Cerebroprotective Effects of Dimeric Copper(II) Bis(o-acetoxybenzoate) on Ischemia-reperfusion Injury in Gerbils

The cerebroprotective effects of copper aspirinate [dimeric copper(II) bis(o-acetoxybenzoate)] were investigated in gerbils subjected to 10-min global cerebral ischemia followed b 60-min reperfusion. The results showed that intragastric copper aspirinate (7.5, 15.0 and 30.0 mg Kg−1) markedly promoted the recovery of the electroencephalogram amplitude, attenuated the increase of lipid peroxide content and the decrease of superoxide dismutase activity in the cortex during ischemia-reperfusion injury. It suggested that copper aspirinate possesses potential neuroprotective properties, the mechanism of which might be related to an increase of the activity of endogenous superoxide dismutase

How do keystones govern their business ecosystems through resource orchestration?

Purpose: Sharing resources with stakeholders is the key for keystones to govern business ecosystems successfully. However, existing research has not paid further attention to how keystones share resources under the condition of resource sufficiency and how keystones balance resource sharing with complementors when they lack resources. Therefore, this paper aims to explore how keystones govern their business ecosystems under the conditions of resource sufficiency and resource insufficiency. Design/methodology/approach: This paper adopts the single case study method. First, by adopting Gioia coding to analyze the relevant data of the case sample, this paper obtains the key concepts of the business ecosystem governance process. Then, it establishes the relationship between the concepts by analyzing the governance process of the case sample. Findings: Under the condition of resource sufficiency, keystones under the condition of resource sufficiency, should make full use of resources to incubate more complementors, and further integrate the resources of the business ecosystem, to create more value for their business ecosystems. Under the condition of resource insufficiency, keystones should break the boundaries of business ecosystems and acquire external resources, to meet the resource needs of complementors. Subsequently, keystones should redeploy idle resources according to the actual needs of complementors, to meet the changing resource needs of complementors. Originality/value: This study subdivides business ecosystem governance conditions and further constructs the business ecosystem governance process model, which provides a theoretical and practical reference for business ecosystem governance

High-level expression and large-scale preparation of soluble HBx antigen from Escherichia coli

The HBx (hepatitis B virus X protein) is a multifunctional regulator of cellular signal transduction and transcription pathways in host-infected cells. Evidence suggests that HBx has a critical role in the pathogenesis of hepatocellular carcinoma. However, the lack of efficient large-scale preparation methods for soluble HBx has hindered studies on the structure and function of HBx. Here, a new pMAL-c2x protein fusion and purification system was used for high-level expression of soluble HBx fusion protein. The high-purity fusion protein was obtained via amylose resin chromatography and Q-Sepharose chromatography. The untagged HBx was efficiently and rapidly purified by Sephadex G-75 chromatography after cleavage by Factor Xa at 23 °C. The purity of active HBx protein was >99% with a very stable secondary structure dominated by α-helix, β-sheet and random structure. The purified HBx protein can be analysed to determine its crystal structure and function and its capabilities as an effective immunogen

Suppression of methane uptake by precipitation pulses and long-term nitrogen addition in a semi-arid meadow steppe in northeast China

In the context of global change, the frequency of precipitation pulses is expected to decrease while nitrogen (N) addition is expected to increase, which will have a crucial effect on soil C cycling processes as well as methane (CH4) fluxes. The interactive effects of precipitation pulses and N addition on ecosystem CH4 fluxes, however, remain largely unknown in grassland. In this study, a series of precipitation pulses (0, 5, 10, 20, and 50 mm) and long-term N addition (0 and 10 g N m-2 yr-1, 10 years) was simulated to investigate their effects on CH4 fluxes in a semi-arid grassland. The results showed that large precipitation pulses (10 mm, 20 mm, and 50 mm) had a negative pulsing effect on CH4 fluxes and relatively decreased the peak CH4 fluxes by 203-362% compared with 0 mm precipitation pulse. The large precipitation pulses significantly inhibited CH4 absorption and decreased the cumulative CH4 fluxes by 68-88%, but small precipitation pulses (5 mm) did not significantly alter it. For the first time, we found that precipitation pulse size increased cumulative CH4 fluxes quadratically in both control and N addition treatments. The increased soil moisture caused by precipitation pulses inhibited CH4 absorption by suppressing CH4 uptake and promoting CH4 release. Nitrogen addition significantly decreased the absorption of CH4 by increasing NH4+-N content and NO3–-N content and increased the production of CH4 by increasing aboveground biomass, ultimately suppressing CH4 uptake. Surprisingly, precipitation pulses and N addition did not interact to affect CH4 uptake because precipitation pulses and N addition had an offset effect on pH and affected CH4 fluxes through different pathways. In summary, precipitation pulses and N addition were able to suppress the absorption of CH4 from the atmosphere by soil, reducing the CH4 sink capacity of grassland ecosystems

Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0–3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5–7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival

A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329) in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (Pmeta = 2.74×10−8, odds ratio = 1.29 [1.18–1.40]). The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment