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Abstract Background & Objective To analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest. Methods Data was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides). Results 119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p

Abstract Medical tests are crucial for treatment decision making. However, over-testing can often occur in any medical speciality or level of expertise. Since over-testing usually results in a financial burden for patients and is also a waste of medical resources, this naturally leads to the question: which medical test items (MTIs) are necessary and should be prioritized for the target patients? It is a nontrivial task to identify the right MTIs due to the diversified health status of patients and the complicated prerequisites of therapies. To this end, in this paper, we propose a data-driven approach to evaluate the priority which should be given to MTIs by modeling the relationships between MTIs and therapies. Specifically, we first develop a dual hierarchical topic model (DHTM), which views the adopted hierarchical therapies as labeled topics and the MTI reports, i.e., the set of hierarchical attribute-value pairs (AVPs), as documents. Then, with the therapy-AVP distribution and the partial MTI reports of the target patient, we can scope the candidate therapies, which are further utilized to evaluate the accumulated gain of MTIs to be tested. Moreover, the next MTI recommendation is conducted based on the gains. Finally, extensive experiments on real-world medical data validate the effectiveness of our approach, and some interesting observations are also provided.

Abstract Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor–ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin αIIbβ3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient’s pathological profile.

Abstract The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Necrozoospermia is a poorly documented condition with a low incidence, and its definition and clinical significance are unclear. Herein, we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes. We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality. Necrozoospermia was present in 3.4% (22/650) of our study population, and the lower cut-off value for sperm vitality was 75.3%. We compared two methods for assessing sperm vitality (eosin-nigrosin head staining and hypo-osmotic swelling test [HOST]), for which the percentage in the eosin-nigrosin group (mean ± standard deviation [s.d.]: 77.5% ± 10.5%) was significantly higher than that in the HOST group (mean ± s.d.: 58.1% ± 6.7% [5–10 min after incubation] and 55.6% ± 8.2% [25–30 min after incubation]; both P < 0.001). The incidence of necrozoospermia increased with age (odds ratio [OR] = 1.116, 95% confidence interval [CI]: 1.048–1.189, P = 0.001), while the percentage of normal sperm morphology and DNA fragmentation index (DFI) were significantly associated with necrozoospermia, with ORs of 0.691 (95% CI: 0.511–0.935, P = 0.017) and 1.281 (95% CI: 1.180–1.390, P < 0.001), respectively. In the following 6 months, we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection (ICSI) and pregnancy outcomes between the two groups. The necrozoospermia group had a significantly lower normal fertilization rate (74.7% vs 78.2%, P = 0.041; OR = 0.822; 95% CI: 0.682–0.992) than that in the nonnecrozoospermia group. This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

Abstract Background Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes. Methods This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group. Results We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p

Deep engineering disasters, such as rockbursts and collapses, are more related to the shear slip of rock joints. A novel multifunctional device was developed to study the shear failure mechanism in rocks. Using this device, the complete shear–deformation process and long-term shear creep tests could be performed on rocks under constant normal stiffness (CNS) or constant normal loading (CNL) conditions in real-time at high temperature and true-triaxial stress. During the research and development process, five key technologies were successfully broken through: (1) the ability to perform true-triaxial compression–shear loading tests on rock samples with high stiffness; (2) a shear box with ultra-low friction throughout the entire stress space of the rock sample during loading; (3) a control system capable of maintaining high stress for a long time and responding rapidly to the brittle fracture of a rock sample as well; (4) a refined ability to measure the volumetric deformation of rock samples subjected to true triaxial shearing; and (5) a heating system capable of maintaining uniform heating of the rock sample over a long time. By developing these technologies, loading under high true triaxial stress conditions was realized. The apparatus has a maximum normal stiffness of 1000 GPa/m and a maximum operating temperature of 300 °C. The differences in the surface temperature of the sample are constant to within ±5 °C. Five types of true triaxial shear tests were conducted on homogeneous sandstone to verify that the apparatus has good performance and reliability. The results show that temperature, lateral stress, normal stress and time influence the shear deformation, failure mode and strength of the sandstone. The novel apparatus can be reliably used to conduct true-triaxial shear tests on rocks subjected to high temperatures and stress.

Abstract Neurodevelopmental disorders are currently one of the major complications faced by patients with congenital heart disease (CHD). Chronic hypoxia in the prenatal and postnatal preoperative brain may be associated with neurological damage and impaired long-term cognitive function, but the exact mechanisms are unknown. In this study, we find that delayed neuronal migration and impaired synaptic development are attributed to altered Atoh1 under chronic hypoxia. This is due to the fact that excessive Atoh1 facilitates expression of Kif21b, which causes excess in free-state α-tubulin, leading to disrupted microtubule dynamic stability. Furthermore, the delay in neonatal brain maturation induces cognitive disabilities in adult mice. Then, by down-regulating Atoh1 we alleviate the impairment of cell migration and synaptic development, improving the cognitive behavior of mice to some extent. Taken together, our work unveil that Atoh1 may be one of the targets to ameliorate hypoxia-induced neurodevelopmental disabilities and cognitive impairment in CHD.

Abstract Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.

