10× single-cell sequencing revealed cellular composition heterogeneity in cardiac myxoma with malignant glandular properties.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

Deploying a Dipole Electric Field at the CsPbI3 Perovskite/Carbon Interface for Enhancing Hole Extraction and Photovoltaic Performance.

Carbon-based CsPbI3 perovskite solar cells without hole transporter (C-PSCs) have achieved intense attention due to its simple device structure and high chemical stability. However, the severe interface energy loss at the CsPbI3/carbon interface, attributed to the lower hole selectivity for inefficient charge separation, greatly limits device performance. Hence, dipole electric field (DEF) is deployed at the above interface to address the above issue by using a pole molecule, 4-trifluoromethyl-Phenylammonium iodide (CF3-PAI), in which the ─NH3 group anchors on the perovskite surface and the ─CF3 group extends away from it and connects with carbon electrode. The DEF is proven to align with the built-in electric field, that is pointing toward carbon electrode, which well enhances hole selectivity and charge separation at the interface. Besides, CF3-PAI molecules also serve as defect passivator for reducing trap state density, which further suppresses defect-induced non-radiative recombination. Consequently, the CsPbI3 C-PSCs achieve an excellent efficiency of 18.33% with a high VOC of 1.144 V for inorganic C-PSCs without hole transporter.

Spatially selective defect management of CsPbI3 films for high-performance carbon-based inorganic perovskite solar cells.

Defects formed at the surface, buried interface and grain boundaries (GB) of CsPbI3 perovskite films considerably limit photovoltaic performance. Such defects could be passivated effectively by the most prevalent post modification strategy without compromising the photoelectric properties of perovskite films, but it is still a great challenge to make this strategy comprehensive to different defects spatially distributed throughout the films. Herein, a spatially selective defect management (SSDM) strategy is developed to roundly passivate various defects at different locations within the perovskite film by a facile one-step treatment procedure using a piperazine-1,4-diium tetrafluoroborate (PZD(BF4)2) solution. The small-size PZD2+ cations could penetrate into the film interior and even make it all the way to the buried interface of CsPbI3 perovskite films, while the BF4- anions, with largely different properties from I- anions, mainly anchor on the film surface. Consequently, virtually all the defects at the surface, buried interface and grain boundaries of CsPbI3 perovskite films are effectively healed, leading to significantly improved film quality, enhanced phase stability, optimized energy level alignment and promoted carrier transport. With these films, the fabricated CsPbI3 PSCs based on carbon electrode (C-PSCs) achieve an efficiency of 18.27%, which is among the highest-reported values for inorganic C-PSCs, and stability of 500 h at 85 °C with 65% efficiency maintenance.

Long-Chain Gemini Surfactant-Assisted Blade Coating Enables Large-Area Carbon-Based Perovskite Solar Modules with Record Performance.

Carbon-based perovskite solar cells show great potential owing to their low-cost production and superior stability in ambient air. However, scaling up to high-efficiency carbon-based solar modules hinges on reliable deposition of uniform defect-free perovskite films over large areas, which is an unsettled but urgent issue. In this work, a long-chain gemini surfactant is introduced into perovskite precursor ink to enforce self-assembly into a network structure, considerably enhancing the coverage and smoothness of the perovskite films. The long gemini surfactant plays a distinctively synergistic role in perovskite film construction, crystallization kinetics modulation and defect passivation, leading to a certified record power conversion efficiency of 15.46% with Voc of 1.13 V and Jsc of 22.92 mA cm-2 for this type of modules. Importantly, all of the functional layers of the module are printed through a simple and high-speed (300 cm min-1) blade coating strategy in ambient atmosphere. These results mark a significant step toward the commercialization of all-printable carbon-based perovskite solar modules.

A new method for predicting the microvascular invasion status of hepatocellular carcinoma through neural network analysis.

AIMS: To determine the relationship between microvascular invasion (MVI) and the clinical features of hepatocellular carcinoma (HCC) and provide a method to evaluate MVI status by neutral network analysis. METHODS: The patients were divided into two groups (MVI-positive group and MVI-negative group). Univariate analysis and multivariate logistic regression analysis were carried out to identify the independent risk factors for MVI positivity. Neural network analysis was used to analyze the different importance of the risk factors in MVI prediction. RESULTS: We enrolled 1697 patients in this study. We found that the independent prognostic factors were age, NEU, multiple tumors, AFP level and tumor diameter. By neural network analysis, we proposed that the level of AFP was the most important risk factor for HCC in predicting MVI status (the AUC was 0.704). However, age was the most important risk factor for early-stage HCC with a single tumor (the AUC was 0.605). CONCLUSION: Through the neutral network analysis, we could conclude that the level of AFP is the most important risk factor for MVI-positive patients and the age is the most important risk factor for early-stage HCC with a single tumor.

