Identifying local associations in biological time series: algorithms, statistical significance, and applications.

Local associations refer to spatial-temporal correlations that emerge from the biological realm, such as time-dependent gene co-expression or seasonal interactions between microbes. One can reveal the intricate dynamics and inherent interactions of biological systems by examining the biological time series data for these associations. To accomplish this goal, local similarity analysis algorithms and statistical methods that facilitate the local alignment of time series and assess the significance of the resulting alignments have been developed. Although these algorithms were initially devised for gene expression analysis from microarrays, they have been adapted and accelerated for multi-omics next generation sequencing datasets, achieving high scientific impact. In this review, we present an overview of the historical developments and recent advances for local similarity analysis algorithms, their statistical properties, and real applications in analyzing biological time series data. The benchmark data and analysis scripts used in this review are freely available at http://github.com/labxscut/lsareview.

Progress of research on aroma absorption mechanism and aroma fixation pathway of jasmine green tea.

This overview summarizes the latest research progress on the aroma absorption mechanism and aroma fixation pathway of jasmine green tea, and discusses in depth the aroma absorption mechanism of green tea, the aroma release mechanism of jasmine flowers, as well as the absorption and fixation mechanism of the aroma components of jasmine green tea in the process of scenting, to provide a theoretical basis for the improvement of the quality of jasmine green tea and the innovation of processing technology. It was found that the aroma absorption mechanism of jasmine green tea is mainly associated with both physical and chemical adsorption, aroma release in jasmine involves the phenylpropanoid/benzoin biosynthetic pathway, ß-glycosidase enzymes interpreting putative glycosidic groups, and heat shock proteins (HSPs) as molecular chaperones to prevent stress damage in postharvest flowers due to high temperatures and to promote the release of aroma components, and so forth. The preparation of aroma-protein nano-complexes, heat stress microcapsules, and the spraying of polymeric substances - ß-cyclodextrin are three examples of aroma-fixing pathways. This overview also summarizes the problems and future development trends of the current research and proposes the method of loading benzyl acetate, the main aroma component of jasmine, through konjac glucomannan (KGM)-based gel to solve the problem of volatile aroma and difficult-to-fix aroma, which provides a reference for the sustainable development of the jasmine green tea industry. © 2024 Society of Chemical Industry.

Simultaneous analysis of derivatized allyl isothiocyanate together with its phase II metabolites by ultra-high-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Allyl isothiocyanate (AITC) in food products such as wasabi is commonly analyzed by gas chromatography/mass spectrometry (GC/MS), while liquid chromatography/mass spectrometry (LC/MS) is more suitable for the polar metabolites. The development of an effective method for the simultaneous determination of AITC and its phase II metabolites is needed to support drug metabolism and pharmacokinetics (DMPK) studies. METHODS: Derivatization of AITC by reaction with N-(tert-butoxycarbonyl)-L-cysteine methyl ester (t BocCysME) was used for ultra-high-performance liquid chromatography/electrospray ionization mass spectrometry (UHPLC/ESI-MS) analysis, allowing the simultaneous determination with its phase II metabolites. At room temperature, reaction conditions have been optimized to maximize the reaction of AITC with t BocCysME quantitively. Reaction selectivity was examined by the presence of AITC metabolites. Quantification of AITC was performed by multiple reaction monitoring (MRM) with an external calibration method and applied on the serum of C57BL/6 J mouse for a DMPK study. RESULTS: The limit of quantification (LOQ) was determined to be 0.842 nM from the derivatization method and by UHPLC/MS/MS analysis. The method accuracy in the mouse serum samples was 75 ± 2% with a relative standard deviation (RSD) of 3.0% of method variation. The UHPLC/MS/MS analysis gave RSDs of 0.2% and 1.8% for intra-day and inter-day variations. With the newly developed method, AITC could be detected in mouse serum upon oral administration for the first time. CONCLUSIONS: An analytical method involving a rapid derivatization pre-treatment and quantitative UHPLC/ESI-QqQ-MS/MS analysis has been developed for a biological sample assay of AITC, enabling selective and sensitive detection of the AITC derivative and AITC metabolites simultaneously. The method developed could be applied to the DMPK study of AITC as well.

Stress tolerance of Staphylococcus aureus with different antibiotic resistance profiles.

