Biochemical mechanisms preventing wilting under grafting: a case study on pumpkin rootstock grafting to wax gourd.

Wax gourd wilt is a devastating fungal disease caused by a specialized form of Fusarium oxysporum Schl. f. sp. benincasae (FOB), which severely restricts the development of the wax gourd industry. Resistant rootstock pumpkin grafting is often used to prevent and control wax gourd wilt. The "Haizhan 1" pumpkin has the characteristic of high resistance to wilt, but the mechanism through which grafted pumpkin rootstock plants acquire resistance to wax gourd wilt is still poorly understood. In this study, grafted wax gourd (GW) and self-grafted wax gourd (SW) were cultured at three concentrations [2.8 × 106 Colony Forming Units (CFU)·g-1, 8.0 × 105 CFU·g-1, and 4.0 × 105 CFU·g-1, expressed by H, M, and L]. Three culture times (6 dpi, 10 dpi, and 13 dpi) were used to observe the incidence of wilt disease in the wax gourd and the number of F. oxysporum spores in different parts of the soil and plants. Moreover, the physiological indices of the roots of plants at 5 dpi, 9 dpi, and 12 dpi in soil supplemented with M (8.0 × 105 CFU·g-1) were determined. No wilt symptoms in GW. Wilt symptoms in SW were exacerbated by the amount of FOB in the inoculated soil and culture time. At any culture time, the amount of FOB in the GW soil under the three treatments was greater than that in the roots. However, for the SW treatments, at 10 dpi and 13 dpi, the amount of FOB in the soil was lower than that in the roots. The total phenol (TP) and lignin (LIG) contents and polyphenol oxidase (PPO) and chitinase (CHI) activities were significantly increased in the GWM roots. The activities of phenylalanine ammonia lyase (PAL) and peroxidase (POD) initially decreased but then increased in the GWM roots. When the TP content decreased significantly, the LIG content and PAL and CHI activities increased initially but then decreased, whereas the PPO and POD activities did not change significantly in the SWM roots. The results indicated that the roots of the "Haizhan 1" pumpkin stock plants initiated a self-defense response after being infected with FOB, and the activities of PPO, POD, PAL, and CHI increased, and additional LIG and TP accumulated, which could effectively prevent FOB infection.

Enhanced Selective Electrosorption of Nitrate from Wastewater by Controllably Doping Nitrogen into Porous Carbon with Micropores.

The biological NO3- removal process might be accompanied by high CO2 emissions and operation costs. Capacitive deionization (CDI) has been widely studied as a very efficient method to purify water. Here, a porous carbon material with a tunable nitrogen configuration was developed. Characterization and density functional theory calculation show that nitrogenous functional groups have a higher NO3- binding energy than Cl-, SO42-, and H2PO4-. In addition, the selectivity of NO3- is improved after the introduction of micropores by using the pore template. The NO3- ion removal and selectivity of MN-C-12 are 4.57 and 3.46-5.42 times that of activated carbon (AC), respectively. The high NO3- selectivity and electrosorption properties of MN-C-12 (the highest N content and micropore area) are due to the synergistic effect of the affinity of nitrogen functional groups to NO3- and microporous ion screening. A CDI unit for the removal of nitrogen from municipal wastewater was constructed and applied to treat wastewater meeting higher discharge standards of A (N: 15 mg L-1) and B (N: 20 mg L-1) ((GB18918-2002), China). This work provides new insights into enhanced carbon materials for the selective electrosorption of wastewater by CDI technology.

A Novel Approach to the Technique of Lung Region Segmentation Based on a Deep Learning Model to Diagnose COVID-19 X-ray Images.