Boron has been considered a promising powdered metal fuel for enhancing composite propellants' energy output due to its high energy density. However, the high ignition temperature and low combustion efficiency limit the application of boron powder due to the high boiling point of the boron oxide layer. Much research is ongoing to overcome these shortcomings, and one potential approach is to introduce a small quantity of metal oxide additives to promote the reaction of boron. This study prepared boron-rich fuels with 10 wt% of eight nano-metal oxide additives by mechanical ball milling. The effect of metal oxides on the thermo-oxidation, ignition, and combustion properties of boron powder was comprehensively studied by the thermogravimetric analysis (TG), the electrically heated filament setup (T-jump), and the laser-induced combustion experiments. TG experiments at 5 K/min found that Bi2O3, MoO3, TiO2, Fe2O3, and CuO can promote thermo-oxidation of boron. Compared to pure boron, Tonset can be reduced from 569 °C to a minimum of 449 °C (B/Bi2O3). Infrared temperature measurement in T-jump tests showed that when heated by an electric heating wire at rates from 1000 K/s to 25000 K/s, the ignition temperatures of B/Bi2O3 are the lowest, even lower than the melting point of boron oxide. Ignition images and SEM for the products further showed that the high heating rate is beneficial to the rapid reaction of boron powder in the single-particle combustion state. Fuels (B/Bi2O3, B/MoO3, and B/CuO) were mixed with the oxidant AP and ignited by laser to study the combustion performance. The results showed that B/CuO/AP has the largest flame area, the highest BO2 characteristic spectral intensity, and the largest burn rate for powder lines. To combine the advantages of CuO and Bi2O3, binary metal oxide (CBO, mass ratio of 3:1) was prepared and the test results showed that CBO can very well improve both ignition and combustion properties of boron. Especially B/CBO/AP has the highest burn rate compared with all fuels containing other additives. It was found that multi-component metal-oxide additive can more synergistically improve the reaction characteristics of boron powder than unary additive. These findings contribute to the development of boron-rich fuels and their application in propellants.

Abstract Several reports have presented that balanced chromosomal rearrangements (BCRs) carriers with normal phenotypes may be carriers of complex rearrangements. However, the incidence and PGT clinical outcomes of cryptic complex chromosome rearrangements (CCCRs) in individuals with BCRs is remain unknown. We recruited a cohort of 1,264 individuals with BCR carriers from 2016 to 2021 at the Reproductive and Genetic Hospital of CITIC Xiangya. Peripheral blood was collected for karyotyping and genomic DNA extraction and the PGT-SR clinical outcomes of CCCRs carriers were analyzed and compared with those of BCR carriers. Our findings revealed that 3.6% (45/1,264) of BCR carriers had CCCRs, involving 3–25 breakpoints on 1–3 chromosomes. Furthermore, when mate-pair sequencing was employed, 63.3% (19/30) of CCCR carriers were found to have chromosome rearrangements that were different from those identified by the MicroSeq technique. And the transferable embryo rate of CCCR carriers with 3 chromosomes was significantly lower than that of CCCR carriers with only 1–2 chromosomes. In this research, we revealed that some of the BCR carriers were actually CCCR carriers, and the prognosis of PGT in CCCR carriers with one or two chromosomes is better than that of CCCR carriers with three chromosomes.

Abstract The mid-Holocene climate optimum saw warm temperatures in large parts of China, but its impact on seasonal environmental changes is not fully understood yet. Here, we use high-resolution geochemical analyses of 7000 to 6000 year-old oyster shells from the Yangtze River Delta to reconstruct climatic and oceanographic patterns. The stable isotope (δ18O, δ13C) and clumped isotope data reflect prominent seasonal changes in temperature, precipitation, and river discharge. Summer months experienced warm temperatures and a distinct increase in rainfalls and river discharge. In contrast, winter months were characterized by a dry season, which might have been longer than today. Stable isotope data also indicate regular summer upwelling in the study area. These results partly disagree with available climate models raising doubts on the models’ reliability. Thus, our palaeo-proxy data offers the possibility to evaluate and correct climate models and thereby improve predictions for the future considering on-going global warming.

The power grid, as the hub connecting the power supply and consumption sides, plays an important role in achieving carbon neutrality in China. In emerging carbon markets, assessing the investment benefits of power-grid enterprises is essential. Thus, studying the impact of the carbon market on the investment and operation of power- grid enterprises is key to ensuring their efficient operation. Notably, few studies have examined the interaction between the carbon and electricity markets using system dynamics models, highlighting a research gap in this area. This study investigates the impact of the carbon market on the investment of power-grid enterprises using a novel evaluation system based on a system dynamics model that considers carbon-emissions from an established carbon-emission accounting model. First, an index system for benefit evaluation was constructed from six aspects: financing ability, economic benefit, reliability, social responsibility, user satisfaction, and carbon-emissions. A system dynamics model was then developed to reflect the causal feedback relationship between the impact of the carbon market on the investment and operation of power-grid enterprises. The simulation results of a provincial power-grid enterprise analyze comprehensive investment evaluation benefits over a 10-year period and the impact of carbon emissions on the investment and operation of power-grid enterprises. This study provides guidelines for the benign development of power-grid enterprises within the context of the carbon market.

