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Abstract Background Sarcomatoid urothelial carcinoma (SUC) is a rare and highly malignant form of bladder cancer with a poor prognosis. Currently, there is limited information on the imaging features of bladder SUC and reliable indicators for distinguishing it from conventional urothelial carcinoma (CUC). The objective of our study was to identify the unique imaging characteristics of bladder SUC and determine factors that aid in its differential diagnosis. Materials and methods This retrospective study enrolled 22 participants with bladder SUC and 61 participants with CUC. The clinical, pathologic, and CT/MRI data from both groups were recorded, and a comparison was conducted using univariate analysis and multinomial logistic regression for distinguishing SUC from CUC. Results The majority of SUCs were located in the trigone of the bladder and exhibited large tumor size, irregular shape, low ADC values, Vesical Imaging-Reporting and Data System (VI-RADS) score ≥ 4, the presence of necrosis, and an invasive nature. Univariate analysis revealed significant differences in terms of tumor location, shape, the maximum long-axis diameter (LAD), the short-axis diameter (SAD), ADC-value, VI-RADS scores, necrosis, extravesical extension (EVE), pelvic peritoneal spread (PPS), and hydronephrosis/ureteral effusion (p

Abstract Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.

Abstract Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium–sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium–sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium–sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm−2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm−2 and electrolyte dosage of 4.8 μL mg−1.

Headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and electronic nose (E-nose) were performed to investigate change of volatile compounds in celery leaves during storage at 20.0 ℃. The results indicated that a total of 108 volatile compounds were identified by HS-SPME-GC-MS, mainly including monoterpenes (43.2%~52.92%) and phthalides (19.93%~28.97%), in which D-limonene was abundant (6600.64~48566.12 μg/kg). The total volatile substance content of fresh celery was 165682.48 μg/kg, which decreased by 40.92% after 9 days of storage. The percent of monoterpenes and phthalides decreased by 9.72% and increased by 8.98% respectively during storage. In celery leaves, 31 substances were detected according to OAV>1. There were 31 kinds of the same characteristic volatile substances during 0~7 d and the number of characteristic volatile substances decreased to 29 at 9 d. During storage, the total OAV value decreased. The cluster analysis confirmed that the celery leaves were mainly minty and grassy odour during 0~3 d, and sweet, wood and camphorated odour at 7 d. After the 9th day, the aroma of celery leaves was spicy and herbal odour. The PCA of E-nose response data showed that E-nose could distinguish the aroma of celery leaves during different storage period. Based on Pearson correlation analysis, the main substances causing changes in the response value of E-nose were terpenoids, alcohols and aromatic volatile compounds of celery (r≥0.80, P

Background & Aims: The functional maturation of the liver largely occurs after birth. In the early stages of life, the liver of a newborn encounters enormous high-fat metabolic stress caused by the consumption of breast milk. It is unclear how the maturing liver adapts to high lipid metabolism. Liver sinusoidal endothelial cells (LSECs) play a fundamental role in establishing liver vasculature and are decorated with many glycoproteins on their surface. The Slc35a1 gene encodes a cytidine-5'-monophosphate (CMP)-sialic acid transporter responsible for transporting CMP-sialic acids between the cytoplasm and the Golgi apparatus for protein sialylation. This study aimed to determine whether endothelial sialylation plays a role in hepatic vasculogenesis and functional maturation. Methods: Endothelial-specific Slc35a1 knockout mice were generated. Liver tissues were collected for histologic analysis, lipidomic profiling, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. Results: Endothelial Slc35a1-deficient mice exhibited excessive neonatal hepatic lipid deposition, severe liver damage, and high mortality. Endothelial deletion of Slc35a1 led to sinusoidal capillarization and disrupted hepatic zonation. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) in LSECs was desialylated and VEGFR2 signaling was enhanced in Slc35a1-deficient mice. Inhibition of VEGFR2 signaling by SU5416 alleviated lipid deposition and restored hepatic vasculature in Slc35a1-deficient mice. Conclusions: Our findings suggest that sialylation of LSECs is critical for maintaining hepatic vascular development and lipid homeostasis. Targeting VEGFR2 signaling may be a new strategy to prevent liver disorders associated with abnormal vasculature and lipid deposition.

The effects of different complex shear stress conditions on grain refinement and texture evolution of Mg-13Gd-4Y-2Zn-0.5Zr alloy were investigated. With increasing strain rate, the average grain size of compression-shear (CS) and compression-torsion (CT) samples are decreased, and the grain size of dynamic recrystallization (DRX) grains is also decreased. This is because that the precipitation number of β phases is increased, and the hindering effect on grain growth can be significantly enhanced. The DRX fractions of CS and CT samples are decreased with increased strain rate. The low DRX fraction at high strain rate is related to the insufficient time for grains to nucleate. The DRX process can be promoted by the PSN mechanism of second phases, and the grain growth can be restricted by the pinning effect. At the same time, the texture strength is enhanced as the strain rate increased. Besides, the kinking degree of lamellar long-period stacking ordered (LPSO) phases is increased. Under complex shear stress conditions, non-basal slip, especially pyramidal slip, is easily activated and the texture is deflected greatly. Compared with the CS samples, CT samples have smaller average grain size, higher DRX fraction, and lower texture strength for a certain strain rate. This is because that the equivalent stress of the CT sample is larger, the stress triaxiality is smaller, so more serious dislocations are piled up near grain boundaries and second phases. At the same time, since CT sample was sheared with torsion, the dislocation movement path can be called “rotational dislocation accumulation”, and the longer distribution path of the CT sample is generated, so more sub-grains and low-angle grain boundaries (LAGBs) are formed. Compared with the CS sample, more huge-angle grain boundaries (HAGBs) and DRX grains are formed from grain boundary to grain interior, so better grain refinement effect is achieved.

