Model-Based Design of Variable Stiffness Soft Gripper Actuated by Smart Hydrogels.

Soft grippers have shown their ability to grasp fragile and irregularly shaped objects, but they often require external mechanisms for actuation, limiting their use in large-scale situations. Their limited capacity to handle loads and deformations also restricts their customized grasping capabilities. To address these issues, a model-based soft gripper with adaptable stiffness was proposed. The proposed actuator comprises a silicone chamber with separate units containing hydrogel spheres. These spheres exhibit temperature-triggered swelling and shrinking behaviors. In addition, variable stiffness strips embedded in the units are introduced as the stiffness variation method. The validated finite element method model was used as the model-based design approach to describe the hydrogel behaviors and explore the affected factors on the bending performance. The results demonstrate that the actuator can be programmed to respond in a desired way, and the stiffness variation method enhances bending stiffness significantly. Specifically, a direct correlation exists between the bending angle and hydrogel sphere layers, with a maximum of 128° achieved. In addition, incorporating gap configurations into the chamber membrane results in a maximum threefold increase in the bending angle. Besides, the membrane type minimally impacts the bending angle from 21.3° to 24.6°. In addition, the embedded variable stiffness strips substantially increase stiffness, resulting in a 30-fold rise in bending stiffness. In conclusion, the novel soft gripper actuator enables substantial bending and stiffness control through active actuation, showcasing the potential for enhancing soft gripper performance in complex and multiscale grasping scenarios.

Imbalance of gut microbiota in gestational diabetes.

AIM: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS: A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS: (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS: Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION: The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).

Analysis of m6A-related lncRNAs for prognostic and immunotherapeutic response in hepatocellular carcinoma.

Background: RNA methylation modifications are important post-translational modifications that are regulated in an epigenetic manner. Recently, N6-methyladenosine (m6A) RNA modifications have emerged as potential epigenetic markers in tumor biology. Methods: Gene expression and clinicopathological data of LIHC were obtained from the cancer genome atlas (TCGA) database. The relationship between long non-coding RNAs (lncRNAs) and m6A-related genes was determined by gene expression analysis using Perl and R software. Co-expression network of m6A-lncRNA was constructed, and the relevant lncRNAs associated with prognosis were identified using univariate Cox regression analysis. These lncRNAs were then divided into two clusters (cluster 1 and cluster 2) to determine the differences in survival, pathoclinical parameters, and immune cell infiltration between the different lncRNA subtypes. The least absolute shrinkage and selection operator (LASSO) was carried out for regression analysis and prognostic model. The HCC patients were randomly divided into a train group and a test group. According to the median risk score of the model, HCC patients were divided into high-risk and low-risk groups. We built models using the train group and confirmed them through the test group. The m6A-lncRNAs derived from the models were analyzed for the tumor mutational burden (TMB), immune evasion and immune function using R software. AL355574.1 was identified as an important m6A-associated lncRNA and selected for further investigation. Finally, in vitro experiments were conducted to confirm the effect of AL355574.1 on the biological function of HCC and the possible biological mechanisms. Huh7 and HepG2 cells were transfected with AL355574.1 siRNA and cell proliferation ability was measured by CCK-8, EdU and colony formation assays. Wound healing and transwell assays were used to determine the cell migration capacity. The expression levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt/mTOR phosphorylation were all determined by Western blotting. Results: The lncRNAs with significant prognostic value were classified into two subtypes by a consistent clustering analysis. We found that the clinical features, immune cell infiltration and tumor microenvironment (TME) were significantly different between the lncRNA subtypes. Our analysis revealed significant correlations between these different lncRNA subtypes and immune infiltrating and stromal cells. We created the final risk profile using LASSO regression, which notably included three lncRNAs (AL355574.1, AL158166.1, TMCC1-AS1). A prognostic signature consisting of the three lncRNAs was constructed, and the model showed excellent prognostic predictive ability. The overall survival (OS) of the low-risk cohort was significantly higher than that of the high-risk cohort in both the train and test group. Both risk score [hazard ratio (HR)=1.062; P<0.001] and stage (HR=1.647; P< 0.001) were considered independent indicators of HCC prognosis by univariate and multivariate Cox regression analysis. In Huh7 and HepG2 cells, AL355574.1 knockdown inhibited cell proliferation and migration, suppressed the protein expression levels of MMP-2, MMP-9, N-cadherin and Akt/mTOR phosphorylation, but promoted the protein expression levels of E-cadherin. Conclusions: This study established a predictive model for the OS of HCC patients, and these OS-related m6A-lncRNAs, especially AL355574.1 may play a potential role in the progression of HCC. In vitro experiments also showed that AL355574.1 could enhance the expression of MMPs and EMT through the Akt/mTOR signaling pathway, thereby affected the proliferation and migration of HCC. This provides a new perspective on the anticancer molecular mechanism of AL355574.1 in HCC.

