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Abstract Cellulose is an important abundant renewable resource on Earth, and the microbial cellulose utilization mechanism has attracted extensive attention. Recently, some signalling molecules have been found to regulate cellulose utilization and the discovery of underlying signals has recently attracted extensive attention. In this paper, we found that the hydrogen sulfide (H2S) concentration under cellulose culture condition increased to approximately 2.3-fold compared with that under glucose culture condition in Ganoderma lucidum. Further evidence shown that cellulase activities of G. lucidum were improved by 18.2-27.6% through increasing H2S concentration. Then, we observed that the carbon repressor CreA inhibited H2S biosynthesis in G. lucidum by binding to the promoter of cbs, a key gene for H2S biosynthesis, at “CTGGGG”. In our study, we reported for the first time that H2S increased the cellulose utilization in G. lucidum, and analyzed the mechanism of H2S biosynthesis induced by cellulose. This study not only enriches the understanding of the microbial cellulose utilization mechanism but also provides a reference for the analysis of the physiological function of H2S signals.

Hydrogen sulfide (H2S) has recently been recognized as an important gaseous transmitter with multiple physiological effects in various species. Previous studies have shown that H2S alleviated heat-induced ganoderic acids (GAs) biosynthesis, an important quality index of Ganoderma lucidum. However, a comprehensive understanding of the physiological effects and molecular mechanisms of H2S in G. lucidum remains unexplored. In this study, we found that heat treatment reduced the mitochondrial membrane potential (MMP) and mitochondrial DNA copy number (mtDNAcn) in G. lucidum. Increasing the intracellular H2S concentration through pharmacological and genetic means increased the MMP level, mtDNAcn, oxygen consumption rate level and ATP content under heat treatment, suggesting a role for H2S in mitigating heat-caused mitochondrial damage in G. lucidum. Further results indicated that H2S activates sulfide-quinone oxidoreductase (SQR) and complex III (Com III), thereby maintaining mitochondrial homeostasis under heat stress in G. lucidum. Moreover, SQR also mediated the negative regulation of H2S to GAs biosynthesis under heat stress. Furthermore, SQR might be persulfidated under heat stress in G. lucidum. Thus, our study reveals a novel physiological function and molecular mechanism of H2S signalling under heat stress in G. lucidum with broad implications for research on the environmental response of microorganisms.

Abstract Background Edible mushrooms are delicious in flavour and rich in high-quality protein and amino acids required by humans. A transcription factor, general control nonderepressible 4 (GCN4), can regulate the expression of genes involved in amino acid metabolism in yeast and mammals. A previous study revealed that GCN4 plays a pivotal role in nitrogen utilization and growth in Ganoderma lucidum. However, its regulation is nearly unknown in mushrooms. Results In this study, we found that the amino acid contents reached 120.51 mg per gram of mycelia in the WT strain under 60 mM asparagine (Asn) conditions, but decreased by 62.96% under 3 mM Asn conditions. Second, silencing of gcn4 resulted in a 54.2% decrease in amino acid contents under 60 mM Asn, especially for the essential and monosodium glutamate-like flavour amino acids. However, these effects were more pronounced under 3 mM Asn. Third, silencing of gcn4 markedly inhibited the expression of amino acid biosynthesis and transport genes. In addition, GCN4 enhanced the tricarboxylic acid cycle (TCA) and glycolytic pathway and inhibited the activity of target of rapamycin complex 1 (TORC1), thus being beneficial for maintaining amino acid homeostasis. Conclusion This study confirmed that GCN4 contributes to maintaining the amino acid contents in mushrooms under low concentrations of nitrogen. In conclusion, our study provides a research basis for GCN4 to regulate amino acid synthesis and improve the nutrient contents of edible mushrooms.