Mycoplasma synoviae (MS) is a primary avian pathogen prevalent worldwide that causes airsacculitis and synovitis in birds. Vaccination is recommended as the most cost-effective strategy in the control of MS infection. Novel alternative vaccines are needed for eradicating and controlling MS infection in flocks. DnaK, enolase, elongation factor Tu (EF-Tu), MSPB, NADH oxidase and LP78 are the major immunogenic antigens of MS and are promising targets for subunit vaccine candidates. In the present study, genes encoding DnaK, enolase, EF-Tu, MSPB, LP78, and NADH oxidase were cloned and expressed in Escherichia coli. Enzyme-linked immunosorbent assay showed that the six recombinant proteins were recognized by convalescent sera, indicating that they were expressed during infection. Two injections of the six subunit vaccines induced a robust antibody response and increased the concentrations of IFN-γ and IL-4, especially rEnolase and rEF-Tu. The proliferation of peripheral blood lymphocytes was enhanced in all of the immunized groups. Chickens immunized with rEnolase, rEF-Tu, rLP78, and rMSPB conferred significant protection against MS infection, as indicated by significantly lower DNA copies in the trachea, lower scores of air sac lesions, and lesser tracheal mucosal thickness than that in the challenge control. Especially, rEnolase provided the best protective efficacy, followed by rEF-Tu, rMSPB, and rLP78. Our finds demonstrate that the subunit vaccines and bacterin can only reduce the lesions caused by MS infection, but not prevent colonization of the organism. Our findings may contribute to the development of novel vaccine agents against MS infection.

Abstract Ferroptosis represents an innovative strategy to overcome the resistance of traditional cancer therapeutic through lethal lipid peroxidation leading to immunogenic cell death. However, the inefficiency of ferroptosis inducers and mild immunogenicity restrict the further clinical applications. Herein, engineering exosome-mimic M1 nanovesicles (MNV) were prepared by serial extrusion of M1 macrophage and served as an efficient vehicle for docosahexaenoic acid (DHA) delivery. MNV loaded with DHA (MNV@DHA) could promote more DHA accumulation in tumor cells, depletion glutathione and reduction of lipid antioxidant glutathione peroxidase-4 facilitating the occurrence of ferroptosis. Furthermore, MNV were able to induce the polarization of M1 and repolarize M2 macrophages to activate tumor immune microenvironments. The activated immune cells would further trigger the ferroptosis of tumor cells. In a murine orthotopic hepatocellular carcinoma model, MNV@DHA could significantly target tumor tissues, increase the proportion of M1 macrophages and CD8+ T cells and lessen the infiltration of M2 macrophages. Accordingly, MNV@DHA characterized with positive feedback regulation between ferroptosis and immune activation exhibited the strongest in vivo therapeutic effect. The synergism of ferroptosis and immunomodulation based on the dietary polyunsaturated fatty acids and engineered exosome-mimic nanovesicles may serve as a promising modality to efficiently complement pharmacological approaches for cancer management.

Abstract Background and aims Studies concerning the impact of air temperature on esophagogastric variceal bleeding (EGVB) have yielded conflicting results. Our study aimed to evaluate the correlation between air temperature and EGVB. Methods A time-stratified case-crossover study design was performed. Patients received emergency gastroscopic hemostasis for upper gastrointestinal bleeding between Jan 1, 2014, and Dec 31, 2018 in the Fifth Medical Center of PLA General Hospital were enrolled. Conditional logistic regression analysis was applied to determine the association between air temperature and EGVB for different lag structures. Results A total of 4204 cirrhotic patients diagnosed with EGVB and received emergency gastroscopic hemostasis were enrolled. The mean number of daily EGVB cases peaked in October (2.65 ± 1.69) and fell to the lowest level in July (1.86 ± 1.38), and was 2.38 ± 1.58 in spring, 2.00 ± 1.46 in summer, 2.37 ± 1.58 in autumn, and 2.45 ± 1.58 in winter, respectively (P

Abstract Background Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. Methods This study assessed the preoperative frailty according to the Fried’s frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. Results In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. Conclusion Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. Trial registration The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Abstract Background Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer’s disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. Methods In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid β-protein (Aβ), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. Results The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aβ deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. Conclusions The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aβ clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.

Abstract A system for itaconic acid synthesis from cellulose by Neurospora crassa was established, resulting in the highest yield of itaconic acid was 354.08 + 35.99 mg/L. Meanwhile, cellulase activity increased significantly, without any strain modifications for improved cellulase production. Multi-omics analyses showed that itaconic acid synthesis reduced energy production, leading to decreases in trehalose, cell wall, fatty acids synthesis and downregulations in MAPK signaling pathway, cell cycle and meiosis. More importantly, the low-energy environment enhanced the energy-efficient cellobionic acid/gluconic acid pathway, and the cellulase composition also changed significantly, manifested as the up-regulation of LPMOs and the down-regulation of β-glucosidases. Enhancing LPMOs-cellobionic acid/gluconic acid system has the potential to reduce energy consumption of the consolidated bioprocessing. These findings offer an overview of resource allocations by N. crassa in response to itaconic acid synthesis and highlight a series of intriguing connections between itaconic acid synthesis and cellulase synthesis in consolidated bioprocessing.

IntroductionAcute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m6A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance.MethodsTo investigate the m6A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m6A modification activity of cells in AML patients based on 23 m6A modification enzymes and further integrated with bulk RNA-seq data.ResultsWe found that m6A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m6A modification status in leukemia cells, while active m6A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m6A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by RUNX1 mutation and KMT2A copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of IGF2BP3 and FMR1, and low expression level of ELAVL1 and YTHDF2. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy.DiscussionCollectively, our findings suggest that m6A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.

BackgroundNon-melanoma skin cancer (NMSC) is a prevalent skin malignancy. It has been indicated in many studies that trihalomethanes (THMs) exposure has a strong association with tumors but has not been associated with NMSC. Our investigation aims to explore the association between THMs exposure and NMSC.MethodsCross-sectional data from the 2011 to 2020 National Health and Nutrition Examination Survey (NHANES) was collected. Poisson regression and subgroup analyses were performed to evaluate the association between individual THMs components and NMSC. Fitted smoothing curves and generalized additive models were also used.ResultsThis study involved 5,715 individuals, 98 (1.7%) of whom self-reported NMSC. After adjusting for covariates, Poisson regression showed that higher blood TBM levels were associated with an increased likelihood of NMSC (OR = 1.03; 95% CI: 1.01–1.05, p = 0.002). However, the correlation between the blood levels of TCM, DBCM, and BDCM and the likelihood of NMSC was not statistically significant (all p > 0.05). Subgroup analysis and interaction tests showed no significant differences between blood TBM concentration and the likelihood of NMSC, indicating that age, gender, and race were significantly independent of this positive association (all p < 0.05).ConclusionsOur results implied that among adults older than 65 years old in the U.S., elevated blood TBM concentrations were positively associated with NMSC. More prospective investigations are required to validate this relationship with the early prevention of NMSC.