Cysteine and glycine rich protein 2 exacerbates vascular fibrosis in pulmonary hypertension through the nuclear translocation of yes-associated protein and transcriptional coactivator with PDZ-binding motif.

Pulmonary hypertension (PH) is a serious cardiovascular disease with a poor prognosis and high mortality. The pathogenesis of PH is complex, and the main pathological changes in PH are abnormal hypertrophy and vessel stiffness. Cysteine and glycine rich protein 2 (Csrp2), a member of the LIM-only family plays a key role in the response to vascular injury. However, its roles in vascular fibrosis and PH have not been clarified. Therefore, this study aimed to investigate whether Csrp2 can promote vascular fibrosis and to further explore the possible mechanisms. Csrp2 expression was increased in both the pulmonary vasculature of rats with PH and hypoxic pulmonary vascular smooth muscle cells (PASMCs). Hypoxia activated TGF-ß1 and its downstream effector, SP1. Additionally, hypoxia activated the ROCK pathway and inhibited KLF4 expression. Silencing SP1 and overexpressing KLF4 reversed the hypoxia-induced increase in Csrp2 expression. Csrp2 knockdown decreased the expression of extracellular matrix (ECM) proteins and inhibited the nuclear translocation and expression of YAP/TAZ in hypoxic PASMCs. These results indicate that hypoxia induces Csrp2 expression through the TGF-ß1/SP1 and ROCK/KLF4 pathways. Elevated Csrp2 promoted the nuclear translocation and expression of YAP/TAZ, leading to vascular fibrosis and the development of PH.

Supplementation with Tex261 provides a possible preventive treatment for hypoxic pulmonary artery hypertension.

Objectives: Pulmonary artery hypertension (PAH) is a serious disease for which there is no effective treatment. Its pathogenesis is complex and has not yet been clarified. Tex261 is a protein-coding gene whose functional enrichment nodes include the transporter activity of COP II. However, the role of Tex261 in PAH remains unknown. Methods: Sugen5416/Hypoxic PAH models were established, and pulmonary arteries (PAs) were isolated for proteomic sequencing. The binding sites between Hif-1α and Tex261 were verified by dual-luciferase reporter gene assay. Cell proliferation was detected by MTS and EdU assays. For determination of the preventive and therapeutic effects of Tex261, intratracheal instillation of adeno-associated virus (AVV6) with Tex261 vectors was performed. Results: Tex261 was screened according to the proteomic sequencing data. Hif-1α inhibited Tex261 promoter activity under hypoxia. Decreased Tex261 expression promoted PASMC proliferation. Tex261 regulated Sec23 via the Ndrg1-mediated Akt pathway. Tex261 overexpression improved the pressure and vessel remodeling of PAs induced by Sugen5416/hypoxia. Conclusion: Hypoxia suppressed Tex261 expression through Hif-1α activation. The decreased Tex261 could promote Ndrg1 and depress Akt activity and then inhibit Sec23 activity, which leads to cell proliferation and vessel remodeling. Elevated Tex261 has some preventive and therapeutic effects on rats with PAH.

Cysteine and glycine-rich protein 2 promotes hypoxic pulmonary vascular smooth muscle cell proliferation through the Wnt3α-ß-catenin/lymphoid enhancer-binding factor 1 pathway.

Pulmonary hypertension (PH) is mainly characterized by abnormal pulmonary vascular hyperplasia and vascular remodeling, but its mechanism is complicated and currently unclear. Cysteine and glycine-rich protein 2 (Csrp2) has been reported to promote cell proliferation and migration, and affect cell cycle progression. As a new invasive actin-binding factor, Csrp2 increased the invasion and even metastasis of some cancer cells. It was associated with tumor recurrence and chemotherapy resistance. However, the role of Csrp2 in PH remains unknown. We found that Csrp2 expression was increased both in pulmonary arteries (PAs) and smooth muscle cells (PASMCs) in PH. Csrp2 enhanced PASMC proliferation and phenotypic transition. The Wnt3α-ß-catenin/lymphoid enhancer-binding factor 1 (LEF1) pathway is involved in cell proliferation and phenotypic transition regulated by Csrp2 expression. These results suggest that hypoxia downregulates YinYang-1 (YY1) and then increases Csrp2 expression. Increased Csrp2 promotes PASMC proliferation and phenotypic transition by activating the Wnt3α-ß-catenin/LEF1 pathways, which leads to pulmonary vascular remodeling and even provides a new theoretical basis for studying the pathogenesis and therapeutic targets of PH.

