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BACKGROUND: Protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) regulates cell cycle and is a part of DNA damage repair (DDR)-related signaling. Recent studies have identified a role for PKMYT1 in tumor immunity and DDR. Thus, we initiated this study aiming to characterize the molecular and immunological portrait of PKMYT1 in cancer. METHODS: Transcriptomic data extrapolated from Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the mRNA expression levels of PKMYT1. PKMYT1 mRNA expression status was correlated with patients’ prognosis as well as immune neoantigens, and immune checkpoints in 34 different tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltrating scores. RESULTS: PKMYT1 mRNA is differentially expressed in common tumors and high expression levels of PKMYT1 mRNA is associated with poor prognosis except for malignant thymoma (THYM). In addition, PKMYT1 mRNA expression was correlated with tumor-infiltrating immune cells particularly in lung squamous cell carcinoma, esophageal carcinoma, THYM, and lung adenocarcinoma. An upregulation of immune checkpoints and neoantigens was observed in tumors with a high PKMYT1 mRNA expression. Data from gene set enrichment analysis (GSEA) revealed that PKMYT1 is involved in tumor immunogenicity, metabolism, and cell cycle progression. CONCLUSIONS: PKMYT1 is differentially expressed in various cancers and exerts an important effect on tumor immunity and progression. The PKMYT1 gene holds the potential as a new potential biomarker. Therefore, further studies are clearly needed to elaborate our findings.

BACKGROUND: Senescence marker protein 30 (SMP30), which plays a pivotal role as a suppressor protein in cell proliferation, among other regulatory actions, is a marker of aging that shows decreased expression during senescence. Decreased SMP30 has been identified in several human cancers, but its expression and role in human non-small cell lung cancer (NSCLC) remain unclear. METHODS: Using tumor tissue and matched adjacent normal tissue from 341 patients with resected NSCLC, we assessed SMP30 expression using immunohistochemical methods. The relationship between SMP30 expression and clinicopathologic characteristics was investigated by Kaplan-Meier survival analysis and multivariate analysis. Cell viability assay, colony formation assay, EdU incorporation assay and in vivo tumor xenograft models were also performed to investigate NSCLC cell proliferation using A549 and H1299 cell lines. Recombinant lentivirus-meditated in vivo gene overexpression and Western blot were performed to clarify the underlying molecular mechanism of SMP30 inhibiting NSCLC proliferation. RESULTS: SMP30 expression was frequently downregulated in NSCLC tissue, as compared with adjacent non-tumor tissue. Kaplan-Meier survival analyses revealed NSCLC patients with low SMP30 expression had a significantly worse overall survival (OS), with median OS of 18 vs. 67 months in high SMP30 expression group. SMP30 overexpression significantly inhibited A549 and H1299 cell proliferation both in vitro and in tumor xenografts and downregulated the expression of c-Myc and CyclinD1 protein. Moreover, Western blot analyses confirmed that SMP30 overexpression significantly inhibited the histone deacetylase 4 (HDAC4) level in NSCLC cells, and HDAC4 overexpression reversed SMP30-mediated NSCLC repression both in vitro and in vivo. CONCLUSIONS: SMP30 inhibited NSCLC proliferation by reducing HDAC4 expression, and SMP30 and HDAC4 may serve as new prognostic biomarkers and future therapeutic targets for NSCLC.

Background Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and is characterized by high morbidity and mortality. However, the detailed molecular mechanisms underlying malignant progression of ESCC remain unclear. Methods 140 patients with esophageal squamous cell carcinoma who underwent surgery were enrolled in this study. Clinicopathologic characteristics and Kaplan–Meier survival analysis were performed to investigate DNMT3A expression and HDAC9 expression. Cell functional experiments were implemented both in vivo and in vitro to investigate the effects on ESCC cell proliferation and metastasis. Recombinant lentivirus–meditated gene overexpression or knockdown showed that HDAC9 participated in DNMT3A-mediated ESCC progression in vivo and in vitro, and this was further confirmed by HDAC inhibitor (SAHA) and immunohistochemical. Results We first demonstrated that DNMT3A expression was significantly higher in ESCC tissues than in corresponding adjacent non-cancerous tissues, and high DNMT3A expression was associated with poor prognosis. Then we confirmed that DNMT3A promoted proliferation and metastasis of ESCC cells in vivo and in vitro, suggesting that DNMT3A may be a promising therapeutic target for preventing esophageal cancer. Additionally, we found that DNMT3A up-regulated HDAC9, and HDAC9 overexpression significantly reversed the inhibitory effect caused by DNMT3A gene knockdown. In addition, we further confirmed the involvement of HDAC9 in DNMT3A-mediated carcinogenesis using HDAC inhibitor (SAHA). At last, we also validated HDAC9 expression was significantly higher in ESCC tissues than in corresponding adjacent non-tumour tissues, and high HDAC9 expression was positively associated with poor prognosis. Interestingly, Spearman correlation analysis confirmed a significant positive correlation between DNMT3A and HDAC9 expression. and ESCC patients with simultaneous DNMT3A and HDAC9 expression have the worst prognosis. Conclusions These results suggest that HDAC9 is involved in DNMT3A-mediated progression of ESCC, and targeting DNMT3A and HDAC9 may be a potential ESCC therapeutic strategy.

