Search

Abstract Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy. The refined protocol involves a two-step TTC staining process (perfusion and immersion) and subsequent Zamboni fixation to differentiate myocardial viability and necrosis, and use of Coomassie brilliant blue to label area-at-risk. After the duo-staining steps were completed, the heart sample was embedded and sliced transversally by a cryostat into a series of thin sections (50 µm) for microscopic analysis. The refined TTC (redTTC) assay yielded remarkably high-quality images with striking color intensity and sharply defined boundaries, permitting unambiguous and reliable delineation of the infarct and area-at-risk. In the same animals, the redTTC assay showed good agreement with the in-vivo gold standard measurements (LGE and MEMRI). Meanwhile, redTTC imaging allows tracking of viable cardiomyocytes at cellular resolution, and with this enhanced capability, we convincingly demonstrated the pro-survival action of stem cells based-therapy. Therefore, the redTTC assay represents a significant technical advance that permits precise detection of the true extent of cardiac injury and cardiomyocyte viability. This approach is cost-effective and may be adapted for use in diverse applications, making it highly appealing to many laboratories performing ischemia/reperfusion injury experiments.

Abstract Background Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. Results We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. Conclusion Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.

Background As one of the most common and abundant internal modifications of eukaryotic mRNA, N6-methyladenosine (m6A) modifications are closely related to placental development. Ferroptosis is a newly discovered form of programmed cell death. During placental development, placental trophoblasts are susceptible to ferroptosis. However, the interactions of m6A and ferroptosis in trophoblast physiology and injury are unclear. Methods Recurrent miscarriage (RM) was selected as the main gestational disease in this study. Published data (GSE76862) were used to analyze the gene expression profiles in patients with RM. The extent of m6A modification in total RNA of villous tissues between patients with RM and healthy controls (HC) was compared. ALKBH5 (encoding AlkB homolog 5, RNA demethylase) was selected as the candidate gene for further research. Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry (IHC) confirmed the elevated expression of ALKBH5 in the cytotrophoblasts of patients with RM. Then, cell counting kit-8 assays, glutathione disulfide/glutathione quantification, 2′,7′-dichlorfluorescein-diacetate staining, and malonaldehyde assays were used to explore the alterations of ferroptosis-related characteristics following RAS-selective lethal (RSL3) stimulation after overexpression of ALKBH5. Thereafter, we re-analyzed the published RNA sequencing data upon knockdown of ALKBH5, combined with published tissue RNA-seq data, and FTL (encoding ferritin light chain) was identified as the ferroptosis-related gene in cytotrophoblasts of patients with RM that is regulated by ALKBH5. Finally, western blotting and IHC confirmed the increased expression of FTL in the cytotrophoblasts from patients with RM. Results Total m6A levels were decreased in patients with RM. The most significant differentially m6A-related gene was ALKBH5, which was increased in patients with RM. In vitro cell experiments showed that treatment with RSL3 resulted in increased cell death and upregulated ALKBH5 expression. Overexpression of ALKBH5 alleviated RSL3-induced HTR8 cell death and caused decreased levels of intracellular oxidation products. Published transcriptome sequencing revealed that FTL was the major ferroptosis-related gene regulated by ALKBH5 in the villous tissues of patients with RM. Consistent with the expression of ALKBH5, FTL was increased by RSL3-induction and increased in patients with RM. Conclusion Elevated ALKBH5 alleviated RSL3-induced cytotrophoblast cell death by promoting the expression of FTL in patients with RM. Our results supported the view that ALKBH5 is an important regulator of the ferroptosis-related etiology of RM and suggested that ALKBH5 could be responsible for epigenetic aberrations in RM pathogenesis.

ABSTRACTUnderstanding the composition and community of airborne mycobiota associated with fungal diseases was critical for mushroom production and disease control. In this study, we first investigated airborne fungi concentrations in different function areas of a Chinese shiitake factory. Then, high-throughput sequencing was employed to characterise the airborne fungal compositions and communities of this factory during high and low incidence seasons of shiitake artificial log rot disease (SLRD). The lowest concentration of culturable airborne fungi was observed in spawn-running greenhouse (250–450 CFU/m3), while the airborne fungi concentrations in cultivation greenhouses were up to 7,000–8,500 CFU/m3. The airborne fungal communities across distinct function areas showed convergence. The four major mushroom contaminants, Trichoderma, Penicillium, Cladosporium, and Aspergillus were the stable core fungi. Seasonal shifts in compositions, abundances, and communities of airborne fungi were systematically analysed and found to be associated with SLRD. Compared with the SLRD low incidence season, the airborne fungal communities were rich but uneven in the SLRD high incidence season, in which Trichoderma was dominant. Further analysis indicated that the favourable temperature and humidity caused the proliferation of Trichoderma and then affected the fungal communities, which presented an SLRD-seasonal variation. SLRD incidence could be significantly reduced by reasonably increasing the ambient temperature. For the first time, we comprehensively characterised the dynamics of airborne fungal communities across the SLRD occurrence in the shiitake factory. Findings here also provided valuable information for fungal exposures in the mushroom industry.

Abstract Background Abnormal placental development is a significant factor contributing to perinatal morbidity and mortality, affecting approximately 5–7% of pregnant women. Trophoblast syncytialization plays a pivotal role in the establishment and maturation of the placenta, and its dysregulation is closely associated with several pregnancy-related disorders, including preeclampsia and intrauterine growth restriction. However, the underlying mechanisms and genetic determinants of syncytialization are largely unknown. Methods We conducted a systematic drug screen using an epigenetic compound library to systematically investigate the epigenetic mechanism essential for syncytialization, and identified mixed lineage leukemia 1 (MLL1), a histone 3 lysine 4 methyltransferase, as a crucial regulator of trophoblast syncytialization. BeWo cells were utilized to investigate the role of MLL1 during trophoblast syncytialization. RNA sequencing and CUT&Tag were further performed to search for potential target genes and the molecular pathways involved. Human placenta tissue was used to investigate the role of MLL1 in TEA domain transcription factor 4 (TEAD4) expression and the upstream signaling during syncytialization. A mouse model was used to examine whether inhibition of MLL1-mediated H3K4me3 regulated placental TEAD4 expression and fetoplacental growth. Results Genetic knockdown of MLL1 or pharmacological inhibition of the MLL1 methyltransferase complex (by MI-3454) markedly enhanced syncytialization, while overexpression of MLL1 inhibited forskolin (FSK)-induced syncytiotrophoblast formation. In human placental villous tissue, MLL1 was predominantly localized in the nuclei of cytotrophoblasts. Moreover, a notable upregulation in MLL1 expression was observed in the villus tissue of patients with preeclampsia compared with that in the control group. Based on RNA sequencing and CUT&Tag analyses, depletion of MLL1 inhibited the Hippo signaling pathway by suppressing TEAD4 expression by modulating H3K4me3 levels on the TEAD4 promoter region. TEAD4 overexpression significantly reversed the FSK-induced or MLL1 silencing-mediated trophoblast syncytialization. Additionally, decreased hypoxia-inducible factor 1A (HIF1A) enrichment at the MLL1 promoter was observed during syncytialization. Under hypoxic conditions, HIF1A could bind to and upregulate MLL1, leading to the activation of the MLL1/TEAD4 axis. In vivo studies demonstrated that the administration of MI-3454 significantly enhanced fetal vessel development and increased the thickness of the syncytial layer, thereby supporting fetoplacental growth. Conclusions These results revealed a novel epigenetic mechanism underlying the progression of syncytialization with MLL1, and suggest potential avenues for identifying new therapeutic targets for pregnancy-related disorders.

