Lateral Habenula Neurons Signal Cold Aversion and Participate in Cold Aversion.

The aversion to cold is a fundamental motivated behavior that contributes to the body temperature homeostasis. However, the involvement of the lateral habenula (LHb) as a regulatory hub for negative emotions in this physiological process remains uninvestigated. In this study, we demonstrate an elevation in the population activity of LHb neurons following exposure to cold stimuli. Additionally, we establish the necessity of Vglut2-expressing neurons within the LHb for the encoding of cold aversion behaviors. Furthermore, we have elucidated a neural circuit from excitatory neurons of the dorsomedial hypothalamus (DMH) to LHb that plays a crucial role in this progress. Manipulation of the DMH-LHb circuit has a significant impact on cold aversion behavior in mice. It is worth noting that this circuit does not exhibit any noticeable effects on autonomic thermoregulation or depression-like behavior. The identification of these neural mechanisms involved in behavioral thermoregulation provides a promising avenue for future research.

Atmospheric chemistry of 2-nitrobenzaldehyde: Initiated by photo-excitation, OH-oxidation, and small TiO2 clusters adsorption catalysis.

The fate of 2-nitrobenzaldehyde (2-NBA) is of interest in atmospheric chemistry as it is a semi-volatile organic compound with high photosensitivity. This study presents a quantum chemical study of the gas-phase reactions of 2-NBA photo-excitation and OH-oxidation in the absence and presence of small TiO2 clusters. To further understand the unknown photolysis mechanism, the photo-reaction pathways of ground singlet state and the lying excited triplet state of 2-NBA were investigated including the initial and subsequent reactions of proton transfer, direct CO, NO2, and HCO elimination routes in the presence of O2 and NO. Meanwhile, the OH-mediated degradation of 2-NBA proceeded via five H-extraction and six OH-addition channels by indirect mechanism, which follows a succession of reaction steps initiated by the formation of weakly stable intermediate complexes. The H-extraction from the -CHO group was the dominant pathway with a negative activation energy of -1.22 kcal/mol. The calculated rate coefficients at 200-600 K were close to the experimental data in literature within 308-352 K, and the kinetic negative temperature independence was found in both experimental literature and computational results. Interestingly, 2-NBA was favored to be captured onto small TiO2 clusters via six adsorption configurations formed via various combination of three types of bonds of Ti···O, Ti···C, and O···H between the molecularly adsorbed 2-NBA and TiO2 clusters. Comparison indicted that the chemisorptions of aldehyde oxygen have largest energies. The results suggested adsorption conformations have a respectable impact on the catalysis barrier. This study is significant for understanding the atmospheric chemistry of 2-nitrobenzaldehyde.

Theoretical Study of the Hydroxyl-Radical-Initiated Degradation Mechanism, Kinetics, and Subsequent Evolution of Methyl and Ethyl Iodides in the Atmosphere.

The degradation and transformation of iodinated alkanes are crucial in the iodine chemical cycle in the marine boundary layer. In this study, MP2 and CCSD(T) methods were adopted to study the atmospheric transformation mechanism and degradation kinetic properties of CH3 I and CH3 CH2 I mediated by ⋅OH radical. The results show that there are three reaction mechanisms including H-abstraction, I-substitution and I-abstraction. The H-abstraction channel producing ⋅CH2 I and CH3 C ⋅ HI radicals are the main degradation pathways of CH3 I and CH3 CH2 I, respectively. By means of the variational transition state theory and small curvature tunnel correction method, the rate constants and branching ratios of each reaction are calculated in the temperature range of 200-600 K. The results show that the tunneling effect contributes more to the reaction at low temperatures. Theoretical reaction rate constants of CH3 I and CH3 CH2 I with ⋅OH are calculated to be 1.42×10-13 and 4.44×10-13  cm3 molecule-1 s-1 at T=298 K, respectively, which are in good agreement with the experimental values. The atmospheric lifetimes of CH3 I and CH3 CH2 I are evaluated to be 81.51 and 26.07 day, respectively. The subsequent evolution mechanism of ⋅CH2 I and CH3 C ⋅ HI in the presence of O2 , NO and HO2 indicates that HCHO, CH3 CHO, and I-atom are the main transformation end-products. This study provides a theoretical basis for insight into the diurnal conversion and environmental implications of iodinated alkanes.

