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1.
Cell ; 179(6): 1342-1356.e23, 2019 11 27.
Article in English | MEDLINE | ID: mdl-31759698

ABSTRACT

Mammalian switch/sucrose non-fermentable (mSWI/SNF) complexes are multi-component machines that remodel chromatin architecture. Dissection of the subunit- and domain-specific contributions to complex activities is needed to advance mechanistic understanding. Here, we examine the molecular, structural, and genome-wide regulatory consequences of recurrent, single-residue mutations in the putative coiled-coil C-terminal domain (CTD) of the SMARCB1 (BAF47) subunit, which cause the intellectual disability disorder Coffin-Siris syndrome (CSS), and are recurrently found in cancers. We find that the SMARCB1 CTD contains a basic α helix that binds directly to the nucleosome acidic patch and that all CSS-associated mutations disrupt this binding. Furthermore, these mutations abrogate mSWI/SNF-mediated nucleosome remodeling activity and enhancer DNA accessibility without changes in genome-wide complex localization. Finally, heterozygous CSS-associated SMARCB1 mutations result in dominant gene regulatory and morphologic changes during iPSC-neuronal differentiation. These studies unmask an evolutionarily conserved structural role for the SMARCB1 CTD that is perturbed in human disease.


Subject(s)
Chromatin Assembly and Disassembly/genetics , Chromosomal Proteins, Non-Histone/metabolism , Mutation/genetics , Nucleosomes/metabolism , SMARCB1 Protein/genetics , Transcription Factors/metabolism , Amino Acid Sequence , Enhancer Elements, Genetic/genetics , Female , Genome, Human , HEK293 Cells , HeLa Cells , Heterozygote , Humans , Male , Models, Molecular , Mutant Proteins/chemistry , Mutant Proteins/metabolism , Protein Binding , Protein Domains , SMARCB1 Protein/chemistry , SMARCB1 Protein/metabolism
2.
J Immunol ; 211(7): 1154-1166, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37610222

ABSTRACT

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-ß1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-ß/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development.


Subject(s)
Bronchiolitis Obliterans Syndrome , Mesenchymal Stem Cells , Humans , Animals , Mice , Bone Marrow , Nestin , Macrophages
3.
Nano Lett ; 24(18): 5562-5569, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38682815

ABSTRACT

Transition metal trichalcogenides (TMTCs) offer remarkable opportunities for tuning electronic states through modifications in chemical composition, temperature, and pressure. Despite considerable interest in TMTCs, there remain significant knowledge gaps concerning the evolution of their electronic properties under compression. In this study, we employ experimental and theoretical approaches to comprehensively explore the high-pressure behavior of the electronic properties of TiS3, a quasi-one-dimensional (Q1D) semiconductor, across various temperature ranges. Through high-pressure electrical resistance and magnetic measurements at elevated pressures, we uncover a distinctive sequence of phase transitions within TiS3, encompassing a transformation from an insulating state at ambient pressure to the emergence of an incipient superconducting state above 70 GPa. Our findings provide compelling evidence that superconductivity at low temperatures of ∼2.9 K is a fundamental characteristic of TiS3, shedding new light on the intriguing high-pressure electronic properties of TiS3 and underscoring the broader implications of our discoveries for TMTCs in general.

4.
Radiology ; 311(3): e231937, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38916510

ABSTRACT

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.


Subject(s)
Absorptiometry, Photon , Neural Networks, Computer , Osteoporosis , Radiography, Thoracic , Humans , Female , Osteoporosis/diagnostic imaging , Male , Radiography, Thoracic/methods , Absorptiometry, Photon/methods , Aged , Mass Screening/methods , Middle Aged
5.
Fish Shellfish Immunol ; 145: 109353, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38184180

