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1.
Dev Comp Immunol ; 126: 104237, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34450128

RESUMO

Clip domain serine protease (cSPs) play an important role in the innate immune defense of crustaceans. In this study, a clip domain serine protease (MncSP) and its alternative transcript (MncSP-isoform) were identified from Macrobrachium nipponense. The full-length cDNA sequences of MncSP and MncSP-isoform were 2447 and 2351 bp with open reading frames comprising 1497 and 1401 bp nucleotides and encoding 498 and 466 amino acids, respectively. The genome of MncSP had 10 exons and 9 introns. MncSP contained all 10 exons, whereas MncSP-isoform lacked the second exon. MncSP and MncSP-isoform contained a signal peptide, a clip domain, and a Tryp_SPc domain. Phylogenetic tree analysis showed that MncSP and MncSP-isoform clustered with cSPs from Palaemonidae. MncSP and MncSP-isoform were widely distributed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine. The expression profiles of MncSP and MncSP-isoform in the hemocytes of M. nipponense changed after simulation by Vibrio parahaemolyticus or Staphylococcus aureus. The RNAi of MncSP could inhibit the expression of antimicrobial peptides (AMPs), including crustins and anti-lipopolysaccharide factors. Phenoloxidase activity was also down-regulated in MncSP-silenced prawns. This study indicated that MncSP participated in the synthesis of AMPs and the activation of prophenoloxidase.

2.
Exp Biol Med (Maywood) ; : 15353702211049149, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743578

RESUMO

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

3.
Front Immunol ; 12: 710513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745091

RESUMO

High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34731283

RESUMO

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing this strategy using a systemic therapy approach was assessed by systemic delivery of major histocompatibility complex class I (MHC-I)-compatible peptides to targeted mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) in mice using a novel HER2-targeting single-lipid nanoparticle (SLNP). Our results show that preexisting influenza A immunity in PR8-immunized mice could be quickly redirected to syngeneic tumors expressing influenza A NP and HA, leading to strong inhibition of tumor growth and metastasis and improvement of survival compared to the findings in antigen-naïve control mice. MHC-I-compatible peptides could be delivered to targeted mammary tumors in mice using the HER2-targeting SLNP for antigen presentation, which subsequently redirected preexisting influenza A immunity to the tumors to exert antitumor activities. In conclusion, preexisting influenza A immunity can be repurposed for cancer immunotherapy through systemic delivery of influenza A-related peptides to targeted tumors. Further development of the strategy for clinical translation is warranted.

5.
Nanoscale ; 13(44): 18546-18557, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34730162

RESUMO

The exploration of MXenes, especially nitride MXenes, in the field of theranostic nanomedicine is still in its infancy. Here, towards synergistic chemo-photothermal oncotherapy, we demonstrate the first kind of 2D titanium nitride (Ti2N) MXene-based nanosystem (Ti2N@oSi) for dual-strategy synergistic oncotherapy. The unique structure of Ti2N nanosheets endows the drug carriers with an ultrahigh loading capacity of 796.3% and an excellent NIR photothermal conversion efficiency of 41.6% for chemo-photothermal therapy. After being coated with a biodegradable organosilica shell, the Ti2N@oSi nanocarriers show excellent characteristics of tumor targeting, pH/glutathione/photothermal-responsive drug release and dual-drug combination chemotherapy. Both in vitro and in vivo therapeutic evaluations demonstrate the pronounced tumor growth inhibition effect and superior biocompatibility of Ti2N@oSi nanocarriers. The excellent drug loading ability, photothermal conversion ability and surface modifiability of Ti2N open up new opportunities for tumor microenvironment-targeted synergistic oncotherapy. This work is supposed to broaden the application of MXenes in nanomedicine and, particularly, provide the first sight to the biomedical application of nitride MXenes.


