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1.
PLoS One ; 19(5): e0303533, 2024.
Article in English | MEDLINE | ID: mdl-38781135

ABSTRACT

As global demand for offshore wind energy continues to rise, the imperative to enhance the profitability of wind power projects and reduce their operational costs becomes increasingly urgent. This study proposes an innovative approach to optimize the inspection routes of offshore wind farms, which integrates the K-means clustering algorithm and genetic algorithm (GA). In this paper, the inspection route planning problem is formulated as a multiple traveling salesman problem (mTSP), and the advantages of the K-means clustering algorithm in distance similarity are utilized to effectively group the positions of wind turbines, thereby optimizing the inspection schedule for vessels. Subsequently, by harnessing the powerful optimization capability and robustness of genetic algorithms, further refinement is conducted to search for the optimal inspection routes, aiming to achieve cost reduction objectives. The results of simulation experiments demonstrate the effectiveness of this integrated approach. Compared to traditional genetic algorithms, the inspection route length has been significantly reduced, from 93 kilometers to 79.36 kilometers. Simultaneously, operational costs have also experienced a notable decrease, dropping from 141,500 Chinese Yuan to 125,600 Chinese Yuan.


Subject(s)
Algorithms , Wind , Power Plants , Cluster Analysis , Computer Simulation
2.
BMC Plant Biol ; 24(1): 459, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797839

ABSTRACT

BACKGROUND: Relict species are important for enhancing the understanding of modern biogeographic distribution patterns. Although both geological and climatic changes since the Cenozoic have affected the relict flora in East Asia, the contributions of geographical processes remain unclear. In this study, we employed restriction-site associated DNA sequencing (RAD-seq) and shallow genome sequencing data, in conjunction with ecological niche modeling (ENM), to investigate the spatial genetic patterns and population differentiation history of the relict species Rehderodendron kwangtungense Chun. RESULTS: A total of 138 individuals from 16 populations were collected, largely covering the natural distribution of R. kwangtungense. The genetic diversity within the R. kwangtungense populations was extremely low (HO = 0.048 ± 0.019; HE = 0.033 ± 0.011). Mantel tests revealed isolation-by-distance pattern (R2 = 0.38, P < 0.001), and AMOVA analysis showed that the genetic variation of R. kwangtungense occurs mainly between populations (86.88%, K = 7). Between 23 and 21 Ma, R. kwangtungense underwent a period of rapid differentiation that coincided with the rise of the Himalayas and the establishment of the East Asian monsoon. According to ENM and population demographic history, the suitable area and effective population size of R. kwangtungense decreased sharply during the glacial period and expanded after the last glacial maximum (LGM). CONCLUSION: Our study shows that the distribution pattern of southern China mountain relict flora may have developed during the panplain stage between the middle Oligocene and the early Miocene. Then, the flora later fragmented under the force of orogenesis, including intermittent uplift during the Cenozoic Himalayan orogeny and the formation of abundant rainfall associated with the East Asian monsoon. The findings emphasized the predominant role of geographical processes in shaping relict plant distribution patterns.


Subject(s)
Climate Change , Genetic Variation , Phylogeography , Asia, Eastern , Plant Dispersal , Sequence Analysis, DNA
3.
BMC Infect Dis ; 24(1): 535, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807038

ABSTRACT

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Immunization Schedule , Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Poliovirus , Humans , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Infant , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/administration & dosage , Male , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cross-Sectional Studies , China , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Poliovirus/immunology , Immunogenicity, Vaccine , Vaccination
4.
bioRxiv ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38766202

ABSTRACT

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression. Cela1-deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg/kg reduced the lung elastase activity of AAT-/- mice treated with 0.2 units of PPE. In this injury model, AAT-/- mice treated with KF4 1 mg/kg weekly, human purified AAT 60 mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 & AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.

5.
Psychother Res ; : 1-11, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38590020

ABSTRACT

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

6.
Curr Probl Cardiol ; 49(7): 102574, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38653443

ABSTRACT

Cardiac amyloidosis (CA) is a condition characterized by the accumulation of amyloid fibrils in the heart muscle, resulting in an infiltrative cardiomyopathy. The presence of amyloid protein can impact different parts of the heart, including the valves. Limited data is available on the prevalence and prognostic significance of valvular heart disease (VHD) in CA. However, advancements in imaging technology have allowed for accurate noninvasive diagnosis of CA, eliminating the need for confirmatory endomyocardial biopsy and improving our understanding of this dual pathology. The development of targeted drug therapies for CA and transcatheter valve replacement or repair for VHD has significantly improved the prognosis for patients with both conditions. This review will discuss the findings of this original research and provide an overview of current researches on VHD in CA, as well as the progress in diagnosing and treating CA with VHD.


