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1.
Biology (Basel) ; 10(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546519

RESUMO

Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, PPO1 and PPO2. High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33554598

RESUMO

Solar-driven conversion of nitrogen (N2) to ammonia (NH3) is highly appealing, yet in its infancy, the low photocatalytic efficiency and unclear adsorption and activation mechanisms of N2 are still issues to be addressed. In this study, ultrathin alloyed Mo1-xWxS2 nanosheets with tunable hexagonal (2H)/trigonal (1T) phase ratios were proposed to boost photoreduction N2 efficiency, while the mechanisms of N2 adsorption and activation were explored simultaneously. The alloyed Mo1-xWxS2 nanosheets for the 1T phase concentration of 33.6% and Mo/W = 0.68:0.32 were proven to reach about 111 µmol gcat-1 h-1 under visible light, which is 3.7 (or 3)-fold higher than that of pristine MoS2 (or WS2). With the aid of density functional theory calculations and in situ N2 adsorption X-ray absorption near-edge fine structure techniques, the adsorption and activation behaviors of N2 over the interface of Mo1-xWxS2 nanosheets were investigated during the N2 reduction process. The results show that the W doping causes a higher electron density state in W 5d orbitals, which can further polarize the adsorbed N2 molecules for adsorption and activation. This work provides a new insight into the adsorption and activation mechanisms for the NH3 synthesis.

3.
BMC Med Inform Decis Mak ; 21(1): 50, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568163

RESUMO

BACKGROUND: This study aims to explore the information chain management model of large instrument and equipment inter-working in the operating room (OR) led by information nurses. METHODS: Through the chain management process of large instruments and equipment in the OR, which was based on information nurses, the management model of inter-working and integrating information chain was established, the key links were controlled, and the whole life cycle management of instruments and equipment from expected procurement to scrapping treatment was realized. Using the cluster sampling method, 1562 surgical patients were selected. Among these patients, 749 patients were assigned to the control group before the running mode, and 813 patients were assigned to the observation group after the running mode. The related indexes for large instrument and equipment management in the department before and after the running mode were compared. RESULTS: In the observation group, the average time of equipment registration was (22.05 ± 2.36), the cost was reduced by 2220 yuan/year, and the satisfaction rate of the nursing staff was 97.62%. These were significantly better, when compared to the control group (P < 0.05). Furthermore, the awareness rate of the whole staff for equipment repair application was 95.12%, and the arrival time of maintenance personnel and the examination and approval time of equipment management were greatly shortened (P < 0.05). CONCLUSION: The integrated management model of large instrument and equipment interworking in the OR based on chain flow realizes the whole life cycle management of instruments and equipment, which is essential to improve management efficiency.

4.
Biochem Pharmacol ; : 114453, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33545119

RESUMO

A novel PMet-P(cdmPEG2K) polymeric micellar carrier was developed for tumor-targeted co-delivery of DOX and nucleic acids (NA), based on polymetformin and a structure designed to lose the PEG shell in response to the acidic extracellular tumor environment. NA/DOX co-loaded micelleplexes exhibited enhanced inhibition of cell proliferation compared to DOX-loaded micelles, and displayed a higher level of cytotoxicity at an acidic pH (6.8) which mimicks the tumor microenvironment. The PMet-P(cdmPEG2K) micelles achieved significantly improved transfection with either a reporter plasmid or Cy3-siRNA, and enhanced DOX intracellular uptake in 4T1.2 cells at pH 6.8. Importantly, PMet-P(cdmPEG2K) micelles showed excellent pEGFP (EGFP expression plasmid) transfection in an aggressive murine breast cancer (4T1.2) model. By using a plasmid encoding IL-12 (pIL-12), we investigated the combined effect of chemotherapy and gene therapy. PMet-P(cdmPEG2K) micelles co-loaded with DOX and pIL-12 were more effective at inhibiting tumor growth compared to micelles loaded with DOX or pIL-12 alone. In addition, this micellar system was effective in co-delivery of siRNA and DOX into tumor cells. Our results suggest that PMet-P(cdmPEG2K) has the potential for chemo and nucleic acid combined cancer therapy.