Staphylococcus aureus (S. aureus) is a zoonotic bacterium and is among the most important pathogens causing bacterial foodborne diseases. In recent years, disease caused by antibiotic-resistant S. aureus is a serious clinical problem that poses a great threat to public health. In this study, we examined the drug-resistance phenotypes and genotypes of 9 S. aureus strains. One strain was obtained from the China Center for Type Culture Collection (CCTCC), and the remaining eight strains were isolated from food. Two common methods (the Kirby-Bauer disk diffusion and broth microdilution methods) were used to detect bacterial drug resistance. Then, we analysed the relationship between the bacterial drug resistance phenotypes and genotypes. We found that some S. aureus strains isolated from food were drug-resistant or even multi-drug resistant and that there was not a perfect match between resistance phenotypes and genotypes. The viabilities of the drug-sensitive (DS), drug-resistant (DR), and multi-drug resistant (MDR) S. aureus strains were also compared when they were exposed to conditions of acid (HCl, pH = 1.5), heat (63 °C), and osmotic pressure (30% NaCl). The results showed that the DR and MDR bacterial strains had survival rates similar to or higher than those of the DS strains under environmental stress.

Ratiometric Fluorescent Nanoprobe for Highly Sensitive Determination of Mercury Ions.

In this study, a novel dual-emission ratiometric fluorescent nanoprobe (RFN) was synthesized and ultilized for highly sensitive determination of mercury ions. In this nanoprobe, fluorescein isothiocyanate (FITC) doped silica (SiO2) served as a reference signal, FITC-SiO2 microspheres were synthesized and modified with amino groups, and then Au Nanoclusters (AuNCs) were combined with the amino groups on the surface of the FITC-SiO2 microspheres to obtain the RFN. The selectivity, stability, and pH of the RFN were then optimized, and the determination of mercury ions was performed under optimal conditions. The probe fluorescence intensity ratio (F520 nm/F680 nm) and Hg2+ concentration (1.0 × 10-10 mol/L to 1.0 × 10-8 mol/L) showed a good linear relationship, with a correlation coefficient of R2 = 0.98802 and a detection limit of 1.0 × 10-10 mol/L, respectively. The probe was used for the determination of trace mercury ion in water samples, and the recovery rate was 98.15~100.45%, suggesting a wide range of applications in monitoring pollutants, such as heavy metal ion and in the area of environmental protection.

Pathway of 5-hydroxymethyl-2-furaldehyde formation in honey.

5-hydroxymethyl-2-furaldehyde (5-HMF) is an important substance that affect quality of honey and shows toxicity for humans and honey bees. The pathway of 5-HMF formation in honey is still unknown. In this study, we tested the effect of thermal treatment (at 90 °C for 4 h) on the formulation of 5-HMF formulation in rapeseed with varied honey composition. 5-HMF content of honey increased at higher water content, Ca2+ and Mg2+ content and lower pH. However, the formation of 5-HMF was not significantly influenced by glucose, fructose, Na+, or K+ contents. Furthermore, different content of proline, the most abundant amino acid in honey (a substance in Maillard reaction), had no effect on 5-HMF formation. Free acids in honey can catalyze fructose and glucose to form 5-HMF. These results suggest that dehydration of glucose or fructose, instead of the Maillard reaction, is the main pathway of 5-HMF formation in honey. This study gives new insights for the mechanisms of 5-HMF formation and provides method for reducing 5-HMF formation during honey processing.

Phenolic Compositions and Antioxidant Activities Differ Significantly among Sorghum Grains with Different Applications.

Sorghum grains with different applications had different phenolic profiles, which were corresponded to various antioxidant capacities. In this study, total phenolic, proanthocyanidins and flavonoids contents, as well as contents of individual phenolic compounds from sorghum grains with various applications were determined, and their antioxidant capacities were evaluated. Total phenolic contents (TPC) and total proanthocyanidins contents (TPAC) showed strong correlation with antioxidant activities (r > 0.95, p < 0.01). Hongyingzi (S-1), one of the brewing sorghums, showed the highest level of TPC and TPAC, while white grain sorghum (S-8) had the lowest. Except for black grain sorghum (S-7), that contained the highest contents of ferulic acid, brewing sorghum grains contained the higher contents of the most individual phenolic compounds, especially the variety S-1. The correlation among individual phenolic compounds and antioxidant activities indicated that the free forms of protocatechuic acid (r = 0.982 of FRAPassay, p < 0.01) and taxifolin (r = 0.826 of FRAP assay, p < 0.01) may be the main functional compounds. These results indicate that brewing sorghum grains can also be utilized as effective materials for functional foods.

Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis.

BACKGROUND: Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. METHODS: A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing. We integrated metagenomic sequence data from those two studies, including six healthy controls, 14 sites representative of stable periodontitis, 16 sites representative of progressing periodontitis, and seven periodontal sites of unknown status. We applied phylogenetic diversity, differential abundance, and network analyses, as well as clustering, to the integrated dataset to compare microbiological community profiles among the different disease states. RESULTS: We found alpha-diversity, i.e., mean species diversity in sites or habitats at a local scale, to be the single strongest predictor of subjects' periodontitis status (P < 0.011). More specifically, healthy subjects had the highest alpha-diversity, while subjects with stable sites had the lowest alpha-diversity. From these results, we developed an alpha-diversity logistic model-based naive classifier able to perfectly predict the disease status of the seven subjects with unknown periodontal status (not used in training). Phylogenetic profiling resulted in the discovery of nine marker microbes, and these species are able to differentiate between stable and progressing periodontitis, achieving an accuracy of 94.4%. Finally, we found that the reduction of negatively correlated species is a notable signature of disease progression. CONCLUSIONS: Our results consistently show a strong association between the loss of oral microbiota diversity and the progression of periodontitis, suggesting that metagenomics sequencing and phylogenetic profiling are predictive of early periodontitis, leading to potential therapeutic intervention. Our results also support a keystone pathogen-mediated polymicrobial synergy and dysbiosis (PSD) model to explain the etiology of periodontitis. Apart from P. gingivalis, we identified three additional keystone species potentially mediating the progression of periodontitis progression based on pathogenic characteristics similar to those of known keystone pathogens.

A comparative study of structural variant calling in WGS from Alzheimer's disease families.

Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in whole-genome sequencing from the Alzheimer's Disease Sequencing Project comprising 578 individuals from 111 families. Employing two complementary pipelines, Scalpel and Parliament, for SV/indel calling, we assessed sensitivity through sample replicates (N = 9) with in silico variant spike-ins. We developed a novel metric, D-score, to evaluate caller specificity for deletions. The accuracy of deletions was evaluated by Sanger sequencing. We generated a high-quality call set of 152,301 deletions of diverse sizes. Sanger sequencing validated 114 of 146 detected deletions (78.1%). Scalpel excelled in accuracy for deletions ≤100 bp, whereas Parliament was optimal for deletions >900 bp. Overall, 83.0% and 72.5% of calls by Scalpel and Parliament were validated, respectively, including all 11 deletions called by both Parliament and Scalpel between 101 and 900 bp. Our flexible protocol successfully generated a high-quality deletion call set and a truth set of Sanger sequencing-validated deletions with precise breakpoints spanning 1-17,000 bp.

Simultaneous determination of bisphenol A, aflatoxin B1, ochratoxin A, and patulin in food matrices by liquid chromatography/mass spectrometry.

RATIONALE: Bisphenol A has been widely used in plastic containers and this has raised safety concerns for fetuses, infants, and young children. Aflatoxin B1, ochratoxin A, and patulin are among the most toxic regulated mycotoxins found as contaminants in agricultural crops and animal products. To facilitate the analysis of these chemicals for regulatory purposes, we have developed an analytical method enabling their simultaneous detection in beverages and food products. METHODS: Analytes were extracted from food matrices such as cereal, peanut butter, cereal-based baby formula and fruit juices, and enriched by solid-phase extraction (SPE). Samples were analyzed by liquid chromatography/mass spectrometry using negative electrospray ionization with selected reaction monitoring, and matrix-matched external calibration was used for quantitation. RESULTS: The method was validated by analysis of five types of food and beverage samples fortified with different levels of these analytes. The SPE clean-up and matrix-matched external calibration were critical for the success of this method. The quantitation limits for these analytes ranged from 0.08 to 2.0 ppb, and the overall recoveries of the analytical method were within 66 to 127%. CONCLUSIONS: This quantitative method provided several advantages including minimal sample pretreatment, rapid and simultaneous analyte determination, high sensitivity and confirmatory identification. This method could be applied to a variety of food and beverages matrices where bisphenol A and these three mycotoxins may be present in suspect food products. Published 2013. This article is a US Government work and is in the public domain in the USA.

