Chronic heart failure is the terminal stage of various cardiovascular diseases， and its occurrence and progression are closely associated with impaired myocardial energy metabolism and mitochondrial dysfunction. Mitochondrial dynamics maintain cardiomyocyte energy homeostasis through fusion， fission， and quality control. Disruption of mitochondrial dynamics may lead to mitochondrial network fragmentation， insufficient adenosine triphosphate （ATP） production， enhanced oxidative stress， and activation of ferroptosis. The theory of Yin at peace and Yang being compact originates from the Chapter Discussion on Interrelationship between Life and Nature in the Plain Questions， and emphasizes that the dynamic balance between Yin and Yang is fundamental to normal life activities. According to this theory and mitochondrial dynamics， this paper explores the pathogenic connotations of Yang failing to remain compact and Yin failing to remain at peace in chronic heart failure. In traditional Chinese medicine （TCM）， chronic heart failure is characterized by deficiency in origin and excess in manifestation. Deficiency of heart Qi and Yang is the root， often accompanied by Yang deficiency or Yin deficiency， while blood stasis， phlegm turbidity， and water retention constitute the manifestations. When Yang fails to remain compact， cardiac propulsion becomes weakened and Qi transformation is impaired. When Yin fails to remain at peace， Yin pathogens are generated and Yin essence is consumed. At the microscopic level， imbalance of mitochondrial dynamics is manifested as insufficient mitochondrial fusion， excessive fission， reduced energy production， excessive ROS generation， expansion of the labile iron pool， and accumulation of lipid peroxidation products， which contribute to Yin-Yang imbalance in chronic heart failure. Furthermore， by integrating formula-pattern correspondence and the approach of inferring patterns from formula effects， this paper summarizes the possible molecular phenotypes corresponding to different syndrome elements and syndrome patterns. It further proposes keeping Yang compact and keeping Yin at peace as therapeutic principle for chronic heart failure， aiming to restore energy metabolism homeostasis by regulating mitochondrial dynamics with TCM and to provide new perspectives and ideas for the treatment of chronic heart failure.

Chinese mitten crab (Eriocheir sinensis) is an important aquaculture species in Crustacea. Functional analysis, although essential, has been hindered due to the lack of sufficient genomic or transcriptomic resources. In this study, transcriptome sequencing was conducted on 59 samples rep-resenting diverse developmental stages (fertilized eggs, zoea, megalopa, three sub-stages of larvae, juvenile crabs, and adult crabs) and different tissues (eyestalk, hepatopancreas, and muscle from juvenile crabs, and eyestalk, hepatopancreas, muscle, heart, stomach, gill, thoracic ganglia, intes-tine, ovary, and testis from adult crabs) of E. sinensis. A comprehensive reference transcriptome was assembled, including 19,023 protein-coding genes. Hierarchical clustering based on 128 differ-entially expressed cuticle-related genes revealed two distinct expression patterns during the early lar-val developmental stages, demonstrating the distinct roles of these genes in 'crab-like"cuticle formation during metamorphosis and cuticle calcification after molting. Phylogenetic analysis of 1406 one-to-one orthologous gene families identified from seven arthropod species andCaenorhabditis elegans strongly supported the hypothesis that Malacostraca and Branchiopoda do not form a monophyletic group. Furthermore, Branchiopoda is more phylogenetically closely related to Hexapoda, and the clade of Hexapoda and Branchiopoda and the clade of Malacostraca belong to the Pancrustacea. This study offers a high-quality transcriptome resource for E. sinensis and demonstrates the evolutionary relationships of major arthropod groups. The differentially expressed genes identified in this study facilitate further investigation of the cuticle-related gene expression networks which are likely associated with'crab-like"cuticle formation during metamor-phosis and cuticle calcification after molting.

Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.
Antigens, Neoplasm ; metabolism ; Data Analysis ; Databases, Genetic ; Humans ; Immunotherapy ; Mutation ; genetics ; Neoplasms ; genetics ; immunology ; Tumor Suppressor Protein p53 ; genetics ; Urinary Bladder Neoplasms ; genetics

Side effects from targeted drugs remain a serious concern.One reason is the nonselective binding of a drug to unintended proteins such as its paralogs,which are highly homologous in sequences and have similar structures and drug-binding pockets.To identify targetable differences between paralogs,we analyzed two types (type-Ⅰ and type-Ⅱ) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level.Paralogous protein receptors in glucagon-like subfamily,glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R),exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes.Our data showed that type-Ⅱ amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR,which had a radical shift in physicochemical properties between GCGR and GLP-1R.We also examined the role of type-Ⅰ amino acids between GCGR and GLP-1R.The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination,thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.

Since pig is an important livestock species worldwide, its gene expression has been investigated intensively, but rarely in brain. In order to study gene expression profiles in the pig central nervous system, we sequenced and analyzed 43,122 highquality 5′ end expressed sequence tags (ESTs) from porcine cerebellum, cortex cerebrum, and brain stem cDNA libraries, involving several different prenatal and postnatal developmental stages. The initial ESTs were assembled into 16,101 clusters and compared to protein and nucleic acid databases in GenBank. Of these sequences, 30.6% clusters matched protein databases and represented function known sequences; 75.1% had significant hits to nucleic acid databases and partial represented known function; 73.3% matched known porcine ESTs; and 21.5% had no matches to any known sequences in GenBank. We used the categories defined by the Gene Ontology to survey gene expression in the porcine brain.

Objective To study effects of baicalin(Bai) on AngⅡ in diabetic nephropathy(DN) rats and to explore its preventive and therapeutic effect on treating DN from the non-hemodynamic mechanism of AngⅡ.Methods Nineteen specific pathogen-free male rats were randomly divided into three groups:normal control group(5 rats),diabetic nephropathy model control group(7 rats),baicalin treated group(7 rats).DN rat model was established by one-dose intraperitoneal injection of streptozotocin.Seven weeks after the modeling,rats in baicalin group recieved intraperitoneal injection of baicalin solution(40 mg/kg),rats in DN model group received intraperitoneal injection of normal saline(1 mL for each rats),and the normal control group did not receive any intraperitoneal injection.After treatment for 6 weeks,orbital blood from all rats was collected to determine plasma AngⅡ by radioimmunoassay.Unilateral kidney was processed by 4 % paraformaldehyde fixation and then was used for the determination of TGF-? by immunohistochemical assay.The other unilateral kidney was got out to prepare for renal cortex homogenate,and then was used for the determination of renal tissue AngⅡ by radioimmuno assay.Results The quantity and degree of TGF-? expression in baicalin group was decreased,and there was statistical significance between baicalin group and the model group(P