5.
PLoS One ; 16(2): e0246877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33566870

RESUMO

BACKGROUND AND PURPOSE: Obesity is an established risk factor for ischemic stroke but the association of increased body mass index (BMI) with survival after ischemic stroke remains controversial. Many studies have shown that increased BMI has a "protective" effect on survival after stroke while other studies have debunked the "obesity paradox". This study aimed at examining the relationship between BMI and all-cause mortality at one year in first-time ischemic stroke patients using a large dataset extracted from different resources including electronic health records. METHODS: This was a retrospective cohort study of consecutive ischemic stroke patients captured in our Geisinger NeuroScience Ischemic Stroke (GNSIS) database. Survival in first-time ischemic stroke patients in different BMI categories was analyzed using Kaplan Meier survival curves. The predictors of mortality at one-year were assessed using a stratified Cox proportional hazards model. RESULTS: Among 6,703 first-time ischemic stroke patients, overweight and obese patients were found to have statistically decreased hazard ratio (HR) compared to the non-overweight patients (overweight patients- HR = 0.61 [95% CI, 0.52-0.72]; obese patients- HR = 0.56 [95% CI, 0.48-0.67]). Predictors with a significant increase in the hazard ratio for one-year mortality were age at the ischemic stroke event, history of neoplasm, atrial fibrillation/flutter, diabetes, myocardial infarction and heart failure. CONCLUSION: Our study results support the obesity paradox in ischemic stroke patients as shown by a significantly decreased hazard ratio for one-year mortality among overweight and obese patients in comparison to non-overweight patients.

6.
Waste Manag ; 123: 80-87, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571832

RESUMO

Enriched in phosphorus, sewage sludge ash has been extensively studied and applied as a secondary source for phosphorus recovery. Wet extraction, especially acid washing, is one of the most feasible methods to recover phosphorus from the ash due to its ease of operation, high efficiency and low cost. However, the management of the resultant acid residue was seldom addressed. In this study, special focus was paid to the reuse and recycling of the acid residue by an alkaline activation method. Its adsorption performance towards four different heavy metals in aqueous solutions was evaluated by batch and fixed-bed column adsorption experiments. The obtained material showed a high BET specific area (98.29 m2/g) and a total pore volume (0.114 cm3/g), and effectively removed Cd(II), Cu(II), Pb(II) and Zn(II) from aqueous solutions with the maximum adsorption capacity of around 26.8, 22.2, 53.3 and 13.5 mg/g respectively. It could be loaded in a fixed-bed column to continuously remove heavy metals especially for Pb(II). The proposed method to recycle the acid residue makes the wet extraction methods designing to recover phosphorus from incinerated sewage sludge complete without the generation of waste, which contributes to circular economy and a sustainable future.

7.
Sci Total Environ ; 775: 145841, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33621881

RESUMO

The present study examined potential effect modifiers between polycyclic aromatic hydrocarbon (PAH) exposure and the development of rheumatoid arthritis (RA) and elucidated the relationship between PAHs and RA in subgroups using data from the National Health and Nutrition Examination Survey (NHANES) (2003-2014). The relatedness between eight PAH metabolites and RA in the whole population and different subgroups was tested using multivariable logistic regression analyses. This study included 6297 participants, including 400 RA patients and 5897 non-RA control participants, with full data. Compared to the lowest quartiles, risk of RA was increased in population with the highest quartiles of 1-hydroxynaphthalene (1-NAP), 2-NAP, 2-hydroxyfluorene (2-FLU), and 3-FLU in a bias factor corrected model. The associations between urinary PAH metabolites and RA were prominent in female, young and middle-aged, obese, smoking and alcohol-consuming populations in the subgroup analysis. Our results demonstrated that PAH exposure was related to RA, and the relationship between urinary PAH metabolites and RA differed between subgroups and depended on specific PAH metabolites.

8.
J Neurol Sci ; 422: 117339, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33592506

RESUMO

INTRODUCTION: The stroke mortality rate has gradually declined due to improved interventions and controlled risk factors. We investigated the associated factors and trends in recurrence and all-cause mortality in ischemic stroke patients from a rural population in the United States between 2004 and 2018. METHODS: This was a retrospective cohort study based on electronic health records (EHR) data. A comprehensive stroke database called "Geisinger NeuroScience Ischemic Stroke (GNSIS)" was built for this study. Clinical data were extracted from multiple sources, including EHR and quality data. RESULTS: The cohort included in the study comprised of 8561 consecutive ischemic stroke patients (mean age: 70.1 ± 13.9 years, men: 51.6%, 95.1% Caucasian). Hypertension was the most prevalent risk factor (75.2%). The one-year recurrence and all-cause mortality rates were 6.3% and 16.1%, respectively. Although the one-year stroke recurrence increased during the study period, the one-year stroke mortality rate decreased significantly. Age > 65 years, atrial fibrillation or flutter, heart failure, and prior ischemic stroke were independently associated with one-year all-cause mortality in stratified Cox proportional hazards model. In the Cause-specific hazard model, diabetes, chronic kidney disease and age < 65 years were found to be associated with one-year ischemic stroke recurrence. CONCLUSION: Although all-cause mortality after stroke has decreased, stroke recurrence has significantly increased in stroke patients from rural population between 2004 and 2018. Older age, atrial fibrillation or flutter, heart failure, and prior ischemic stroke were independently associated with one-year all-cause mortality while diabetes, chronic kidney disease and age less than 65 years were predictors of ischemic stroke recurrence.

