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Background. Adiponectin is a recognized antiatherogenic molecule; this study was aimed at clarifying the effects of adiponectin variants on lipid and adiponectin levels. Methods. By searching PubMed and Cochrane databases for studies published before March 31, 2022, a total of 86,610 individuals were included in the analysis. Results. Variants of rs2241766 and rs266729 were associated with decreased adiponectin and high-density lipoprotein cholesterol (HDL-C), as well as increased triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the rs1501299 variant was correlated with increased adiponectin and HDL-C, as well as decreased TG, TC, and LDL-C levels. Subgroup analysis indicated that the significant effect of the rs2241766 and rs266729 variants on lipid profile was predominant in Chinese, while the significant effect of the rs1501299 variant on lipid profile was primarily in Caucasians. Moreover, a stronger effect of the rs2241766 and rs1501299 variants on LDL-C levels was observed in males, while a considerable effect of the rs266729 variant on LDL-C levels was observed in children. Conclusions. The present study indicated that Chinese with the rs2241766 and rs266729 variants were at high risk of dyslipidemia, atherosclerosis, or coronary artery disease (CAD). Males with the rs2241766 variant were at high risk of CAD. Children with the rs266729 variant had a high risk to develop dyslipidemia, atherosclerosis, and even early onset of CAD in the future. These findings are beneficial to clinical physicians to choose different management strategies for cardiovascular disease (CVD) prevention.

The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

R2R3 MYB transcription factors play key functions in the regulation of secondary metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was identified from Chinese narcissus (Narcissus tazetta L. var. Chinensis Roem) and functionally characterized. NtMYB2 belongs to subgroup 4 of the R2R3 MYB transcription factor family that are related to repressor MYBs involved in the regulation of anthocyanin and flavonoids. Transient expression confirmed that NtMYB2 strongly reduced the red pigmentation induced by MYB- anthocyanin activators in agro-infiltrated tobacco leaves. Ectopic expression of NtMYB2 in tobacco significantly reduced the pigmentation and altered the floral phenotypes in transgenic tobacco flowers. Gene expression analysis suggested that NtMYB2 repressed the transcript levels of structural genes involved in anthocyanin biosynthesis pathway, especially the UFGT gene. NtMYB2 gene is expressed in all examined narcissus tissues; the levels of transcription in petals and corona is higher than other tissues and the transcription level at the bud stage was highest. These results show that NtMYB2 is involved in the regulation of anthocyanin biosynthesis pathway and may act as a repressor by down regulating the transcripts of key enzyme genes in Chinese narcissus.

Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis. Elevated plasma LDL cholesterol levels increase the risk of atherosclerotic cardiovascular disease. Here, the authors show that inhibition of MT1-MMP reduces plasma LDL cholesterol levels and the risk of atherosclerosis, indicating the potential of MT1-MMP inhibition as a lipid-lowering therapy.

The natural convection heat transfer of horizontal rectangle enclosures with different aspect ratios ( A  = 2:1 and A  = 4:1) filled with Ag-Ga nanofluid (different nanoparticle volume fractions φ  = 0.01, φ  = 0.03, φ  = 0.05 and radiuses r  = 20 nm, r  = 40 nm, r  = 80 nm) at different Rayleigh numbers ( Ra  = 1 × 10 3 and Ra  = 1 × 10 5 ) is investigated by a two-phase lattice Boltzmann model. It is found that the Nusselt number enhancement ratios of two enclosures ( A  = 2:1 and A  = 4:1) filled with Ag-Ga nanofluid ( r  = 20 nm) are the same compared with those of the water at the corresponding aspect ratio enclosure. The more flat horizontal rectangular enclosure ( A  = 4:1) has the higher Nusselt number than the less flat horizontal rectangular enclosure ( A  = 2:1). It is also found that Nusselt number increases with the decreasing nanoparticle radius. Nusselt number enhancement ratios for every nanoparticle radius reducing by half at high Rayleigh number are higher than those at low Rayleigh number in most cases. The interaction forces between particles are also investigated in this paper. It is found that the Brownian force F B is about two magnitudes greater than that of drag force F D , and the value of driving force F S in A  = 4:1 enclosure is about twice the value of driving force F S in A  = 2:1 enclosure while other forces are almost the same.

