Mutation of TL1, encoding a novel C2H2 zinc finger protein, improves grains eating and cooking quality in rice.

KEY MESSAGE: The cloning and characterization of a novel C2H2 zinc finger protein that affects rice eating and cooking quality by regulating amylose content and amylopectin chain-length distribution in rice. One of the major objectives in rice breeding aims to increase simultaneously yield and grain quality especially eating and cooking quality (ECQ). Controlling amylose content (AC) and amylopectin chain-length distribution (ACLD) in rice is a major strategy for improving rice ECQ. Previous studies show that some starch synthesis-related genes (SSRGs) are required for normal AC and ACLD, but its underlying regulating network is still unclear. Here, we report the cloning and characterization of a novel C2H2 zinc finger protein TL1 (Translucent endosperm 1) that positively regulates amylose synthesis in rice grains. Loss of TL1 function reduced apparent amylose content (AAC), total starch, gel consistency, and gelatinisation temperature, whereas increased viscosity, total lipid, and ratio of amylopectin A chains with degree of polymerization (DP) 6-12 to B1 chains with DP 13-24, resulting in an enhanced grain ECQ. The improved ECQ was accompanied by altered expression patterns of several tested SSRGs in tl1 mutant grains. Furthermore, knockout of TL1 in the high-yielding rice variety JiaHua NO.1 reduced AAC without obvious side effects on major agronomic traits. These findings expand our understanding of the regulating networks of grain starch metabolism and provide new insights into how rice ECQ quality can be improved via genetic approach.

Chemokine C-C motif ligand 21 synergized with programmed death-ligand 1 blockade restrains tumor growth.

Programmed death-ligand 1 (PD-L1) blockade has revolutionized the prognosis of several cancers, but shows a weak effect on pancreatic cancer (PC) due to poor effective immune infiltration. Chemokine C-C motif ligand 21 (CCL21), a chemokine promoting T cell immunity by recruiting and colocalizing dendritic cells (DCs) and T cells, serves as a potential antitumor agent in many cancers. However, its antitumor response and mechanism combined with PD-L1 blockade in PC remain unclear. In our study, we found CCL21 played an important role in leukocyte chemotaxis, inflammatory response, and positive regulation of PI3K-AKT signaling in PC using Metascape and gene set enrichment analysis. The CCL21 level was verified to be positively correlated with infiltration of CD8+ T cells by the CIBERSORT algorithm, but no significant difference in survival was observed in either The Cancer Genome Atlas or the International Cancer Genome Consortium cohort when stratified by CCL21 expression. Additionally, we found the growth rate of allograft tumors was reduced and T cell infiltration was increased, but tumor PD-L1 abundance elevated simultaneously in the CCL21-overexpressed tumors. Then, CCL21 was further verified to increase tumor PD-L1 level through the AKT-glycogen synthase kinase-3ß axis in human PC cells, which partly impaired the antitumor T cell immunity. Finally, the combination of CCL21 and PD-L1 blockade showed superior synergistic tumor suppression in vitro and in vivo. Together, our findings suggested that CCL21 in combination with PD-L1 blockade might be an efficient and promising option for the treatment of PC.

CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer.

CD73 is a glycosylphosphatidylinositol (GPI)-anchored protein that attenuates tumour immunity via cooperating with CD39 to generate immunosuppressive adenosine. Therefore, CD73 blockade has been incorporated into clinical trials for cancers based on preclinical efficacy. However, the biological role and underlying mechanism of CD73 in pancreatic cancer (PC) microenvironment and its prognostic impact have not been comprehensively studied. In this article, we found that the expression of CD73 was up-regulated in PC tissues and patients with higher CD73 expression had poorer overall survival (OS) and disease-free survival (DFS) in multiple publicly available databases. Higher CD73 expression was significantly associated with its reduced methylation, and only the hypomethylation of CpG site at cg23172664 was obviously correlated with poorer OS. Then, Metascape analysis and GSEA showed that CD73 may play an important role in PC progression and immune regulations. Notably, CD73 was verified to be negatively correlated with infiltrating levels of CD8+ T cells and γδ+ T cells in both TCGA and GEO cohorts via the CIBERSORT algorithm. In addition, patients with higher CD73 expression also tended to have higher PD-L1 expression and tumour mutation load. It seemed that CD73 might be a promising biomarker for the response to the anti-PD-1/PD-L1 treatment in PC. In conclusion, these results reveal that CD73 may function as a promotor in cancer progression and a regulator in immune patterns via CD73-related pathways. Blockade of CD73 might be a promising therapeutic strategy for PC.