BACKGROUND: The novel coronavirus pandemic has caused a global health crisis, placing immense strain on healthcare systems worldwide. Chest X-ray technology has emerged as a critical tool for the diagnosis and treatment of COVID-19. However, the manual interpretation of chest X-ray films has proven to be inefficient and time-consuming, necessitating the development of an automated classification system. OBJECTIVE: In response to the challenges posed by the COVID-19 pandemic, we aimed to develop a deep learning model that accurately classifies chest X-ray images, specifically focusing on lung regions, to enhance the efficiency and accuracy of COVID-19 and pneumonia diagnosis. METHODS: We have proposed a novel deep network called "FocusNet" for precise segmentation of lung regions in chest radiographs. This segmentation allows for the accurate extraction of lung contours from chest X-ray images, which are then input into the classification network, ResNet18. By training the model on these segmented lung datasets, we sought to improve the accuracy of classification. RESULTS: The performance of our proposed system was evaluated on three types of lung regions in normal individuals, COVID-19 patients, and those with pneumonia. The average accuracy of the segmentation model (FocusNet) in segmenting lung regions was found to be above 90%. After reclassification of the segmented lung images, the specificities and sensitivities for normal, COVID-19, and pneumonia were excellent, with values of 98.00%, 99.00%, 99.50%, and 98.50%, 100.00%, and 99.00%, respectively. ResNet18 achieved impressive area under the curve (AUC) values of 0.99, 1.00, and 0.99 for classifying normal, COVID-19, and pneumonia, respectively, on the segmented lung datasets. Moreover, the AUC values of the three groups increased by 0.02, 0.02, and 0.06, respectively, when compared to the direct classification of unsegmented original images. Overall, the accuracy of lung region classification after processing the datasets was 99.3%. CONCLUSION: Our deep learning-based automated chest X-ray classification system, incorporating lung region segmentation using FocusNet and subsequent classification with ResNet18, has significantly improved the accuracy of diagnosing respiratory lung diseases, including COVID-19. The proposed approach has great potential to revolutionize the diagnosis of COVID-19 and other respiratory lung diseases, offering a valuable tool to support healthcare professionals during health crises.

Short-Term Mortality Among Pediatric Patients With Heart Diseases Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short-term mortality in these patients. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short-term mortality of pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation. To estimate short-term mortality, we used random-effects meta-analysis. Furthermore, we conducted meta-regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short-term mortality (defined as in-hospital or 30-day mortality) of 45.6% (95% CI, 38.7%-52.4%). We found a significant difference (P<0.001) in mortality rates between acute fulminant myocarditis and congenital heart disease, with acute fulminant myocarditis exhibiting a lower mortality rate. Our findings revealed a negative correlation between older age and weight and short-term mortality in patients undergoing veno-arterial extracorporeal membrane oxygenation. Male sex, bleeding, renal damage, and central cannulation were associated with an increased risk of short-term mortality. CONCLUSIONS: The short-term mortality among pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation for severe heart diseases was 45.6%. Patients with acute fulminant myocarditis exhibited more favorable survival rates compared with those with congenital heart disease. Several risk factors, including male sex, bleeding, renal damage, and central cannulation contributed to an increased risk of short-term mortality. Conversely, older age and greater weight appeared to be protective factors.

Development of a novel hypochlorite ratio probe based on coumarin and its application in living cells.

Hypochlorous acid is a reactive oxygen species that is widely present in the body and has been found to exhibit an elevated concentration in tumors. As a result, fluorescent probes for tumor detection have recently gained significant attention. In this study, we designed and synthesized a novel ratiometric fluorescent probe, LW-1, using coumarin as a scaffold, and characterized its spectral properties. LW-1 displayed indigo blue fluorescence at low concentrations of hypochlorous acid. As the concentration of hypochlorous acid increased, the probe underwent a reaction, resulting in a red shift in its fluorescence peak and exhibiting green fluorescence. The fluorescence intensity ratio (green/blue) was a susceptible detection signal for HClO. LW-1 exhibited favorable characteristics, including a low detection limit, high sensitivity, good stability, and low background interference. The detection limit has reached 2.4642 nM. Moreover, we successfully employed LW-1 to image normal human liver and colon cancer cells in vitro, demonstrating its potential as a promising tool for tumor detection. Overall, our findings suggest that LW-1 could serve as a valuable addition to the current arsenal of fluorescent probes for tumor detection, with potential applications in the diagnosis and treatment of cancer.

Could continuous rice cropping increase soil fertility and rice productivity by rice straw carbonized utilization in cold areas? - A 6-year field-located trial.

Biochar amendment can benefit rice growth, but the long-term effects of rice straw carbonized utilization (RSCU, biochar, and biochar-based fertilizer) on rice production in cold areas are still unclear. Herein, we conducted a field experiment over 6 years with four treatments: F (conventional fertilization) as the control, RB1 (biochar, 3 t·ha-1), RB2 (biochar, 6 t·ha-1), and RBF (biochar-based fertilizer, 0.75 t·ha-1). We found that rice straw biochar significantly improved soil physical properties by reducing soil bulk density, increasing soil porosity and liquid and gas phases ratio, and enhancing soil aggregate stability. RSCU also increased soil fertility by improving soil organic carbon (SOC), active organic carbon, and soil nutrients (N, P, K) and their availability, as indicated by an increase in soil C:N and a decrease in soil N:P. Moreover, biochar increased soil microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and enzyme activities. As a result, RSCU increased rice yield, which was positively correlated with soil total porosity, total phosphorus, available potassium, dissolved organic carbon (DOC), easily oxidizable carbon (EOC), labile fraction of organic carbon (LFOC), and urease activity. RB2 had the highest rice yield (5.94% higher than F). Our study suggests that RSCU can synergistically improve the rice straw utilization rate, soil fertility, and rice productivity in cold areas.

