The advanced development of molecular targeted therapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.

Characterization and Fine Mapping of a Novel Rice Albino Mutant low temperature albino 1

Albino mutants are useful genetic resource for studying chlorophyll biosynthesis and chloroplast development and cloning genes involved in these processes in plants. Here we report a novel rice mutant low temperature albino I （ltal） that showed albino leaves before 4-leaf stage when grown under temperature lower than 20℃, but developed normal green leaves under temperature higher than 24℃ or similar morphological phenotypes in dark as did the wild-type （WT）. Our analysis showed that the contents of chlorophylls and chlo- rophyll precursors were remarkably decreased in the Ital mutant under low temperature compared to WT. Transmission electron microscope observation revealed that chloroplasts were defectively developed in the albino ltal leaves, which lacked of well-stacked granum and contained less stroma lamellae. These results suggested that the ltal mutation may delay the light-induced thylakoid assembly under low temperature. Genetic analysis indicated that the albino phenotype was controlled by a single recessive locus. Through map-based approach, we finally located the Ltal gene to a region of 40.3 kb on the short arm of chromosome 11. There are 8 predicted open reading frames （ORFs） in this region and two of them were deleted in ltal genome compared with the WT genome. The further characterization of the Ltal gene would provide a good approach to uncover the novel molecular mechanisms involved in chloroplast development under low temperature stress.

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.

Tribological Behaviors of Ni_3Al Intermetallics with MoO_3 Multilayer Ribbon Crystal Prepared by Spark Plasma Sintering

This study reports that small amounts of MoO3 multilayer ribbon crystal （MOO3 MLRC） in Ni3Al intermetallics showed the decreased friction coefficients and improved wear resistance at different contact loads. Specifically, the friction coefficients （0.32-0.34） and wear rates [（2-4）× 10^-5 mm^3 N^-1 m^-1] are significantly reduced for NiaAl at 2-8 N. A possible explanation for the friction and wear reduction is that MoO3 MLRC as a multilayer material shears easily in the tribo-layer during the sliding contact, and provides low friction. In addition, this MoO3 MLRC with excellent bending strength is found to dissipate shear stress and suppress severe plastic deformation under a cyclic stress, thus drastically improving wear resistance of Ni3Al.

Effects of groove-textured surfaces filled with Sn-Ag-Cu and MXene-Ti_(3)C_(2) composite lubricants on tribological properties of CSS-42L bearing steel

To improve the tribological performance of CSS-42L bearing steel,smooth surfaces(SSs),groovetextured surfaces(GSs),GSs with Sn-Ag-Cu(GSs-SAC),and GSs with Sn-Ag-Cu-Ti_(3)C_(2)(GSs-SACT)were prepared on CSS-42L.In addition,experimental studies were conducted on tribological properties.The obtained results indicated that GSs-SACT exhibited the best anti-friction and noise reduction performances.These remarkable tribological performances were attributed to the synergistic effects of grooves,Sn-Ag-Cu,and MXene-Ti_(3)C_(2).The inconsistent rules of frictional forces were improved by the grooves and SACT,which inhibit the friction-induced noise.The micro-nano size-effects of MXene-Ti_(3)C_(2) enhanced the repairing effect and anti-friction property of composite lubricants,which improved the profile characteristics of GSs-SACT.

TSC1 enables plastid development under dark conditions, contributing to rice adaptation to transplantation shock

Since its domestication from wild rice thousands of years ago, rice has been cultivated largely through transplantation. During transplantation from the nursery to the paddy field, rice seedlings experience transplantation shock which affects their physiology and production.However, the mechanisms underlying transplantation shock and rice adaptation to this shock are largely unknown. Here,we isolated a transplant-sensitive chloroplast-deficient（tsc_1）rice mutant that produces albino leaves after transplantation.Blocking light from reaching the juvenile leaves and leaf primordia caused chloroplast deficiencies in transplanted tsc_1 seedlings. TSC_1 encodes a noncanonical adenosine triphosphate-binding cassette（ABC） transporter homologous to At NAP_（14） and is of cyanobacterial origin. We demonstrate that TSC_1 controls plastid development in rice under dark conditions, and functions independently of light signaling.However, light rescued the tsc_1 mutant phenotype in a spectrum-independent manner. TSC_1 was upregulated following transplantation, and modulated the iron and copper levels, thereby regulating prolamellar body formation during the early P_4 stage of leaf development. Therefore, TSC_1 is indispensable for plastid development in the absence of light,and contributes to adaptation to transplantation shock.Our study provides insight into the regulation of plastid development and establishes a framework for improving recovery from transplantation shock in rice.