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1.
Acad Radiol ; 2024 May 29.
Article En | MEDLINE | ID: mdl-38816317

BACKGROUND: To investigate the association between cardiovascular risk estimated using the Framingham Risk Score (FRS) and carotid stiffening determined using ultrafast pulse wave velocity (ufPWV) measurements in apparently healthy individuals. METHODS: We enrolled 1034 apparently healthy participants without known cardiovascular disease who underwent ufPWV measurements. Clinical and laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (PWV-BS), and pulse wave velocity at the end of systole (PWV-ES) were assessed. In FRS assessments based on major cardiovascular risk factors (CVRFs), participants were assigned into three risk categories: low risk (<10%, n = 679), intermediate risk (10-20%, n = 191), and high risk (>20%, n = 164); the low-risk category was further subdivided into three subcategories: < 1% (n = 58), 1%- 5% (n = 374) and > 5% (n = 247). Multivariate logistic regression analyses with crude and adjusted odds ratios (ORs) were used to evaluate the association of carotid stiffening and FRS-based risk stratification. RESULTS: Carotid stiffening indicated by PWV-BS and PWV-ES differed notably between the FRS-estimated low-risk vs. intermediate-risk and high-risk categories, but only PWV-ES differed notably among the low-risk subcategories (all p < 0.010), and correlated notably with the FRS-estimated risk most obviously in low-risk participants (r = 0.517). In participants with cIMT < 0.050 cm, only PWV-ES differed significantly among the FRS-estimated risk categories (all p < 0.001). Increased PWV-BS (adjusted OR: 1.49; p = 0.003) and PWV-ES (adjusted OR: 1.29; p = 0.007) were both associated with FRS categories independent of conventional CVRFs in low- vs. intermediate-risk categories, but not in low- vs. high-risk categories (all p > 0.050). CONCLUSION: In vivo imaging of carotid stiffening by ufPWV measurements is independently linked to FRS categories, and ufPWV indices may help stratify differing levels of cardiovascular risk in apparently healthy young people. AVAILABILITY OF DATA AND MATERIAL: Data generated or analyzed during the study are available from the corresponding author by reasonable request.

2.
PLoS Pathog ; 20(4): e1012116, 2024 Apr.
Article En | MEDLINE | ID: mdl-38557908

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.


COVID-19 , mRNA Vaccines , Animals , Humans , Mice , COVID-19 Vaccines , Macaca mulatta , COVID-19/prevention & control , Immunization, Secondary , Mice, Transgenic , RNA, Messenger/genetics , SARS-CoV-2/genetics , Antibodies, Neutralizing , Antibodies, Viral
3.
Quant Imaging Med Surg ; 14(1): 75-85, 2024 Jan 03.
Article En | MEDLINE | ID: mdl-38223093

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

4.
Sci Bull (Beijing) ; 68(23): 3003-3012, 2023 Dec 15.
Article En | MEDLINE | ID: mdl-37919162

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number of variants, particularly with the emergence of Omicron with many sub-variants. These variants have exhibited increased immune escape, leading to reduced efficacy of existing vaccines and therapeutic antibodies. Given the diminished cross-neutralization observed among these variants, it is plausible that SARS-CoV-2 has developed multiple serotypes. As the major antigenic site, the receptor-binding domain (RBD) of viral spike (S) protein was chosen for serotyping. We selected 23 representative variants, including pre-Omicron variants and Omicron sub-variants, and classified them into five serotypes based on systematic evaluation of the antigenicities of their RBDs. Each serotype includes several genetically distinct variants. Serotype-I encompasses all pre-Omicron variants (with two subtypes), while the remaining four serotypes are all comprised of Omicron sub-variants at different stages of evolution. We propose that these serotypes can serve as a foundation for rapid classification of newly emerging SARS-CoV-2 variants, and guide the development of future broad-spectrum vaccines and neutralizing antibodies against the coronavirus disease 2019 (COVID-19).


