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Background Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized with poor prognosis and high metastatic potential. Although traditional chemotherapy, radiation, and surgical resection remain the standard treatment options for TNBC, bispecific antibody-based immunotherapy is emerging as new strategy in TNBC treatment. Here, we found that the receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) was highly expressed in TNBC but minimally expressed in normal tissue. A bispecific ROR1-targeted CD3 T cell engager (TCE) was designed in IgG-based format with extended half-life. Method The expression of ROR1 in TNBC was detected by RT-qPCR and immunohistology analysis. The killing of ROR1/CD3 antibody on TNBC cells was determined by the in vitro cytotoxicity assay and in vivo PBMC reconstituted mouse model. The activation of ROR1/CD3 on T cells was analyzed by the flow cytometry and ELISA assay. Pharmacokinetics study of ROR1/CD3 was performed in mouse. Results The ROR1/CD3 TCE triggered T cell activation and proliferation, which showed potent and specific killing to TNBC cells in ROR1-depedent manner. In vivo mouse model indicated that ROR1/CD3 TCE redirected the cytotoxic activity of T cells to lyse TNBC cells and induced significant tumor regression. Additionally, the ROR1/CD3 bispecific antibody exhibited an extended half-life in mouse, which may enable intermittent administration in clinic. Conclusions Collectively, these results demonstrated that ROR1/CD3 TCE has a promising efficacy profile in preclinical studies, which suggested it as a possible option for the treatment of ROR1-expressing TNBC.

The Kalpin foreland thrust belt, which is in the southwestern Tianshan Mountains, has some of the most intense tectonic deformation and seismic activity on the continent. The range-front Maidan fault represents part of the boundary zone between the Tarim Basin and the southern Tianshan orogenic belt. In contrast with the other range-front faults in the Tianshan region that have been inactive during the late Quaternary, the Maidan fault displayed strong activity in the Holocene. Studying characteristics of paleoearthquake activity along the Maidan fault is highly important to understand the seismic risk and tectonic deformation in this area. On the basis of methods of remote sensing image interpretation, field surveys, trench excavation, and late Quaternary chronology determination, four paleoearthquake events were identified as follows: Event E1: (46.8 ± 4.2)-(49.0 ± 4.8) ka; Event E2: (13.1 ± 0.6)-(22.5 ± 1.7) ka; Event E3: (7.0 ± 0.6)-(7.7 ± 0.4) ka, and Event E4: after (5.1 ± 0.3) ka. Our results show that the range-front Maidan fault was still active during the late Quaternary and that several strong earthquake events ruptured the ground surface. This deformation pattern and strain distribution indicate that the range-front fault and frontal structure of the foreland thrust belt are both experiencing strong deformation, which highlights new challenges in studying paleoearthquake activity sequences and large earthquake risk analysis.

Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple‐negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T‐cell function, especially antibodies against programmed cell death 1 (PD‐1) or its ligand PD‐L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti‐PD‐1 treatment. Dysfunction of CD8+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome‐derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR‐20a‐5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR‐20a‐5p was correlated with a worse prognosis of TNBC. cirmiR‐20a‐5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR‐20a‐5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR‐20a‐5p targeted the nuclear protein ataxia‐telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR‐20a‐5p conferred TNBC to anti‐PD‐1 treatment resistance. Collectively, these findings indicated that cirmiR‐20a‐5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR‐20a‐5p might be a novel strategy for overcoming the resistance of TNBC to anti‐PD‐1 immunotherapy. Exosomal cirmiR‐20a‐5p was upregulated in triple‐negative breast cancer (TNBC) and correlated with the poor prognosis of TNBC patients. cirmiR‐20a‐5p released via exosomes by TNBC cells was uptaken by CD8+ T cells and led to the dysfunction of CD8+ T cells by targeting nuclear protein ataxia‐telangiectasia. Increased cirmiR‐20a‐5p enhanced the resistance of TNBC to anti‐PD‐1 therapy. These results suggest that targeting cirmiR‐20a‐5p may be a novel strategy for improving the immunotherapy efficacy of TNBC patients.