Abstract Interleukin 27 (IL-27), a heterodimeric cytokine composed of Epstein-Barr virus-induced 3 and p28, is a pleiotropic cytokine with both pro-and anti-inflammatory properties. However, the precise role of IL-27 in acute graft-versus-host disease is not yet fully understood. In this study, utilizing mice with IL-27 p28 deficiency in dendritic cells (DCs), we demonstrated that IL-27 p28 deficiency resulted in impaired Treg cell function and enhanced effector T cell responses, corresponding to aggravated aGVHD in mice. In addition, using single-cell RNA sequencing, we found that loss of IL-27 p28 impaired Treg cell generation and promoted IL-1R2+TIGIT+ pathogenic CD4+ T cells in the thymus at a steady state. Mechanistically, IL-27 p28 deficiency promoted STAT1 phosphorylation and Th1 cell responses, leading to the inhibition of Treg cell differentiation and function. Finally, patients with high levels of IL-27 p28 in serum showed a substantially decreased occurrence of grade II-IV aGVHD and more favorable overall survival than those with low levels of IL-27 p28. Thus, our results suggest a protective role of DC-derived IL-27 p28 in the pathogenesis of aGVHD through modulation of the Treg/Teff cell balance during thymic development. IL-27 p28 may be a valuable marker for predicting aGVHD development after transplantation in humans.

Abstract Background Undifferentiated pleomorphic sarcoma (UPS) is considered one of the most common types of soft tissue sarcoma (STS). Current studies have shown that the prognosis of UPS is related to some of its clinical characteristics, but no survival prediction model for the overall survival (OS) of UPS patients has been reported. The purpose of this study is to construct and validate a nomogram for predicting OS in UPS patients at 3, 5 years after the diagnosis. Methods According to the inclusion and exclusion criteria, 1079 patients with UPS were screened from the SEER database and randomly divided into the training cohort (n = 755) and the validation cohort (n = 324). Patient demographic and clinicopathological characteristics were first described, and the correlation between the two groups was compared, using the Kaplan–Meier method and Cox regression analysis to determine independent prognostic factors. Based on the identified independent prognostic factors, a nomogram for OS in UPS patients was established using R language. The nomogram’s performance was then validated using multiple indicators, including the area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). Results Both the C-index of the OS nomogram in the training cohort and the validation cohort were greater than 0 .75, and both the values of AUC were greater than 0.78. These four values were higher than their corresponding values in the TNM staging system, respectively. The calibration curves of the Nomogram prediction model and the TNM staging system were well fitted with the 45° line. Decision curve analysis showed that both the nomogram model and the TNM staging system had clinical net benefits over a wide range of threshold probabilities, and the nomogram had higher clinical net benefits than the TNM staging system as a whole. Conclusion With good discrimination, accuracy, and clinical practicability, the nomogram can individualize the prediction of 3-year and 5-year OS in patients with UPS, which can provide a reference for clinicians and patients to make better clinical decisions.

Summary: The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.

IntroductionThe incidence of hospital-acquired pneumonia (HAP) is high in the medical setting for mental disorders. To date, effective measurements for preventing HAP in hospitalized mental disorder patients are unavailable.MethodsThis study was conducted at the Large-Scale Mental Health Center of Renmin Hospital of Wuhan University (Wuhan, China) in two phases: baseline phase (January 2017–December 2019) and intervention phase (May 2020–April 2022). In the intervention phase, the HAP bundle management strategy was implemented in the Mental Health Center, and the data on HAP were collected continuously for analysis.ResultsA total of 18,795 and 9,618 patients were included in the baseline and intervention phases, respectively. The age, gender, ward admitted to, type of mental disorder, and Charlson comorbidity index did not differ significantly. After intervention, the rate of HAP occurrence decreased from 0.95 to 0.52% (P < 0.001). Specifically, the HAP rate decreased from 1.70 to 0.95% (P = 0.007) in the closed ward and from 0.63 to 0.35% (P = 0.009) in the open ward. The HAP rate in the subgroups was higher in patients with schizophrenia spectrum disorders (1.66 vs. 0.74%) and organic mental disorders (4.92 vs. 1.41%), and in those ≥65 years old (2.82 vs. 1.11%) but decreased significantly after intervention (all P < 0.05).ConclusionThe implementation of the HAP bundle management strategy reduced the occurrence of HAP in hospitalized patients with mental disorders.

In this study, a novel synergistic photocatalyst (Fe3O4/GO/g-C3N4 composites) were constructed by chemical precipitation of Fe3O4 nanoparticles on surface of GO/g-C3N4 suspension. The characterization results indicated that Fe3O4/GO/g-C3N4 composites exhibited high efficient separation of photogenerated electron–hole pair, narrow bandgap (∼2.38 eV) and wide absorption range. The incorporation of Fe3O4 significantly increased the photocatalytic performance of GO/g-C3N4 composites due to synergistic effect. More than 90% of U(VI) was photo-reduced by Fe3O4/GO/g-C3N4 composites within 2 h under visible light irradiation. The trapping experiments and XPS analysis indicated that the photogenerated electrons and superoxide (⋅O2) radicals are responsible for U(VI) removal. These findings indicated that magnetic g-C3N4 composites can be used as excellent candidates for the high efficient removal of U(VI) in actual environmental cleanup.

AimTo define and analyze the concept of psychological birth trauma.DesignThe concept analysis method of Walker and Avant was used.MethodEight databases (PubMed, CINAHL Complete, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and Chinese BioMedicine Literature Database) were searched from inception to July 2022 for studies focused on psychological birth trauma.ResultsOf the 5,372 studies identified, 44 ultimately met the inclusion criteria. The attributes identified were (1) women’s subjective feelings, (2) intertwined painful emotional experiences, (3) originating in the birth process, and (4) lasting until postpartum. Antecedents were divided into two groups: pre-existing antecedents and birth-related antecedents. Consequences were identified as negative and positive.ConclusionPsychological birth trauma is a more complex and comprehensive concept than previously thought, and should be regarded as a separate postpartum mental health problem. This study deepens the understanding of psychological birth trauma through a comprehensive concept analysis and also puts forward some suggestions for the prevention, identification, and intervention of psychological birth trauma, which provides a basis for assisting in the identification of psychological birth trauma and provides a reference for the development of rigorous assessment tools and the design of appropriate interventions in the future. Further research is needed to update and refine this concept.