Background: Multimodal therapies, such as perioperative chemotherapy and neoadjuvant chemoradiotherapy together with surgical advances, have improved the outcomes of patients with resectableesophageal cancer (EC).However, the 5-year survival of these patients remains below 50%. The advent of immunotherapy has resulted in novel approaches to advanced or metastatic disease, but the role of immunotherapy in the neoadjuvant settings has not yet to be established. In this single-arm study, the efficacy and safetyofneoadjuvant pembrolizumab plus chemotherapy were evaluatedin patients with resectableesophageal squamous cell carcinoma (ESCC).Methods: This study was conducted at 2 hospitals(in Xi'an and Tianjin)and included patients with ESCC of clinical stage II–IVAwho underwent surgery within 4 to 6 weeks after completing treatment withpembrolizumab(200mg) combined with a conventional chemotherapy regimen (3 cycles). The efficacy and safety of this combination treatment were evaluated as primary endpointsof the study. This study was retrospectively registered (Registration number: ChiCTR2100048917).Results:A total of 22 patients (including 18 men) were enrolled, of whom 17 patients progressed to surgery,4 patients refused surgery due to tumor regression and symptomatic relief, and 1 patient had progressive disease. As determinedby the Response Evaluation Criteria in Solid Tumors(RECIST,version 1.1), 7 patients (31.8%) had a partial response and 4 (18.2%) patients hada complete response, which translated to an objective response rate of 50%. The symptom remission rate was 90.9% according to the Stooler classification. Five patients (22.7%) experienced serious treatment-related adverse events of grade 3–4 (including anorexia, vomiting, fatigue, alopecia and hypoadrenalism). Postoperative pathology revealed a major pathological response in 14 cases (82.3%) and a complete pathological response in 8 cases (47.1%). Programmed death-ligand 1expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT)(r=-0.55, p=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens wereweakly correlated with RVT(r=0.71; p=0.07), while a positive correlation was observed between postoperative Foxp3+T cells/CD4+Tcellsratios and RVT(r=0.84, p=0.03).Conclusion: The combination of neoadjuvantimmunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment. It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials.Trial registration: ChiCTR, ChiCTR2100048917. Registered 19 July 2021 - Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=130073&htm=4

Neoadjuvant immunotherapy for patients with locally advanced esophageal cancer (EC) has developed rapidly in recent years. The efficacy and safety outcomes may change the recommended neoadjuvant therapeutic regimens for patients with EC.Systematic screening for articles focusing on the efficacy and safety of neoadjuvant immunotherapy in locally advanced and surgically resectable EC was performed using PubMed, Embase, Web of Science and international tumor congresses. Meta-analysis of non-comparative binary outcomes was carried out to combine the main results. The pooled results were compared with the traditional neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) using direct comparative analysis. The results were expressed as the risk ratio (RR).A total of 20 articles with 621 patients were included in the present study. The pooled pathological complete response and major pathological response rates were 33.8% (95% CI: 29.6%-37.9%) and 53.5% (95% CI: 47.9%-59%), respectively, in the neoadjuvant immunotherapy combined with chemotherapy (nICT) group and 39.8% (95% CI: 27%-53.9%) and 88.8% (95% CI: 64.8%-97.2%) in the neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) group, respectively. In addition, the pooled grade 3-4 treatment-related adverse events (TRAEs) rate was 19.4% (95% CI: 11.5%-31.5%) in the nICT group. The results of direct comparison showed that compared with nCRT and nICRT, nICT could improve safety while achieving comparable efficacy. The results of subgroup analysis, sensitivity analysis and publication bias evaluation indicated that the above findings were stable and reliable.The current meta-analysis revealed that neoadjuvant immunotherapy in patients with locally advanced EC was safe and effective and nICT could be used as the recommended neoadjuvant therapeutic option for patients with EC. However, additional studies are urgently needed to reveal the long-term outcomes of neoadjuvant immunotherapy.

The moisture storaged in soil-vadose zone is the important components of natural water cycles, which has a close relationship with water-soil-plant system and plays an important role for the healthy development of ecological environment. The study of the article developed the remote sensing quantitative model for soil moisture retrieval by statistics regression analysis based upon the soil sample parameters collected from the field, spectral data gathered simultaneously and simulated the bands of Landsat7 ETM in the typical fissure sites of coal mining area in the Northern of Shaanxi. The results showed that band4 of Landsat7 ETM is the most sensitive band for soil moisture retrieval using spectrum method. The quadratic model that was developed by remote sensing reflectance (Rrs4) (corresponding to the band4) as independent variable, is the best patterns. The root mean square error ( RMSE) is 0.59%.

Apparent Optical Properties(AOPs) and Inherent Optical Properties (IOPs) of waters are the important contents on the research of regional water characteristics. The study of the article analyzed the Apparent Optical Properties(AOPs) and Inherent Optical Properties (IOPs) of waters in the Caofeidian region, according to the water sample parameters collected from the field, spectral data gathered simultaneously and the coefficients for absorption a and backscattering b b of the waters calculated by Mie theory, Based on this, we developed the correlation analysis model between AOPs and IOPs of waters. Meanwhile, we analyzed the relationship of AOPs and IOPs on the single band corresponding to landsat5 and found the correlation between AOPs and IOPs in band3 was the best. The results of this study will be the basis for analyzing water characteristics and inversion water quality parameters by remote sensing in this area.