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result(s) for
"Hu, Xue-Da"
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Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution
The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8
+
T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8
+
T and immune-suppressive TNFRSF4
+
Treg cells in tumours might derive from peripheral CX3CR1
+
CD8
+
T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3
+
DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3
+
DCs, Treg, exhausted CD8
+
T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.
Nasopharyngeal carcinoma is a diverse cancer characterised by a heterogeneous microenvironment. Here, the authors use single cell sequencing to analyse the tumour microenvironment in 10 nasopharyngeal carcinoma tumours and identify different cell types including immune-suppressive T regulatory, tolerogenic dendritic, and exhausted CD8 T cells.
Journal Article
Genetic landscape of esophageal squamous cell carcinoma
Jie He and colleagues report exome sequencing of 113 tumor-normal pairs of esophageal squamous cell carcinoma. They highlight mutations in genes involved in cell cycle and apoptosis regulation, histone modifier genes and genes encoding members of the Hippo and Notch pathways.
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers
1
. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of
TP53
(93%),
CCND1
(33%),
CDKN2A
(20%),
NFE2L2
(10%) and
RB1
(9%). Histone modifier genes were frequently mutated, including
KMT2D
(also called
MLL2
; 19%),
KMT2C
(
MLL3
; 6%),
KDM6A
(7%),
EP300
(10%) and
CREBBP
(6%).
EP300
mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in
FAT1
,
FAT2
,
FAT3
or
FAT4
(27%) or
AJUBA
(
JUB
; 7%) and
NOTCH1
,
NOTCH2
or
NOTCH3
(22%) or
FBXW7
(5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
Journal Article
Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells
Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using secondgeneration sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.
Journal Article
Case report: Significant response of alpha-fetoprotein-producing gastric cancer from combined chemotherapy and immunotherapy
Alpha-fetoprotein-producing gastric cancer (AFPGC) represents a particularly aggressive subtype of gastric carcinoma characterized by elevated rates of vascular invasion, lymphatic dissemination, hepatic metastasis, and an unfavorable clinical outcome. Treatment strategies for AFPGC have historically lacked specificity. Herein, a case is presented involving AFPGC in which the patient exhibited a notable response to combined anti-PD-1 antibody immunotherapy and SOX chemotherapy, potentially achieving a cure. This report marks the first application of this regimen in neoadjuvant therapy for AFP gastric cancer, followed by radical resection and postoperative adjuvant therapy.
A 62-year-old male patient presented with persistent upper abdominal distension and discomfort lasting over 2 months. Initial investigations revealed markedly elevated serum alpha-fetoprotein (AFP) levels, and subsequent pathological examination confirmed the diagnosis of AFPGC via gastroscopy. Due to the patient's condition, surgical resection was initially deemed unfeasible. Therefore, a chemo-immunotherapy regimen consisting of SOX chemotherapy and the PD-1 inhibitor tislelizumab was administered for 3 cycles. Following this, successful laparoscopic radical gastrectomy was performed. The treatment protocol was continued with an additional 3 cycles postoperatively. At the time of this case report, the patient maintained a good quality of life with no evidence of disease recurrence or adverse events.
The present report highlights a case of AFPGC where significant therapeutic success was achieved through a combined regimen of chemotherapy and immunotherapy, both before and after surgery. The use of anti-PD-1 antibody (tislelizumab) in combination with SOX regimen (S-1 and oxaliplatin) demonstrated effective treatment of AFPGC, potentially offering a curative approach. This approach represents a promising targeted therapy option for patients with AFPGC.
Journal Article
Dissecting yield-associated loci in super hybrid rice by resequencing recombinant inbred lines and improving parental genome sequences
The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang–You–Pei–Jiu , the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93–11 and maternal cultivar PA64s of Liang–You–Pei–Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1 , and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.
Journal Article
Mapping of QTLs for source and sink associated traits under elevated CO2 in rice (Oryza sativa L.)