Hepatocellular carcinoma (HCC) has a high prevalence and mortality rate worldwide. Sorafenib monotherapy has been the standard of first-line treatment for advanced HCC for a long time, but there are still many shortcomings. In recent years, with the deepening of research on tumor immune microenvironment, researchers have begun to explore new approaches in immunotherapy, and the introduction of immune checkpoint inhibitors has brought fundamental changes to the treatment of HCC. Programmed cell death protein 1 (PD-1) is an immune checkpoint molecule that plays an important role in down-regulating immune system function and promoting tolerance. Programmed cell death ligand 1 (PDL-1) is involved in tumor immune evasion by binding to PD-1, resulting in failure of treatment. Currently, immunotherapy targeting the PD-1/PD-L1 axis has achieved unprecedented success in HCC, but it also faces great challenges, with its low remission rate still to be solved. For most patients with HCC, the PD-1/PD-L1 pathway is not the only rate limiting factor of antitumor immunity, and blocking only the PD-1/PD-L1 axis is not enough to stimulate an effective antitumor immune response; thus, combination therapy may be a better option. In this study, changes in the immune microenvironment of HCC patients were reviewed to clarify the feasibility of anti-PD-1/PD-L1 therapy, and a series of monotherapy and combination therapy clinical trials were summarized to verify the safety and efficacy of this newly developed treatment in patients with advanced HCC. Furthermore, we focused on hyperprogressive disease and drug resistance to gain a better understanding of PD-1/PD-L1 blockade as a promising treatment.

ObjectiveTo investigate the adaptability of Comprehensive Behavioral Intervention for Tics (CBIT) for a Chinese population, and evaluate the efficacy of combined CBIT and pharmacotherapy (CBIT + PT) compared to CBIT or pharmacotherapy (PT) alone for reducing tics and for improving the quality of life (QoL) in a sample of Chinese children with chronic tic disorders (CTD) and Tourette syndrome (TS).Materials and methodsIn this 10-week randomized controlled pilot trial, 37 outpatients aged between 6 and 16 years affected by TS and CTD were randomly assigned to receive CBIT (n = 22) or PT alone (n = 15). Considering the feasibility, the patients allocated to the CBIT treatment group could further choose whether to simultaneously take medicine voluntarily, resulting in a CBIT alone group (n = 12) and a CBIT + PT group (n = 10).ResultsAt baseline, no significant difference was found between the three groups in the demographic and clinical characteristics (p > 0.05). All three groups showed a significant reduction in tic severity after treatment assessed by the Yale Global Tic Severity Scale (YGTSS) severity score [F(2,33) = 35.05, p < 0.001, ηp2 = 0.51], the score of the Clinical Global Impression scale for Improvement (CGI-I) [F(1,34) = 13.87, p = 0.001, ηp2 = 0.29], and YGTSS impairment score [F(2,33) = 31.71, p < 0.001, ηp2 = 0.48]. Significant interactions were found between the time-point and group in emotional functioning [F(2,29) = 4.39, p = 0.02, ηp2 = 0.23], psychosocial functioning [F(2,29) = 5.93, p = 0.007, ηp2 = 0.29], and total QoL score [F(1,34) = 3.72, p = 0.04, ηp2 = 0.20] of Pediatric Quality of Life Inventory (PedsQL 4.0) for children suggesting a significantly larger improvement in emotional functioning, psychosocial functioning, and total QoL score of the life quality in the CBIT group for children self-report. PedsQL for proxy report only showed a significant main effect of time-point in physical functioning [F(1,33) = 8.35, p = 0.01, ηp2 = 0.2], emotional functioning [F(1,33) = 10.75, p = 0.002, ηp2 = 0.25], psychosocial functioning [F(1,34) = 11.38, p = 0.002, ηp2 = 0.26], and total Qol score [F(1,34) = 13.21, p = 0.001, ηp2 = 0.29].ConclusionCBIT is probably effective in reducing tic severity in Chinese children with tic disorders. CBIT + PT may not be superior to CBIT alone in reducing tic severity and improving quality of life. CBIT alone showed advantages in improving quality of life over CBIT + PT and PT alone. CBIT might be an appropriate treatment option for patients with tic disorder in Chinese mainland.

With the aging population and the increasing incidence of basic illnesses such as hypertension and diabetes (DM), the incidence of atrial fibrillation (AF) has increased significantly. AF is the most common arrhythmia in clinical practice, which can cause heart failure (HF) and ischemic stroke (IS), increasing disability and mortality. Current studies point out that myocardial fibrosis (MF) is one of the most critical substrates for the occurrence and maintenance of AF. Although myocardial biopsy is the gold standard for evaluating MF, it is rarely used in clinical practice because it is an invasive procedure. In addition, serological indicators and imaging methods have also been used to evaluate MF. Nevertheless, the accuracy of serological markers in evaluating MF is controversial. This review focuses on the pathogenesis of MF, serological evaluation, imaging evaluation, and anti-fibrosis treatment to discuss the existing problems and provide new ideas for MF and AF evaluation and treatment.

IntroductionCommunity-acquired pneumonia (CAP) is an important cause of hospitalization and death in patients with mental disorders. It is critical to understand the risk factors of CAP and determine prevention strategies to reduce CAP. The aim of this study is to explore the characteristics of inpatients with mental disorders who have CAP and analyze the risk factors.MethodsThis retrospective study included 16,934 inpatients with mental disorders who were admitted for the first time to a tertiary general hospital between January 2017 and July 2021 (excluding January 2020–May 2020). Risk factors for CAP were identified by logistic regression analysis after propensity score matching (PSM, 1:4) for age, gender, and BMI.ResultsThe CAP rate of inpatients with mental disorders was 1.78%. Inpatients who had CAP had a significantly prolonged hospital stay, and were more often admitted to a closed ward or the ICU. After PSM, the multivariable analysis revealed that clozapine use (OR = 3.212, 95% CI = 1.744–5.915, P < 0.001), schizophrenia spectrum disorder (OR = 2.785, 95% CI = 1.684–4.607, P < 0.001), alcohol consumption (OR = 2.549, 95% CI = 1.586–4.096, P < 0.001), cardiovascular disease (OR = 2.299, 95% CI = 1.362–3.879, P = 0.002), Charlson comorbidity index (CCI) ≥ 3 (OR = 2.092, 95% CI = 1.342–3.260, P = 0.001), organic mental disorder (OR = 1.941, 95% CI = 1.194–3.156, P = 0.007), antipsychotic drug use (OR = 1.886, 95% CI = 1.312–2.711, P = 0.001), unmarried status (OR = 1.720, 95% CI = 1.164–2.541, P = 0.006) and junior high school education (OR = 1.591, 95%CI = 1.010–2.508, P = 0.045) were independent risk factors for CAP in inpatients with mental disorders.ConclusionCAP was common in inpatients with mental disorders. Patients with mental disorders have unique risk factors for CAP. Further research is required to explore the relationship and mechanism between different mental disorders, antipsychotic drugs and CAP.