Ksak: A high-throughput tool for alignment-free phylogenetics.

Phylogenetic tools are fundamental to the studies of evolutionary relationships. In this paper, we present Ksak, a novel high-throughput tool for alignment-free phylogenetic analysis. Ksak computes the pairwise distance matrix between molecular sequences, using seven widely accepted k-mer based distance measures. Based on the distance matrix, Ksak constructs the phylogenetic tree with standard algorithms. When benchmarked with a golden standard 16S rRNA dataset, Ksak was found to be the most accurate tool among all five tools compared and was 19% more accurate than ClustalW2, a high-accuracy multiple sequence aligner. Above all, Ksak was tens to hundreds of times faster than ClustalW2, which helps eliminate the computation limit currently encountered in large-scale multiple sequence alignment. Ksak is freely available at https://github.com/labxscut/ksak.

Identification of Erectile Dysfunction Drugs in Dietary Supplements by Liquid Chromatography Ion Trap Mass Spectrometry.

With the rise in consumption of dietary supplements for various ailments such as erectile dysfunction (ED), there is concern that these supplements may contain illegally added phosphodiesterase type 5 (PDE-5) inhibitor and its analogs. HPLC or LC is a general separation method, and MS is a detection technique, together LC/MS/MS technology provides the mass spectral confirmation in identifying sildenafil, vardenafil, tadalafil and their analogs. In our present study, a sample extraction technique with 1:1 acetonitrile: water solvents and sonication was used for screening, then identification was performed using an LC coupled with Velos Pro linear ion trap mass spectrometry. This was a simple and reliable method for a variety of matrices of dietary supplements and pharmaceutical formulations in tablet, capsule or liquid form. The run time is only 6.5 min, allowing for a quick screening and identification of all of analytes of ED drugs using full scan and data-dependent scan MS/MS, except for tadalafil and aminotadalafil (MS/MS/MS). To conclude this study, Sildenafil, tadalafil, vardenafil, and other 16 analogs in dietary supplements could be quickly screened and identified by HPLC coupled with ion trap MS using data dependent scanning function. The main method using the short column is very rapid, and saves a lot of running time and solvents, and the identification is further confirmed by MS/MS information. The current study develops and validates a quick and reliable method to screen for ED drugs.

Simultaneous attenuation of phytoaccumulation of Cd and As in soil treated with inorganic and organic amendments.

A novel FeSiCa rich material (IS), chicken manure (CM) and its biochar were investigated for their efficiency in simultaneous remediation of Cd and As uptake by the vegetable Brassica chinensis L. Wet chemistry analysis and X-ray powder diffraction, scanning electron microscopy/energy dispersive X-ray spectroscopy as well as Fourier transform infrared spectroscopy were used to reveal the mechanisms responsible for Cd and As fixation in the amended soils. The IS treatment performed best in reducing Cd uptake, while the combination of IS and CM was the optimal one for As fixation. The precipitation/co-precipitation (in cadmium silicate/phosphate/phosphate hydroxide, cadmium iron and manganese oxides under alkaline conditions, and calcium/magnesium/ferric arsenates) and specific chemisorption (by amorphous iron/manganese oxides) were proved to be more efficient in simultaneously lowering As and Cd phytoavailability than was organic complexation. These findings demonstrate that FeSiCa and FeSiCaC amendments are highly efficient and promising in-situ remediation systems for safe crop production on soils contaminated with Cd and As.

Controls on rare-earth element transport in a river impacted by ion-adsorption rare-earth mining.