COVID-19 , Vaccines , Humans , SARS-CoV-2/genetics , Serogroup
5.
Biosaf Health ; 5(2): 89-100, 2023 Apr.
Article En | MEDLINE | ID: mdl-37123450

With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine (IV) in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

6.
Ultrasonography ; 42(1): 89-99, 2023 Jan.
Article En | MEDLINE | ID: mdl-36588181

PURPOSE: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). METHODS: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)-normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292). Correlation analyses and comparisons were performed among the groups and in the cIMT subgroups (cIMT ≥0.050 cm and <0.050 cm). RESULTS: cIMT and PWV-ES significantly differed among the BP groups (P<0.05). The BP groups had similar PWV-BS when cIMT <0.050 cm or cIMT ≥0.050 cm (all P>0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P<0.001 and P=0.024) and HT (all P<0.001) groups in both cIMT categories, while the PWV-ES in the PHT group were not significantly lower than in the HT group (all P>0.05). CONCLUSION: Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.

7.
Article En | MEDLINE | ID: mdl-36159583

CAG is the most common precancerous disease of gastric cancer, which belongs to a kind of chronic gastritis. CAG is in close association with gastric cancer, which makes itself a critical node clinically in cancer prevention and treatment. Curcumol is a main active monomer in Fuzheng Huowei decoction, which has the properties of antioxidant, antiviral, and antitumor. In this study, the expression of SDF-1α/CXCR4/NF-κB was detected by in vivo and in vitro methods. Then, we found that the expressions of NF-κB, SDF-1α, CXCR4, and p-NF-κB were decreased in the curcumol treatment group. Curcumol inhibited gastric cancer cells' viability, migration, and invasion and induced their apoptosis. After adding the lentivirus overexpressing SDF-1α to the curcumol treatment group, it was found that SDF-1α, CXCR4, NF-κB, and p-NF-κB protein expressions were all increased, and the effect of curcumol on gastric cancer cells was reversed. In the nude mouse experiment, the tumor volume in the curcumol + SDF-1α group was the largest, and the tumor volume in the Fuzheng Huowei decoction + NC group was the smallest. In conclusion, curcumol effectively protects gastric tissue and inhibits the viability of gastric cancer cells, and curcumol regulates SDF-1α/CXCR4/NF-κB to play a therapeutic role in chronic atrophic gastritis and gastric cancer.

8.
J Oncol ; 2022: 3919053, 2022.
Article En | MEDLINE | ID: mdl-36131788

CAG is an essential procession of the transformation from gastritis into gastric cancer. A series of timely moves of diagnosis, treatment, and monitoring towards CAG to anticipate the potential population at risk of gastric cancer is an effective means to prevent gastric cancer occurrence. The main active monomer in Fuzheng Huowei Decoction is Curcumol, which is an indispensable ingredient in the treatment to CAG and gastric cancer. In this study, the CAG model, in vitro cultured gastric cancer cells, and participating nude mice were treated with Curcumol, and alterations in SDF-1α/CXCR4/VEGF expression were estimated using the assays of immunohistochemistry and Western blot. MTT, flow cytometry, transwell, HE staining, and tumor volume determination were applied for the verification of the regulatory effects of Curcumol on CAG and gastric cancer cells. The results showed that the expressions of VEGF, SDF-1α, CXCR4, and CD34 decreased in our CAG model with Curcumol treatment. Curcumol is in procession of an inhibitory effect toward the activity, migration, and invasion of gastric cancer cells, and it would also result in gastric cancer cells' apoptosis. We subsequently added SDF-1α overexpressing lentivirus to the Curcumol-treated group and found that the expressions of SDF-1α, CXCR4, and VEGF protein increased, and the inhibitory effect of Curcumol on gastric cancer cells was withdrawn. Our nude mouse experiment showed that Curcumol + SDF-1α group ended up with the largest tumor volume, while Fuzheng Huowei + NC group was with the smallest tumor volume. In conclusion, Curcumol is able to effectively protect the gastric tissue and suppress gastric cancer cells' viability. Curcumol functions as a therapeutic factor in chronic atrophic gastritis and gastric cancer by downregulating SDF-1α/CXCR4/VEGF expression.

9.
J Med Virol ; 94(11): 5492-5506, 2022 11.
Article En | MEDLINE | ID: mdl-35879101

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression.


