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1.
Ultrason Sonochem ; 73: 105543, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33845245

RESUMO

Hydrodynamic cavitation is a promising technique for water disinfection. In the present paper, the disinfection characteristics of an advanced hydrodynamic cavitation reactor (ARHCR) in pilot scale were studied. The effects of various flow rates (1.4-2.6 m3/h) and rotational speeds (2600-4200 rpm) on the removal of Escherichia coli (E. coli) were revealed and analyzed. The variation regularities of the log reduction and reaction rate constant at various cavitation numbers were established. A disinfection rate of 100% was achieved in only 4 min for 15 L of simulated effluent under 4200 rpm and 1.4 m3/h, with energy efficiency at 0.0499 kWh/L. A comprehensive comparison with previously introduced HCRs demonstrates the superior performance of the presented ARHCR system. The morphological changes in E. coli were studied by scanning electron microscopy. The results indicate that the ARHCR can lead to serious cleavage and surface damages to E. coli, which cannot be obtained by conventional HCRs. Finally, a possible damage mechanism of the ARHCR, including both the hydrodynamical and sonochemical effects, was proposed. The findings of the present study can provide strong support to the fundamental understanding and applications of ARHCRs for water disinfection.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33834336

RESUMO

Glass fiber sphere (GFS), used as support of MIL-100(Fe) to treat dye wastewater, was successfully synthesized using glass fibers from waste printed circuit board. Structural and textural features of MIL-100(Fe) supported by GFS (GFS/MIL-100(Fe)) were characterized by different techniques. GFS/MIL-100(Fe) showed higher specific surface area and better rhodamine B (RHB) removal performance as well as reusability. RHB removal percentage by GFS/MIL-100(Fe) reached 92% in 11 h, compared with 79% in 7 h of MIL-100(Fe). The highest RHB removal rate was obtained with the GFS/MIL-100(Fe) concentration of 20 g/L. Increasing RHB concentration over 100 mg/L reduced the time needed for saturated adsorption from 11 to 7 h. The best RHB removal performance of GFS/MIL-100(Fe) was obtained at pH = 3, and the removal percentage was almost the same in the pH range 5-11. The adsorption data fitted the pseudo-second-order kinetics better than the pseudo-first-order kinetics, and the adsorption isotherm data fitted Langmuir model better than Freundlich model. MIL-100(Fe) synthesized in organic solvents showed higher loading rate than that obtained in water. GFS/MIL-100(Fe) also showed promising removal performances for methylene blue, acid orange 7, and malachite green in water. The removal percentage of RHB was still 80% even after being used for 3 times. The results of this study indicate the prospect of synthesizing GFS with glass fibers from waste printed circuit boards and its use as the support of MIL-100(Fe).

3.
Development ; 148(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33658224

RESUMO

Starch accumulation is key for the maturity of rice pollen grains; however, the regulatory mechanism underlying this process remains unknown. Here, we have isolated a male-sterile rice mutant, abnormal pollen 1 (ap1), which produces nonviable pollen grains with defective starch accumulation. Functional analysis revealed that AP1 encodes an active L-type lectin receptor-like kinase (L-LecRLK). AP1 is localized to the plasma membrane and its transcript is highly accumulated in pollen during the starch synthesis phase. RNA-seq and phosphoproteomic analysis revealed that the expression/phosphorylation levels of numerous genes/proteins involved in starch and sucrose metabolism pathway were significantly altered in the mutant pollen, including a known rice UDP-glucose pyrophosphorylase (OsUGP2). We further found that AP1 physically interacts with OsUGP2 to elevate its enzymatic activity, likely through targeted phosphorylation. These findings revealed a novel role of L-LecRLK in controlling pollen maturity via modulating sucrose and starch metabolism.