Rare-earth elements (REEs) are known to be a group of emerging pollutants, but the geochemistry of REEs in river waters in ion-adsorption rare-earth mining areas has attracted little attention. In this study, samples of the <0.45 µm and 0.22-0.45 µm (large colloids) water fractions and acid-soluble particles (ASPs) were collected from a river impacted by ion-adsorption rare-earth mining activities. The roles of ligand complexation, colloid binding, and particle adsorption in REE transport and distribution were also investigated. Results showed higher concentrations of REEs in the <0.45 µm fraction of all sampling sites (3.30 × 10-2-9.42 µM) compared with that in the control site (1.21 × 10-3 µM); this fraction was also characterized by middle REE enrichment at upstream sites, where REEs are mainly controlled by the <0.22 µm fraction (55%-94% of the species found in the <0.45 µm fraction) and ligand complexation (REE3+, REE(SO4)+, and REE(CO3)+). At downstream sites, heavy REE enrichment was observed, which was largely determined by binding to large colloids (68%-83% of the species found in the <0.45 µm fraction) and adsorption to particles (>90% of the acidified bulk water). Furthermore, REE patterns indicated that the REE-associated large colloids were mineral or mixed mineral-organic matter (OM) at upstream sites and OM-dominated or functionalized at downstream sites. The particles were mainly coated by inorganic matter substances (e.g., Fe/Al oxyhydroxides). In summary, our results reveal that REE patterns provide a useful tool to study the fate of REEs in ion-adsorption rare-earth mining catchments.

SVEngine: an efficient and versatile simulator of genome structural variations with features of cancer clonal evolution.

Background: Simulating genome sequence data with variant features facilitates the development and benchmarking of structural variant analysis programs. However, there are only a few data simulators that provide structural variants in silico and even fewer that provide variants with different allelic fraction and haplotypes. Findings: We developed SVEngine, an open-source tool to address this need. SVEngine simulates next-generation sequencing data with embedded structural variations. As input, SVEngine takes template haploid sequences (FASTA) and an external variant file, a variant distribution file, and/or a clonal phylogeny tree file (NEWICK) as input. Subsequently, it simulates and outputs sequence contigs (FASTAs), sequence reads (FASTQs), and/or post-alignment files (BAMs). All of the files contain the desired variants, along with BED files containing the ground truth. SVEngine's flexible design process enables one to specify size, position, and allelic fraction for deletions, insertions, duplications, inversions, and translocations. Finally, SVEngine simulates sequence data that replicate the characteristics of a sequencing library with mixed sizes of DNA insert molecules. To improve the compute speed, SVEngine is highly parallelized to reduce the simulation time. Conclusions: We demonstrated the versatile features of SVEngine and its improved runtime comparisons with other available simulators. SVEngine's features include the simulation of locus-specific variant frequency designed to mimic the phylogeny of cancer clonal evolution. We validated SVEngine's accuracy by simulating genome-wide structural variants of NA12878 and a heterogeneous cancer genome. Our evaluation included checking various sequencing mapping features such as coverage change, read clipping, insert size shift, and neighboring hanging read pairs for representative variant types. Structural variant callers Lumpy and Manta and tumor heterogeneity estimator THetA2 were able to perform realistically on the simulated data. SVEngine is implemented as a standard Python package and is freely available for academic use .

Correlation detection strategies in microbial data sets vary widely in sensitivity and precision.

Disruption of healthy microbial communities has been linked to numerous diseases, yet microbial interactions are little understood. This is due in part to the large number of bacteria, and the much larger number of interactions (easily in the millions), making experimental investigation very difficult at best and necessitating the nascent field of computational exploration through microbial correlation networks. We benchmark the performance of eight correlation techniques on simulated and real data in response to challenges specific to microbiome studies: fractional sampling of ribosomal RNA sequences, uneven sampling depths, rare microbes and a high proportion of zero counts. Also tested is the ability to distinguish signals from noise, and detect a range of ecological and time-series relationships. Finally, we provide specific recommendations for correlation technique usage. Although some methods perform better than others, there is still considerable need for improvement in current techniques.

Formation and characterization of glutathione adducts derived from polybrominated diphenyl ethers.