Abstract Background To compare the repeatability and reproducibility of corneal and corneal epithelial thickness mapping using anterior segment optical coherence tomography (AS-OCT) according to tear film break-up time (TBUT). Methods The included eyes were divided into three subgroups according to TBUT (group 1: TBUT ≤ 5 s, group 2: 5 s 10 s). All eyes were imaged separately thrice by two operators to obtain the thickness maps (TMs) of the cornea and corneal epithelium based on spatial zones encompassing a 9-mm-diameter area. Each TM consisted of 25 areas. Intraoperator (repeatability) and interoperator (reproducibility) standard deviations (Sws), coefficients of variation (CoVs), and intraclass correlation coefficients (ICCs) among the tests were calculated and compared in all the areas. Results Altogether, 132 eyes of 67 subjects were included (50, 47, and 35 eyes in groups 1, 2, and 3; respectively). The ICCs of corneal epithelial thickness and corneal thickness were > 0.75 in most of the areas. Pairwise comparisons showed that AS-OCT exhibited lower repeatability in group 1 than in groups 2 and 3 (P

Abstract Background Sows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG (n = 10) and control group (n = 10). Results In sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota. Conclusions We provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

Introduction: The herbal formula Chouchunpi San (CCPS) is a traditional formula that has been widely used and proven effective in various clinical cancer treatments. However, the mechanism of its anticancer effect remains unclear. This study aims to determine the anti-tumor effect of CCPS on colorectal cancer (CRC) in vivo and in vitro and to explore the underlying molecular mechanisms. Methods: Cell counting kit-8 assays, colony-forming assays, and flow cytometry for cell cycle and apoptosis assays were employed to determine the anti-tumor roles of CCPS. Liquid chromatography-mass spectrometry (LC-MS), network pharmacology, molecular docking, analysis of real-world clinical datasets of CRC, and western blotting were conducted to explore the molecular mechanism of CCPS on CRC. CRC xenografted mouse model, western blotting, and public CRC data analysis were conducted to evaluate the anti-tumor efficacy and mechanisms of CCPS on CRC. Results: CCPS suppresses the growth of CRC cells and increases the number of apoptotic cells dose-dependently. CCPS targets and significantly downregulates RPA1 and enhances the phosphorylation of its downstream effectors, ATR and CHK1, which are critical for CRC progression. Additionally, CCPS shows a comparable anti-tumor effect in CRC xenografted mouse models compared to Capecitabine, a chemotherapy drug commonly used in clinics. Discussion: Our findings demonstrate the potential use of CCPS in cancer treatment by suppressing cancer cell growth and modulating the RPA1/ATR/CHK1 signaling pathway in CRC. Further investigations on the application of CCPS in cancer therapies could be extended to evaluate the potential in vivo toxicity and adverse events, as well as the synergistic effect of CCPS in combination with other chemotherapeutic agents.

Background This study aimed to evaluate the efficiency of noninvasive prenatal screening (NIPS) technology in screening for microdeletions in the 7q11.23 region.Methods 19,607 pregnant women underwent NIPS in our hospital. Maternal peripheral cell-free foetal DNA (cffDNA) was routinely screened for aneuploidy by cffDNA enrichment and simultaneously analyzed for pathogenic copy number variants (CNVs). The Williams syndrome (WS) 7q11.23 region was targeted in this study. Chromosomal microarray analysis (CMA) was used to verify the screen-positive samples.Results The mean concentration of cffDNA before and after enrichment increased from 9.44% to 19.32%, with a statistically significant difference. Two out of 19,607 samples tested for CNVs were found to have a heterozygous deletion at the 7q11.23 region, indicating a high risk for WS. CMA results confirmed the 1.5 megabase (Mb) deletions at the 7q11.23 region in amniotic fluid samples. One of the two WS foetuses had a small left ventricle by ultrasound screening, and the other did not have a significant cardiovascular abnormality phenotype.Conclusions NIPS screening for Williams syndrome can be achieved by enriching cell-free foetal DNA and improving bioinformatic analysis algorithms.

Purpose: Sex-based differences in lumbar spine's fat content in adults are minimal, but significant variations exist in diffusion-weighted imaging (DWI) signal characteristics. This study aimed to investigate fat content’s impact on DWI performance in lumbar spine and potential sex differences. Methods: A retrospective analysis was conducted on upper abdominal MRI examinations in asymptomatic adult. The lumbar 1 vertebral apparent diffusion coefficient (ADC) values and fat fraction were measured. Using DWI images (b = 800 s/mm2), the lumbar 1 vertebral signal was categorized into high and iso-low signal groups. A univariate and multivariate analysis was conducted to investigate the influence of fat fraction on DWI performance. Finally, the participants were divided into three groups to analyze sex differences in the effect of fat content on DWI performance. Results: 202 subjects, 99 men were included. Fat content significantly influenced lumbar spine DWI signal in both sexes (p < 0.05). The effect on ADC values was significant only in women (p < 0.001). Women demonstrated a significantly higher proportion of high DWI signal than men in the low (p = 0.002) and middle (p = 0.012) fat content groups. Additionally, women had higher ADC values in the low fat group (p = 0.004) but lower values in the high fat group (p = 0.004). Conclusion: Fat content significantly impacts the DWI signal of lumbar spine, with a slight sex difference observed. These sex differences suggest that DWI signals may provide valuable information about the bone marrow beyond fat content.