4.
Chemosphere ; 276: 130090, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33740651

RESUMO

In this study, 4 Lactobacillus plantarum strains and 5 Lactobacillus fermentum strains adapting well to the unfavorable fruit system were isolated under different fruit environments. The fermentation ability of these autochthonous lactic acid bacteria (LAB) strains in blueberry juice, and the influence of microbial metabolism on juice composition were explored. After 48 h of fermentation, the viable cell counts exceeded 10.0 log CFU/mL, malic acid content decreased from 511.47 ± 10.50 mg/L to below 146.38 ± 3.79 mg/L, and lactic acid content increased from 0 mg/L to above 2184.90 ± 335.80 mg/L. Moreover, the metabolism of these strains exerted a profound influence on the phenolic composition of juice. Total phenolic content in blueberry juice increased by 6.1-81.2% under lactic acid fermentation, and the antioxidant capacity in vitro enhanced by at least 34.0%. Anthocyanin content showed a declining trend, while the profile of non-anthocyaninic phenolics exhibited complex changes. The increments of rutin, myricetin and gallic acid contents through 48 h lactic acid fermentation exceeded 136%, 71% and 38%, respectively. Instead, the contents of p-hydroxybenzoic acid and caffeic acid decreased with fermentation. Overall, Lactobacillus plantarum LSJ-TY-HYB-T9 and LSJ-TY-HYB-T7, and Lactobacillus fermentum LSJ-TY-HYB-C22 and LSJ-TY-HYB-L16 could be the suitable strains to produce fermented fruit juices, including blueberry in practical applications.

5.
ACS Nano ; 15(3): 5201-5208, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33625219

RESUMO

While offering high-precision control of neural circuits, optogenetics is hampered by the necessity to implant fiber-optic waveguides in order to deliver photons to genetically engineered light-gated neurons in the brain. Unlike laser light, X-rays freely pass biological barriers. Here we show that radioluminescent Gd2(WO4)3:Eu nanoparticles, which absorb external X-rays energy and then downconvert it into optical photons with wavelengths of ∼610 nm, can be used for the transcranial stimulation of cortical neurons expressing red-shifted, ∼590-630 nm, channelrhodopsin ReaChR, thereby promoting optogenetic neural control to the practical implementation of minimally invasive wireless deep brain stimulation.

6.
Ultrason Sonochem ; 73: 105486, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33639530

RESUMO

In this work, low-intensity ultrasonication (58.3 and 93.6 W/L) was performed at lag, logarithmic and stationary growth phases of Lactobacillus plantarum in apple juice fermentation, separately. Microbial responses to sonication, including microbial growth, profiles of organic acids profile, amino acids, phenolics, and antioxidant capacity, were examined. The results revealed that obvious responses were made by Lactobacillus plantarum to ultrasonication at lag and logarithmic phases, whereas sonication at stationary phase had a negligible impact. Sonication at lag and logarithmic phases promoted microbial growth and intensified biotransformation of malic acid to lactic acid. For example, after sonication at lag phase for 0.5 h, microbial count and lactic acid content in the ultrasound-treated samples at 58.3 W/L reached 7.91 ± 0.01 Log CFU/mL and 133.70 ± 7.39 mg/L, which were significantly higher than that in the non-sonicated samples. However, the ultrasonic effect on microbial growth and metabolism of organic acids attenuated with fermentation. Moreover, ultrasonication at lag and logarithmic phases had complex influences on the metabolism of apple phenolics such as chlorogenic acid, caffeic acid, procyanidin B2, catechin and gallic acid. Ultrasound could positively affect the hydrolysis of chlorogenic acid to caffeic acid, the transformation of procyanidin B2 and decarboxylation of gallic acid. The metabolism of organic acids and free amino acids in the sonicated samples was statistically correlated with phenolic metabolism, implying that ultrasound may benefit phenolic derivation by improving the microbial metabolism of organic acids and amino acids.

