Low expression of SEMA4D as a potential predictive molecular marker of poor survival in patients with melanoma combined with liver cancer.

This study explored the correlation between semaphorin 4D (SEMA4D) and the prognosis and survival time of patients with melanoma combined with liver cancer. A total of 272 patients were recruited, and clinical and follow-up data were recorded. The expression levels of SEMA4D and SEMA3B were determined. Pearson's χ2 test and Spearman's rank correlation coefficient were used to analyze the relationship between prognosis and the assessed parameters of melanoma patients. Univariate and multivariate Logistic regression and Cox proportional risk regression analyses were used for further analysis. Additionally, receiver operating characteristic curve and survival curves of subjects were plotted. The Pearson's χ2 test showed that the prognosis of melanoma patients was significantly correlated with age, tumor grade, and decreased SEMA4D expression. Additionally, Spearman's correlation coefficient analysis showed that age, tumor grade, and SEMA4D expression were significantly correlated with prognosis. Univariate logistic regression analysis showed that age and tumor grade, and SEMA4D expression, were significantly correlated with prognosis. Older patients, a higher tumor grade, and lower SEMA4D expression were associated with a poorer prognosis. Multivariate logistic regression analysis showed that older patients had a poorer prognosis, and patients with lower SEMA4D expression levels had a significantly worse prognosis than patients with higher SEMA4D expression levels. Kaplan-Meier analysis showed that the survival time of older patients was lower than that of the younger patients. The survival times of patients with lower SEMA4D expression levels were significantly lower than that of patients with higher SEMA4D expression levels. Multivariate Cox regression analysis showed that the survival time of older patients was lower than that of younger patients. The survival time of melanoma patients with low SEMA4D expression was significantly lower than that of patients with higher SEMA4D expression. SEMA4D was significantly associated with melanoma, and lower SEMA4D expression was associated with a poorer survival prognosis in melanoma patients.

Demographic, clinical and biochemical correlates of the length of stay for different polarities in Chinese inpatients with bipolar disorder: A real-world study.

Introduction: Many patients with bipolar disorder (BD) need hospitalization, while the number of hospital beds for these patients is limited. Managing the length of stay (LOS) is an effective solution to this issue. Research on LOS and its influencing factors in BD is limited in China. This study aimed to identify the factors relevant to LOS in different polarities in Chinese patients with BD. Method: This was a real-world, cross-sectional study. Data were obtained from the electronic medical record system. Patients admitted to Beijing Anding Hospital between Jan 2014 and Dec 2017 and diagnosed with BD were included. Demographic information, clinical characteristics, and biochemical variables were collected. Patients were classified into short and long LOS groups based on a cutoff value. A univariate study and a multivariate logistic regression analysis were performed to identify variables related to LOS in various BD polarities. The receiver operating characteristic (ROC) analysis was utilized to evaluate the discrimination accuracy of the regression model. Result: Four thousand six hundred and seventy-five visits from 4,451 individuals were included in the analysis. For the whole sample, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). There was an additive interaction between a family history of mental disorders and polarities (p < 0.05). For manic episodes, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). For depressive episodes, psychotic features and high-density lipoprotein cholesterol (HDLC) levels were positively associated with long LOS (all p < 0.05). For mixed states, unmarried status was positively associated with long LOS, while low-density lipoprotein cholesterol (LDLC) levels were negatively associated with LOS (all p < 0.05). The area under the curve (AUC) values for depressive episodes, manic episodes, and mixed states in the combined model were 0.587, 0.553, and 0.619, respectively (all p < 0.05). Discussion: The findings suggested that LOS correlates differed by polarity, with marital status, psychotic features, a family history of mental disorders, and lipid levels strongly linked with LOS in patients with BD.

STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice.