AbstractObjective Long-term re-intervention after ultrasound-guided high intensity focused ultrasound (USgHIFU) ablation was reported, and the prediction of non-perfusion volume ratio (NPVR) in differently aged patients with uterine fibroids (UFs) was explored.Materials and Methods Patients with UFs who underwent USgHIFU ablation from January 2012 to December 2019 were enrolled and divided into < 40-year-old and ≥ 40-year-old groups. Cox regression was used to analyze the influencing factors of re-intervention rate, and receiver operating characteristic (ROC) curve was used to analyze the correlation between NPVR and re-intervention rate.Results A total of 2141 patients were enrolled, and 1558 patients were successfully followed up. The 10-year cumulative re-intervention rate was 21.9%, and the < 40-year-old group had a significantly higher rate than the ≥ 40-year-old group (30.8% vs. 19.1%, p

Abstract Background: Cognitive impairment is the most common long‐term complication in children with congenital heart disease (CHD) and is closely related to the brain network. However, little is known about the impact of CHD on brain network organization. This study aims to investigate brain structural network properties that may underpin cognitive deficits observed in children with Tetralogy of Fallot (TOF). Methods: In this prospective study, 29 preschool‐aged children diagnosed with TOF and 19 without CHD (non‐CHD) were enrolled. Participants underwent diffusion tensor imaging (DTI) scans alongside cognitive assessment using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence—fourth edition (WPPSI‐IV). We constructed a brain structural network based on DTI and applied graph analysis methodology to investigate alterations in diverse network topological properties in TOF compared with non‐CHD. Additionally, we explored the correlation between brain network topology and cognitive performance in TOF. Results: Although both TOF and non‐CHD exhibited small‐world characteristics in their brain networks, children with TOF significantly demonstrated increased characteristic path length and decreased clustering coefficient, global efficiency, and local efficiency compared with non‐CHD (p < 0.05). Regionally, reduced nodal betweenness and degree were found in the left cingulate gyrus, and nodal efficiency was decreased in the right precentral gyrus and cingulate gyrus, left inferior frontal gyrus (triangular part), and insula (p < 0.05). Furthermore, a positive correlation was identified between local efficiency and cognitive performance (p < 0.05). Conclusion: This study elucidates a disrupted brain structural network characterized by impaired integration and segregation in preschool TOF, correlating with cognitive performance. These findings indicated that the brain structural network may be a promising imaging biomarker and potential target for neurobehavioral interventions aimed at improving brain development and preventing lasting impairments across the lifetime.

BackgroundNeuropathic pain (NPP) is a multifaceted pain syndrome that occurs as a consequence of physical injury or underlying diseases, with an incidence rate of 7%-10%, NPP poses a significant clinical challenge as current treatment options are ineffective. The accumulation of apoptotic cells and neuroinflammation play crucial roles in the pathological mechanisms of NPP. Here, we aim to investigate strategies for effectively clearing apoptotic cells and provide therapeutic interventions for NPP.MethodsCCI mice were treated with different concentrations of ozone (15μg, 30μg, 45μg) to investigate the effects on the accumulation of apoptotic cells and neuroinflammation. In vitro, the phagocytic function of BMDM towards apoptotic neutrophils after ozone treatment was examined.ResultsWe found ozone at a concentration of 30μg significantly alleviated mechanical hypersensitivity in CCI mice and ozone significantly upregulates the phagocytic activity of BMDM. Furthermore, we investigated the mechanisms and found ozone could activate AMPK, upregulate Gas6 (but not Protein S), activate MerTK (a key receptor involved in apoptosis), and enhance the phagocytic function of BMDM towards apoptotic neutrophils. It caused the promotion of SOCS3 expression and the suppression of inflammatory factors IL-1β, IL-6, and TNF-a. Interestingly, the effect of ozone in alleviating CCI-induced pain was abolished by the AMPK inhibitor CC and the MerTK receptor inhibitor UNC2541.ConclusionOzone facilitated macrophage clearance of apoptotic cells, decreased neuroinflammation by activation of p-AMPK/Gas6/MerTK/SOCS3 signaling pathway, which may become an effective therapeutic approach for neuropathic pain after further clinical validation.

IntroductionPrimary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary glands. The re-establishment of salivary glands (SGs) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, its potential to restore SGs function during pSS has not yet been investigated.MethodsNonobese diabetic (NOD)/LtJ mice (pSS model) were intravenously administered with adeno-associated viruses carrying MYDGF at 11 weeks of age. Salivary flow rates were determined before and after treatment. Mice were killed 5 weeks after MYDGF treatment, and submandibular glands were collected for analyses of histological disease scores, inflammatory cell infiltration, PCR determination of genes, and Western blotting of functional proteins. Furthermore, mRNA sequencing and bioinformatics were used to predict the mechanism underlying the therapeutic effect of MYDGF.ResultsTreatment of NOD/LtJ mice with MYDGF alleviated pSS, as indicated by increased salivary flow rate, reduced lymphocyte infiltration, attenuated glandular inflammation, and enhanced AQP5 and NKCC1 expression. The gene expression levels of cytokines and chemokines, including Ccl12, Ccl3, Il1r1, Ccr2, Cx3cr1, Il7, Mmp2, Mmp14, Il1b, and Il7, significantly decreased after treatment with MYDGF, as determined by RNA sequencing. Meanwhile, MYDGF inhibits infiltration of macrophages (Mϕ) in SGs, induces polarization of M2ϕ, and suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C motif receptor 1 (CX3CR1) axis.ConclusionsOur findings showed that MYDGF could revitalize the SGs function of pSS, inhibit infiltration of Mϕ, and promote M2ϕ polarization via suppression of the CX3CL1/CX3CR1 axis, which has implications for potential therapy for pSS.

