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Chen, L.

Publications and source records attributed to Chen, L..

At least 505 records · Page 28Linked to original sources
bioRxiv2023

Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids

Due to proteostasis stress induced by aging or disease, misfolded proteins can form toxic intermediate species of aggregates and eventually mature into less toxic inclusion bodies (IBs). Here, using a yeast imaging-based screen, we identified 84 potential synphilin-1 (SY1) IB regulators and isolated the conserved sphingolipid metabolic components in the most enriched groups. Furthermore, we show that, in both yeast cells and mammalian cells, SY1 IBs are associated with mitochondria. Pharmacological inhibition of the sphingolipid metabolism pathway or knockout of its key genes results in a delayed IB maturation and increased SY1 cytotoxicity. We postulate that SY1 IB matures by association with the mitochondrion membrane, and that sphingolipids stimulate the maturation via their membrane-modulating function and thereby protecting cells from SY1 cytotoxicity. Our findings identify a conserved cellular component essential for IB maturation and suggest a mechanism by which cells may detoxify the pathogenic protein aggregates through forming mitochondrion-associated IBs.

cell biology↗
bioRxiv2023

Gut microbial genomes with paired isolates from China signify probiotic and cardiometabolic effects

The gut microbiome displays significant genetic differences between populations while systematic characterization of the genomic landscape of the gut microbiome in Asia populations remains limited. Here, we present the Chinese gut microbial reference (CGMR) set, comprising 101,060 high quality metagenomic assembled genomes (MAGs) of 3,707 non-redundant species paired with 1,376 live isolates from a national wide collection of 3,234 fecal samples across China. This improved reference set contains 987 novel species compared with existing resources worldwide. By associating MAGs with geographic and phenotypic characteristics, we observed regional-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. We further conducted mice experiments to confirm the probiotic effects of two Faecalibacterium intestinalis isolates in alleviating constipation, the cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and the functional potential of isolates from the two new species belonging to the genera Parabacteroides and Lactobacillus in host lipids metabolism. Our study not only expands the current microbial genomes with paired isolates but also demonstrates their probiotic and cardiometabolic effects on hosts, contributing to the mechanistic understanding of host-microbe interactions and the translation of microbiome-based personalized therapies.

microbiology↗
bioRxiv2023

Quantitative monitoring of neuronal regeneration by functional assay and wireless neural recording

Brain injury is heterozygous in nature and no single scheme is ideal for diagnosis and prognosis. Assessing proteins in cerebrospinal fluid is limited or not applicable after surgery whereas plasma biomarkers can only report occurrence of injury. The lack of regeneration markers renders the difficulty during drug discovery. This study aims to establish a potential reporter that correlates the regeneration progress of injured brain neurons. According to our recent publication, treatment of mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) could rescue motor function deficit of mice after traumatic brain injury. We thus measured the local field potential (LFP) at sites proximal to the injury region. The recorded neuronal activity reported stimulation of right forelimb of mice. Our experimental results indicate that the recovery of evoked LFP correlates with FCCP treatment and could potentially be used as a regeneration biomarker. These promising findings suggest future application of a wireless, non-invasive recording system as a potential companion diagnosis device during drug development.

bioengineering↗
bioRxiv2023

Morphological, molecular, and functional characterization of mouse glutamatergic myenteric neurons

The enteric nervous system (ENS) functions largely independently of the central nervous system (CNS). Correspondingly, glutamate, the dominant neurotransmitter in the CNS and sensory afferents, is not a primary neurotransmitter in the ENS. Only a fraction (approximately 2%) of myenteric neurons in the mouse distal colon and rectum (colorectum) are positive for vesicular glutamate transporter type 2 (VGLUT2), the structure and function of which remain undetermined. Here, we systematically characterized VGLUT2-positive enteric neurons (VGLUT2-ENs) through sparse labeling with adeno-associated virus, single-cell mRNA sequencing (scRNA-seq), and GCaMP6f calcium imaging. Our results reveal that the majority of VGLUT2-ENs (29 out of 31, 93.5%) exhibited Dogiel type I morphology with a single aborally projecting axon; most axons (26 out of 29, 89.7%) are between 4 and 10 mm long, each traversing 19 to 34 myenteric ganglia. These anatomical features exclude the VGLUT2-ENs from being intrinsic primary afferent or motor neurons. The scRNA-seq conducted on 52 VGLUT2-ENs suggests different expression profiles from conventional descending interneurons. Ex vivo GCaMP6f recordings from flattened colorectum indicate that almost all VGLUT2-EN (181 out of 215, 84.2%) are indirectly activated by colorectal stretch via nicotinic cholinergic neural transmission. In conclusion, VGLUT2-ENs are a functionally unique group of enteric neurons with single aborally projecting long axons that traverse multiple myenteric ganglia and are activated indirectly by colorectal mechanical stretch. This knowledge will provide a solid foundation for subsequent studies on the potential interactions of VGLUT2-EN with extrinsic colorectal afferents via glutamatergic neurotransmission. New & NoteworthyWe reveal that VGLUT2-positive enteric neurons (EN), although constituting a small fraction of total EN, are homogeneously expressed in the myenteric ganglia, with a slight concentration at the intermediate region between the colon and rectum. This concentration coincides with the entry zone of extrinsic afferents into the colorectum. Given that VGLUT2-ENs are indirectly activated by colorectal mechanical stretch, they are likely to participate in visceral nociception through glutamatergic neural transmission with extrinsic afferents.