High-fat diet (HFD) intake provokes obesity and cardiac anomalies. Recent studies have found that ferroptosis plays a role in HFD-induced cardiac injury, but the underlying mechanism is largely unclear. Ferritinophagy is an important part of ferroptosis that is regulated by nuclear receptor coactivator 4 (NCOA4). However, the relationship between ferritinophagy and HFD-induced cardiac damage has not been explored. In this study, we found that oleic acid/palmitic acid (OA/PA) increased the level of ferroptotic events including iron and ROS accumulation, upregulation of PTGS2 mRNA and protein levels, reduced SOD and GSH levels, and significant mitochondrial damage in H9C2 cells, which could be reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Intriguingly, we found that the autophagy inhibitor 3-methyladenine mitigated OA/PA-induced ferritin downregulation, iron overload and ferroptosis. OA/PA increased the protein level of NCOA4. Knockdown of NCOA4 by SiRNA partly reversed the reduction in ferritin, mitigated iron overload and lipid peroxidation, and subsequently alleviated OA/PA-induced cell death, indicating that NCOA4-mediated ferritinophagy was required for OA/PA-induced ferroptosis. Furthermore, we demonstrated that NCOA4 was regulated by IL-6/STAT3 signaling. Inhibition or knockdown of STAT3 effectively reduced NCOA4 levels to protect H9C2 cells from ferritinophagy-mediated ferroptosis, whereas STAT3 overexpression by plasmid appeared to increase NCOA4 expression and contribute to classical ferroptotic events. Consistently, phosphorylated STAT3 upregulation, ferritinophagy activation, and ferroptosis induction also occurred in HFD-fed mice and were responsible for HFD-induced cardiac injury. In addition, we found evidence that piperlongumine, a natural compound, effectively reduced phosphorylated STAT3 levels to protect cardiomyocytes from ferritinophagy-mediated ferroptosis both in vitro and in vivo. Based on these findings, we concluded that ferritinophagy-mediated ferroptosis was one of the critical mechanisms contributing to HFD-induced cardiac injury. The STAT3/NCOA4/FTH1 axis might be a novel therapeutic target for the treatment of HFD-induced cardiac injury.

Endoscopic treatment and management of rectal neuroendocrine tumors less than 10 mm in diameter.

Rectal neuroendocrine tumors (rNETs) measuring less than 10 mm in diameter are defined as small rNETs. Due to the low risk of distant invasion and metastasis, endoscopic treatments, including modified endoscopic mucosal resection, endoscopic submucosal dissection, and other transanal surgical procedures, are effective. This review article proposes a follow-up plan according to the size and histopathology of the tumor after operation.

HSV: The scout and assault for digestive system tumors.

More than 25% of all malignant tumors are digestive system tumors (DSTs), which mostly include esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, gallbladder cancer and cholangiocarcinoma, and colorectal cancer. DSTs have emerged as one of the prominent reasons of morbidity and death in many nations and areas around the world, posing a serious threat to human life and health. General treatments such as radiotherapy, chemotherapy, and surgical resection can poorly cure the patients and have a bad prognosis. A type of immunotherapy known as oncolytic virus therapy, have recently shown extraordinary anti-tumor effectiveness. One of the viruses that has been the subject of the greatest research in this field, the herpes simplex virus (HSV), has shown excellent potential in DSTs. With a discussion of HSV-1 based on recent studies, we outline the therapeutic effects of HSV on a number of DSTs in this review. Additionally, the critical function of HSV in the detection of cancers is discussed, and some HSV future possibilities are shown.

Pteris laeta Wall. and Its New Phytochemical, Pterosinsade A, Promote Hippocampal Neurogenesis via Activating the Wnt Signaling Pathway.

Pteris laeta Wall., as a traditional tea, is popular in Southwest China, but its role in preventing cognitive impairment is unclear. In this study, Pteris laeta Wall. extracts (PW) and its active compounds were evaluated for preventive effects on Alzheimer's disease (AD) in vivo and in vitro. The results showed that PW diminished oxidative stress damage and apoptosis of Aß-induced HT22 cells and also rescued cognitive deficits, and ameliorated pathological injury and inflammatory response in APP/PS1 mice. Besides, a new pterosin sesquiterpene, named pterosinsade A (PA), and nine known compounds were discovered from the EtOAc extract that possessed the best neuroprotective activity. PA reduced apoptosis of APP-overexpressing neural stem cells and promoted their proliferation and neuronal differentiation. Meanwhile, PW and PA promoted hippocampal neurogenesis, which proved to be associated with activating the Wnt signaling pathway. These findings suggest that PW and PA are candidates for AD prevention.