Subject(s)
Amyloidosis , Cardiomyopathies , Heart Valve Diseases , Humans , Prevalence , Amyloidosis/epidemiology , Amyloidosis/diagnosis , Amyloidosis/therapy , Heart Valve Diseases/epidemiology , Heart Valve Diseases/diagnosis , Cardiomyopathies/epidemiology , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Prognosis
7.
Sci Data ; 11(1): 406, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649372

ABSTRACT

Cotoneaster glaucophyllus is a semi-evergreen plant that blossoms in late summer, producing dense, attractive, fragrant white flowers with significant ornamental and ecological value. Here, a chromosome-scale genome assembly was obtained by integrating PacBio and Illumina sequencing data with the aid of Hi-C technology. The genome assembly was 563.3 Mb in length, with contig N50 and scaffold N50 values of ~6 Mb and ~31 Mb, respectively. Most (95.59%) of the sequences were anchored onto 17 pseudochromosomes (538.4 Mb). We predicted 35,856 protein-coding genes, 1,401 miRNAs, 655 tRNAs, 425 rRNAs, and 795 snRNAs. The functions of 34,967 genes (97.52%) were predicted. The availability of this chromosome-level genome will provide valuable resources for molecular studies of this species, facilitating future research on speciation, functional genomics, and comparative genomics within the Rosaceae family.


Subject(s)
Chromosomes, Plant , Genome, Plant , Chromosomes, Plant/genetics , Molecular Sequence Annotation , Rosaceae/genetics
8.
Ecotoxicol Environ Saf ; 274: 116124, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38503108

ABSTRACT

OBJECTIVE: The primary objective of this study was to investigate the toxicological impact of Dibutyl phthalate (DBP) on the process of liver fibrosis transitioning into cirrhosis and the subsequent development of portal hypertension (PHT) through the mechanism of epithelial-mesenchymal transition (EMT) mediated by the ROS/TGF-ß/Snail-1 signaling pathway. METHOD: Carbon tetrachloride (CCl4) (1 mg/kg) was introduced in adult rats by oral feeding in CCl4 and CCl4+DBP groups twice a week for 8 weeks, and twice for another 8 week in CCl4 group. DBP was introduced by oral feeding in the CCl4+DBP group twice over the following 8 weeks. We subsequently analyzed hemodynamics measurements and liver cirrhosis degree, hepatic inflammation and liver function in the different groups. EMT related genes expression in rats in the groups of Control, DBP, CCl4 and CCl4+DBP were measured by immunohistochemistry (IHC). Enzyme-linked immunosorbent Assay (ELISA), qRT-PCR, western blot were used to detect the EMT related proteins and mRNA gene expression levels in rats and primary hepatocytes (PHCs). Reactive oxygen species (ROS) were examined with a ROS detection kit. RESULTS: The results showed that the CCl4+DBP group had higher portal pressure (PP) and lower mean arterial pressure (MAP) than the other groups. Elevated collagen deposition, profibrotic factor, inflammation, EMT levels were detected in DBP and CCl4+DBP groups. ROS, TGF-ß1 and Snail-1 were highly expressed after DBP exposure in vitro. TGF-ß1 had the potential to regulate Snail-1, and both of them were subject to regulation by ROS. CONCLUSION: DBP could influence the progression of EMT through its toxicological effect by ROS/TGF-ß1/Snail-1 signalling pathway, causing cirrhosis and PHT in final. The findings of this research might contribute to a novel comprehension of the underlying toxicological mechanisms and animal model involved in the progression of cirrhosis and PHT, and potentially offered a promising therapeutic target for the treatment of the disease.


