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Objectives & Methods: The entire ≪Lingshu·Jingjin≫ content was analyzed to find repetitive patterns, as well as to analyze commonly used terms. Through this, the guidelines for interpretation were presented.Results & Conclusions: ≪Lingshu·Jingjin≫ is not a question-and-answer format, but a simple enumerated narrative format. There is no part corresponding to the introduction, only the descriptions of 12 individual Meridian-muscle exist. Each Meridian-muscle is divided into ‘Flow of Muscle Mechanics(流́走)’ part and ‘Diseases’ part, and ‘Flow of Muscle Mechanics’ of each Meridian-muscle can be divided into ‘Main Flow’ and ‘Branch’. ‘Main Flow’ is the most central ‘Flow’ in each ‘Meridian-muscle’, and ‘Branch’ is the part where ‘Main Flow’ ends and the description of another ‘Flow’ begins. ‘Branch’ has different expressions according to the importance. The expression also varies depending on the dynamics. ‘Meridian-muscle’ should be interpreted based on this.

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder in which patients present with core symptoms of social communication impairment, restricted interest, and repetitive behaviors. Although various studies have been performed to identify ASD-related mechanisms, ASD pathology is still poorly understood. CNTNAP2 genetic variants have been found that represent ASD genetic risk factors, and disruption of Cntnap2 expression has been associated with ASD phenotypes in mice. In this study, we performed an integrative multi-omics analysis by combining quantitative proteometabolomic data obtained with Cntnap2 knockout (KO) mice with multi-omics data obtained from ASD patients and forebrain organoids to elucidate Cntnap2-dependent molecular networks in ASD. To this end, a mass spectrometry-based proteometabolomic analysis of the medial prefrontal cortex in Cntnap2 KO mice led to the identification of Cntnap2-associated molecular features, and these features were assessed in combination with multi-omics data obtained on the prefrontal cortex in ASD patients to identify bona fide ASD cellular processes. Furthermore, a reanalysis of single-cell RNA sequencing data obtained from forebrain organoids derived from patients with CNTNAP2-associated ASD revealed that the aforementioned identified ASD processes were mainly linked to excitatory neurons. On the basis of these data, we constructed Cntnap2-associated ASD network models showing mitochondrial dysfunction, axonal impairment, and synaptic activity. Our results may shed light on the Cntnap2-dependent molecular networks in ASD.

Objectives: This study was done to establish the anatomical meaning of the term ‘Geun(筋)’.Methods: Through analysis of ≪HwangJeNaeGyeong(黃帝內經)≫, the meaning of ‘Geun(筋)’, ‘GeunMag(筋膜)’, ‘Yug(肉)’, and ‘Gi(肌)’ were established. Based on analysis, the anatomical meaning of the ‘Meridian-muscle(經筋)’ was studied by comparing it with anatomy.Results & Conclusions: ‘Gyeong(經)’ is recognized as a metaphysical expression and "Geun(筋)" means myofascia in anatomy. The concept of ‘Geun(筋)’ includes the epimysium and perimysium, as well as tendons and ligaments, which are extensions of these. ‘Fascia’, refers to the fascia of the whole body, and also appertain to ‘Geun(筋)’. ‘Yug(肉)’ means endomysium, muscle fiber, and adipose tissue and layer. The word ‘GeunMag(筋膜)’ used in the ≪HwangJeNaeGyeong(黃帝內經)≫ means anatomically a ‘tendon’. Therefore, ‘Muscle’ should be translated as ‘GeunYug(筋肉)’ in Traditional medicine. ‘Meridian-muscle(經筋)’ can be defined as the longitudinal muscle and fascia system, which is the basis of whole body encompassing dynamics.

MYPT1 and PSMC5 expression in 3 different subtypes (basal, HER-2 positive and ER positive) of breast cancer.