The challenging imaging and histopathologic features of diffusely infiltrating breast cancer.

PURPOSE: Clinical, imaging and outcome observations indicate that diffusely infiltrating breast cancer, presenting as a large region of architectural distortion on the mammogram and conventionally termed classic infiltrating lobular carcinoma of diffuse type, represents a very unusual breast malignancy. This article aims to draw attention to the complex clinical, imaging, and large format thin and thick section histopathologic features of this malignancy, which challenges our current diagnostic and therapeutic management practices. METHODS: Prospectively collected data from the randomized controlled trial (1977-85) and from the subsequent, ongoing population-based mammography service screening (1985-2019) with more than four decades of follow up in Dalarna County, Sweden provided the database for investigating this breast cancer subtype. Large format thick (subgross) and thin section histopathologic images of breast cancers diagnosed as "diffusely infiltrating lobular carcinoma of the breast" were correlated with their mammographic tumour features (imaging biomarkers) and the long-term patient outcome. RESULTS: This malignancy does not have a distinct tumour mass or focal skin retraction at clinical breast examination; instead, it causes an indistinct "thickening" and eventually shrinks the entire breast. A dominant feature is extensive architectural distortion on the mammograms caused by an excessive amount of cancer-associated connective tissue. Unlike other invasive breast malignancies, this subtype forms concave contours with the surrounding adipose connective tissue, a feature that makes it difficult to detect on mammograms. Women with this diffusely infiltrating breast malignancy have a 60% long-term survival. Its long-term patient outcome is surprisingly poor compared to that expected from its relatively favourable immunohistochemical biomarkers, including a low proliferation index and remains unaffected by adjuvant therapy. CONCLUSIONS: The unusual clinical, histopathologic and imaging features of this diffusely infiltrating breast cancer subtype are consistent with a site of origin quite different from that of other breast cancers. Additionally, the immunohistochemical biomarkers are deceptive and unreliable because they indicate a cancer with favourable prognostic features predictive of a good long-term outcome. The low proliferation index is usually indicative of a breast cancer with a good prognosis, but in this subtype the prognosis is poor. If we are to improve the dismal outcome of this malignancy, it will be necessary to clarify its true site of origin, which will be a prerequisite for gaining a better understanding why current management efforts often fail and why the fatality rate is so unfortunately high. Breast radiologists should be watchful for the development of subtle signs of architectural distortion at mammography. Large format histopathologic technique enables adequate correlation of the imaging and histopathologic findings.

Deep information-guided feature refinement network for colorectal gland segmentation.

PURPOSE: Reliable quantification of colorectal histopathological images is based on the precise segmentation of glands but precise segmentation of glands is challenging as glandular morphology varies widely across histological grades, such as malignant glands and non-gland tissues are too similar to be identified, and tightly connected glands are even highly possibly to be incorrectly segmented as one gland. METHODS: A deep information-guided feature refinement network is proposed to improve gland segmentation. Specifically, the backbone deepens the network structure to obtain effective features while maximizing the retained information, and a Multi-Scale Fusion module is proposed to increase the receptive field. In addition, to segment dense glands individually, a Multi-Scale Edge-Refined module is designed to strengthen the boundaries of glands. RESULTS: The comparative experiments on the eight recently proposed deep learning methods demonstrated that our proposed network has better overall performance and is more competitive on Test B. The F1 score of Test A and Test B is 0.917 and 0.876, respectively; the object-level Dice is 0.921 and 0.884; and the object-level Hausdorff is 43.428 and 87.132, respectively. CONCLUSION: The proposed colorectal gland segmentation network can effectively extract features with high representational ability and enhance edge features while retaining details to the maximum, dramatically improving the segmentation performance on malignant glands, and better segmentation results of multi-scale and closed glands can also be obtained.

