OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

As a biocatalyst, laccase has been widely studied and applied in the papermaking industry. However, the low catalytic efficiency and poor stability of natural laccase limit its application in the pulping process. To develop the laccase with high activity and strong tolerance, we carried out directed evolution for modification of the laccase derived from Bacillus pumilus and screened out the mutants F282L/F306L and Q275P from the random mutant library by high-throughput screening. The specific activities of F282L/F306L and Q275P were 280.87 U/mg and 453.94 U/mg, respectively, which were 1.42 times and 2.30 times that of the wild-type laccase. Q275P demonstrated significantly improved thermal stability, with the relative activity 20% higher than that of the wild-type laccase after incubation at 40 ℃, 50 ℃, and 70 ℃ for 4 h. F282L/F306L and Q275P showed greater tolerance to metal ions and organic solvents than the wild-type laccase. The K_m value of the wild-type laccase was 374.97 μmo/L, and those of F282L/F306L and Q275P were reduced to 318.96 μmo/L and 360.71 μmo/L, respectively, which suggested that the substrate affinity of laccase was improved after mutation. The k_cat values of F282L/F306L and Q275P for the substrate ABTS were 574.00 s^-1 and 898.03 s^-1, respectively, which were 1.1 times and 1.7 times that of the wild-type laccase, indicating the improved catalytic efficiency. Q275P demonstrated better performance than the wild-type laccase in pulping, as manifested by the reduction of 0.82 in the Kappa number and the increases of 2.00% ISO, 7.8%, and 7.2% in whiteness, tensile index, and breaking length, respectively. This work lays a foundation for improving the adaptation of laccase to the environment of the papermaking industry.
Laccase/chemistry* ; Directed Molecular Evolution ; Enzyme Stability ; Bacillus pumilus/genetics* ; Mutation ; Biocatalysis ; Catalysis

So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
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Humans ; Lung Neoplasms/genetics* ; Clinical Relevance ; Evolution, Molecular ; Mutation ; Tumor Microenvironment

OBJECTIVES: To study the clinical characteristics and prognosis of T-lineage acute lymphoblastic leukemia (T-ALL) and related prognostic factors. METHODS: A retrospective analysis was conducted on the children with T-ALL who were treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL) regimen in Guangzhou Women and Children's Medical Center between April 2015 and December 2022. RESULTS: A total of 80 children were included, with a median age of 7 years and 3 months and a male/female ratio of 6:1. Among these children, the children with mediastinal mass accounted for 20% (16/80), those with central nervous system leukemia accounted for 4% (3/80), and those with testicular leukemia accounted for 1% (1/69). SIL/TAL1 was the most common fusion gene (22%, 18/80), and NOTCH1 was the most common mutation gene (69%, 37/54). The median follow-up time was 52 months, with a 5-year overall survival (OS) rate of 87.3%±4.0% and a 5-year event-free survival rate of 84.0%±4.3%. The non-central nervous system-1 group had a significantly lower 5-year OS rate than the central nervous system-1 group (66.7%±16.1% vs 90.3%±3.8%; P<0.05), and the group with minimal residual disease (MRD) ≥0.01% on day 46 of induction therapy had a significantly lower 5-year OS rate than the group with MRD <0.01% (68.6%±13.5% vs 94.8%±3.0%; P<0.05). CONCLUSIONS Children treated with the CCCG-ALL regimen tend to have a good treatment outcome. Non-central nervous system-1 status and MRD ≥0.01% on day 46 of induction therapy are associated with the poor prognosis in these children.
Humans ; Male ; Female ; Child ; Prognosis ; Child, Preschool ; Retrospective Studies ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Infant ; Adolescent ; Receptor, Notch1/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Survival Rate

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.
Child ; Humans ; Mutation Rate ; Membrane Transport Proteins/genetics* ; China ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Vestibular Aqueduct ; Vestibular Diseases/pathology* ; Deafness/genetics*

BACKGROUND: Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes. METHODS: Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method. RESULTS: A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports. CONCLUSIONS Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.
Humans ; Male ; Female ; Aged ; Lung Neoplasms/genetics* ; Adenocarcinoma/pathology* ; Prognosis ; Survival Rate ; Mutation ; ErbB Receptors/genetics* ; Neoplasm Staging ; Retrospective Studies