Oxidation/Alkylation of Amino Acids with α-Bromo Carbonyls Catalyzed by Copper and Quick Access to HDAC Inhibitor.

A facile and efficient method was reported for Cu-catalyzed selective α-alkylation processes of amino acids/peptides and α-bromo esters/ketones through a radical-radical coupling pathway. The reaction displays an excellent functional group tolerance and broad substrate scope, allowing access to desired products in moderate to excellent yields. Notably, this method is distinguished by site-specificity and exhibits total selectivity for aryl glycine motifs over other amino acid units. Furthermore, the practicality of this strategy is certified by the efficient synthesis of the novel SAHA phenylalanine-containing analogue (SPACA).

Alkenyl Thioetherification Enabled by Nickel Catalysis.

This paper describes an efficient strategy to promote alkenyl thioetherifications via the Ni-catalyzed cross-coupling of inactivated or ß-aryl-substituted (E)-alkenyl halides with thio-alcohols/phenols. The present strategy with easy-to-operate reaction conditions represents one of the most effective alkenyl C(sp2)-S bond-forming methods via readily accessible nickel catalysis. Notably, the mildly basic conditions employed facilitate access to a broad scope including protected amino acids, saccharides, and heterocycles. Moreover, this work presents its attractive usefulness by the application in late-stage modifications of several structurally complex natural products and pharmaceuticals.

A novel antioxidant protein of non-phycobiliprotein family derived from marine red alga Porphyra haitanensis.

BACKGROUND: Oxidation has been reported as the one of the deterioration reactions of proteins in aquatic products. Searching for new bioactive substances from marine algae has been one of the main areas in food science and additives. RESULTS: In this study, a novel protein from the red alga Porphyra haitanensis was determined after ammonium sulfate precipitation and gel filtration chromatography. It closely corresponded to the antioxidant activity and was identified as an uncharacterized protein with a molecular mass of 43 kDa, designated Ph43. Bioinformatic analysis revealed that Ph43 is a novel protein of non-phycobiliprotein family with putative chordin domains and rich in α-helical conformation. Recombinant protein (rPh43) was expressed in Escherichia coli as a Hig-tagged protein using a pET-22b vector system and purified by affinity high-performance liquid chromatography. Spectroscopy analysis revealed that there were no structural differences between rPh43 and natural recovered Ph43. Moreover, rPh43 showed equal/higher antioxidant activity compared with Ph43. rPh43 has the potential for application as a natural antioxidant for food stabilization. CONCLUSION: Our results identified a novel antioxidant protein with molecular mass of 43 kDa derived from Porphyra haitanensis that belongs to the non-phycobiliprotein family. © 2023 Society of Chemical Industry.

Transforming the fermented fish landscape: Microbiota enable novel, safe, flavorful, and healthy products for modern consumers.

Regular consumption of fish promotes sustainable health while reducing negative environmental impacts. Fermentation has long been used for preserving perishable foods, including fish. Fermented fish products are popular consumer foods of historical and cultural significance owing to their abundant essential nutrients and distinct flavor. This review discusses the recent scientific progress on fermented fish, especially the involved flavor formation processes, microbial metabolic activities, and interconnected biochemical pathways (e.g., enzymatic/non-enzymatic reactions associated with lipids, proteins, and their interactions). The multiple roles of fermentation in preservation of fish, development of desirable flavors, and production of health-promoting nutrients and bioactive substances are also discussed. Finally, prospects for further studies on fermented fish are proposed, including the need of monitoring microorganisms, along with the precise control of a fermentation process to transform the traditional fermented fish to novel, flavorful, healthy, and affordable products for modern consumers. Microbial-enabled innovative fermented fish products that consider both flavor and health benefits are expected to become a significant segment in global food markets. The integration of multi-omics technologies, biotechnology-based approaches (including synthetic biology and metabolic engineering) and sensory and consumer sciences, is crucial for technological innovations related to fermented fish. The findings of this review will provide guidance on future development of new or improved fermented fish products through regulating microbial metabolic processes and enzymatic activities.