ObjectiveThis study was aimed to investigate the risk of recurrence in patients with atrial fibrillation (AF) after radiofrequency ablation and predict risk of recurrence using C2HEST and HATCH scores.MethodsWe retrospectively included 322 patients with AF from Second Hospital of Lanzhou University, and 261 patients were included in the analysis finally. They had AF and were admitted for radiofrequency catheter ablation. We compared the ability of C2HEST and HATCH scores to predict recurrence after radiofrequency ablation of AF. The predictive ability of C2HEST and HATCH scores for AF recurrence was estimated by the area under the receiver operating characteristic curve (AUROC). The difference in receiver operating characteristic curve between the two models was compared using the DeLong test.ResultsOf the 261 patients included in the analysis, 83 (31.6%) patients suffered a late recurrence of AF after radiofrequency ablation. The risk of postoperative recurrence of AF increased with increasing C2HEST and HATCH scores. The AUROC of C2HEST and HATCH scores in predicting postoperative recurrence of AF was 0.773 (95%CI, 0.713–0.833) and 0.801 (95% CI, 0.740–0.861), respectively. There was no significant difference between the two models in their ability to evaluate patients for postoperative recurrence of AF (DeLong test p-value = 0.36). Among the risk factors in both models, hypertension and heart failure (HF) contributed the most to postoperative recurrence after AF, and higher blood pressure and lower cardiac ejection fraction (EF) were associated with a higher risk of recurrence.ConclusionBoth C2HEST and HATCH scores were significantly associated with the risk of late recurrence after radiofrequency ablation of AF. Besides hypertension and HF contributed the most to postoperative recurrence after AF.

BackgroundCardiac surgery with cardiopulmonary bypass (CPB) is considered to be one of the surgical types with the highest incidence of post-operative delirium (POD). POD has been associated with a prolonged intensive care and hospital stay, long-term neurocognitive deterioration, and increased mortality. However, the specific pathogenesis of POD is still unclear. Untargeted metabolomics techniques can be used to understand the changes of serum metabolites in early POD to discover the relationship between serum metabolites and disease.Materials and MethodsThe present study recruited 58 elderly patients undergoing cardiac surgery with CPB. Serum was collected within the first 24 h after surgery. The Confusion Assessment Method (CAM) and ICU-CAM assessments were used to identify patients who experienced POD. All patients with normal post-operative cognitive assessment were included in the non-POD groups. Moreover, we collected serum from 20 healthy adult volunteers. We performed untargeted analyses of post-operative serum metabolites in all surgical groups, as well as serum metabolites in healthy non-surgical adults by using liquid chromatography mass spectrometry (LC/MS) and analyzed metabolic profiles and related metabolites.ResultsThe probability of POD after cardiac surgery were 31%. There were statistically significant differences in post-operative mechanical ventilation time, ICU stay time and post-operative hospital stay between POD and non-POD group (P < 0.05). And ICU stay time was an independent risk factor for POD. The analysis revealed that a total of 51 differentially expressed metabolites (DEMs) were identified by comparing the POD and non-POD group, mostly lipids and lipid-like molecules. Three phosphatidylinositol (PI) were down-regulated in POD group, i.e., PI [18:0/18:2 (9Z, 12Z)], PI [20:4 (8Z, 11Z, 14Z, 17Z)/18:0], and PI [18:1 (9Z)/20:3 (8Z, 11Z, 14Z)]. The receiver operating characteristic (ROC) curve analysis showed that three kinds of PI metabolites had the highest area under the curve (AUC), which were 0.789, 0.781, and 0.715, respectively. Correlation analysis showed that the expression of three PIs was negatively correlated with the incidence of POD.ConclusionOur findings suggest that lipid metabolism plays an important role in the serum metabolic profile of elderly patients with POD in the early post-operative period. Low serum lipid metabolic PI was associated with incidence of POD in elderly following cardiac bypass surgery, which may provide new insights into the pathogenesis of POD.

Abstract Background In cervical cancer, most patients die of metastasis. The epithelial-to-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of cervical cancer. C-phycocyanin (C-PC) is a natural marine product isolated and purified from Spirulina platensis, has been investigated that has anti-cancer function. The aim of this study was to explore the inhibitory effect of C-phycocyanin on the migration and invasion of cervical cancer cells induced by transforming growth factor-β1 (TGF-β1), so as to provide a new idea for the treatment and prognosis of cervical cancer. Methods A wound-healing assay, an invasion assay, immunofluorescence assay, western blot, flow cytometry and real-time reverse transcriptione polymerase chain reaction were explored in cervical cancer Caski cell lines. TGF-β/smad signaling pathway was evaluated of in Caski cell lines. Results Our study indicated that TGF-β1 induced EMT in cervical cancer cells. C-phycocyanin inhibited EMT in Caski cells by down-regulating N-cadherin and up-regulating E-cadherin protein expression. Furthermore, C-phycocyanin could inhibit the expression and proteins Twist, Snail and Zeb1 transcription factors related to EMT. In addition, C-phycocyanin could inhibit the migration and invasion of Caski cells induced by TGF-β1. Besides, C-phycocyanin inhibited EMT through TGF-β/smads signaling pathway. We also found C-phycocyanin induced cell cycle G0/G1 arrest by decreasing protein expression levels of Cyclin D1 and p27. Conclusions C-phycocyanin reversed TGF-β1-induced epithelial-to-mesenchymal transition in cervical cancer cells and down-regulated the TGF-β/samd signaling pathway induced G0/G1 arrest of tumor cell cycle.

