Lung cancer has the highest mortality rate among all cancers worldwide. The 5-year overall survival rate for non-small cell lung cancer (NSCLC) is estimated at around 26%, whereas for small cell lung cancer (SCLC), the survival rate is only approximately 7%. This disease places a significant financial and psychological burden on individuals worldwide. The symbiotic microbiota in the human body has been significantly associated with the occurrence, progression, and prognosis of various diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Studies have demonstrated that respiratory symbiotic microorganisms and their metabolites play a crucial role in modulating immune function and contributing to the pathophysiology of lung cancer through their interactions with the host. In this review, we provide a comprehensive overview of the microbial characteristics associated with lung cancer, with a focus on the respiratory tract microbiota from different locations, including saliva, sputum, bronchoalveolar lavage fluid (BALF), bronchial brush samples, and tissue. We describe the respiratory tract microbiota\'s biodiversity characteristics by anatomical region, elucidating distinct pathological features, staging, metastasis, host chromosomal mutations, immune therapies, and the differentiated symbiotic microbiota under the influence of environmental factors. Our exploration investigates the intrinsic mechanisms linking the microbiota and its host. Furthermore, we have also provided a comprehensive review of the immune mechanisms by which microbiota are implicated in the development of lung cancer. Dysbiosis of the respiratory microbiota can promote or inhibit tumor progression through various mechanisms, including DNA damage and genomic instability, activation and regulation of the innate and adaptive immune systems, and stimulation of epithelial cells leading to the upregulation of carcinogenesis-related pathways.

Uniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. This study describes clinical phenotypes and genetic findings of three patients with UPD 2, 9, and 14, respectively. Chromosomal microarray (CMA), UPDtool, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and whole-exome sequencing (WES) analysis were performed to characterize the genetic etiology. The CMA revealed a homozygous region involving the whole chromosome 2 and 9, a partial region of homozygosity in chromosome 14. UPD-tool revealed a paternal origin of the UPD2. MS-MLPA showed hypomethylation of imprinting gene MEG3 from maternal origin in the UPD14 case. In addition, UPD14 case displayed complex symptoms including growth failure, hypotonia and acute respiratory distress syndrome (ARDS), accompanied by several gene mutations with heterozygous genotype by WES analysis. Furthermore, we reviewed the documented UPDs and summarized the clinical characteristics and prognosis. This study highlighted the importance to confirm the diagnosis and origin of UPD using genetic testing. Therefore, it is suggested that expanding of the detailed phenotypes and genotypes provide effective guidance for molecule testing and genetic counseling, and promote further biological investigation to the underlying mechanisms of imprinted disorders and accompanied copy number variations.

BACKGROUND: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses.
METHODS: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated.
RESULTS: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome.
CONCLUSIONS: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.

Tetracycline (TC) is a commonly used antibiotic that affects various physiological processes in plants. However, its negative effects on plants remain poorly understood at the molecular level. To ascertain the TC toxicity in the roots, transcriptomic, cytological, and physiological analyses were performed to explore the molecular mechanisms of TC influencing the growth of hulless barley root. At a low concentration (1 mg/L), TC promoted root growth by upregulating the genes related to the flavonoid pathway. At high concentrations (10, 100, and 200 mg/L), TC downregulated genes related to homologous recombination in the root meristem zone and inhibited the mitosis index by 16.4%. Disruption of the DNA repair process can lead to chromosomal aberrations, resulting in a 6.8% C-mitosis rate in the most severe cases. Finally, root growth was inhibited by TC, as evidenced by a reduction in root viability, an increase in reactive oxygen species content, and an inhibition of root length. Cross-comparison of physiological and cytological characterizations and transcriptomic information revealed changes in genetic processes under TC stress. Overall, we present an early genetic strategy to study the significant influence of TC stress on roots.

Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.
目的： 分析医疗放射工作人员淋巴细胞染色体畸变水平及影响因素。 方法： 于2020年7至9月，选取某三甲医院252名医疗放射工作人员作为放射组并依据工种、工龄分为不同亚组，以同期岗前体检拟从事放射工作的107名健康成年人为对照组，收集研究对照信息，采用常规细胞遗传学方法检测外周血淋巴细胞的染色体畸变，统计分析各组间检测结果。 结果： 放射组\"dic+r\"率、染色体总畸变率及异常检出率均明显高于对照组（Z=2.59、3.74、9.99，P<0.05）；不同工种间\"dic+r\"率、ace率及染色体总畸变率的差异有统计学意义（χ(2)=8.59、8.17、11.39，P<0.05），其中介入放射学组的\"dic+r\"率明显高于放射诊断组（χ(2)=2.90，P<0.05），核医学组的ace率及染色体总畸变率明显高于放射诊断组（χ(2)=2.81、3.19，P<0.05）；不同工种放射工作人员染色体畸变异常检出率差异有统计学意义（P<0.05），其中介入放射学组明显高于放射诊断组（χ(2)=7.66，P<0.05）。不同工龄组间染色体畸变水平及异常检出率的差异均无统计学意义（P>0.05）。Possion回归分析显示，与放射诊断组比较，核医学组、放射治疗组及介入放射学组（IRR=2.31、1.66、1.78，P<0.05）导致染色体畸变风险升高。 结论： 电离辐射对医疗放射工作人员产生一定的辐射损伤，核医学与介入放射学工作人员的染色体畸变水平相对较高，需加强辐射防护以保障相关从业人员的健康。.