Assuntos
Hipertermia Induzida , Nanopartículas , Linhagem Celular Tumoral , Doxorrubicina , Portadores de Fármacos , Liberação Controlada de Fármacos , Fototerapia , Nanomedicina Teranóstica , Titânio
6.
Appl Microbiol Biotechnol ; 105(23): 8783-8793, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34741642

RESUMO

The established human health benefits of carotenoids along with the contemporary consumption of natural carotenoids bring the necessity to sustainable production of carotenoids. Among, marine diatoms have emerged as the potential biological resources for carotenoid production; however, their relatively lower yield in native strains provides the impetus to genetically improve the diatoms to cope with the burgeoning demand. In this study, we genetically improved the diatom Phaeodactylum tricornutum by overexpressing key carotenogenic genes involved in methylerythritol phosphate (MEP) pathway. The genes with lower relative transcript level under optimum conditions such as CMK and CMS were selected and overexpressed in P. tricornutum individually. Both CMK and CMS overexpressing lines exhibited elevated growth and photosynthesis. The expression of key carotenogenic genes such as PSY, PDS, ZDS, CRT, and LCYB was significantly upregulated. Furthermore, total carotenoid content was significantly increased; particularly, fucoxanthin content was increased by 1.83- and 1.82-fold in engineered lines CMK and CMS, respectively. Together, the results identify the potential metabolic targets and also uncover the crucial role of MEP pathway in redirecting metabolic precursors towards carotenogenesis. KEY POINTS: • Low abundant genes CMS and CMK of MEP pathway were overexpressed in the diatom • Total carotenoid content was increased, particularly fucoxanthin • Critical metabolic nodes were uncovered to accelerate fucoxanthin biosynthesis.


Assuntos
Diatomáceas , Carotenoides , Diatomáceas/genética , Humanos , Fosfatos , Xantofilas
7.
Dalton Trans ; 50(46): 17120-17128, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34779809

RESUMO

The lithium polysulfide (LiPS) shuttle effect and low redox kinetics are the key problems that hinder performance improvement and prevent achieving the commercial requirements for lithium-sulfur batteries (LSBs), and the reasonable construction of sulfur hosts is one effective strategy to relieve the polysulfide shuttle effect and improve redox kinetics. Herein, N-doped carbon nanocages decorated with homogeneously dispersed TiN nanoparticles (TiN@C NCs) as multifunctional sulfur hosts are designed for superior LSBs. Carbon nanocages provide space to mitigate volume expansion and provide additional physical adsorption to trap the LiPSs. Polar TiN nanoparticles not only exhibit the chemisorption capacity for LiPSs, but also catalyze and promote the conversion of long-chain LiPSs to Li2S2/Li2S in the reduction process as well as the decomposition of Li2S in the oxidation reaction, which significantly boosts electron/ion transport and decreases the potential barrier. Therefore, the S/TiN@C NC cathode has an excellent electrochemical capacity of 1485.7 mA h g-1 at 0.1 C. In particular, the cathode demonstrates high capacity reversibility after 500 cycles at 3 C with a retention of about 73.1%, which is equivalent to a slow capacity decay rate of 0.053% per cycle.

8.
BMC Pregnancy Childbirth ; 21(1): 784, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798869

RESUMO

BACKGROUND: Analysis of "maternal near-misses" is expected to facilitate assessment of the quality of maternity care in health facilities. Therefore, this study aimed to investigate incidence, risk factors and causes of maternal near-misses (MNM) admitted to the intensive care unit (ICU) within five years by using the World Health Organization's MNM approach. METHODS: A five-year retrospective study was conducted in Subei People's Hospital of Yangzhou, Jiangsu Province from January 1, 2015 to December 31, 2019. Risk factors in 65 women with MNM in the intensive care unit (ICU) were explored by using chi-square tests and multivariable logistic regression analysis. Causes and interventions in MNM were investigated by descriptive analysis. RESULTS: Average maternal near-miss incidence ratio (MNMIR) for ICU admission was 3.5 per 1000 live births. Average maternal mortality ratio (MMR) was 5 per 100,000 live births. MI for all MNM was 0.7%. Steady growth of MNMIR in ICU was witnessed in the five-year study period. Women who were referred from other hospitals (aOR 3.32; 95%CI 1.40-7.32) and had cesarean birth (aOR 4.96; 95%CI 1.66-14.86) were more likely to be admitted in ICU. Neonates born to women with MNM admitted in ICU had lower birthweight (aOR 5.41; 95%CI 2.53-11.58) and Apgar score at 5 min (aOR 6.39; 95%CI 2.20-18.55) compared with women with MNM outside ICU. ICU admission because of MNM occurred mostly postpartum (n = 63; 96.9%). Leading direct obstetric causes of MNM admitted in ICU were hypertensive diseases of pregnancy (n = 24; 36.9%), followed by postpartum hemorrhage (n = 14; 21.5%), while the leading indirect obstetric cause was heart diseases (n = 3; 4.6%). CONCLUSIONS: Risk factors that were associated with MNM in ICU were referral and cesarean birth. Hypertensive disease of pregnancy and postpartum hemorrhage were the main obstetric causes of MNM in ICU. These findings would provide guidance to improve professional skills of primary health care providers and encourage vaginal birth in the absence of medical indications for cesarean birth.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Serviços de Saúde Materna/estatística & dados numéricos , Near Miss/estatística & dados numéricos , Adulto , Cesárea/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Mortalidade Materna , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
9.
Biomaterials ; : 121260, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34823885

