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Background Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood. Methods The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells. Results Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo. Conclusion Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.

The combination of immunotherapy with platinum-based chemotherapy has become the first-line treatment for patients with advanced non–small cell lung cancer (NSCLC) with negative driver gene mutations. However, finding an ideal chemotherapeutic regimen for immunotherapy and exploring the underlying mechanism have noticeably attracted clinicians’ attention. In this study, we found that cisplatin induced ferroptosis of tumor cells, followed by N1 neutrophil polarization in the tumor microenvironment, which in turn remodeled the “cold” tumor to a “hot” one through enhancing T-cell infiltration and Th1 differentiation. Based on the important role of tumor ferroptosis in the immune-promoting effect of cisplatin, we noticed that the combination of a ferroptosis activator showed a synergistic effect with chemoimmunotherapy of epidermal growth factor receptor (EGFR)-mutant NSCLC, which would be an effective strategy to overcome immunotherapy resistance in NSCLC patients harboring driver mutations.

Abstract Background: Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory-particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. Methods: We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. Results: Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. Conclusion: The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. Trial Registration: ClinicalTrials.gov, NCT02879526.

Relevant studies have demonstrated the poor treatment outcomes and prognosis for double-expressor diffuse large B cell lymphoma (DE-DLBCL) in the rituximab era. Zanubrutinib plus R-CHOP (rituximab, cyclophosphamide, doxorubicin/liposomal doxorubicin, vincristine, prednisone; ZR-CHOP) has shown efficacy in untreated non-GCB DLBCL patients with extranodal involvement. However, its efficacy in newly diagnosed DE-DLBCL remains uncertain. This retrospective study sought to assess the efficacy and safety of ZR-CHOP in comparison to R-CHOP in treatment-naïve patients with DE-DLBCL. This study assessed 78 patients with newly diagnosed DE-DLBCL who were admitted between June 2017 and January 2024. Among them, 55 patients received the R-CHOP regimen, while 23 patients were treated with the ZR-CHOP regimen. The clinical characteristics were well balanced between the two groups. The complete response rates (CRR) were higher in the ZR-CHOP group than the R-CHOP group, regardless of whether patients completed 4 or 6 treatment cycles (P= 0.019; P= 0.025). ORR in the ZR-CHOP group showed a higher trend than that in the R-CHOP group (P= 0.624; P= 0.219). The median follow-up period was 23.3 months, and the predicted median progression free survival (PFS) in the R-CHOP group was 22.8 months, whereas the median PFS in the ZR-CHOP group was not reached. The 1-, 2-, and 3-year PFS rates in the ZR-CHOP group showed a beneficial trend compared with the R-CHOP group, but there was no statistical difference (P= 0.072). However, the PFS of the ZR-CHOP group was longer than that of the R-CHOP group in patients with Ki67 index >75% (P= 0.034) and p53 expression >50% (P= 0.0033). The predicted median overall survival (OS) in the ZR-CHOP and R-CHOP groups were not reached. The 1-, 2- and 3-year OS rates were not significantly different between the two groups (P= 0.29). The most common adverse event in both groups was hematotoxicity, but there was no significant difference in the incidence of all adverse events between the two groups. First-line treatment with the ZR-CHOP regimen improved CRR in the untreated patients with DE-DLBCL and prolonged PFS in the Ki67 index >75% subgroup and the p53 expression >50% subgroup.

Dengue virus (DENV) continues to be a major public health problem. DENV infection will cause mild dengue and severe dengue. Severe dengue is clinically manifested as serious complications, including dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS), which is mainly characterized by vascular leakage. Currently, the pathogenesis of severe dengue is not elucidated thoroughly, and there are no known therapeutic targets for controlling the disease effectively. This study aimed to further reveal the potential molecular mechanism of severe dengue. In this study, the long non-coding RNA, ERG-associated lncRNA (lncRNA-ERGAL), was activated and significantly up-regulated in DENV-infected vascular endothelial cells. After knockdown of lncRNA-ERGAL, the expression of ERG, VE-cadherin, and claudin-5 was repressed; besides, cell apoptosis was enhanced, and cytoskeletal remodeling was disordered, leading to instability and increased permeability of vascular endothelial barrier during DENV infection. Fluorescence hybridization (FISH) assay showed lncRNA-ERGAL to be mainly expressed in the cytoplasm. Moreover, the expression of miR-183-5p was found to increase during DENV infection and revealed to regulate ERG, junction-associated proteins, and the cytoskeletal structure after overexpression and knockdown. Then, ERGAL was confirmed to interact with miR-183-5p by luciferase reporter assay. Collectively, ERGAL acted as a miRNA sponge that can promote stability and integrity of vascular endothelial barrier during DENV infection via binding to miR-183-5p, thus revealing the potential molecular mechanism of severe dengue and providing a foundation for a promising clinical target in the future.