Improving the sustainability and processability of shape memory composites is key to expanding their applications. This work introduces a novel bio-based shape memory composite resin with renewable cellulose nanocrystals, suitable for stereolithography (SLA) printing. We prepared epoxy soybean oil-based composites by incorporating Itaconic acid monomethyl ester (IAME) modified cellulose nanocrystals (CNCs-IAME) into IAME modified epoxy soybean oil (IESO). The CNCs-IAME/IESO composite resin, with a viscosity of 1.01–1.22 Pa•s, is ideal for SLA printing. Adding 0.75 wt% CNCs-IAME particles enhances mechanical properties, yielding a tensile strength of 19.54 MPa and elongation at a break of 34.03%. Demonstrated applications include flexible supports and temperature-responsive sensors. This innovative composite offers excellent sustainability and SLA-printability, showing great potential for new bio-based heat-activated shape memory materials.

Abstract Background and aims Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. Methods Data were retrieved from the SPARK study (Effect of Cardiac Function on Short‐Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo‐oxygenase regression analysis and Kaplan–Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. Results Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16‐fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21‐fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan–Meier curves demonstrated early separation among groups, persisting throughout the follow‐up period (all p

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durumDesf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulks were annotated and analyzed by Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew.

The growth of vegetation directly maintains the ecological security of coal mining areas. It is of great significance to monitor the dynamic changes in vegetation in mining areas and study the driving factors of vegetation spatial division. This study focuses on the Yima mining area in Henan Province. Utilizing MODIS and multi-dimensional explanatory variable data, the Theil–Sen Median + Mann–Kendall trend analysis, variation index, Hurst index, and optimal-parameter-based geographical detector model (OPGD) are employed to analyze the spatiotemporal changes and future trends in the EVI (enhanced vegetation index) from 2000 to 2020. This study further investigates the underlying factors that contribute to the spatial variation in vegetation. The results indicate the following: (1) During the period studied, the Yima mining area was primarily characterized by a moderate-to-low vegetation cover. The area exhibited significant spatial variation, with a notable pattern of “western improvement and eastern degradation”. This pattern indicated that the areas that experienced improvement greatly outnumbered the areas that underwent degradation. Moreover, there was an inclination towards a deterioration in vegetation in the future. (2) Based on the optimal parameter geographic detector, it was found that 2 km was the optimal spatial scale for the analysis of the driving factors of vegetation change in this area. The optimal parameter combination was determined by employing five spatial data discretization methods and selecting an interval classification range of 5–10. This approach effectively addresses the subjective bias in spatial scales and data discretization, leading to enhanced accuracy in vegetation change analysis and the identification of its driving factors. (3) The spatial heterogeneity of vegetation is influenced by various factors, such as topography, socio-economic conditions, climate, etc. Among these factors, population density and mean annual temperature were the primary driving forces in the study area, with Q > 0.29 and elevation being the strongest explanatory factor (Q = 0.326). The interaction between temperature and night light was the most powerful explanation (Q = 0.541), and the average Q value of the interaction between the average annual temperature and other driving factors was 0.478, which was the strongest cofactor among the interactions. The interactions between any two factors enhanced their impact on the vegetation’s spatial changes, and each driving factor had its suitable range for affecting vegetative growth within this region. This research provides scientific support for conserving vegetation and restoring the ecological system.

Background and objective: The association between cardiac dysfunction and functional outcome in acute ischemic stroke (AIS) is not clear. We aimed to investigate the relationship between the routinely assessed left ventricular ejection fraction (LVEF) and functional outcomes in patients with AIS. Methods: Data came from a prospective, observational, single-center study (Effect of Cardiac Function on Short-term Functional Prognosis in Patients with Acute Ischemic Stroke, SPARK). The LVEF was assessed with transthoracic echocardiography within 7 days of stroke onset. The primary outcome was functional disability, defined as a modified Rankin Scale score of 3–6 at 90 days (range: 0–6, with higher scores indicating greater disability). We also investigated the association of the LVEF with mortality, early neurological deterioration, hospital stay, and costs. Multivariate logistic regression analysis and 2:1 propensity score matching (PSM) were performed to compare the differences in outcomes. Results: A total of 1181 patients were included in this analysis, of which 87 (7.4 %) patients were found to have LVEF of

BackgroundBread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor.Aim and methodsTo analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties.ResultsDelayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing.ConclusionThe impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

BackgroundInterstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD.MethodsFrom 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS).ResultsThe community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.

IntroductionOsteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels.MethodsBased on information from the 2013–2014, 2017–2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes.ResultsIn 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease.ConclusionOur findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.

BackgroundSerum albumin plays a pivotal role in regulating plasma oncotic pressure and modulating fluid distribution among various body compartments. Previous research examining the association between maternal serum albumin levels and fetal growth yielded limited and inconclusive findings. Therefore, the specific influence of serum albumin on fetal growth remains poorly understood and warrants further investigation.MethodsA retrospective study involved 39200 women who had a singleton live birth at a tertiary-care academic medical center during the period from January 2017 to December 2020. Women were categorized into four groups according to the quartile of albumin concentration during early pregnancy: Q1 group, ≤41.0 g/L; Q2 group, 41.1-42.6 g/L; Q3 group, 42.7-44.3 g/L and Q4 group, >44.3 g/L. The main outcome measures were mid-term estimated fetal weight, birthweight and gestational age. Multivariate linear and logistic regression analysis were performed to detect the independent effect of maternal serum albumin level on fetal growth after adjusting for important confounding variables.ResultsIn the crude analysis, a significant inverse correlation was found between early pregnancy maternal serum albumin levels and fetal growth status, including mid-term ultrasound measurements, mid-term estimated fetal weight, birthweight, and gestational age. After adjustment for a number of confounding factors, mid-term estimated fetal weight, birthweight, and birth height decreased significantly with increasing albumin levels. Compared to the Q2 group, the Q4 group had higher rates of preterm birth (aOR, 1.16; 95% CI, 1.01–1.34), small-for-gestational-age (aOR, 1.27; 95% CI, 1.11–1.45) and low birthweight (aOR, 1.41; 95% CI, 1.18–1.69), and lower rate of large-for-gestational-age (aOR, 0.85; 95% CI, 0.78–0.94). Moreover, to achieve the optimal neonatal outcome, women with higher early pregnancy albumin levels required a greater reduction in albumin levels in later pregnancy stages.ConclusionsA higher maternal serum albumin level during early pregnancy was associated with poor fetal growth, with the detrimental effects becoming apparent as early as the mid-gestation period. These findings provided vital information for clinicians to predict fetal growth status and identify cases with a high risk of adverse neonatal outcomes early on.

