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1.
Artigo em Inglês | MEDLINE | ID: mdl-35500147

RESUMO

ABSTRACT: Dual antiplatelet therapy (DAPT) is recommended among patients with established acute coronary syndrome (ACS). In this meta-analysis, we sought to compare the clinical outcomes between de-escalation versus unchanged DAPT based on both randomized controlled trials (RCTs) and observational studies. The primary outcomes were major adverse cardiovascular events (MACE) for observational studies and net clinical events for RCTs. Four RCTs and 17 observational studies with a total of 38741 patients were included. Net clinical events were more common with unchanged DAPT than with de-escalation in RCTs (OR:1.71; 95% CI:1.21-2.43; I2=69.4%), which was mainly due to higher risks of any bleeding (OR:1.81; 95% CI:1.14-2.88; I2=75.5%) and major bleeding (OR:1.58; 95% CI:1.02-2.46; I2=0), without significant differences in ischaemic events. However, trial sequential analysis revealed that sufficient information was obtained just for net clinical events, not for respective ischaemic or bleeding events in RCTs. In the analysis based on real-world observational studies, the risks of myocardial infarction (OR:0.77; 95% CI:0.61-0.98; I2=0) and stroke (OR:0.42; 95% CI:0.22-0.81; I2=0) were lower with unchanged DAPT group. Therefore, de-escalation of DAPT led to a marked reduction in net clinical events compared with unchanged DAPT in RCTs, which was mainly due to reduced bleeding events. However, sufficient information for ischaemic events was not obtained. In the analysis based on real-world observational studies, myocardial infarction and stroke were more common with de-escalation, which should arise our attention.

2.
Proc Natl Acad Sci U S A ; 119(19): e2116380119, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35500124

RESUMO

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

3.
BMC Surg ; 22(1): 156, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509041

RESUMO

BACKGROUND: Relapsed childhood polymicrobial osteomyelitis associated with dermatophytosis has not been reported in the literature. CASE PRESENTATION: Here we report on a case of a 45-year-old man who had left tibial osteomyelitis for 29 years, accompanied by skin fungal infection of the ipsilateral heel for 20 years, and underwent a second operation due to recurrence of polymicrobial infection 6 years ago. The patient had a history of injury from a rusty object, which penetrated the anterior skin of the left tibia middle segment causing subsequent bone infection, but was asymptomatic after receiving treatments in 1983. The patient was physically normal until dermatophytosis occurred on the ipsilateral heel skin in 1998. The patient complained that the dermatophytosis was gradually getting worse, and the tibial wound site became itchy, red, and swollen. The left tibial infection resurged in May 2012, leading to the patient receiving debridement and antibiotic treatment. H&E and Gram-stained histology was performed on biopsy specimens of sequestrum and surrounding inflammatory tissue. Tissue culture and microbiology examination confirmed polymicrobial infection with Staphylococcus aureus (S. aureus) and Corynebacterium and a fungus. Additionally, the patient also received potassium permanganate for dermatophytosis when he was admitted into the hospital. CONCLUSIONS: Together with longitudinal follow-up of medical history, surgical findings, histopathological and microbiology culture evidence, we conclude that boyhood tibia polymicrobial osteomyelitis with S. aureus and Corynebacterium occurred in this patient, and the fungal activation of dermatophytosis may have led to osteomyelitis relapse.


Assuntos
Coinfecção , Osteomielite , Infecções Estafilocócicas , Tinha , Antibacterianos , Criança , Coinfecção/complicações , Coinfecção/diagnóstico , Desbridamento , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/complicações , Osteomielite/diagnóstico , Infecções Estafilocócicas/complicações , Staphylococcus aureus , Tíbia/cirurgia , Tinha/complicações
4.
Adv Mater ; : e2202382, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526081

RESUMO

The practical application of Zn metal anode for aqueous batteries is greatly restricted by the catastrophic dendrite growth, intricate hydrogen evolution and parasitic surface passivation. Herein, a polyanionic hydrogel film is introduced as a protective layer on Zn anode with the assistance of saline coupling agent (denote as Zn-SHn). The hydrogel framework with zincophilic -SO3 - functional group uniformizes the zinc ions flux and transport. Furthermore, such a hydrogel layer chemically bonded on the Zn surface possesses an anti-catalysis effect, which effectively suppresses both hydrogen evolution reaction and Zn dendrites formation. As a result, stable and reversible Zn stripping/plating at various currents and capacities is achieved. A full cell by pairing the Zn-SHn anode with a NaV3 O8 •1.5 H2 O cathode shows a capacity of around 176 mAh g-1 with a retention around 67% over 4000 cycles at 10 A g-1 . This polyanionic hydrogel film protection strategy paves a new way for future Zn anode design and safe aqueous batteries construction. This article is protected by copyright. All rights reserved.

