcription factors (TFs) involved in key pathways, such as LEF and STAT5B, were identified. Finally, RNA-seq results were confirmed by RT-qPCR. Conclusion This study highlights critical genes and pathways in the telogen-anagen transition, and transcriptome sequencing along with bioinformatics analysis provides new insights into the regulatory mechanisms of the HF cycle and development.

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

Background This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).Methods We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.Results Twenty-nine RCTs (n = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28–15.41; I2 = 33%; P

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

The cellular uptake and tissue dispersion efficiency of nanomedicines are crucial for realizing their biological functionality. As a cutting-edge category of nanomedicine, covalent organic frameworks (COFs)-based photosensitizers, have been extensively employed in cancer phototherapy in recent years. However, the inherent aggregation tendency of COFs hinders their uptake by tumor cells and dispersion within tumor tissues, thereby limiting their therapeutic efficacy. In this study, we employed Fusobacterium nucleatum (F.n.), a prevalent intratumoral bacterium, to construct a bacterium membrane-wrapped COF, COF-306@FM, which is readily taken up by cancer cells and uniformly dispersed within tumor tissues. Meanwhile, the F.n. membrane can also serve as an immune adjuvant to warm up the “cold” tumor immune microenvironment by enhancing the CD8+ T and B cells infiltration, and inducing the formation of tumor-located tertiary lymphoid structures. Consequently, the response rate of αPD-L1 immunotherapy was drastically promoted to efficiently prevent tumor metastasis and recurrence, causing 84.6 % distant tumor inhibition and complete suppression of tumor metastasis. In summary, this innovative approach not only enhances the therapeutic potential of COFs but also opens up new avenues for integrating microbial and nanotechnological strategies in cancer treatment.

Poly(glycolic acid) (PGA) has displayed excellent tensile strength, degradability and renewability, but it still faces dilemmas in practical because of its low toughness, poor melt strength and the ease of thermal degradation. In this work, in order to take full advantages of its degradability and high strength, the PGA was toughened by poly(butyleneadipate-co-terephthalate) (PBAT) and reinforced by chopped carbon fibers (CFs) through melt compounding with the help of compatibilizers which facilitated the regulation of interfacial morphology and thereby performance. The evolution of tensile properties, dispersion state of PBAT domains, interface region and rheological behaviors of the blends were analyzed to explore the intrinsic improvement mechanism. Specifically, the increased grafting density of molecular chains revealed from the blend melt viscoelasticity was proposed to be responsible for the greatly enhanced toughness, resulting in an elongation at break of ∼90.45% and a toughness of 49.65 MJ/m3 which were dozens of times higher than PGA itself. Such blend is well capable of incorporating of CFs, showing an ultimate tensile strength ∼135 MPa whereas remaining ductility and aqua-degradability. Overall, this work provided a great potential in replacing metal alloys with the reinforced and toughened PGA composites for the applications of sacrificed tools.

Grass carp (Ctenopharyngodon idella) is the most important economic freshwater fish species in China. The stable production of high-quality grass carp depends significantly on excellent germplasm. In recent years, the generation of new germplasm based on genome editing has been applied to various cultured fish species. However, until now, there has been very few reports on the application of genome editing technology in grass carp. In this study, one-cell-stage embryos of grass carp were acquired through hormone-induced artificial spawning, thereby enabling the performance of genome editing in this species. The tyrb gene was isolated and chosen as the target of CRISPR/Cas9, because of its easily observable phenotype in F0 mutants. RT-PCR results indicated a high expression level of the tyrb gene in both skin and fin tissues. Subsequently, after the microinjection of the guide RNA (gRNA) and Cas9 protein mixture, targeted mutations were successfully identified through Sanger sequencing. Phenotypic analysis of the F0 mutants revealed that the disruption of tyrb led to a distinct golden phenotype, accompanied by a reduction or even absence of melanophores. Moreover, our data demonstrated that the combined utilization of two or three gRNAs caused large DNA fragment loss and a higher mutation rate in the F0 generation. Overall, this represents an application of CRISPR/Cas9 genome-editing technology in grass carp and may hold great significance for the future generation of new golden grass carp germplasm.

