Summary
Regulatory T cells (Tregs) play a key role in the prevention of acute graft‐versus‐host disease (aGVHD). To investigate the association between Treg subsets and aGVHD, we prospectively ...analysed T cell subsets in the allografts of 35 patients undergoing myeloablative unmanipulated haematopoietic stem cell transplantation. Multivariate analysis found that patients infused with less than 0·29 × 106/kg of CD4+CD25highCD45RA+CD62L+ T cells during transplantation exhibited an increased incidence of II−IV aGVHD hazard ratio (HR) = 0·000, 95% CI = 0·000–0·106, P = 0·013. Next, we compared the reconstitution characteristics of T cell subsets between haploidentical haematopoietic stem cell transplantation (HSCT) and sibling HSCT by collecting peripheral blood samples at regular intervals (days 30, 60 and 90) after transplantation. No significant differences were observed in the reconstitution of conventional T cells between haploidentical HSCT and sibling identical HSCT. However, total counts of recovered naiveTregs and CD62L+ naive Tregs from haploidentical HSCT were significantly lower compared to sibling identical HSCT; P‐values were 0·045 and 0·021, respectively. Although total counts of conventional T cells in aGVHD patients reached similar levels compared to non‐aGVHD patients before day 60 post‐HSCT, total counts of naive Tregs and CD62L+ naive Tregs in aGVHD patients did not reach similar levels to non‐aGVHD patients until 90 days post‐HSCT. Taken together, our findings demonstrate that a large population of CD62L+ naive Tregs in allografts reduces the incidence of aGVHD. Further, development of aGVHD is related closely to the delayed reconstitution of the naive Treg population.
The EGFR-RAS-ERK pathway is one of the most important signaling cascades in cell survival, growth, and proliferation. Aberrant activation of this pathway is a common mechanism in various cancers. ...Here, we report that CDK2 is a novel regulator of the ERK pathway via USP37 deubiquitinase (DUB). Mechanistically, CDK2 phosphorylates USP37, which is required for USP37 DUB activity. Further, USP37 deubiquitinates and stabilizes ERK1/2, thereby enhancing cancer cell proliferation. Thus, CDK2 is able to promote cell proliferation by activating USP37 and, in turn, stabilizing ERK1/2. Importantly, combined CDK1/2 and EGFR inhibitors have a synergetic anticancer effect through the downregulation of ERK1/2 stability and activity. Indeed, our patient-derived xenograft (PDX) results suggest that targeting both ERK1/2 stability and activity kills cancer cells more efficiently even at lower doses of these two inhibitors, which may reduce their associated side effects and indicate a potential new combination strategy for cancer therapy.
To investigate the protective effects of glucosamine (GlcN) using oxidative stress and rat models of ischemia-reperfusion (I/R) injury and to determine the antiapoptotic and anti-inflammatory ...mechanisms of GlcN treatment.
We determined the effects of GlcN and the levels of O-linked N-acetylglucosamine (O-GlcNAc) in in vitro retinal ganglion cells (RGCs) treated with or without H₂O₂. The survival and apoptosis rates of RGCs were compared after the addition of GlcN, glucose, or O-(2-acetamido-2-deoxy-Dglucopyranosylidene) amino-N-phenylcarbamate (PUGNAc). Retinal I/R injury was induced in Sprague-Dawley rats by elevating the IOP to 110 mm Hg for 60 minutes. An intraperitoneal injection of GlcN (1000 mg/kg) or normal saline was administered in the different groups, including a control group, a GlcN group, an I/R group, a GlcN+I/R group (1000 mg/kg GlcN 24 hours before I/R injury), and an I/R+GlcN group (7-day period of 1000 mg/kg GlcN 24 hours after I/R injury). The rats were killed 7 days after the I/R injury, and the retinas were collected from each rat for thickness measurements. Quantitative analysis of RGC survival was further determined using labeling with FluoroGold.
The GlcN increased levels of O-GlcNAc in a dose-dependent manner in the RGCs treated with or without H₂O₂. The GlcN resulted in increased cell survival and reduced apoptosis in the RGCs under oxidative stress conditions. In the rat model of I/R injury, GlcN significantly protected against I/R-induced retinal thinning and suppressed the I/R-induced reductions in a- and b-wave amplitudes of the ERG. In terms of RGC survival, significant incremental density of RGCs was found in the I/R+GlcN group compared with the I/R group. Notably, the use of GlcN in the rat retina decreased apoptosis and the formation of reactive oxygen species (ROS) after I/R injury. We also found that mitogen-activated protein kinase signal pathways played a critical role in the GlcN-mediated attenuation of ROS-induced damage in vitro and I/R injury in vivo.
Glucosamine treatment provides multiple levels of retinal protection, including antiapoptotic, anti-inflammatory, and antioxidative benefits. More research on the role of GlcN as a potential agent for the prevention and treatment of glaucoma is warranted.