ABSTRACT

In the past decade, the outbreak of Streptococcus agalactiae has caused significant economic losses in tilapia farming. Vaccine immunization methods and strategies have gradually evolved from single-mode to multi-mode overall prevention and control strategies. In this study, an inactivated vaccine of S. agalactiae with a chitosan oligosaccharide (COS) adjuvant was constructed using different administration methods: intraperitoneal injection (Ip), immersion combined with intraperitoneal injection (Im + Ip), immersion combined with oral administration (Im + Or), and oral administration (Or). Safety analysis revealed no adverse effects on tilapia, and the vaccine significantly promoted fish growth and development when administered through Im + Or or Or immunization. Following vaccination, innate immunity parameters including SOD, ACP and CAT activities were all significantly enhanced. Additionally, specific serum IgM antibodies reached their highest level at the 6th week post vaccination. Skin and intestinal mucus IgT antibodies reached peaked at the 6th and 7th week post vaccination, respectively. The relative peak expression values for IL-8, IL-12, MHC-I, MHC-II, IgM, IgT, CD4, CD8, TNFα, IFNγ from Im + Ip group were significantly higher than those in Ip group, Im + Or group and Or group in most cases (p < 0.05). Importantly, the relative protection survival of Im + Ip group was the highest (78.6%), followed by the Ip group (71.4%), the Or group (64.3%) and the Im + Or group (57.1%). In summary, this study encourages further research on multi-channel immunization strategies of other kinds of vaccines in other aquatic economic animals to improve their disease resistance.


Subject(s)
Chitosan , Cichlids , Fish Diseases , Streptococcal Infections , Tilapia , Animals , Streptococcus agalactiae , Bacterial Vaccines , Vaccination , Immunity, Innate , Immunoglobulin M , Oligosaccharides
6.
Cardiol Young ; 34(4): 748-753, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37814585

ABSTRACT

BACKGROUND: Early diagnosis of acute coronary syndrome is more and more important because of its mortality and morbidity. Hypertension is one of the pathogenesis of acute coronary syndrome, which often leads to stenosis and ischaemia. Ischaemia-modified albumin is sensitive for the occurrence of ischaemia, which attracted us in the significance of ischaemia-modified albumin in patients with chest pain, especially patients complicated with hypertension. METHODS: In total, 200 patients with acute chest pain were included in the study. According to the diagnostic criteria, patients were divided into acute coronary syndrome group and non-ischaemic chest pain group. Cardiac biomarkers were measured with 30 minutes in emergency department, including cardiac troponin T, creatine kinase MB, and ischaemia-modified albumin. Receiver operating characteristic curve (ROC) analysis was used for the sensitivity and specificity of ischaemia-modified albumin in the early diagnosis of acute coronary syndrome. Comparisons between ischaemia-modified albumin and cardiac Troponin T were done between groups. RESULTS: The demographics in two groups were not significantly different in most aspects. Compared with non-ischaemic chest pain group, serum levels of ischaemia-modified albumin and cardiac Troponin T were significantly higher in acute coronary syndrome group. ROC analysis showed that ischaemia-modified albumin had a good sensitivity and specificity in early diagnosis of acute coronary syndrome. The level of ischaemia-modified albumin in acute coronary syndrome patients with hypertension was higher than that in non-ischaemic chest pain patients. CONCLUSIONS: In patients complained with acute chest pain, the serum measurement of ischaemia-modified albumin is potential valuable for the early diagnosis of acute coronary syndrome, especially combined with ECG. The serum level of ischaemia-modified albumin in acute coronary syndrome patients is significantly associated with hypertension.


Subject(s)
Acute Coronary Syndrome , Hypertension , Serum Albumin, Human , Humans , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnosis , Troponin T , Biomarkers , Clinical Relevance , Serum Albumin , Sensitivity and Specificity , Chest Pain/diagnosis , Chest Pain/etiology , Hypertension/complications , Hypertension/diagnosis , Ischemia
7.
Nano Lett ; 23(22): 10282-10289, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37906179

ABSTRACT

Quasiparticles consisting of correlated electron(s) and hole(s), such as excitons and trions, play important roles in the optical phenomena of van der Waals semiconductors and serve as unique platforms for studies of many-body physics. Herein, we report a gate-tunable exciton-to-trion transition in pressurized monolayer MoSe2, in which the electronic band structures are modulated continuously within a diamond anvil cell. The emission energies of both the exciton and trion undergo large blueshifts over 90 meV with increasing pressure. Surprisingly, the trion binding energy remains constant at 30 meV, regardless of the applied pressure. Combining ab initio density functional theory calculations and quantum Monte Carlo simulations, we find that the remarkable robustness of the trion binding energy originates from the spatially diffused nature of the trion wave function and the weak correlation between its constituent electron-hole pairs. Our findings shed light on the optical properties of correlated excitonic quasiparticles in low-dimensional materials.