Dielectric elastomer is a kind of electronic electroactive polymer, which plays an important role in the application of soft robots and flexible electronics. In this study, an all-organic polyaniline/copper phthalocyanine/silicone rubber (PANI/CuPc/PDMS) dielectric composite with superior comprehensive properties was prepared by manipulating the arrangement of filler in a polymer matrix assisted by electric fields. Both CuPc particles and PANI particles can form network structures in the PDMS matrix by self-assembly under electric fields, which can enhance the dielectric properties of the composites at low filler content. The dielectric constant of the assembled PANI/CuPc/PDMS composites can reach up to 140 at 100 Hz when the content of CuPc and PANI particles is 4 wt% and 2.5 wt%, respectively. Moreover, the elastic modulus of the composites remains below 2 MPa, which is important for electro-deforming. The strain of assembled PANI/CuPc/PDMS three-phase composites at low electric field strength (2 kV/mm) can increase up to five times the composites with randomly dispersed particles, which makes this composite have potential application in the field of soft robots and flexible electronics.

Abstract Background Two-dimensional ultrathin Ti3C2 nanosheets are increasingly being used in biomedical applications owing to their special physicochemical properties. But, the biological effects of its exposure on the reproductive system is still unclear. This study evaluated the reproductive toxicity of Ti3C2 nanosheets in the testes. Results Ti3C2 nanosheets at doses of 2.5 mg/kg bw and 5 mg/kg bw in mice caused defects in spermatogenic function, and we also clarified an underlying molecular mechanism of it in vivo and in vitro model. Ti3C2 nanosheets induced an increase of reactive oxygen species (ROS) in testicular and GC-1 cells, which in turn led to the imbalance in oxidative and antioxidant systems (also known as oxidative stress). Additionally, oxidative stress often induces cellular DNA strand damages via the oxidative DNA damages, which triggered cell cycle arrest in the G1/G0 phase, leading to cell proliferation inhibition and irreversible apoptosis. ATM/p53 signaling manifest key role in DNA damage repair (DDR), and we demonstrate that ATM/p53 signaling was activated, and mediated the toxic damage process caused by Ti3C2 nanosheet exposure. Conclusion Ti3C2 nanosheet-induced disruption of proliferation and apoptosis of spermatogonia perturbed normal spermatogenic function that was mediated by ATM/p53 signaling pathway. Our findings shed more light on the mechanisms of male reproductive toxicity induced by Ti3C2 nanosheets. Graphical abstract

BackgroundA link between food-induced inflammation and common chronic diseases has been identified in studies. However, there was uncertainty about the influence of dietary inflammatory potential on the risk of chronic kidney disease (CKD) among middle-aged and older groups. Our research aimed to examine the connection between dietary inflammatory index (DII) to CKD in people aged 40 years and older.MethodsThis study comprised ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Linear associations of DII with CKD, low-eGFR, and albuminuria were examined using multiple logistic regression, whereas non-linear associations were assessed by smoothed curve fitting. Besides, we conducted subgroup analyses and interaction tests.ResultsOf the 23,175 middle-aged and older individuals, a total of 5,847 suffered from CKD, making up 25.23% of all participants. After adjustment for all covariates, we found that increased DII scores were positive with an increased hazard of CKD (OR = 1.08, 95% CI: 1.05, 1.10, p < 0.0001), and the same was shown between DII and low-eGFR (OR = 1.16, 95% CI: 1.13, 1.19, p < 0.0001). After further converting DII into categorical variables, the above relationship still existed. These relations were consistent in different ages, genders, BMI, whether smoking, whether suffering from hypertension, and whether suffering from diabetes, with no significant stratification differences (all P for interaction >0.05). Surprisingly, we did not find a statistically significant correlation of DII to albuminuria after complete adjustment for covariates (OR = 1.02, 95% CI: 1.00, 1.05, p = 0.0742). Even when DII was considered as a categorical variable, this relation was still not statistically significant. Furthermore, we found an association in the shape of a U between DII and low-eGFR in the fully adjusted model, with a turning point at a DII of 1.6.ConclusionOur findings indicated that middle-aged and older persons with greater levels of DII had a significantly higher risk of CKD.

ABSTRACT The antifungal susceptibility profile and epidemiological cut-off values (ECOFFs) of Yarrowia lipolytica, a rare opportunistic yeast, remain unclear. We conducted a comprehensive multi-method study on clinical isolates from various central hospitals, based on the China Hospital Invasive Fungal Surveillance Network (2009–2022). Our objective was to evaluate the antifungal susceptibility of Y. lipolytica, establish its local ECOFFs (L-ECOFFs), and compare the performance of the ATB FUNGUS 3 (ATB), Sensititre YeastOne (SYO), and minimum inhibitory concentration (MIC) test strip (MTS) with that of the broth microdilution (BMD) method. L-ECOFFs were established using ECOFFinder, and we examined ERG11 mutations to assess the reliability of the L-ECOFFs. The L-ECOFF for fluconazole was 8 µg/mL. Non-wild-type isolates of antifungal drugs, such as flucytosine and azoles, were exclusively isolated from patients. Additionally, we detected that four strains with the ERG11 A395T mutation (azole MIC >L-ECOFF) may be associated with the exposure to azole drugs. For azoles, ATB showed the highest essential agreement with the BMD (98.18%–100%), followed by SYO (85.45%–100%). However, ATB could not detect susceptibility to echinocandins, while SYO exhibited the highest agreement (98.18%–100%) in detecting echinocandin susceptibility. Our findings indicate that acquired azole cross-resistance has emerged despite Y. lipolytica infections being rare. This research provides crucial antifungal susceptibility data and establishes the initial L-ECOFFs for Y. lipolytica. The SYO is recommended as the optimal laboratory antifungal susceptibility testing method for Y. lipolytica, followed by ATB, whereas the use of MTS requires caution. We hope that this study will facilitate improved clinical management of Y. lipolytica infections. IMPORTANCE Yarrowia lipolytica, also known as Candida lipolytica, is an emerging opportunistic “rare pathogenic yeast”. Due to the limited data on its antifungal susceptibility, the clinical treatments become challenging. Based on the China Hospital Invasive Fungal Surveillance Network (2009–2022), we conducted a comprehensive multi-method study on clinical isolates from various central hospitals. This study is currently the largest study carried out to assess the antifungal susceptibility of Y. lipolytica. It is also the first to establish local epidemiological cut-off values (L-ECOFFs), identify its ERG11 mutations, and assess the consistency between the three prevalent commercial antifungal susceptibility testing methods and the broth microdilution method. We recommend the Sensititre YeastOne as the best option for antifungal susceptibility testing for Y. lipolytica, followed by the ATB FUNGUS 3. Nevertheless, practitioners should use the MIC test strip with discretion.

IntroductionAccording to reports, obesity has a significant impact on bone health. And the weight-adjusted-waist index (WWI), superior to BMI and waist circumference (WC), is a new obesity indicator arising in recent years. This research investigated the relationship between WWI and total bone mineral density (BMD) for adults aged 20 to 59.MethodsUsing data from the 2011–2018 NHANES, we looked into the independent link between WWI and total BMD as well as its nonlinearity using weighted multiple linear regression and smooth curve fitting. Two-stage linear regression models were employed to calculate the threshold effects. There were additional subgroup analyses and testing for interactions.ResultsMultiple linear regression studies on a total of 10,372 individuals showed a significant inverse link between WWI and total BMD in adults between 20 and 59 [β = -0.04, 95% CI: (-0.04, -0.03), P0.05). In addition, we found a nonlinear relationship between WWI and total BMD in diabetic and CKD patients, for which the saturation point was 11.38 cm/√kg in the CKD patient group and 10.29 cm/√kg in the diabetic patient group.ConclusionOur analysis demonstrated a significant inverse association between WWI and total BMD in adults aged 20-59.