5.
Nat Metab ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551509

RESUMO

Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of type-2 diabetes. However, cellular signaling machineries that control GSIS remain incompletely understood. Here, we report that ß-klotho (KLB), a single-pass transmembrane protein known as a co-receptor for fibroblast growth factor 21 (FGF21), fine tunes GSIS via modulation of glycolysis in pancreatic ß-cells independent of the actions of FGF21. ß-cell-specific deletion of Klb but not Fgf21 deletion causes defective GSIS and glucose intolerance in mice and defective GSIS in islets of type-2 diabetic mice is mitigated by adenovirus-mediated restoration of KLB. Mechanistically, KLB interacts with and stabilizes the cytokine receptor subunit GP130 by blockage of ubiquitin-dependent lysosomal degradation, thereby facilitating interleukin-6-evoked STAT3-HIF1α signaling, which in turn transactivates a cluster of glycolytic genes for adenosine triphosphate production and GSIS. The defective glycolysis and GSIS in Klb-deficient islets are rescued by adenovirus-mediated replenishment of STAT3 or HIF1α. Thus, KLB functions as a key cell-surface regulator of GSIS by coupling the GP130 receptor signaling to glucose catabolism in ß-cells and represents a promising therapeutic target for diabetes.

7.
Aging (Albany NY) ; 14(undefined)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503998

RESUMO

OBJECTIVE: To uncover novel prognostic and therapeutic targets for BLCA, our study is the first to investigate the role of hsa-mir-183 and its up-regulated predicted target genes in bladder urothelial carcinoma. METHODS: To address this issue, our study explored the roles of hsa-mir-183 predicted target genes in the prognosis of BLCA via UALCAN, Metascape, Kaplan-Meier plotter, Human Protein Atlas, TIMER2.0, cBioPortal and Genomics of Drug Sensitivity in Cancer databases. RESULTS: High transcriptional expressions of PDCD6, GNG5, PHF6 and MAL2 were markedly relevant to favorable OS in BLCA patients, whereas SLC25A15 and PTDSS1 had opposite expression significance. Additionally, high transcriptional expression of PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 were significantly correlated with BLCA individual cancer stages and molecular subtypes. Furthermore, high mutation rate of PDCD6, MAL2, SLC25A15 and PTDSS1 were observed. Finally, TP53 mutation of PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 has guiding significance for drug selection in BLCA. CONCLUSIONS: PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 could be the advanced independent indicators for prognosis of BLCA patients, and TP53-mutation might be a biomarker for drug option in BLCA patients.

8.
IEEE Trans Cybern ; PP2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35560093

RESUMO

In this work, a novel dynamic-memory event-triggered load frequency control (LFC) approach for the power system is proposed considering the existence of hybrid attacks. A dynamic-memory event-triggered mechanism (DMETM) is first presented under denial-of-service (DoS) attacks to reduce the occupation of network communication bandwidth. Different from the existing event-triggered mechanisms (ETMs), the superiority of DMETM is that not only the past transmitted packets can be utilized but also the amount of utilized packets can be adjusted according to the state error of the power system. Then, the general LFC model of the power system is reconstructed as a switched system on account of the existence of DoS attacks and deception attacks. Based on the reconstructed switched model, an exponentially mean-square stability criterion with an performance index is derived by constructing appropriate Lyapunov-Krasovskii functionals (LKFs). Furthermore, the DMETM controllers and event-triggered weighting matrices can be obtained by solving the relevant linear matrix inequalities (LMIs). Finally, some illustrated examples are presented to demonstrate the feasibility and effectiveness of the approach proposed.