8.
Plant Biotechnol J ; 21(2): 342-353, 2023 02.
Article in English | MEDLINE | ID: mdl-36278914

ABSTRACT

The widespread application of isoproturon (IPU) can cause serious pollution to the environment and threaten ecological functions. In this study, the IPU bacterial N-demethylase gene pdmAB was transferred and expressed in the chloroplast of soybean (Glycine max L. 'Zhonghuang13'). The transgenic soybeans exhibited significant tolerance to IPU and demethylated IPU to a less phytotoxic metabolite 3-(4-isopropylphenyl)-1-methylurea (MDIPU) in vivo. The transgenic soybeans removed 98% and 84% IPU from water and soil within 5 and 14 days, respectively, while accumulating less IPU in plant tissues compared with the wild-type (WT). Under IPU stress, transgenic soybeans showed a higher symbiotic nitrogen fixation performance (with higher total nodule biomass and nitrogenase activity) and a more stable rhizosphere bacterial community than the WT. This study developed a transgenic (TS) soybean capable of efficiently removing IPU from its growing environment and recovering a high-symbiotic nitrogen fixation capacity under IPU stress, and provides new insights into the interactions between rhizosphere microorganisms and TS legumes under herbicide stress.


Subject(s)
Glycine max , Soil , Biodegradation, Environmental , Glycine max/genetics , Glycine max/metabolism , Phenylurea Compounds/metabolism
9.
Nat Mater ; 21(7): 773-778, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35710630

ABSTRACT

Complex correlated states emerging from many-body interactions between quasiparticles (electrons, excitons and phonons) are at the core of condensed matter physics and material science. In low-dimensional materials, quantum confinement affects the electronic, and subsequently, optical properties for these correlated states. Here, by combining photoluminescence, optical reflection measurements and ab initio theoretical calculations, we demonstrate an unconventional excitonic state and its bound phonon sideband in layered silicon diphosphide (SiP2), where the bound electron-hole pair is composed of electrons confined within one-dimensional phosphorus-phosphorus chains and holes extended in two-dimensional SiP2 layers. The excitonic state and emergent phonon sideband show linear dichroism and large energy redshifts with increasing temperature. Our ab initio many-body calculations confirm that the observed phonon sideband results from the correlated interaction between excitons and optical phonons. With these results, we propose layered SiP2 as a platform for the study of excitonic physics and many-particle effects.

10.
J Org Chem ; 88(23): 16581-16588, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37976463

ABSTRACT

An iron-catalyzed efficient C-H amination for the construction of imidazole-fused-ring systems was developed under aerobic conditions. Compared to previous studies, this work exhibited green features. The reaction was conducted in the green solvent anisole, with water as the only byproduct. Four C(sp3)-H bonds were cleaved and three C-N bonds were formed in this transformation. Imidazo[1,5-a]pyridine-, imidazo[5,1-b]oxazole-, imidazo[5,1-b]thiazole-, imidazo[1,5-a]pyrazine-, and imidazo[1,5-a]imidazole-related N-heterocycles were obtained in acceptable-to-excellent yield.

11.
Org Biomol Chem ; 21(29): 5985-5989, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37435618

ABSTRACT

A convenient method for the alkylation of 3-arylbenzo[d]isoxazoles with maleimides under redox-neutral conditions has been developed, giving a series of substituted succinimides in up to 99% yield. This transformation is highly selective to give succinimides, and Heck-type products are successfully avoided. This protocol features 100% atom-economy and broad substrate tolerance, and provides a novel strategy for the synthesis of diverse succinimides and an opportunity for the succinylation of protein medication and for pharmacologists to discover first-in-class drugs.