Currently, most designs for interlayer toughening of carbon-based filler/polymer nanocomposites are highly dependent on experimental iterative trial and error, and there is no rational design framework. This work uses machine learning to build a fast and accurate predictive model and assess the extent to which key features affect performance, giving researchers ideas for designing new materials and greatly improving efficiency. A training database is built by first collecting the features of the domain that affect the interlaminar performance. A stacking model fusion of the three machine learning models was then performed to construct a highly accurate fast prediction model. Besides, the importance of key features is evaluated during model training using the Random Forest Algorithm (RFA). Finally, by predicting the performance of materials and analyzing the importance of characteristics to guide material preparation, the development cycle is shortened and costs are reduced.

The ERF subfamily, a significant part of the APETALA2/ethylene-responsive element-binding factor (AP2/ERF) transcription family, plays a crucial role in plant growth, development, and stress responses. Despite its importance, research on this gene family in sweet cherry (Prunus avium L.) is limited. This study identified and analyzed the sweet cherry ERF subfamily in terms of classification, physicochemical properties, structural characteristics, chromosome distribution, gene replication and collinearity, Cis-acting elements, and potential protein interactions. Preliminary investigations of transcription during fruit cracking and normal development were also conducted. Fifty ERFs (PatiERF1~50) were identified, distributed unevenly across eight chromosomes and classified into ten groups with nineteen conserved motifs. Collinearity analysis with other plant species revealed homology, with the highest number of ERF orthologous genes found in apple (Malus domestica L.). Cis-acting elements, particularly abscisic acid response factor, were abundant in PatiERF promoters. Weighted gene co-expression network analysis (WGCNA) and quantitative real-time PCR (RT-qPCR) analysis indicated the involvement of PatiERFs in sweet cherry fruit development and cracking, and nine and four significant candidates related to these processes were speculated, respectively. Furthermore, four other classes of transcription factors (TFs), namely MYB, GRAS, BHLH, and BZIP, as well as 23 structure genes, were predicted to have co-expression and interaction relationships with PatiERFs during fruit development. This suggests their potential synergistic regulation with ERFs in the cherry fruit development process. Our study represents the first comprehensive genome-wide analysis of the ERF subfamily in sweet cherry, laying a crucial foundation for a deeper understanding of the molecular mechanisms correlated with fruit growth, development, and cracking mediated by ERF genes.

In plants exposed to ultraviolet B radiation (UV-B; 280–315 nm), metabolic responses are activated, which reduce the damage caused by UV-B. Although several metabolites responding to UV-B stress have been identified in plants, the accumulation of these metabolites at different time points under UV-B stress remains largely unclear, and the transcription factors regulating these metabolites have not been well characterized. Here, we explored the changes in metabolites in rice after UV-B treatment for 0 h, 6 h, 12 h, and 24 h and identified six patterns of metabolic change. We show that the rice transcription factor OsbZIP18 plays an important role in regulating phenylpropanoid and flavonoid biosynthesis under UV-B stress in rice. Metabolic profiling revealed that the contents of phenylpropanoid and flavonoid were significantly reduced in osbzip18 mutants compared with the wild-type plants (WT) under UV-B stress. Further analysis showed that the expression of many genes involved in the phenylpropanoid and flavonoid biosynthesis pathways was lower in osbzip18 mutants than in WT plants, including OsPAL5, OsC4H, Os4CL, OsCHS, OsCHIL2, and OsF3H. Electrophoretic mobility shift assays (EMSA) revealed that OsbZIP18 bind to the promoters of these genes, suggesting that OsbZIP18 function is an important positive regulator of phenylpropanoid and flavonoid biosynthesis under UV-B stress. In conclusion, our findings revealed that OsbZIP18 is an essential regulator for phenylpropanoid and flavonoid biosynthesis and plays a crucial role in regulating UV-B stress responses in rice.

Aluminum butylmethylphosphinate AiBMP as a flame retardant and phenolphthalein as a synergistic agent were applied in a thermoplastic polyester elastomer (TPEE)) in the current study. The thermal properties, flame retardancy, crystallization and mechanical properties of TPEE/AiMBP with or without phenolphthalein were investigated using various characterizations, including the limiting oxygen index (LOI), vertical burning test (UL 94), thermogravimetric analysis TG, differential scanning calorimetry, microcombustion calorimeter (MCC), scanning electron microscopy (SEM), and mechanical tests. The results revealed that AiBMP alone is an efficient flame retardant of TPEE. Adding 15 wt.% AiBMP increases the LOI value of TPEE from 20% to 36%. The formula TPEE-15 AiBMP passed the UL 94 V-0 rating with no dripping occurring. The MCC test shows that AiBMP depresses the heat release of TPEE. In comparison with pure TPEE, the heat release rate at peak temperature and the heat release capacity of TPEE-15AiBMP are reduced by 46.1% and 55.5%, respectively. With the phenolphthalein added, the formula TPEE/13AiBMP/2Ph shows a higher char yield at high temperatures (>600 °C), and the char layer is stronger and more condensed than TPEE-15AiBMP.The tensile strength and elongation at break values of TPEE-13AiBMP-2Ph are increased by 29.63% and 4.8% in comparison with TPEE-15AiBMP. The SEM morphology of the fracture surface of the sample shows that phenolphthalein acts as a plasticizer to improve the dispersion of AiBMP within the matrix. The good char charming ability of phenolphthalein itself and improved dispersion of AiBMP make the TPEE composites achieve both satisfying flame retardancy and high mechanical properties.

The red flesh coloration of apples is a result of a biochemical pathway involved in the biosynthesis of anthocyanins and anthocyanidins. Based on apple genome analysis, a high number of regulatory genes, mainly transcription factors such as MYB, which are components of regulatory complex MYB-bHLH-WD40, and several structural genes (PAL, 4CL, CHS, CHI, F3H, DFR, ANS, UFGT) involved in anthocyanin biosynthesis, have been identified. In this study, we investigated novel genes related to the red-flesh apple phenotype. These genes could be deemed molecular markers for the early selection of new apple cultivars. Based on a comparative transcriptome analysis of apples with different fruit-flesh coloration, we successfully identified and characterized ten potential genes from the plant hormone transduction pathway of auxin (GH3); cytokinins (B-ARR); gibberellins (DELLA); abscisic acid (SnRK2 and ABF); brassinosteroids (BRI1, BZR1 and TCH4); jasmonic acid (MYC2); and salicylic acid (NPR1). An analysis of expression profiles was performed in immature and ripe fruits of red-fleshed cultivars. We have uncovered genes mediating the regulation of abscisic acid, salicylic acid, cytokinin, and jasmonic acid signaling and described their role in anthocyanin biosynthesis, accumulation, and degradation. The presented results underline the relationship between genes from the hormone signal transduction pathway and UFGT genes, which are directly responsible for anthocyanin color transformation as well as anthocyanin accumulation during apple-fruit ripening.