Systematic analysis of the role of LDHs subtype in pan-cancer demonstrates the importance of LDHD in the prognosis of hepatocellular carcinoma patients.

BACKGROUND: Lactate dehydrogenase (LDHs) is an enzyme involved in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Given the regulatory role in the biological progression of certain tumors, we analyzed the role of LDHs in pan-cancers. METHODS: Cox regression, Kaplan-Meier curves, Receiver Operating Characteristic (ROC) curves, and correlation of clinical indicators in tumor patients were used to assess the prognostic significance of LDHs in pan-cancer. The TCGA, HPA, TIMER, UALCAN, TISIDB, and Cellminer databases were used to investigate the correlation between the expression of LDHs and immune subtypes, immune checkpoint genes, methylation levels, tumor mutational load, microsatellite instability, tumor-infiltrating immune cells and drug sensitivity. The cBioPortal database was also used to identify genomic abnormalities of LDHs in pan-cancer. A comprehensive assessment of the biological functions of LDHs was performed using GSEA. In vitro, HepG2 and Huh7 cells were transfected with LDHD siRNA and GFP-LDHD, the proliferation capacity of cells was examined using CCK-8, EdU, and colony formation assays; the migration and invasion of cells was detected by wound healing and transwell assays; western blotting was used to detect the levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt phosphorylation. RESULTS: LDHs were differentially expressed in a variety of human tumor tissues. LDHs subtypes can act as pro-oncogenes or anti-oncogenes in different types of cancer and have an impact on the prognosis of patients with tumors by influencing their clinicopathological characteristics. LDHs were differentially expressed in tumor immune subtypes and molecular subtypes. In addition, LDHs expression correlated with immune checkpoint genes, tumor mutational load, and microsatellite instability. LDHD was identified to play an important role in the prognosis of HCC patients, according to a comprehensive analysis of LDHs in pan-cancer. In HepG2 and Huh7 cells, knockdown of LDHD promoted cell proliferation, migration, and invasion, promoted the protein expression levels of MMP-2, MMP-9, N-cadherin, and Akt phosphorylation, but inhibited the protein expression level of E-cadherin. In addition, LDHD overexpression showed the opposite changes. CONCLUSION: LDHs subtypes can be used as potential prognostic markers for certain cancers. Prognostic and immunotherapeutic analysis indicated that LDHD plays an important role in the prognosis of HCC patients. In vitro experiments revealed that LDHD can affect HCC proliferation, migration, and invasion by regulating MMPs expression and EMT via Akt signaling pathway, which provides a new perspective on the anti-cancer molecular mechanism of LDHD in HCC.

Distributed Consensus Algorithms in Sensor Networks with Higher-Order Topology.

Information aggregation in distributed sensor networks has received significant attention from researchers in various disciplines. Distributed consensus algorithms are broadly developed to accelerate the convergence to consensus under different communication and/or energy limitations. Non-Bayesian social learning strategies are representative algorithms for distributed agents to learn progressively an underlying state of nature by information communications and evolutions. This work designs a new non-Bayesian social learning strategy named the hypergraph social learning by introducing the higher-order topology as the underlying communication network structure, with its convergence as well as the convergence rate theoretically analyzed. Extensive numerical examples are provided to demonstrate the effectiveness of the framework and reveal its superior performance when applying to sensor networks in tasks such as cooperative positioning. The designed framework can assist sensor network designers to develop more efficient communication topology, which can better resist environmental obstructions, and also has theoretical and applied values in broad areas such as distributed parameter estimation, dispersed information aggregation and social networks.

Knowledge domain and research trends for Gestational Diabetes Mellitus and nutrition from 2011 to 2021: a bibliometric analysis.