7.
Food Chem ; 348: 129083, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33517000

RESUMO

In this study, three potential probiotic strains were selected to ferment blueberry and blackberry juices. The viable cell counts of selected strains were increased by 0.4-0.7 log CFU/mL in berry juices environments after 48-h fermentation. Meanwhile, the contents of cyanindin-3-glucoside and peonidin-3-glucoside decreased over 30%. Heatmap presented an upgrade trend of syringic acid, ferulic acid, gallic acid and lactic acid during fermentation. However, the contents of p-coumaric acid, protocatechuic acid, chlorogenic acid, critic acid and malic acid showed downgrade trend. The metabolism of phenolics probably contributed to the enhancement of the ABTS radical scavenging activity (40%-60%) in fermented berry juices. Moreover, the three strains presented different capacities on changing the quality of berry juices according to the PCA and LDA analysis. The contents of individual organic acids had positive correlations with sensory quality, especially for sourness. Overall, probiotic fermentation could improve the sensory quality of berry juices.


Assuntos
Bactérias/metabolismo , Mirtilos Azuis (Planta)/química , Fermentação , Sucos de Frutas e Vegetais/microbiologia , Fenóis/análise , Probióticos/metabolismo , Rubus/química , Antioxidantes/análise , Bifidobacterium bifidum/metabolismo , Frutas/química , Sucos de Frutas e Vegetais/análise , Humanos , Lactobacillus plantarum/metabolismo , Streptococcus thermophilus/metabolismo , Paladar
8.
Annu Rev Food Sci Technol ; 12: 287-305, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33317321

RESUMO

The contamination risks of microorganisms and mycotoxins in low-moisture foods have heightened public concern. Developing novel decontamination technologies to improve the safety of low-moisture foods is of great interest in both economics and public health. This review summarizes the working principles and applications of novel thermal decontamination technologies such as superheated steam, infrared, microwave, and radio-frequency heating as well as extrusion cooking. These methods of decontamination can effectively reduce the microbial load on products andmoderately destruct the mycotoxins. Meanwhile, several integrated technologies have been developed that take advantage of synergistic effects to achieve the maximum destruction of contaminants and minimize the deterioration of products.

9.
Ultrason Sonochem ; 72: 105410, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33341708

RESUMO

This study aimed at investigating the performances of air drying of blackberries assisted by airborne ultrasound and contact ultrasound. The drying experiments were conducted in a self-designed dryer coupled with a 20-kHz ultrasound probe. A numerical model for unsteady heat and mass transfer considering temperature dependent diffusivity, shrinkage pattern and input ultrasonic energies were applied to explore the drying mechanism, while the energy consumption and quality were analyzed experimentally. Generally, both airborne ultrasound and contact ultrasound accelerated the drying process, reduced the energy consumption and enhanced the retentions of blackberry anthocyanins and organic acids in comparison to air drying alone. At the same input ultrasound intensity level, blackberries received more ultrasound energies under contact sonication (0.299 W) than airborne sonication (0.245 W), thus avoiding the attenuation of ultrasonic energies by air. The modeling results revealed that contact ultrasound was more capable than airborne ultrasound to intensify the inner moisture diffusion and heat conduction, as well as surface exchange of heat and moisture with air. During air drying, contact ultrasound treatment eliminated the gradients of temperature and moisture inside blackberry easier than airborne ultrasound, leading to more homogenous distributions. Moreover, the total energy consumption under air drying with contact ultrasound assistance was 27.0% lower than that with airborne ultrasound assistance. Besides, blackberries dehydrated by contact ultrasound contained more anthocyanins and organic acids than those dried by airborne ultrasound, implying a higher quality. Overall, direct contact sonication can well benefit blackberry drying in both energy and quality aspects.