Vibrio, Gram-negative pathogenic bacterium, are commonly found in aquatic environments. Not only it can cause food poisoning and wound infection in humans, but also easily lead to spoilage in seafood. Biofilm formation regulated by quorum sensing is an important reason for Vibrio resistance and infection. In this study, the action mechanism of quorum sensing, biofilm formation and drug resistance in Vibrio are reviewed. The quorum sensing system in Vibrio is summarized. The correlation between quorum sensing system and biofilm in Vibrio is discussed. Effect of biofilm formation on drug resistance of Vibrio is mainly elaborated from three aspects in limiting the penetration of fungicides, inducing the adaptability of bacterial phenotype and horizontal transmission of drug resistance genes. In addition, the research status of quorum sensing inhibitors (QSIs）for control Vibrio biofilm, including chemical synthetic QSIs, QSIs derived from plant and microbiological, is further summarized. The study aims at providing reference for solving the problem of seafood spoilage and foodborne diseases caused by Vibrio.

In order to promote marine technology innovation and marine industry development of Shandong Province, this paper summarized the development status of marine technology innovation platform of Shandong, analyzed the problems, and proposed corresponding countermeasures and suggestions. The results showed that the construction of marine technology innovation platform system was continually being improved, new breakthroughs had been made in variety and quantity, and high-quality development of marine industry had been promoted. However, there were still some problems, such as low overall development level, unbalance of regional and industrial layout, lack of provincial platforms and advanced platforms, and weak role of enterprise innovation force. In the future, Shandong should focus on top-level design, enhance enterprise technological innovation, innovate process management, improve the regulatory system, strengthen policy support and promote collaborative innovation in the development of marine technology innovation platform.

Diagnosing and treating secondary psychiatric symptoms with accuracy can be challenging in clinical settings. In this case study, we report on a female patient with Cushing’s disease who was misdiagnosed with anxiety disorder during her first psychiatric visit. Following initial ineffective psychiatric intervention, unexplained hypokalemia, and hypothyroidism, the patient visited the endocrinology clinic and was diagnosed with Cushing’s disease. During the medical and surgical procedures that followed, high doses of psychotropic medication were continued to treat persisting anxiety. After discharge, the patient developed autonomic dysfunction and impaired consciousness. Upon readmission, serotonin syndrome due to inappropriate psychiatric medication was diagnosed. The management of secondary psychiatric syndromes must be adapted to changes in the patient’s primary condition, which necessitates interdisciplinary collaboration in general hospital settings.

The environmental pollutant Benzo(a)pyrene (BaP) has an adverse effect on the reproductive performance of mammals. We previously showed that BaP treatment during early pregnancy damages endometrial morphology and impairs embryo implantation. Endometrial decidualization at the implantation site (IS) after embryo implantation is crucial for pregnancy maintenance and placental development. The balance between proliferation and differentiation in endometrial stromal cells (ESCs) is a crucial event of decidualization, which is regulated by the cell cycle. Here, we report that abnormal decidualization caused by BaP is associated with cell cycle disturbance of stromal cells. The mice in the treatment group were gavaged with 0.2 mg/kg/day BaP from day 1–8 of pregnancy, while those in control were gavaged with corn oil in parallel. BaP damaged the decidualization of ESCs and reduced the number of polyploid cells. Meanwhile, BaP up-regulated the expression of Ki67 and PCNA, affecting the differentiation of stromal cells. The cell cycle progression analysis during decidualization in vivo and in vitro showed that BaP induced polyploid cells deficiency with enhanced expressions of CyclinA(E)/CDK2, CyclinD/CDK4 and CyclinB/CDK1, which promote the transformation of cells from G1 to S phase and simultaneously activate the G2/M phase. The above results indicated that BaP exposure accelerates cell cycle progression, promotes ESC proliferation, inhibits differentiation, and impedes proper decidualization and polyploidy development. Thus, the imbalance of ESC proliferation and differentiation would be an important mechanism for BaP-induced defective decidualization.

Abstract Vitamin D insufficiency/deficiency has been linked to an increased risk of preeclampsia. Impaired placental amino acid transport is suggested to contribute to abnormal fetal intrauterine growth in pregnancies complicated by preeclampsia. However, if vitamin D-regulated amino acid transporter is involved in the pathophysiologic mechanism of preeclampsia has not been clarified yet. The aberrant expression of key isoform of L-type amino acid transporter LAT1 was determined by western blot and immunohistochemistry in the placenta from normotensive and preeclamptic pregnancies. The role for vitamin D on placental LAT1 expression was investigated through the exposure of HTR-8/SVneo human trophoblast cells to the biologically active 1,25(OH)2D3 and the oxidative stress-inducer cobalt chloride (CoCl2). Our results showed that placental LAT1 expression was reduced in women with preeclampsia compared to normotensive pregnancies, which was associated with decreased expression of vitamin D receptor (VDR). 1,25(OH)2D3 significantly upregulated LAT1 expression in placental trophoblasts, and also prevented the decrease of mTOR activity under CoCl2-induced oxidative stress. siRNA targeting VDR significantly attenuated 1,25(OH)2D3-stimulated LAT1 expression and mTOR signaling activity. Moreover, treatment of rapamycin specifically inhibited the activity of mTOR signaling and resulted in decrease of LAT1 expression. In conclusion, LAT1 expression was downregulated in the placenta from women with preeclampsia. 1,25(OH)2D3/VDR could stimulate LAT1 expression, which was likely mediated by mTOR signaling in placental trophoblasts. Regulation on placental amino acid transport may be one of the mechanisms by which vitamin D affects fetal growth in preeclampsia.

Abstract Background Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of Ti3C2 on human health remain poorly understood. Results To explore the influence on foetal or offspring after exposure to Ti3C2 nanosheets, we established a mouse model exposed to different doses of Ti3C2 nanosheets during early pregnancy in this study. We found that Ti3C2 nanosheets had negligible effect on the reproductive ability of maternal mice, including average pregnancy days, number of new-borns, and neonatal weight, etc. Unexpectedly, abnormal neurobehavior and pathological changes in the cerebral hippocampus and cortex in adult offspring were observed following Ti3C2 nanosheet treatment. In further studies, it was found that Ti3C2 exposure led to developmental and functional defects in the placenta, including reduced area of labyrinth, disordered secretion of placental hormones, and metabolic function derailment. The long-chain unsaturated fatty acids were significantly higher in the placenta after Ti3C2 exposure, especially docosahexaenoic acid (DHA) and linoleic acid. The metabolic pathway analysis showed that biosynthesis of unsaturated fatty acids was upregulated while linoleic acid metabolism was downregulated. Conclusions These developmental and functional defects, particularly metabolic function derailment in placenta may be the cause for the neuropathology in the offspring. This is the first report about the effects of Ti3C2 nanosheet exposure on pregnancy and offspring. The data provides a better understanding of Ti3C2 nanosheets safety. It is suggested that future studies should pay more attention to the long-term effects of nanomaterials exposure, including the health of offspring in adulthood, rather than only focus on short-term effects, such as pregnancy outcomes. Metabolomics could provide clues for finding the prevention targets of the biological negative effect of Ti3C2 nanosheets. Graphical Abstract