Global warming has been reported to cause reductions in crop yields. However, it was suggested that warming temperature might benefit crop productivity in some cool areas at high latitude. In this study, we conducted a 17‐year field experiment (2002–2018) on spring wheat in Inner Mongolia. Temperature changes during each growth stage of spring wheat were investigated. Responses of spring wheat yield to temperature changes during the specific growing stages were evaluated. Average annual maximum temperature (Tmax) and minimum temperature (Tmin) significantly increased over the past 17 years. However, Tmax did not show obvious increase trend during spring wheat growing seasons (p = 0.0672). Furthermore, Tmax also had no distinct change before or after anthesis. Tmin significantly increased during the whole growing season, as well as in pre‐ and post‐anthesis stages. Correlation analysis indicated that Tmax in the entire growing season and post‐anthesis did not affect spring wheat yield, but high Tmax during pre‐anthesis can improve grain yield. The Tmin during the life cycle and pre‐anthesis both had positive relationship with grain yield. Moreover, elevated temperature from seedling to stem elongation can benefit tiller formation and thus increasing spike number, which contributed to the significant yield increase (p = 0.0093). Overall, climate warming affect spring wheat yield in cool area, and increasing temperature that was below the optimum temperature can benefit wheat productivity. Temperature changes in different stages of spring wheat are inconsistent. Increasing temperature before anthesis benefits spring wheat yield. High temperature from seedling to jointing in cool area increases spike number.

Measuring the distribution of the fishing effort of trawlers is of great significance for describing marine fishery activities, quantifying fishing systems in terms of marine ecological pressure, and revising the regulations of fishing. The purpose of this paper is to develop an efficient learning algorithm to detect the fishing behavior of trawlers to analyze the distribution of fishing effort. The vessel-monitoring system data of more than 4600 trawlers from September 2019 to April 2023 were used for feature extraction. According to the spatiotemporal information provided by the vessel position data, 11-dimensional features were extracted to form the feature vectors. A Slime Mould Algorithm-optimized Light Gradient-Boosting Machine (SMA-LightGBM) algorithm was proposed to classify the feature vectors to recognize fishing behavior. The presented method showed a remarkable generalization ability and high accuracy, sensitivity, specificity, and Matthews correlation coefficient in the test results, with scores of 98.23%, 98.75%, 97.75%, and 0.9646, respectively. Subsequently, the trained model was used to identify the fishing behavior of trawlers belonging to the coastal provinces of the Bohai Sea and the Yellow Sea in the sea area of 117° E~132° E, 26° N~41° N. The fishing effort was calculated and evaluated according to the fishing behavior recognition results. The mean absolute error was 0.3031 kW·h, and the coefficient of determination score was 0.9772. The thermal map of the fishing effort of the trawler was mapped, and the spatiotemporal characteristics were estimated in the region of interest from 2019 to 2023 with a spatial resolution of 18 degree × 18 degree. This method is an efficient way of analyzing the spatiotemporal characteristics of the fishing effort of trawlers. It provides a quantitative basis for the assessment of fishery resources and can inform fishing policies.

Purpose: For better understanding of radiotherapy resistance and its potential mechanism. Methods: We established radioresistance cell lines of non-small cell lung cancer (NSCLC) followed by microarray analysis. 529 differentially expressed genes (DEGs) were then screened between radiation resistant cell lines compared with the sensitive cell lines. The biological functions and enrichment pathways of the above DEGs were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Gene Set Enrichment Analysis (GSEA) revealed that the radiation resistance group had the most gene sets enriched in altered immune response, such as TNF signaling pathway, when compared to the radiation sensitive group. Protein-protein interaction (PPI) network was carried out through the STRING database, and then five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened by Cytoscape software. RT-PCR confirmed the expression of the above hub genes. ChIP-X Enrichment Analysis showed that STAT1 might be the transcription factor of the above hub genes. Considering that PD-L1 could be activated by STAT1 in a variety of tumors and ultimately lead to immune exhaustion, RT-PCR and Western blot verified the expression level of PD-L1. Results: Five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened and verified to be highly expressed in radioresistance group, STAT1 might be the transcription factor of the above hub genes. Our study found that the expression level of PD-L1 was increased after radiotherapy resistance. Conclusion: Although immune system activation occurs followed by radiation resistance, we hypothesized that the upregulation of PD-L1 expression caused by STAT1 activation might be one of the mechanisms of radiotherapy resistance. Keywords: NSCLC, radioresistance, DEGs, hub gene, STAT1