Subject(s)
Dibutyl Phthalate , Epithelial-Mesenchymal Transition , Hypertension, Portal , Transforming Growth Factor beta1 , Animals , Rats , Dibutyl Phthalate/toxicity , Fibrosis , Hypertension, Portal/chemically induced , Inflammation , Liver Cirrhosis/chemically induced , Reactive Oxygen Species , Signal Transduction , Snail Family Transcription Factors/metabolism , Transforming Growth Factor beta1/metabolism
9.
Article in English | MEDLINE | ID: mdl-38517782

ABSTRACT

OBJECTIVE: This study involved an analysis of preoperative deep vein thrombosis (DVT) incidence and changes in coagulation function among elderly patients suffering from hip fractures. The objective was to offer guidance on the prevention and management of preoperative DVT in the lower extremities of elderly individuals with hip fractures. METHODS: A total of 282 elderly individuals with a hip fracture were enrolled and divided into two groups based on the location of the fracture: femoral intertrochanteric fracture (FIF, 161 individuals) and femoral neck fracture (FNF, 121 individuals). The two groups were compared with respect to baseline characteristics, including gender, age, and comorbid chronic diseases. Furthermore, the analysis encompassed the incidence of preoperative DVT in both lower extremities, along with seven coagulation parameters and platelet count before the surgical procedure. RESULTS: There was no significant difference in baseline information between the two groups. The incidence of preoperative DVT in the FIF group was higher than that in the FNF group, along with a significantly higher percentage of patients exhibiting increased levels of D-dimer and fibrinogen/fibrin degradation products (FDPs). CONCLUSION: Preoperative hypercoagulability and a greater prevalence of DVT were observed in elderly individuals with FIF compared to individuals with FNF. This indicates that clinicians should pay attention to elderly patients with FIFs, especially those with increased D-dimer and FDP levels.

10.
IET Syst Biol ; 18(2): 55-75, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458989

ABSTRACT

The main objective was to establish a prognostic model utilising long non-coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA-Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan-Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis-related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors' model, the high-risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , RNA, Long Noncoding , Humans , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , RNA, Long Noncoding/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Kaplan-Meier Estimate , Mutation , Tumor Microenvironment
11.
Chemistry ; 30(24): e202304056, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38379208

ABSTRACT

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

12.
PhytoKeys ; 237: 245-255, 2024.
Article in English | MEDLINE | ID: mdl-38333589

ABSTRACT

A new species of the genus Camellia (Theaceae), Camelliazijinica, discovered in the Danxia landscape from Guangdong Province, China, is characterized and illustrated. Phylogenetic analysis based on chloroplast genomes suggested its affinity with C.drupifera, C.oleifera and C.fluviatilis, however, it morphologically differs from all of the latter by leaf shape and size. Phonologically, it most closely resembles C.microphylla, but can be distinguished from the latter by its young branchlets glabrous (vs. densely pubescent), fewer bracteoles and sepals, diverse leaf shape, midvein raised slightly with sparsely pubescent or glabrous (vs. prominently with densely pubescent) and leaf adaxially matt (vs. vernicose) when dried. By morphological and molecular analyses, Camelliazijinica represented a distinct new species of C.sect.Paracamellia.

13.
PhytoKeys ; 237: 257-268, 2024.
Article in English | MEDLINE | ID: mdl-38333592

ABSTRACT

Lysimachiadanxiashanensis, a new Primulaceae species, endemic to the Danxia landscape in Guangdong Province, China, is described and illustrated. This new species is morphologically similar to L.pseudohenryi, L.phyllocephala, L.congestiflora and L.kwangtungensis, but it differs from the similar species by its purplish-red plants, petiole without wings, calyx with orange glandular and the corolla margin serrated on upper half with orange-red glandular punctates. This new species belongs to Lysimachiasubgen.Lysimachiasect.Nummularia. Phylogenetic analysis confirmed that L.danxiashanensis is a distinct clade, based on the combined data of ITS and rbcL sequences. The conservation status of the new species was evaluated as Endangered (EN) according to IUCN Red List Categories and Criteria.