12.
Cancer ; 128(11): 2138-2147, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35315510

ABSTRACT

BACKGROUND: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. METHODS: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse events (AEs). RESULTS: Twenty-six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%-91.5%) and an ORR of 88.5% (95% CI, 71.0%-96.0%). Twenty patients survived, and 6 died. The 2-year EFS and OS rates were 75.0% (95% CI, 54.5%-88.3%) and 76.9% (95% CI, 54.2%-90.4%), respectively. Six patients experienced grade 3 or 4 treatment-related AEs, including moderate chronic graft-vs-host disease (n = 3), grade 3 or 4 acute graft-vs-host disease (n = 2), and grade 3 skin rash (n = 1). No treatment-related deaths occurred during the therapy of refractory CNSL. CONCLUSIONS: Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. LAY SUMMARY: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.


Subject(s)
Central Nervous System Neoplasms , Graft vs Host Disease , Leukemia , Central Nervous System , Central Nervous System Neoplasms/drug therapy , Humans , Recurrence , Retrospective Studies , Sorafenib
13.
Appl Environ Microbiol ; 87(11)2021 05 11.
Article in English | MEDLINE | ID: mdl-33771783

ABSTRACT

1-Naphthol, a widely used raw material for organic synthesis, is also a well-known organic pollutant. Due to its high toxicity, 1-naphthol is rarely used by microorganisms as the sole carbon source for growth. In this study, catabolism of 1-naphthol by Sphingobium sp. strain B2 was found to be greatly enhanced by additional supplementation with primary carbon sources (e.g., glucose, maltose, and sucrose), and 1-naphthol was even used as the carbon source for growth when strain B2 cells had been preinduced by both 1-naphthol and glucose. A distinct two-component flavin-dependent monooxygenase, NdcA1A2, was found to be responsible for the initial hydroxylation of 1-naphthol to 1,2-dihydroxynaphthalene, a more toxic compound. Transcriptional levels of ndcA1A2 genes were significantly upregulated when strain B2 cells were cultured with both 1-naphthol and glucose compared to cells cultured with only 1-naphthol or glucose. Two transcriptional regulators, the activator NdcS and the inhibitor NdcR, were found to play key roles in the synergistic regulation of the transcription of the 1-naphthol initial catabolism genes ndcA1A2IMPORTANCE Cometabolism is a widely observed phenomenon, especially in the field of microbial catabolism of highly toxic xenobiotics. However, the mechanisms of cometabolism are ambiguous, and the roles of the obligately coexisting growth substrates remain largely unknown. In this study, we revealed that the roles of the coexisting primary carbon sources (e.g., glucose) in the enhanced catabolism of the toxic compound 1-naphthol in Sphingobium sp. strain B2 were not solely because they were used as growth substrates to support cell growth but, more importantly, because they acted as coinducers to interact with two transcriptional regulators, the activator NdcS and the inhibitor NdcR, to synergistically regulate the transcription of the 1-naphthol initial catabolism genes ndcA1A2 Our findings provide new insights into the cometabolic mechanism of highly toxic compounds in microorganisms.


Subject(s)
Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Mixed Function Oxygenases/genetics , Naphthols/metabolism , Sphingomonadaceae/genetics , Bacterial Proteins/metabolism , Mixed Function Oxygenases/metabolism , Sphingomonadaceae/enzymology
14.
Adv Exp Med Biol ; 1280: 277-290, 2021.
Article in English | MEDLINE | ID: mdl-33791989

ABSTRACT

Oral/head and neck cancer is the sixth most common human malignancies in the world. Despite the treatment advances in surgery, chemotherapy, and radiotherapy, the patient survival has not been significantly improved in the past several decades. As a new methodological approach, metabolomics may help reveal the metabolic reprogramming mechanisms underlying head and neck cancer cell proliferation, invasion, and metastasis and may be used to identify metabolite biomarkers for clinical applications of the disease. In this chapter, we briefly review recent metabolomic applications in head and neck cancer.