10.
Food Res Int ; 137: 109405, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233092

RESUMO

In a food-processing environment, bacterial cells often adhere to surfaces and form biofilms to protect themselves from external adverse influences. Our study aimed to identify the influence of environmental factors and cell properties on Listeria monocytogenes biofilm formation. Biofilm formation was quantified through measuring the optical density at 590 nm (OD590 nm) after crystal violet staining. Neutral pH and 37oC were beneficial for biofilm formation whereas the influence of glucose (0.0-1.0%) and sodium chloride (0.0-1.0%) were strain-dependent. In general, the addition of sodium chloride and glucose increased biofilm formation in most strains compared to that in controls with no sodium chloride or glucose added. Bacteria with strong biofilm-forming capacity always produced large amounts of biofilm in most instances. Biofilm formation positively correlated with the cell surface hydrophobicity and motility but was independent from planktonic cell growth. The expression of flagella-related flaA, motB, and the two-component chemotactic system cheA/Y genes in biofilm cells increased compared to that in planktonic cells. Meanwhile, a cheY knockout mutant was constructed, and decreased biofilm-formation ability along with reduced cell-surface hydrophobicity were found in the non-motile mutant. Furthermore, the cheY knockout mutant showed no change in growth, and pH susceptibility compared to that in the wild-type strain.

11.
Food Res Int ; 137: 109707, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233281

RESUMO

This study aimed to evaluate the effects of metal salts on α-amylase-catalyzed hydrolysis of broken rice under a moderate electric field (MEF) by monitoring changes in hydrolysis efficiency, temperature, α-amylase activity, starch-metal ion interaction, and the structural and physicochemical properties of hydrolysates. Results showed that metal salts affected the hydrolysis mainly by altering α-amylase activity rather than by inducing thermal effect or interacting with starch. Reducing sugar content reached 125.0 g/L, while α-amylase activity increased by 18.16% when treated with 0.12 mmol/L Ca2+. Holes on hydrolysates treated with Ca2+ and Mg2+ were larger than those treated with Mn2+ and Cu2+. No M-O bond was formed after the hydrolysis. The crystallinity was slightly increased with the hydrolysis and the values for Ca2+- and Mg2+-treated samples were larger. The water and oil absorption capacity of the hydrolysate treated with Ca2+ was the highest. This study extended the knowledge of the roles of metal ions on MEF-assisted enzymatic hydrolysis and will contribute to the development of an innovative technology for starch modification.

12.
Front Genet ; 11: 602495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193748

RESUMO

Plant height (PH) plays a pivotal role in plant morphological architecture and is associated with yield potential in wheat. For the quantitative trait locus (QTL) analysis, a recombinant inbred line population was developed between varieties differing significantly in PH. Two major QTL were identified on chromosomes 4B (QPh.sicau-4B) and 6D (QPh.sicau-6D) in multiple environments, which were then validated in two different backgrounds by using closely linked markers. QPh.sicau-4B explained 10.1-21.3% of the phenotypic variance, and the location corresponded to the dwarfing gene Rht-B1. QPh.sicau-6D might be a novel QTL for PH, explaining 6.6-13.6% of the phenotypic variance and affecting spike length, thousand-kernel weight, and spikelet compactness. Three candidate genes associated with plant growth and development were identified in the physical interval of QPh.sicau-6D. Collectively, we identified a novel stable and major PH QTL, QPh.sicau-6D, which could aid in the development of closely linked markers for marker-assisted breeding and cloning genes underlying this QTL.