AimsTo assess the predictive value of estradiol (E2) related parameters on the incidence of gestational diabetes mellitus (GDM) in women undergoing fresh embryo transfer.Materials and methodsA Post-hoc analysis of a prospective cohort study.ResultsWe identified an optimal E2/follicle (E2/F) ratio threshold of 246.03 pg/ml on the day of human chorionic gonadotropin (hCG) administration. Women with an E2/F ratio exceeding this threshold had significantly lower rates of GDM (12.75% vs. 20.41%, P < 0.001) and ovarian hyperstimulation syndrome (OHSS) (11.75% vs. 15.48%, P = 0.03). Additional E2 parameters were also evaluated: baseline E2, E2 on hCG day, E2 increase, and E2 fold change. Lower GDM rates were observed in women with baseline E2 above 31.50 pg/ml (13.51% vs. 19.42%, P

The proliferation of vigorous lianas usually forms liana canopies over the crowns of host trees and liana mats on the ground of open areas or large forest gaps. While research on liana canopies has increased significantly in recent decades, our understanding of liana mats remains limited. Merremia boisiana (Convolvulaceae), a fast-growing liana, forms mature liana mats that can persist for decades, characterized by numerous upright searcher shoots that extend from the liana mats in search of supports. However, the reasons behind the proliferation of these searchers, as well as their growth and branching patterns in mature liana mats that lack support, are not well understood. We hypothesize that searchers are an inevitable phase in the growth rhythm of M. boisiana within these mature liana mats. We tested our hypothesis by tracking the lifespan and status of M. boisiana searchers during the early, middle, and late periods of the year. Our findings reveal the following: (1) M. boisiana searchers exhibit apical dominance and have a short lifespan; over 95% of searchers lost their terminal buds within two months during the early period, while it took only one month during the middle and late periods. (2) The original lateral buds of the searchers also have a limited lifespan, yet the nodes can sprout new lateral buds after the loss of their originals. (3) With the withering of terminal buds, the total number of lateral shoots decreased, while the quantity of long lateral shoots (≥ 50 cm) and their elongation rates increased. (4) Each surviving segment of a searcher typically develops one or two long lateral shoots, none of which grow into searchers. We conclude that the shoots of M. boisiana in mature liana mats periodically alternate between searchers and stolons, collectively forming a zigzag branching system. The high rate of lateral bud resprouting may facilitate the rapid recovery of mature liana mats early in the year, while the reduced lifespan of searchers and limited number of long lateral shoots represent effective strategies for M. boisiana, balancing the investment and risk associated with foraging in mature liana mats.

Abstract Objective To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. Materials and methods Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan–Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. Main results A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR

Abstract Objective This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. Methods For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). Results Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. Conclusion In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.

Parathyroid cancer is an extremely rare form of neuroendocrine malignancy. Apart from surgery, the effectiveness of chemotherapy and radiotherapy is limited, and the efficacy of targeted drugs remains unclear. In this study, we demonstrate the therapeutic effectiveness and adverse reaction of the targeted drug surufatinib in treating a case of parathyroid cancer, and concurrently review the recent advancements in the treatment of parathyroid cancer. The patient, a 55-year-old male, underwent his first surgery for a “right cervical mass” in May 2011. Postoperative pathology indicated an atypical adenoma of the parathyroid gland. In August 2016, the patient underwent a second surgery for recurrence of the right cervical tumor, with a pathological diagnosis of parathyroid cancer based on clinical history. In November 2017, the patient underwent a third surgery for recurrence of the right cervical tumor. In December 2017, the patient underwent adjuvant external radiation therapy. In August 2022, the patient developed spinal and lung metastases and underwent spinal surgery. Subsequently, the patient received three rounds of chemotherapy on October 5, 2022, October 28, 2022, and November 18, 2022, but the tumor showed slight enlargement. In January 2023, the patient began treatment with surufatinib. After two cycles of treatment, the tumor showed regression. Given the scarcity of systemic treatment options for parathyroid cancer, the targeted drug surufatinib may offer a promising potential treatment option.

Bladder cancer is one of the leading causes of mortality globally. The development of bladder cancer is closely associated with alternative splicing, which regulates human gene expression and enhances the diversity of functional proteins. Alternative splicing is a distinctive feature of bladder cancer, and as such, it may hold promise as a therapeutic target. This review aims to comprehensively discuss the current knowledge of alternative splicing in the context of bladder cancer. We review the process of alternative splicing and its regulation in bladder cancer. Moreover, we emphasize the significance of abnormal alternative splicing and splicing factor irregularities during bladder cancer progression. Finally, we explore the impact of alternative splicing on bladder cancer drug resistance and the potential of alternative splicing as a therapeutic target.