Cytomegalovirus Infections , Immediate-Early Proteins , Adenosine Triphosphatases/metabolism , Cytomegalovirus/genetics , DNA-Binding Proteins/metabolism , Humans , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Promyelocytic Leukemia Protein/genetics , Promyelocytic Leukemia Protein/metabolism , Virus Replication
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121346, 2022 Oct 15.
Article En | MEDLINE | ID: mdl-35660144

RhB@ZrT-1-OH composite was constructed by introduction of Rhodamine B (RhB) into the cages of zirconium-based metal-organic cage that had two fluorescence emission peaks at 466 and 612 nm upon excitation at 327 nm. The dual-emission fluorescence sensor exhibits ultra-high sensitive detection for malachite green (MG) and glycine (Gly) in phosphate buffer solution (pH = 6.86). RhB@ZrT-1-OH as a ratiometric fluorescence probe was applied to detect MG with a low LOD of 0.2879 µM and presented obvious fluorescence visual changes from orange to purple to blue under 254 nm UV-vis lamp. Moreover, RhB@ZrT-1-OH also can be utilized as a "turn-on" fluorescence sensor to recognize Gly with a low LOD of 0.3747 µM and exhibits fluorescence color changes from orange to pink to purple. Notably, the corresponding test papers for sensing MG and Gly were designed for recognize the concentration of MG and Gly. Furthermore, the dual-emission fluorescence sensor can be used to detect MG and Gly in fish and human serum with high sensitivity and reliable. The possible detecting mechanisms of RhB@ZrT-1-OH for sensing MG and Gly were detailedly explored.


Fluorescent Dyes , Glycine , Animals , Fluorescence , Metals , Rhodamines , Rosaniline Dyes
11.
Ultrasound Med Biol ; 48(8): 1528-1536, 2022 08.
Article En | MEDLINE | ID: mdl-35595590

To establish and preliminarily validate an individualized reference of carotid stiffness quantified by ultrafast pulse wave velocity (ufPWV), our study included 225 healthy individuals in the modeling cohort and 628 individuals in the validation cohort. All participants underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole and pulse wave velocity-end of systole (PWV-ES). A threshold equation of estimated PWV-ES was obtained by multiple linear regression analysis in the modeling cohort as follows: estimated PWV-ES (m/s) = 0.080 × age (y) + 0.767 × low-density lipoprotein (mmol/L) + 0.040 × systolic blood pressure (mm Hg) + 0.372 × sex (male = 1, female = 0) - 2.803. With this equation, the validation cohort was divided into the low PWV-ES (actual PWV-ES ≤ estimated PWV-ES) and high PWV-ES (actual PWV-ES > estimated PWV-ES) groups. A clear boundary was found to be present between the low PWV-ES and high PWV-ES groups in the validation cohort. Participants with increasing PWV-ES increased with age gradually. We further subdivided participants into cIMT subgroups using a cutoff thickness of 0.050 cm. Diagnostic performance analysis revealed that the sensitivity and specificity of the threshold equation were 78.9% and 73.9%, respectively. We established and validated a novel individualized reference equation for estimated PWV-ES, which can likely expand the application of prospective ufPWV assessment.


Carotid Arteries/diagnostic imaging , Carotid Intima-Media Thickness , Pulse Wave Analysis , Vascular Stiffness/physiology , Cohort Studies , Female , Humans , Linear Models , Male , Prospective Studies , Sensitivity and Specificity , Ultrasonography
12.
Ultrasonography ; 41(3): 462-472, 2022 Jul.
Article En | MEDLINE | ID: mdl-35589550

PURPOSE: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV). METHODS: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs. RESULTS: cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P<0.05), but only PWV-ES increased gradually in age and SCORE-estimated risk subgroups (all P<0.05). Compared with cIMT (r=0.388, P<0.001) and PWV-BS (r=0.159, P<0.001), PWV-ES was more strongly correlated with SCORE categories (r=0.405, P<0.001). Higher PWV-ES values were associated with SCORE categories independently of sex, SBP, TC, and smoking in moderate-risk and high-risk subgroups (OR, 1.63; P<0.001 and OR, 2.12; P=0.024, respectively), but were not independent of age in all risk subgroups (all P>0.05). CONCLUSION: Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.