Objective To investigate the differences in efficacy and safety between haploidentical donor hematopoietic stem cell transplantation (HID‐HSCT) and matched sibling donor HSCT (MSD‐HSCT) in patients with T‐cell lymphoblastic lymphoma (T‐LBL). Methods In this retrospective analysis, we enrolled 38 patients who had undergone allogeneic HSCT at our institution between 2013 and 2021. The study participants included 28 patients who underwent HID‐HSCT and 10 patients who underwent MSD‐HSCT. We compared the patient characteristics and treatment effectiveness and safety between the two groups and evaluated potential prognostic variables for patients with T‐LBL. Results The median follow‐up durations in the HID‐HSCT and MSD‐HSCT groups were 23.5 (range: 4–111) and 28.5 (range: 13–56) months, respectively. All patients showed full‐donor chimerism after hematopoietic stem cell transplantation (HSCT). Except for two patients in the HID‐HSCT cohort who developed poor graft function, all patients showed neutrophil and platelet engraftments after HSCT. The cumulative incidences of grades III–IV acute graft‐versus‐host disease were 37.5% and 28.57% in the HID‐HSCT and MSD‐HSCT groups, respectively (p = 0.84). The cumulative incidences of limited (34.13% vs. 28.57%, p = 0.82) and extensive (31.22% vs. 37.50%, p = 0.53) chronic graft‐versus‐host disease did not differ between the two cohorts. In the HID‐HSCT and MSD‐HSCT cohorts, the estimated 2‐year overall survival rates were 70.3% (95% confidence interval [CI]: 54.9%–90.0%) and 56.2% (95% CI: 31.6%–100%), respectively (p = 1.00), and the estimated 2‐year progression‐free survival (PFS) rates were 48.5% (95% CI: 32.8%–71.6%) and 48.0% (95% CI: 24.6%–93.8%), respectively (p = 0.94). Furthermore, the Cox proportional‐hazards model showed that a positive positron emission tomography/computed tomography (PET/CT) status before HSCT in patients who had completed chemotherapy was an independent risk factor for PFS in the multivariate analysis (p = 0.0367). Conclusion This study showed that HID‐HSCT had comparable effectiveness and safety to MSD‐HSCT in treating T‐LBL. HID‐HSCT could serve as an alternate treatment option for T‐LBL in patients without an eligible identical donor. Achievement of the PET/CT‐negative status before HSCT may contribute to better survival.

Background Diffuse large B‐cell lymphoma (DLBCL) patients refractory to rituximab‐based immunochemotherapy have a dismal prognosis. However, the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries. To validate the definition and outcomes of refractory DLBCL in China, we conducted a multicenter, retrospective cohort study. Methods The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL (REAL‐TREND) study was performed using real‐world data from 8 centers in China. DLBCL patients with curative intent were included in the REAL‐TREND dataset. Overall survival (OS) was estimated using the Kaplan‐Meier method and compared by the log‐rank test. Due to heterogeneity in response rates among different centers, the response rates of refractory patients were pooled using random‐effect models. Multivariate survival analysis was performed using the Cox regression model. Results A total of 2778 DLBCL patients diagnosed between January, 2010 and December, 2015 were enrolled to this study. After validating previous definitions, the SCHOLAR‐1 study was most suitable to define refractory DLBCL. The estimated 5‐year cumulative incidence of refractory patients was 20% (95% confidence Interval [CI] = 18%‐22%). After the determination of refractory disease, overall response rate and complete remission rate were 30% (95% CI = 22%‐38%) and 9% (95% CI = 4%‐15%), respectively. Patients with either no response to immunochemotherapy or relapse within 12 months after stem‐cell transplantation had inferior survival with a median OS of 5.9 months (95% CI = 5.5‐7.1 months) and 2‐year OS rate of 16% (95% CI = 12%‐20%). International prognostic index score 4‐5 (hazard ratio [HR] = 2.22; 95% CI = 1.47‐3.35), central nervous system relapse (HR = 1.43; 95% CI = 1.04‐1.97), and best response status (HR = 2.68; 95% CI = 1.42‐5.03 for partial remission. HR = 5.97, 95% CI = 3.21‐11.11 for stable disease/progressive disease) were independent unfavorable prognostic factors. Conclusions This is the first large‐scale Asian cohort study focusing on outcomes of refractory DLBCL. The definition of the SCHOLAR‐1 study identifies patients with homogenously inferior survival, thus is appropriate to select refractory DLBCL. Due to poor clinical outcomes in the rituximab era, patients with refractory DLBCL may be potential candidates for novel treatment modalities.