Subject(s)
Head and Neck Neoplasms , Biomarkers , Humans , Metabolomics
15.
Ecotoxicol Environ Saf ; 226: 112874, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34628155

ABSTRACT

Pharmaceuticals in aquatic environment displayed adverse effects to fish. The effects are usually related to the internal levels of pharmaceuticals accumulated in specific fish tissues. In this study, we investigated the uptake, elimination, and toxicokinetics of six pharmaceuticals, e.g. naproxen (NAX), diclofenac (DCF), ibuprofen (IBU), carbamazepine (CBZ), fluoxetine (FLX), and sertraline (SER), in 11 fish tissues of Nile tilapia. The experiments were conducted in a flow-through system with an 8-day uptake/8-day elimination periods. The fish exposure groups involved the control, single FLX, and mixture of six pharmaceuticals at environmentally relevant concentration of 4 µg/L. FLX and SER showed the maximum concentrations of 145 and 201 ng/g wet weight, respectively, in fish spleen tissue, while NAX and IBU were not detected in any tissue. The mean concentrations for the pharmaceuticals in Nile tilapia tissues generally followed the order: bile> kidney, gut, stomach, liver> brain, gill, spleen> plasma, skin, muscle. The steady-state bioconcentration factors in various tissues generally range at 0.74-437.58 L/kg. The uptake and elimination toxicokinetics illustrated the rapid accumulation and depuration of pharmaceuticals in fish tissues. The results help to understand the internal bioconcentration, tissue distribution, and toxicokinetics of pharmaceuticals in multiple fish biological compartments.


Subject(s)
Cichlids , Pharmaceutical Preparations , Water Pollutants, Chemical , Animals , Bioaccumulation , Toxicokinetics , Water Pollutants, Chemical/toxicity
16.
Environ Microbiol ; 22(1): 286-296, 2020 01.
Article in English | MEDLINE | ID: mdl-31667998

ABSTRACT

The (R)- and (S)-enantiomers of the chiral herbicide napropamide (NAP) show different biological activities and ecotoxicities. These two enantiomers behave differently in the environment due to enantioselective catabolism by microorganisms. However, the molecular mechanisms underlying this enantioselective catabolism remain largely unknown. In this study, the genes (snaH and snpd) involved in the catabolism of NAP were cloned from Sphingobium sp. B2, which was capable of catabolizing both NAP enantiomers. Compared with (R)-NAP, (S)-NAP was much more rapidly transformed by the amidase SnaH, which initially cleaved the amide bonds of (S)/(R)-NAP to form (S)/(R)-2-(1-naphthalenyloxy)-propanoic acid [(S)/(R)-NP] and diethylamine. The α-ketoglutarate-dependent dioxygenase Snpd, showing strict stereoselectivity for (S)-NP, further transformed (S)-NP to 1-naphthol and pyruvate. Molecular docking and site-directed mutagenesis analyses revealed that when the (S)-enantiomers of NAP and NP occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated formation of the transition state complex. This study enhances our understanding of the preferential catabolism of the (S)-enantiomer of NAP on the molecular level.


Subject(s)
Amidohydrolases/metabolism , Dioxygenases/metabolism , Herbicides/chemistry , Herbicides/metabolism , Naphthalenes/chemistry , Naphthalenes/metabolism , Amidohydrolases/chemistry , Amidohydrolases/genetics , Dioxygenases/chemistry , Dioxygenases/genetics , Molecular Docking Simulation , Mutagenesis, Site-Directed , Sphingomonadaceae/enzymology , Sphingomonadaceae/genetics , Stereoisomerism
17.
BMC Infect Dis ; 20(1): 899, 2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33256643

ABSTRACT

BACKGROUND: COVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission. METHODS: COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson's χ2-test or Fisher's exact test, and continuous variables were analyzed using Student's t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method. RESULTS: A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P < 0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P < 0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P = 0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P = 0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P < 0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P < 0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P < 0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973). CONCLUSIONS: A nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Heart Diseases/epidemiology , Nomograms , Pandemics , Patient Admission , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/virology , China/epidemiology , Chronic Disease/epidemiology , Comorbidity , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Lymphocytes , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment/methods , Risk Factors , Survival Rate
18.
Chaos ; 30(1): 013104, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32013467