13.
J Hazard Mater ; : 124345, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33153798

RESUMO

This paper evaluates routes towards the fabrication of deep eutectic solvents (DESs) based supported liquid membrane (SLM) using choline chloride (ChCl)/glycerol, ChCl/ethylene glycol, graphene oxide (GO) and cellulose acetate (CA) via immersion and pressure-based impregnation method. The permeation results demonstrated that the impregnation of GO-ChCl/glycerol and GO-ChCl/ethylene glycol DESs into CA support has efficiently enhanced the CO2 permeability from 15.1 to 63.8 Barrer, respectively. Meanwhile, CO2/CH4 and CO2/N2 ideal selectivities were improved from 10.8 to 30.4 and 7.9 to 25.5, respectively, upon the impregnation of DESs into CA support. In addition, GO-ChCl/ethylene glycol DES/CA based SLMs demonstrated higher CO2 permeability, CO2/CH4 and CO2/N2 ideal selectivities compared the values obtained for GO-ChCl/glycerol DES/CA based SLMs. Furthermore, GO-ChCl/ethylene glycol DES/CA based SLM fabricated using pressure-based impregnation method demonstrated the highest CO2 permeability, CO2/CH4 and CO2/N2 ideal selectivities of 63.8 Barrer, 30.4 and 25.5, respectively which were 322.5%, 181.6% and 221.1%, respectively higher compared to the neat CA support. Besides, it also exhibits long-term durability up to 66 h for CO2 separation. Overall, current research work will provide understanding on the fundamentals for future research on membranes. Current study will also open the door for future research on SLMs for liquids and gas separation.

14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 521-530, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895105

RESUMO

Objective To explore the optimal therapy time for the treatment of severe coronavirus disease 2019(COVID-19)by traditional Chinese medicine(TCM)and its influence on the therapeutic effect and prognosis. Methods The clinical data,laboratory findings,and outcomes of 64 patients with severe COVID-19 treated with TCM and western medicine in Chongqing from January 20,2020, to March 11,2020 were retrospectively analyzed.Patients were divided into early intervention group[TCM was initiated within 3 days (including day 3) after the first diagnosis of severe type/critical type COVID-19]and late intervention group[TCM was initiated after 7 days (including day 7) after the first diagnosis of severe type /critical type COVID-19].The changes in clinical parameters during the course of disease were compared between the two groups. Results On day 14,the oxygenation index was 292.5(252.0,351.0)mmHg in the early intervention group,which was significantly higher than that in the late intervention group [246.0(170.0,292.5)mmHg](P=0.005).The length of hospital stay [(18.56±1.11)d vs.(24.87±1.64)d,P=0.001],duration of ICU stay [(14.12±0.91)d vs.(20.00±1.53)d,P=0.000] and time to negativity [(16.77±1.04)d vs.(22.48±1.66)d,P=0.001] in the early intervention group were significantly shorter than those in the late intervention group.The intubation rate(7.3%)in the early intervention group was significantly lower than that in the late intervention group(30.4%)(P=0.028). Conclusion Early TCM therapy within three days after a diagnosis of severe COVID-19 can shorten the length of hospital stay,duration of ICU stay,and time to negativity and decrease intubation rate.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
15.
IEEE J Biomed Health Inform ; 24(12): 3384-3396, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32750941

RESUMO

Automated retinal vessel segmentation is among the most significant application and research topics in ophthalmologic image analysis. Deep learning based retinal vessel segmentation models have attracted much attention in the recent years. However, current deep network designs tend to predominantly focus on vessels which are easy to segment, while overlooking vessels which are more difficult to segment, such as thin vessels or those with uncertain boundaries. To address this critical gap, we propose a new end-to-end deep learning architecture for retinal vessel segmentation: hard attention net (HAnet). Our design is composed of three decoder networks: the first of which dynamically locates which image regions are "hard" or "easy" to analyze, while the other two aim to segment retinal vessels in these "hard" and "easy" regions independently. We introduce attention mechanisms in the network to reinforce focus on image features in the "hard" regions. Finally, a final vessel segmentation map is generated by fusing all decoder outputs. To quantify the network's performance, we evaluate our model on four public fundus photography datasets (DRIVE, STARE, CHASE_DB1, HRF), two recent published color scanning laser ophthalmoscopy image datasets (IOSTAR, RC-SLO), and a self-collected indocyanine green angiography dataset. Compared to existing state-of-the-art models, the proposed architecture achieves better/comparable performances in segmentation accuracy, area under the receiver operating characteristic curve (AUC), and f1-score. To further gauge the ability to generalize our model, cross-dataset and cross-modality evaluations are conducted, and demonstrate promising extendibility of our proposed network architecture.