RESUMO

An increasing number of works have highlighted the importance of metal implants surface modification in enhancing bone defect healing through the synergistic osteogenesis-angiogenesis regulation. Studies have shown that pitavastatin has the effect of promoting osteogenesis and angiogenesis. However, how to prepare pitavastatin functionalized implants and how pitavastatin regulates the synergies of osteogenesis and angiogenesis around implants as well as the related mechanisms remain unclear. In the present study, multilayer films with osteogenic and angiogenic properties were constructed on pure titanium substrates via the layer-by-layer assembly of pitavastatin-loaded ß-cyclodextrin grafted chitosan and gelatin. In vitro experiments demonstrated that locally applied pitavastatin could dramatically enhance osteogenic potential of mesenchymal stem cells (MSCs) and angiogenic potential of endothelial cells (ECs). Moreover, pitavastatin loaded multilayer films could regulate the paracrine signaling mediated crosstalk between MSCs and ECs, and indirectly increase the angiogenic potential of MSCs and osteogenic potential of ECs via multiple paracrine signaling. The results of subcutaneous and femur implantation confirmed that locally released pitavastatin had potentially triggered a chain of biological events: mobilizing endogenous stem cells and ECs to the implant-bone interface, in turn facilitating coupled osteogenesis and angiogenesis, and eventually enhancing peri-implant osseointegration. This study enlarges the application scope of pitavastatin and provides an optional choice for developing a multifunctional bioactive coating on the surfaces of mental implants.

10.
Microsyst Nanoeng ; 7: 92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804586

RESUMO

Monitoring biophysical signals such as body or organ movements and other physical phenomena is necessary for patient rehabilitation. However, stretchable flexible pressure sensors with high sensitivity and a broad range that can meet these requirements are still lacking. Herein, we successfully monitored various vital biophysical features and implemented in-sensor dynamic deep learning for knee rehabilitation using an ultrabroad linear range and high-sensitivity stretchable iontronic pressure sensor (SIPS). We optimized the topological structure and material composition of the electrode to build a fully stretching on-skin sensor. The high sensitivity (12.43 kPa-1), ultrabroad linear sensing range (1 MPa), high pressure resolution (6.4 Pa), long-term durability (no decay after 12000 cycles), and excellent stretchability (up to 20%) allow the sensor to maintain operating stability, even in emergency cases with a high sudden impact force (near 1 MPa) applied to the sensor. As a practical demonstration, the SIPS can positively track biophysical signals such as pulse waves, muscle movements, and plantar pressure. Importantly, with the help of a neuro-inspired fully convolutional network algorithm, the SIPS can accurately predict knee joint postures for better rehabilitation after orthopedic surgery. Our SIPS has potential as a promising candidate for wearable electronics and artificial intelligent medical engineering owing to its unique high signal-to-noise ratio and ultrabroad linear range. An ultrabroad-linear range (1 MPa) iontronic pressure sensor with superior sensitivity (12.43 kPa-1) and stretchability (up to 20%) was proposed for biophysical monitoring and deep learning-based knee-rehabilitation training.