neuroscience↗
bioRxiv2023

Reduced glutamate decarboxylase 1 underlies morphine-promoted lung metastasis of triple-negative breast cancer in mice

IntroductionMorphine is commonly used for cancer-related pain management. Long-term morphine use is not only addictive but also has been associated with risk factor for cancer. MethodsWe intraperitoneally administered morphine to mice for 14 days and then implanted EO771 cells, triple negative breast cancer cells, into their mammary fat pad. After primary tumors were removed on 38th day, a subset of mice were continuously giving saline or morphine until the 68th day. Tumor size, organ metastasis, and tumor RNA expression were analyzed. ResultsOur results revealed that long-term morphine treatment increased lung metastasis in the triple-negative breast cancer mouse model. To determine cellular pathways responsible for morphine-mediated metastasis, we performed RNA sequencing analysis to compare transcriptional profiles during metastasis. Transcriptional analysis revealed a significant number of genes down-regulated by morphine treatment. Based on pathway analysis, we focused on the novel effect of morphine on down-regulating taurine/hypotaurine biosynthesis. Considering that morphine, droperidol (dopamine receptor antagonist), and naloxone (opioid receptor antagonist) may act through opioid receptor or dopamine receptor, we further demonstrated that taurine reduced EO771 cell invasion caused by morphine, but not by droperidol, or naloxone treatment. In addition, morphine treatment significantly reduced the expression of GAD1, one of the enzymes required for biosynthesis of taurine, whereas droperidol and naloxone did not. ConclusionThese novel findings of morphine reduces GAD1 level and taurine reverses invasion suggest that taurine could potentially be employed as a supplement for triple negative breast cancer patients using morphine as pain management. Key MessagesO_LIMorphine usage has been implicated in modulating immune system and affecting cancer progression. C_LIO_LILong-term usage of morphine promotes metastasis of triple negative breast cancer through reducing taurine biosynthesis. C_LIO_LIThese novel findings of morphine reduces GAD1 level and taurine reverses invasion suggest that taurine could potentially be employed as a supplement for triple negative breast cancer patients using morphine as pain management. C_LI

cancer biology↗
bioRxiv2023

SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients

BackgroundThe inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. MethodsIn this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, follicular helper T (Tfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 weeks and 20 weeks after Omicron BA.5 infection. ResultsTwelve months after the third CoronaVac vaccination, spike-specific antibody and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity and durability of serum neutralization activities, Fc-mediated phagocytosis, and nasal spike-specific IgA responses, memory B cells, activated Tfh cells memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently higher than for the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous SARS-CoV-2 infection. ConclusionOur data provides detailed insight into the protective role of inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection. Trial registrationClinicalTrials.gov NCT05680896 FundingThis study was supported by the National Natural Science Foundation of China (92269118, 92269205), Nanjing Important Science & Technology Specific Projects (2021-11005), Scientific Research Project of Jiangsu Health Commission (M2022013), Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-PY-9), and Jiangsu graduate practice innovation project (JX22013929).

immunology↗
bioRxiv2023

Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer

KRASG12C inhibitors including adagrasib and sortorasib have shown clinical promise in targeting KRASG12C-mutated lung cancers, however, most patients eventually develop drug resistance. In lung adenocarcinoma patients with co-occurring KRASG12C and STK11/LKB1 mutations, we found a high squamous gene signature at baseline significantly correlated with poor adagrasib response. Through integrative studies of Lkb1-deficient KRASG12Cand KrasG12D lung cancer mouse models and/or organoids treated with KRAS inhibitors, we found tumor cells invoked a lineage plasticity program: adeno-to-squamous transition (AST) that mediated resistance to KRAS inhibition. Transcriptomic and epigenomic analyses revealed {Delta}Np63 drives AST and modulates response to KRAS inhibition. We identified an intermediate high-plasticity cell state with distinct gene expression program marked by Krt6a upregulation. Notably, higher KRT6A expression at baseline correlated with shorter overall survival in KRAS-mutant patients receiving adagrasib. These data support the role of AST in KRAS inhibitor resistance and provide predictive biomarker for KRAS-targeted therapies in lung cancer.