9.
Clin Pharmacol Ther ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483974

RESUMO

Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and liver cancer patient survival was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Conclusion: TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.

10.
ACS Nano ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33428399

RESUMO

Taking advantage of outstanding precision in target recognition and trans-cleavage ability, the recently discovered CRISPR/Cas12a system provides an alternative opportunity for designing fluorescence biosensors. To fully exploit the analytical potential, we introduce here some meaningful concepts. First, the collateral cleavage of CRISPR/Cas12a is efficiently activated in a functional DNA regulation manner and the bottleneck which largely applicable to nucleic acids detection is broken. After selection of a representative aptamer and DNAzyme as the transduction pathways, the sensing coverage is extended to a small organic compound (ATP) and a metal ion (Na+). The assay sensitivity is significantly improved by utilizing a bead-supported enrichment strategy wherein emerging holographic optical tweezers are used to enhance imaging stability and simultaneously achieve multiflux analysis. Last, a sandwich-structured energy-concentrating upconversion nanoparticle triggered boosting luminescent resonance energy transfer mode is comined to face with complicated biological samples by skillfully confining the emitters into a very limited inner shell. Following the above attempts, the developed CRISPR/Cas12a biosensors not only present an ultrasensitive assay behavior toward these model non-nucleic acid analytes but also can serve as a formidable toolbox for determining real samples including single cell lysates and human plasma, proving a good practical application capacity.

11.
Gut ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431576

RESUMO

OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

12.
Org Lett ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438394

RESUMO

A visible-light photoredox catalyzed radical cascade cyclization of simple ethers with cyanamides is developed at room temperature. This strategy involves sequential inert Csp3-H/Csp2-H functionalizations through intermolecular addition reaction of oxyalkyl radicals to N-cyano groups followed by radical cyclization of iminyl radicals in situ generated with C-2 aryl rings. This method allows for efficient synthesis of tetracyclic benzo[4,5]imidazo[1,2-c]quinazolines. Importantly, this is the first example of an intermolecular-intramolecular radical cascade cyclization reaction of cyanamides.

13.
Soft Matter ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439210

RESUMO

The dynamics of the wrapping of a charged flexible microfiber around an oppositely charged curved particle immersed in a viscous fluid is investigated. We observe that the wrapping behavior varies with the radius and Young's modulus of the fiber, the radius of the particle, and the ionic strength of the surrounding solution. We find that wrapping is primarily a function of the favorable interaction energy due to electrostatics and the unfavorable deformation energy needed to conform the fiber to the curvature of the particle. We perform an energy balance to predict the critical particle radius for wrapping, finding reasonably good agreement with experimental observations. In addition, we use mathematical modeling and observations of the deflected shape of the free end of the fiber during wrapping to extract a measurement of the Young's modulus of the fiber. We evaluate the accuracy and potential limitations of this in situ measurement when compared to independent mechanical tests.

15.
Nat Mater ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432142

RESUMO

Structure-activity relationships built on descriptors of bulk and bulk-terminated surfaces are the basis for the rational design of electrocatalysts. However, electrochemically driven surface transformations complicate the identification of such descriptors. Here we demonstrate how the as-prepared surface composition of (001)-terminated LaNiO3 epitaxial thin films dictates the surface transformation and the electrocatalytic activity for the oxygen evolution reaction. Specifically, the Ni termination (in the as-prepared state) is considerably more active than the La termination, with overpotential differences of up to 150 mV. A combined electrochemical, spectroscopic and density-functional theory investigation suggests that this activity trend originates from a thermodynamically stable, disordered NiO2 surface layer that forms during the operation of Ni-terminated surfaces, which is kinetically inaccessible when starting with a La termination. Our work thus demonstrates the tunability of surface transformation pathways by modifying a single atomic layer at the surface and that active surface phases only develop for select as-synthesized surface terminations.

