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Supplementary Tables S1-S6 and Supplementary Figures S1-S2. Table S1: Data collection and refinement statistics, related to Figure 1B; Table S2: Summary of cell line related information; Table S3: BGB-283 is a reversible B-RAF inhibitor; Table S4. Kinase inhibition profile of BGB-283. BGB-283 selectively inhibited multiple kinases at concentration of 10 μM; Table S5: IC50 values of BGB-283 in inhibiting various kinases; Table S6. Anti-tumor efficacy of BGB-283 in CRC xenograft models; Figure S1: BGB-283 is a slow-off B-RAF inhibitor showing potent anti-EGFR activity in multiple cell lines; Figure S2. The effect of BGB-283 on body weight of nude mice subcutaneously implanted with human cancer xenografts.

Supplementary Methods, Figures 1-9 from Modulation of Gene Expression and Tumor Cell Growth by Redox Modification of STAT3

Intestinal smooth muscles are the workhorse of the digestive system. Inside the millions of finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic vessel, called the lacteal, sending fats into blood circulation for energy production. Despite this vital function, how villus smooth muscles form, how they assemble alongside lacteals, and how they repair throughout life remain unknown. Here we combine single-cell RNA sequencing of the mouse intestine with quantitative lineage tracing to reveal the mechanisms of formation and differentiation of villus smooth muscle cells. Within the highly regenerative villus, we uncover a local hierarchy of subepithelial fibroblast progenitors that progress to become mature smooth muscle fibers, via an intermediate contractile myofibroblast-like phenotype, a long-studied hallmark of wound healing. This continuum persists in the adult intestine as the major source of smooth muscle reservoir capable of continuous self-renewal throughout life. We further discover that the NOTCH3-DLL4 signaling axis governs the assembly of villus smooth muscles alongside their adjacent lacteal, which is necessary for gut absorptive function. Overall, our data shed light on the genesis of a poorly defined class of intestinal smooth muscle and pave the way for new opportunities to accelerate recovery of digestive function by stimulating muscle repair.One Sentence SummaryVillus smooth muscles arise and renew via local myofibroblast-like intermediates governed by the NOTCH3-DLL4 signaling axis

The vertebrate intestine forms by asymmetric gut rotation and elongation, and errors cause lethal obstructions in human infants. Rotation begins with tissue deformation of the dorsal mesentery, which is dependent on left-sided expression of the Paired-like transcription factor Pitx2 . The conserved morphogen Nodal induces asymmetric Pitx2 to govern embryonic laterality, but organ-level regulation of Pitx2 during gut asymmetry remains unknown. We found Nodal to be dispensable for Pitx2 expression during mesentery deformation. Intestinal rotation instead required a mechanosensitive latent transforming growth factor–β (TGFβ), tuning a second wave of Pitx2 that induced reciprocal tissue stiffness in the left mesentery as mechanical feedback with the right side. This signaling regulator, an accelerator (right) and brake (left), combines biochemical and biomechanical inputs to break gut morphological symmetry and direct intestinal rotation.

The mutation of K‐RAS represents one of the most frequent genetic alterations in cancer. Targeting of downstream effectors of RAS, including of MEK and ERK, has limited clinical success in cancer patients with K‐RAS mutations. The reduced sensitivity of K‐RAS‐mutated cells to certain MEK inhibitors (MEKi) is associated with the feedback phosphorylation of MEK by C‐RAF and with the reactivation of mitogen‐activated protein kinase (MAPK) signaling. Here, we report that the RAF dimer inhibitors lifirafenib (BGB‐283) and compound C show a strong synergistic effect with MEKi, including mirdametinib (PD‐0325901) and selumetinib, in suppressing the proliferation of K‐RAS‐mutated non‐small‐cell lung cancer and colorectal cancer (CRC) cell lines. This synergistic effect was not observed with the B‐RAFV600E selective inhibitor vemurafenib. Our mechanistic analysis revealed that RAF dimer inhibition suppresses RAF‐dependent MEK reactivation and leads to the sustained inhibition of MAPK signaling in K‐RAS‐mutated cells. This synergistic effect was also observed in several K‐RAS mutant mouse xenograft models. A pharmacodynamic analysis supported a role for the synergistic phospho‐ERK blockade in enhancing the antitumor activity observed in the K‐RAS mutant models. These findings support a vertical inhibition strategy in which RAF dimer and MEKi are combined to target K‐RAS‐mutated cancers, and have led to a Phase 1b/2 combination therapy study of lifirafenib and mirdametinib in solid tumor patients with K‐RAS mutations and other MAPK pathway aberrations., The reduced sensitivity of K‐RAS‐mutated cancer cells to MEK inhibitors (MEKi), such as selumetinib and mirdametinib, is associated with feedback phosphorylation of MEK by upstream RAF reactivation. RAF dimer inhibitors, such as lifirafenib and compound C, in combination with MEKi potently suppress RAF‐dependent MEK phosphorylation and lead to sustained inhibition of MAPK signaling and tumor growth.