CD25 and TGF-ß blockade based on predictive integrated immune ratio inhibits tumor growth in pancreatic cancer.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor due to the difficulty of disease diagnosis and therapy. Immunotherapy has had robust performance against several malignancies, including PDAC. In this study, we aim to analyze the expression of CD8 and FoxP3 on T lymphocytes and TGF-ß expression in tumor tissues, and then analyze the possible clinical significance of these finding in order to find a novel effective immunotherapy target in PDAC using a murine model. METHODS: A tissue microarray using patient PDAC samples was stained and analyzed for associations with clinicopathological characteristics. A preclinical murine model administrated with various immunotherapies were analyzed by growth inhibitor, flow cytometry, enzyme-linked immuno sorbent assay and immunohistochemistry. RESULTS: The infiltrating FoxP3+ regulatory T cells (Tregs) in tumor tissues were associated with survival, while CD8+ tumor infiltrating lymphocytes (TILs) were not. Considering the drawbacks of these measure alone, the number of CD8+ and FoxP3+ T cells were combined to create a new estimated value-integrated immune ratio (IIR), which showed excellent validity in survival risk stratification. IIR was further verified as an independent prognostic factor according to multivariate analysis as well as TGF-ß expression. Association between TGF-ß expression and infiltrating Tregs was also verified. Then, in our preclinical murine model, CD25 and TGF-ß combination blockade had a higher tumor growth inhibitor value. This combination therapy significantly depleted periphery and intra-tumor FoxP3+ Tregs while increasing intra-tumor CD8+ TILs levels compared to controls or anti-TGF-ß monotherapy (p < 0.05). Anti-CD25 monotherapy alone also had the ability to deplete periphery and intra-tumor Tregs (p < 0.05). The excretion of intra-tumor IL-10, TGF-ß was notably lower but higher IFN-γ excretion in this combination immunotherapy. Such combination immunotherapy was further confirmed to synergize with anti-PD-1 monotherapy to improve tumor growth inhibition and cure rates. CONCLUSIONS: The combination of CD25, TGF-ß and PD-1 blockade plays a potentially effective role in inhibiting tumor formation and progression. Our results also provide a strong rational strategy for use of IIR in future immunotherapy clinical trials.

Survival prediction in pancreatic cancer patients with no distant metastasis: a large-scale population-based estimate.

AIM: To identify the risk factors for overall survival (OS) of pancreatic ductal adenocarcinoma patients with no distant metastasis, and formulate a novel nomogram for prognostic prediction. PATIENTS & METHODS: Data were obtained from Surveillance, Epidemiology, and End Results database of pancreatic ductal adenocarcinoma patients with no distant metastasis as the primary cohort, and 127 patients at our institution were enrolled as the validation cohort. The prognostic nomogram integrating all independent risk factors for predicting OS was established to achieve superior discriminatory ability. RESULTS: The constructed nomogram showed excellent performance and superior predictive accuracy for OS according to the concordance index and calibration curve. CONCLUSION: One more advanced and accurate predictive model will be obtained to assist in risk stratification via the constructed nomogram.

Neutralizing TGF-ß promotes anti-tumor immunity of dendritic cells against pancreatic cancer by regulating T lymphocytes.

Previous fundamental or clinical trials of dendritic cell (DC) vaccine against pancreatic ductal adenocarcinoma (PDAC) revealed the burgeoning neoadjuvant immunotherapy. Microarray studies indicated that multiple ingredients of the transfer growth factor beta (TGF-ß) pathway were overexpressed in PDAC, which inhibited the intratumoral immune response. To explore whether the DC volume in tumor microenvironment contributes to the differentiation of T cell cohort and test the hypothesis that combining DC vaccine with TGF-ß inhibitors will elevate the anti-tumor immune response, we managed to co-culture T cells in vitro with pancreatic cancer cells and DCs in different concentrations, and combine TGF-ß blockage with DC vaccine therapy in a murine model of pancreatic cancer. In in vitro studies, we discovered that CD8+ T cytotoxic cell (Tc) presented a significant advantage and lower volume of CD4+ T helper cell (Th) existed with a certain elevated DC concentration (p < 0.05), associated with declined interleukin (IL)-10 and increased interferon (IFN)-γ, which suggested with the DC volume increasing, the enhancing immune effect may represent a great advantage in such a system (p < 0.05). When interfered with anti-TGF-ß antibody or TGF-ß cytokine, respectively, in the co-culture system, we found IFN-γ producing was extremely higher and T cell apoptosis relatively descent with TGF-ß blockage (p < 0.05). The murine PDAC model demonstrated a survival advantage treated with anti-TGF-ß antibody combined with DC vaccine when compared with monotherapy controls (p < 0.05). Therefore, these findings indicated that, through neutralizing TGF-ß associated with DC vaccine, the anti-tumor immunity is highly elevated and this combinational therapy will provide an efficacious prospect.

