Antitumor Activity of Carboxymethyl Pachymaran with Different Molecular Weights Based on Immunomodulatory and Gut Microbiota

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP

Intrashelf basin record of redox and productivity changes along the Arabian margin of Neo-Tethys during Oceanic Anoxic Event 1a

The biotic, environmental, climatic, oceanic, and sea-level perturbations during the Early Aptian Oceanic Anoxic Event (OAE) 1a have been extensively documented from both deep- and shallow-marine deposits worldwide. However, there has been relatively little comparative assessment of the simultaneous interplay among organic carbon burial, redox conditions, terrigenous output, and productivity, leading to a lack of precise constraints on these relationships. Here, we use analyses of stable carbon isotopes (δ13Corg, δ13Ccarb, and Δ13C), total organic carbon (TOC), detrital proxies (Al, Si, Ti, K), redox-sensitive (RSTE: U, V, Mo) and productive-sensitive (PSTE: P, Cu, Ni) trace elements from a continuous, predominantly carbonate succession of the Kazhdumi Intrashelf Basin to evaluate the culprits for the OAE1a-associated changes in bottom-water oxygenation, organic-rich layer formation, and biotic shifts along the Arabian margin of the Neo-Tethys. Concentrations of Al-normalized RSTE and TOC values indicate that the bottom water conditions ranged from oxic prior to and at the onset of the OAE 1a (carbon-isotope segments C2 to basalmost C4 sensu Menegatti et al., 1998), to anoxic-suboxic but not euxinic (Mo 100 m), continental-margin basins during major oceanic perturbations

A deep semantic network-based image segmentation of soybean rust pathogens

IntroductionAsian soybean rust is a highly aggressive leaf-based disease triggered by the obligate biotrophic fungus Phakopsora pachyrhizi which can cause up to 80% yield loss in soybean. The precise image segmentation of fungus can characterize fungal phenotype transitions during growth and help to discover new medicines and agricultural biocides using large-scale phenotypic screens.MethodsThe improved Mask R-CNN method is proposed to accomplish the segmentation of densely distributed, overlapping and intersecting microimages. First, Res2net is utilized to layer the residual connections in a single residual block to replace the backbone of the original Mask R-CNN, which is then combined with FPG to enhance the feature extraction capability of the network model. Secondly, the loss function is optimized and the CIoU loss function is adopted as the loss function for boundary box regression prediction, which accelerates the convergence speed of the model and meets the accurate classification of high-density spore images.ResultsThe experimental results show that the mAP for detection and segmentation, accuracy of the improved algorithm is improved by 6.4%, 12.3% and 2.2% respectively over the original Mask R-CNN algorithm.DiscussionThis method is more suitable for the segmentation of fungi images and provide an effective tool for large-scale phenotypic screens of plant fungal pathogens

Post-marketing safety surveillance of pneumococcal vaccines: a real-world pharmacovigilance study using the U.S. vaccine adverse event reporting system (VAERS) database

BackgroundPneumococcal vaccines have been utilized in the United States for decades with extensive clinical safety records. However, comprehensive post-marketing pharmacovigilance evaluations for all available types remain lacking. This study aimed to assess adverse events following immunization (AEFI) using the VAERS database and analyze potential associations between adverse events (AEs) and vaccine administration based on VAERS data.MethodsWe retrieved all AEs associated with pneumococcal vaccines recorded in the VAERS database from 1990 through March 2025. Descriptive analyses were conducted to summarize the demographics, clinical characteristics, and vaccination profiles of reported cases. Disproportionality analysis was performed to detect potential safety signals between AEs and vaccine administration.ResultsThe VAERS database documented 157,244 individuals receiving pneumococcal vaccines, with 158,778 doses administered, capturing 632,481 AE reports following vaccination during the study period. Females showed higher AE reporting rates (54.29%) compared to males (36.88%), with the majority of cases (38.20%) occurring in individuals aged < 18 years. Complete recovery (44.20%) and hospitalization (14.94%) were the most common outcomes. Most AEs (77.11%) occurred within 0–30 days post-vaccination (median onset: 0 day). Pneumococcal polysaccharide vaccine (PPSV, 48.92%) and 13-valent pneumococcal conjugate vaccine (PCV13, 27.57%) constituted the predominant vaccine types. Disproportionality analysis identified 929 positive AE signals across 24 system organ classes (SOCs), with injection site erythema [reporting odds ratio (ROR) = 4.24], injection site swelling (ROR = 4.19), and injection site pain (ROR = 2.75) being the most frequent. Designated Medical Event (DME) screening revealed erythema multiforme (n = 398) and product contamination microbial (ROR = 11.25) as key safety signals. General disorders (ROR = 1.73) and skin conditions (ROR = 1.69) were the predominant SOC categories.ConclusionsThis post-marketing surveillance has revealed predominantly non-serious AEs, with most adverse events clustered within 30 days post-vaccination. These observations reinforce the established safety profile of pneumococcal vaccines while emphasizing temporal risk patterns to guide post-vaccination monitoring protocols and risk-benefit evaluations