Robert Edward T Ang,1 Pedro Tañá-Rivero,2 Francisco Pastor-Pascual,3 Pavel Stodulka,4 Manfred Tetz,5 Isaak Fischinger6 1Cataract and Refractive Surgery Department, Asian Eye Institute, Makati City, Philippines; 2Cataract and Refractive Surgery Department, Oftalvist, Alicante, Spain; 3Cataract and Refractive Surgery Department, Oftalvist, Valencia, Spain; 4Cataract and Refractive Surgery Department, Gemini Eye Clinic, Zlin, Czech Republic; 5Cataract and Refractive Surgery Department, Augentagesklinik Spreebogen, Berlin, Germany; 6Medical Faculty, Johannes Kepler University Linz, Linz, AustriaCorrespondence: Robert Edward T Ang, Asian Eye Institute, 8th Floor PHINMA Plaza, Rockwell Center, Makati City, Philippines, Email angbobby@hotmail.comPurpose: To show the visual and refractive outcomes in cataract patients with corneal astigmatism when bilaterally implanted with a biconvex aspheric toric monofocal intraocular lens (IOL) with a double C-loop haptic-design.Methods: Forty-seven cataract patients (94 eyes) with corneal astigmatism (≥ 0.75D) were implanted with the monofocal PODEYE toric IOL and assessed for 4– 6 months post-surgery. Measurements included monocular and binocular uncorrected-distance visual acuity (UDVA) and corrected-distance visual acuity (CDVA), under both photopic and mesopic lighting conditions. Refraction, photopic and mesopic contrast sensitivity (with and without glare), and rotational stability were also recorded at the last postoperative visit.Results: At 4– 6 months, 78.2% and 98.9% of eyes were within ± 0.50D and ± 1.00D of the target refraction, respectively. The mean spherical equivalent and refractive cylinder values were 0.09± 0.35D and − 0.36± 0.35D, respectively. 76.5% and 98.8% of eyes presented a postoperative refractive cylinder of ≤ 0.50D and ≤ 1.00D, respectively. 91.5% and 100% of patients had a binocular UDVA and CDVA of ≥ 20/25, respectively. The mean binocular UDVA and CDVA were 0.02± 0.08 and − 0.02± 0.07 logMAR, respectively. Under mesopic conditions, 78.7% and 83.0% of patients presented a binocular UDVA and CDVA ≥ 20/32, respectively. The mean binocular UDVA and CDVA were 0.15± 0.11 and 0.12± 0.11 logMAR, respectively. The patients showed good contrast sensitivity under photopic and mesopic conditions. The mean absolute IOL rotation was 1.22± 2.21 degrees with 97.87% of eyes having a rotation of < 10 degrees.Conclusion: This study shows good visual and refractive outcomes for the PODEYE toric IOL when implanted bilaterally in cataract patients with corneal astigmatism.Keywords: monofocal toric, astigmatism, double C-loop, intraocular lens, cataract

Robert Edward T Ang,1 Pavel Stodulka,2 Francisco Poyales3 1Cataract and Refractive Surgery Department, Asian Eye Institute, Makati City, Philippines; 2Cataract and Refractive Surgery Department, Gemini Eye Clinic, Zlín and Gemini Eye Clinic, Prague, Czech Republic; 3Cataract and Refractive Surgery Department, Miranza IOA, Madrid, Madrid, SpainCorrespondence: Robert Edward T Ang, Cataract and Refractive Surgery Department, Asian Eye Institute, 8th Floor PHINMA Plaza, Rockwell Center, Makati City, Philippines, Email angbobby@hotmail.comPurpose: To assess refractive and visual outcomes of bilateral implantation of an isofocal optic-design intraocular lens (IOL) or a monofocal IOL following cataract surgery.Methods: A total of 127 patients were recruited into a prospective, single-masked, randomized trial. Sixty-five patients bilaterally implanted with the Isopure Isofocal IOL and 62 patients with the Micropure Monofocal IOL were followed for 4– 6 months. Refraction, monocular and binocular uncorrected-distance-visual acuity, corrected-distance-visual acuity (CDVA), uncorrected-intermediate-visual acuity and distance-corrected-intermediate-visual acuity (DCIVA, 66/80 cm), uncorrected-near-visual acuity, and distance-corrected-near-visual acuity (DCNVA, 40 cm) were evaluated. Binocular defocus curve, binocular contrast sensitivity (photopic, mesopic with/without glare), and glare and halo phenomena were also measured.Results: 99.23% of eyes were within ± 1.00D and 84.62% of eyes within ± 0.50D for the Isopure patients and 98.39% and 82.26% for the Micropure patients, respectively. The mean spherical-equivalent was − 0.06 ± 0.36D and 0.10 ± 0.32D for the Isopure and Micropure patients, respectively. 98.5% and 100% of patients implanted with the Isopure and Micropure IOLs showed a cumulative binocular CDVA value ≥ 20/20, respectively. 80% and 67.70% of patients implanted with the Isopure presented a binocular DCIVA ≥ 20/25 at 80 and 66 cm, respectively. These percentages were 46.8% and 40.3% with the Micropure IOL, respectively. For Isopure, 7.7%, 30.8%, and 58.5% of patients presented a DCNVA ≥ 20/25, ≥ 20/32 and ≥ 20/40, respectively. These values were lower for the Micropure: 1.6%, 19.4% and 46.8%, respectively. Defocus curves showed similar good visual acuity at distance for both lenses with better intermediate vision for the Isopure. Both groups presented good contrast sensitivity, and the size and intensity of halo and glare phenomena were similar between the two. No adverse-events were reported.Conclusion: Our trial shows that both IOLs provide excellent visual acuity and contrast sensitivity for far vision with similar photic phenomena, and the Isopure IOL improved unaided intermediate vision performance.Keywords: intraocular lens, phacoemulsification, cataract, visual acuity, defocus curve