Next-generation sequencing identification and multiplex RT-PCR detection for viruses infecting cigar and flue-cured tobacco.

BACKGROUND: Early, precise and simultaneous identification of plant viruses is of great significance for preventing virus spread and reducing losses in agricultural yields. METHODS AND RESULTS: In this study, the identification of plant viruses from symptomatic samples collected from a cigar tobacco planting area in Deyang and a flue-cured tobacco planting area in Luzhou city, Sichuan Province, China, was conducted by deep sequencing of small RNAs (sRNAs) through an Illumina sequencing platform, and plant virus-specific contigs were generated based on virus-derived siRNA sequences. Additionally, sequence alignment and phylogenetic analysis were performed to determine the species or strains of these viruses. A total of 27930450, 21537662 and 28194021 clean reads were generated from three pooled samples, with a total of 105 contigs mapped to the closest plant viruses with lengths ranging from 34 ~ 1720 nt. The results indicated that the major viruses were potato virus Y, Chilli veinal mottle virus, tobacco vein banding mosaic virus, tobacco mosaic virus and cucumber mosaic virus. Subsequently, a fast and sensitive multiplex reverse transcription polymerase chain reaction assay was developed for the simultaneous detection of the most frequent RNA viruses infecting cigar and flue-cured tobacco in Sichuan. CONCLUSIONS: These results provide a theoretical basis and convenient methods for the rapid detection and control of viruses in cigar- and flue-cured tobacco.

Theoretical insights into the gaseous and heterogeneous reactions of halogenated phenols with ˙OH radicals: mechanism, kinetics and role of (TiO2)n clusters in degradation processes.

Halogenated phenols are highly toxic chemicals with serious health risks, and the removal of these persistent environmental pollutants remains a challenge. Based on quantum chemistry calculations, the homogeneous/heterogeneous degradation mechanism and kinetics of C6X5OH (X = F, Cl, and Br) initiated by ˙OH radicals in the gas phase and TiO2 cluster surfaces are investigated in this work. Four ˙OH-addition and one proton-coupled electron-transfer (PCET) reaction channels for each halogenated phenol were found and the ˙OH-addition channels were more favorable than the PCET pathway without TiO2 clusters. At 296 K, the calculated total rate constant for ˙OH with C6F5OH in the atmosphere well agreed with the limited experimental data of (6.88 ± 1.37) × 10-12 cm3 molecule-1 s-1. The lifetimes of C6F5OH, C6Cl5OH, and C6Br5OH were about 12.04-12.86 h at 296 K, which favored their medium-range transport in the atmosphere. In the presence of (TiO2)n clusters (n = 4, 6, 8, 12, and 16), the PCET mechanism for hydrogen transfer reaction of C6F5OH with ˙OH radicals was changed from the previous four-electron/three-center into four-electron/two-center, which results in the PCET pathway becoming more favorable than the ˙OH-addition channels. Meanwhile, the heterogeneous degradation rate constants of C6F5OH were accelerated by more than 10 orders of magnitude within 200-430 K compared with those of the naked reaction. The effects of (TiO2)n cluster (n = 4, 6, 8, 12, and 16) size on the degradation rates were analyzed at 200-430 K, and the reaction on the (TiO2)8 cluster had a faster rate. The subsequent reactions including the bond cleavage of the benzene ring and O2 addition or abstraction were studied. This work provides new insights into halogenated aromatic atmospheric chemistry and nanoscale TiO2 photocatalysis in air or wastewater management.

Antioxidant Activity of Gracilaria lemaneiformis Polysaccharide Degradation Based on Nrf-2/Keap-1 Signaling Pathway in HepG2 Cells with Oxidative Stress Induced by H2O2.