Objective: Nutrient management and lifestyle changes are the frontlines of treatment for all pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). This study aimed to identify the global research architecture, trends, and hotpots of GDM and nutrition. Methods: We obtained publications from the sub-databases of Science Citation Index Expanded and Social Science Citation Index sourced from the Web of Science Core Collection database on January 4, 2022, using publication years between 2011 and 2021. CiteSpace software, VOSviewer, and Microsoft Excel 2019 were used to conduct the bibliometric analyses. Results: A growing publication trend was observed for GDM and nutrition, and this field has great potential. More GDM and nutrition research has been conducted in developed countries than developing countries. The top three authors with a high publication frequency, co-citations, and a good h-index were from the United States. There were the four studies of randomized controlled trials (RCTs) or meta-analyses of RCTs, as well as one review in the top five items of cited literature. Keywords were categorized into four clusters based on the keywords visualization. Conclusion: It is important to strengthen the collaboration between nations of different economies to produce more high-quality research on GDM and nutrition. It may be beneficial to further study the etiology, diagnosis, and treatment of GDM based on current results to provide a new perspective on GDM and nutrition.

Cation-defect-induced self-reduction towards efficient mechanoluminescence in Mn2+-activated perovskites.

Mechanoluminescent (ML) materials have shown promising prospects for various applications, e.g. in stress sensing, information anti-counterfeiting and bio stress imaging fields. However, the development of trap-controlled ML materials is still limited, because the trap formation mechanism is not always clear. Here, inspired by a defect-induced Mn4+ → Mn2+ self-reduction process in suitable host crystal structures, a cation vacancy model is creatively proposed to determine the potential trap-controlled ML mechanism. Combined with the theoretical prediction and experimental results, both the self-reduction process and ML mechanism are clarified in detail, where the contribution of and defects dominates the ML luminescent process. Electrons/holes are mainly captured by the anionic/cationic defects, followed by the combination of electrons and holes to transfer energy to the Mn2+ 3d states under mechanical stimuli. Based on the multi-mode luminescent features excited by X-ray, 980 nm laser and 254 nm UV lamp, together with the excellent persistent luminescence and ML, a potential application in advanced anti-counterfeiting is demonstrated. These results will deepen the understanding of the defect-controlled ML mechanism, and inspire more defect-engineering strategies to develop more high-performance ML phosphors for practical application.

CD146+ mural cells from infantile hemangioma display proangiogenic ability and adipogenesis potential in vitro and in xenograft models.

Objective: Infantile hemangioma (IH), the most common infantile vascular neoplasm, is uniquely characterized by rapid proliferation followed by slow spontaneous involution lasting for years. In IH lesions, perivascular cells are the most dynamic cell subset during the transition from the proliferation phase to the involution phase, and we aimed to systematically study this kind of cell. Methods and results: CD146-selective microbeads were used to isolate IH-derived mural-like cells (HemMCs). Mesenchymal markers of HemMCs were detected by flow cytometry, and the multilineage differentiation potential of HemMCs was detected by specific staining after conditioned culture. CD146-selected nonendothelial cells from IH samples showed characteristics of mesenchymal stem cells with distinct angiogenesis-promoting effects detected by transcriptome sequencing. HemMCs spontaneously differentiated into adipocytes 2 weeks after implantation into immunodeficient mice, and almost all HemMCs had differentiated into adipocytes within 4 weeks. HemMCs could not be induced to differentiate into endothelial cells in vitro. However, 2 weeks after implantation in vivo, HemMCs in combination with human umbilical vein endothelial cells (HUVECs) formed GLUT1+ IH-like blood vessels, which spontaneously involuted into adipose tissue 4 weeks after implantation. Conclusions: In conclusion, we identified a specific cell subset that not only showed behavior consistent with the evolution of IH but also recapitulated the unique course of IH. Thus, we speculate that proangiogenic HemMCs may be a potential target for the construction of hemangioma animal models and the study of IH pathogenesis.

Efficient and Broadband Emission in Dy3+-Doped Glass-Ceramic Fibers for Tunable Yellow Fiber Laser.