ABSTRACT In the current study, the silencing of protein arginine methyltransferase 5 (PRMT5) decreased the polysaccharide content of Ganoderma lucidum compared to that of the wild-type (WT) strain. Furthermore, RNA-seq screening showed that the glycan degradation process-related gene thaumatin-like protein (TLP) was alternatively spliced in WT strains via retained introns, leading to the production of a longer TLP1 isoform and a shorter TLP2 isoform; however, only the TLP2 isoform was observed in PRMT5i strains. Experiments examining the polysaccharide content of the TLP silencing, TLP1 overexpression (OE-TLP1), and TLP2 overexpression (OE-TLP2) transformants revealed that TLP2 plays a more important role than TLP1 in polysaccharide degradation. Through a combination of yeast two-hybrid, bimolecular fluorescence complementation and surface plasmon resonance assays, we found that TLP2 directly physically interacted with phosphoglucose isomerase (PGI), a key enzyme in polysaccharide synthesis, and thereby increased PGI activity. However, TLP1 failed to interact with PGI, and PGI activity was not affected. Further inspection showed that the polysaccharide content was decreased in the OE-TLP2 strains but not significantly changed in the OE-TLP1 strains compared with that in the WT strains. In addition, the polysaccharide content of the PRMT5-TLP-cosilenced strains was not significantly different from that of the WT strains. These results demonstrate that PRMT5 modulates TLP processing of pre-mRNA transcripts and thereby decreases the polysaccharide content. IMPORTANCE PRMT5 contributes to secondary metabolite biosynthesis in Ganoderma lucidum. However, the mechanism through which PRMT5 regulates the biosynthesis of secondary metabolites remains unclear. In the current study, PRMT5 silencing led to a significant decrease in the biosynthesis of polysaccharides from G. lucidum through the action of the alternative splicing of TLP. A shorter TLP2 isoform can directly bind to PGI and regulated polysaccharide biosynthesis. These results suggest that PRMT5 enhances PGI activity by regulating TLP binding to PGI. The results of the current study reveal a novel target gene for PRMT5-mediated alternative splicing and provide a reference for the identification of PRMT5 regulatory target genes.

The transition-metal dichalcogenides provided a good platform for the investigation of superconductivity and charge-density-wave (CDW) order. A series of high quality 6R-TaS2-xSex (0≤x≤1.6) single crystals were fabricated by the chemical-vapor-transport method and systematically investigated. The CDW becomes more stable with more S being replaced by Se, which causes expansion of the lattice, and produces a negative chemical pressure in the system. The x dependence of the onset of superconductivity (Tconset) shows a dome-like shape with a maximum of Tconset=2.7K at x=0.8. The magnetic susceptibility (4πχ) of x=0.8 under the hydrostatic pressure P=1.0 GPa was also measured, which showed a small increase of Tc and superconducting volume fraction. A pronounced peak effect was observed in the isothermal hysteresis with magnetic field (H) parallel to c-axis, which may arise from the quenching inhomogeneity and/or the stacking disorder. Finally, the evolution of the electronic states tuned by Se-doping was summarized in the phase diagram. [ABSTRACT FROM AUTHOR]