CathAction:A Benchmark for Endovascular Intervention Understanding

Real-time visual feedback from catheterization analysis is crucial for enhancing surgical safety and efficiency during endovascular interventions. However, existing datasets are often limited to specific tasks, small scale, and lack the comprehensive annotations necessary for broader endovascular intervention understanding. To tackle these limitations, we introduce CathAction, a large-scale dataset for catheterization understanding. Our CathAction dataset encompasses approximately 500,000 annotated frames for catheterization action understanding and collision detection, and 25,000 ground truth masks for catheter and guidewire segmentation. For each task, we benchmark recent related works in the field. We further discuss the challenges of endovascular intentions compared to traditional computer vision tasks and point out open research questions. We hope that CathAction will facilitate the development of endovascular intervention understanding methods that can be applied to real-world applications. The dataset is available at https://airvlab.github.io/cathaction/

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Molecular Cloning and Characterization of the Calcineurin Subunit A from Plutella xylostella

Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This gene contains an ORF of 1488 bp that encodes a 495 amino acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and humans respectively. The full-length of PxCNA and its catalytic domain (CNA1–341, defined as PxCNα) were both expressed in Escherichia coli. Purified recombinant PxCNA displayed no phosphatase activity, whereas recombinant PxCNα showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66 S−1 against pNPP. It could be activated at different degrees by Mn2+, Ni2+, Mg2+, and Ca2+. The optimum reaction pH was about 7.5 and the optimum reaction temperature was around 45 °C. An in vitro inhibition assay showed that okadaic acid (OA) and cantharidin (CTD) competitively inhibited recombinant PxCNα activity with the IC50 values of 8.95 μM and 77.64 μM, respectively. However, unlike previous reports, pyrethroid insecticides were unable to inhibit recombinant PxCNα, indicating that the P. xylostella calcineurin appears not to be sensitive to class II pyrethroid insecticides

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

AbstractBackground Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells.Methods The PC12 cells were incubated by hydrogen peroxide (H2O2) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1α expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1α was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/β-catenin pathways was tested by western blot.Results Dex attenuated H2O2-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1α expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3′-UTR of HIF-1α. In addition, Dex activated PI3K/AKT/mTOR and Wnt/β-catenin pathways by declining miR-199a level.Conclusions This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/HIF-1α

Identification and Biochemical Characterization of Protein Phosphatase 5 from the Cantharidin-Producing Blister Beetle, Epicauta chinensis

Protein phosphatase 5 (PP5) is a unique member of serine/threonine phosphatases which has been recognized in regulation of diverse cellular processes. A cDNA fragment encoding PP5 (EcPP5) was cloned and characterized from the cantharidin-producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of 1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans, respectively. Analysis of the primary sequence shows that EcPP5 has three TPR (tetratricopeptide repeat) motifs at its N-terminal region and contains a highly conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5) was produced in Escherichia coli and purified to homogeneity. The purified protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate) and phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro inhibition study revealed that protein phosphatase inhibitors, okadaic acid, cantharidin, norcantharidin and endothall, inhibited its activity. Further, protein phosphatase activity of total soluble protein extract from E. chinensis adults could be impeded by these inhibitors suggesting there might be some mechanism to protect this beetle from being damaged by its self-produced cantharidin