Development and integration of LensHooke® R10 for automatic and standardized diagnosis for sperm DNA fragmentation.

BACKGROUND: The sperm chromatin dispersion assay is commonly used to assess sperm DNA integrity. This approach is time-consuming, demonstrates poor chromatin preservation, and provides an ambiguous and unstandardized evaluation of fragmented chromatin. OBJECTIVES: We aimed to (i) develop an optimized sperm chromatin dispersion assay with reduced operation time, (ii) validate R10 test accuracy by comparing it to a conventional sperm chromatin dispersion assay, and (iii) standardize the sperm DNA fragmentation analysis procedure by integrating artificial intelligence optical microscopic technology. MATERIALS AND METHODS: This cross-section study included 620 semen samples. Aliquots were analyzed by a conventional Halosperm® G2 assay (G2) and LensHooke® R10 assay (R10). The DNA fragmentation index was scored manually, and R10 slides were automatically determined by a LensHooke® X12 PRO semen analysis system (X12). RESULTS: We demonstrated significant improvements in total assay time (40 vs. 72 min, p < 0.001) and in the halo-cytological resolution using R10 compared to G2. Comparing the G2 and R10, DNA fragmentation index results demonstrated good agreement between the two methods (Spearman's rank correlation, rho = 0.8517, p < 0.0001). We introduced the integration of an auto-calculation system to diagnose sperm DNA fragmentation. X12 interpretation showed excellent agreement with manual interpretation (Spearman's rank correlation, rho = 0.9323, p < 0.0001), but had a low coefficient of variation compared to manual interpretation (4% for R10 by X12 vs. 19% for R10 by manual scoring vs. 25% for G2 by manual scoring). DNA fragmentation index was more correlated with total motility (coefficients = -0.3607, p < 0.0001) than sperm morphology and was positively associated with asthenozoospermic semen samples (p = 0.0001). CONCLUSION: The R10 sperm chromatin dispersion assay combined with the X12 semen analysis system is faster, more objective, and provides standardization for sperm DNA fragmentation.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin.

BACKGROUND: Serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a promising biomarker for hepatocellular carcinoma (HCC) surveillance. AIM: To identify the contributing factors related to the abnormal elevation of PIVKA-II level and assess their potential influence on the performance of PIVKA-II in detecting HCC. METHODS: This study retrospectively enrolled in 784 chronic liver disease (CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-II for HCC, respectively. RESULTS: Elevated PIVKA-II levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase (ALP), and total bilirubin (TBIL) for CLD patients and aspartate aminotransferase (AST) and tumor size for HCC patients (all P < 0.05). Serum PIVKA-II were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal (ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST (all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-II was significantly higher compared to that in patients with TBIL > 1 × ULN (0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant (0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone. CONCLUSION: Serum PIVKA-II has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Ungulates' Behavioral Responses to Humans as an Apex Predator in a Hunting-Prohibited Area of China.

Large mammals can perceive humans as predators and therefore adjust their behavior to achieve coexistence with humans. However, lack of research at sites with low hunting intensity limits our understanding of how behavioral responses of animals adapt to different predation risks by humans. At Heshun County in North China, where hunting has been banned for over three decades and only low-intensity poaching exists, we exposed two large ungulates (Siberian roe deer Capreolus pygarus and wild boar Sus scrofa) to the sounds of humans, an extant predator (leopard Panthera pardus) and a control (wind), and examined their flight responses and detection probabilities when hearing different type of sounds. Both species showed higher flight probabilities when hearing human vocalization than wind, and wild boar were even more likely to flee upon hearing human vocalization than leopard roar, suggesting the behavioral response to humans can equal or exceed that of large carnivores in these two ungulates even in an area without hunting practices. Recorded sounds had no effect on detection probability of both ungulates. Additionally, with repeated exposure to sounds, regardless of treatment, roe deer were less likely to flee and wild boars were more likely to be detected, indicating a habituation-type response to sound stimuli. We speculate that the immediate flight behavior rather than shifts in habitat use of the two species reflect the low hunting/poaching pressure at our study site and suggest further examination of physiological status and demographic dynamics of the study species to understand human influence on their long-term persistence.