A folded chain, with one end fixed at the ceiling and the other end released from the same elevation, is commonly modeled as an energy-conserving system in one dimension. However, the analytical paradigm in the existing literature is unsatisfying: The theoretical prediction of the tension at the fixed end becomes infinitely large when the free end reaches the bottom, contradicting the experimental observations. Furthermore, the dependency of the total falling time on the link number demonstrated in numerical simulations is still unexplained. Here, considering the link transition between the two sub-chains and the geometry of each link, we introduce an additional term for the relation of balance of kinetic energy to account for the jump of link velocity at the fold. We derive analytical solutions of the maximal tension as well as the total falling time, in agreement with simulation results and experimental data reported in previous studies. This theoretical perspective extends the classical standard treatment, shows a simple representation of the complicated two-dimensional falling chain system and, in particular, specifies the signature of the chain properties.

SUMMARYIntestinal lacteals are the essential lymphatic channels for absorption and transport of dietary lipids and drive pathogenesis of debilitating metabolic diseases. Yet, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover a novel intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer, ASE, alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic-dependent lipid transport. Surprisingly, activation of lymphatic-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. In summary, our studies reveal the molecular mechanism linking gut lymphatic development to the earliest symmetry-breaking Pitx2 and highlight the important relationship between intestinal lymphangiogenesis and gut-liver axis. GRAPHICAL ABSTRACTHIGHLIGHTS∼ Gut lymphangiogenesis is linked to Pitx2-driven LR asymmetry∼ Lacteal-associated smooth muscle requires ASE∼ ASE deletion leads to redox imbalance in intestinal smooth muscle lineage∼ ASE is required for the normal route of dietary lipid transport∼ Pitx2ASE/ASE neonates develop diet-induced fatty liver disease

Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. In this study, we identified the molecular mechanism by which androgen regulates ADTRP expression and tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression. Luciferase assays with an ADTRP promoter luciferase reporter revealed that androgen regulated ADTRP transcription in a dose- and time-dependent manner, and the effect was abolished by three different androgen inhibitors, including pyrvinium pamoate, bicalutamide, and cyproterone acetate. Chromatin-immunoprecipitation showed that the androgen receptor bound to a half androgen response element (ARE, TGTTCT) located at + 324 bp from the ADTRP transcription start site. The ARE is required for concentration-dependent transcriptional activation of ADTRP. HL-60 monocyte adhesion to EAhy926 endothelial cells (ECs) and transmigration across the EC layer, the two processes critical to development of CAD and MI, were inhibited by androgen, but the effect was rescued by ADTRP siRNA and exacerbated by overexpression of ADTRP and its downstream genes PIK3R3 and MIA3. These data suggest that one molecular mechanism by which androgen confers protection against CAD is stimulation of ADTRP expression.