Yellow lasers are of great interest in biology, medicine and display technology. However, nonlinear emission of near-infrared lasers at yellow still presents particularly complex optical alignment to date. Here, to the best of our knowledge, we demonstrate the fabrication of a NaLa(WO4)2: Dy3+ glass-ceramic fiber (GCF) for the first time. More importantly, the emission band of the GCF, which is around 575 nm, has a wide full-width half maximum (FWHM) of 18~22 nm, which is remarkably larger than that of the Dy3+-doped YAG crystal (<7 nm). The precursor fiber (PF) was drawn using the molten core drawing (MCD) method. In particular, benefiting from the in situ nanocrystals fabricated in the amorphous fiber core after thermal treatment, the resultant glass-ceramic fiber exhibits a five-times enhancement of luminescence intensity around 575 nm, compared with the precursor fiber, while retaining its broadband emission. Overall, this work is anticipated to offer a high potential GCF with prominent bandwidth for the direct access of a tunable yellow laser.

Distribution of problematic localized facial infantile haemangiomas and their response to propranolol: a retrospective cohort study.

BACKGROUND: The distribution and response to propranolol of problematic facial infantile haemangiomas (IHs) has rarely been described in the literature. AIM: To map problematic facial IHs and observe their response to propranolol. METHODS: Eligible patients were categorized according to focal location and cohorts corresponding to these (buccal, medial, zygomatic, lateral and multiregional) were created. The primary efficacy variable was regression score ranging from 1 to 4, calculated using results of colour Doppler ultrasonography. RESULTS: In total, 104 patients met the inclusion criteria. There were 32 (30·8%) IHs located in the buccal area, 12 (11·5%) in the medial area, 49 (47·1%) in the lateral area and 1 (1·0%) in the zygomatic area, with 10 (9·6%) IH cases having multiregional lesions. We found that the distribution pattern of most IHs matched the surface projection of the trunk of the external carotid and the facial arteries. Further analysis showed that the median regression score in the buccal and medial groups were significantly lower than those in the lateral and multiregional groups. CONCLUSION: Treatment of buccal and medial haemangiomas tends to be more challenging and their distribution pattern mainly reflects the direction of the facial vessels.

Apelin Receptor Can Act as a Specific Marker and Promising Therapeutic Target for Infantile Hemangioma.

Infantile hemangioma (IH), the most common benign tumor in infancy, is generally sensitive to propranolol treatment. However, the challenge remains because resistance or recurrence could occur in some patients, and the mechanism or target of propranolol remains unknown. Therefore, advancement in the drug development is needed. In this study, we explored whether apelin receptor (APJ) can become a candidate target. We found that APJ is expressed only in endothelial cells of IH (HemECs) but not in other vascular anomalies, and its antagonist, ML221, can negatively regulate cellular viability and functions of HemECs. This inhibitory effect could be replicated in a murine hemangioma model. Importantly, in vitro experiments also indicated that ML221 failed to affect the proliferation or angiogenesis of normal endothelial cells or APJ-knockout HemECs. Through analysis of the phosphoantibody microarray data, ML221 was revealed to have an inhibitory effect on HemECs by suppressing the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These results verified the distinctive expression of APJ in IH and specific inhibition of HemEC activity caused by ML221. In addition, APJ was also detected in propranolol-resistant IH. Collectively, we propose that APJ can act as a specific marker and a promising therapeutic target for IH, which will facilitate further drug development.

Nitric oxide-mediated regulation of mitochondrial protective autophagy for enhanced chemodynamic therapy based on mesoporous Mo-doped Cu9S5 nanozymes.