A Rice Ca2+ Binding Protein Is Required for Tapetum Function and Pollen Formation.

In flowering plants, successful male reproduction requires the sophisticated interaction between somatic anther wall layers and reproductive cells. Timely degradation of the innermost tissue of the anther wall layer, the tapetal layer, is critical for pollen development. Ca2+ is a well-known stimulus for plant development, but whether it plays a role in affecting male reproduction remains elusive. Here we report a role of Defective in Exine Formation 1 (OsDEX1) in rice (Oryza sativa), a Ca2+ binding protein, in regulating rice tapetal cell degradation and pollen formation. In osdex1 anthers, tapetal cell degeneration is delayed and degradation of the callose wall surrounding the microspores is compromised, leading to aborted pollen formation and complete male sterility. OsDEX1 is expressed in tapetal cells and microspores during early anther development. Recombinant OsDEX1 is able to bind Ca2+ and regulate Ca2+ homeostasis in vitro, and osdex1 exhibited disturbed Ca2+ homeostasis in tapetal cells. Phylogenetic analysis suggested that OsDEX1 may have a conserved function in binding Ca2+ in flowering plants, and genetic complementation of pollen wall defects of an Arabidopsis (Arabidopsis thaliana) dex1 mutant confirmed its evolutionary conservation in pollen development. Collectively, these findings suggest that OsDEX1 plays a fundamental role in the development of tapetal cells and pollen formation, possibly via modulating the Ca2+ homeostasis during pollen development.

Low intratumoral regulatory T cells and high peritumoral CD8(+) T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy.

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Recent studies have focused on the role of lymphocytes in the PDAC microenvironment. Using immunohistochemistry, our study explored the clinical significance of intratumoral or peritumoral CD4(+)Foxp3(+) regulatory T cells (Tregs) and CD8(+) T cells in the tumor microenvironment and analyzed their relation to the prognosis of PDAC in a consecutive series of 92 patients after resection. CD8(+) T cells were more frequently seen within peritumoral sites, while CD4(+)Foxp3(+) Tregs were more frequent within intratumoral areas. Neither exhibited any relationship with other clinicopathologic factors. Patients with low levels of intratumoral Tregs had longer disease-free survival than those with higher levels (DFS 22.2 vs. 11.2 months, p < 0.001), and patients with higher levels of peritumoral CD8(+) T cells had longer overall survival than those with lower levels (OS 31.0 vs. 14.2 months, p < 0.001). Multivariate analysis demonstrated that intratumoral Tregs (hazard ratio, HR 3.39, p = 0.010) and peritumoral CD8(+) T cells (HR 0.10, p < 0.001) are related to DFS and OS, respectively. These results indicate that intratumoral Tregs are a negative predictor of DFS, while peritumoral CD8(+) T cells are a positive predictor of OS for PDAC patients with pancreatectomy.

Two ATP Binding Cassette G Transporters, Rice ATP Binding Cassette G26 and ATP Binding Cassette G15, Collaboratively Regulate Rice Male Reproduction.

Male reproduction in higher plants requires the support of various metabolites, including lipid molecules produced in the innermost anther wall layer (the tapetum), but how the molecules are allocated among different anther tissues remains largely unknown. Previously, rice (Oryza sativa) ATP binding cassette G15 (ABCG15) and its Arabidopsis (Arabidopsis thaliana) ortholog were shown to be required for pollen exine formation. Here, we report the significant role of OsABCG26 in regulating the development of anther cuticle and pollen exine together with OsABCG15 in rice. Cytological and chemical analyses indicate that osabcg26 shows reduced transport of lipidic molecules from tapetal cells for anther cuticle development. Supportively, the localization of OsABCG26 is on the plasma membrane of the anther wall layers. By contrast, OsABCG15 is polarly localized in tapetal plasma membrane facing anther locules. osabcg26 osabcg15 double mutant displays an almost complete absence of anther cuticle and pollen exine, similar to that of osabcg15 single mutant. Taken together, we propose that OsABCG26 and OsABCG15 collaboratively regulate rice male reproduction: OsABCG26 is mainly responsible for the transport of lipidic molecules from tapetal cells to anther wall layers, whereas OsABCG15 mainly is responsible for the export of lipidic molecules from the tapetal cells to anther locules for pollen exine development.