Robert Edward T Ang Cataract and Refractive Surgery Department, Asian Eye Institute, Makati City, PhilippinesCorrespondence: Robert Edward T Ang, Asian Eye Institute, 8th Floor PHINMA Plaza, Rockwell Center, Makati City, Philippines, Email angbobby@hotmail.comPurpose: To show the visual and refractive outcomes in Asian eyes with cataract when bilaterally implanted with either a hydrophobic FineVision POD F GF or a hydrophilic FineVision POD F intraocular lens (IOL).Methods: Forty-six patients were randomized to receive POD F GF or POD F IOLs. Visual and refractive outcomes were assessed up to 24 months post-surgery. Measurements included uncorrected-distance visual acuity, corrected-distance visual acuity (CDVA), distance-corrected intermediate visual acuity (DCIVA), distance-corrected near visual acuity (DCNVA), refraction, defocus curve, photopic and mesopic contrast sensitivity, and patient-reported outcomes.Results: Mean spherical equivalent was close to emmetropia for both groups and stable across postoperative visits. Overall, 97.73% and 100% of eyes in the POD F GF IOL group and 95.65% and 100%, of eyes in the POD F IOL group were within ± 1.00D of the target refraction at 12 and 24 months, respectively. All patients showed a CDVA of ≥ 20/25 at 12- and 24-months post-surgery. In both groups, 24 months post-surgery 91% of patients presented a DCIVA of ≥ 20/25 and 83.3% of patients had a DCNVA of ≥ 20/25. Defocus curve showed continuous visual acuity, being 20/32 or better in both groups over a 4.00D range between 1.00D and − 3.00/-3.50D. Both groups showed good contrast sensitivity values for photopic and mesopic conditions. Overall, 86.4%, 86.4%, and 72.7% of patients implanted with the POD F GF IOL reported not wearing glasses at all for distance, intermediate, and near vision, respectively. These values were 81.8%, 86.4%, and 90.9% for patients implanted with the POD F IOL. Both groups of patients reported similar satisfaction percentages (100% very satisfied/satisfied) and would recommend the procedure (100% definitively yes/probably yes).Conclusion: This study demonstrates good visual and refractive outcomes for both the FineVision POD F GF and the FineVision POD F IOLs when implanted in Asian eyes.Keywords: trifocal, Asian, glistening-free, intraocular lens, cataract

We have performed temperature-dependent synchrotron radiation x-ray absorption fine structure (XAFS) spectra of layered transition metal dichalcogenide 1T-TaS2-xSex to elucidate the local electronic and atomic structure especially associated with the occurrence of superconductivity for the first time. We observed a corresponding temperature-dependent phase transition from nearly commensurate to commensurate charge density wave, as well as a characteristic of p-d hybridization between Ta 5d and Se 4p states, which is favorable to boost superconductivity, determined by x-ray absorption near edge structure (XANES) spectra at the Ta L3-edge and Se K-edge, respectively. And also, the periodic lattice distortion accompanied by the occurrence of charge density wave is clearly demonstrated by extended XAFS (EXAFS) spectra at the Ta L3-edge of the pristine sample 1T-TaS2, which is clearly suppressed in the Se-doping sample 1T-TaSSe with a maximum transition temperature. The present results reveal that the p-d hybridization and the loss of long-range coherence of the CDW state play an important role in manipulating the superconductivity, shedding new light on the physics mechanism of the interplay between superconductivity, charge order, and electron correlation. [ABSTRACT FROM AUTHOR]

The metal-oxide-semiconductor field-effect transistor (MOSFET) device containing silicon nanocrystals (nc-Si) is fabricated by an ion-beam technique. The parasitic effect in the subthreshold region is only observed by the application of high erasing pulses. By using the second derivative method, the formation of the parasitic transistor is confirmed. The parasitic transistor is only activated upon the trapping of holes into the nc-Si at the edge channel. In addition, electron or hole trapping in the nc-Si depend on the voltage polarity and magnitude, which lead to positive or negative shifts in the threshold voltage. This demonstrates the feasibility of memory applications in MOSFET device. [ABSTRACT FROM AUTHOR]

We investigate the exchange bias phenomenon in the layered cobaltite Sr1.5Pr0.5CoO4 by using magnetometry. The exchange bias is strongly dependent on the cooling magnetic field as well as the measuring field. These results suggest that the exchange coupling at the interfaces between the ferromagnetic (FM) regions and the spin-glass (SG) regions may induce an exchange anisotropy. The observed exchange bias effect is suggested to originate from the pinning to FM moments by frozen spins in the SG regions along the cooling field direction. Our results also expand the concept of the magnetically tunable exchange bias, which can contribute to the potential applications for spintronic devices. [ABSTRACT FROM AUTHOR]

We investigate the exchange bias phenomenon in the layered cobaltite Sr1.5Pr0.5CoO4 by using magnetometry. The exchange bias is strongly dependent on the cooling magnetic field as well as the measuring field. These results suggest that the exchange coupling at the interfaces between the ferromagnetic (FM) regions and the spin-glass (SG) regions may induce an exchange anisotropy. The observed exchange bias effect is suggested to originate from the pinning to FM moments by frozen spins in the SG regions along the cooling field direction. Our results also expand the concept of the magnetically tunable exchange bias, which can contribute to the potential applications for spintronic devices. [ABSTRACT FROM AUTHOR]