Metatranscriptomic Analysis Reveals Disordered Alterations in Oropharyngeal Microbiome during the Infection and Clearance Processes of SARS-CoV-2: A Warning for Secondary Infections.

This study was conducted to investigate oropharyngeal microbiota alterations during the progression of coronavirus disease 2019 (COVID-19) by analyzing these alterations during the infection and clearance processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnosis of COVID-19 was confirmed by using positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR). The alterations in abundance, diversity, and potential function of the oropharyngeal microbiome were identified using metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 47 patients with COVID-19 (within a week after diagnosis and within two months after recovery from COVID-19) and 40 healthy individuals. As a result, in the infection process of SARS-CoV-2, compared to the healthy individuals, the relative abundances of Prevotella, Aspergillus, and Epstein-Barr virus were elevated; the alpha diversity was decreased; the beta diversity was disordered; the relative abundance of Gram-negative bacteria was increased; and the relative abundance of Gram-positive bacteria was decreased. After the clearance of SARS-CoV-2, compared to the healthy individuals and patients with COVID-19, the above disordered alterations persisted in the patients who had recovered from COVID-19 and did not return to the normal level observed in the healthy individuals. Additionally, the expressions of several antibiotic resistance genes (especially multi-drug resistance, glycopeptide, and tetracycline) in the patients with COVID-19 were higher than those in the healthy individuals. After SARS-CoV-2 was cleared, the expressions of these genes in the patients who had recovered from COVID-19 were lower than those in the patients with COVID-19, and they were different from those in the healthy individuals. In conclusion, our findings provide evidence that potential secondary infections with oropharyngeal bacteria, fungi, and viruses in patients who have recovered from COVID-19 should not be ignored; this evidence also highlights the clinical significance of the oropharyngeal microbiome in the early prevention of potential secondary infections of COVID-19 and suggests that it is imperative to choose appropriate antibiotics for subsequent bacterial secondary infection in patients with COVID-19.

Impact of Perioperative Massive Transfusion on Long Term Outcomes of Liver Transplantation: a Retrospective Cohort Study.

Background: Liver transplantation (LT) is associated with a significant risk of intraoperative hemorrhage and massive blood transfusion. However, there are few relevant reports addressing the long-term impacts of massive transfusion (MT) on liver transplantation recipients. Aim: To assess the effects of MT on the short and long-term outcomes of adult liver transplantation recipients. Methods: We included adult patients who underwent liver transplantation at West China Hospital from January 2011 to February 2015. MT was defined as red blood cell (RBC) transfusion of ≥10 units within 48 hours since the application of LT. Preoperative, intraoperative and postoperative information were collected for data analyzing. We used one-to-one propensity-matching to create pairs. Kaplan-Meier survival analysis was used to compare long-term outcomes of LT recipients between the MT and non-MT groups. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors associated with MT in LT. Results: Finally, a total of 227 patients were included in our study. After propensity score matching, 59 patients were categorized into the MT and 59 patients in non-MT groups. Compared with the non-MT group, the MT group had a higher 30-day mortality (15.3% vs 0, p=0.006), and a higher incidence of postoperative complications, including postoperative pulmonary infection, abdominal hemorrhage, pleural effusion and severe acute kidney injury. Furthermore, MT group had prolonged postoperative ventilation support (42 vs 25 h, p=0.007) and prolonged durations of ICU (12.9 vs 9.5 d, p<0.001) stay. Multivariate COX regression indicated that massive transfusion (OR: 2.393, 95% CI: 1.164-4.923, p=0.018) and acute rejection (OR: 7.295, 95% CI: 2.108-25.246, p=0.02) were significant risk factors affecting long-term survivals of LT patients. The 1-year and 3-year survival rates patients in MT group were 82.5% and 67.3%, respectively, while those of non-MT group were 93.9% and 90.5%, respectively. The MT group exhibited a lower long-term survival rate than the non-MT group (HR: 2.393, 95% CI: 1.164-4.923, p<0.001). Finally, the multivariate logistic regression revealed that preoperative hemoglobin <118 g/L (OR: 5.062, 95% CI: 2.292-11.181, p<0.001) and intraoperative blood loss ≥1100 ml (OR: 3.212, 95% CI: 1.586-6.506, p = 0.001) were the independent risk factor of MT in patients undergoing LT. Conclusion: Patients receiving MT in perioperative periods of LT had worse short-term and long-term outcomes than the non-MT patients. Massive transfusion and acute rejection were significant risk factors affecting long-term survivals of LT patients, and intraoperative blood loss of over 1100 ml was the independent risk factor of MT in patients undergoing LT. The results may offer valuable information on perioperative management in LT recipients who experience high risk of MT.