As one of the members of the kinesin family, the role and potential mechanism of kinesin family member C1 (KIFC1) in the development of liver hepatocellular carcinoma (LIHC), especially in the immune infiltration, have not been fully elucidated. In this study, multiple databases and immunohistochemistry were employed to analyze the role and molecular mechanism including the immune infiltration of KIFC1 in LIHC. Generally, KIFC1 mRNA expression was overexpressed in LIHC tissues than normal tissues, and its protein was also highly expressed in the LIHC. KIFC1 mRNA expression was correlated with tumor grade and TNM staging, which was negatively correlated with overall survival and disease-free survival. Moreover, univariable and multivariate Cox analysis revealed that upregulated KIFC1 mRNA is an independent prognostic factor for LIHC. The KIFC1 promoter methylation level was negatively associated with KIFC1 mRNA expression and advanced stages and grade in LIHC. The different methylation sites of KIFC1 had a different effect on the prognosis of LIHC. Specifically, the KIFC1 mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and immune scores as well as multiple immune-related genes. Moreover, KIFC1 co-expressed with some immune checkpoints and related to the responses to immune checkpoint blockade (ICB) and chemotherapies. Significant GO analysis showed that genes correlated with KIFC1 served as catalytic activity, acting on DNA, tubulin binding, histone binding, ATPase activity, and protein serine/threonine kinase activity. KEGG pathway analysis showed that these genes related to KIFC1 are mainly enriched in signal pathways such as cell cycle, spliceosome, pyrimidine metabolism, and RNA transport. Conclusively, KIFC1 was upregulated and displayed a prognostic value in LIHC. Moreover, KIFC1 may be involved in the LIHC progression partially through immune evasion and serve as a predictor of ICB therapies and chemotherapies.

In this study, a lumped parameter model, developed and extensively validated by the authors, is used to simulate the impact of three different dehumidification technologies (mechanical refrigeration dehumidifier, liquid desiccant dehumidifier, and a heat recovery ventilation unit), at a commercial greenhouse growing potted roses in southwestern Ontario, Canada. Typical meteorological year (TMY) data from nearby Vineland, Ontario was used to provide the external weather data used in the model. Each greenhouse bay containing a dehumidification unit was simulated for spring, fall, and winter conditions. The potential reductions in energy use (kWh), greenhouse gas emissions (kg CO2e), and operating cost were estimated for each test case. The potential energy savings from switching from high-pressure sodium (HPS) to light-emitting diode (LED) lights were also examined. The simulation results showed that switching to LED lamps could reduce the electrical energy usage by up to 60% but would increase the space heating requirements. The expected energy-savings from using dehumidification equipment and switching from HPS to LED lighting in Canadian greenhouses is underrepresented in the literature. With the industry growing in the region, this study provides insight into the expected impact that these systems will have on the energy use in commercial greenhouses.

In this study, we investigated the transport mechanism of immune-active peptide fragments isolated from casein gastrointestinal hydrolysates via a Caco-2 monolayer. The casein gastrointestinal hydrolysates could stimulate B-lymphocyte proliferation and reduce the TNF-α level. Then, we identified the bioactive peptide fragments derived from casein gastrointestinal hydrolysis using LC-MS/MS. Our results demonstrated that the transport mechanism of five immune-active peptides at the cell level was bypass transport. In addition, the majority of peptide RYPLGYL was transported through the monolayer cell membrane as an intact form for playing immune-active functions. The KHPIK and FFSDK were mainly degraded into small fragments, except for a small amount passing through Caco-2 cells in an entire form. Overall, these results suggested that casein or its immune-active peptides might play a role in regulation of the intestinal immune system.

Metabolic reprogramming has been suggested as a hallmark of cancer progression. Metabolomic analysis of various metabolic profiles represents a powerful and technically feasible method to monitor dynamic changes in tumor metabolism and response to treatment over the course of the disease. To date, numerous original studies have highlighted the application of metabolomics to various aspects of tumor metabolic reprogramming research. In this review, we summarize how metabolomics techniques can help understand the effects that changes in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Various non-invasive biofluids are available that produce accurate and useful clinical information on tumor metabolism to identify early biomarkers of tumor development. Similarly, metabolomics can predict individual metabolic differences in response to tumor drugs, assess drug efficacy, and monitor drug resistance. On this basis, we also discuss the application of stable isotope tracer technology as a method for the study of tumor metabolism, which enables the tracking of metabolite activity in the body and deep metabolic pathways. We summarize the multifaceted application of metabolomics in cancer metabolic reprogramming to reveal its important role in cancer development and treatment.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

Recent research indicates that graphene oxide (GO) nanosheets can be used to regulate ice formation by controlling critical ice nucleus growth in water at supercooling temperatures. In addition, the study of ice formation mechanisms regulated by GO nanosheets, a good model system for antifreeze proteins (AFPs), will shed light on how AFPs regulate ice formation in nature. In this work, time-resolved small-angle x-ray scattering (TR-SAXS) and quasi-elastic neutron scattering (QENS) experiments were carried out to investigate the structural and dynamical mechanisms of ice formation regulated by GO nanosheets. Strikingly, a transient intermediate state was observed in TR-SAXS experiments that only exists in the aqueous dispersions with a larger GO size (11 nm). This serves as evidence that the size of GO is critical for regulating ice formation. Elastic neutron scattering results indicate that ice is formed in all samples and thermal hysteresis occurs in GO aqueous dispersions in both H2O and D2O. The structural and dynamics information about water molecules in GO, extracted from QENS, reveals different dynamical behaviors of water molecules in GO aqueous dispersions when approaching the ice formation temperature.

Abstract Activity‐based approaches for designing AIEgens possess prominent advantages including high selectivity, sensitivity, and signal‐to‐noise ratio, and they have received more attention in recent years. Excellent activatable AIE probes have been reported for detecting toxic substances, imaging intracellular active molecules/biomolecules, as well as monitoring the activity of overexpressed enzymes in cancers. Moreover, the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation, while they have no distinct effect on normal cells, demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy. Thus, in this review, we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications. The challenges of activatable AIE probes and the corresponding solutions are described. We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.

Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin’s B-cell lymphoma with poor prognosis. Despite recent advances, resistance to therapy and relapse remain significant clinical problems. G-protein-coupled estrogen receptor (GPER)-mediated estrogenic rapid signaling is implicated in the development of many cancers. However, its role in MCL is unknown. Here we report that GPER activation with selective agonist G-1 induced cell cycle arrest, DNA damage, mitochondria membrane potential abnormality, and eventually apoptosis of MCL cell lines. We found that G-1 induced DNA damage and apoptosis of MCL cells by promoting the expression of nicotinamide adenine dinucleotide phosphate oxidase and the generation of reactive oxygen species. In addition, G-1 inhibited MCL cell proliferation by inactivation of NF-κB signaling and exhibited anti-tumor functions in MCL xenografted mice. Most significantly, G-1 showed synergistic effect with ibrutinib making it a potential candidate for chemotherapy-free therapies against MCL.