cancer biology↗
bioRxiv2023

Hsa_circ_0005397 could promote hepatocellular carcinoma progression and metastasis through EIF4A3

PurposeThe purpose was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma metabolism. MethodsThe quantitative real-time PCR (qPCR) was used to measure the expression of hsa_circ_0005397 and EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. The ROC curve was draw to analysis clinical value. The actinomycin D assay and Nuclear and Cytoplasmic Extraction assay were utilized to evaluate the characteristic of hsa_circ_0005397. The CCK-8 and colony formation assays were performed to detect cell proliferation. The flow cytometry analysis was used to detect the cycle distribution. The transwell assays and Xenograft tumor model were conducted to explore cell metabolism. The RNA-binding proteins of hsa_circ_0005397 in HCC were explored in bioinformatics websites. The relationship between hsa_circ_0005397 and EIF4A3 was verified by RIP assays and rescue experiments. ResultsHsa_circ_0005397 and EIF4A3 were overexpressed in HCC. Through ROC analysis, hsa_circ_0005397 shown a big role in diagnosis and prognosis. Hsa_circ_0005397 was stable and almost distributed in the cytoplasm. The upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, metastatic potency of HCC cells, while downregulation of hsa_circ_0005397 yielded opposite results. Tumor volume and size were notably reduced while downregulation of hsa_circ_0005397, showing significant difference in tumor growth. EIF4A3 was the RNA-binding protein of hsa_circ_0005397, the expression of hsa_circ_0005397 decreased equally when depletion of EIF4A3. Knockdown of EIF4A3 could reverse the function on HCC progression. ConclusionsHsa_circ_0005397 could promote the progression of hepatocellular carcinoma through EIF4A3. These research findings may present a novel clinical value for HCC.

cancer biology↗
bioRxiv2023

CLOCK Mediates Delay in Cardiac Myofibroblast Formation and Attenuates Progression of Myocardial Fibrosis through Inhibition of Smad 3 Transcriptional Activity

IntroductionMyocardial fibrosis, characterized by excessive extracellular matrix deposition, leading to adverse cardiac remodeling and impaired function. The differentiation of cardiac fibroblasts into myofibroblasts plays a pivotal role in this process. The involvement of the core clock protein CLOCK in the formation of cardiac myofibroblasts and the advancement of myocardial fibrosis is not well understood. This study aims to investigate how CLOCK modulates cardiac myofibroblast differentiation and attenuates myocardial fibrosis by inhibiting Smad3 transcriptional activity. MethodsIn vivo, adeno-associated virus 9 was utilized for overexpression or silencing of the CLOCK gene via mice intravenous injection. In vitro experiments were conducted using primary cultures of cardiac fibroblasts isolated from mouse hearts to examine the expression levels of molecular markers associated with myofibroblast differentiation, such as -smooth muscle actin (-SMA) and collagen I. Additionally, a Smad3 luciferase reporter gene experiment was employed to assess the transcriptional activity of Smad3 under CLOCK regulation. ResultsThe results demonstrate that CLOCK overexpression significantly reduces the expression of -SMA and collagen I in cardiac fibroblasts, indicating a suppression of myofibroblast formation. Conversely, CLOCK knockdown enhances the expression of these fibrotic markers. Interestingly, CLOCK was found to negatively regulate the transcriptional activity of Smad3, suggesting a potential mechanism by which CLOCK exerts its inhibitory effect on cardiac fibrosis. Specifically, CLOCK interacts with Smad3, inhibiting its nuclear translocation and subsequent activation of fibro genic gene expression. ConclusionThese findings highlight the crucial role of CLOCK in the regulation of cardiac myofibroblast formation and the progression of myocardial fibrosis. CLOCK appears to exert an inhibitory effect on fibrotic signaling pathways, partially through the inhibition of Smad3 transcriptional activity. This study provides novel insights into the molecular mechanisms underlying cardiac fibrosis and emphasizes the therapeutic potential of targeting CLOCK-mediated pathways for treating myocardial fibrosis.