The objective of this research was to investigate the antioxidant activity of Gracilarialemaneiformis polysaccharide degradation and its underlying mechanism involved in the Nrf-2/Keap-1 signaling pathway in HepG2 cells with oxidative stress induced by H2O2. The result of the scavenging ability of free radicals showed that GLP-HV (polysaccharide degraded by H2O2-vitamin C (Vc)) performed a better scavenging ability than GLP (G.lemaneiformis polysaccharide). Moreover, the scavenging ability of polysaccharide to these free radicals from strong to weak was as follows: superoxide radical, ferric ion, ABTS+, and DPPH radical, and their IC50 values were 3.56 ± 0.0028, 4.97 ± 0.18, 9.62 ± 0.35, and 23.85 ± 1.78 mg/mL, respectively. Furthermore, GLP-HV obviously relieved oxidative stress in HepG2 cells, which strengthened the activity of T-AOC, CAT, GSH-PX, and SOD, and diminished the intensity of MDA, intracellular ROS, and calcium ion based on the Nrf-2/Keap-1 signaling pathway. The PCR result revealed that polysaccharide upregulated the expression of the genes Nrf-2, HO-1, NQO-1, and ZO-1 and downregulated Keap-1. The correlation between chemical properties and antioxidant mechanism of GLP-HV was evaluated via a heat map. The results illustrated that reducing sugar and active groups presented a positive correlation, and molecular weight and viscosity exhibited a negative relation with antioxidant activity.

A New Ratiometric Fluorescent Probe Based on BODIPY for Highly Selective Detection of Hydrogen Sulfide.

Hydrogen sulfide (H2S) as small molecular signal messenger plays key functions in numerous biological processes. The imaging detection of intracellular hydrogen sulfide is of great significance. In this work, a ratiometric fluorescent probe BH based on an asymmetric BODIPY dye for detection of H2S was designed and synthesized. After the interaction with hydrogen sulfide, probe display colorimetric and ratiometric fluorescence response, with its maximum emission fluorescence wavelength red-shifted from 542 nm to 594 nm, which is attributed to the sequential nucleophilic reaction of H2S leading to enhanced molecular conjugation after ring formation of the BODIPY skeleton. A special response mechanism has been fully investigated by NMR titration and MS, so that the probe has excellent detection selectivity. Furthermore, probe BH has low cytotoxicity and fluorescence imaging experiments indicate that it can be used to monitor hydrogen sulfide in living cells.

Improving the color and functional properties of seabuckthorn seed protein with phytase treatment combined with alkaline solubilization and isoelectric precipitation.

BACKGROUND: Reducing anti-nutritional factors like phytates in seed protein products requires an ongoing effort. This study was the first to investigate the phytic acid content in seabuckthorn seed protein (SSP) and its reduction by an exogenous phytase during protein isolation from seabuckthorn seed meal through the common alkaline solubilization-isoelectric precipitation process. RESULTS: The additional phytase treatment could reduce the content of phytic acid from 22.46 to 13.27 g kg-1 , leading to SSP products with lighter color (lower ΔE* ), higher protein solubility, higher in vitro digestibility, but lower phenolic antioxidant content (including flavonoids and procyanidins) and some beneficial ions like Ca, Fe, Mg, and Zn. The Fourier transform infrared (FTIR) results indicated that the secondary structure of protein changed under the treatment with phytase. Correlation analysis showed that L* was significantly negatively correlated with TP, TPC and TF (P < 0.001), while a* and b* were significantly positively correlated with them (P < 0.001). CONCLUSIONS: There may be a trade-off between protein functionalities and other health-promoting components when a phytase treatment is included in SSP isolation. © 2021 Society of Chemical Industry.

Prospective trial of a 2940 nm Er:YAG laser for the treatment of meibomian gland dysfunction.