17.
ACS Appl Mater Interfaces ; 12(35): 39515-39523, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32805862

RESUMO

Although promising progress has been made in near-infrared (NIR) electron acceptors for broadening photoresponse of optoelectronics, there are still strong needs for efficient NIR materials with low synthetic complexities. In this work, three simple NIR acceptors are developed with absorption up to 1000 nm and possessing the same dithiophene cores with varied heteroatom linkages to carbon (C) atom for W1, to silicon (Si) for W2, and to nitrogen (N) for W3. It is found that the tuning of only one atom for simple acceptors can surprisingly lead to a large difference in photoelectric properties and solid stacking, as well as the performance in optoelectronics. Although quite simple, these electron acceptors, especially W1 (C), can also perform quite efficiently as organic photovoltaics (OPVs) as well as sensitive organic photodetectors (OPDs) when blended with PTB7-Th polymer. It is worthy to note that, among the representative NIR acceptors with over 950 nm absorption, W1 possesses one of the best figure-of-merit when considering the photoelectric performance versus synthetic complexity of materials. As a result, the PTB7-Th:W1-based OPDs reach a fast temporal response, ultralow-light intensity detection of 1.70 × 10-11 W·cm-2, and a high specific detectivity of 4.28 × 1012 cm·Hz1/2·W-1 at 830 nm, representing a highly sensitive self-powered OPD approach the commercial broadband silicon detectors. These simple structure materials provide a potential example for further application of NIR electron acceptor.

18.
Aging (Albany NY) ; 12(16): 16368-16389, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32862153

RESUMO

This study aimed to evaluate the role of FRT in ROS/DNA regulation with or without PARP-1 in radiation-injured thymus cells. The administration of FRT to PARP-1-/- (KO) mice demonstrated that FRT significantly increased the viability of thymus cells and decreased their rate of apoptosis through PARP-1. Radiation increased the levels of ROS, γ-H2AX and 53BP1, and induced DNA double strand breaks. Compared with wild type (WT) mice, levels of ROS, γ-H2AX and 53BP1 in KO mice were much less elevated. The FRT treatment groups also showed little reduction in these indicators in KO mice compared with WT mice. The results of the KO mice study indicated that FRT reduced ROS activation through inhibition of PARP-1. Furthermore, FRT reduced the concentrations of γ-H2AX by decreasing ROS activation. However, we found that FRT did not regulate 53BP1, a marker of DNA damage, because of its elimination of ROS. Levels of apoptosis-inducing factor (AIF), exhibited no significant difference after irradiation in KO mice. To summarize, ROS suppression by PARP-1 knockout in KO mice highlights potential therapeutic target either by PARP-1 inhibition combined with radiation or by treatment with a drug therapy alone. AIF-induced apoptosis could not be activated in KO mice.

19.
Ther Adv Endocrinol Metab ; 11: 2042018820934307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612802

RESUMO

Diabetic ketoacidosis (DKA) and thyroid storm (TS) are severe metabolic and endocrine disorders. Both usually manifest with multiple systemic clinical signs and symptoms, and digestive symptoms, such as nausea and vomiting, are most common in these patients. Moreover, the presence of a concurrent severe or rare complication may worsen the condition or even cause death due to misdiagnosis, delayed diagnosis, or inappropriate treatment. The identification of these symptoms is usually closely related to the severity and prognosis of the disease. Although clinical prognosis might be improved by prompt diagnosis and aggressive treatment, some rare and insidious metabolic complications are difficult to identify early. Moreover, life-threatening gastrointestinal symptoms are very rare in patients with DKA and TS. Here, we report an inpatient diagnosed with DKA and Graves' disease who developed life-threatening intractable hiccups resulting in TS and respiratory failure during the treatment of DKA. In addition, we review the literature to discuss the possible underlying mechanism of intractable hiccups in the development of TS.

20.
Liver Int ; 40(11): 2834-2847, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32594568

RESUMO

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

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