Introduction: Mouse embryonic stem cell (ESC) self-renewal can be maintained through dual inhibition of GSK3 and MEK kinases. MEK has two highly homologous downstream kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2). However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear.Methods: We selectively deleted or inhibited ERK1, ERK2, or both using genetic and chemical genetic approaches combined with small molecule inhibitors. The effects of ERK paralog-specific inhibition on mouse ESC self-renewal and differentiation were then assessed.Results: ERK1/2 were found to be dispensable for mouse ESC survival and self-renewal. The inhibition of both ERK paralogs, in conjunction with GSK3 inhibition, was sufficient to maintain mouse ESC self-renewal. In contrast, selective deletion or inhibition of only one ERK paralog did not mimic the effect of MEK inhibition in promoting mouse ESC self-renewal. Regarding ESC differentiation, inhibition of ERK1/2 prevented mesendoderm differentiation. Additionally, selective inhibition of ERK1, but not ERK2, promoted mesendoderm differentiation.Discussion: These findings suggest that ERK1 and ERK2 have both overlapping and distinct roles in regulating ESC self-renewal and differentiation. This study provides new insights into the molecular mechanisms of ERK1/2 in governing ESC maintenance and lineage commitment, potentially informing future strategies for controlling stem cell fate in research and therapeutic applications.

Abstract Interdisciplinary research is increasingly recognized as one of the solutions to today’s challenging scientific and societal issues. Many studies have aimed to explore the relationship between the interdisciplinarity of research and the attention they receive from the scientific community as well as society. However, the relationship between interdisciplinarity and attention from policy documents remains unclear. In this study, we utilize publications data on the COVID-19 topic to explore such a relationship. Through the analysis and interpretation of empirical datasets, this research finds that there is a positive correlation between the interdisciplinarity of scientific publications and the attention they receive from policy documents in almost all fields. Among the three dimensions (i.e., variety, balance, and disparity) of interdisciplinarity, variety exhibits the most pronounced positive impact on political attention. This study fills a previous research gap and provides insights for researchers and policymakers, highlighting that interdisciplinary research holds greater potential to impact policy formulation and implementation processes.

Abstract This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis.

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 10[6] sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 10[6] sperm) and the group with low acrosin activity (

Abstract The study aims to develop and validate the Curriculum-related Physical Activity Recall questionnaire (CUPAR) as a measure of physical activity in adolescents. 83 middle-school students (13.23 ± 0.74 yrs) completed the CUPAR and whore ActiGraph accelerometers for seven consecutive days. Correlations and Bland–Altman plots were to examine the agreement between these two measures. Significant correlations were observed between the CUPAR and ActiGraph accelerometer for 5-day MPA (r = 0.29, p

The annular flow payload is among the first batch of space science experimental projects carried out on the Fluid Physics Rack of the China Space Station. This paper provides a detailed introduction to the development of the payload, ground validation, and in orbit experiments. The payload, sized 320 mm × 200 mm × 220 mm, includes an annular flow model and supports supply (24 V, 12 V, and 5 V), communication, and data transmission. A multi-functional heating column in the annular flow model was designed, allowing for the column to operate in fixed, rotating, and lifting scenarios. In the first round, 96 sets of space experiments covering volume ratio ranges from 0.45 to 1.06 were carried out. The annular flow liquid surface state, temperature oscillation, and infrared temperature field evolution were obtained. Mode decomposition shows the oscillatory convection of the m = 4 travelling wave, and contains m = 3, m = 6, and m = 8 waves.

High-voltage initial anode-free lithium metal batteries (AFLMBs) promise the maximized energy densities of rechargeable lithium batteries. However, the reversibility of the high-voltage cathode and lithium metal anode is unsatisfactory in sustaining their long lifespan. In this research, a concentrated electrolyte comprising dual salts of LiTFSI and LiDFOB dissolved in mixing solvents of dimethyl carbonate (DMC) and fluoroethylene carbonate (FEC) with a LiNO3 additive was formulated to address this challenge. FEC and LiNO3 regulate the anion-rich solvation structure and help form a LiF, Li3N-rich solid electrolyte interphase (SEI) with a high lithium plating/stripping Coulombic efficiency of 98.3%. LiDFOB preferentially decomposes to effectively suppress the side reaction at the high-voltage operation of the Li-rich Li1.2Mn0.54Ni0.13Co0.13O2 cathode. Moreover, the large irreversible capacity during the initial charge/discharge cycle of the cathode provides supplementary lithium sources for cycle life extension. Owing to these merits, the as-fabricated AFLMBs can operate stably for 80 cycles even at an ultrahigh voltage of 4.6 V. This study sheds new insights on the formulation of advanced electrolytes for highly reversible high-voltage cathodes and lithium metal anodes and could facilitate the practical application of AFLMBs.