SUMMARY Intestinal lacteals are essential lymphatic channels for absorption and transport of dietary lipids and drive the pathogenesis of debilitating metabolic diseases. However, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover an intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer ASE alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic system-dependent lipid transport. Surprisingly, activation of lymphatic system-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. Our study reveals the molecular mechanism linking gut lymphatic function to the earliest symmetry-breaking Pitx2 and highlights the important relationship between intestinal lymphangiogenesis and the gut-liver axis., Graphical Abstract, In brief Lacteals drive dietary lipid absorption, but how they form remains mostly unknown. Hu et al. demonstrate how the Pitx2 gene directs lacteal development through the adjacent muscle lineage and protects against fatty liver disease. This holds promise for combating intestinal diseases and identifying regulators of alternative fat absorption pathways.

Accurate and precise measurements of the Hubble constant are critical for testing our current standard cosmological model and revealing possibly new physics. With Hubble Space Telescope (HST) imaging, each strong gravitational lens system with measured time delays can allow one to determine the Hubble constant with an uncertainty of $\sim 7\%$. Since HST will not last forever, we explore adaptive-optics (AO) imaging as an alternative that can provide higher angular resolution than HST imaging but has a less stable point spread function (PSF) due to atmospheric distortion. To make AO imaging useful for time-delay-lens cosmography, we develop a method to extract the unknown PSF directly from the imaging of strongly lensed quasars. In a blind test with two mock data sets created with different PSFs, we are able to recover the important cosmological parameters (time-delay distance, external shear, lens mass profile slope, and total Einstein radius). Our analysis of the Keck AO image of the strong lens system RXJ1131-1231 shows that the important parameters for cosmography agree with those based on HST imaging and modeling within 1-$\sigma$ uncertainties. Most importantly, the constraint on the model time-delay distance by using AO imaging with $0.045"$resolution is tighter by $\sim 50\%$ than the constraint of time-delay distance by using HST imaging with $0.09"$when a power-law mass distribution for the lens system is adopted. Our PSF reconstruction technique is generic and applicable to data sets that have multiple nearby point sources, enabling scientific studies that require high-precision models of the PSF., Comment: 20 pages, 15 figures

K-RAS mutation represents one of the most frequent genetic alterations in cancers. Monotherapy approaches targeting RAS downstream effectors such as MEK and ERK have had limited clinical success in patients with K-RAS-mutated cancers. The reduced sensitivity of K-RAS-mutated cells to certain MEK inhibitors is associated with feedback phosphorylation of MEK and reactivation of mitogen-activated protein kinase (MAPK) signaling. Herein, we report that RAF dimer inhibitor lifirafenib (BGB-283) shows strong synergistic effect with MEK inhibitor mirdametinib (PD-0325901) in suppressing proliferation of K-RAS-mutated cancer cell lines. This synergistic effect was not observed using vemurafenib, a first-generation B-RAFV600E selective inhibitor. Mechanistic analysis revealed that RAF dimer inhibition could suppress RAF-dependent MEK reactivation and led to sustained inhibition of MAPK signaling in K-RAS-mutated cells. Furthermore, combination synergy was observed in K-RAS mutant xenograft models. Pharmacodynamic analysis supported the role of synergistic phospho-ERK blockade in enhancing the antitumor activity in the K-RAS mutant models. These findings support the rationale to combine a RAF dimer inhibitor and a MEK inhibitor to treat K-RAS-mutated cancers and led to the ongoing a Phase Ib/II clinical trial of lifirafenib and mirdametinib in patients with K-RAS mutations or other MAPK pathway aberrations (Clinical Trial ID: NCT03905148). Citation Format: Xi Yuan, Xinwen Zhang, Rong Du, Shing-Hu Cheung, Min Wei, Changyou Zhou, Lai Wang, Todd Shearer, Badreddin Edris, Mary Smith, Zhan Yao, Claire N. Thant, Neal Rosen, Lusong Luo. RAF dimer inhibitor lifirafenib enhances the antitumor activity of MEK inhibitor mirdametinib in RAS mutant tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6415.

