BackgroundAlthough clear cell renal cell carcinoma (ccRCC) is well known as a highly immunogenic tumor, only a small subset of patients could benefit from current immunotherapy, which might be due to ...the heterogeneity of immune microenvironment in ccRCC. So, it is meaningful to explore novel immunotherapy or combination therapy for improving therapeutic efficacy. HHLA2, a newly discovered B7 family member, is prevalently expressed in numerous tumors, including ccRCC. This study aimed to investigate the prognostic impact of HHLA2/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs).MethodsThe expression levels of HHLA2, PD-L1, CD8, and CD4 in cancer tissues from cases (206 in the training cohort and 197 in the validation cohort) with surgically resectable primary ccRCC were evaluated by immunohistochemistry.ResultsThe positive rates of HHLA2 were much higher than those of PD-L1 in ccRCC tissues. HHLA2-positive expression was significantly associated with necrosis, microvascular invasion, advanced Fuhrman nuclear, and TNM stage and indicated a shorter progression-free survival (PFS) and overall survival (OS) in both cohorts. Moreover, patients with HHLA2/PD-L1 co-expression suffered the highest risk of disease progression and death by a significant margin. Besides, HHLA2/PD-L1 co-expression was significantly associated with a high density of CD8+ and CD4+ TILs. Notably, a new immune classification, based on HHLA2/PD-L1 co-expression and TILs, successfully stratified PFS and OS, especially in patients with TILs positivity.ConclusionsThe expression of HHLA2 is more frequent than PD-L1 in ccRCC. HHLA2/PD-L1 co-expression had an adverse impact on the prognoses of patients with ccRCC; this finding provides a rationale for combination immunotherapy with anti-HHLA2 and PD-L1 blockage for patients with ccRCC in the future.
The efficacy of immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1) or its ligand 1 (PD-L1) antibody, in hepatocellular carcinoma (HCC) is limited, and it is ...recommended that they be combined with other therapies. We evaluated the combination of pegylated interferon-α (Peg-IFNα) with PD-1 blockade in HCC mouse models.
We analyzed the effects of Peg-IFNα on tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 pathway. The in vivo efficacy of anti-PD-1 and Peg-IFNα was evaluated in both subcutaneous and orthotopic mouse models of HCC.
The combination of Peg-IFNα with PD-1 blockade dramatically enhanced T-cell infiltration, improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody monotherapy. Mechanistically, Peg-IFNα could recruit cytotoxic CD8
T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine CCL4. Nevertheless, the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8
T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling pathway. The combination of PD-1 blockade with Peg-IFNα could restore the cytotoxic capacity of CD8
T cells and exerted a significant synergistic effect on HCC.
These results indicate that in addition to initiating the antitumor immune response itself, Peg-IFNα can also generate a microenvironment favoring PD-1 blockade. Thus, the combination of Peg-IFNα and PD-1 blockade can be a promising strategy for HCC.
In this paper, a high-performance field-programmable gate array (FPGA) based privacy amplification (PA) scheme for both continuous variable and discrete variable - quantum key distribution (QKD) is ...presented, which can provide more than 1.5 Gbps throughput at the input block size close to <inline-formula><tex-math notation="LaTeX">10^{8}</tex-math></inline-formula>. Besides, the resource consumption is so economical that there is no need of any external storage. To the best of our knowledge, our scheme outperforms existing FPGA based PA schemes by over an order of magnitude in terms of throughput and input block size. To achieve this feature, we design a novel FPGA-based hybrid hash PA algorithm combining multilinear modular hash and modular arithmetic hash (MMH-MH) based on number theoretical transform (NTT). Based on the hybrid hash algorithm, many optimization strategies are designed in our FPGA based PA scheme, such as an NTT-based optimization unit, an NTT-reusable architecture, a memory-saving modular accumulation unit for multilinear modular hash and a pipelined binary modulo unit for modular arithmetic hash. Plentiful experiment results demonstrate the high performance and reliability of our scheme. It can be embedded in most standalone QKD devices conveniently. What's more, it is also a good candidate for a chip-based QKD system.
Acronycine and noracronycine are chromene-containing alkaloids with significant biological activity. We have accomplished a concise total synthesis of acronycine and noracronycine. The key step, ...regioselective nucleophilic addition of anthranilate to chromene-type arynes under mild and transition-metal-free conditions was achieved. In addition, further modifications of nucleophilic addition products, such as hydrogenation, O-functionalization and palladium-catalyzed coupling reactions have also been developed, providing a concise procedure for these alkaloids and their derivatives.