molecular biology↗
bioRxiv2023

Mechano-signaling of prostate tumor initiating cells facilitates their tropism to stiff metastatic niche

Analysis of clinical datasets indicate that cancer stem-like cells/tumor-initiating cells (CSCs/TICs) derived from prostate cancer (PCa) patients display an elevated expression of genes for cell-matrix interactions, cell adhesion proteins and of the putative mechanotransducer TAZ. Here we combined measurements on the cellular mechano-responses to matrix stiffness, including cell-generated forces, zebrafish and PDX-derived organoid models, to show that mechanotransduction serves as a key determinant for PCa CSC maintenance during metastatic onset. The {beta}1-integrin-ILK-CDC42-N-Wasp dependent cytoskeletal tension and TAZ nucleus-translocation mediate this mechano-signaling axis. As a result, expression of the stemness genes NANOG and OCT4 are induced, leading to metastatic tumor initiation. It is further demonstrated that pharmaceutical perturbation of this mechano-signaling using a novel YAP/TAZ inhibitor K975 constrains PCa metastasis in zebrafish, and development of PDX-derived organoids. Our data highlights the essential role of mechanotransduction in PCa aggressiveness, thereby underlying this pathway as a therapeutic target for future studies.

cancer biology↗
bioRxiv2023

Rationally designed multimeric nanovaccines using icosahedral DNA origami for molecularly controlled display of SARS-CoV-2 receptor binding domain

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employed an icosahedral DNA origami (ICO) as a display particle for SARS-CoV-2 RBD nanovaccines. The morphology and diameter of the particles were close to those of the virus (91 {+/-} 11 nm). The surface addressability of the DNA origami permitted facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoked stronger and more enduring humoral and T cell immune responses in mouse models compared to soluble RBD antigens. Our vaccines activated similar humoral immunity and slightly stronger cellular immunity compared to mRNA vaccines. These results provide reference principles for the rational design of nanovaccines and exemplify the utility of DNA origami as a display platform for vaccines against infectious disease.

bioengineering↗
bioRxiv2023

Overestimation in time reproduction: Influences of accuracy feedback and attentional sharing

Duration reproduction is often subjective to biases, with a general tendency to overestimate durations, which has been observed in many studies. Yet, this overestimation is frequently dismissed as a nuisance error, and its underlying mechanisms remain elusive. Here, we conducted two experiments to investigate this general overestimation in duration reproduction. To pin down the origin of the error, we manipulated the reproduction output through shortened visual feedback in Experiment 1, while varying the presence of accuracy feedback in Experiment 2. Across both experiments, we observed a consistent overestimation in reproduction when accuracy feedback was absent. This overestimation, amounting to approximately 13.5% on a ratio basis across different durations and sessions, was unaffected by shortened visual feedback. We propose that this consistent overestimation is likely due to the attentional sharing between the action execution and the monitoring of the passage of time during the reproduction process.

neuroscience↗
bioRxiv2023

Extended toolboxes enable efficient biosynthesis of valuable chemicals directly from CO2 in fast-growing Synechococcus sp. PCC 11901

CO2 recycle is crucial to the global carbon neutrality. Though cyanobacteria are known to be photoautotrophic cell factories capable of converting CO2 into valuable chemicals, their slower growth rate and lower biomass accumulation compared to those of the heterotrophic organisms significantly restrict their application at commercial scale. The newly discovered marine cyanobacterium, Synechococcus sp. PCC 11901 (hereafter PCC 11901) offers several advantages like rapid growth, high biomass and high salinity tolerance, and could become a new generation of cyanobacterial chassis. To promote its application, in this study we developed genetic toolboxes applicable to PCC11901. First, a cobalamin (VB12)-independent chassis was constructed, allowing for its cheaper cultivation. Second, genome copy numbers and transformation methods were respectively measured and optimized. The 14 neutral sites were identified and characterized within the genome PCC 11901, providing locations for genetic integration of exogenous cassettes. Subsequently, libraries were developed, reaching an expression range of approximately 800 folds for constitutive promoters and an induction fold of up to approximately 400 for inducible promotor, respectively. As a proof of concept of its utilization, we engineered the synthetic pathways of glucosylglycerol (GG) into PCC 11901 using the established toolboxes, yielding 590.41 {+/-} 21.48 mg/L for GG production. Notably, we found the cobalamin-independent PCC 11901 chassis exhibited superior self-sedimentation ability compared to the wild-type chassis. Our work here made it possible to develop the fast-growing PCC 11901 as efficient carbon-neutral cell factory in the future.