16.
Orthop Surg ; 13(1): 338-341, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410291

RESUMO

BACKGROUND: Pedicle screw insertion has been known to have several complications even in the most skilled surgical hands. However, injury to the thoracic aorta during pedicle screw insertion is rare, delayed presentation secondary to pseudoaneurysm is even rarer, the pseudoaneurysm formation caused by a series of malpositioned pedicle screws has perhaps not been reported so far. CASE PRESENTATION: In this paper, we report here a case in which inadvertent injury to the thoracic aorta resulted in pseudoaneurysm, its manifestation was initially vague, resulting in a delayed diagnosis. Delayed aortic pseudoaneurysm or injury can be asymptomatic for a long time. Patients with renewed or continued back pain should alert orthopaedic surgeons regarding the possibility of pseudoaneurysms, regardless of the period that has elapsed after pedicle screw implantation.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33410725

RESUMO

This paper presents a computational fluid dynamics (CFD) study of air-particle flows in the upper tracheobronchial tree. Two respiratory tract models, including a parametrically controlled approximate airway model developed by Kitaoka (KG model) and a CT-based patient specific airway (realistic model) were used. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting ultrafine particles in sequentially bifurcating rigid bronchial airways, airflow patterns and particle transport/deposition in these two airway models were evaluated and compared. Overall deposition efficiency data was compared with the widely adopted ICRP data published by The International Commission on Radiological Protection. Good deposition efficiency agreements were observed between the present respiratory tract models and the ICRP data, which validated the numerical prediction accuracy of the present computational fluid-particle dynamics (CFPD) model. For the two respiratory models, the comparison showed both difference and similarity between the approximate KG model and the realistic model. Specifically, the realistic model showed more complicated airflow patterns due to the increased surface irregularity. The deposition efficiency data revealed a deposition preference in the first-generation airways compared to the rest regions. For ultrafine particles smaller than 10 nm, Brownian diffusion remains the dominant particle deposition mechanism. However, for ultrafine particles with size ranging from 10 nm to 100 nm, the deposition efficiency decreased dramatically with the 100 nm particles approaching to zero deposition in the present bronchial tree scope. The generation-by-generation deposition data presented in this paper is indispensable to the formulation of new lung inhalation exposure models.

18.
Adv Healthc Mater ; : e2001718, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33458966

RESUMO

Materials that can regulate the composition and structure of the cell membrane to fabricate engineered cells with defined functions are in high demand. Compared with other biomolecules, DNA has unique advantages in cell membrane engineering due to its excellent programmability and biocompatibility. Especially, the near-atomic scale precision of DNA nanostructures facilitates the investigation of structure-property relations on the cell membrane. In this review, first the state of the art of functional DNA nanostructures is summarized, and then the overview of the use of DNA nanostructures to engineer the cell membrane is presented. Subsequently, applications of DNA nanostructures in modifying cell membrane morphology, controlling ions transport, and synthesizing high precise liposomes are highlighted. Finally, the challenges and outlook on using DNA nanostructures for cell membrane engineering are discussed.

19.
J Gen Virol ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459587

RESUMO

Baculoviruses are large DNA viruses that replicate within the nucleus of infected host cells. Therefore, many viral proteins must gain access to the nucleus for efficient viral genome replication, gene transcription and virion assembly. To date, the global protein localization pattern of baculoviral proteins is unknown. In this study, we systematically analysed the nuclear localization of 154 ORFs encoded by the prototypic baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), either during transient expression or with super-infection of the virus. By transient expression of vectors containing egfp-fused ORFs, we found that in the absence of virus infection, 25 viral proteins were localized in the nucleus. Most of these, which we called 'auto-nuclear localization' proteins, are related to virus replication, transcription or virion structure, and 20 of them contain predicted classical nuclear localization signal. Upon virus infection, 11 proteins, which originally localized in the cytoplasm or both cytoplasm and nucleus in the transfection assays, were completely translocated into the nucleus, suggesting that their nuclear import is facilitated by other viral or host proteins. Further co-transfection experiments identified that four of the 11 proteins, including P143, P33, AC73 and AC114, were imported into the nucleus with the assistance of the auto-nuclear localization proteins LEF-3 (for P143), TLP (for P33) and VP80 (for both AC73 and AC114). This study presents the first global nuclear localization profile of AcMNPV proteins and provides useful information for further elucidation of the mechanisms of baculovirus nuclear entry and gene functions.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33491864

RESUMO

Understanding the complex interplay among gasotransmitters is of great significance but remains technically challenging. In this study, we present the design and synthesis of a dually responsive BOD-NH-SC reporter for probing the dynamic and alternating existence of NO and H 2 S in living cells. This designed reporter can repeatedly cycle S-nitrosation and transnitrosation reactions when successively treated with NO and H 2 S, thus affording the interchange of NIR fluorescence at 645 nm (NO) and NIR II fluorescence at 936 nm (H 2 S). In light of this unique fluorescence alternation between two colors, we synthesized water-soluble BOD-NH-SC dots to visualize the intracellular dynamics of NO and H 2 S. These molecular probes thus provide a toolbox to elucidate the interplaying roles of NO and H 2 S in the complex interaction networks of various signal transduction pathways.

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