The depletion of reactive oxygen species (ROS) by glutathione (GSH) and oxidative stress induced protective autophagy severely impaired the therapeutic effect of chemodynamic therapy (CDT). Therefore, how to construct a CDT treatment nanosystem with high yield and full utilization of ROS in tumor site is the main issue of CDT. Herein, a multifunctional cascade bioreactor based on mesoporous Mo-doped Cu9S5 (m-MCS) nanozymes loaded with L-Arginine (LA), abbreviated as m-MCS@LA, is constructed for realizing enhanced CDT promoted by ultrasound (US) triggered gas therapy. The m-MCS based on the catalytic performance of multivalent metal ions, which were served as nanozymes, exhibit enhanced Fenton-like and glutathione (GSH) peroxidase-like activities in comparison to Cu9S5 nanoparticles without Mo-doping. Once placed in tumor microenvironment (TME), the existence of redox couples (Cu+/Cu2+ and Mo4+/Mo6+) in m-MCS enabled it to react with hydrogen peroxide (H2O2) to generate ·OH for achieving CDT effect via Fenton-like reaction. Meanwhile, m-MCS could consume overexpressed GSH in tumor microenvironment (TME) to alleviate antioxidant capability for enhancing CDT effect. Moreover, m-MCS with mesoporous structure could be employed as the carrier to load natural nitric oxide (NO) donor LA. US as the excitation source with high tissue penetration can trigger m-MCS@LA to produce NO. As the gas transmitter with physiological functions, NO could play dual roles to kill cancer cells through gas therapy directly, and enhance CDT effect by inhibiting protective autophagy simultaneously. As a result, this US-triggered and NO-mediated synergetic cancer chemodynamic/gas therapy based on m-MCS@LA NPs can effectively eliminate primary tumor and achieved tumor-specific treatment, which provide a possible strategy for developing more effective CDT in future practical applications. STATEMENT OF SIGNIFICANCE: The depletion of reactive oxygen species (ROS) by glutathione (GSH) and oxidative stress induced protective autophagy severely impaired the therapeutic effect of chemodynamic therapy (CDT). Herein, a multifunctional cascade bioreactor based on mesoporous Mo-doped Cu9S5 (m-MCS) nanozymes loaded with L-Arginine (m-MCS@LA) is constructed for realizing enhanced CDT promoted by ultrasound (US) triggered gas therapy. The m-MCS with double redox couples presents the enhanced enzyme-like activities to perform cascade reactions for reducing GSH and generating ROS. LA loaded by m-MCS can produce NO triggered by US to inhibit the mitochondria protective autophagy for reactivating mitochondria involved apoptosis pathway. The US-triggered and NO-mediated CDT based on m-MCS@LA can effectively eliminate primary tumor through the high yield and full utilization of ROS.

Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas.

Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy.

Immunomodulatory effect of N-acetyl-seryl-aspartyl-proline and vasoactive intestinal peptide on chronic obstructive pulmonary disease pathophysiology.

Chronic obstructive pulmonary disease (COPD) as an inflammatory respiratory system disease is caused by exposure to cigarette smoke and tobacco in long-term. Some anti-inflammatory peptides can control inflammation in COPD. N-acetyl-seryl-aspartyl-proline (Ac-SDKP) and vasoactive intestinal peptide (VIP) as peptide have anti-inflammatory effect, and, in this study, the effect of Ac-SDKP and VIP on COPD inflammation was studied. After producing cigarette smoke-induced COPD mice model, which were treated with VIP and Ac-SDKP, the levels of antioxidant-related factors (malondialdehyde (MDA) and superoxide dismutase (SOD)), fibrotic factors (hydroxyproline (HP) and TGF-ß), pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), and inflammation in histopathological examination were studied. MDA, Remodeling factors, pro-inflammatory cytokines, and inflammation in lung tissue were controlled by VIP and Ac-SDKP treatment. These treatments could enhance SOD. VIP and Ac-SDKP as immuno-regulatory factors had benefit effect in treatment of COPD. The anti-inflammatory, anti-fibrosis, and anti-oxidant properties of VIP and Ac-SDKP may be effective therapy in COPD.

Surface-Functionalized NdVO4:Gd3+ Nanoplates as Active Agents for Near-Infrared-Light-Triggered and Multimodal-Imaging-Guided Photothermal Therapy.

Development of nanotheranostic agents with near-infrared (NIR) absorption offers an effective tool for fighting malignant diseases. Lanthanide ion neodymium (Nd3+)-based nanomaterials, due to the maximum absorption at around 800 nm and unique optical properties, have caught great attention as potential agents for simultaneous cancer diagnosis and therapy. Herein, we employed an active nanoplatform based on gadolinium-ion-doped NdVO4 nanoplates (NdVO4:Gd3+ NPs) for multiple-imaging-assisted photothermal therapy. These NPs exhibited enhanced NIR absorption and excellent biocompatibility after being grafted with polydopamine (pDA) and bovine serum albumin (BSA) layers on their surface. Upon expose to an 808 nm laser, these resulting NPs were able to trigger hyperthermia rapidly and cause photo-destruction of cancer cells. In a xenograft tumor model, tumor growth was also significantly inhibited by these photothermal agents under NIR laser irradiation. Owing to the multicomponent nanostructures, we demonstrated these nanoagents as being novel contrast agents for in vivo magnetic resonance (MR) imaging, X-ray computed tomography (CT), photoacoustic (PA) imaging, and second biological window fluorescent imaging of tumor models. Thus, we believe that this new kind of nanotherapeutic will benefit the development of emerging nanosystems for biological imaging and cancer therapy.