9.
J Sep Sci ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562644

RESUMO

In this study, a new method for determination of fipronil and its three metabolites in environmental water samples was developed based on meltblown nonwoven fabric solid-phase extraction combining with gas chromatography-electron capture detection. As the core material of medical mask, meltblown nonwoven fabric is made of polypropylene superfine fibers which are randomly distributed and bonded together with a relatively large specific surface area and good permeability. Polypropylene as a high molecular hydrocarbon-based polymer, has the characteristics of good hydrophobicity and lipophilicity, which can be applied for separation and enrichment of hydrophobic substances in food, environment and biology samples. The meltblown nonwoven fabric is soft and can fill the solid-phase extraction cartridge tightly. This aspect also makes it suitable to be used as an ideal solid-phase extraction sorbent. A series of parameters influencing the extraction efficiency were investigated, and under the optimized conditions, fipronil and its three metabolites had good linear relationship in the range of 0.2-100 µg/L with correlation coefficient R2 more than 0.999. The recoveries at three spiked concentrations were in the range of 99.2-107.3% with the relative standard deviations less than 9.8% (intra-day) and 8.1% (inter-day). The limit of detection for the four target analytes were in the range of 0.02-0.06 µg/L. Finally, this method was successfully applied in the analysis of fipronil and its three metabolites in various types of environmental water samples. This article is protected by copyright. All rights reserved.

10.
Carbohydr Polym ; 290: 119469, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550764

RESUMO

Three-dimensional (3D) bioprinting holds promise for precise repair of bone defects, but rapid formation of effective vascularized tissue by 3D-printed construct is still a challenge. In this study, deferoxamine (DFO)-loaded ethosomes (Eth) were combined with gelatin methacrylate (GelMA)/gellan gum methacrylate (GGMA) hybrid bioink to fabricate 3D-printed scaffold by photo- and ion-crosslinking. The GelMA/GGMA bioinks showed excellent printability and improved mechanical property through the double-crosslinking method. In vitro experiments showed that Eth-DFO@GelMA/GGMA scaffold had good cytocompatibility while achieved sustained release of DFO, which significantly promoted endothelial cells migration and tube formation, mineralized matrix deposition and alkaline phosphatase expression of osteoblast. In vivo experiments of rat cranial defect model demonstrated that composite scaffold could promote angiogenesis and bone regeneration by activating the hypoxia-inducible factor 1-α (HIF1-α) signaling pathway. In conclusion, this 3D bioprinted Eth-DFO@GelMA/GGMA scaffold can couple angiogenesis and osteogenesis, and will be a promising candidate for the bone defects treatment.

11.
Planta ; 255(6): 122, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35554686

RESUMO

MAIN CONCLUSION: AaZFP1, a C2H2-type transcription factor, was found to bind the AGT-N1-10-AGT box of AaIPPI1pro and activate the expression of AaIPPI1 involved in artemisinin biosynthesis. Artemisinin, an endoperoxide sesquiterpene lactone, is a widely used antimalarial drug isolated from Artemisia annua L. Isopentenyl pyrophosphate isomerase (AaIPPI1) catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate and is the key gene involved in the biosynthesis of artemisinin. However, the AaIPPI1 gene regulation network remains largely unknown. Here, we isolated the AaIPPI1 promoter (AaIPPI1pro) and predicted that it contains cis-elements involved in stress responses, including the TGACG motif (a methyl jasmonate-responsive element), GARE motif (a gibberellin-responsive element), ABRE (an abscisic acid-responsive element), TC-rich repeats (a stress-responsive element), and the AGT-N1-10-AGT box, which is the binding site of Cys/His2 zinc finger protein (C2H2 ZFP). The C2H2 ZFP gene AaZFP1 was discovered by screening a cDNA library using AaIPPI1pro as bait in yeast. AaZFP1 contains two conserved C2H2 regions, a nuclear localization domain (B box), a Leu-rich domain (L box), and a conserved DLN sequence (DLN box) close to its C terminus. A subcellular localization assay indicated that AaZFP1 protein is localized in the nucleus and cytoplasm. An electrophoretic mobility shift assay demonstrated that AaZFP1 binds to the AGT-N1-10-AGT box of AaIPPI1pro. A dual-luciferase assay indicated that AaZFP1 enhanced the promoter activity of AaIPPI1 in vivo. Transient overexpression of AaZFP1 in A. annua increased the expression of AaIPPI1 and the content of artemisinin. Our data demonstrated that AaZFP1 functions as a transcriptional activator that regulates the expression of AaIPPI1 by directly binding to its promoter. The present study provides insights into the transcriptional regulation of genes involved in artemisinin biosynthesis in A. annua.