Genomic variants in both ADTRP and TFPI genes are associated with risk of coronary artery disease (CAD). ADTRP regulates TFPI expression and endothelial cell functions involved in the initiation of atherosclerotic CAD. ADTRP also specifies primitive myelopoiesis and definitive hematopoiesis by upregulating TFPI expression. However, the underlying molecular mechanism is unknown. Here we show that transcription factor POU1F1 is the key by which ADTRP regulates TFPI expression. Luciferase reporter assays, chromatin-immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) in combination with analysis of large and small deletions of the TFPI promoter/regulatory region were used to identify the molecular mechanism by which ADTRP regulates TFPI expression. Genetic association was assessed using case-control association analysis and phenome-wide association analysis (PhenGWA). ADTRP regulates TFPI expression at the transcription level in a dose-dependent manner. The ADTRP-response element was localized to a 50 bp region between −806 bp and −756 bp upstream of TFPI transcription start site, which contains a binding site for POU1F1. Deletion of POU1F1-binding site or knockdown of POU1F1 expression abolished ADTRP-mediated transcription of TFPI. ChIP and EMSA demonstrated that POU1F1 binds to the ADTRP response element. Genetic analysis identified significant association between POU1F1 variants and risk of CAD. PhenGWA identified other phenotypic traits associated with the ADTRP-POU1F1-TFPI axis such as lymphocyte count (ADTRP), waist circumference (TFPI), and standing height (POU1F1). These data identify POU1F1 as a transcription factor that regulates TFPI transcription in response to ADTRP, and link POU1F1 variants to risk of CAD for the first time.

The leading cause of death worldwide is disease of the coronary arteries, the vessels that nourish the heart muscle. However, mechanisms that control their development and possible regeneration remain unknown. Recent work is challenging current dogma of coronary artery origins and illuminating key programs that govern coronary artery formation.

Oncogenic BRAF, which drives cell transformation and proliferation, has been detected in approximately 50% of human malignant melanomas and 5% to 15% of colorectal cancers. Despite the remarkable clinical activities achieved by vemurafenib and dabrafenib in treating BRAFV600E metastatic melanoma, their clinical efficacy in BRAFV600E colorectal cancer is far less impressive. Prior studies suggested that feedback activation of EGFR and MAPK signaling upon BRAF inhibition might contribute to the relative unresponsiveness of colorectal cancer to the first-generation BRAF inhibitors. Here, we report characterization of a dual RAF kinase/EGFR inhibitor, BGB-283, which is currently under clinical investigation. In vitro, BGB-283 potently inhibits BRAFV600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harboring BRAFV600E and EGFR mutation/amplification. In BRAFV600E colorectal cancer cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell line-derived and primary human colorectal tumor xenografts bearing BRAFV600E mutation. These findings support BGB-283 as a potent antitumor drug candidate with clinical potential for treating colorectal cancer harboring BRAFV600E mutation. Mol Cancer Ther; 14(10); 2187–97. ©2015 AACR.

Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. Here, we tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression. Luciferase assays with an ADTRP promoter luciferase reporter revealed that androgen regulated ADTRP transcription. Chromatin-immunoprecipitation showed that the androgen receptor bound to a half androgen response element (ARE) located at +324bp from the ADTRP transcription start site. The ARE is required for the transcriptional activation of ADTRP . HL-60 monocyte adhesion to EAhy926 endothelial cells (ECs) and transmigration across the EC layer, the two processes critical to development of CAD and MI, were inhibited by androgen, but the effect was reduced by ADTRP siRNA and enhanced by overexpression of ADTRP . These data suggest that one molecular mechanism by which androgen confers protection against CAD is stimulation of ADTRP expression.

Researchers put efforts to discover more efficient ways to classification problems for a period of time. Recent years, the support vector machine (SVM) becomes a well-popular intelligence algorithm developed for dealing this kind of problem. In this paper, we used the core idea of multi-objective optimization to transform SVM into a new form. This form of SVM could help to solve the situation: in tradition, SVM is usually a single optimization equation, and parameters for this algorithm can only be determined by user’s experience, such as penalty parameter. Therefore, our algorithm is developed to help user prevent from suffering to use this algorithm in the above condition. We use multi-objective Particle Swarm Optimization algorithm in our research and successfully proved that user do not need to use trial – and – error method to determine penalty parameter C. Finally, we apply it to NIST-4 database to assess our proposed algorithm feasibility, and the experiment results shows our method can have great results as we expect.