As a leading cause of cancer-related fatalities among women, triple negative breast cancer (TNBC) still remains a clinical challenge. Increasing evidence points to long non-coding RNAs (lncRNAs) as significant regulators in its progression. The aim of this study is to investigate the function and working mechanism of LINC02159 in TNBC. The expression of LINC02159 in TNBC tissues and cells was detected by RT-qPCR analysis. Regulation of LINC02159 on TNBC is determined by the in vitro proliferation and migration assay. Binding of LINC02159 with the targets was tested by the luciferase reporter assay. The function of LINC02159 in the glycolysis of TNBC cells was evaluated via detecting the glucose uptake and lactate production. Our study identified that LINC02159 is overexpressed in TNBC tissues and correlates with decreased overall survival in patients. Functionally, silencing LINC02159 reduced TNBC cell proliferation and migration in vitro and suppressed the tumor growth in vivo. By acting as a competing endogenous RNA (ceRNA), LINC02159 directly engaged with miR-1285-3p to increase the expression of Glucose-6-phosphate isomerase (G6PI). In line with G6PI’s role in glycolysis, reducing LINC02159 expression decreased glucose uptake and lactate production in TNBC cells. Restoring G6PI greatly reversed the impact of LINC02159 silencing on the proliferation and glycolysis of TNBC cells. These results demonstrated that LINC02159 drives the aerobic glycolysis and TNBC progression via modulating the miR-1285-3p/G6PI axis, and it might act as a potential target for TNBC anti-tumor therapy.

Road network data are an important part of many applications, e.g., intelligent transportation and urban planning. At present, most of the approaches to road network generation are dominated by single data sources including images, point cloud data, trajectories, etc., which may cause the fragmentation of information. This study proposes a novel strategy to obtain the vector data of road networks by combining images and trajectory data with a postprocessing method named RNITP. The designed RNITP includes two parts: an initial generation layer of road network detection and a postprocessing layer of vector map acquirement. At the first layer, there are three steps of road network detection including road information interpretation from images based on a new deep learning model (denoted as SPBAM-LinkNet), road detection from trajectories data by rasterizing, and road information fusion by using OR operation. The last layer is used to generate a vector map based on a postprocessing method that is focused on error identification and removal. Experiments were conducted using two kinds of datasets: CHN6-CUG road datasets and HB road datasets. The results show that the accuracy, F1 score, and MIoU of SPBAM-LinkNet on CHN6-CUG and HB were (0.9695, 0.7369, 0.7760) and (0.9387, 0.7257, 0.7514), respectively, which are better than other typical models (e.g., Unet, DeepLabv3+, D-Linknet, NL-Linknet). In addition, the F1 score, IoU, and recall of the vector map obtained from RNITP are 0.8883, 0.7991, and 0.9065, respectively.

Triple-negative breast cancer shows worse outcome compared with other subtypes of breast cancer. The discovery of dysregulated microRNAs and their roles in the progression of triple-negative breast cancer provide novel strategies for the treatment of patients with triple-negative breast cancer. In this study, we identified the significant reduction of miR-133 in triple-negative breast cancer tissues and cell lines. Ectopic overexpression of miR-133 suppressed the proliferation, colony formation, and upregulated the apoptosis of triple-negative breast cancer cells. Mechanism study revealed that the YES Proto-Oncogene 1 was a target of miR-133. miR-133 bound the 3′-untranslated region of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1 in triple-negative breast cancer cells. Consistent with miR-133 downregulation, YES1 was significantly increased in triple-negative breast cancer, which was inversely correlated with the level of miR-133. Restoration of YES Proto-Oncogene 1 attenuated the inhibitory effects of miR-133 on the proliferation and colony formation of triple-negative breast cancer cells. Consistent with the decreased expression of YES Proto-Oncogene 1, overexpression of miR-133 suppressed the phosphorylation of YAP1 in triple-negative breast cancer cells. Our results provided novel evidence for the role of miR-133/YES1 axis in the development of triple-negative breast cancer, which indicated miR-133 might be a potential therapeutic strategy for triple-negative breast cancer.