We present the results of systematic study of structure, magnetic properties, and electrical transport in layered cobaltites Sr2-xPrxCoO4 (0.5≤x≤1.5). The variations of Jahn–Teller distortion of CoO6 octahedron reflected by two different Co–O bond lengths indicate that all the samples are mostly accommodated in the t2g orbital states. For x<1 samples, with increasing Pr-doping level, the tolerance factor decreases and the distortion of CoO6 octahedron enhances, which result in the increased bending of Co–O–Co bond, the narrowing of the bandwidth, and the decrease of the mobility of eg electrons caused by the substitution of smaller Pr3+ ions for a larger Sr2+ ion. For x>1 samples, the contribution of carrier density should be considered besides the tolerance factor. [ABSTRACT FROM AUTHOR]

We present the results of systematic study of structure, magnetic properties, and electrical transport in layered cobaltites Sr2-xPrxCoO4 (0.5≤x≤1.5). The variations of Jahn–Teller distortion of CoO6 octahedron reflected by two different Co–O bond lengths indicate that all the samples are mostly accommodated in the t2g orbital states. For x<1 samples, with increasing Pr-doping level, the tolerance factor decreases and the distortion of CoO6 octahedron enhances, which result in the increased bending of Co–O–Co bond, the narrowing of the bandwidth, and the decrease of the mobility of eg electrons caused by the substitution of smaller Pr3+ ions for a larger Sr2+ ion. For x>1 samples, the contribution of carrier density should be considered besides the tolerance factor. [ABSTRACT FROM AUTHOR]

We have systematically investigated the influence of the Ag doping on magnetization M(T), resistivity ρ(T), thermoelectric power S(T), and thermal conductivity κ(T) in the layered cobaltites Bi2Ba3-xAgxCo2Oy (0≤x≤2) samples. For Ag-doped sample, the magnetic susceptibility indicates the ground state is dominated by the low-spin states of the combination of Co3+ and Co4+. The metal-insulator transition existing in Ag-free sample is suppressed and replaced by metallic behavior due to Ag doping. Moreover, S is remarkably large and temperature independent with metallic ρ(T) at high temperatures, which is suggested to be the evidence of a narrow a1g band. A steep upturn of ρ is observed at low temperature while no corresponding change appears in the S(T) curve. Such an abnormal behavior is attributed to Anderson localization in a narrow band. Additionally, the Ag doping not only introduces holes into the conducting CoO2 layers but also enhances the disorder which decreases the upper mobility edge EC. As to κ(T), it plays an important role for the contribution of mobile electronic carrier component κe besides the contribution of phononic component κph. The behavior of κe is ascribed to the effect of the competition between magnetic interaction and the disorder. The variation of κph is analyzed according to the combined effect due to the impurity and disorder because of Ag doping, which is favorable to the scattering of phonon leading to the decrease of κph, and the decreased scattering of interface between the CoO2 and the Bi–Ba–O blocks due to Ag doping, which contributes to the increase of κph. [ABSTRACT FROM AUTHOR]

We have systematically investigated the influence of the Ag doping on magnetization M(T), resistivity ρ(T), thermoelectric power S(T), and thermal conductivity κ(T) in the layered cobaltites Bi2Ba3-xAgxCo2Oy (0≤x≤2) samples. For Ag-doped sample, the magnetic susceptibility indicates the ground state is dominated by the low-spin states of the combination of Co3+ and Co4+. The metal-insulator transition existing in Ag-free sample is suppressed and replaced by metallic behavior due to Ag doping. Moreover, S is remarkably large and temperature independent with metallic ρ(T) at high temperatures, which is suggested to be the evidence of a narrow a1g band. A steep upturn of ρ is observed at low temperature while no corresponding change appears in the S(T) curve. Such an abnormal behavior is attributed to Anderson localization in a narrow band. Additionally, the Ag doping not only introduces holes into the conducting CoO2 layers but also enhances the disorder which decreases the upper mobility edge EC. As to κ(T), it plays an important role for the contribution of mobile electronic carrier component κe besides the contribution of phononic component κph. The behavior of κe is ascribed to the effect of the competition between magnetic interaction and the disorder. The variation of κph is analyzed according to the combined effect due to the impurity and disorder because of Ag doping, which is favorable to the scattering of phonon leading to the decrease of κph, and the decreased scattering of interface between the CoO2 and the Bi–Ba–O blocks due to Ag doping, which contributes to the increase of κph. [ABSTRACT FROM AUTHOR]