Introduction In pulse diagnosis, three positions ( Cun , Guan , Chi ) and three levels or depths ( Fu , Zhong , Chen ), called the Three Positions and Nine Indicators (TPNI) are generally used as a finger-reading method, to obtain a holistic view of the patient. However, single pulse signals at nine TPNI locations (three depths at three positions) look quite similar in a waveform. Hence, the aim of this study was to determine if there was a significant difference between pulse-taking depths (Fu, Zhong, and Chen) and pulse-taking positions (Cun, Guan, and Chi). Method To explore the significance of array pulses at the nine TPNI locations, a Bi-Sensing Pulse Diagnosis Instrument (BSPDI) with array sensors was used to measure wrist artery pulse signals. It was proposed that a three-dimensional pulse mapping (3DPM) could present array pulses mimicking the fingertips’ sensations of a physician. Four parameters, namely peak value ( P _ V max ), power ( P _ P ), ascending slope ( P _AS), and descending slope ( P _DS) were elucidated from 3DPM using a two-way analysis of variance. Eight volunteers with TPNI health rule of thumb from the R.O.C. Air Force Academy participated in this research. Results The variance of four parameters at nine TPNI locations all reached the level of significance ( p Conclusions The differences in wrist artery signals exist between TPNI locations. TPNI pulse diagnosis could be used to check the holistic health of a patient as determined by TCM.

The problem of fingerprint classification is discussed for many years. Support Vector Machine (SVM) is a traditional artificial intelligence algorithm developed for dealing classification problems. In this paper, we used the idea of multi-objective optimization to transform SVM into a new form, since the core concept of SVM is built up on a single optimization equation, and some parameters for this algorithm still need user to make tons of experiment to determine. Our algorithm has successfully proved that user do not need to make experiment to determine the penalty parameter C. NIST-4 database is used to assess our proposed algorithm. The experiment results show our method can get good classification results.

At present, the synthesizing faces of different ages does not emphasize on feature alignment and rectification of twisted images. If these situations do happen, they might cause failure and inaccuracy on synthesizing images. In this paper, we propose a reversible human facial aging/rejuvenating synthesis system which is implemented by Active Shape Model (ASM) integrated with Log-Gabor Wavelet, which can be used to search for the dementia elderly. First, we use AdaBoost and ASM algorithm to extract the feature set of human face, and rectify them by the concept of facial geometric invariance. The invariant concepts are the distance between inner corners of both eyes and the distance between the nose and chin. Then, we find manually one target image which is similar to the test image from the database, and analyze age texture of this human image by Log-Gabor wavelet in order to retrieve decomposition maps. Finally, we can effectively simulate human facial images of people of different ages by controlling the number of decomposition map of images and objectively judge the results via the density of wrinkles.

Conventional 2D face recognition methods often struggle when a subject's head is turned even slightly to the side. In this study, a face recognition system based on 3D head modeling that is able to tolerate facial rotation angles was constructed by leveraging the Open source graphic library (OpenGL) framework. To minimize the extensive angle searching time that often occurs in conventional 3D modeling, Particle Swarm Optimization (PSO) was used to determine the correct facial angle in 3D. This reduced the angle computation time to 6 seconds, which is significantly faster than other methods. Experimental results showed that successful ID recognition can be achieved with a high recognition rate of 90%.

In this paper, a robust and efficient face recognition system based on luminance distribution by using maximum likelihood estimation is proposed. The distribution of luminance components of the face region is acquired and applied to maximum likelihood test for face matching. The experimental results showed that the proposed method has a high recognition rate and requires less computation time.