11.
Front Cell Dev Biol ; 9: 770621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805176

RESUMO

Intercellular communication in the decidua plays important roles in relaying information between the maternal and fetal systems in the maintenance of pregnancy and the transition to labor. To date, several studies have explored cell-cell communications in the decidua during different periods of pregnancy, but studies systematically decoding the intercellular communication network, its internal cascades, and their involvement in labor are still lacking. In this study, we reconstructed a decidual cell-cell communication network based on scRNA-seq of peripartum decidua via the CellCall method. The results showed that endometrial cells (EECs) and extravillous trophoblasts relayed most of the common intercellular signals in the decidua both before delivery (DBD) and after delivery (DAD). Endothelial cells and EECs controlled many WNT-signaling-related intercellular communication factors that differed between DBD and DAD, some of which could be candidate biomarkers for the diagnosis of labor. Analysis of intercellular communications related to T cells identified abundant maternal-fetal immune-tolerance-related communication, such as TNFSF14-TNFRSF14/LTBR and FASLG-FAS signalings. We further explored the characteristics of the B cell receptor (BCR) and T cell receptor (TCR) repertoires by single-cell BCR/TCR sequencing. The results showed no significant differences in clonal expansion of B/T cells between DAD and DBD, indicating there was no significant change to adaptive immunity at the maternal-fetal interface during delivery. In summary, the findings provide a comprehensive view of the intercellular communication landscape in the peripartum decidua and identified some key intercellular communications involved in labor and maternal-fetal immune tolerance. We believe that our study provides valuable clues for understanding the mechanisms of pregnancy and provides possible diagnostic strategies for the onset of labor.

12.
Opt Express ; 29(23): 38347-38358, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808889

RESUMO

We propose a radial shearing interferometric approach to measure spherical wavefronts as both of the reflective and transmissive optical configurations. The modified cyclic radial shearing interferometer uses a single lens in the optical layout, which can conveniently adjust the radial shearing ratio between two shearing spherical wavefronts, and the use of a polarization camera enables to reconstruct the wavefront by a single image. The wavefront mapped onto the camera plane can be identified and quantified throughout an optimized wavefront reconstruction algorithm. In the experiments, plano-convex lenses and concave mirrors were used to generate spherical wavefronts, and the proposed system was able to reconstruct the surface figures after system characterization and calibration. Further investigations were performed to evaluate the system measurement accuracy by the radius of curvature comparison with design value and a commercial Shack-Hartmann wavefront sensor.

13.
Surg Clin North Am ; 101(6): 939-949, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774273

RESUMO

Incisional hernia remains a common complication following abdominal surgery, and its incidence can be reduced with standardized wound closure techniques. Robust evidence exists to support certain fascial closure methods, such as using a small bites, 4-to-1, continuous slow absorbable suture technique for elective midline laparotomies. On the other hand, there are other common surgical practices that lack quality data to support their routine use, such as abdominal binders, negative-pressure wound therapy, and reapproximation of subcutaneous tissue.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Laparotomia , Músculos Abdominais/cirurgia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparotomia/efeitos adversos , Laparotomia/métodos , Implantação de Prótese , Telas Cirúrgicas , Técnicas de Sutura
14.
Materials (Basel) ; 14(22)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34832345

RESUMO

In this study, hydrogen (H2) and methane (CH4) were used as reactive gases, and chemical vapor deposition (CVD) was used to grow single-layer graphene on a copper foil substrate. The single-layer graphene obtained was transferred to a single-crystal silicon substrate by PMMA transfer technology for the subsequent growth of nano zinc oxide. The characteristics of CVD-deposited graphene were analyzed by a Raman spectrometer, an optical microscope, a four-point probe, and an ultraviolet/visible spectrometer. The sol-gel method was applied to prepare the zinc oxide seed layer film with the spin-coating method, with methanol, zinc acetate, and sodium hydroxide as the precursors for growing ZnO nanostructures. On top of the ZnO seed layer, a one-dimensional zinc oxide nanostructure was grown by a hydrothermal method at 95 °C, using a zinc nitrate and hexamethylenetetramine mixture solution. The characteristics of the nano zinc oxide were analyzed by scanning electron microscope(SEM),x-ray diffractometer(XRD), and Raman spectrometer. The obtained graphene/zinc oxide nano-heterostructure sensor has a sensitivity of 1.06 at a sensing temperature of 205 °C and a concentration of hydrogen as low as 5 ppm, with excellent sensing repeatability. The main reason for this is that the zinc oxide nanostructure has a large specific surface area, and many oxygen vacancy defects exist on its surface. In addition, the P-N heterojunction formed between the n-type zinc oxide and the p-type graphene also contributes to hydrogen sensing.