synthetic biology↗
bioRxiv2023

ClairS: a deep-learning method for long-read somatic small variant calling

Identifying somatic variants in tumor samples is a crucial task, which is often performed using statistical methods and heuristic filters applied to short-read data. However, with the increasing demand for long-read somatic variant calling, existing methods have fallen short. To address this gap, we present ClairS, the first deep-learning-based, long-read somatic small variant caller. ClairS was trained on massive synthetic somatic variants with diverse coverages and variant allele frequencies (VAF), enabling it to accurately detect a wide range of somatic variants from paired tumor and normal samples. We evaluated ClairS using the latest Nanopore Q20+ HCC1395-HCC1395BL dataset. With 50-fold/25-fold tumor/normal, ClairS achieved a 93.01%/86.86% precision/recall rate for Single Nucleotide Variation (SNVs), and 66.54%/66.89% for somatic insertions and deletions (Indels). Applying ClairS to short-read datasets from multiple sources showed comparable or better performance than Strelka2 and Mutect2. Our findings suggest that improved read phasing enabled by long-read sequencing is key to accurate long-read SNV calling, especially for variants with low VAF. Through experiments across various coverage, purity, and contamination settings, we demonstrated that ClairS is a reliable somatic variant caller. ClairS is open-source at https://github.com/HKU-BAL/ClairS.

bioinformatics↗
bioRxiv2023

Epstein-Barr virus BRRF1 induces butyrophilin 2A1 in nasopharyngeal carcinoma cells via the IL-22/JAK3-STAT3 pathway

Epstein-Barr virus is highly associated with nasopharyngeal carcinoma (NPC) with genes expressed for tumor transformation or maintenance of viral latency, but there are certain genes that can modulate immune molecules. Butyrophilin 2A1 (BTN2A1) is an important activating protein for presenting phosphoantigen presentation for recognition by V{gamma}9V{delta}2 T cells to achieve anti-tumor activities. We have previously shown that V{gamma}9V{delta}2 T cells achieve efficacy against NPC when BTN2A1 and BTN3A1 are upregulated by stimulating EBV gene expression, particularly LMP1. Whilst BTN3A1 can be induced by LMP1 mediated IFN-{gamma}/JNK/NLRC5 pathway, the viral gene that can regulate BTN2A1 remains elusive. Here, we showed that BTN2A1 expression is directly mediated by EBV BRRF1, which can trigger BTN2A1 promoter and downstream JAK3-STAT3 pathway in NPC43 cells as enlightened by RNA-seq data and verified by inhibitor experiments. Further, BRRF1 downregulated IL-22 binding protein (IL-22RA2) to complement the EBNA1-targeting probe (P4) induced IL-22 expression. These functions act in concordance to enhance the expression of BTN2A1, which likely lead to increased tumor cell killing by V{gamma}9V{delta}2 T cells. Overall, this study elucidated a new mechanism of stimulating BTN2A1 expression in nasopharyngeal carcinoma cells by the EBV gene BRRF1. Summary statementThis study demonstrated a new function Epstein-Barr Virus BRRF1 to induce BTN2A1 in nasopharyngeal carcinoma via the IL-22/JAK3-STAT3 pathway, which potentiates V{gamma}9V{delta}2 T cells against NPC.

immunology↗
bioRxiv2023

Simultaneous targeting of AMPK and mTOR is a novel therapeutic strategy against prostate cancer

Metastatic colonization by circulating cancer cells is a highly inefficient process. To colonize distant organs, disseminating cancer cells must overcome many obstacles in foreign microenvironments, and only a small fraction of them survives this process. How these disseminating cancer cells cope with stress and initiate metastatic process is not fully understood. In this study, we report that the metastatic onset of prostate cancer cells is associated with the dynamic conversion of metabolism signaling pathways governed by the energy sensors AMPK and mTOR. While in circulation in blood flow, the disseminating cancer cells display decreased mTOR and increased AMPK activities that protect them from stress-induced death. However, after metastatic onset, the mTOR-AMPK activities are reversed, enabling mTOR-dependent tumor growth. Suppression of this dynamic conversion by co-targeting of AMPK and mTOR signaling significantly suppresses prostate cancer cell and tumor organoid growth in vitro and experimental metastasis in vivo, suggesting that this can be a therapeutic approach against metastasizing prostate cancer.

cancer biology↗
bioRxiv2023

ccTCM: a quantitative component and compound platform for promoting the research of traditional Chinese medicine

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001%, and a total of 1 449 were extracted. Subsequently, we collected 40767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform for that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.

bioinformatics↗