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Abstract Background Cellular dedifferentiation is a regenerative prerequisite that warrants cell cycle reentry and appropriate mitotic division during de novo formation of cardiomyocytes. In the light of our previous finding that expression of injury-responsive element, Wilms Tumor factor 1 (WT1), in pericardial adipose stromal cells (ADSC) conferred a compelling reparative activity with concomitant IL-6 upregulation, we then aim to unravel the mechanistic network that governs the process of regenerative dedifferentiation after ADSC-based therapy. Methods and results WT1-expressing ADSC (eGFP:WT1) were irreversibly labeled in transgenic mice (WT1-iCre/Gt(ROSA)26Sor-eGFP) primed with myocardial infarction. EGFP:WT1 cells were enzymatically isolated from the pericardial adipose tissue and cytometrically purified (ADSCgfp+). Bulk RNA-seq revealed upregulation of cardiac-related genes and trophic factors in ADSCgfp+ subset, of which IL-6 was most abundant as compared to non-WT1 ADSC (ADSCgfp−). Injection of ADSCgfp+ subset into the infarcted hearts yielded striking structural repair and functional improvement in comparison to ADSCgfp− subset. Notably, ADSCgfp+ injection triggered significant quantity of dedifferentiated cardiomyocytes recognized as round-sharp, marginalization of sarcomeric proteins, expression of molecular signature of non-myogenic genes (Vimentin, RunX1), and proliferative markers (Ki-67, Aurora B and pH3). In the cultured neonatal cardiomyocytes, spontaneous dedifferentiation was accelerated by adding tissue extracts from the ADSC-treated hearts, which was neutralized by IL-6 antibody. Genetical lack of IL-6 in ADSC dampened cardiac dedifferentiation and reparative activity. Conclusions Taken collectively, our results revealed a previous unappreciated effect of IL-6 on cardiac dedifferentiation and regeneration. The finding, therefore, fulfills the promise of stem cell therapy and may represent an innovative strategy in the treatment of ischemic heart disease.

IntroductionSocial stress in adolescents precipitates stress-related emotional disorders. In this study we aimed to investigate oligodendrogenesis in three stress-associated brain regions, medial prefrontal cortex (mPFC), habenula, and amygdala in adolescent mice exposed to social defeat stress.MethodsFour-week-old adolescent mice were subjected to social defeat for 10 days, followed by behavioral tests and evaluations of oligodendroglial proliferation and differentiation.ResultsStressed mice showed reduced social interaction, more stretched approach posture, lower sucrose preference, but no changes in the forced swimming test. EdU labeled proliferative cells, newly formed NG2+EdU + oligodendrocyte precursor cells (OPCs), and Olig2+EdU+ oligodendrocyte lineage cells (OLLs) were significantly decreased in the mPFC and the lateral habenula, but not in the amygdala and the medial habenula in socially defeated mice. APC+Edu+ newly-generated mature oligodendrocytes (OLs) were decreased in the mPFC in stressed mice. However, the total number of NG2+ OPCs, APC+ mature OLs, and Olig2+ OLLs were comparable in all the brain regions examined between stressed and control mice except for a decrease of APC+ mature OLs in the prelimbic cortex of stressed mice.ConclusionOur findings indicate that adolescent social stress causes emotion-related behavioral changes and region-specific impairment of oligodendrogenesis.

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in de novo DNA methylation. There was an alteration in maternal (F0) endometrial function, which might lead to growth and developmental disorder in offspring (F1). In this study, we investigated the effect of maternal endometrial DNMT3B deficiency on the metabolism in offspring. We constructed endometrial DNMT3B conditional knockout female mice (cKO) which were mated with normal C57BL/6 male mice to obtain the F1 generation. Further, to study the development of these offspring, we observed them at three different life stages which included the 6-week-old juvenile, 9-week-old sub-adult and 12-week-old adult. Follow the detection of a range of metabolism-related indicators, we found that in the cKO F1 generation, liver triglyceride level was significantly elevated in 9-week-old female mice, lipid droplet deposition was significantly increased in 9-week-old and 12-week-old mice, and the expression of lipid metabolism key factors in the liver was markedly decreased except of 6-week-old male mice. These results indicate that maternal endometrial DNMT3B conditional knockout leads to imbalance in hepatic metabolism in F1 generation, the mechanism of which requires further discussion.

Powdery mildew of wheat (Triticum aestivum), caused by Blumeria graminis f.sp. tritici (Bgt), is a destructive disease that seriously threatens the yield and quality of its host. Identifying resistance genes is the most attractive and effective strategy for developing disease-resistant cultivars and controlling this disease. In this study, a wheat breeding line Yannong 99102-06188 (YN99102), an elite derivative line from the same breeding process as the famous wheat cultivar Yannong 999, showed high resistance to powdery mildew at the whole growth stages. Genetic analysis was carried out using Bgt isolate E09 and a population of YN99102 crossed with a susceptible parent Jinhe 13–205 (JH13–205). The result indicated that a single recessive gene, tentatively designated pmYN99102, conferred seedling resistance to the Bgt isolate E09. Using bulked segregant exome capture sequencing (BSE-Seq), pmYN99102 was physically located to a ~33.7 Mb (691.0–724.7 Mb) interval on the chromosome arm 2BL, and this interval was further locked in a 1.5 cM genetic interval using molecular markers, which was aligned to a 9.0 Mb physical interval (699.2–708.2 Mb). Based on the analysis of physical location, origin, resistant spectrum, and inherited pattern, pmYN99102 differed from those of the reported powdery mildew (Pm) resistance genes on 2BL, suggesting pmYN99102 is most likely a new Pm gene/allele in the targeted interval. To transfer pmYN99102 to different genetic backgrounds using marker-assisted selection (MAS), 18 closely linked markers were tested for their availability in different genetic backgrounds for MAS, and all markers expect for YTU103-97 can be used in MAS for tracking pmYN99102 when it transferred into those susceptible cultivars.

Breast cancer is a major disease affecting women worldwide. A woman has 1 in 8 lifetime risk of developing breast cancer, and morbidity and mortality due to this disease are expected to continue to rise globally. Breast cancer remains a challenging disease due to its heterogeneity, propensity for recurrence and metastasis to distant vital organs including bones, lungs, liver and brain ultimately leading to patient death. Despite the development of various therapeutic strategies to treat breast cancer, still there are no effective treatments once metastasis has occurred. Loss of differentiation and increased cellular plasticity and stemness are being recognized molecularly and clinically as major derivers of heterogeneity, tumor evolution, relapse, metastasis, and therapeutic failure. In solid tumors, breast cancer is one of the leading cancer types in which tumor differentiation state has long been known to influence cancer behavior. Reprograming and/or restoring differentiation of cancer cells has been proposed to provide a viable approach to reverse the cancer through differentiation and terminal maturation. The hormone prolactin (PRL) is known to play a critical role in mammary gland lobuloalveolar development/remodeling and the terminal differentiation of the mammary epithelial cells promoting milk proteins gene expression and lactation. Here, we will highlight recent discoveries supporting an anti-tumorigenic role for PRL in breast cancer as a “pro/forward-differentiation” pathway restricting plasticity, stemness and tumorigenesis.