MOF-Derived Ni/ZIF-8/ZnO Arrays on Carbon Fiber Cloth for Efficient Adsorption-Catalytic Oxidation.

The catalytic oxidation of toxic organic pollutants in water requires enhanced efficiency for commercial applications. A ZnO nanorod array grown on a carbon fiber cloth (CFC) serves as the zinc source to ensure that the Ni/ZIF-8/ZnO nanoreactor is constructed. The Ni/ZIF-8/ZnO/CFC nanoreactor efficiently activates peroxymonosulfate (PMS) for bisphenol A (BPA) degradation owing to its high density of active sites, high adsorbability, and dispersibility structure, which concentrates catalytic and adsorptive sites within a confined space. Experimental and theoretical calculations clearly show that the introduction of Ni is beneficial for improving the adsorption of BPA and the activation of PMS. The synergistic mechanism of BPA adsorption-PMS activation is also investigated, and the degradation pathway of BPA is examined. Moreover, a filter catalytic unit is constructed using Ni/ZIF-8/ZnO/CFC to achieve a continuous zero discharge of BPA, which is convenient for nanocatalyst recycling. This study aims to develop a new strategy for the removal of emerging organic pollutants from water using a system with strong adsorption and catalytic capabilities.

GPR81-mediated reprogramming of glucose metabolism contributes to the immune landscape in breast cancer.

BACKGROUND: Local tumor microenvironment (TME) plays a crucial role in immunotherapy for breast cancer (BC). Whereas, the molecular mechanism responsible for the crosstalk between BC cells and surrounding immune cells remains unclear. The present study aimed to determine the interplay between GPR81-mediated glucometabolic reprogramming of BC and the immune landscape in TME. MATERIALS AND METHODS: Immunohistochemistry (IHC) assay was first performed to evaluate the association between GPR81 and the immune landscape. Then, several stable BC cell lines with down-regulated GPR81 expression were established to directly identify the role of GPR81 in glucometabolic reprogramming, and western blotting assay was used to detect the underlying molecular mechanism. Finally, a transwell co-culture system confirmed the crosstalk between glucometabolic regulation mediated by GPR81 in BC and induced immune attenuation. RESULTS: IHC analysis demonstrated that the representation of infiltrating CD8+ T cells and FOXP3+ T cells were dramatically higher in BC with a triple negative (TN) subtype in comparison with that with a non-TN subtype (P < 0.001). Additionally, the ratio of infiltrating CD8+ to FOXP3+ T cells was significantly negatively associated with GPR81 expression in BC with a TN subtype (P < 0.001). Furthermore, GPR81 was found to be substantially correlated with the glycolytic capability (P < 0.001) of BC cells depending on a Hippo-YAP signaling pathway (P < 0.001). In the transwell co-culture system, GPR81-mediated reprogramming of glucose metabolism in BC significantly contributed to a decreased proportion of CD8+ T (P < 0.001) and an increased percentage of FOXP3+ T (P < 0.001) in the co-cultured lymphocytes. CONCLUSION: Glucometabolic reprogramming through a GPR81-mediated Hippo-YAP signaling pathway was responsible for the distinct immune landscape in BC. GPR81 was a potential biomarker to stratify patients before immunotherapy to improve BC's clinical prospect.

An Oxalate Transporter Gene, AtOT, Enhances Aluminum Tolerance in Arabidopsis thaliana by Regulating Oxalate Efflux.

Secretion and efflux of oxalic acid from roots is an important aluminum detoxification mechanism for various plants; however, how this process is completed remains unclear. In this study, the candidate oxalate transporter gene AtOT, encoding 287 amino acids, was cloned and identified from Arabidopsis thaliana. AtOT was upregulated in response to aluminum stress at the transcriptional level, which was closely related to aluminum treatment concentration and time. The root growth of Arabidopsis was inhibited after knocking out AtOT, and this effect was amplified by aluminum stress. Yeast cells expressing AtOT enhanced oxalic acid resistance and aluminum tolerance, which was closely correlated with the secretion of oxalic acid by membrane vesicle transport. Collectively, these results underline an external exclusion mechanism of oxalate involving AtOT to enhance oxalic acid resistance and aluminum tolerance.

