Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Dipotassium samarium(III) molybdate(VI) phosphate(V), K2Sm(MoO4)(PO4)

The title compound, K2Sm(MoO4)(PO4), has been prepared under atmospheric conditions using a high temperature solution growth (HTSG) method. The structure of K2Sm(MoO4)(PO4) is isotypic with other A 2 M(MoO4)(PO4) compounds, where A = Na or K, and M = trivalent rare earth cation. It can be described as being built up from two-dimensional anionic layers with composition [Sm(MoO4)(PO4)]2− that are stacked along the c axis and are inter­connected by K+ cations which are in an eightfold coordination by O atoms. The SmO8, MoO4 and PO4 polyhedra exhibit 2 symmetry

Lithium samarium polyphosphate, LiSm(PO3)4

The mixed-metal rare-earth polyphosphate LiSm(PO3)4 consists of a three-dimensional framework in which zigzag [(PO3)n]n− chains with a periodicity of four PO4 tetrahedra are connected through Li+ and Sm3+ ions (both with 2. symmetry)

Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts

BACKGROUND: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes. METHODS: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS). RESULTS: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21–6.84), multiple lacunes (aOR 3.5, CI 1.29–9.48) and higher total SVD burden (aOR 1.68, CI 1.11–2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up. CONCLUSIONS: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation

Scheelite-type NaEr(MoO4)2

Explorations of the A 1+–RE 3+–Mo6+–O2− (A 1+ is an alkali metal cation, RE 3+ is a rare-earth metal cation) quaternary systems prepared by the high-temperature solution growth method led to the title structure, sodium erbium bis­(molyb­date), NaEr(MoO4)2. It is isostructural to the scheelite structure (CaWO4) and is composed of [MoO4]2− tetra­hedra with symmetry and [(Na/Er)O8]14− polyhedra. The [(Na/Er)O8]14− polyhedron is a distorted tetra­gonal anti­prism, also with symmetry, with statistically mixed Na/Er atoms at its centre. There are two sets of Na/Er—O bond lengths [2.420 (4) and 2.435 (3) Å], but just one set of Mo—O bond lengths [1.774 (4) Å]

Effects of rumen-protective γ-aminobutyric acid additive on lactation performance and serum biochemistry in heat-stressed cows

In the context of global warming, heat stress has become one of the major stress factors limiting dairy cattle production. Although many methods have been explored to help cows mitigate the negative effects of heat stress during the hot summer months, maintaining the performance of high-yielding cows under heat stress is still a great challenge. The aim of this trial was to investigate the effect of RP-GABA in the diet on milk yield, milk composition and serum biochemical parameters in heat-stressed cows. Twenty Chinese Holstein cows in early lactation (51.00 ± 4.92 kg milk/d, 71 ± 10.94 d in milk and 2.68 ± 0.73 parities) were included in this experiment and randomly divided into four groups (n = 5/group). The four experimental groups consisted of one control group (0 g RP-GABA/d) and three treatment groups, given 5, 7.5 and 10 g RP-GABA/d of dry matter (DM) per cow, respectively. The results showed that supplementing high-yielding cows with 10 g/d of RP-GABA improved milk protein production but had no effect on the improvement of other production performance, the alleviation of heat stress in cows, or the improvement of immune function and antioxidant capacity. Ultimately, we conclude that the supplementation of 10 g/d RP-GABA to heat-stressed, high-yielding dairy cows can provide a degree of performance enhancement. Furthermore, our study provides some reference for nutritional improvement measures for summer heat stress in dairy cows, especially high-yielding cows

Mendelian randomization based on genome-wide association studies and expression quantitative trait loci, predicting gene targets for the complexity of osteoarthritis as well as the clinical prognosis of the condition

BackgroundOsteoarthritis (OA) entails a prevalent chronic ailment, marked by the widespread involvement of entire joints. Prolonged low-grade synovial inflammation serves as the key instigator for a cascade of pathological alterations in the joints.ObjectiveThe study seeks to explore potential therapeutic targets for OA and investigate the associated mechanistic pathways.MethodsSummary-level data for OA were downloaded from the genome-wide association studies (GWAS) database, expression quantitative trait loci (eQTL) data were acquired from the eQTLGen consortium, and synovial chip data for OA were obtained from the GEO database. Following the integration of data and subsequent Mendelian randomization analysis, differential analysis, and weighted gene co-expression network analysis (WGCNA) analysis, core genes that exhibit a significant causal relationship with OA traits were pinpointed. Subsequently, by employing three machine learning algorithms, additional identification of gene targets for the complexity of OA was achieved. Additionally, corresponding ROC curves and nomogram models were established for the assessment of clinical prognosis in patients. Finally, western blotting analysis and ELISA methodology were employed for the initial validation of marker genes and their linked pathways.ResultsTwenty-two core genes with a significant causal relationship to OA traits were obtained. Through the application of distinct machine learning algorithms, MAT2A and RBM6 emerged as diagnostic marker genes. ROC curves and nomogram models were utilized for evaluating both the effectiveness of the two identified marker genes associated with OA in diagnosis. MAT2A governs the synthesis of SAM within synovial cells, thereby thwarting synovial fibrosis induced by the TGF-β1-activated Smad3/4 signaling pathway.ConclusionThe first evidence that MAT2A and RBM6 serve as robust diagnostic for OA is presented in this study. MAT2A, through its involvement in regulating the synthesis of SAM, inhibits the activation of the TGF-β1-induced Smad3/4 signaling pathway, thereby effectively averting the possibility of synovial fibrosis. Concurrently, the development of a prognostic risk model facilitates early OA diagnosis, functional recovery evaluation, and offers direction for further therapy

Treatment of avulsion fracture of posterior cruciate ligament tibial insertion by minimally invasive approach in posterior medial knee

ObjectiveThe study aims to explore the feasibility and clinical effect of posterior minimally invasive treatment of cruciate ligament tibial avulsion fracture.MethodsPosterior knee minimally invasive approach was used to treat avulsion fracture of posterior cruciate ligament (PCL) tibia in 15 males and 11 females. The length of the incision, intraoperative blood loss, operation time, postoperative hospital stay, residual relaxation, and fracture healing time were analyzed to evaluate the curative effect, learning curve, and advantages of the new technology. Neurovascular complications were recorded. During the postoperative follow-up, the International Knee Joint Documentation Committee (IKDC), Lysholm knee joint score, and knee joint range of motion were recorded to evaluate the function.ResultsAll 26 patients were followed up for 18–24 months, with an average of 24.42 ± 5.00 months. The incision length was 3–6 cm, with an average of 4.04 ± 0.82 cm. The intraoperative blood loss was about 45–60 ml, with an average of 48.85 ± 5.88 ml. The operation time was 39–64 min, with an average of 52.46 ± 7.64 min. The postoperative hospital stay was 2–5 days, with an average of 2.73 ± 0.87 days. All incisions healed grade I without neurovascular injury. All fractures healed well with an average healing time of 9.46 ± 1.33 weeks (range, 8–12 weeks). The Lysholm score of the affected knee was 89–98 (mean, 94.12 ± 2.49) at 12-month follow-up. The IKDC score was 87–95 with an average of 91.85 ± 2.19, and the knee range of motion was 129–148° with an average of 137.08 ± 5.59°. The residual relaxation was 1–3 mm, with an average of 1.46 ± 0.65 mm.ConclusionThis minimally invasive method provides sufficient exposure for internal fixation of PCL tibial avulsion fractures without the surgical complications associated with traditional open surgical methods. The process is safe, less invasive, and does not require a long learning curve