While MRI contrast agents such as those based on Gadolinium are needed for high-resolution mapping of brain metabolism, these contrast agents require intravenous administration, and there are rising concerns over their safety and invasiveness. Furthermore, non-contrast MRI scans are more commonly performed than those with contrast agents and are readily available for analysis in public databases such as the Alzheimer's Disease Neuroimaging Initiative (ADNI). In this article, we hypothesize that a deep learning model, trained using quantitative steady-state contrast-enhanced structural MRI datasets, in mice and humans, can generate contrast-equivalent information from a single non-contrast MRI scan. The model was first trained, optimized, and validated in mice, and was then transferred and adapted to humans. We observe that the model can substitute for Gadolinium-based contrast agents in approximating cerebral blood volume, a quantitative representation of brain activity, at sub-millimeter granularity. Furthermore, we validate the use of our deep-learned prediction maps to identify functional abnormalities in the aging brain using locally obtained MRI scans, and in the brain of patients with Alzheimer's disease using publicly available MRI scans from ADNI. Since it is derived from a commonly-acquired MRI protocol, this framework has the potential for broad clinical utility and can also be applied retrospectively to research scans across a host of neurological/functional diseases.

Abstract Background After the implementation of the universal two-child policy in China, the increase in parity has led to an increase in adverse pregnancy outcomes. The impact of one and two fetuses on the incidence of fetal macrosomia has not been fully confirmed in China. This study aimed to explore the differences in the incidence of fetal macrosomia in first and second pregnancies in Western China after the implementation of the universal two-child policy. Methods A total of 1598 pregnant women from three hospitals were investigated by means of a cross-sectional study from August 2017 to January 2018. Participants were recruited by convenience and divided into first and second pregnancy groups. These groups included 1094 primiparas and 504 women giving birth to their second child. Univariate and multivariate logistic regression analyses were performed to discuss the differences in the incidence of fetal macrosomia in first and second pregnancies. Results No significant difference was found in the incidence of macrosomia in the first pregnancy group (7.2%) and the second pregnancy group (7.1%). In the second-time pregnant mothers, no significant association was found between the macrosomia of the second child (5.5%) and that of the first child (4.7%). The multivariate logistic regression model showed that mothers older than 30 years are not likely to give birth to children with macrosomia (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4,0.9). Conclusions The incidence of macrosomia in Western China is might not be affected by the birth of the second child and is not increased by low parity.

The fertilization process is a critical step in plant reproduction. However, the mechanism of action and mode of regulation of the fertilization process in gymnosperms remain unclear. In this study, we investigated the molecular regulatory networks involved in the fertilization process in Korean pine ovules through anatomical observation, physiological and biochemical assays, and transcriptome sequencing technology. The morphological and physiological results indicated that fertilization proceeds through the demise of the proteinaceous vacuole, egg cell division, and pollen tube elongation. Auxin, cytokinin, soluble sugar, and soluble starch contents begin to decline upon fertilization. Transcriptomic data analysis revealed a large number of differentially expressed genes at different times before and after fertilization. These genes were primarily involved in pathways associated with plant hormone signal transduction, protein processing in the endoplasmic reticulum, fructose metabolism, and mannose metabolism. The expression levels of several key genes were further confirmed by qRT-PCR. These findings represent an important step towards understanding the mechanisms underlying morphological changes in the Korean pine ovule during fertilization, and the physiological and transcriptional analyses lay a foundation for in-depth studies of the molecular regulatory network of the Korean pine fertilization process.

The AP2/ERF (APETALA2/Ethylene−Responsive element binding factor) family genes play crucial roles in plant growth and development, and responses to environmental factors; however, this family has not been characterized in Diospyros species. In Diospyros, the diploid Oily persimmon (D. oleifera, 2n = 2x = 30) has been released with complete genome assembly, which makes it possible for genome-wide gene family identification and exploration of molecular function in cultivated persimmon (D. kaki, 2n = 6x = 90). Here, we identified the AP2/ERF family in Oily persimmon for the first time and investigated its classification, main physicochemical properties, structural characteristic, chromosome distribution, gene replication and collinearity, cis-factor binding sites deduction, GO term annotation, and PPI interaction, as well as its expression profiles in different tissue and under the treatment of polyamines. A total of 157 AP2/ERF genes, including four subfamilies (AP2, RAV, Soloist, and ERF), were identified with distribution on all 15 chromosomes. DkAP2/ERF gene expression patterns were extensive and diverse. They were detected expression in every examined tissue, with the highest number of DkAP2/ERF genes expressed in the root. DkAP2/ERF gene expression analysis in adventitious root generation and elongation of polyamines showed their different responses to the action of polyamines, and more pairs of DkAP2/ERF genes with high correlation in gene expression were obtained. In addition, some DkAP2/ERF genes were detected remarkably correlated with genes related to polyamine synthesis and cell metabolism, including S-adenosyl-L-methionine Decarboxyla2 (SAMDC2), D-type cyclin1 (CYCD1), and D-type cyclin2 (CYCD2) genes,. indicating that DkAP2/ERF genes may play a synergistic role in adventitious root development This study was the first to analyze the AP2/ERF gene comprehensively in Diospyros on a genome−wide scale and will provide insights into the application of adventitious root formation in cultivated persimmon.

This study aims at investigating the applicability of the commonly used water saturation test methods such as distillation extraction method, nuclear magnetic resonance (NMR) method, constant weight method, and Coulomb method in the water saturation test of tight sandstone gas reservoirs. The above methods were studied and optimized to overcome the difficulties of low water content determination caused by low porosity, low permeability, small pore throat, high capillary force, and high bound water saturation of tight sandstone, to obtain relatively accurate water saturation data. The results showed that the water content data determined by the constant weight method were consistent with the known water content saturation, and the average error was 3.6%. By shortening the echo interval, the average error of water content saturation tested by the NMR method for tight sandstone samples was 4.8%. The two methods of the distillation method and Coulomb method had large errors, and both failed to meet the requirements of water saturation determination of tight sandstone, of which the average error of the former was 27.9% and the average error of the latter was 50.7%. Therefore, for tight sandstone, the constant weight method and NMR method were recommended to be used for water content saturation testing, and the distillation extraction method and Coulomb method were not recommended. The research results provided a new method for the accurate determination of water content saturation in tight sandstone gas reservoirs.

AimRecurrent miscarriage (RM) is associated with numerous clinical factors. However, some RM occurred without specific factors. It has been revealed that some molecules such as hormones, miRNAs, and transcription factors are involved in RM by regulating proliferation, apoptosis, etc. However, the mechanism of RM has yet to be identified clearly. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that often act as sponges for miRNAs or binds to proteins involved in biological processes. However, the functional role of circRNAs in the uterine decidua of patients with early RM is still unclear. In this study, we aimed to investigate the mechanisms of circ-CYP24A1 in RM.MethodsThe Dual-Luciferase Activity Assay was designed to analyze the bonding between circ-CYP24A1 and miR-224, and miR-224 and prolactin receptor (PRLR) mRNA 3′UTR. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to observe the expression of circ-CYP24A1 and PRLR in the decidua. Rescue experiments were performed to investigate the regulating effects of circ-CYP24A1, miR-224, and PRLR. Western blotting was conducted to test the expression level of PRLR. The proliferation and apoptosis-related markers in Ishikawa cells were analyzed using CCK8, immunofluorescence staining, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay.ResultsIn this study, based on the microarray analysis data, we identified a high level of circ-CYP24A1 and PRLR in the decidua of patients with early RM. Based on the bioinformatics prediction, the binding relationship between circ-CYP24A1 and miR-224, as well as miR-224 and PRLR, were verified. Functional experiments demonstrated that circ-CYP24A1 regulated proliferation and apoptosis by binding to and inhibiting miR-224, resulting in increased PRLR expression. Taken together, this study provides new insights into the mechanism of RM.ConclusionIn this study, we found that circ-CYP24A1 plays a role in RM by impairing the balance of cell proliferation and apoptosis by sponging miR-224, thereby regulating PRLR.