Ultrasonic Treatment Enhances the Antioxidant and Immune-Stimulatory Properties of the Polysaccharide from Sinopodophyllum hexandrum Fruit.

We aimed to assess the potential of ultrasonic treatment on the processing of polysaccharides as functional foods or food additives. The polysaccharide from Sinopodophyllum hexandrum fruit (SHP, 52.46 kDa, 1.91 nm) was isolated and purified. SHP was treated with various levels of ultrasound (250 W and 500 W), resulting in the formation of two polysaccharides, SHP1 (29.37 kD, 1.40 nm) and SHP2 (36.91 kDa, 0.987 nm). Ultrasonic treatment was found to reduce the surface roughness and molecular weight of the polysaccharides, leading to thinning and fracturing. The effect of ultrasonic treatment on polysaccharide activity was evaluated in vitro and in vivo. In vivo experiments showed that ultrasonic treatment improved the organ index. Simultaneously, it enhanced the activity of superoxide dismutase, total antioxidant capacity, and decreased the content of malondialdehyde in the liver. In vitro experiments demonstrated that ultrasonic treatment also promoted proliferation, nitric oxide secretion, phagocytic efficiency, costimulatory factors (CD80+, CD86+) expression, and cytokine(IL-6, IL-1ß) production of RAW264.7 macrophages.

Cross-Channel Constraints on Resonant Antikaon-Nucleon Scattering.

Chiral perturbation theory and its unitarized versions have played an important role in our understanding of the low-energy strong interaction. Yet, so far, such studies typically deal exclusively with perturbative or nonperturbative channels. In this Letter, we report on the first global study of meson-baryon scattering up to one-loop order. It is shown that covariant baryon chiral perturbation theory, including its unitarization for the negative strangeness sector, can describe meson-baryon scattering data remarkably well. This provides a highly nontrivial check on the validity of this important low-energy effective field theory of QCD. We show that the K[over ¯]N related quantities can be better described in comparison with those of lower-order studies, and with reduced uncertainties due to the stringent constraints from the πN and KN phase shifts. In particular, we find that the two-pole structure of Λ(1405) persists up to one-loop order reinforcing the existence of two-pole structures in dynamically generated states.

Risk factors of cardiovascular involvement in patients with Behcet's disease.

Objectives: Behcet's disease (BD) is a multi-systemic inflammatory vasculitis which may be life-threatening if combined with cardiovascular problems. The aim of the study was to identify potential risk factors associated with cardiovascular involvement in BD. Methods: We reviewed the medical databases of a single center. All BD patients identified as fulfilling the 1990 International Study Group criteria or the International Criteria for Behcet's Disease criteria. Cardiovascular involvement, clinical manifestations, laboratory features, and treatments were recorded. The relationship between parameters and cardiovascular involvement was analyzed. Results: 111 BD patients were included: 21 (18.9%) had documented cardiovascular involvement (CV BD group) and 99 (81.1%) had no cardiovascular involvement (non-CV BD group). Compared with non-CV BD, the proportion of males and smokers were significantly increased in CV BD (p = 0.024 and p < 0.001, respectively). Levels of activated partial thromboplastin time (APTT), cardiac troponin I and C-reactive protein were significantly higher (p = 0.001, p = 0.031, and p = 0.034, respectively) in the CV BD group. Cardiovascular involvement was associated with smoking state, the presence of papulopustular lesions, and higher APTT in multivariate analyzed (p = 0.029, p = 0.021, and p = 0.006, respectively). The ROC curve showed that APTT predicts the risk of cardiovascular involvement (p < 0.01) at a cut-off value of 33.15 s with a sensitivity of 57.1% and specificity of 82.2%. Conclusion: Cardiovascular involvement in BD patients was associated with gender, smoking state, the presence of papulopustular lesions, and higher APTT. All patients newly diagnosed with BD should be systematically screened for cardiovascular involvement.