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Recognition of tea plant variety and grade is essential for tea germplasm resources protection. The rapid and accurate acquisition of phenotype of tea leaves is a crucial step in exploring the ...variety type, nutrition status, and yield prediction. Monitoring the phenotypic characteristics of tea leaves is necessary for intelligent tea germplasm management. This study analyzed phenotypic features of tea leaves based on multispectral imaging technology. Tea leaf images of 12242 sets from 25 different types, along with 61 groups of chemical characteristics of fresh tea leaves were obtained. A total of 92 indicators were extracted, and 38 indicators were screened using the successive projection algorithm and the shuffled frog leaping algorithm, which showed significant differences among different tea varieties. The phenotypic indexes of different tea varieties were analyzed, and a tea variety recognition model was established based on these indexes combined with gray wolf optimization-support vector machine algorithm. The average accuracy of the training, test, and validation sets were 99.74 %, 92.17 %, and 91.56 %, respectively. Additionally, quantitative evaluation for tea plant germplasm resources was explored. Stepwise Fisher discriminant analysis was used to identify the 61 tea plant germplasm resources, achieving an accuracy of 93.44 % with the discrimination accuracy of each grade is above 90 %.
•Multispectral imaging technique can be used to obtain tea leaf phenotype quickly.•Tea leaf phenotypic information can realize accurate identification of tea variety.•Multispectral information of leaf can identify tea germplasm grade.
Al-Zn-Si-RE coating was deposited on mild steel by arc spraying Al-Zn based alloy wire with a high Al content. The corrosion behavior of Al-Zn-Si-RE coating was investigated by corrosion morphologies ...and electrochemical measurements. The results indicated that Al-Zn-Si-RE coating exhibited homogeneous distributions of elements and a dense homogeneous lamellar microstructure with good scale adhesion. The phases of the coatings are Zn-rich phase, Al-rich phase, Al sub(0.403)Zn sub(0.597) and Al sub(9)Si phase. Corrosion products had been deposited in the defects, which caused self-sealing behavior and hindered further corrosion. Corrosion products formed on Al-Zn-Si-RE coating surface consisted mainly of simonkolleite Zn sub(5)(OH) sub(8)Cl sub(2)middotH sub(2)O, zinc aluminum hydrotalcites Zn sub(0.71)Al sub(0.29)(OH) sub(2)(CO sub(3)) sub(0.145)middotxH sub(2) O, Zn sub(0.70)Al sub(0.30)(OH) sub(2)(CO sub(3)) sub(0.15)middotxH sub(2)O, Zn sub(6)Al sub(2)(OH) sub( 16)CO sub(3)middot4H sub(2)O and aluminum chloride hydroxide hydrate Al sub(5)Cl sub(3)(OH) sub(12)middot4H sub(2)O. Corrosion products had been deposited in the defects, which caused self-sealing behavior and hindered further corrosion. Furthermore, sacrificial anodic protection played a dominant role during the corrosion process. There were different corrosion stages of the coating in sodium chloride solution, such as pitting-dissolution-redeposition, active dissolution, cathodic protection and physical barriers caused by corrosion products. Finally, schematic model of the protective mechanisms of Al-Zn-Si-RE coating during immersion in sodium chloride solution was given.
Metastasis is the major cause of prostate cancer (PCa)‐related mortality. Epithelial‐mesenchymal transition (EMT) is a vital characteristic feature that empowers cancer cells to adapt and survive at ...the beginning of metastasis. Therefore, it is essential to identify the regulatory mechanism of EMT in metastatic prostate cancer (mPCa) and to develop a novel therapy to block PCa metastasis. Here, we discovered a novel PCa metastasis oncogene, DEP domain containing 1B (DEPDC1B), which was positively correlated with the metastasis status, high Gleason score, advanced tumor stage, and poor prognosis. Functional assays revealed that DEPDC1B enhanced the migration, invasion, and proliferation of PCa cells in vitro and promoted tumor metastasis and growth in vivo. Mechanistic investigations clarified that DEPDC1B induced EMT and enhanced proliferation by binding to Rac1 and enhancing the Rac1‐PAK1 pathway. This DEPDC1B‐mediated oncogenic effect was reversed by a Rac1‐GTP inhibitor or Rac1 knockdown. In conclusion, we discover that the DEPDC1B‐Rac1‐PAK1 signaling pathway may serve as a multipotent target for clinical intervention in mPCa.