There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.

Chromosome aberration (CA) is a serious genotoxicity of a compound, leading to carcinogenicity and developmental side effects. In the present manuscript, we developed a QSAR model for CA prediction using artificial intelligence methodologies. The reliable QSAR model was constructed based on an enlarged data set of 3208 compounds by optimizing machine learning and deep learning algorithms based on hyperparametric iterations and using multiple descriptors of molecular fingerprint in combination with drug-like molecular properties (MP) screened by entropy weight methodology on the open-source Python platform. Furthermore, molecular similarity for returning search and molecular connection index for additional descriptor were additionally introduced to differentiate the compounds with high similarity for correct CA prediction for QSAR model generation. The final generated CA-(Q)SAR model exhibited good prediction accuracy of 80.6%. The bias of the final model is about 0.9793. On the basis of generated QSAR model, data analyses were further performed to analyze the typical structure features in numerical intervals (MPI) of molecular properties MW, XlogP, and TPSA, respectively, for potential CA or non-CA toxicity with a normalized occurrence probability (NOP) more than 70%, which may provide useful clues for drug design of leads or candidate devoid of CA genotoxicity.

Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease. The aim of this study was to develop an effective prognosis prediction model for NB patients.
We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p (Chr1p_del) and chromosome 11q (Chr11q_del) as well as chromosome 11q whole loss (Chr11q_wls). We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets (the number of samples ranges from 94 to 498, with a total of 2120) generated from both RNA sequencing and microarray platforms.
MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression. Similarly, the Chr1p_del score was more prognostic than Chr1p status. The activity scores of MYCN, Chr1p_del and Chr11q_del were associated with poor prognosis, while the Chr11q_wls score was linked to good outcome. We integrated the activity scores of MYCN, Chr1p_del, Chr11q_del, and Chr11q_wls and clinical variables into an integrative prognostic model, which displayed significant performance over the clinical variables or each genomic aberration alone.
Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information, and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs.

Cardiovascular diseases (CVDs) are the leading cause of death in the world; however, current agents for CVDs prevention are still limited. Owing to the serious bleeding risk of Aspirin, FDA recently recommended against it from preventing first heart attacks. Nattokinase (NK), a serine protease possessing many key beneficial effects on cardiovascular system, is being pursued as a promising alternative agent. In light of this, the safety profile of NK, in particular its potential genotoxicity, need to be characterized. The present study is therefore aimed to evaluate the toxicological profile of NK. To assess acute safety, mice were orally administrated with NK at its maximum concentration and the maximum feeding volume twice in a single day, no mortality or toxicological signs were observed. Hence, the maximum daily tolerant dose of NK in mice is up to 480000 FU/kg, which is 1000 times more compared to the recommended daily dose for human. In the genotoxicity studies, NK showed no mutagenic activity as tested by both Ames test and in vivo micronucleus assay. Moreover, NK demonstrated no evidence of potential to induce chromosome aberrations in CHL cells. These results indicate that there is no safety concern for NK in the present preclinical safety studies, supporting the safety of NK as an agent for CVDs prevention.

TERF1-interacting nuclear factor 2 (TIN2) is a key member of the protein complexes that protect telomeres. TIN2 contributes an important role in biological processes. In a previous study by the present authors, an association was reported between high TIN2 protein expression and gastric cancer. Therefore, it was hypothesized that abnormal TIN2 expression may cause the development of malignancies, including, gastric carcinomas. To investigate this hypothesis, the present study employed peptide nucleic acid fluorescence in situ hybridization technology to analyze the human gastric epithelial GES-1 cells with high TIN2 expression or inhibited TIN2 expression. The results indicated that GES-1 cell lines with high TIN2 expression exhibited greater telomere dysfunction-induced damage compared with GES-1 cell lines with inhibited TIN2 expression. Chromosome analysis indicated that GES-1 cells with high TIN2 expression exhibited 2.48±1.30 aberrant chromosomal changes per 100 cells, that may contribute to telomere DNA damage. Therefore, aberrant chromosomal alterations may provide a novel perspective for the pathogenesis of gastric cancer.