Rice source- and sink-associated traits are important for grain yield and are sensitive to environmental conditions. The continuing increase of CO2 concentrations in the atmosphere will become a major challenge for rice growth and development in the future due to changes in our climate such as extremes in temperature. To guarantee food safety, novel genetic loci need to be identified for source- and sink-associated traits that are specifically expressed under elevated CO2 conditions. Eighty chromosome segment substitution lines carrying japonica (Nipponbare) chromosome segments in the indica (9311) background were used in this study. QTL analysis was conducted for source- and sink-related traits, including flag leaf length, flag leaf width, flag leaf fresh weight, flag leaf dry weight, primary branch number, secondary branch number, grain number per panicle, panicle weight per plant, chlorophyll a, chlorophyll b, and carotenoid contents, under ambient CO2 concentrations and free-air CO2 enrichment. A total of 49 QTLs for these traits were detected on chromosomes 1, 3, 5, 6, 7, 9, and 12 under the two conditions; the variance explained by these QTLs varied from 6.22 to 38.15%. Among these QTLs, 19 of them were detected under the natural field conditions and 30 were detected in the elevated CO2 conditions. In addition, 2 and 13 QTLs were specifically expressed in the natural and CO2-enriched conditions, respectively. Our findings have important implications on the utilization of germplasm resources for ensuring food security under elevated CO2 levels, especially for QTLs that were specifically detected under the elevated CO2 condition.
Journal Article
Map-based cloning of a spotted-leaf mutant gene OsSL5 in Japonica rice
A japonica rice mutant, spotted-leaf 5 (sl5), was identified from YUN32 by EMS mutagenesis. The number of spots in leaves increased from maturity to late maturity in sl5, however, the leaves did not dry and withered. The sl5 mutant exhibited significantly lower height, spike length, primary branch number, second branch number, and 1,000-grain weight than YUN32. Genetic analysis shows that sl5 is controlled by a single recessive gene. OsSL5 was mapped into a 40-kb interval flanked by markers MX4 and MX5 on chromosome 7 by map-based cloning. Four ORFs, including one SPL5 gene, were identified in this region. Sequencing reveals that the G base at site 3,647 of the OsSL5 coding region was changed to A. The mutant OsSL5 site was different from that of the SPL5 mutant, with the background of indica rice. OsSL5 is thus a new SPL5 allele which encodes a putative splicing factor 3b subunit 3. QPCR shows that OsSL5 expression in the sl5 mutant is significantly lower than that in YUN32. The spotted leaf-related genes RLIN1, SPL28, and SPL18 expressions were significantly decreased, whereas the SPL7 and SL gene expressions significantly increased. The OsSL5 gene may be important for rice cell apoptosis regulation.
Journal Article
The Effects of Climate Change on the Distribution of Snub-Nosed Monkey in China
Study on effects of climate change on species is very popular and necessary at present. This paper investigated the effects of climate change on the distribution of snub-nosed monkey in China using Arcgis and Maxent model. It compared the historical and modern distribution of snub-nosed monkey in China, and evaluated the effects of climate change on Rhinopithecus bieti to explore effects on the distribution of snub-nosed monkey, so as to protect them. Results indicate that the distribution range of snub-nosed monkey has decreased greatly from the previous 17 to 8 provinces. The distribution trends are from north to south, east to west, dense to sparse and form several isolated distribution areas. Moreover, six precipitation variables are identified as having remarkable effects on the habitat suitability of Rhinopithecus bieti and therefore protective actions can be taken accordingly.
Journal Article
A Novel Frequency Synchronization Algorithm Based on PN Sequences and Pilots for TFU-OFDM Systems
In this paper, a novel frequency synchronization algorithm for a new modulation scheme named time domain and frequency domain united orthogonal frequency division multiplexing (TFU-OFDM) is introduced. The frequency synchronization method has two-steps, which joints time and frequency domain estimation based on PN sequences and pilots. We utilize the PN sequences as guard intervals in time domain to achieve the first-step estimation and the second-step is realized by the pilots in data blocks in frequency domain. The simulation results and analysis show that the proposed frequency synchronization method could achieve fast and reliable synchronization and sufficient precision, and provides excellent performance for TFU-OFDM systems.
Journal Article