Copper nanoparticles induce the formation of fatty liver in Takifugu fasciatus triggered by the PERK-EIF2α- SREBP-1c pathway.

Copper nanoparticles (CuNPs), a new pollutant in water environments, were widely used in various industrial and commercial applications. This study indicated that the presence of CuNPs exposure under environmental related concentration is an inducing factor that contributes to the fatty liver formation in Takifugu fasciatus. Furthermore, we explored the fatty liver formation mechanism. The results shown, (1) the cloned genes related to endoplasmic reticulum stress (ERS) (GRP78, IRE-1α, PERK, and ATF-6α) were highly expressed in the liver of T. fasciatus. (2) after 30-days exposure, CuNPs accumulated in the endoplasmic reticulum of liver and induced the appearance of ERS, then activated unfolded protein response (UPR) signaling pathway. Furthermore, the SREBP-1c pathway that plays a key role in lipid synthesis was activated. (3) by using 4-PBA and GSK inhibitors to respectively stimulate ERS and PKR-like ER kinase (PERK) through in vitro experiments, we confirmed that CuNPs induced the fatty liver formation in T. fasciatus triggered by the PERK-EIF2α pathway by activating the SREBP-1c pathway to promote fatty liver formation. This study provides a new perspective for identifying the pathogens of fatty liver formation, and adds to the knowledge of the ecological safety data service of CuNPs in water.

Co-immobilized recombinant glycosyltransferases efficiently convert rebaudioside A to M in cascade.

Rebaudioside M (Reb M), as a natural and healthy Stevia sweetener, is produced by two glycosyltransferases that catalyze the serial glycosylation of Rebaudioside A (Reb A) and Rebaudioside D (Reb D) in cascade. Meanwhile, it is of great importance in developing an immobilization strategy to improve the reusability of glycosyltransferases in reducing the production cost of Reb M. Here, the recombinant glycosyltransferases, i.e., OsEUGT11 (UGT1) and SrUGT76G1 (UGT2), were expressed in Escherichia coli and covalently immobilized onto chitosan beads. UGT1 and UGT2 were individually immobilized and co-immobilized onto the beads that catalyze Reb A to Reb M in one-pot. The co-immobilized enzymes system exhibited ∼3.2-fold higher activity than that of the mixed immobilized enzymes system. A fairly high Reb A conversion rate (97.3%) and a high Reb M yield of 72.2% (4.82 ± 0.11 g L-1) were obtained with a feeding Reb A concentration of 5 g L-1. Eventually, after 4 and 8 reused cycles, the co-immobilized enzymes retained 72.5% and 53.1% of their original activity, respectively, showing a high stability to minimize the total cost of enzymes and suggesting that the co-immobilized UGTs is of potentially signficant value for the production of Reb M.

Sevoflurane- and propofol-based regimens show comparable effect on oxygenation in patients undergoing cardiac valve replacement with cardiopulmonary bypass.

BACKGROUND: Our study aimed to compare the effects of Sevoflurane- and propofol-based anaesthetic regimens on oxygenation during the early period of cardiopulmonary bypass (CPB) in patients undergoing cardiac valve-replacement surgery. METHODS: Patients undergoing mechanical mitral, aortic or double valve replacement were enrolled and randomly divided into two groups: the sevoflurane-based anaesthetic regimen group consisted of patients who received 1-3% sevoflurane inhalation during anaesthesia maintenance and the propofol-based anaesthetic regimen group consisted of patients who received 6-10 mg/kg/h of propofol infusion during anaesthesia maintenance. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), respiratory mechanics and haemodynamics were recorded during CPB. RESULTS: Forty-two patients met the eligibility criteria for the study. The groups did not differ in terms of clinical and demographic characteristics, and pre- and intra-operative features. Changes in oxygenation were mild (mean PaO2/FiO2 from 358 ± 82 to 471 ± 106 mmHg) within one hour of CPB in our patients. There were no differences in PaO2/FiO2, respiratory mechanics and haemodynamics between the sevoflurane and propofol groups. CONCLUSIONS: In patients undergoing cardiac valve replacement with CPB, lung injury was mild, and sevoflurane- and propofol-based anaesthetic regimens showed similar effect on oxygenation, respiratory mechanics and haemodynamics during the early stage of CPB.