ABSTRACT

Complex networks have found many applications in various fields. An important problem in theories of complex networks is to find factors that aid link prediction, which is needed for network reconstruction and to study network evolution mechanisms. Though current similarity-based algorithms study factors of common neighbors and local paths connecting a target node pair, they ignore factor information on paths between a node and its neighbors. Therefore, this paper first supposes that paths between nodes and neighbors provide basic similarity features. Accordingly, we propose a so-called relative-path-based method. This method utilizes factor information on paths between nodes and neighbors, besides paths between node pairs, in similarity calculation for link prediction. Furthermore, we solve the problem of determining the parameters in our algorithm as well as in other algorithms after a series of discoveries and validations. Experimental results on six disparate real networks demonstrate that the relative-path-based method can obtain greater prediction accuracy than other methods, as well as performance robustness.

19.
Am J Respir Cell Mol Biol ; 60(6): 705-716, 2019 06.
Article in English | MEDLINE | ID: mdl-30742493

ABSTRACT

Bicarbonate facilitates mucin unpacking and bacterial killing; however, its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through the cystic fibrosis (CF) transmembrane conductance regulator (CFTR; ABCC7) anion channel, and this is defective in CF. The anion exchanger pendrin (SLC26A4) also mediates HCO3- efflux and is upregulated by proinflammatory cytokines. Here, we examined pendrin and CFTR expression and their contributions to HCO3- secretion by human nasal and bronchial epithelia. In native tissue, both proteins were most abundant at the apical pole of ciliated surface cells with little expression in submucosal glands. In well-differentiated primary nasal and bronchial cell cultures, IL-4 dramatically increased pendrin mRNA levels and apical immunostaining. Exposure to low-Cl- apical solution caused intracellular alkalinization (ΔpHi) that was enhanced fourfold by IL-4 pretreatment. ΔpHi was unaffected by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) or CFTR inhibitor CFTRinh-172, but was reduced by adenoviral shRNA targeting pendrin. Forskolin increased ΔpHi, and this stimulation was prevented by CFTRinh-172, implicating CFTR, yet forskolin only increased ΔpHi after pendrin expression had been induced by IL-4. The dependence of ΔpHi on pendrin suggests there is minimal electrical coupling between Cl- and HCO3- fluxes and that CFTR activation increases anion exchange-mediated HCO3- influx. Conversely, inducing pendrin expression increased forskolin-stimulated, CFTRinh-172-sensitive current by approximately twofold in epithelial and nonepithelial cells. We conclude that pendrin mediates most HCO3- secretion across airway surface epithelium during inflammation and enhances electrogenic Cl- secretion via CFTR, as described for other SLC26A transporters.


Subject(s)
Bicarbonates/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Lung/metabolism , Respiratory Mucosa/metabolism , Sulfate Transporters/metabolism , Animals , Antiporters/metabolism , Cell Line , Chloride-Bicarbonate Antiporters/metabolism , Colforsin/pharmacology , Cyclic AMP/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Hydrogen-Ion Concentration , Interleukin-4/genetics , Interleukin-4/metabolism , Ion Transport/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Respiratory Mucosa/drug effects , Sulfate Transporters/genetics
20.
Phys Rev Lett ; 123(4): 047203, 2019 Jul 26.
Article in English | MEDLINE | ID: mdl-31491273

ABSTRACT

The recent discovery of intrinsic ferromagnetic order in the atomically thin van der Waals crystal CrXTe_{3} (X=Si, Ge) stimulates intensive studies on the nature of low-dimensional magnetism because the presence of long-range magnetic order in two-dimensional systems with continuous symmetry is strictly prohibited by thermal fluctuations. By combining advanced many-body calculations with angle-resolved photoemission spectroscopy we investigate CrSiTe_{3} single crystals and unveil the pivotal role played by the strong electronic correlations at both high- and low-temperature regimes. Above the Curie temperature (T_{c}), Coulomb repulsion (U) drives the system into a charge transfer insulating phase. In contrast, below T_{c} the crystal field arranges the Cr-3d orbitals such that the ferromagnetic superexchange profits, giving rise to the bulk ferromagnetic ground state with which the electronic correlations compete. The excellent agreement between theory and experiment establishes CrSiTe_{3} as a prototype low-dimensional crystal with the cooperation and interplay of electronic correlation and ferromagnetism.

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