Identification of hub genes associated with COVID-19 and idiopathic pulmonary fibrosis by integrated bioinformatics analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), emerged in late 2019, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk factors for idiopathic pulmonary fibrosis (IPF) and COVID-19 are reported to be common. This study aimed to determine the potential role of differentially expressed genes (DEGs) common in IPF and COVID-19. MATERIALS AND METHODS: Based on GEO database, we obtained DEGs from one SARS-CoV-2 dataset and five IPF datasets. A series of enrichment analysis were performed to identify the function of upregulated and downregulated DEGs, respectively. Two plugins in Cytoscape, Cytohubba and MCODE, were utilized to identify hub genes after a protein-protein interaction (PPI) network. Finally, candidate drugs were predicted to target the upregulated DEGs. RESULTS: A total of 188 DEGs were found between COVID-19 and IPF, out of which 117 were upregulated and 71 were downregulated. The upregulated DEGs were involved in cytokine function, while downregulated DEGs were associated with extracellular matrix disassembly. Twenty-two hub genes were upregulated in COVID-19 and IPF, for which 155 candidate drugs were predicted (adj.P.value < 0.01). CONCLUSION: Identifying the hub genes aberrantly regulated in both COVID-19 and IPF may enable development of molecules, encoded by those genes, as therapeutic targets for preventing IPF progression and SARS-CoV-2 infections.

Enhancement of anthocyanin and chromatic profiles in 'Cabernet Sauvignon' (Vitis vinifera L.) by foliar nitrogen fertilizer during veraison.

BACKGROUND: The influence of foliar nitrogen fertilizer during veraison (FNFV) on anthocyanin accumulation and chromatic characteristics of 'Cabernet Sauvignon' grapes over two seasons was investigated. RESULTS: Urea and phenylalanine fertilizers (TU and TP, respectively) and a control were sprayed three times at veraison. In 2018, TU displayed a significant enhancement in total individual anthocyanin content and a* and Cab * profiles. In 2019, FNAV significantly improved the content of total non-acylated, acylated anthocyanin and total individual anthocyanin, and the profiles of L*, a* and Cab *, except a* in TU. The whole process from phenylalanine variation to anthocyanin accumulation in grape skins was analyzed. On the whole, after the first FNFV to harvest, the increase in phenylalanine metabolism, abscisic acid content, effects of PAL (Phenylalanine ammonia lyase), UFGT (UDP glucose-flavonoid 3-O-glucosyltransferase) and transcript concentrations of VvPAL and VvUFGT involved in anthocyanin biosynthesis were also strong evidence explaining the increased anthocyanin and chromatic profiles in 2019. CONCLUSION: Overall, FNFV for nitrogen-deficient grapevines could significantly improve grape color, especially in the 2019 veraison with a proper climate. © 2021 Society of Chemical Industry.

CARD11 is a prognostic biomarker and correlated with immune infiltrates in uveal melanoma.

Uveal melanoma (UVM), the most common primary intraocular malignancy, has a high mortality because of a high propensity to metastasize. Our study analyzed prognostic value and immune-related characteristics of CARD11 in UVM, hoping to provide a potential management and research direction. The RNA-sequence data of 80 UVM patients were downloaded from The Cancer Genome Atlas database and divided them into high- and low-expression groups. We analyzed the differentially expressed genes, enrichment analyses and the infiltration of immune cells using the R package and Gene-Set Enrichment Analysis. A clinical prediction nomogram and protein-protein interaction network were constructed and the first 8 genes were considered as the hub-genes. Finally, we constructed a competing endogenous RNA (ceRNA) network by Cytoscape and analyzed the statistical data via the R software. Here we found that CARD11 expression had notable correlation with UVM clinicopathological features, which was also an independent predictor for overall survival (OS). Intriguingly, CARD11 had a positively correlation to autophagy, cellular senescence and apoptosis. Infiltration of monocytes was significantly higher in low CARD11 expression group, and infiltration of T cells regulatory was lower in the same group. Functional enrichment analyses revealed that CARD11 was positively related to T cell activation pathways and cell adhesion molecules. The expressions of hub-genes were all increased in the high CARD11 expression group and the ceRNA network showed the interaction among mRNA, miRNA and lncRNA. These findings show that high CARD11 expression in UVM is associated with poor OS, indicating that CARD11 may serve as a potential biomarker for the diagnosis and prognosis of the UVM.