ABSTRACT: Objectives: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type β-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii (P. monteilii) isolate obtained from the human gut through whole-genome sequencing. Methods: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened as single clonal on Mueller Hinton Agar (MHA) plates containing rifampicin and meropenem. Verification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI/TOF-MS) and polymerase chain reaction (PCR) with Pseudomonas aeruginosa PAO1Ri as the recipient strain. Results: L2757hy was identified as P. monteilii through sequencing and average nucleotide identity (ANI) analysis. The genome was assigned as ST147 and comprised a 6, 130, 057 bp chromosome with a GC content of 61.8% and a 49, 704 bp plasmid. Several resistance genes, including blaIMP-1, aac(6′)-IIa and tmexCD-toprJ, as well as virulence genes, such as iroN and wzaJ, were identified on the chromosome. A novel VIM-type blaVIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring blaVIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-blaVIM-84-tniR-tniQ-tniB-tniA, likely derived from Tn402. Conclusions: Our study revealed that the novel blaVIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

In this paper, a new hybrid singular value thresholding with diagonal-modify algorithm based on the augmented Lagrange multiplier (ALM) method was proposed for low-rank matrix recovery, in which only part singular values were treated by a hybrid threshold operator with diagonal-update, and which allowed the algorithm to make use of simple arithmetic operation and keep the computational cost of each iteration low. The new algorithm decreased the complexity of the singular value decomposition and shortened the computing time. The convergence of the new algorithm was discussed. Finally, numerical experiments shown that the new algorithm greatly improved the solving efficiency of a matrix recovery problem and saved the calculation cost, and its effect was obviously better than that of the other algorithms mentioned in experiments.

We have recently proposed a novel process named low frequency electro-magnetic stirring assisted near-liquidus squeeze cast (NSC), which has been shown effective grain refinement effect in pure Mg and binary Mg-RE alloys. In this work, the NSC process was introduced for fabricating of a cup-shaped casting by Mg-Gd-Y-Zr alloy (VW103K). The cup-shaped VW103K alloy castings fabricated by NSC process show good surface quality and dimensional accuracy, as well as with fine microstructures and no megascopic pores and surface shrinkages. At the cross section of the cup-shaped castings, the grain size, phase compositions and hardness are nearly equally distributed. The NSC processed VW103K alloy show finer average grain size and higher yield strength than that of gravity cast, squeeze cast and rheo-squeeze cast counter parts. Pouring temperature is critical and may influence the microstructure and mechanical properties of NSC processed alloys. With the decrease of pouring temperature from ∼660 to ∼630 °C, the grain size is decreased initially and then coarsened slightly, while the distribution of eutectic phase gets worse continuously. An optimal pouring temperature range of ∼660 to ∼640 °C was obtained for fabricating of VW103K alloy. The mechanisms on formation of fine microstructures in NSC processed VW103K alloys is the combined effects influenced by applied pressure, pouring temperature and the shape of mold cavity.

The current situation and future development trend of the intelligent construction market in coal mines are the focus of attention for industry management departments, coal production enterprises, technology support enterprises, and other potential enterprises. It is also an important guiding direction for capital investment, technology research and development, and talent cultivation in the industry. Construct a six dimensional Porter diamond model based on production factors, demand conditions, supporting industries, enterprise strategies, industry opportunities, and government support policies to macroscopically analyze the competitive advantages of the coal mine intelligent construction market; Based on historical data such as the number of coal mines, production capacity, fixed assets investment in mining and dressing industry, total investment in intelligent construction, and construction results from 2013 to 2023, select data in different dimensions such as quantity indicators, production capacity indicators, and investment indicators, calculate the market penetration rate of intelligent construction of coal mines and perform curve fitting, and further modify the fitted curve according to the concentration of coal enterprise scale, concentration of coal production capacity distribution, and concentration of coal enterprise attributes; To further measure the market vitality of coal mine intelligent construction, taking the first batch of 71 intelligent demonstration coal mines in China as samples, the market capacity of coal mine intelligent construction from 2025 to 2035 is predicted. In the case where it is difficult to obtain comprehensive and accurate market data of all subsystems of coal mine intelligent construction over the years, SAC, SAM, and SAP product market statistical data are used to verify the reliability of coal mine intelligent market analysis and prediction results; Based on policy guidance, technological status, and actual construction, five stages of the development of the coal mine intelligent construction market have been proposed: budding, cultivating pilot projects, demonstration construction, comprehensive construction, and advanced intelligence. Based on the Jeffrey Moore divide theory, the characteristics of each stage of intelligent construction and the characteristics of early and mainstream markets have been analyzed, and the market gap and its factors in coal mine intelligent construction have been explored. Specific measures to bridge the gap have been proposed. China’s coal mine intelligent construction market has strong and sustained competitiveness; The market penetration rate is expected to reach 10% by 2026, with a market penetration rate of approximately 4.74% in 2023. This is a golden period for social capital investment, and lower investment can be used to leverage higher market share in the future; The market capacity for intelligent construction of coal mines is expected to exceed 320 billion yuan by 2025 and reach trillions of yuan by 2035; The current intelligent construction of coal mines is in a gap area between the early market and the mainstream market, and it is expected to cross the gap in 2−3 years.