Rice glycosyltransferase1 encodes a glycosyltransferase essential for pollen wall formation.

The pollen wall consists of an exine and an intine. The mechanism underlying its formation is not well understood. Glycosyltransferases catalyze the modification of biological molecules by attaching a single or multiple sugars and play key roles in a wide range of biological processes. We examined the role of GLYCOSYLTRANSFERASE1 (OsGT1) in pollen wall development in rice (Oryza sativa). This gene is highly expressed in mature pollen, and plants containing alleles caused by transfer DNA insertion do not produce homozygous progeny. Reciprocal crosses between OsGT1/osgt1 and the wild type indicated that the mutation leads to a male gametophyte defect. Microscopic analyses revealed that osgt1 pollen developed normally to the pollen mitosis stage but failed to produce mature grains. In osgt1 pollen, intine structure was disrupted. In addition, starch and protein levels were much lower in the mutant grains. Recombinant OsGT1 transferred glucose from UDP-glucose to the third and seventh positions of quercetin, a universal substrate of glycosyltransferases. Consistent with the role of OsGT1, an OsGT1-green fluorescent protein fusion protein was localized to the Golgi apparatus. Taken together, our results suggest that OsGT1 is a Golgi-localized glycosyltransferase essential for intine construction and pollen maturation, providing new insight into male reproductive development.

Characterization of rotary valve control vibration system for vibration stress relief applications.

To enhance the vibration system characteristic distortion and pressure loss, we propose a novel rotary valve control vibration system. The paper presents the designed structural composition and generation mechanism of the rotary valve control vibration system. It also derives the mathematical model for the rotary valve distribution process and the overall system. The flow field inside the rotary valve is dynamically simulated using the multiple reference frame model, allowing for the determination of the change rule of the rotary valve's output characteristics. An AMESim model was developed to analyze the vibration characteristics of the rotary valve control system. The effects of parameters such as inlet pressure, motor speed, and oil supply pump displacement were investigated. A rotary valve control vibration system experimental bench was constructed to experimentally verify the output characteristics of the rotary valve and the vibration characteristics of the system. The results indicate that the characteristic curve of the designed vibration system closely resembles a sinusoidal wave. Additionally, the rotary valve exhibits low pressure loss, making it more suitable for vibration stress relief applications. By appropriately increasing the inlet pressure and decreasing the motor speed, the vibration characteristics of the system can be improved.

Experimental and numerical evaluation for drum dynamic reliability under extremely complex working conditions.

Coal mining machine drums are prone to damage and malfunction under extremely complex working conditions, which seriously affects the efficiency and safety of coal production. In this paper, based on the theory of coal rock cutting and virtual simulation technology, finite element models of drum cutting coal rock were established and then verified by physical experiments. Through simulation analysis, the dynamic reliability of the drum was studied from three aspects: load, stress and wear, and a mathematical model of drum load was established with respect to the traction speed and drum rotation speed; based on the orthogonal test, the optimal working parameters to improve the wear resistance of the drum were derived. The results of the study found that when the traction speed increases, the load on the drum increases, and when the drum rotation speed increases, the load on the drum decreases; when the traction speed is increased from 2 to 6 m/min, the stress on the pick body under different rotation speeds increases to different degrees, with an average increase rate of 27.394%; when the drum rotation speed is 90 r/min, the traction speed is 3 m/min, and the coal loading mode is projectile loading, the wear depth of the picks and spiral blades is relatively small. The research method and results of this paper can provide a reference for the selection of the drum working parameters.

Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Serum Interleukin-6 as a Biomarker for Early Prediction of Post-Operative Infectious Complications After Elective Pancreatectomy.