13.
ISA Trans ; 129(Pt A): 157-168, 2022 Oct.
Article En | MEDLINE | ID: mdl-35131093

This paper proposes an adaptive dual control with outlier detection that is robust to the occurrence of outliers in uncertain systems. Outliers occasionally exist in system process noise and observation noise, which could cause poor parameter estimation and degraded control performance of uncertain systems. For this reason, we devise an online outlier detection mechanism to filter the outliers so as to enhance the parameter estimation of uncertain systems. The devised mechanism makes decisions on outlier detection via the generated predicted regions where the newly arriving data is expected to locate, and the predicted regions are updated in real-time according to the historical data. The detection mechanism is integrated into the design of adaptive dual control, which is derived based on the bicriterial method. Compared with classical dual control merely considering uncertainty in input and output data stream, we are the first to include the uncontrollable excitations into the structure of dual control to fit practical scenarios, and this inclusion also provides an extensive cover on outliers to be detected. The improved performance of the proposed approach is verified using a mathematical model through one-time simulation and Monte Carlo simulations under different conditions, and we also evaluate our method in the control of fermentation sterilization process for more convincing results.


Models, Theoretical , Computer Simulation , Monte Carlo Method , Uncertainty
14.
J Virol ; 96(5): e0182721, 2022 03 09.
Article En | MEDLINE | ID: mdl-35020472

Human cytomegalovirus (HCMV) has a large (∼235 kb) genome with more than 200 predicted open reading frames that exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here, we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was upregulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and colocalized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. IMPORTANCE During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for antiviral treatment.


Cytomegalovirus Infections , Cytomegalovirus , Host Microbial Interactions , WD40 Repeats , Cytomegalovirus/genetics , Cytomegalovirus/metabolism , Cytomegalovirus Infections/physiopathology , Cytomegalovirus Infections/virology , Humans , Morphogenesis , Virion/metabolism , Virus Assembly/genetics , Virus Replication/genetics , WD40 Repeats/genetics , trans-Golgi Network/metabolism
15.
ISA Trans ; 123: 110-121, 2022 Apr.
Article En | MEDLINE | ID: mdl-34090667

Adaptive control has been successfully developed in deriving control law for stochastic systems with unknown parameters. The generation of reasonable control law depends on accurate parameter estimation. Recursive least square is widely used to estimate unknown parameters for stochastic systems; however, this approach only fits systems with Gaussian noises. In this paper, the adaptive quantile control is first proposed to cover the case where stochastic system noise follows sharp and thick tail distribution rather than Gaussian distribution. In the proposed approach, the system noise is modeled by the Asymmetric Laplace Distribution, and the unknown parameter is online estimated by our developed Bayesian quantile sum estimator, which combines recursive quantile estimations weighted by Bayesian posterior probabilities. With the real-time estimated parameter, the adaptive quantile control law is constructed based on the certainty equivalence principle. Our proposed estimator and controller are not computationally consuming and can be easily conducted in the Micro Controller Unit to fit practical applications. The comparison with some dominant controllers for the unknown stochastic system is conducted to verify the effectiveness of the adaptive quantile control.

16.
J Virol ; 95(8)2021 03 25.
Article En | MEDLINE | ID: mdl-33504601

We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WD repeat-containing protein 5 (WDR5) to facilitate capsid nuclear egress. Here, we further show that HCMV infection results in WDR5 localization in a juxtanuclear region, and that its localization to this cellular site is associated with viral replication and late viral gene expression. Furthermore, WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin (γ-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 co-immunoprecipitated with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain WDR5 accumulation in the vAC during infection. WDR5 fractionated with virions either in the presence or absence of Triton X-100 and was present in purified viral particles, suggesting that WDR5 was incorporated into HCMV virions. Thus, WDR5 localized to the vAC and was incorporated into virions, raising the possibility that in addition to capsid nuclear egress, WDR5 could also participate in cytoplasmic HCMV virion morphogenesis.Importance Human cytomegalovirus (HCMV) has a large (∼235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are reorganized to establish the virion assembly compartment (vAC), which has been shown to necessary for efficient assembly of progeny virions. We previously reported that WDR5 facilitates HCMV nuclear egress. Here, we show that WDR5 is localized to the vAC and incorporated into virions, perhaps contributing to efficient virion maturation. Thus, findings in this study identified a potential role for WDR5 in HCMV assembly in the cytoplasmic phase of virion morphogenesis.