14.
JCI Insight ; 9(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38193533

ABSTRACT

There are no therapies to prevent emphysema progression. Chymotrypsin-like elastase 1 (CELA1) is a serine protease that binds and cleaves lung elastin in a stretch-dependent manner and is required for emphysema in a murine antisense oligonucleotide model of α-1 antitrypsin (AAT) deficiency. This study tested whether CELA1 is important in strain-mediated lung matrix destruction in non-AAT-deficient emphysema and the efficacy of CELA1 neutralization. Airspace simplification was quantified after administration of tracheal porcine pancreatic elastase (PPE), after 8 months of cigarette smoke (CS) exposure, and in aging. In all 3 models, Cela1-/- mice had less emphysema and preserved lung elastin despite increased lung immune cells. A CELA1-neutralizing antibody was developed (KF4), and it inhibited stretch-inducible lung elastase in ex vivo mouse and human lung and immunoprecipitated CELA1 from human lung. In mice, systemically administered KF4 penetrated lung tissue in a dose-dependent manner and 5 mg/kg weekly prevented emphysema in the PPE model with both pre- and postinjury initiation and in the CS model. KF4 did not increase lung immune cells. CELA1-mediated lung matrix remodeling in response to strain is an important contributor to postnatal airspace simplification, and we believe that KF4 could be developed as a lung matrix-stabilizing therapy in emphysema.


Subject(s)
Emphysema , Pulmonary Emphysema , Animals , Humans , Mice , Aging , Elastin , Pancreatic Elastase , Pulmonary Emphysema/prevention & control , Swine
15.
Nat Struct Mol Biol ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38243114

ABSTRACT

During the first lineage segregation, a mammalian totipotent embryo differentiates into the inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell-fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first lineage specification in early mouse embryos, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found that TFAP2C, a trophoblast regulator, bound and activated both early TE and inner cell mass (ICM) genes at the totipotent (two- to eight-cell) stages ('bipotency activation'). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, and Tdgf1, and early TE genes, including Tfeb and Itgb5, in eight-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early ICM genes but acquired binding to late TE genes in blastocysts, where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes, where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, 'bipotency activation' in totipotent embryos also applied to a pluripotency regulator NR5A2, which similarly bound and activated both ICM and TE lineage genes at the eight-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.

16.
Article in English | MEDLINE | ID: mdl-38192148

ABSTRACT

OBJECTIVE: In recent years, it has been known that mesenchymal stem cells (MSCs) have the potential to treat osteoarthritis (OA). This study aimed to investigate the effects of intraarticular injection of human adipose-derived stem cells (hADSCs) in a new double-damage rabbit osteoarthritis model. METHODS: The OA model was established surgically first by medial collateral ligament and anterior insertional ligament transection and medical meniscectomy, then by articular cartilage full-thickness defect. At six weeks following surgery, hADSCs were labeled with Enhanced Green Fluorescence Protein expressing lentivirus FG12 and injected into the knee joints. All rabbits were sacrificed at 4- and 8 weeks post-surgery. Assessments were carried out by macroscopic examination, immunohistochemistry staining, magnetic resonance imaging, qRT-PCR and ELISA analysis. RESULTS: At 4- and 8 weeks, hADSCs injection showed less cartilage loss, few fissures and few cracks, decreased volume of joint effusion and cartilage defect measured with MRI. Furthermore, ELISA and qRT-PCR methods showed that hADSCs treatment increased the level of IGF-1. CONCLUSIONS: Our data suggest that hADSC transplantation promotes articular cartilage healing in the double-damage rabbit osteoarthritis model, IGF-1 may play an essential role in the hADSC-based cartilage repair process. Transplantation of hADSCs may be suitable for clinical application in the treatment of osteoarthritis.

17.
Eur J Pharmacol ; 964: 176278, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38158116

ABSTRACT

Portal hypertension (PHT) is a syndrome caused by systemic and portal hemodynamic disturbances with the progression of cirrhosis. However, the exact mechanisms regulating angiogenesis-related responses in PHT remain unclear. Cediranib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, exhibiting a greater affinity for VEGFR-2. Liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague-Dawley rats. Sham-operated rats were controls. BDL and sham rats were randomly allocated to receive Cediranib or vehicle after BDL. On the 28th day, portal hypertension related parameters were surveyed. Cediranib treatment could significantly reduce the portal pressure (PP) in BDL rats, while it did not affect the mean arterial pressure (MAP) in sham groups and BDL groups. Cediranib treatment could significantly affect the stroke volume (SV), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), superior mesenteric artery (SMA) flow and SMA resistance in BDL groups and BDL with Cediranib groups. Cediranib treatment could improve the mesenteric vascular remodeling and contractility. Cediranib treatment significantly reduced mesenteric vascular density. And phospho-VEGFR-2 was significantly downregulated by Cediranib. On the other hand, phospho-endothelial Nitric Oxide Synthases (phospho-eNOS) expressions were upregulated. Cediranib not only improved splanchnic hemodynamics, extrahepatic vascular remodeling and vasodilation, but also alleviated intrahepatic fibrosis and collagen deposition significantly. Cediranib treatment could reduce intrahepatic angiogenesis between BDL-vehicle and BDL-Cediranib rats. In conclusion, Cediranib could improve extrahepatic hyperdynamic circulation by inhibiting extrahepatic angiogenesis through inhibition of the VEGFR-2 signaling pathway, portal collateral circulation formation, as well as eNOS-mediated vasodilatation and vascular remodeling, and at the same time, Cediranib improved intrahepatic fibrogenesis and angiogenesis, which together alleviate cirrhotic PHT syndrome.


