The prognostic analysis of further axillary dissection in breast cancer with 1-2 positive sentinel lymph nodes undergoing mastectomy

BackgroundThe ACOSOG Z0011 study has shown that axillary lymph node dissection (ALND) is an option to be considered in patients who had 1-2 metastatic sentinel lymph nodes (SLNs) who proceed with breast-conserving along with postoperative radiotherapy. However, there remains controversy regarding the applicability of this approach in patients who had a mastectomy. The aim of our study is to determine the prognostic differences and risk factors associated with the decision to opt for ALND in breast cancer patients who had 1-2 metastatic SLNs who receive a mastectomy.MethodsThe study conducted a retrospective analysis of patients diagnosed with cT1-2N0 breast cancer and treated at The Fourth Hospital of Hebei Medical University between January 2016 and December 2021, and patients were divided into two cohorts according to whether ALND was performed after sentinel lymph node biopsy (SLNB): SLNB cohort and SLNB + ALND cohort. Outcomes included the locoregional recurrence rate (LRR), disease-free survival (DFS), and overall survival (OS). Propensity score matching (PSM) was conducted to ensure the balance of variables between the two cohorts. Cox proportional hazard models were employed to ascertain the univariate and multivariate relative risks associated with survival.ResultsThere were 812 cases enrolled. After the PSM, 234 receiving ALND and 234 not receiving ALND were matched. A median follow-up period of 56.72 ± 20.29 months was observed. During that time, no significant difference was identified in the DFS and OS in the SLNB + ALND cohort and the SLNB cohort (P = 0.208 and P = 0.102), except for those under 40 years old, SLNB + ALND group showed a reduction in LRR compared to SLNB group (11.1% vs. 2.12%, P = 0.044). Multivariate Cox analysis showed that younger (≤ 40 years), progesterone receptor (PR)-negative, and SLNB alone were independent risk factors for LRR; perineural invasion was a risk factor, while endocrinotherapy was a beneficial prognostic indicator for DFS and OS among patients with positive hormone receptor.ConclusionALND does not impact DFS and OS in patients with 1-2 metastatic SLNs who have completed a mastectomy. Being younger (≤ 40 years), having a negative PR, and undergoing SLNB alone were independent risk factors for LRR. Given this finding, we recommend avoiding axillary treatment such as ALND or radiotherapy in patients without risk factors

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

BackgroundIntervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.ObjectiveThis study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.MethodsWe exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.ResultsDigoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.ConclusionThese findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases

TensorMD: Scalable Tensor-Diagram based Machine Learning Interatomic Potential on Heterogeneous Many-Core Processors

Molecular dynamics simulations have emerged as a potent tool for investigating the physical properties and kinetic behaviors of materials at the atomic scale, particularly in extreme conditions. Ab initio accuracy is now achievable with machine learning based interatomic potentials. With recent advancements in high-performance computing, highly accurate and large-scale simulations become feasible. This study introduces TensorMD, a new machine learning interatomic potential (MLIP) model that integrates physical principles and tensor diagrams. The tensor formalism provides a more efficient computation and greater flexibility for use with other scientific codes. Additionally, we proposed several portable optimization strategies and developed a highly optimized version for the new Sunway supercomputer. Our optimized TensorMD can achieve unprecedented performance on the new Sunway, enabling simulations of up to 52 billion atoms with a time-to-solution of 31 ps/step/atom, setting new records for HPC + AI + MD

Comprehensive analysis of the WRKY gene family in Cucumis metuliferus and their expression profile in response to an early stage of root knot nematode infection

Root-knot nematode (RKN) is a major factor that limits the growth and productivity of important Cucumis crops, such as cucumber and melon, which lack RKN-resistance genes in their genome. Cucumis metuliferus is a wild Cucumis species that displays a high degree of RKN-resistance. WRKY transcription factors were involved in plant response to biotic stresses. However, little is known on the function of WRKY genes in response to RKN infection in Cucumis crops. In this study, Cucumis metuliferus 60 WRKY genes (CmWRKY) were identified in the C. metuliferus genome, and their conserved domains were classified into three main groups based on multiple sequence alignment and phylogenetic analysis. Synteny analysis indicated that the WRKY genes were highly conserved in Cucumis crops. Transcriptome data from of C. metuliferus roots inoculated with RKN revealed that 16 CmWRKY genes showed differential expression, of which 13 genes were upregulated and three genes were downregulated, indicating that these CmWRKY genes are important to C. metuliferus response to RKN infection. Two differentially expression CmWRKY genes (CmWRKY10 and CmWRKY28) were selected for further functional analysis. Both CmWRKY genes were localized in nucleus, indicating they may play roles in transcriptional regulation. This study provides a foundation for further research on the function of CmWRKY genes in RKN stress resistance and elucidation of the regulatory mechanism