13.
Front Plant Sci ; 13: 871006, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557722

RESUMO

When homozygously fertile plants were induced using doubled haploid (DH) induction lines Y3380 and Y3560, the morphology of the induced F1 generation was basically consistent with the female parent, but the fertility was separated, showing characteristics similar to cytoplasmic male sterile (CMS) and maintainer lines. In this study, the morphology, fertility, ploidy, and cytoplasm genotype of the induced progeny were identified, and the results showed that the sterile progeny was polima cytoplasm sterile (pol CMS) and the fertile progeny was nap cytoplasm. The molecular marker and test-cross experimental results showed that the fertile progeny did not carry the restorer gene of pol CMS and the genetic distance between the female parent and the offspring was 0.002. This suggested that those inductions which produced sterile and fertile progeny were coordinated to CMS and maintainer lines. Through the co-linearity analysis of the mitochondrial DNA (mtDNA), it was found that the rearrangement of mtDNA by DH induction was the key factor that caused the transformation of fertility (nap) into sterility (pol). Also, when heterozygous females were induced with DH induction lines, the induction F2 generation also showed the segregation of fertile and sterile lines, and the genetic distance between sterile and fertile lines was approximately 0.075. Therefore, the induction line can induce different types of female parents, and the breeding of the sterile line and the maintainer line can be achieved through the rapid synchronization of sister crosses and self-crosses. The induction of DH inducer in B. napus can provide a new model for the innovation of germplasm resources and open up a new way for its application.

14.
Front Immunol ; 13: 798583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558067

RESUMO

Purpose: Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level. Experimental Design: Single-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors. Results: HNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance. Conclusion: At the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35543248

RESUMO

Acinetobacter baumannii  is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii  LPS, four Kdo-containing inner core glycans from A. baumannii  strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7- O -di- tert -butylsilylene or 5- O -benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against  A. baumannii.

17.
Cancer Discov ; : OF1-OF12, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543554

RESUMO

The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection.

18.
Comput Biol Med ; 146: 105573, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35533460

RESUMO

Chromosome aberration (CA) is a serious genotoxicity of a compound, leading to carcinogenicity and developmental side effects. In the present manuscript, we developed a QSAR model for CA prediction using artificial intelligence methodologies. The reliable QSAR model was constructed based on an enlarged data set of 3208 compounds by optimizing machine learning and deep learning algorithms based on hyperparametric iterations and using multiple descriptors of molecular fingerprint in combination with drug-like molecular properties (MP) screened by entropy weight methodology on the open-source Python platform. Furthermore, molecular similarity for returning search and molecular connection index for additional descriptor were additionally introduced to differentiate the compounds with high similarity for correct CA prediction for QSAR model generation. The final generated CA-(Q)SAR model exhibited good prediction accuracy of 80.6%. The bias of the final model is about 0.9793. On the basis of generated QSAR model, data analyses were further performed to analyze the typical structure features in numerical intervals (MPI) of molecular properties MW, XlogP, and TPSA, respectively, for potential CA or non-CA toxicity with a normalized occurrence probability (NOP) more than 70%, which may provide useful clues for drug design of leads or candidate devoid of CA genotoxicity.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35564363

RESUMO

The effect of a specific Chinese swimmer's trunk oscillation on dolphin kick was investigated in order to optimize competitive swimming movement. Using a numerical simulation method based on multi-body motion, different swimmer's trunk oscillation during a dolphin kick was analyzed. The simulation was conducted using 3D incompressible Navier-Stokes equations and renormalization group k-ε turbulence model, combined with the Volume of Fluid method to capture the water surface. The simulation's results were evaluated by comparing them with experimental data and with previous studies. The net streamwise forces, mean swimming velocity, and joint moments were also investigated. There was a positive correlation between the mean swimming velocity and the amplitudes of the swimmer's trunk oscillation, where the Pearson correlation coefficient was 0.986 and the selected model was statistically significant (p < 0.05). In addition, as the mean swimming velocity increased from 1.42 m/s in Variant 1 to 2 m/s in Variant 5, the maximum positive moments of joints increased by about 24.7% for the ankles, 27.4% for the knees, -3.9% for the hips, and 5.8% for the upper waist, whereas the maximum negative moments of joints increased by about 64.5% for the ankles, 28.1% for the knees, 23.1% for the hips, and 10.1% for the upper waist. The relationship between the trunk oscillation and the vortices was also investigated. Therefore, it is recommended that swimmers should try to increase the amplitudes of trunk oscillation to increase their swimming velocity. In order to achieve this goal, swimmers should increase strength training for the ankles, knees, and upper waist during the upkick. Moreover, extra strength training is warranted for the ankles, knees, hips, and upper waist during the downkick.

20.
J Clin Med ; 11(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35566588

RESUMO

BACKGROUND: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. METHODS: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. RESULTS: During a median follow-up of 8.0 months (range, 1.9-15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. CONCLUSIONS: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

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