Distributed optical fiber biosensor based on optical frequency domain reflectometry.

In situ acquisition of spatial distribution of biochemical substances is important in cell analysis, cancer detection and other fields. Optical fiber biosensors can achieve label-free, fast and accurate measurements. However, current optical fiber biosensors only acquire single-point of biochemical substance content. In this paper, we present a distributed optical fiber biosensor based on tapered fiber in optical frequency domain reflectometry (OFDR) for the first time. To enhance evanescent field at a relative long sensing range, we fabricate a tapered fiber with a taper waist diameter of 6 µm and a total stretching length of 140 mm. Then the human IgG layer is coated on the entire tapered region by polydopamine (PDA) -assisted immobilization as the sensing element to achieve to sense anti-human IgG. We measure shifts of the local Rayleigh backscattering spectra (RBS) caused by the refractive index (RI) change of an external medium surrounding a tapered fiber after immunoaffinity interactions by using OFDR. The measurable concentration of anti-human IgG and RBS shift has an excellent linearity in a range from 0 ng/ml to 14 ng/ml with an effective sensing range of 50 mm. The concentration measurement limit of the proposed distributed biosensor is 2 ng/ml for anti-human IgG. Distributed biosensing based on OFDR can locate a concentration change of anti-human IgG with an ultra-high sensing spatial resolution of 680 µm. The proposed sensor has a potential to realize a micron-level localization of biochemical substances such as cancer cells, which will open a door to transform single-point biosensor to distributed biosensor.

Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells.

Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury (SCI). These disorders are currently incurable, while human pluripotent stem cells (hPSCs)-derived spinal motor neurons are promising but suffered from inappropriate regional identity and functional immaturity for the study and treatment of posterior spinal cord related injuries. In this study, we have established human spinal cord neural progenitor cells (hSCNPCs) via hPSCs differentiated neuromesodermal progenitors (NMPs) and demonstrated the hSCNPCs can be continuously expanded up to 40 passages. hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency. The functional maturity has been examined in detail. Moreover, a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction (NMJ) formation in vitro. Together, these studies highlight the potential avenues for generating clinically relevant spinal motor neurons and modeling neuromuscular diseases through our defined hSCNPCs.

M2 Macrophage-Derived sEV Regulate Pro-Inflammatory CCR2+ Macrophage Subpopulations to Favor Post-AMI Cardiac Repair.

Tissue-resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)-expressing macrophages have phenotypical similarities to M1-polarized macrophages, are pro-inflammatory, and recruit CCR2+ circulating monocytes to infarcted myocardium. Small extracellular vesicles (sEV) from CCR2̶ macrophages, which phenotypically resemble M2-polarized macrophages, promote anti-inflammatory activity and cardiac repair. Here, the authors harvested M2 macrophage-derived sEV (M2EV ) from M2-polarized bone-marrow-derived macrophages for intramyocardial injection and recapitulation of sEV-mediated anti-inflammatory activity in ischemic-reperfusion (I/R) injured hearts. Rats and pigs received sham surgery; I/R without treatment; or I/R with autologous M2EV treatment. M2EV rescued cardiac function and attenuated injury markers, infarct size, and scar size. M2EV inhibited CCR2+ macrophage numbers, reduced monocyte-derived CCR2+ macrophage recruitment to infarct sites, induced M1-to-M2 macrophage switching and promoted neovascularization. Analysis of M2EV microRNA content revealed abundant miR-181b-5p, which regulated macrophage glucose uptake, glycolysis, and mitigated mitochondrial reactive oxygen species generation. Functional blockade of miR-181b-5p is detrimental to beneficial M2EV actions and resulted in failure to inhibit CCR2+ macrophage numbers and infarct size. Taken together, this investigation showed that M2EV rescued myocardial function, improved myocardial repair, and regulated CCR2+ macrophages via miR-181b-5p-dependent mechanisms, indicating an option for cell-free therapy for AMI.