Subject(s)
Hypertension, Portal , Indoles , Quinazolines , Vascular Endothelial Growth Factor Receptor-2 , Animals , Rats , Disease Models, Animal , Hemodynamics/physiology , Hypertension, Portal/complications , Hypertension, Portal/drug therapy , Indoles/pharmacology , Indoles/therapeutic use , Liver Cirrhosis/chemically induced , Quinazolines/pharmacology , Quinazolines/therapeutic use , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vascular Remodeling
18.
Science ; 382(6676): eadi5516, 2023 12 15.
Article in English | MEDLINE | ID: mdl-38096290

ABSTRACT

Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF-enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.


Subject(s)
Blastocyst , Cell Lineage , Chromatin , Enhancer Elements, Genetic , Gene Expression Regulation, Developmental , SOXB1 Transcription Factors , Animals , Mice , Blastocyst/cytology , Blastocyst/metabolism , Cells, Cultured , Chromatin/metabolism , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Cell Differentiation/genetics , Cell Lineage/genetics
19.
PhytoKeys ; 236: 39-52, 2023.
Article in English | MEDLINE | ID: mdl-38058313

ABSTRACT

Cotoneasterdensiflorus, a new species of Rosaceae from western Sichuan, China, is described and illustrated. Morphologically, we inferred that the new species belongs to CotoneasterSer.Salicifolii sensu Yü et al. (1974) in the Flora of China and Fryer and Hylmö (2009). This species is most similar to C.salicifolius, but differs in its leaf blade of ovate-lanceolate to obovate shape (vs. elliptic-oblong to ovate-lanceolate), smaller length-width ratio of 2.37 ± 0.31 (vs. 3.17 ± 0.32), slightly conduplicate (vs. not conduplicate), less lateral veins of 6-8 pairs (vs. 12-16 pairs), upper surface slightly rugose (vs. rugose), leaf margin plane (vs. revolute), lower surface densely grey tomentose (vs. grey tomentose, with bloom), greater corolla diameter of 7-9 mm (vs. 5-6 mm), styles 2 (vs. 2-3), pyrenes 2 (vs. 2-3), larger pollen grains P/E values of 2.05 ± 0.12 (vs. 1.19 ± 0.05) and leaf epidermis type W (vs. type I). Based on phylogenetic analysis of the whole chloroplast genome, C.densiflorus is sister to C.rhytidophyllus, but distantly related to C.salicifolius.

20.
Sensors (Basel) ; 23(24)2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38139532

ABSTRACT

Multi-input multi-output and non-orthogonal multiple access (MIMO-NOMA) Internet-of-Things (IoT) systems can improve channel capacity and spectrum efficiency distinctly to support real-time applications. Age of information (AoI) plays a crucial role in real-time applications as it determines the timeliness of the extracted information. In MIMO-NOMA IoT systems, the base station (BS) determines the sample collection commands and allocates the transmit power for each IoT device. Each device determines whether to sample data according to the sample collection commands and adopts the allocated power to transmit the sampled data to the BS over the MIMO-NOMA channel. Afterwards, the BS employs the successive interference cancellation (SIC) technique to decode the signal of the data transmitted by each device. The sample collection commands and power allocation may affect the AoI and energy consumption of the system. Optimizing the sample collection commands and power allocation is essential for minimizing both AoI and energy consumption in MIMO-NOMA IoT systems. In this paper, we propose the optimal power allocation to achieve it based on deep reinforcement learning (DRL). Simulations have demonstrated that the optimal power allocation effectively achieves lower AoI and energy consumption compared to other algorithms. Overall, the reward is reduced by 6.44% and 11.78% compared the to GA algorithm and random algorithm, respectively.

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