A compact review of progress and prospects of deep learning in drug discovery.

BACKGROUND: Drug discovery processes, such as new drug development, drug synergy, and drug repurposing, consume significant yearly resources. Computer-aided drug discovery can effectively improve the efficiency of drug discovery. Traditional computer methods such as virtual screening and molecular docking have achieved many gratifying results in drug development. However, with the rapid growth of computer science, data structures have changed considerably; with more extensive and dimensional data and more significant amounts of data, traditional computer methods can no longer be applied well. Deep learning methods are based on deep neural network structures that can handle high-dimensional data very well, so they are used in current drug development. RESULTS: This review summarized the applications of deep learning methods in drug discovery, such as drug target discovery, drug de novo design, drug recommendation, drug synergy, and drug response prediction. While applying deep learning methods to drug discovery suffers from a lack of data, transfer learning is an excellent solution to this problem. Furthermore, deep learning methods can extract deeper features and have higher predictive power than other machine learning methods. Deep learning methods have great potential in drug discovery and are expected to facilitate drug discovery development.

QX-type infectious bronchitis virus infection in roosters can seriously injure the reproductive system and cause sex hormone secretion disorder.

Since its discovery, QX-type avian infectious bronchitis virus (IBV) has rapidly spread worldwide and become the most prevalent dominant genotype in Asia and Europe. Currently, although the pathogenicity of QX-type IBV in the reproductive system of hens is widely and deeply understood, its pathogenicity in the reproductive system of roosters remains largely unknown. In this study, 30-week-old specific pathogen-free (SPF) roosters were used to investigate the pathogenicity of QX-type IBV in the reproductive system after infection. The results showed that QX-type IBV infection caused abnormal testicular morphology, moderate atrophy and obvious dilatation of seminiferous tubules, and produced intense inflammation and obvious pathological injuries in the ductus deferens of infected chickens. Immunohistochemistry results showed that QX-type IBV can replicate in spermatogenic cells at various stages and in the mucous layer of the ductus deferens. Further studies showed that QX-type IBV infection affects plasma levels of testosterone, luteinizing hormone, and follicle-stimulating hormone as well as causes changes in transcription levels of their receptors in the testis. Furthermore, the transcription levels of StAR, P450scc, 3ßHSD and 17ßHSD4 also changed during testosterone synthesis after QX-type IBV infection, indicating that the virus can directly affect steroidogenesis. Finally, we found that QX-type IBV infection leads to extensive germ cell apoptosis in the testis. Collectively, our results suggest that QX-type IBV replicates in the testis and ductus deferens, causing severe tissue damage and disruption of reproductive hormone secretion. These adverse events eventually lead to mass germ cell apoptosis in the testis, affecting the reproductive function of roosters.

Smart Chemical Oxidative Polymerization Strategy To Construct Au@PPy Core-Shell Nanoparticles for Cancer Diagnosis and Imaging-Guided Photothermal Therapy.

Imaging-guided photothermal therapy (PTT) in a single nanoscale platform has aroused extensive research interest in precision medicine, yet only a few methods have gained wide acceptance. Thus, it remained an urgent need to facilely develop biocompatible and green probes with excellent theranostic capacity for superior biomedical applications. In this study, a smart chemical oxidative polymerization strategy was successfully developed for the synthesis of Au@PPy core-shell nanoparticles with polyvinyl alcohol (PVA) as the hydrophile. In the reaction, the reactant tetrachloroauric acid (HAuCl4) was reduced by pyrrole to fabricate a gold (Au) core, and pyrrole was oxidized to deposit around the Au core to form a polypyrrole (PPy) shell. The as-synthesized Au@PPy nanoparticles showed a regular core-shell morphology and good colloidal stability. Relying on the high X-ray attenuation of Au and strong near-infrared (NIR) absorbance of PPy and Au, Au@PPy nanoparticles exhibited excellent performance in blood pool/tumor imaging and PTT treatment by a series of in vivo experiments, in which tumor could be precisely positioned and thoroughly eradicated. Hence, the facile chemical oxidative polymerization strategy for constructing monodisperse Au@PPy core-shell nanoparticles with potential for cancer diagnosis and imaging-guided photothermal therapy shed light on an innovative design concept for the facile fabrication of biomedical materials.