We present the results of a systematic study of the transport mechanism and magnetothermoelectric power (MTEP) of electron-doped manganites La0.85Te0.15Mn1-xCuxO3 (0<=x<=0.20). Two peaks are observed in thermoelectric power S(T) curves for x<0.10 samples. For x>0.10 samples, the very large S value with over 100 μV/K at low temperatures appears, which is attributed to the destruction of ferromagnetic (FM) order and the strong carrier localization at low temperatures due to Cu doping. In addition, a sign variation of S(T) for Cu-doped samples is also observed, which may originate from the narrowing of the concomitant σ(eg↑-2p) band. Particularly, an anomalous behavior of S(T) is observed in x=0.10 sample, which is suggested to be related to the contribution of spin polarization and phonon drag. Based on the results of resistivity ρ(T) and S(T), the transport mechanism in the high-temperature paramagnetic region for all the samples and low-temperature FM insulating region below TC for the samples with x<=0.10 can be described by the variable-range-hopping model. However, in the intermediate-temperature FM metallic region below TC, ρ(T) and S(T) of the samples with x<=0.10 are well fitted by the formula ρ=ρ0+ρ2.5T2.5 and S=S0+S3/2T3/2+S4T4, respectively, implying the importance of electron-magnon scattering. As to the MTEP, only a negative MTEP peak close to TC is observed in the whole measured temperature range for the samples with x>0.10, which is suggested to originate from the spin alignment induced by applied magnetic fields. However, for x<=0.10 samples, an additional positive MTEP peak is induced by Cu doping below TC besides a large negative MTEP peak in the vicinity of TC, which is ascribed to the enhancement of electron-magnon interaction caused by the Cu doping and the decrease of magnetic entropy around TC, respectively. [ABSTRACT FROM AUTHOR]

The effects of V doping on field-cooled magnetization MFC(T), zero-field-cooled magnetization MZFC(T), resistivity ρ, thermoelectric power S, and thermal conductivity κ in manganites CaMn1-xVxO3 (0.02<=x<=0.08) have been investigated systematically. As the V doping level exceeds 0.02, an anomalous “diamagnetism” has been observed. It is suggested that the force generated by the orbit rotation of eg electron in Mn3+O6 octahedron makes the spin tilt, as a result, the vector sum of individual spins may be along or opposite to the direction of the applied magnetic field, and macroscopically, the average magnetization exhibits positive or negative values. In addition, the transport mechanism in the high and low temperature ranges is dominated by the small polaron conduction and the variable-range-hopping conduction, respectively, according to the fitting analysis of the temperature dependence of Seebeck coefficient S(T) and resistivity ρ(T). Both S and κ peaks appearing at low temperature is gradually suppressed by V doping. Additionally, obvious magnetothermoelectric power and magnetothermal conductivity are observed in the temperature region which an anomalous diamagnetism appears. The results are discussed based on spin-orbital coupling and spin-phonon coupling induced due to V doping, respectively. Moreover, the large thermoelectric figure of merit Z=S2/ρκ for the slightly V-doped sample suggests that the V-doped manganite may be a good candidate for thermoelectric materials. [ABSTRACT FROM AUTHOR]

Ian JY Wee,1 Fiona NN Moe,1 Rehena Sultana,2 Reiko WT Ang,1 Pearly PS Quek,3 Brian Kim Poh Goh,1 Chung Yip Chan,1 Peng Chung Cheow,1 Alexander YF Chung,1 Prema Raj Jeyaraj,1 Ye Xin Koh,1 Peter OP Mack,1 London Lucien PJ Ooi,1 Ek Khoon Tan,1 Jin Yao Teo,1 Juinn Huar Kam,1 Jacelyn SS Chua,1 Ashley WY Ng,1 Jade SQ Goh,1 Pierce KH Chow1,4 1Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore; 2Center of Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore; 3Ministry of Health Holdings, Singapore, Singapore; 4Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, SingaporeCorrespondence: Pierce KH Chow, Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore, Tel +65 6576 2151, Email pierce.chow@duke-nus.edu.sgObjective: We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour.Methods: This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7).Results: A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03– 2.08) and B2-S (HR 1.65, 95% CI 1.25– 2.18).Conclusion: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.Keywords: hepatocellular carcinoma, surgical resection, Barcelona clinic liver cancer