The stability and natural convection heat transfer characteristics of TiO 2 -water nanofluid in enclosures with different rotation angles ( α  = −45°, α  = 0°, α  = 45°, and α  = 90°) are experimentally investigated. The effects of different pH values and doses ( m ) of dispersant agent on the stability of TiO 2 -water nanofluid are investigated. It is found that TiO 2 -water nanofluid with m  = 6 wt% and pH = 8 has the lowest transmittance and has the best stability. The effects of different rotation angles ( α  = −45°, α  = 0°, α  = 45°, and α  = 90°), nanoparticle mass fractions (wt% = 0.1%, wt% = 0.3%, and wt% = 0.5%) and heating powers ( Q  = 1 W, Q  = 5 W, Q  = 10 W, Q  = 15 W, and Q  = 20 W) on the natural convection heat transfer characteristics are also studied. It is found that the enclosure with rotation angle α = 0° has the highest Nusselt number, followed by the enclosure with rotation angles α  = 45° and α  = 90°, the enclosure with rotation angle α  = −45° has the lowest Nusselt number. It is also found that natural convection heat transfer performance increases with the nanoparticle mass fraction and heating power, but the enhancement ratio decreases with the heating power.

Objective To analyze the diagnostic value of MRI in placenta previa. Methods 100 pregnant women with placenta previa admitted to our hospital from January 2017 to January 2020 were selected as the research objects. They were randomly divided into groups by digital table. Group A (50 cases) carried out magnetic resonance imaging (MRI) examination, and Group B (50 cases) carried out Doppler ultrasound examination. The detection of disease types and diagnostic accuracy were compared, and the imaging manifestations of MRI in the diagnosis of placenta accreta and non placenta accreta were analyzed. Results The detection rate of central type, marginal type and partial type in group A was higher than that in group B ( P  < 0.05). With surgery and pathology as the gold standard, the diagnostic accuracy and sensitivity of group A were higher than that of group B, and the rate of missed diagnosis was lower than that of group B ( P  < 0.05). Among the 50 pregnant women in Group A, 9 had placenta implantation and 41 had no placenta implantation. There were differences in the imaging manifestations of the pregnant women, such as the uneven signal in the placenta, the increased/thickened blood vessels in the placenta, and the unclear boundary between the placenta and the uterus ( P  < 0.05). Conclusion MRI examination is an important way for clinical diagnosis of placenta previa, and it is worth popularizing.

In 2014 the United States experienced a nationwide outbreak of Enterovirus D68 (EV-D68) infection. There were no confirmed cases of EV-D68 in 2015 and CDC was only aware of limited sporadic EV-D68 detection in the US in 2016. In this report, we analyzed 749 nasopharyngeal (NP) specimens collected in 2015 and 2016 from patients in the Lower Hudson Valley, New York using a previously validated EV-D68-specific rRT-PCR assay. EV-D68 was detected in none of 199 NP specimens collected in 2015, and in one of 108 (0.9%) samples from January to May and 159 of 442 (36.0%) samples from July to October 2016. Complete EV-D68 genome sequences from 22 patients in 2016 were obtained using a metagenomic next-generation sequencing assay. Comparative genome analysis confirmed that a new EV-D68 strain belonging to subclade B3, with 3.2–4.8% divergence in nucleotide from subclade B1 strains identified during the 2014 US outbreak, was circulating in the US in 2016 and caused an outbreak in the Lower Hudson Valley, New York with 160 laboratory-confirmed cases. Our data highlight the genetic variability and capacity in causing outbreak by diverse EV-D68 strains, and the necessity of awareness and more surveillance on their active circulation worldwide.

Osteoarthritis (OA), a chronic joint disease affecting over 500 million individuals globally, is characterized by the destruction of articular cartilage and joint inflammation. Conventional treatments are insufficient for repairing damaged joint tissue, necessitating novel therapeutic approaches. Mesenchymal stem cells (MSCs), with their potential for differentiation and self-renewal, hold great promise as a treatment for OA. However, challenges such as MSC viability and apoptosis in the ischemic joint environment hinder their therapeutic effectiveness. Hydrogels with biocompatibility and degradability offer a three-dimensional scaffold that support cell viability and differentiation, making them ideal for MSC delivery in OA treatment. This review discusses the pathological features of OA, the properties of MSCs, the challenges associated with MSC therapy, and methods for hydrogel preparation and functionalization. Furthermore, it highlights the advantages of hydrogel-based MSC delivery systems while providing insights into future research directions and the clinical potential of this approach.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.