The MDM2 binding protein (MTBP) has been considered an important regulator of human malignancies. In this study, we demonstrate that the high level of MTBP’s endogenous expression is correlated with poor prognosis of advanced hepatocellular carcinoma (HCC) patients who received sorafenib. MTBP interacted with the Pregnane X receptor (PXR) and enhanced the transcription factor activity of PXR. Moreover, MTBP enhanced the accumulation of PXR in HCC cells’ nuclear and the recruitment of PXR to its downstream gene’s (cyp3a4’s) promoter region. Mechanically, the knockdown of MTBP in MHCC97-H cells with high levels of MTBP decelerated the clearance or metabolism of sorafenib in HCC cells and led to the resistance of HCC cells to sorafenib. Whereas overexpression of MTBP in in MHCC97-L cells with low levels of MTBP showed the opposite trend. By establishing the interaction between MTBP and PXR, our results indicate that MTBP could function as a co-activator of PXR and could be a promising therapeutic target to enhance the sensitivity of HCC cells to molecular targeting agents.

The primary objective of science postgraduate education is to foster students' capacity for creative thinking and problem-solving, particularly in the context of scientific research quality. In order to achieve this goal, the "7E" teaching mood has been implemented in the cell biology course for postgraduate students to promote student-centered active inquiry learning instead of breaking away from traditional indoctrination-based teaching methods. This study demonstrates that the implementation of the "7E" teaching mode, through content programming, process design, and effect evaluation, effectively meets the needs of the majority of students, fosters their interest in learning, enhances their performance in comprehensive questioning, and enhances their innovative abilities in scientific research. Consequently, this research offers a theoretical framework and practical foundation for the development of the "7E" teaching mode in postgraduate courses, aiming to cultivate highly skilled scientific professionals.

Abstract Background Toll-like receptor 4 (TLR4) is well known for activating the innate immune system; however, it is also highly expressed in adaptive immune cells, such as CD4+ T-helper 17 (Th17) cells, which play a key role in multiple sclerosis (MS) pathology. However, the function and governing mechanism of TLR4 in Th17 remain unclear. Methods The changes of TLR4 in CD4+ T cells from MS patients and experimental autoimmune encephalomyelitis (EAE) mice were tested. TLR4-deficient (TLR4−/−) naïve T cells were induced in vitro and transferred into Rag1−/− mice to measure Th17 differentiation and EAE pathology. DNA sequence analyses combining with deletion fragments and mutation analyses, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA) were used to explore the mechanism of TLR4 signaling pathway in regulating Th17 differentiation. Results The levels of TLR4 were increased in CD4+ Th17 cells both from MS patients and EAE mice, as well as during Th17 differentiation in vitro. TLR4−/− CD4+ naïve T cells inhibited their differentiation into Th17, and transfer of TLR4−/− CD4+ naïve T cells into Rag1−/− mice was defective in promoting EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. TLR4 signal enhanced Th17 differentiation by activating RelA, downregulating the expression of miR-30a, a negative regulator of Th17 differentiation. Inhibition of RelA activity increased miR-30a level, but decreased Th17 differentiation rate. Furthermore, RelA directly regulated the expression of miR-30a via specific binding to a conserved element of miR-30a gene. Conclusions TLR4−/− CD4+ naïve T cells are inadequate in differentiating to Th17 cells both in vitro and in vivo. TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation via direct binding of RelA to the regulatory element of miR-30a gene. Our results indicate modulating TLR4-RelA-miR-30a signal in Th17 may be a therapeutic target for Th17-mediated neurodegeneration in neuroinflammatory diseases.

Condensation on greenhouse interior surfaces plays an important role in reducing indoor air humidity. There is no standard method to measure condensation rate in greenhouses or in any other buildings. In this study, a commercially available leaf wetness sensor was calibrated in an environment chamber under different room temperature and RH conditions, which included five temperatures of 18, 20, 22, 24, and 26 °C, and five RH levels of 40, 55, 65, 75, and 85%. The sensor surface temperature was maintained the same as the room temperature. Room temperature water was sprayed on the sensor surface, simulating condensate. The voltage output of the sensor changed due to varying amounts of condensate on the sensor surface. The amount of condensate on the sensor surface was divided into five groups from 0 to 0.5 g (or 0–0.015 g per square centimeter of sensor surface area) with an interval of 0.1 g. The statistical analysis showed that both sensor temperature and indoor RH had no significant effect on the sensor voltage output. The voltage output was solely determined by the amount of condensate mass on the sensor surface. A linear regression model was developed between the voltage output and the amount of condensate. This tool is considered as a breakthrough of technology for condensation rate measurement on greenhouse interiors surface, or on any other surfaces with condensation. Anyone can use this sensor and the development relationship for measuring condensation rate as the sensor is not pricy and the method is easy to use, thus the method should be widely used as a standard method. Keywords: Condensation sensor, Leaf wetness sensor, Greenhouse

Elevated atmospheric CO2 (eCO2) results in plant growth and N limitation, yet how root-associated nitrogen-fixing bacterial communities respond to increasing atmospheric CO2 and nitrogen fertilization (eN) during the growth stages of rice is unclear. Using the nifH gene as a molecular marker, we studied the combined effect of eCO2 and eN on the diazotrophic community and abundance at two growth stages in rice (tillering, TI and heading, HI). Quantitative polymerase chain reaction (qPCR) showed that eN had no obvious effect on nifH abundance in rice roots under either ambient CO2 (aCO2) or eCO2 treatment at the TI stage; in contrast, at the HI, nifH copy numbers were increased under eCO2 and decreased under aCO2. For rhizosphere soils, eN significantly reduced the abundance of nifH under both aCO2 and eCO2 treatment at the HI stage. Elevated CO2 significantly increased the nifH abundance in rice roots and rhizosphere soils with nitrogen fertilization, but had no obvious effect without N addition at the HI stage. There was a significant interaction [CO2 × N fertilization] effect on nifH abundance in root zone at the HI stage. In addition, the nifH copy numbers in rice roots were significantly higher at the HI stage than at the TI stage. Sequencing analysis indicated that the root-associated diazotrophic community structure tended to cluster according to the nitrogen fertilization treatment and that Rhizobiales were the dominant diazotrophs in all root samples at the HI stage. Additionally, nitrogen fertilization significantly increased the relative abundance of Methylosinus (Methylocystaceae) under eCO2 treatment, but significantly decreased the relative abundance of Rhizobium (Rhizobiaceae) under aCO2 treatment. Overall, the combined effect of eN and eCO2 stimulates root-associated diazotrophic methane-oxidizing bacteria while inhibits heterotrophic diazotrophs.