Nitrogen application improves salt tolerance of grape seedlings via regulating hormone metabolism.

Salt stress is a dominant environmental factor that restricts the growth and yield of crops. Nitrogen is an essential mineral element for plants, regulates various physiological and biochemical processes, and has been reported to enhance salt tolerance in plants. However, the crosstalk between salt and nitrogen in grapes is not well understood. In this study, we found that nitrogen supplementation (0.01 mol L-1 and 0.1 mol L-1 NH4 NO3 ) significantly increased the accumulation of proline, chlorophyll, Na+ , NH4 + and NO3 - , while it reduced the malondialdehyde content and inhibited photosynthetic performance under salt stress conditions (200 mmol L-1 NaCl). Further transcriptome and metabolome analyses showed that a total of 4890 differentially expressed genes (DEGs) and 753 differential accumulation metabolites (DAMs) were identified. Joint omics results revealed that plant hormone signal transduction pathway connected the DEGs and DAMs. In-depth analysis revealed that nitrogen supplementation increased the levels of endogenous abscisic acid (ABA), salicylic acid (SA) and jasmonic acid (JA) by inducing the expression of 11, 4 and 13 genes related to their respective biosynthesis pathway. In contrast, endogenous indoleacetic acid (IAA) content was significantly reduced due to the remarkable regulation of 7 genes of its biosynthetic pathway. The modulation in hormone contents subsequently activated the differential expression of 13, 10, 12 and 29 genes of the respective downstream hormone signaling transduction pathways. Overall, all results indicate that moderate nitrogen supplementation could improve salt tolerance by regulating grape physiology and endogenous hormone homeostasis, as well as the expression of key genes in signaling pathways, which provides new insights into the interactions between mineral elements and salt stress. This article is protected by copyright. All rights reserved.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity.

Small ubiquitin-related modifier (SUMOylation) is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload. However, the function of SUMOylation after myocardial infarction (MI) and the molecular details of heart cell responses to SUMO1 deficiency have not been determined. In this study, we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI. However, SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury. Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells. Among cardiomyocytes, SUMO1 deletion increased the Nppa + Nppb + Ankrd1 + cardiomyocyte subcluster proportion after MI. In addition, the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice. Importantly, SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes. Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium. Mice preinjected with cardiomyocyte-specific AAV-SUMO1, but not the endothelial cell-specific form, and exhibited ameliorated cardiac remodeling following MI. Collectively, our results identified the role of SUMO1 in cardiomyocytes, fibroblasts, and endothelial cells after MI. These findings provide new insights into SUMO1 involvement in the pathogenesis of MI and reveal novel therapeutic targets.

Separation and Analysis of Oxygen-Containing Compounds in a Shaanxi Middle/Low-Temperature Coal Tar.

A middle/low-temperature coal tar (M/LTCT) was obtained from a low-temperature carbonization plant in Shaanxi, China. The M/LTCT was separated into light components and coal tar pitch through extraction. A series of alkanes, aromatic hydrocarbons, oxygen-containing arenes (OCAs), and nitrogen-containing arenes were fractionated from light components by medium-pressure preparative chromatography with gradient elution using petroleum ether and ethyl acetate. They were analyzed using a gas chromatography-mass spectrometer (GC-MS) and a Fourier transform infrared spectrometer. The OCAs were analyzed by a Fourier transform Orbitrap MS (quadrupole exactive Orbitrap mass spectrometer), and the molecular distribution of the O 1-O 6 species was studied. OCAs are mainly oxygen-containing aromatic compounds, including aromatic phenols, furans, alkoxy aromatic hydrocarbons, aromatic ethers, aromatic aldehydes, aromatic ketones, and aromatic acids. The position of the oxygen atom on the aromatic ring and the condensation form of the aromatic ring are studied.