Y‐chromosome‐specific haplotypes (Y‐haplotypes) constructed using single nucleotide polymorphisms (Y‐SNPs) in the MSY (male‐specific region of the Y‐chromosome) are valuable in population genetic ...studies. But sequence variants in the yak MSY region have been poorly characterized so far. In this study, we screened a total of 16 Y‐chromosome‐specific gene segments from the ZFY, SRY, UTY, USP9Y, AMELY and OFD1Y genes to identify Y‐SNPs in domestic yaks. Six novel Y‐SNPs distributed in the USP9Y (g.223C>T), UTY19 (g.158A>C and g.169C>T), AMELY2 (g.261C>T), OFD1Y9 (g.165A>G) and SRY4 (g.104G>A) loci, which can define three Y‐haplotypes (YH1, YH2 and YH3) in yaks, were discovered. YH1 was the dominant and presumably most ancient haplotype based on the comparison of UTY19 locus with other bovid species. Interestingly, we found informative UTY19 markers (g.158A>C and g.169C>T) that can effectively distinguish the three yak Y‐haplotypes. The nucleotide diversity was 1.7 × 10⁻⁴ ± 0.3 × 10⁻⁴, indicating rich Y‐chromosome diversity in yaks. We identified two highly divergent lineages (YH1 and YH2 vs. YH3) that share similar frequencies (YH1 + YH2: 0.82–0.89, YH3: 0.11–0.18) among all three populations. In agreement with previous mtDNA studies, we supported the hypothesis that the two highly divergent lineages (YH1 and YH2 vs. YH3) derived from a single gene pool, which can be explained by the reunion of at least two paternal populations with the divergent lineages already accumulated before domestication. We estimated a divergence time of 408 110 years between the two divergent lineages, which is consistent with the data from mitochondrial DNA in yaks.
Terahertz pulsed imaging (TPI) is a non-ionizing and non-destructive imaging technique that has been recently used to study a wide range of biological materials. The severe attenuation of terahertz ...radiation in samples with high water content means that biological samples need to be very thin if they are to be measured in transmission geometry. To overcome this limitation, samples could be measured in reflection geometry and this is the most feasible way in which TPI could be performed in a clinical setting. In this study, we therefore used TPI in reflection geometry to characterize the terahertz properties of several organ samples freshly harvested from laboratory rats. We observed differences in the measured time domain responses and determined the frequency-dependent optical properties to characterize the samples further. We found statistically significant differences between the tissue types. These results show that TPI has the potential to accurately differentiate between tissue types non-invasively.
IntroductionThe COVID-19 pandemic has caused unprecedented disruptions around the world. Adding to the existing stress surrounding pregnancy and childbirth, the threat of infection and social ...isolation policies may negatively impact pregnant women and new mothers. Literature on the effect of COVID-19 on fear during pregnancy and childbirth experience is limited. As the COVID-19 pandemic continues to affect the global population, it is important to understand how it has impacted pregnant women and new mothers’ experiences worldwide to inform perinatal care and interventions.Methods and analysisThis multicountry study involving China and Canada targets to recruit 1000 pregnant women and new mothers who gave birth since 2020 in each participating country. Participants will be recruited online in the local language through mothers’ groups, antenatal and postnatal clinics and hospital wards. All questionnaires will be completed online. Participants’ level of fear, depression and childbirth experience will be assessed along with other sociodemographic, medical and COVID-related measures. Regression models will be used to compare the outcomes among the participating countries.Ethics and disseminationThe study has been reviewed and approved by the institutional review boards of the participating countries. Findings will be disseminated in peer-reviewed journals and academic conferences. Results from this study may guide the formulation of future health guidelines and policies in the face of a pandemic.
Abstract
This research was carried out with focus on the multi-scale structure of meretrix lusoria shell. In mesoscopic, meretrix lusoria shell contains three layers; the thickness of different ...layers is 0.6mm, 0.8mm and 0.7mm respectively. Compared to mesoscopic structure, the microstructure also has three layers, it refers to cuticle, prismatic layer and nacre. The cuticle is composed of a great number of particles, and its main composition is protein.The prismatic layer is composed of stagger structure. The inner layer presents orthogonal-sheets arrangement. This microstructure might show a special enhanced effect for the whole shell. The different inorganic layers’ crystal is same, which is aragonite. The mechanical properties of Meretrix lusoria shell are excellent, its elastic modulus was the same order of magnitude of high strength glass fiber composites. From this research will provide the theoretical basis for designing and producing bioinspired composite materials.
Abstract
In this study, Polybenzoxazole (PBO) nanofiber membranes are prepared by applying a three-step process, including synthesis of the electrospinning precursor with ortho-hydroxyl, ...electrospinning, and thermal conversion. Electrospinning is conducted at 10 kV with a distance of 10 cm and the solution concentration is 17.8% (w/v). Different flow rates are adopted to prepare polymer nanofiber membranes and test their properties. At the rate of 0.5 μL/min and 1 μL/min, uniform and compact films with nanofibers are obtained. The high-temperature transition from the precursor to PBO is then investigated systematically. Thermal treatment at 420°C is needed for complete cyclodecarboxylation conversion from the precursor to PBO. Diameters of the fibers in the as-prepared PBO nanofiber membrane are within the range of 120-130 nm. The membrane shows high thermal stability with the decomposition temperature of 619.8°C in N
2
and 513.6°C in air respectively, presenting a promising application prospect in high-temperature areas.
Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on ...modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately.
We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application.
Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025.
This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.
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