Background: Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms. Methods: Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay. Results: Melatonin promoted the release of exosome from plasma, concurrently amplifying their anti-inflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR-138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p′s regulation of microglia polarization. Conclusions: We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI. The translational potential of this article: This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment.

Abstract Applying anammox to municipal wastewater treatment promises enormous energy and resource savings; however, seasonally cold conditions pose a considerable challenge, impeding its future applications towards non-tropical regions. In this study, we establish a pilot-scale wastewater treatment plant (50 m3/d) in northern China and implement the partial denitrification coupling anammox process on actual municipal wastewater. Despite seasonal cooling, the nitrogen removal efficiency remains high, ranging from 75.0 ± 4.6% at 27.8–20.0 °C to 70.4 ± 4.5% at 10–7.5 °C. This process exhibits remarkable low-temperature tolerance, achieving an in-situ anammox rate of 32.7 ± 4.7 g-N/(m3·d) at 10–7.5 °C and contributing up to 39.7 ± 6.7% to nitrogen removal. Further 15N stable isotope tracing and kinetic tests reveal that the partial denitrification is capable of supplying increasingly abundant NO2 - to anammox with decreasing temperature, enabling robust mainstream anammox against seasonal cooling. From 27.8 °C to 7.5 °C, anammox bacteria not only survive but thrive under mainstream conditions, with absolute and relative abundances increasing by 429.1% and 343.5%, respectively. This pilot-scale study sheds fresh light on extending mainstream anammox towards non-tropical regions, taking a necessary step forward toward the sustainability goals of the wastewater treatment sector.

In this study, whole genome sequencing of Bacillus velezensis L-39, an extracellular polysaccharide-producing strain isolated from Pixian Douban, was carried out through the combined use of second-generation Illumina HiSeq and third-generation PacBio platforms. The genomic analysis covered gene assembly, prediction, annotation, and the elucidation of secondary metabolite biosynthetic gene clusters and crucial gene functions, focusing on the gene clusters for carbohydrate metabolism, the nucleoside sugar synthesis pathways, and extracellular polysaccharide biosynthesis. The results showed that the whole genome size of B. velezensis L-39 was 3 970 591 bp in length, encoding a total of 3 770 genes. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the eps gene cluster and 32 functional genes were predicted from the genome, and a complete extracellular polysaccharide (EPS) synthesis pathway was mapped. Subsequently, polymerase chain reaction (PCR) was performed on the pivotal genes, with results expected. The aim of this study is to discover genes closely related to extracellular polysaccharide synthesis by B. velezensis L-39 in order to provide a scientific foundation for an in-depth analysis of the molecular basis for extracellular polysaccharide production by this strain and for its practical application and development.

Abstract Objective To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis. Methods The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed. Results With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs (P

Abstract Body composition assessment is very useful for evaluating a patient’s status in the clinic, but recognizing, labeling, and calculating the body compositions would be burdensome. This study aims to develop a web-based service that could automate calculating the areas of skeleton muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) according to L3 computed tomography (CT) images. 1500 L3 CT images were gathered from Xuzhou Central Hospital. Of these, 70% were used as the training dataset, while the remaining 30% were used as the validating dataset. The UNet framework was combined with attention gate (AG), Squeeze and Excitation block (SEblock), and Atrous Spatial Pyramid Pooling (ASSP) modules to construct the segmentation deep learning model. The model’s efficacy was externally validated using two other test datasets with multiple metrics, the consistency test and manual result checking. A graphic user interface was also created and deployed using the Streamlit Python package. The custom deep learning model named L3 Body Composition Segmentation Model (L3BCSM) was constructed. The model’s Median Dice is 0.954(0.930, 0.963)(SATA), 0.849(0.774,0.901)(VATA), and 0.920(0.901, 0.936)(SMA), which is equal to or better than classic models, including UNETR and AHNet. L3BCSM also achieved satisfactory metrics in two external test datasets, consistent with the qualified label. An internet-based application was developed using L3BCSM, which has four functional modules: population analysis, time series analysis, consistency analysis, and manual result checking. The body composition assessment application was well developed, which would benefit the clinical practice and related research.