Glycogen synthase kinase-3β (GSK-3β) has been identified to promote inflammation and its inhibitors have also been proven to treat some inflammatory-mediated diseases in animal models. Allosteric inhibitors inherently have better therapeutical value due to their higher specificity than ATP-competitive ones. In this paper, we reported the discovery of a novel series of N, N-dibenzylcinnamamide (DBCA) compounds as allosteric GSK-3β inhibitors via a scaffold hopping strategy. The in vitro enzymatic evaluation showed most DBCA derivatives have inhibitory effects on GSK-3β in a micromolar scale. Among them, seven compounds D-27 ∼ 33 showed activities at lower micromolar levels. Kinetic analysis revealed this type of compound inhibited GSK-3β by an allosteric modulation. The in vitro cytokine release assay demonstrated that D-33 could reduce the release of proinflammatory cytokines IL-1β and IL-6 while keeping IL-12 and TNF-α intact, indicating it might be a potential safer candidate for certain inflammatory conditions, such as neuroinflammatory diseases. Finally, docking studies were performed to suggest binding modes that explain the impacts of candidates on the enzyme.

BackgroundVitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes.DesignPost-hoc analysis of a prospective observational cohort.SettingSingle-center study.Participants2569 women receiving embryo transfer.InterventionNone.Main outcome measuresThe main outcomes were oocyte and embryo quality as well as pregnancy outcomes.ResultsDBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF.

Abstract Fluorescent poly(N‐isopropylacrylamide‐co‐Nile blue) (pNIPAm‐co‐NB) microgels were synthesized that exhibited fluorescence intensity changes in a water temperature‐dependent fashion. NB is well known to exhibit fluorescence intensity that depends on the hydrophobicity of the environment, while pNIPAm‐based microgels are well known to transition from swollen (hydrophilic) to collapsed (relatively hydrophobic) at temperatures greater than 32 °C; hence, we attribute the above behavior to the hydrophobicity changes of the microgels with increasing temperature. This phenomenon is ultimately due to NB dimers (relatively quenched fluorescence) being broken in the hydrophobic environment of the microgels leading to relatively enhanced fluorescence. We went on to show that the introduction of cucurbit[7]uril (CB[7]) into the pNIPAm‐co‐NB microgels enhanced their fluorescence allowing them to be used for polyamine (e.g., spermine [SPM]) detection. Specifically, CB[7] forms a host–guest interaction with NB in the microgels, which prevents NB dimerization and enhances their fluorescence. When SPM is present, it forms a host–guest complex that is favored over the CB[7]‐NB host–guest interaction, which frees the NB for dimerization and leads to fluorescence quenching. As a result, we could generate an SPM sensor capable of SPM detection down to ~0.5 µmol/L in complicated matrixes such as serum and urine.

Converting solar energy into fuels/chemicals through photochemical approaches holds significant promise for addressing global energy demands. Currently, semiconductor photocatalysis combined with redox techniques has been intensively researched in pollutant degradation and secondary energy generation owing to its dual advantages of oxidizability and reducibility; however, challenges remain, particularly with improving conversion efficiency. Since graphene’s initial introduction in 2004, three-dimensional (3D) graphene-based photocatalysts have garnered considerable attention due to their exceptional properties, such as their large specific surface area, abundant pore structure, diverse surface chemistry, adjustable band gap, and high electrical conductivity. Herein, this review provides an in-depth analysis of the commonly used photocatalysts based on 3D graphene, outlining their construction strategies and recent applications in photocatalytic degradation of organic pollutants, H2 evolution, and CO2 reduction. Additionally, the paper explores the multifaceted roles that 3D graphene plays in enhancing photocatalytic performance. By offering a comprehensive overview, we hope to highlight the potential of 3D graphene as an environmentally beneficial material and to inspire the development of more efficient, versatile graphene-based aerogel photocatalysts for future applications.

High-performance computing (HPC) plays a crucial role in scientific computing, and the efficient utilization of HPC to accomplish computational tasks remains a focal point of research. This study addresses the issue of parameter tuning for Earth system models by proposing a comprehensive solution based on the concept of scientific workflows. This solution encompasses detailed methods from sensitivity analysis to parameter tuning and incorporates various approaches to enhance result accuracy. We validated the reliability of our methods using five cases in the Single Column Atmosphere Model (SCAM). Specifically, we investigated the influence of fluctuations of 11 typical parameters on 10 output variables. The experimental results show that the magnitude of the impact on the results varies significantly when different parameters are perturbed. These findings will help researchers develop more reasonable parameterization schemes for different regions and seasons.

Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).

Peritonitis is a common and life-threatening inflammatory disease. Myeloid cells are elevated in the peripheral blood and contribute to peritonitis, but their circulating dynamics are not clear. In vivo flow cytometry (IVFC) is a noninvasive technique for monitoring the dynamics of circulating cells in live animals. It has been extensively used to detect circulating tumor cells, but rarely for monitoring immune cells. Here, we describe a method adapting an intravital microscope for IVFC so that we can monitor LysM-EGFP-labeled circulating myeloid cells in a tumor necrosis factor (TNF) α-induced peritonitis mouse model. Using this IVFC method, we quantified the blood flow velocity and cell concentration in circulation. We observed a significant increase in LysM-EGFP+ cells in circulation after TNFα intraperitoneal (i.p.) injection, which reached a plateau in ~20 min. Conventional cytometry analysis showed that most LysM-EGFP+ cells were neutrophils. Increasing blood neutrophils were accompanied by neutrophil recruitment to the peritoneal cavity and neutrophil emigration from the bone marrow. We then monitored neutrophil CD64 expression in vivo and found a significant increase in TNFα-induced peritonitis. We also found that CD18 blockade doubled the circulating neutrophil number in TNFα-induced peritonitis, suggesting that CD18 is critical for neutrophil recruitment in peritonitis. Overall, we demonstrate that IVFC techniques are useful for studying the circulating dynamics of immune cells during inflammatory diseases.