Spontaneous imbibition is an effective method of tight sandstone reservoirs development. However, their underlying mechanisms are still unclear due to the representative issue caused by strong heterogeneity and complex oil-brine properties. In this research, physical properties and thin-section images were systematically analyzed, and the spontaneous imbibition efficiency was examined from core tests. The results show that quartz and feldspar predominantly contribute to mineralogy. Low brine salinity, high oil viscosity, and high interfacial tension corresponded to strong spontaneous imbibition ability and fast process. High interfacial tension is the dominant controlling factor in this field. Furthermore, the parameter simulation model established by the dimension reduction method could catalyze the prediction of spontaneous imbibition efficiency, which is confirmed by higher reliability.

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs that play important roles in gene expression regulation. This study aimed to evaluate the potential role of circRNAs in decidual tissue of patients with early recurrent miscarriage (RM). We constructed circRNA expression profiles in decidual tissue using microarray data. A total of 123 differentially expressed circRNAs, including 78 upregulated and 45 downregulated circRNAs were detected in the early RM group compared with the control group (P

We show that Si MOSFETs, AlGaN/GaN HEMTs, AlGaAs/InGaAs HEMTs, and p-diamond FETs with feature sizes ranging from 20 nm to 130 nm could operate at room temperature as THz spectrometers in the frequency range from 110 GHz to 9.2 THz with different subranges corresponding to the transistors with different features sizes and tunable by the gate bias. The spectrometer uses a symmetrical FET with interchangeable source and drain with the rectified THz voltage between the source and drain being proportional to the sine of the phase shift between the voltages induced by the THz signal between gate-to-drain and gate-to-source. This phase difference could be created by using different antennas for the source-to-gate and drain-to gate contacts or by using a delay line introducing a phase shift or even by manipulating the impinging angle of the two antennas. The spectrometers are simulated using the multi-segment unified charge control model implemented in SPICE and ADS and accounting for the electron inertia effect and the distributed channel resistances, capacitances and Drude inductances.

Due to the trend of multi-function, integration, and miniaturization of electronics, traditional dielectric materials are difficult to satisfy new requirements, such as balanced dielectric properties and good designability. Therefore, high dielectric polymer composites have attracted wide attention due to their outstanding processibility, good designability, and dielectric properties. A number of polymer composites are employed in capacitors and sensors. All these applications are directly affected by the composite’s dielectric properties, which are highly depended on the compositions and internal structure design, including the polymer matrix, fillers, structural design, etc. In this review, the influences of matrix, fillers, and filler arrangement on dielectric properties are systematically and comprehensively summarized and the regulation strategies of dielectric loss are introduced as well. Finally, the challenges and prospects of high dielectric polymer composites are proposed.

Abstract Fetal bovine serum (FBS) is widely used in cell cultures due to its high stability and easy access. It was also used as a substitute for porcine follicular fluid (PFF) in previous studies. However, FBS components are unclear, and the presence of FBS in culture media may introduce a variation from batch to batch. This study aimed to establish an effective method to screen FBS in place of PFF in the culture media for porcine oocytes in vitro. We screened FBS from different sources by using porcine fetal fibroblast cells. The effects of six FBS samples on porcine fetal fibroblast cell growth were tested via frozen cell survival assay, cell clone formation assay, cell growth curve, and cell passage activity assay. The best serum that we called GFBS (heat‐inactivated FBS, cat. no. 10500‐64; Gibco) showed a similar effect on the maturation and development of porcine oocytes to that of PFF and can be used as a good substitute for PFF. These results suggested that the porcine fetal fibroblast cell culture test can be used as a valuable method to screen FBS for porcine oocyte maturation and embryonic development in vitro.

The plant cuticle is the outermost layer of the aerial organs and an important barrier against biotic and abiotic stresses. The climate varies greatly between the north and south of China, with large differences in temperature and humidity, but Chinese chestnut is found in both regions. This study investigated the relationship between the wax layer of chestnut leaves and environmental adaptation. Firstly, semi-thin sections were used to verify that there is a significant difference in the thickness of the epicuticular wax layer between wild chestnut leaves in northwest and southeast China. Secondly, a whole-genome selective sweep was used to resequence wild chestnut samples from two typical regional populations, and significant genetic divergence was identified between the two populations in the CmCER1-1, CmCER1-5 and CmCER3 genes. Thirty-four CER genes were identified in the whole chestnut genome, and a series of predictive analyses were performed on the identified CmCER genes. The expression patterns of CmCER genes were classified into three trends—upregulation, upregulation followed by downregulation and continuous downregulation—when chestnut seedlings were treated with drought stress. Analysis of cultivars from two resource beds in Beijing and Liyang showed that the wax layer of the northern variety was thicker than that of the southern variety. For the Y-2 (Castanea mollissima genome sequencing material) cultivar, there were significant differences in the expression of CmCER1-1, CmCER1-5 and CmCER3 between the southern variety and the northern one-year-grafted variety. Therefore, this study suggests that the CER family genes play a role in environmental adaptations in chestnut, laying the foundation for further exploration of CmCER genes. It also demonstrates the importance of studying the adaptation of Chinese chestnut wax biosynthesis to the southern and northern environments.

Pomegranates (Punica granatum L.) are one of the most fashionable fruits and can be cultivated in both tropical and subtropical regions of the world. It is a shiny and attractive pome due to its cultivation. It belongs to the Lythraceae family. In this study, we analyzed the chloroplast genome of wild pomegranate based on whole genome shotgun sequences. In wild pomegranate, we found 158,645 bp in size, 132 genes containing 84 protein genes, 37 tRNA genes, 8 rRNA genes, and 36.92% of GC content, one infA and two duplicated ycf15 pseudogenes. Moreover, 21 chloroplast genes contained intros that are detected in a large single copy (LSC), small single copy (SSC), and two inverted repeats (IRA and IRB) regions, 17 of which were involved in single introns, while four genes (ycf3, rps12, clpP and rsp12) located in LSC, IRA, and IRB region. In total, 26,272 codons are found in protein-coding genes (PCGs); relative synonymous codon usage (RSCU) analysis revealed that the most abundant amino acid is leucine containing 2773 codons (10.55%), less abundant is methionine amino acid containing 1 codon (0.0032) in the PCGs. Furthermore, a total of 233 cpSSRs were identified in the wild pomegranate cp genome, and their distribution was analyzed in three regions, namely IR, LSC, and SSC. However, 155 cpSSR were found in the LSC (66.5%), followed by 40 cpSSR in the SSC (17.2%) and 38 cpSSR in the IR (16.3%) regions. Phylogenetic validation revealed that wild pomegranate is close to the pemphis acidula species. We believe that the cp genome allocates significant information promising for breeding research of wild pomegranate to Lythraceae.