Background: To investigate whether interleukin (IL)-6 could predict the post-operative complications of elective pancreatectomy early. Patients and Methods: Overall, 122 patients who underwent elective pancreatectomy from June 2020 to May 2021 in our hospital were enrolled. Interleukin-6 was measured on the day before and at six hours after surgery, and on post-operative day one, three, and five. The associations between IL-6 level and post-operative complications were analyzed, and the predictive value of IL-6 for complications was assessed. Results: Sixty-three patients developed post-operative complications. Higher IL-6 was observed in patients with post-operative complications on post-operative day one, post-operative day three, and post-operative day five, with odd ratios of 1.43, 1.68, and 2.54 (p = 0.01, p = 0.01, and p = 0.01), respectively. These trends were also observed in patients with infectious complications preoperatively, on post-operative day one, post-operative day three, and post-operative day five, with ORs of 2.46, 1.95, 2.01, and 2.49 (p = 0.00, 0.00, 0.01, 0.00) respectively. Multivariate regression revealed that IL-6 is the only predictor for infectious complications on post-operative day one (p = 0.016). Based on the optimal cutoffs, pre-operative IL-6, IL-6 on post-operative day one and post-operative day three for predicting infectious complications yielded area under the curve (AUC) of 0.73, 0.70, and 0.70, with high negative predictive value of 82.7%, 92.2%, and of 91.3%, respectively. Conclusions: This study validated the early predictive value of IL-6 on infectious complications after pancreatectomy. Because of the performance of serum IL-6 in predicting infectious complications and high NPV, we endorse that IL-6 could be a potential biomarker for early prediction and antibiotic optimization after pancreatectomy.

Computer-aided efficient design and performance optimization of cutting head for roadheader.

The cutting head is the core working mechanism of the roadheader for coal-rock materials cutting. The efficient and high performance design of cutting head is the key to improve the road head digging and mining technology. In this paper, based on cutting head design theory and virtual prototype technology, we propose a computer-aided structure design and performance optimization method for cutting head. We compile the calculation code and realize the reading and storing of relevant data through Excel. In particular, to obtain more realistic cutting performance data of the cutting head, we construct a coupling model of cutting head cutting rock wall based on virtual prototype technology, and then establish a database matching structural parameters, working parameters, coal-rock properties and cutting performance through extensive simulations. Based on the method, we complete the design of EBZ220 roadheader cutting head. We show that our method can realize the fast and efficient design of cutting head, and the designed cutting head has good working performance.

A metabolism-relevant signature as a predictor for prognosis and therapeutic response in pancreatic cancer.

Although several altered metabolic genes have been identified to be involved in the tumorigenesis and advance of pancreatic cancer (PC), their prognostic values remained unclear. The purpose of this study was to explore new targets and establish a metabolic signature to predict prognosis and chemotherapy response for optimal individualized treatment. The expression data of PC patients from two independent cohorts and metabolism-related genes from KEGG were utilized and analyzed for the establishment of the signature via lasso regression. Then, the differentially expressed candidate genes were further confirmed via online data mining platform and qRT-PCR of clinical specimens. Then, the analyses of gene set enrichment, mutation, and chemotherapeutic response were performed via R package. As results showed, 109 differentially expressed metabolic genes were screened out in PC. Then a metabolism-related five-gene signature comprising B3GNT3, BCAT1, KYNU, LDHA, and TYMS was constructed and showed excellent ability for predicting survival. A novel nomogram coordinating the metabolic signature and other independent prognostic parameters was developed and showed better predictive power in predicting survival. In addition, this metabolic signature was significantly involved in the activation of multiple oncological pathways and regulation of the tumor immune microenvironment. The patients with high risk scores had higher tumor mutation burdens and were prone to be more sensitive to chemotherapy. In summary, our work identified a new metabolic signature and established a superior prognostic nomogram which may supply more indications to explore novel strategies for diagnosis and treatment.

Natural variation and underlying genetic loci of γ-oryzanol in Asian cultivated rice seeds.

γ-oryzanol is the most studied component in rice (Oryza sativa L.) bran oil. It is not only associated with physiological processes of rice growth and development but also grain quality that is related to human health. Previous studies focused mainly on γ-oryzanol composition and content in various rice cultivars, while its biosynthetic and regulatory pathways remain unknown. Here we present the quantitative identification of γ-oryzanol in rice seeds across 179 Asian cultivated accessions using ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOF/MS), which revealed a significant natural variation in γ-oryzanol content among these tested rice accessions. In addition, we present, for the first time, the genome-wide association study (GWAS) on rice seed γ-oryzanol, which identified 187 GWAS signal hot spots and 13 candidate genes that are associated with variable γ-oryzanol content and provided the top 10 rice haplotypes with high γ-oryzanol content for breeding. Collectively, our study provides valuable germplasms for breeding rice cultivars rich in γ-oryzanol and genetic resources for elucidating genetic and biochemical bases of variable γ-oryzanol in rice.