[Effect of early mechanical ventilation on the expression of inflammatory factors and prognosis in patients with severe traumatic brain injury].

OBJECTIVE: To observe the effect of early mechanical ventilation on the expression of inflammatory factors and prognosis of patients with severe traumatic brain injury (sTBI). METHODS: From January 2017 to December 2020, 138 patients with sTBI admitted to the department of the emergency of Xinhua Hospital Chongming Branch were enrolled. Although some patients were admitted to hospital without acute respiratory failure, their Glasgow coma score (GCS) were less than 8, they bad risk of hypoxia, so early mechanical ventilation was required. According to the patient's condition and the willingness of family members, patients were divided into mechanical ventilation group (tracheal intubation mechanical ventilation) and conventional oxygen inhalation group (nasal catheter or mask oxygen inhalation) in the end. The arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6, IL-10) levels at admission, preoperation and 72 hours postoperation, as well as GCS before operation and 1 week after operation, the duration and number of patients successfully evacuated from the ventilator within 1 week after surgery were observed and analyzed. RESULTS: A total of 138 sTBI patients were enrolled in the study, including 72 cases in the mechanical ventilation group and 66 cases in the routine oxygen inhalation group. In the two groups, PaO2, PaO2/FiO2 and IL-10 were higher, and PaCO2, TNF-α and IL-6 were lower at 72 hours post operation than that before operation. Moreover, the changes in the mechanical ventilation group were more significant than those in the conventional oxygen inhalation group [PaO2 (1 mmHg = 0.133 kPa): 94.6±7.7 vs. 92.5±6.8, PaO2/FiO2 (mmHg): 351±94 vs. 319±89, IL-10 (ng/L): 8.2±2.7 vs. 7.4±1.8, PaCO2 (mmHg): 35.6±1.8 vs. 37.5±2.7, TNF-α(ng/L): 71.5±6.3 vs. 96.8±15.5, IL-6 (ng/L): 10.8±3.9 vs. 14.4±6.5, all P < 0.05]. There were 17 patients with severe respiratory insufficiency or failure in the conventional oxygen inhalation group before operation. Compared with the conventional oxygen inhalation group, the GCS score (11.7±3.1 vs. 9.1±4.6) and the proportion of successful weaning [62.5% (45/72) vs. 44.0% (29/66)] were significantly higher, and the duration of successful weaning (hours: 63.5±28.6 vs. 88.1±33.9) was significantly shorter in the mechanical ventilation group 1 week after operation. CONCLUSIONS: Early mechanical ventilation in sTBI patients can significantly improve oxygen supply, inhibit the release of pro-inflammatory factors, reduce secondary brain damage, and effectively improve the prognosis.

[Effect of Competitive Antagonist of Transmembrane Glutamine Flux V-9302 on Apoptosis of Acute Myeloid Leukemia Cell Lines HL-60 and KG-1].

OBJECTIVE: To investigate the effect of V-9302 (an antagonist of transmembrane glutamine flux) on the proliferation and apoptosis of acute myeloid leukemia cells HL-60 and KG-1. METHODS: HL-60 and KG-1 cells at logarithmic phase were treated by different concentrations of V-9302. CCK-8 assay was used to detect the proliferation of the cells. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of HL-60 and KG-1 cells. The expressions of BAX, BCL-2 and Caspase3 were detected by RT-qPCR and Western blot. RESULTS: V-9302 could significantly inhibit the growth of HL-60 and KG-1 cells. The concentration of V-9302 at 10, 20 µmol/L could significantly promote the apoptosis of HL-60 and KG-1 cells(P<0.05). The results of apoptosis related gene detection showed that when V-9302 was applied to HL-60 and KG-1 cell lines at 10 and 20 µmol/L, the expression levels of Pro-apoptotic protein genes BAX and Caspase3 in HL-60 and KG-1 were significantly higher than those in control group (P<0.05), while the expression level of anti-apoptotic protein gene BCL-2 was significantly lower than that in the control group (P<0.05). The results of Western blot were basically consistent with that of RT-qPCR. CONCLUSION: Competitive antagonist of transmembrane glutamine flux V-9302 can significantly promote the apoptosis of acute myeloid leukemia cell lines HL-60 and KG-1.