Cloning, Expression Analysis, and Functional Characterization of Candidate Oxalate Transporter Genes of HbOT1 and HbOT2 from Rubber Tree (Hevea brasiliensis).

Secretion of oxalic acid from roots is an important aluminum detoxification mechanism for many plants such as Hevea brasiliensis (rubber tree). However, the underlying molecular mechanism and oxalate transporter genes in plants have not yet been reported. In this study, the oxalate transporter candidate genes HbOT1 and HbOT2 from the rubber tree were cloned and preliminarily identified. It was found that HbOT1 had a full length of 1163 bp with CDS size of 792 bp, encoding 263 amino acids, and HbOT2 had a full length of 1647 bp with a CDS region length of 840 bp, encoding 279 amino acid residues. HbOT1 and HbOT2 were both stable hydrophobic proteins with transmembrane structure and SNARE_assoc domains, possibly belonging to the SNARE_assoc subfamily proteins of the SNARE superfamily. qRT-PCR assays revealed that HbOT1 and HbOT2 were constitutively expressed in different tissues, with HbOT1 highly expressed in roots, stems, barks, and latex, while HbOT2 was highly expressed in latex. In addition, the expressions of HbOT1 and HbOT2 were up-regulated in response to aluminum stress, and they were inducible by metals, such as copper and manganese. Heterologous expression of HbOT1 and HbOT2 in the yeast mutant AD12345678 enhanced the tolerance to oxalic acid and high concentration aluminum stress, which was closely correlated with the secretion of oxalic acid. This study is the first report on oxalate transporter genes in plants, which provides a theoretical reference for the study on the molecular mechanism of oxalic acid secretion to relieve aluminum toxicity and on aluminum-tolerance genetic engineering breeding.

Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity.

Vascular remodeling during microgravity exposure results in postflight cardiovascular deconditioning and orthostatic intolerance in astronauts. To clarify the underlying mechanism, we investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) under simulated microgravity. Phenotypic markers, mtDNA copy number and mitochondrial biogenesis, mitochondrial dynamics and mitophagy in rat thoracic artery smooth muscle cells were examined. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats and 10% serum was used to induce VSMCs dedifferentiation in vitro. The effects of ERα-NRF1-OMI signaling on mitophagy, phenotypic switching and proliferation of VSMCs, and cerebrovascular remodeling in HU rats were studied by genetic manipulation and chronic drug intervention. We found that ERα is positively associated with contractile phenotype switching but inversely correlated with synthetic phenotype switching and proliferation of VSMCs both in vivo and in vitro. During the dedifferentiation process of VSMCs, reduced mtDNA copy number, disturbed mitochondrial biogenesis and respiration, and perturbed fission-fusion-mitophagy signaling were detected, which were reversed by ERα overexpression. Mechanistically, the ERα downstream protein OMI preserved the mitochondrial Parkin level by increasing its protein stability, thereby protecting mitophagy. In line with this, we found that activating ERα signaling by propyl pyrazole triol (PPT) could alleviate the synthetic phenotype switching and proliferation of HU rat cerebral VSMCs by reestablishing fission-fusion-mitophagy hemostasis. The current study clarified a novel mechanism by which inhibited ERα-NRF1-OMI-mitophagy signaling resulted in synthetic phenotype switching and proliferation of VSMCs and cerebrovascular remodeling under simulated microgravity.

A Review of The Application of Spectroscopy to Flavonoids from Medicine and Food Homology Materials.

Medicinal and food homology materials are a group of drugs in herbal medicine that have nutritional value and can be used as functional food, with great potential for development and application. Flavonoids are one of the major groups of components in pharmaceutical and food materials that have been found to possess a variety of biological activities and pharmacological effects. More and more analytical techniques are being used in the study of flavonoid components of medicinal and food homology materials. Compared to traditional analytical methods, spectroscopic analysis has the advantages of being rapid, economical and free of chemical waste. It is therefore widely used for the identification and analysis of herbal components. This paper reviews the application of spectroscopic techniques in the study of flavonoid components in medicinal and food homology materials, including structure determination, content determination, quality identification, interaction studies, and the corresponding chemometrics. This review may provide some reference and assistance for future studies on the flavonoid composition of other medicinal and food homology materials.