The reactions of glutathione (GSH) with polybrominated diphenyl ethers (PBDEs) quinones with different degrees of bromination on the PBDEs ring were studied. Liquid chromatography coupled with mass spectrometric (LC-MS) analysis showed that four types of adducts were formed from the reaction of each PBDEs quinone (PBDE-Q) with GSH. The proposed reaction pathway was confirmed using ion trap-MS/MS technique. Our results demonstrate that adduct-1 was formed following the Michael Addition, a reaction of the sulfhydryl group from GSH with electron deficient carbon from PBDEs-Q ring. Compared with other carbons on the quinone ring, carbon in position 6 has a smaller steric hindrance, thus the addition reaction is likely to occur in that position. Hydrated quinone-GSH adduct-1 is easily oxidized to generate an adduct-2 in an aqueous solution. Substitution reaction from bromine atom on adduct-2 quinone ring with sulfhydryl group from GSH further generates adduct-3 that is unstable and can be readily hydrolyzed to adduct-4 in aqueous solution. Both adduct-1 and adduct-4 were unstable as well, immediately oxidized to adduct-2 and adduct-3 in the air, respectively. The results reveal that brominated quinones undergo a rapid non-enzymatic debromination upon reaction with GSH, and open a new view for our understanding on mechanism of metabolism and the toxicity of this class of compounds.

Interaction of 2-(2',4'-bromophenoxyl)-benzoquinone with deoxynucleosides and DNA in vitro.

Polybrominated diphenyl ethers (PBDEs) may be metabolized to form hydroxylated and quinone products. Study on the formation of DNA adducts altered by PBDEs quinones was conducted. Various types of DNA adducts generated from in vitro reaction of deoxyguanosine (dG), 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), thymidine (T) and DNA with a PBDE-quinone metabolite, namely 2-(2',4'-bromophenoxyl)-benzoquinone (2'4'BrPhO-BQ) were characterized. The results suggest that the quinone compound could form various DNA adducts with dG, dA and dC via Michael Addition, which was confirmed from analyses by electrospray ionization tandem mass spectrometry. Two adducts were respectively generated from the reactions of 2'4'BrPhO-BQ with dC and dG, while three adducts were produced with dA. The formation of adducts of 2'4'BrPhO-BQ-deoxynucleoside changed with different pH of reaction solution. The obtained results demonstrated that 2'4'BrPhO-BQ could covalently bind to DNA mediated by quinone group. The in vitro data of the formation of DNA adducts might be valuable to elucidate the mechanism of interaction between PBDEs and DNA in vivo.

Determination of 2,8-dichlorodibenzo-p-dioxin in toothpaste and mouthwash consumer products using GC-MS.

A gas chromatography-mass spectrometry (GC-MS) method was developed for the identification and quantification of 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD) in toothpaste and mouthwash consumer products. Liquid-liquid extraction and solid-phase extraction were used in the sample preparation. The limit of detection was 0.96 ng/g in toothpaste and 0.83 ng/g in mouthwash. The accuracy represented by relative errors was less than 12.5%. The intra-day and inter-day precision, which are represented by the relative standard deviation values, were within 11.2 and 10.6%, respectively. The method was successfully applied to analyze 2,8-DCDD in toothpaste and mouthwash products, as well as that from the photo-degradation of triclosan spiked in both sample matrix.

Chinese medicines for prevention and treatment of human hepatocellular carcinoma: current progress on pharmacological actions and mechanisms.

Hepatocellular carcinoma (HCC) is one of leading causes of death in the world. Although various treatments have been developed, the therapeutic side effects are far from desirable. Chinese medicines (CMs, including plants, animal parts and minerals) have drawn a great deal of attention in recent years for their potential in the treatment of HCC. Most studies have shown that CMs may be able to retard HCC progression with multiple actions, either alone or in combination with other conventional therapies to improve quality of life in HCC patients. Additionally, CMs are used for preventing HCC occurrence. The aim of this study is to review the potential prophylactic and curative effects of CMs on human HCC and the possible mechanisms that underlie these pharmacological actions. Publications were collected and reviewed from PubMed and China National Knowledge Infrastructure from 2000 to 2014. Keywords for literature searches include "Chinese medicine", "Chinese herb", "traditional Chinese Medicine", "hepatocellular carcinoma" and "liver cancer". CMs in forms of pure compounds, isolated fractions, and composite formulas are included. Combination therapies are also considered. Both in vitro and in vivo efficacies of CMs are being discussed and the translational potential to bedside is to be discussed with clinical cases, which show the actions of CMs on HCC may include tumor growth inhibition, antimetastatic activities, anti-inflammation, anti-liver cancer stem cells, reversal on multi-drug resistance and induction/reduction of oxidative stress. Multiple types of molecules are found to contribute in the above actions. The review paper indicated that CMs might have potential to both prevent HCC occurrence and retard HCC progression with several molecular targets involved.