Genome and secretome analysis of Pochonia chlamydosporia provide new insight into egg-parasitic mechanisms

Pochonia chlamydosporia infects eggs and females of economically important plant-parasitic nematodes. The fungal isolates parasitizing different nematodes are genetically distinct. To understand their intraspecific genetic differentiation, parasitic mechanisms, and adaptive evolution, we assembled seven putative chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs (~44 Mb, including 7.19% of transposable elements) and compared them with the genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode. We focus on secretomes of the fungus, which play important roles in pathogenicity and fungus-host/environment interactions, and identified 1,750 secreted proteins, with a high proportion of carboxypeptidases, subtilisins, and chitinases. We analyzed the phylogenies of these genes and predicted new pathogenic molecules. By comparative transcriptome analysis, we found that secreted proteins involved in responses to nutrient stress are mainly comprised of proteases and glycoside hydrolases. Moreover, 32 secreted proteins undergoing positive selection and 71 duplicated gene pairs encoding secreted proteins are identified. Two duplicated pairs encoding secreted glycosyl hydrolases (GH30), which may be related to fungal endophytic process and lost in many insect-pathogenic fungi but exist in nematophagous fungi, are putatively acquired from bacteria by horizontal gene transfer. The results help understanding genetic origins and evolution of parasitism-related genes.This work was supported by the National Key Research and Development (R&D) Plan of China (2016YFC1201100), and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IVFCAAS)

Genome-wide analysis of WRKY gene family in Cucumis sativus

<p>Abstract</p> <p>Background</p> <p>WRKY proteins are a large family of transcriptional regulators in higher plant. They are involved in many biological processes, such as plant development, metabolism, and responses to biotic and abiotic stresses. Prior to the present study, only one full-length cucumber WRKY protein had been reported. The recent publication of the draft genome sequence of cucumber allowed us to conduct a genome-wide search for cucumber WRKY proteins, and to compare these positively identified proteins with their homologs in model plants, such as <it>Arabidopsis</it>.</p> <p>Results</p> <p>We identified a total of 55 WRKY genes in the cucumber genome. According to structural features of their encoded proteins, the cucumber WRKY (<it>CsWRKY</it>) genes were classified into three groups (group 1-3). Analysis of expression profiles of <it>CsWRKY </it>genes indicated that 48 WRKY genes display differential expression either in their transcript abundance or in their expression patterns under normal growth conditions, and 23 WRKY genes were differentially expressed in response to at least one abiotic stresses (cold, drought or salinity). The expression profile of stress-inducible <it>CsWRKY </it>genes were correlated with those of their putative <it>Arabidopsis WRKY (AtWRKY) </it>orthologs, except for the group 3 WRKY genes. Interestingly, duplicated group 3 <it>AtWRKY </it>genes appear to have been under positive selection pressure during evolution. In contrast, there was no evidence of recent gene duplication or positive selection pressure among <it>CsWRKY </it>group 3 genes, which may have led to the expressional divergence of group 3 orthologs.</p> <p>Conclusions</p> <p>Fifty-five WRKY genes were identified in cucumber and the structure of their encoded proteins, their expression, and their evolution were examined. Considering that there has been extensive expansion of group 3 WRKY genes in angiosperms, the occurrence of different evolutionary events could explain the functional divergence of these genes.</p

Feasibility Study of a Novel Magnetic Bone Cement for the Treatment of Bone Metastases

Bone cement is a crucial material to treat bone metastases defects, and can fill the bone defect and provide mechanical support simultaneously, but the antitumor effect is very limited. Magnetic bone cement not only supports bone metastasis defects but can also achieve magnetic hyperthermia to eliminate tumor cells around the bone defect. However, the physicochemical properties of the bone cement matrix will change if the weight ratio of the magnetic nanoparticles in the cement is too high. We mixed 1 weight percent Zn0.3Fe2.7O4 with good biocompatibility and high heating efficiency into a polymethyl methacrylate matrix to prepare magnetic bone cement, which minimized the affection for physicochemical properties and satisfied the hyperthermia requirement of the alternating magnetic field