Abstract In order to prevent leakage of pyrolysed oil and gas and the release of contaminants from the top and bottom strata, it is essential to carry out a comprehensive study of the seepage behaviour of these strata under high temperature triaxial stress conditions. The findings of this study will contribute to the development of effective strategies for the containment and integrity monitoring of subsurface reservoirs and storage environments. Mudstone, serving as both the upper and lower strata, offers an effective barrier due to its inherently low permeability. In order to explore the change rule of mudstone sealing performance under high temperature triaxial stress, an air-heated low permeability rock mass air permeability measurement system is used to measure the ground stress buried 500 m deep and the temperature variation characteristics of mudstone permeability on the roof and floor of Jimsar oil shale in Xinjiang under 100 °C. It was found that the permeability of stressed mudstone decreased with the temperature rising up to 100 °C. The primary factor influencing the outcome was the thermal expansion of the mudstone. The magnitude of the drop value was contingent upon the triaxial stresses that could potentially be induced by the application of significant tensile forces, resulting in a relatively minor drop value. The average hydraulic radius of pore in the mudstone was also calculated, which also exhibited continuous reduction as heating up to 100 °C and the degree of reduction could reach 68%. The capacity, that prevent oil & gas and contaminant from moving cross strata as a barrier, would be strengthened when the mudstone strata from roof and floor experienced the temperature low than 100 °C. The barrier performance of mudstone as a pollutant migration barrier layer to gas pollutant migration during in-situ heat injection mining of oil shale was further evaluated.

Abstract Background The aim of this study is to summarize our center’s experience with patent ductus arteriosus (PDA) ligation during extracorporeal membrane oxygenation (ECMO) treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN). Methods We retrospectively collected and analyzed clinical data from five newborns with severe respiratory failure due to PPHN who underwent PDA ligation during ECMO treatment at our hospital between January 2021 and August 2023. Results All five patients had large PDAs, measuring 10 mm, 6 mm, 6 mm, 7 mm, and 6 mm, respectively. Significant left-to-right shunting through the PDA was observed after 29 h, 14 h, 3 h, 7 h, and 5 h of ECMO treatment, respectively, at which point successful PDA ligation was performed. The surgical durations were 52 min, 45 min, 55 min, 50 min, and 40 min, respectively. Post-ligation, blood lactate levels significantly decreased compared to preoperative values. Four patients were successfully weaned off ECMO, with ECMO support durations of 64 h, 92 h, 70 h, and 87 h, respectively. After ECMO removal, mechanical ventilation was discontinued after 5.2 days, 7.2 days, 9.5 days, and 5.5 days, respectively. None of the four surviving patients experienced complications such as residual shunting, bleeding, chylothorax, neurologic injury, pneumothorax, poor wound healing, or sepsis. Conclusion During ECMO treatment for PPHN in newborns with large PDAs, the direction of blood flow through the PDA should be closely monitored. PDA ligation is a feasible and reasonable intervention when pulmonary artery pressure decreases and left-to-right shunting through the PDA becomes evident.

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with an unmet clinical need, but its epigenetic regulation remains largely undefined. By performing multiomic profiling, we recently revealed distinct super-enhancer (SE) patterns in different subtypes of breast cancer and identified a number of TNBC-specific SEs that drive oncogene expression. One of these SEs, TCOF1 SE, was discovered to play an important oncogenic role in TNBC. However, the molecular mechanisms by which TCOF1 SE promotes the expression of the TCOF1 gene remain to be elucidated. Here, by using combinatorial approaches of DNA pull-down assay, bioinformatics analysis and functional studies, we identified FOSL1 as a key transcription factor that binds to TCOF1 SE and drives its overexpression. shRNA-mediated depletion of FOSL1 results in significant downregulation of TCOF1 mRNA and protein levels. Using a dual-luciferase reporter assay and ChIP-qPCR, we showed that binding of FOSL1 to TCOF1 SE promotes the transcription of TCOF1 in TNBC cells. Importantly, our data demonstrated that overexpression of FOSL1 drives the activation of TCOF1 SE. Lastly, depletion of FOSL1 inhibits tumor spheroid growth and stemness properties of TNBC cells. Taken together, these findings uncover the key epigenetic role of FOSL1 and highlight the potential of targeting the FOSL1-TCOF1 axis for TNBC treatment.