15.
BMC Med Inform Decis Mak ; 21(1): 332, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34838025

RESUMO

BACKGROUND: An increase in the incidence of central venous catheter (CVC)-associated deep venous thrombosis (CADVT) has been reported in pediatric patients over the past decade. At the same time, current screening guidelines for venous thromboembolism risk have low sensitivity for CADVT in hospitalized children. This study utilized a multimodal deep learning model to predict CADVT before it occurs. METHODS: Children who were admitted to intensive care units (ICUs) between December 2015 and December 2018 and with CVC placement at least 3 days were included. The variables analyzed included demographic characteristics, clinical conditions, laboratory test results, vital signs and medications. A multimodal deep learning (MMDL) model that can handle temporal data using long short-term memory (LSTM) and gated recurrent units (GRUs) was proposed for this prediction task. Four benchmark machine learning models, logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT) and a published cutting edge MMDL, were used to compare and evaluate the models with a fivefold cross-validation approach. Accuracy, recall, area under the ROC curve (AUC), and average precision (AP) were used to evaluate the discrimination of each model at three time points (24 h, 48 h and 72 h) before CADVT occurred. Brier score and Spiegelhalter's z test were used measure the calibration of these prediction models. RESULTS: A total of 1830 patients were included in this study, and approximately 15% developed CADVT. In the CADVT prediction task, the model proposed in this paper significantly outperforms both traditional machine learning models and existing multimodal deep learning models at all 3 time points. It achieved 77% accuracy and 90% recall at 24 h before CADVT was discovered. It can be used to accurately predict the occurrence of CADVT 72 h in advance with an accuracy of greater than 75%, a recall of more than 87%, and an AUC value of 0.82. CONCLUSION: In this study, a machine learning method was successfully established to predict CADVT in advance. These findings demonstrate that artificial intelligence (AI) could provide measures for thromboprophylaxis in a pediatric intensive care setting.

16.
Ann Transl Med ; 9(18): 1401, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733953

RESUMO

Background: Dilated cardiomyopathy (DCM) is a common cause of heart failure. Cardiac remodeling is the main pathological change in DCM, yet the molecular mechanism is still unclear. Therefore, the present study aims to find potential crucial genes and regulators through bulk and single-cell transcriptomic analysis. Methods: Three microarray datasets of DCM (GSE57338, GSE42955, GSE79962) were chosen from gene expression omnibus (GEO) to analyze the differentially expressed genes (DEGs). LASSO regression, SVM-RFE, and PPI network methods were then carried out to identify key genes. Another dataset (GSE116250) was used to validate these findings. To further identify DCM-associated specific cell types, transcription factors, and cell-cell interaction networks, GSEA, SCENIC, and CellPhoneDB were conducted on public datasets for single-cell RNA sequencing analysis of DCM (GSE109816 and GSE121893). Finally, reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemical were performed to validate DPT expression in fibroblasts and DCM. Results: There were 281 DEGs between DCM and non-failing donors. CCL5 and DPT were identified to be key genes and both genes had a 0.844 area under the receiver operating curve (AUC) in the validation dataset. Further single-cell sequencing analysis revealed three main findings: (I) DPT was mainly expressed in fibroblasts and was significantly upregulated in DCM fibroblasts; (II) DPT+ fibroblasts were involved in the organization of the extracellular matrix (ECM) and collagen fibrils and were regulated by the transcription factor STAT3; and (III) DPT+ fibroblasts had high interactions with endothelial cells through including Ephrin-Eph, ACKR-CXCL, and JAG-NOTCH signal pathways. RT-PCR, western blot, and immunohistochemical confirmed that DPT was highly expressed and co-localized with Vimentin and p-STAT3 in DCM patients. STAT3 inhibitor S3I-201 reduced the expression of DPT in mouse cardiac fibroblasts. Conclusions: DPT could be used as a diagnostic marker and therapeutic target of DCM. DPT+ fibroblasts could be a novel regulator of the cardiac remodeling process in DCM.