Objective: To assess the incidence of dengue fever and E gene evolution of dengue virus in Guangzhou in 2020 and understand the local epidemiological characteristics of dengue fever and spreading of dengue virus. Methods: The information of dengue fever cases in Guangzhou in 2020 was collected from Notifiable Infectious Disease System of Chinese Center for Disease Control and Prevention Information System. Serum samples from the cases were detected by real-time PCR. The E gene was sequenced and analyzed. Maximum likelihood phylogenetic trees were constructed using software MEGA 5.05. The statistical analysis was conducted using software SPSS 20.0. Results: A total of 33 dengue fever cases were reported in Guangzhou in 2020, including 31 (93.94%) imported cases and 2 (6.06%) local cases. Compared with the data during 2016 to 2019, the number of cases, overall incidence and local incidence all decreased with statistically significant differences (all P<0.05). The imported cases from Southeast Asia constituted 90.32% (28/31) of imported cases. The E gene sequences and the phylogenetic trees of imported and local cases demonstrated close relationship with the virus sequences from Southeast Asian, and they were less homologous with the sequences of dengue virus isolated in Guangzhou in previous years. Conclusions: The incidence of dengue in Guangzhou in 2020 was significantly affected by the imported cases, especially those from Southeast Asian countries. The study result demonstrated that dengue fever was not endemic in Guangzhou and it was caused by imported ones.
China/epidemiology* ; Dengue/epidemiology* ; Dengue Virus/genetics* ; Disease Outbreaks ; Evolution, Molecular ; Genotype ; Humans ; Phylogeny

To explore the different chloroplast genome characteristics of Sinopodophyllum hexandrum, five chloroplast genome sequences of S. hexandrum were compared. Its genome map, repeat sequence, codon preference, inverted repeat (IR)/single-copy (SC) boundary, alignment of chloroplast genome sequences and phylogenetic were analyzed using bioinformatics tools. The results showed that: the total length of five chloroplast genomes of S. hexandrum, with a typical tetrad structure, were 157 203-157 940 bp, and a total of 133-137 genes were annotated, reflecting the diversity of chloroplast genomes of S. hexandrum. Different chloroplast genomes of S. hexandrum has different simple sequence repeat (SSR), where simple repeat of single nucleotide of A/T were the majority among the SSR detected. The interspersed repetitive sequences included direct, palindromic and inverted repeats. The value of effective number of codon (ENc) which was analyzed by using codon bias was 51.14~51.17, the proportion of GC and GC3s was less than 50%, the codon usage pattern tended towards frequently use of A/U-ending bases. Genome sequences and the IR/SC boundaries of five chloroplast genomes of S. hexandrum were relatively conservative. Phylogenetic analysis showed that S. hexandrum and Podophyllum pettatum had the closest genetic relationship. In summary, the chloroplast genome characteristics and evolutionary relationship of different chloroplast genomes of S. hexandrum were obtained, which may facilitate the utilization, protection, variety identification and genetic evolution of S. hexandrum resources.
Phylogeny ; Genome, Chloroplast ; Chloroplasts/genetics* ; Genomics ; Evolution, Molecular

Enzymes and cell factories are the core of industrial biotechnology. They play important roles in various fields such as medicine, chemical industry, food, agriculture, and energy. Usually, natural enzymes and cells need to be engineered to improve the catalytic efficiency, stability and enantioselectivity. Directed evolution makes it possible to rapidly improve the properties of enzymes and cell factories. Sensitive and reliable high-throughput screening approaches are the key for successful and efficient engineering of enzymes and cell factories. In this review, we first summarize the advantages and disadvantages of different screening methods and signal generation strategies as well as their application scope; we then describe the latest advances of ultra-high throughput screening technology applied in the directed evolution of enzymes and cell factories in the past three years. On this basis, we discuss the limiting factors that need to be further improved for high-throughput screening systems and forecast the future development trends of high-throughput screening methods, hoping that researchers in various fields including biotechnology and instrument development can cooperate closely to enhance the reliability and applicability of the high-throughput screening techniques.
Biotechnology ; Directed Molecular Evolution ; Enzymes ; High-Throughput Screening Assays ; Reproducibility of Results