A stringlike pulse is highly related to hypertension, and many classification approaches have been proposed in which the differentiation pulse wave (dPW) can effectively classify the stringlike pulse indicating hypertension. Unfortunately, the dPW method cannot distinguish the spring stringlike pulse from the stringlike pulse so labeled by physicians in clinics.By using a Bi-Sensing Pulse Diagnosis Instrument (BSPDI), this study proposed a novel Plain Pulse Wave (PPW) to classify a stringlike pulse based on an array of pulse signals, mimicking a Traditional Chinese Medicine physician's finger-reading skill.In comparison to PPWs at different pulse taking positions, phase delay Δθand correlation coefficient r can be elucidated as the quantification parameters of stringlike pulse. As a result, the recognition rates of a hypertensive stringlike pulse, spring stringlike pulse, and non-stringlike pulse are 100%, 100%, 77% for PPW and 70%, 0%, 59% for dPW, respectively.Integrating dPW and PPW can unify the classification of stringlike pulse including hypertensive stringlike pulse and spring stringlike pulse. Hence, the proposed novel method, PPW, enhances quantification of stringlike pulse.

Aim of this study Through the use of a Bi-Sensing Pulse Diagnosis Instrument (BSPDI) to quantify the finger-reading skills and sensations of TCM physicians, this study was intended to determine whether a subject defined as healthy by Western medicine could be confirmed by the Three Positions and Nine Indicators Health Rule of Thumb (TPNI-HRT) regarding QI circulation. Materials and methods According to the definitions of TCM, Zangfu possesses the spreading, escalating, descending, and reservation properties characteristic of whole-body QI circulation. These properties create the TPNI-HRT, which describes the sequential appearance of a pulse at the distal-middle-proximal ( CUN-GUAN-CHI ) positions in the wrist artery as the fingertip displacement moves from superficial ( Fu ) to deep ( Chen ). Results A total of 50 male undergraduates (age 19.3 ± 1.1 years) in the Taiwan Air Force Academy in excellent health demonstrated normal pulses according to cardiovascular kinetics. The BSPDI was used to mimic the TCM physicians’ finger-reading skills, and the TPNI-HRT agreement ratio between the finger-reading sensations of TCM physicians and the BSPDI measurements was 94% (34:36 pulse appearances). Conclusions Through the use of BSPDI to evaluate the holistic QI circulation, only 4% of the 50 patients in this study demonstrated both excellent health according to Western medicine standards and completely met the conditions of the TPNI-HRT. This result suggests that there should be consideration as to whether the TPNI-HRT should be included in standard health examinations as well as whether TCM researchers should adopt quantitative TCM methodologies rather than utilizing the quantitative tools of Western medicine.

Aim of this study This paper reports the construction and functionality of a newly designed Bi-Sensing Pulse Diagnosis Instrument (BSPDI) with a Pressure-Displacement Bi-Sensing System (PDBSS) coupled to a robot finger system. The BSPDI is used to simulate the three positions and nine indicators (TPNI) using the finger-reading rule, which addresses the three levels of superficial ( Fu ), medium ( Zhong ), and deep ( Chen ) at the three positions of distal ( CUN ), middle ( GUAN ) and proximal ( CHI ) on the wrist during pulse diagnosis. Materials and methods A strain gauge and polyvinylidene fluoride pressure sensor were integrated as a PDBSS to separately record finger-reading skills and sense a physician's fingertip sensations. The corresponding sensation and pulse-taking displacement between the physician's fingertips and the BSPDI and the relationship between the pulse diagnosis and the nine TPNI displacements were used to determine the feasibility of the BSPDI. Results TPNI displacements, representing a physician's finger-reading skill, were recorded using a PDBSS. In this scenario, the BSPDI robot fingertips with pressure sensors were placed at the nine recorded TPNI displacements. The pressure sensors recorded pulse signals to simulate a physician's fingertip sensations. Two groups of participants with different health statuses were evaluated by both the BSPDI and TCM physicians. Both groups received similar diagnoses, and the results of a two-way ANOVA indicated that pulse diagnoses were highly related to the clinical experiences of the pulse-taking displacements and positions. Conclusions The novel BSPDI can be used to successfully mimic a TCM physician's finger-reading skill, as this technique obtained pulse signals at the nine TPNI displacements representing fingertip sensations.