Highlights
1. DEPDC1B positively correlates with prostate cancer metastasis, tumor stage, Gleason score, and poor prognosis.
2. DEPDC1B enhances prostate cancer cell metastasis and tumor growth in vitro and in vivo.
3. DEPDC1B enhances the Rac1‐PAK1 signaling pathway to induce EMT.
4. DEPDC1B contributing to metastasis and proliferation through Rac1‐PAK1 signaling.
Estimating whether to treat the rupture risk of small intracranial aneurysms (IAs) with size ≤ 7 mm in diameter is difficult but crucial. We aimed to construct and externally validate a convenient ...machine learning (ML) model for assessing the rupture risk of small IAs. One thousand four patients with small IAs recruited from two hospitals were included in our retrospective research. The patients at hospital 1 were stratified into training (70%) and internal validation set (30%) randomly, and the patients at hospital 2 were used for external validation. We selected predictive features using the least absolute shrinkage and selection operator (LASSO) method and constructed five ML models applying diverse algorithms including random forest classifier (RFC), categorical boosting (CatBoost), support vector machine (SVM) with linear kernel, light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best ML model. The training, internal, and external validation cohorts included 658, 282, and 64 IAs, respectively. The best performance was presented by SVM as AUC of 0.817 in the internal 95% confidence interval (CI), 0.769–0.866 and 0.893 in the external (95% CI, 0.808–0.979) validation cohorts, which overperformed compared with the PHASES score significantly (all
P
< 0.001). SHAP analysis showed maximum size, location, and irregular shape were the top three important features to predict rupture. Our SVM model based on readily accessible features presented satisfying ability of discrimination in predicting the rupture IAs with small size. Morphological parameters made important contributions to prediction result.
N
6
-methyladenosine (m
6
A) methylation is the most prevalent internal modification of post-transcriptional modifications in mRNA, tRNA, miRNA, and long non-coding RNA in eukaryotes. m
6
A ...methylation has been proven to be involved in plant resistance to pathogens. However, there are no reports on wheat (
Triticum aestivum
) m
6
A transcriptome-wide map and its potential biological function in wheat resistance to wheat yellow mosaic virus (WYMV). To the best of our knowledge, this study is the first to determine the transcriptome-wide m
6
A profile of two wheat varieties with different resistances to WYMV. By analyzing m
6
A-sequencing (m
6
A-seq) data, we identified 25,752 common m
6
A peaks and 30,582 common m
6
A genes in two groups WYMV-infected resistant wheat variety (WRV) and WYMV-infected sensitive wheat variety (WSV), and all these peaks were mainly enriched in 3′ untranslated regions and stop codons of coding sequences. Gene Ontology analysis of m
6
A-seq and RNA-sequencing data revealed that genes that showed significant changes in both m
6
A and mRNA levels were associated with plant defense responses. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these selected genes were enriched in the plant–pathogen interaction pathway. We further verified these changes in m
6
A and mRNA levels through gene-specific m
6
A real-time quantitative PCR (RT-qPCR) and normal RT-qPCR. This study highlights the role of m
6
A methylation in wheat resistance to WYMV, providing a solid basis for the potential functional role of m
6
A RNA methylation in wheat resistance to infection by RNA viruses.
The tea plant is a valuable and evergreen crop that is extensively cultivated in China and many other countries. Currently, there is growing research interest in this plant. For the tea industry, it ...is crucial to develop rapid and non-invasive methods to evaluate tea plants in their natural environment. This article provides a comprehensive overview of non-invasive sensing techniques used for in-situ detection of tea plants. The topics covered include leaf, canopy, and field-level assessments, as well as statistical analysis techniques and characteristics specific to the research. Non-invasive testing technology is primarily used for monitoring and predicting tea pests and diseases, monitoring quality, and nutrients, determining tenderness and grade, identifying tea plant varieties, automatically detecting, and identifying tea buds, monitoring tea plant growth, and extracting tea garden areas through remote sensing. It also helps to evaluate planting suitability, assess disasters, and estimate yields. Additionally, the article examines the challenges and prospects of emerging techniques aimed at resolving the in-situ detection problem for tea plants. It can assist researchers and producers in comprehensively understanding the tea environment, quality characteristics, and growth process, thereby enhancing tea production quality, and fostering tea industry development.
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