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration. Methods: SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment. Discussion: This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population. Trial Registration: Chinese Clinical Trials Register ChiCTR2200061938.

Potential of immune-related genes as promising biomarkers for premature coronary heart disease through high throughput sequencing and integrated bioinformatics analysis.

Background: Coronary heart disease (CHD) is the most common progressive disease that is difficult to diagnose and predict in the young asymptomatic period. Our study explored a mechanistic understanding of the genetic effects of premature CHD (PCHD) and provided potential biomarkers and treatment targets for further research through high throughput sequencing and integrated bioinformatics analysis. Methods: High throughput sequencing was performed among recruited patients with PCHD and young healthy individuals, and CHD-related microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using R software. Enrichment analysis and CIBERSORT were performed to explore the enriched pathways of DEGs and the characteristics of infiltrating immune cells. Hub genes identified by protein-protein interaction (PPI) networks were used to construct the competitive endogenous RNA (ceRNA) networks. Potential drugs were predicted by using the Drug Gene Interaction Database (DGIdb). Results: A total of 35 DEGs were identified from the sequencing dataset and GEO database by the Venn Diagram. Enrichment analysis indicated that DEGs are mostly enriched in excessive immune activation pathways and signal transduction. CIBERSORT exhibited that resting memory CD4 T cells and neutrophils were more abundant, and M2 macrophages, CD8 T cells, and naïve CD4 T cells were relatively scarce in patients with PCHD. After the identification of 10 hub gens, three ceRNA networks of CD83, CXCL8, and NR4A2 were constructed by data retrieval and validation. In addition, CXCL8 might interact most with multiple chemical compounds mainly consisting of anti-inflammatory drugs. Conclusions: The immune dysfunction mainly contributes to the pathogenesis of PCHD, and three ceRNA networks of CD83, CXCL8, and NR4A2 may be potential candidate biomarkers for early diagnosis and treatment targets of PCHD.

Osteoblast Derived Exosomes Alleviate Radiation- Induced Hematopoietic Injury.

As hematopoietic stem cells can differentiate into all hematopoietic lineages, mitigating the damage to hematopoietic stem cells is important for recovery from overdose radiation injury. Cells in bone marrow microenvironment are essential for hematopoietic stem cells maintenance and protection, and many of the paracrine mediators have been discovered in shaping hematopoietic function. Several recent reports support exosomes as effective regulators of hematopoietic stem cells, but the role of osteoblast derived exosomes in hematopoietic stem cells protection is less understood. Here, we investigated that osteoblast derived exosomes could alleviate radiation damage to hematopoietic stem cells. We show that intravenous injection of osteoblast derived exosomes promoted WBC, lymphocyte, monocyte and hematopoietic stem cells recovery after irradiation significantly. By sequencing osteoblast derived exosomes derived miRNAs and verified in vitro, we identified miR-21 is involved in hematopoietic stem cells protection via targeting PDCD4. Collectively, our data demonstrate that osteoblast derived exosomes derived miR-21 is a resultful regulator to radio-protection of hematopoietic stem cells and provide a new strategy for reducing radiation induced hematopoietic injury.

Pathogenesis of premature coronary artery disease: Focus on risk factors and genetic variants.

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

Prediction of HER2 expression in breast cancer by combining PET/CT radiomic analysis and machine learning.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) expression status determination significantly contributes to HER2-targeted therapy in breast cancer (BC). The purpose of this study was to evaluate the role of radiomics and machine learning based on PET/CT images in HER2 status prediction, and to identify the most effective combination of machine learning model and radiomic features. METHODS: A total of 217 BC patients who underwent PET/CT examination were involved in the study and randomly divided into a training set (n = 151) and a testing set (n = 66). For all four models, the model parameters were determined using a threefold cross-validation in the training set. Each model's performance was evaluated on the independent testing set using the receiver operating characteristic (ROC) curve, and AUC was calculated to get a quantified performance measurement of each model. RESULTS: Among the four developed machine learning models, the XGBoost model outperformed other machine learning models in HER2 status prediction. Furthermore, compared to the XGBoost model based on PET alone or CT alone radiomic features, the predictive power for HER2 status by using XGBoost model based on PET/CTmean or PET/CTconcat radiomic fusion features was dramatically improved with an AUC of 0.76 (95% confidence interval [CI] 0.69-0.83) and 0.72 (0.65-0.80), respectively. CONCLUSIONS: The established machine learning classifier based on PET/CT radiomic features is potentially predictive of HER2 status in BC.