Integrated application of multi-omics provides insights into cold stress responses in pufferfish Takifugu fasciatus.

BACKGROUND: T. fasciatus (Takifugu fasciatus) faces the same problem as most warm water fish: the water temperature falls far below the optimal growth temperature in winter, causing a massive death of T. fasciatus and large economic losses. Understanding of the cold-tolerance mechanisms of this species is still limited. Integrated application of multi-omics research can provide a wealth of information to help us improve our understanding of low-temperature tolerance in fish. RESULTS: To gain a comprehensive and unbiased molecular understanding of cold-tolerance in T. fasciatus, we characterized mRNA-seq and metabolomics of T. fasciatus livers using Illumina HiSeq 2500 and UHPLC-Q-TOF MS. We identified 2544 up-regulated and 2622 down-regulated genes in the liver of T. fasciatus. A total of 40 differential metabolites were identified, including 9 down-regulated and 31 up-regulated metabolites. In combination with previous studies on proteomics, we have established an mRNA-protein-metabolite interaction network. There are 17 DEMs (differentially-expressed metabolites) and 14 DEGs-DEPs (differentially co-expressed genes and proteins) in the interaction network that are mainly involved in fatty acids metabolism, membrane transport, signal transduction, and DNA damage and defense. We then validated a number of genes in the interaction network by qRT-PCR. Additionally, a number of SNPs (single nucleotide polymorphisms) were revealed through the transcriptome data. These results provide key information for further understanding of the molecular mechanisms of T. fasciatus under cold stress. CONCLUSION: The data generated by integrated application of multi-omics can facilitate our understanding of the molecular mechanisms of fish response to low temperature stress. We have not only identified potential genes and SNPs involved in cold tolerance, but also show that some nutrient metabolites may be added to the diet to help the overwintering of T. fasciatus.

Studies of the mechanism of fatty liver formation in Takifugu fasciatus following copper exposure.

Fatty liver is widely observed during Takifugu fasciatus production, but the mechanisms underlying fatty liver formation remain unknown. The present study was conducted to determine the potential effects of copper (Cu) on hepatic lipid deposition and metabolism in T. fasciatus after 21 days of exposure to Cu (levels: 0, 20 and 100 µg/L). Copper exposure decreased the weight gain rate (WG) in T. fasciatus, but increased the values of the viscerosomatic index (VSI) and hepatosomatic index (HSI) compared with the control. The time-dependent Cu accumulation in tissues increased as the Cu concentration increased. The order of Cu accumulation was liver > intestine > muscle. The lipid content, triglyceride (TG) content and lipoprotein lipase (LPL) activity increased after Cu exposure compared with the control. In addition, more lipid droplets and greater vacuolization were observed in the liver after exposure to 20 µg/L Cu than after 100 µg/L Cu. The expression of genes involved in lipogenesis (g6pd, 6pgd, lpl, fas and acc), lipolysis (hsl and cpt 1) and transcription (ppar α and ppar ©) was dependent on Cu. An analysis of the intestinal microbiome community showed that the highest values of the Chao 1 index, ACE, Shannon index and Simpson index were obtained in fish exposed to 20 µg/L Cu, whereas the lowest values were obtained after the 100 µg/L Cu treatment. The Principal Coordinates Analysis (PCoA) plots of the data revealed structural differences in the groups treated with Cu compared with the control group. At the phylum level, the intestinal microbiota in the Cu-treated and control fish were dominated by Proteobacteria and Bacteroidetes. The higher Firmicutes to Bacteroidetes ratio was observed in fish treated with 20 µg/L Cu compared with other groups, while the lowest ratio was observed in fish exposed to 100 µg/L Cu. Our study revealed the mechanisms by which Cu exposure altered (i) lipid deposition in the body and (ii) the intestinal microbiome, which may contribute to maintain the health status of T. fasciatus for the aquaculture.