17.
J Basic Microbiol ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34738230

RESUMO

Various mechanisms are involved in plant disease resistance mediated by entomopathogenic fungi; however, the role of plant endophytic microbes in disease resistance is unknown. In the present study, we showed that the disease incidence of northern corn leaf blight caused by Exserohilum turcicum (Et) on maize was reduced significantly by soil inoculation with Beauveria bassiana (Bb). Meanwhile, B. bassiana colonization and E. turcicum infection increased the diversity and abundance and diversity of endophytic bacteria and fungi, respectively, while the abundance of endophytic bacterial of the Bb + Et treatment decreased significantly compared with that of Et treatment alone. However, Bb + Et treatment increased the relative abundance of plant beneficial bacteria significantly, for example, Burkholderia and Pseudomonas. Network analyses showed that the microbiome complexity increased after soil inoculation with B. bassiana. Taken together, these results revealed the potential mechanism by which entomopathogenic fungi exert biological control of maize leaf spot disease.

18.
Environ Sci Technol ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723492

RESUMO

Mainstream anaerobic wastewater treatment has received increasing attention for the recovery of methane-rich biogas from biodegradable organics, but subsequent mainstream nitrogen and dissolved methane removal at low temperatures remains a critical challenge in practical applications. In this study, granular sludge coupling n-DAMO with Anammox was employed for mainstream nitrogen removal, and the dissolved methane removal potential of granular sludge at low temperatures was investigated. A stable nitrogen removal rate (0.94 kg N m-3 d-1 at 20 °C) was achieved with a high-level effluent quality (<3.0 mg TN L-1) in a lab-scale membrane granular sludge reactor (MGSR). With decreasing temperature, the nitrogen removal rate dropped to 0.55 kg N m-3 d-1 at 10 °C, while the effluent concentration remained <1.0 mg TN L-1. The granular sludge with an average diameter of 1.8 mm proved to retain sufficient biomass (27 g VSS L-1), which enabled n-DAMO and Anammox activity at a hydraulic retention time as low as 2.16 h even at 10 °C. 16S rRNA gene sequencing and scanning electron microscopy revealed a stable community composition and compact structure of granular sludge during long-term operation. Energy recovery could be maximized by recovering most of the dissolved methane in mainstream anaerobic effluent, as only a small amount of dissolved methane was capable of supporting denitrifying methanotrophs in granular sludge, which enabled high-level nitrogen removal.

19.
Pharm Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773182

RESUMO

PURPOSE: Sulcardine sulfate (Sul) is a novel antiarrhythmic agent with promising pharmacological properties, which is currently being evaluated in several clinical trials as an oral formulation. To meet the medication needs of patients with acute conditions, the injection formulation of Sul has been developed. The objective of this study was to systemically investigate the pharmacokinetic profiles of Sul after intravenous infusion. METHODS: This research included the plasma protein binding and metabolic stability studies in vitro, plasma pharmacokinetics, biodistribution, excretion studies in animals, and the prediction of the clinical PK of Sul injection using a physiologically based pharmacokinetics (PBPK) model. RESULTS: The metabolic stability was similarly in dogs and humans but lower in rats. The plasma protein binding rates showed a concentration-dependent manner and species differences. The pharmacokinetic behavior after intravenous administration was linear in rats within the dose range of 30-90 mg/kg, but nonlinear in dogs within 30-60 mg/kg. Sul could be rapidly and widely distributed in multiple tissues after intravenous administration. About 12% of the parent compound were excreted via the urine and only a small fraction via bile and feces,and eight metabolites were found and identified in the rat excretion. The PBPK models were developed and simulated the observed PK date well in both rats and dogs. The PBPK model refined with human data predicted the PK characteristics of the first intravenous infusion of Sul in human. CONCLUSIONS: Our study systematically explored the pharmacokinetic characteristics of Sul and successfully developed the PBPK model to predict of its clinical PK.

20.
Phys Rev Lett ; 127(18): 186401, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767429

RESUMO

Through infrared spectroscopy, we systematically study the pressure effect on electronic structures of few-layer black phosphorus (BP) with layer number ranging from 2 to 13. We reveal that the pressure-induced shift of optical transitions exhibits strong layer dependence. In sharp contrast to the bulk counterpart which undergoes a semiconductor to semimetal transition under ∼1.8 GPa, the band gap of 2 L increases with increasing pressure until beyond 2 GPa. Meanwhile, for a sample with a given layer number, the pressure-induced shift also differs for transitions with different indices. Through the tight-binding model in conjunction with a Morse potential for the interlayer coupling, this layer- and transition-index-dependent pressure effect can be fully accounted. Our study paves a way for versatile van der Waals engineering of two-dimensional BP.

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