Poplar leaf blight caused by Alternaria alternata , a common disease in Northeast China, can cause abnormal abscission of poplar leaves and even lead to plant death in severe cases. WRKY transcription factors have been implicated in the regulation of disease resistance associated with plant immune responses to secondary metabolism via a complicated gene network. However, little is known about how the metabolites regulated by the PsnWRKY70 gene trigger changes in the phyllosphere microbiome, leading to increased resistance to foliar pathogens. Here, the PsnWRKY70 overexpressing line of Populus ( Populus simonii × P. nigra ) exhibited increased coumarin synthesis in the leaves, triggering changes in microbial species central in phyllosphere microbial networks and leading to increased resistance to A. alternata infection. This study provides insights into the role of the PsnWRKY70 gene in triggering the resistance mechanism to A . alternata in Populus .

Under the influence of the far-field effect of the India-Asia convergence, the Tianshan Mountains have become a typical area of Cenozoic resurrection orogeny, a natural laboratory for continental geodynamics. However, the study of its uplift exhumation history is still controversial. Based on a detailed magnetostratigraphic study of sediments in a 501.29 m deep drill core, located in the Yili Basin that is sandwiched between the Northern and Southern Tianshan Mountains, a total of 202 samples were used to establish magnetostratigraphy. Characteristic remnant magnetization with both normal (N1–N7) and reversed (R1–R7) polarity was isolated by thermal demagnetization. The maximum age can be obtained at the bottom of the borehole profile is 1.95 Ma. Our results show that a significant increase in sedimentation rate as well as notable shift in depositional environment occurred at ~ 0.99–0.78 Ma, which represents the uplift of the northwest Tianshan Mountain and one subsequent rapid uplift event in early Pleistocene time.

Circular RNA (circRNA) has been confirmed to regulate breast cancer (BC) progression. However, the role of circ_0059457 in BC progression is still unclear.The expression of circ_0059457, taspase 1 (TASP1), microRNA (miR)-140-3p and ubiquitin-binding enzyme E2C (UBE2C) was detected by quantitative real-time PCR. Cell proliferation, migration, invasion and sphere formation ability were assessed by cell counting kit-8 assay, EdU assay, wound healing assay, transwell assay and sphere formation assay. Cell glycolysis was assessed by detecting glucose uptake, lactate levels and ATP/ADP ratio. Dual-luciferase reporter assay, RIP assay, RNA pull-down assay were used to validate RNA interaction. Xenograft tumor model to assess the effect of circ_0059457 on BC tumor growth in vivo. Circ_0059457 had elevated expression in BC tissues and cells. C irc_0059457 knockdown inhibited BC cell proliferation, metastasis, sphere formation ability, and glycolysis. In terms of mechanism, circ_0059457 sponged miR-140-3p, and miR-140-3p targeted UBE2C. MiR-140-3p inhibition reversed the effect of circ_0059457 knockdown on BC cell malignant behaviors. Besides, miR-140-3p overexpression inhibited BC cell proliferation, metastasis, sphere formation ability and glycolysis, and these effects were abrogated by UBE2C enhancement. Furthermore, circ_0059457 regulated UBE2C expression through sponging miR-140-3p. Additionally, circ_0059457 knockdown obviously inhibited BC tumor growth in vivo. Circ_0059457 promoted BC progression via miR-140-3p/UBE2C axis, which provided potential target for the treatment of BC.

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and has a poor prognosis. Therefore, the development of novel drugs and understanding the molecular mechanisms that may contribute to the initiation and development of TNBC are urgently required. Chidamide, a histone deacetylase inhibitor, has been reported as possessing anti-cancer properties in several cancers, however, the function of chidamide in TNBC remains to be elucidated. The present study revealed that chidamide inhibited the proliferation, colony formation and migration of TNBC cells. Experiments investigating the underlying mechanism revealed that chidamide upregulated the expression of microRNA (miR)-33a-5p in TNBC cells via RT-qPCR. Luciferase reporter assay demonstrated that miR-33a-5p was bound to the 3′-untranslated region of lactate dehydrogenase A (LDHA) and decreased the expression of LDHA in TNBC cells. In addition, chidamide suppressed the expression of LDHA and significantly decreased the glycolysis of TNBC cells. Collectively, the results of the present study demonstrated that chidamide reprogramed glucose metabolism, partially by targeting the miR-33a-5p/LDHA pathway, in TNBC. These findings indicate that chidamide may be a promising novel drug in the treatment of patients with TNBC.