PURPOSE: The primary objective was to evaluate the efficacy and safety of Er:YAG laser treatment for meibomian gland dysfunction (MGD) in a prospective study. METHODS: A total of 128 eyes from 64 patients with MGD were enrolled to receive either three Er:YAG laser treatments with meibomian gland expression (MGX) or MGX-alone treatment sessions at 3-week intervals. The Standard Patient Evaluation of Eye Dryness (SPEED) validated questionnaire; fluorescein breakup time of the tear film (FBUT); corneal fluorescein staining (CFS); lid margin abnormalities; meibomian gland morphology (meiboscore); lower tear meniscus height (TMH); and assessment of 15 meibomian glands in the lower eyelids, including total meibomian gland secretion quality (TMGS), the number of glands secreting any liquid (GSAL), and the number of glands yielding optimal clear liquid secretion (GYCL), were assessed at day (D)0, D21, D42, and D63 for the Er:YAG-MGX group and D0 and D63 for the MGX group. RESULTS: At D63, significant decreases in SPEED scores and lid margin abnormalities as well as significant increases in FBUT, TMGS, and GSAL were observed in both groups (all p < 0.05). The Er:YAG-MGX group showed a significantly better improvement in SPEED scores, TMGS, and GYCL than the MGX group (all p < 0.05). CONCLUSION: Although preliminary, the study results of Er:YAG laser treatment for dry eye syndrome caused by MGD are promising. Er:YAG laser treatment may be a new direction for managing MGD. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn : ChiCTR1900026004.

Optimized Degradation and Inhibition of α-glucosidase Activity by Gracilaria lemaneiformis Polysaccharide and Its Production In Vitro.

Gracilaria lemaneiformis polysaccharide (GLP) exhibits good physiological activities, and it is more beneficial as it is degraded. After its degradation by hydrogen peroxide combined with vitamin C (H2O2-Vc) and optimized by Box-Behnken Design (BBD), a new product of GLP-HV will be generated. While using GLP as control, two products of GLP-H (H2O2-treated) and GLP-V (Vc-treated) were also produced. These products chemical characteristics (total sugar content, molecular weight, monosaccharide composition, UV spectrum, morphological structure, and hypolipidemic activity in vitro) were assessed. The results showed that the optimal conditions for H2O2-Vc degradation were as follows: H2O2-Vc concentration was 18.7 mM, reaction time was 0.5 h, and reaction temperature was 56 °C. The total sugar content of GLP and its degradation products (GLP-HV, GLP-H and GLP-V) were more than 97%, and their monosaccharides are mainly glucose and galactose. The SEM analysis demonstrated that H2O2-Vc made the structure loose and broken. Moreover, GLP, GLP-HV, GLP-H, and GLP-V had significantly inhibition effect on α-glucosidase, and their IC50 value were 3.957, 0.265, 1.651, and 1.923 mg/mL, respectively. GLP-HV had the best inhibition effect on α-glucosidase in a dose-dependent manner, which was the mixed type of competitive and non-competitive. It had a certain quenching effect on fluorescence of α-glucosidase, which may be dynamic quenching.

Competing Dehalogenation versus Borylation of Aryl Iodides and Bromides under Transition-Metal-Free Basic Conditions.

In this work, selectivity-controllable base-promoted transition-metal-free borylation and dehalogenation of aryl halides are described. Under the conditions of borylation, the dehalogenation which emerges as a competitive side reaction has been well-controlled by carefully controlling the borylation conditions. On the other hand, the dehalogenation using benzaldehyde as a hydrogen source has also been accomplished. The applications of direct radical borylation and dehalogenation of aryl halides demonstrate their synthetic practicability in pharmaceutical-oriented organic synthesis. Based on the experimental evidences, the tBuOK/1,10-Phen-triggered radical nature of both competitive reactions has been revealed.

[Comparative study of the corticosterone and glutamate induced PC12 cells depression model by 1H NMR metabolomics].

This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance ( 1H NMR) metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

[Intervention mechanism of psychological sub-health by Baihe Dihuang Tang based on network pharmacology].