Rare inherited variations in multiplex families with Gilles de la Tourette syndrome (GTS) are suggested to play an important role in the genetic etiology of GTS. In order to explore the rare inherited variations with the risk of GTS, whole-exome sequencing (WES) was performed in a family with three affected patients with GTS. Among the five novel rare variations identified by WES, CLCN2 G161S was presented in three patients, but not in four unaffected individuals, and thus co-segregated with GTS. A validation study was also performed in a cohort of Chinses Han population to further examine the identified rare variants. CLCN2 G161S was genotyped in 207 sporadic patients with tic disorder including 111 patients with GTS and 489 healthy controls. Compared with that in controls [allele frequency (AF) = 0], CLCN2 G161S had higher variant AF in patients with tic (AF = 0.00483) and in patients with GTS (0.00900), respectively. However, this variant was absent from the current 1000 Genome databases, and the variant AF is very low in the current public databases including ExAC (AF = 0.00001) and gnomAD (AF = 0.00003). Our results suggest that CLCN2 G161S might play a major role in the genetic etiology of GTS, at least in a Chinese Han population.

In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-β, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.

Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides with important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferase. To address this question, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1-/-). The major phenotype of Plt Slc35a1-/- mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1-/- mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Kupffer cells in the liver of Plt Slc35a1-/- mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenic purpura and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.

Objectives: Previous genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression. Methods: A total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from 72 patients during surgery. The gene expression level of IL33 and GLDC was evaluated by qPCR. Patients were classified into two groups according to the 5-year overall survival (death/survival). The chi-square test was used to analyze difference of genotype frequency. The Student t-test was used to compare the gene expression level between different genotypes. Cumulative survival time was calculated by the Kaplan–Meier method and analyzed by the log-rank test. Results: Genotype TT of rs55933544 was significantly associated with the event of death (0.176 vs. 0.061, p

MicroRNAs are powerful regulators of gene expression in physiological and pathological conditions. We previously showed that the dysregulation of miR-384 resulted in a T helper cell 17 (Th17) imbalance and contributed to the pathogenesis of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. In this study, we evaluated the molecular mechanisms underlying the abnormal increase in miR-384. We did not detect typical CpG islands in the Mir384 promoter. Based on a bioinformatics analysis of the promoter, we identified three conserved transcription factor binding regions (RI, RII, and RIII), two of which (RII and RIII) were cis-regulatory elements. Furthermore, we showed that signal transducer and activator of transcription 3 (STAT3) bound to specific sites in RII and RIII based on chromatin immunoprecipitation, electrophoretic mobility shift assays, and site-specific mutagenesis. During Th17 polarization in vitro, STAT3 activation up-regulated miR-384, while a STAT3 phosphorylation inhibitor decreased miR-384 levels and reduced the percentage of IL-17+ cells, IL-17 secretion, and expression of the Th17 lineage marker Rorγt. Moreover, the simultaneous inhibition of STAT3 and miR-384 could further block Th17 polarization. These results indicate that STAT3, rather than DNA methylation, contributes to the regulation of miR-384 during Th17 polarization.

Early prediction of job failures and specific disposal steps in advance could significantly improve the efficiency of resource utilization in large-scale data center. The existing machine learning-based prediction methods commonly adopt offline working pattern, which cannot be used for online prediction in practical operations, in which data arrive sequentially. To solve this problem, a new method based on online sequential extreme learning machine (OS-ELM) is proposed in this paper to predict online job termination status. With this method, real-time data are collected according to the sequence of job arriving, the job status could be predicted and the operation model is thus updated based on these data. The method with online incremental learning strategy has fast learning speed and good generalization. Comparative study using Google trace data shows that prediction accuracy of the proposed method is 93% with updating model in 0.01 s. Compared with some state-of-the-art methods, such, as support vector machine (SVM), ELM, and OS-SVM, the method developed in this paper has many advantages, such as less time-consuming in establishing and updating the model, higher prediction accuracy and precision, and better false negative performance.

Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has been shown to have anti-inflammatory and immunomodulatory properties without significant immunosuppression. We therefore hypothesized that DMF could be potentially harnessed for the treatment of aGVHD with retention of graft-versus-tumor effect. In this study, we showed that DMF significantly inhibited alloreactive T cell responses in vitro in mixed lymphocyte reaction assay. Administration of DMF significantly alleviated the severity, histological damage, and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF administration reduced the activation and effector function of donor T cells in vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes heme oxygenase-1 and glutathione S-transferase-α1 expressions. Furthermore, DMF treatment markedly increased the frequencies of Treg cells. Depletion of CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG control recipients. DMF could promote Treg cell differentiation in a dose dependent manner by upregulating TGF-β expression in vitro. Most importantly, DMF administration preserved graft-versus-leukemia effect after bone marrow transplantation. In conclusion, our findings demonstrated DMF as a promising agent for the prevention of aGVHD after allo-HSCT.

Diabetic cardiomyopathy (DCM) is one of the most severe complications of diabetes without a clear pathogenesis. Th is study investigated the adiponectin (APN) and leptin levels in type II DCM, as well as their correlation with advanced glycation end-products (AGEs). From 2011–2013, 78 type II diabetes mellitus (T2DM) cases (40–65 years old) in the Taian region were randomly selected. Based on the results of colour Doppler ultrasonography and coronary angiography, the cases were divided into a simple T2DM group (40 cases) and a DCM group (38 cases). Forty healthy subjects were used as normal control (NC). An enzyme-linked immunosorbent assay was performed to determine the levels of fa tty infl ammatory factors such as APN, leptin and AGEs, and a correlation analysis was conducted. In the T2DM group, the APN levels were decreased but the leptin and AGE levels were signifi cantly increased compared to the NC group. In the DCM group, the APN levels were decreased but the leptin and AGE levels were signifi cantly increased (P