Blowers are widely used in tasks such as ventilation, exhaust, drying, cooling, heat dissipation, or conveying medium, and they usually consume a lot of energy. There is an inevitable gap between the rotating impeller and static volute casing due to manufacturing tolerance and thermal deformation. The circulating flow in the gap has an important effect on the performance of the blower. In this study, computational fluid dynamics (CFD) was used to investigate the performance of the blower under different flow conditions and gaps, and the accuracy of the numerical simulation was verified by performance experiments. The results show that the flow separation under low flow conditions in the impeller channel can be suppressed by the circulating flow. However, the efficiency of the blower is decreased because a part of the power is used to maintain the circulating flow. Under design conditions, efficiency is reduced by 5.3~8.2%, depending on the gap sizes. Due to the increased flow rate in the impeller channel caused by the gap circulating flow, the net flow rate of the impeller under design conditions is about 12% higher than the inlet flow rate of the blower. Therefore, it leads to an increase of about 12% in impeller efficiency calculated by the net flow rate compared with the inlet flow rate. Finally, the flow field distribution on the impeller channel under different gap conditions was compared, and the effects of the gap on the blower performance were analyzed from the perspective of flow field structure.

Most space shuttle fuel tanks use a center column to hold the Propellant Management Device (PMD). This paper analyzes the gas–liquid interface state in the tanks with a central column during microgravity experiments conducted in the Chinese Space Station. It launches an extended study to investigate the gas–liquid interface state under different gravity conditions. Using the perturbation method and boundary layer theory, we numerically calculated the morphology of the gas–liquid interface under varying gravity conditions based on the Young–Laplace equation. The results were then compared to those obtained from existing commercial software and were found to be consistent. Based on this, the study develops two types of calculation procedures. The first procedure generates the corresponding shape of the liquid surface by inputting the height of the liquid surface endpoints and the gravity level. The second procedure is based on the targeting method and generates the corresponding liquid surface by inputting the volume of the liquid in the storage tank and the gravity level. The procedures were used to analyze the variation of gas–liquid interface properties under different gravity conditions. This study offers theoretical support for liquid management in aerospace engineering fuel tanks.

The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common. More potent and durable HER2-targeted therapies are desperately needed for patients with HER2-positive cancers. In this study, we developed a lipid nanoparticle (LNP)-based therapy formulated with mRNA encoding a novel HER2-CD3-Fc bispecific antibody (bsAb) for HER2-positive cancers. The LNPs efficiently transfected various types of cells, such as HEK293S, SKOV-3, and A1847, leading to robust and sustained secretion of the HER2-CD3-Fc bsAb with high binding affinity to both HER2 and CD3. The bsAb induced potent T-cell-directed cytotoxicity, along with secretion of IFN-λ, TNF-α, and granzyme B, against various types of HER2-positive tumor cells in vitro, including A549, NCI-H460, SKOV-3, A1847, SKBR3, and MDA-MB-231. The bsAb-mediated antitumor effect is highly specific and strictly dependent on its binding to HER2, as evidenced by the gained resistance of A549 and A1847 her2 knockout cells and the acquired sensitivity of mouse 4T1 cells overexpressing the human HER2 extracellular domain (ECD) or epitope-containing subdomain IV to the bsAb-induced T cell cytotoxicity. The bsAb also relies on its binding to CD3 for T-cell recruitment, as ablation of CD3 binding abolished the bsAb’s ability to elicit antitumor activity. Importantly, intratumoral injection of the HER2-CD3-Fc mRNA-LNPs triggers a strong antitumor response and completely blocks HER2-positive tumor growth in a mouse xenograft model of human ovarian cancer. These results indicate that the novel HER2-CD3-Fc mRNA-LNP-based therapy has the potential to effectively treat HER2-positive cancer.

Abstract Carbonyl aromatic compounds are promising cathode candidates for lithium‐ion batteries (LIBs) because of their low weight and absence of cobalt and other metals, but they face constraints of limited redox‐potential and low stability compared to traditional inorganic cathode materials. Herein, by means of first‐principles calculations, a significant improvement of the electrochemical performance for carbonyl‐bridged heterotriangulenes (CBHTs) is reported by introducing pyridinic N in their skeletons. Different center atoms (B, N, and P) and different types of functionalization with nitrogen effectively regulate the redox activity, conductivity, and solubility of CBHTs by influencing their electron affinity, energy levels of frontier orbitals and molecular polarity. By incorporating pyridinic N adjacent to the carbonyl groups, the electrochemical performance of N‐functionalized CBHTs is significantly improved. Foremost, the estimated energy density reaches 1524 Wh kg−1 for carbonyl‐bridged tri (3,5‐pyrimidyl) borane, 50% higher than in the inorganic reference material LiCoO2, rendering N‐functionalized CBHTs promising organic cathode materials for LIBs. The investigation reveals the underlying structure‐performance relationship of conjugated carbonyl compounds and sheds new lights for the rational design of redox‐active organic molecules for high‐performance lithium ion batteries (LIBs).