This study was designed to screen the targets of bioactive ingredients of Baihe Dihuang Tang, and investigate the "multi-components, multi-targets and multi-pathways" intervention mechanism of Baihe Dihuang Tang on psychological sub-health. The ADME/T calculation method was used to screen the active ingredient of Baihe Dihuang Tang, and then using ADME/T calculation method to filtrate the active components of Baihe Dihuang Tang, then Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Pharm Mapper database and Medical Subject Headings (MeSH) were combined to forecast and filtrate the targets of the main active ingredients. In addition, the predicted targets were verified by the Surflex-dock in Sybyl. The Cytoscape software was used to construct the Baihe Dihuang Tang ingredients-targets-disease network, while Clue GO software was used to analyze the molecular function and biological process of the targets. There are total 11 active ingredients and 21 targets in Baihe Dihuang Tang. A good interaction between them was supported by the score. The 21 targets were mainly involved in gamma-aminobutyric acid signaling pathway, c AMP metabolic process and monoamine transport relevant biological processes. Thus, Baihe Dihuang Tang may play a role in the intervention of psychological sub-health by regulating the activity of G-protein coupled amine receptor and the expression of monoamine neurotransmitter, which reflects the features of traditional Chinese medicine multi-components, multi-targets and multi-pathways. This research provides evidences on the pharmacological mechanism of Baihe Dihuang Tang effect on psychological sub-health.

[1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model].

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.

In-depth discovery and taste presentation mechanism studies on umami peptides derived from fermented sea bass based on peptidomics and machine learning.

Umami peptides originating from fermented sea bass impart a distinctive flavor to food. Nevertheless, large-scale and rapid screening for umami peptides using conventional techniques is challenging because of problems such as prolonged duration and complicated operation. Therefore, we aimed to screen fermented sea bass using peptidomics and machine learning approaches. The taste presentation mechanism of umami peptides was assessed by molecular docking of T1R1/T1R3. Seventy umami peptides identified in fermented sea bass predominantly originated from 28 precursor proteins, including troponin, myosin, motor protein, and creatine kinase. Six umami peptides with the lowest energies formed stable complexes by binding to T1R3. SER170, SER147, GLN389, and HIS145 are critical binding sites for T1R1/T1R3. Four dominant interacting surface forces were identified: aromatic interactions, hydrogen bonding, hydrophilic bonds, and solvent-accessible surfaces. Our study unveils a method to screen umami peptides efficiently, providing a basis for further exploration of their flavor in fermented sea bass.

The relationship of exercise and cancer-related fatigue in patients with advanced liver cancer: a cross-sectional study.

There is increasing interest in understanding exercise as a potential treatment for cancer-related fatigue (CRF); however, rarely research has been conducted on more aggressive cancers with short survival, such as liver cancer. The purpose of this study was to provide educational ideas for insufficient exercise and provide clues for the design of effective and safe exercise intervention programs with high compliance in patients of advanced liver cancer in the future. Participants were recruited from a tertiary cancer hospital using convenience sampling. All participants were asked to complete self-report questionnaires that assessed their medical and demographic variables, exercise habits and CRF during their hospitalization in the interventional department. Spearman's correlation analysis and Nonparametric test was used to explore correlations between exercise subgroups and CRF. The Baron and Kenny's Approach was used to investigate the mediating effect of exercise index between P-EX and CRF. 207 out of 255 participants were enrolled in this study, with an average age of 55.4 years. The CRF score was 33 (28, 36), and 93.2% had insufficient exercise. Exercise frequency (≥ 3 Times/week) (Z = 4.34, p = 0.037) and maintaining exercise trend (Z = 15.85, p = 0.001) had a positive effect on CRF. P-EX had a great impact on exercise index and affecting CRF directly. Participants in the study showed serious fatigue and insufficient exercise. Exercise education can be initiated earlier, particularly those without regular exercise experience. Sustained light exercise, compliant with exercise habits and interests, three times a week may be a practical way to reduce the risk of CRF in advanced liver cancer.