Identification of an Immune-Related BAT Signature for Predicting Adjuvant Chemotherapy Response and Overall Survival in Patients with Resected Ductal Adenocarcinoma of the Pancreas.

BACKGROUND: Adjuvant chemotherapy (ACT) is widely accepted in patients with pancreatic ductal adenocarcinoma (PDAC) after surgery; however, effective models for predicting ACT response are scarce. Thus, the objective of this study was to develop a novel signature for predicting its response and overall survival (OS) in resected PDAC patients. METHODS: A total of 50 PDAC patients with the transcriptome expression profiles, information about chemotherapy, and relevant clinical data were retrieved from the Cancer Genome Atlas (TCGA), and twenty-nine patients with tissue specimens and clinical data from our hospital were included as a validation. A novel gene signature was developed using bioinformatic differentially expressed genes (DEGs) analysis, Lasso-penalized Cox regression, and multivariate Cox regression studies. RESULTS: Between chemotherapy-resistant and chemotherapy-sensitive cohorts, 569 DEGs were identified, with 490 upregulated and 79 downregulated genes mainly specialized in the regulation of peptide/protein/hormone secretion, calcium ion homeostasis, and T cell activation regulation in biological processes. After Lasso-penalized Cox and multivariate Cox regression analysis, BAT (BCHE, ADH1A, and TNS4) signature was established to predict ACT response and OS. Moreover, BAT signature was verified as an independent risk factor for ACT response (p = 0.042) and OS (median OS: 17.5 months vs. 34.8 months, p = 0.040) and significantly associated with immune infiltrations (p < 0.05). Then, this signature was further validated as the independent risk factor for recurrence-free survival (RFS) in PDAC patients receiving postoperative ACT (median RFS: 9.0 months vs. not reached, p = 0.014), and tumor-infiltrating CD4+ and CD8+ T cells were further validated to be significantly decreased in tissues with higher BAT signature scores (p = 0.015 and 0.021, respectively). CONCLUSION: The BAT signature is a novel formulated and independent risk factor for predicting ACT response and long-term survival in patients with resected PDAC. This signature could comprehensively reflect local immune-related response, tumor purity, potential biological behavior, and chemo drug susceptibility.

Application of dynamic contrast enhanced ultrasound in distinguishing focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

OBJECTIVE: To explore the value of dynamic contrast enhanced ultrasound (DCE-US) in preoperative differential diagnosis of focal-type autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: From May 2016 to March 2020, patients with biopsy and histopathologically confirmed focal-type AIP (n = 9) were retrospectively included. All patients received contrast enhanced ultrasound (CEUS) examinations one week before surgery/biopsy. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Eighteen cases of resection and histopathologically proved PDAC lesions were also included as control group. B mode ultrasound (BMUS) features, CEUS enhancement patterns, time intensity curves (TICs) and CEUS quantitative parameters were obtained and compared between AIP and PDAC lesions. RESULTS: After injection of ultrasound contrast agents, most focal-type AIP lesions displayed hyper-enhancement (2/9, 22.2%) or iso-enhancement (6/9, 66.7%) during arterial phase of CEUS, while most of PDAC lesions showed hypo-enhancement (88.9%) (P < 0.01). During late phase, most of AIP lesions showed iso-enhancement (8/9, 88.9%), while most of PDAC lesions showed hypo-enhancement (94.4%) (P < 0.001). Compared with PDAC lesions, TICs of AIP lesions showed delayed and higher enhancement. Among all CEUS perfusion parameters, ratio of PE (peak enhancement), WiAUC (wash-in area under the curve), WiR (wash-in rate), WiPI (wash-in perfusion index, WiPI = WiAUC/ rise time), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve) and WoR (wash-out rate) between pancreatic lesion and surrounding normal pancreatic tissue were significantly higher in AIP lesions than PDAC lesions (P < 0.05). CONCLUSION: DCE-US with quantitative analysis has the potential to make preoperative differential diagnosis between focal-type AIP and PDAC non-invasively.

Basophils as a potential therapeutic target in cancer.

Basophils, which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation, have been neglected by researchers in the past decades. Previous studies have revealed their vital roles in allergic diseases and parasitic infections. Intriguingly, recent studies even reported that basophils might be associated with cancer development, as activated basophils synthesize and release a variety of cytokines and chemokines in response to cancers. However, it is still subject to debate whether basophils function as tumor-protecting or tumor-promoting components; the answer may depend on the tumor biology and the microenvironment. Herein, we reviewed the role of basophils in cancers, and highlighted some potential and promising therapeutic strategies.