Western blots showing the antibody responses for PSMC5, MYPT1 and TFRC in patients with greater than and less than 3 years disease free survival

Selection criteria used to narrow the proteins identified in the screen to those shown in this study.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies–based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination. The SASI approach uses immunoprecipitation with patient-derived antibodies that is coupled to quantitative stable isotope–labeled amino acids in cell culture (SILAC). Using mass spectrometric analysis, we identified more than 150 different proteins that induce an antibody response after vaccination. The regulatory subunit 12A of protein phosphatase 1 (MYPT1 or PPP1R12A), regulatory subunit 8 of the 26S proteasome (PSMC5), and the transferrin receptor (TFRC) were shown to be pancreatic cancer–associated antigens recognized by postvaccination antibodies in the sera of patients with favorable disease-free survival after GVAX therapy. We further interrogated these proteins in over 80 GVAX-treated patients' pancreases and uniformly found a significant increase in the expression of MYPT1, PSMC5, and TFRC in neoplastic compared with non-neoplastic pancreatic ductal epithelium. We show that the novel SASI approach can identify antibody targets specifically expressed in patients with improved disease-free survival after cancer vaccine therapy. These targets need further validation to be considered as possible pancreatic cancer biomarkers. Cancer Immunol Res; 4(3); 225–33. ©2016 AACR.

Venn diagram showing overlap of proteins identified in 3 patients after the SASI screen.

Additional immunohistochemical validation showing PSMC5, MYPT1 and TFRC expression in an independent set of pancreatic cancers.

N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. On the 42 dpi, both groups were challenged with the wild-type virus. The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs.

BackgroundHypertension (HBP) is a common disease associated with aging, but the rate of recognition and control of the condition remains low. Most guidelines related to HBP have consisted of only peripheral blood pressure (BP) measurement. However, according to many studies, central BP (CBP) has a clearer relationship with the prediction of cardiovascular (CV) events than does peripheral BP and can more clearly express an individual’s BP status. Therefore, we aimed to evaluate the effect of CBP on the prediction of CV events and to investigate the prediction of CV events by phenotype of central and peripheral BP in subjects without hypertension.MethodA total of 2,910 patients were enrolled from June 2011 to December 2016 and were followed up through October 2022. CBP was measured using radial tonometry. The primary endpoint was a composite outcome.ResultThe median follow-up period for enrolled patients was 7.5 years. Out of a total of 722 patients (mean age of 52.5 ± 13.7 years) without HBP, 21 patients (2.9%) had events of the primary endpoint during the follow-up period. Systolic BP averaged 126 mmHg (±15 mmHg) in the event-free group and 136 mmHg (±15 mmHg) in the CV event group, while CBP measured 115 mmHg (±16 mmHg) in the event-free group and 126 mmHg (±16 mmHg) in the CV event group. In a Cox proportional hazards model, every 10 mmHg increase in CBP and systolic BP showed an increase in risk of 30% and 40%, respectively. Isolated central systolic hypertension and dual central and peripheral systolic hypertension showed 4.9% and 6% of the CV event rate, respectively (p=0.897).ConclusionIrrespective of the brachial BP status, isolated central hypertension increased CV events. Therefore, to prevent CV events, it is essential to control not only peripheral BP but also CBP.

Mo0.67W0.33Se2 devices show gate-voltage-induced electrical phase transitions.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for whole exome sequencing (WES) and RNA sequencing analyses of PDAC samples, including tissue processing for proteogenomic analysis, DNA and RNA extraction, experimental procedures for WES and RNA sequencing, and WES and RNA sequencing data analyses.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for mass spectrometry-based proteomic analysis of PDAC samples, including sample preparation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and data analyses (peptide/protein identification and quantitation).

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for cell-based assays for potential prognostic biomarkers in PDAC, including cell culture, viral transduction, and cell-based assays.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for assays for orthotopic PDAC mouse models, including mouse tumour tissue processing, ultrasound imaging, Masson-trichrome staining, and IHC analysis for immune cell markers.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for bioinformatics analysis of PDAC subtypes, including tumour purity estimation, subtype prediction for tumour samples in previous cohorts, pathway enrichment analysis, kinase activity analysis, and pan-omics analysis.