17.
RSC Adv ; 11(58): 36913-36919, 2021 Nov 10.
Article En | MEDLINE | ID: mdl-35494380

A novel anionic Cd(ii)-based metal-organic framework, H2[Cd9(DDB)4(BPP)4(H2O)14]·4H2O·2DMA (1), was successfully obtained with a rigid carboxylate ligand 3,5-di(2',4'-dicarboxylphenyl)benzoic acid (H5DDB) and a flexible pyridyl ligand 1,3-bis(4-pyridyl)propane (BPP). Complex 1 contains two-dimensional (2D) honeycomb structures and one-dimensional (1D) chain structures. The adjacent 2D structures are linked by strong intermolecular hydrogen bonds to form an ABAB 3D supramolecular structure, where the 1D chain structures traverse the channels of the 2D structures. Due to the anionic framework, Ln(iii) ions (Ln = Eu and Tb) can be encapsulated in the framework of 1 by a post-synthetic modification process to obtain Ln(iii)@1, where 1.09Eu(iii)@1 (1a) and 0.658Tb(iii)@1 (1b) can be obtained by soaking complex 1 in a Eu(NO3)3·6H2O or Tb(NO3)3·6H2O aqueous solution for 48 h. The liquid-state emission spectra of Ln(iii)@1 can be tuned to be a white light emission by changing the Eu(iii)/Tb(iii) molar ratio in solution. Moreover, 1b can be used as a "turn-off" fluorescent probe for bilirubin with a low detection limit of 0.250 µM in phosphate buffer solution (pH = 7.4), which presents excellent sensitivity, high selectivity, and reusability. Furthermore, the devised fluorescent probe in serum also exhibits the fluorescence "turn-off" process with a low detection limit of 0.279 µM, and the recovery rate of bilirubin is 99.20-101.9%. The possible mechanisms of the fluorescence "turn-off" process can be explained by resonance energy transfer, and the weak interaction between 1b and bilirubin.

18.
Eur Radiol ; 31(5): 3195-3206, 2021 May.
Article En | MEDLINE | ID: mdl-33068187

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.


Atherosclerosis , Carotid Intima-Media Thickness , Adult , Atherosclerosis/diagnostic imaging , Humans , Infant , Male , Pulse Wave Analysis , Risk Factors , Ultrasonography
19.
Dalton Trans ; 49(41): 14361-14372, 2020 Oct 27.
Article En | MEDLINE | ID: mdl-33030153

The large-scale use of pesticides such as organophosphate pesticides (OPPs) and organochlorine pesticides (OCPs) has led to serious environmental problems worldwide, and their high toxicity could cause serious damage to human health. It is crucial to remove and track them precisely in the environment and food resources. As novel nanomaterials, metal-organic frameworks (MOFs) have attracted significant attention in the fields of adsorption and luminescence sensing due to their rich topology, tunable pore size and shape, high surface area, and abundant active sites. Luminescent metal-organic frameworks (LMOFs) have sprung up as great potential chemical sensors to detect pesticides with fast response, high sensitivity, high selectivity and easy operation. Therefore, in this highlight, we focus on recent progress of MOFs in sensing and adsorbing pesticides, as well as in the possible mechanism of sensing, so as to attract more attention to pesticide detection and adsorption.


Chemistry Techniques, Analytical/instrumentation , Metal-Organic Frameworks/chemistry , Pesticides/analysis , Pesticides/chemistry , Adsorption
20.
Sensors (Basel) ; 19(23)2019 Nov 21.
Article En | MEDLINE | ID: mdl-31766356

The detection of water pipeline leakage is important to ensure that water supply networks can operate safely and conserve water resources. To address the lack of intelligent and the low efficiency of conventional leakage detection methods, this paper designs a leakage detection method based on machine learning and wireless sensor networks (WSNs). The system employs wireless sensors installed on pipelines to collect data and utilizes the 4G network to perform remote data transmission. A leakage triggered networking method is proposed to reduce the wireless sensor network's energy consumption and prolong the system life cycle effectively. To enhance the precision and intelligence of leakage detection, we propose a leakage identification method that employs the intrinsic mode function, approximate entropy, and principal component analysis to construct a signal feature set and that uses a support vector machine (SVM) as a classifier to perform leakage detection. Simulation analysis and experimental results indicate that the proposed leakage identification method can effectively identify the water pipeline leakage and has lower energy consumption than the networking methods used in conventional wireless sensor networks.

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