Identification of a novel reactive oxygen species (ROS)-related genes model combined with RT-qPCR experiments for prognosis and immunotherapy in gastric cancer

Reactive oxygen species play a crucial role in the prognosis and tumor microenvironment (TME) of malignant tumors. An ROS-related signature was constructed in gastric cancer (GC) samples from TCGA database. ROS-related genes were obtained from the Molecular Signatures Database. Consensus clustering was used to establish distinct ROS-related subtypes related to different survival and immune cell infiltration patterns. Sequentially, prognostic genes were identified in the ROS-related subtypes, which were used to identify a stable ROS-related signature that predicted the prognosis of GC. Correlation analysis revealed the significance of immune cell iniltration, immunotherapy, and drug sensitivity in gastric cancers with different risks. The putative molecular mechanisms of the different gastric cancer risks were revealed by functional enrichment analysis. A robust nomogram was established to predict the outcome of each gastric cancer. Finally, we verified the expression of the genes involved in the model using RT-qPCR. In conclusion, the ROS-related signature in this study is a novel and stable biomarker associated with TME and immunotherapy responses

Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy

IntroductionCellular senescence is a hallmark of tumors and has potential for cancer therapy. Cellular senescence of tumor cells plays a role in tumor progression, and patient prognosis is related to the tumor microenvironment (TME). This study aimed to explore the predictive value of senescence-related genes in thyroid cancer (THCA) and their relationship with the TME.MethodsSenescence-related genes were identified from the Molecular Signatures Database and used to conduct consensus clustering across TCGA-THCA. Differentially expressed genes (DEGs) were identified between the clusters used to perform multivariate Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a senescence-related signature. TCGA dataset was randomly divided into training and test datasets to verify the prognostic ability of the signature. Subsequently, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. Finally, the expression of signature genes was detected across TCGA-THCA and GSE33630 datasets, and further validated by RT-qPCR.ResultsThree senescence clusters were identified based on the expression of 432 senescence-related genes. Then, 23 prognostic DEGs were identified in TCGA dataset. The signature, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-risk THCA shows a better prognosis and higher immunotherapy response than high-risk THCA. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. The validation part demonstrated that ADAMTSL4, DOCK6, FAM111B, and SEMA6B were expressed at higher levels in the tumor tissue, whereas lower expression of MRPS10 and PSMB7 was observed.DiscussionIn conclusion, the senescence-related signature is a promising biomarker for predicting the outcome of THCA and has the potential to guide immunotherapy

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

Gene duplication is supposed to be the major source for genetic innovations. However, how a new duplicate gene acquires functions by integrating into a pathway and results in adaptively important phenotypes has remained largely unknown. Here, we investigated the biological roles and the underlying molecular mechanism of the young kep1 gene family in the Drosophila melanogaster species subgroup to understand the origin and evolution of new genes with new functions. Sequence and expression analysis demonstrates that one of the new duplicates, nsr (novel spermatogenesis regulator), exhibits positive selection signals and novel subcellular localization pattern. Targeted mutagenesis and whole-transcriptome sequencing analysis provide evidence that nsr is required for male reproduction associated with sperm individualization, coiling, and structural integrity of the sperm axoneme via regulation of several Y chromosome fertility genes post-transcriptionally. The absence of nsr-like expression pattern and the presence of the corresponding cis-regulatory elements of the parental gene kep1 in the pre-duplication species Drosophila yakuba indicate that kep1 might not be ancestrally required for male functions and that nsr possibly has experienced the neofunctionalization process, facilitated by changes of trans-regulatory repertories. These findings not only present a comprehensive picture about the evolution of a new duplicate gene but also show that recently originated duplicate genes can acquire multiple biological roles and establish novel functional pathways by regulating essential genes

The Ninth Visual Object Tracking VOT2021 Challenge Results

acceptedVersionPeer reviewe

Stability Analysis for Milling Process with Variable Pitch and Variable Helix Tools by High-Order Full-Discretization Methods

Chatter is one of the significant limitations in the milling process, which may cause poor surface quality, reduced productivity, and accelerated tool wear. Variable pitch and variable helix tools can be used to suppress regenerative chatter. This study extends the high-order full-discretization methods (FDMs) to predict the stability of milling with variable pitch and variable helix tools. The time-periodic delay-differential equation (DDE) with multiple delays is used to model the milling process using variable pitch and variable helix tools. Then, the DDE with multiple delays is reexpressed by the state-space equation. Meanwhile, the spindle rotational period is divided into many small-time intervals, and the state space equation is integrated on the small-time interval. Then, the high-order interpolation polynomials are used to approximate the state term, and the weights related to the time delay are employed to approximate the time-delay term. The second-order, third-order, and fourth-order extended FDMs (2nd EFDM, 3rd EFDM, and 4th EFDM) are compared with the benchmark in terms of the rate of convergence. It is found that the 2nd EFDM, 3rd EFDM, and 4th EFDM converge faster than the benchmark method. The difference between the curves obtained by different EFDMs and the reference curve is very small. There is no need to extend hypersecond FDMs to analyze the stability of milling with variable pitch and variable helix tools