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Introduction: The selection of an optimal scale or granularity in landscape analysis is pivotal for uncovering inherent patterns and changes driven by processes. Variations in spatial resolution can significantly alter the proportions and distributions of various landscape types, thereby impacting the assessment of landscape patterns. Despite its importance, the scale factor is frequently neglected in studies focusing on long-term landscape dynamics. Methods: Bridging this gap, we utilized remote sensing imagery data from 1986 to 2020 for Lushui City, integrating remote sensing (RS) and geographic information system (GIS) technologies to generate land cover maps. Our focus centered on investigating the sensitivity of landscape pattern indices within the 30-1000m scale. Combining the first scale domain with an information loss assessment model, we identified the optimal granularity for the analysis, conducting a detailed spatiotemporal examination of landscape pattern from 1986 to 2020 using the index analysis method. Results and discussion: The results show that: (1) The dominance of forests in Lushui City, yet reveal a significant increase in construction land area over the study period, primarily driven by the conversion of forest and grassland. (2) Among the 10 examined indices, four (PD, ED, TE, and LSI) demonstrated predictable responses to changes in granularity, while three (PAFEAC, COHESION, AI) exhibited unpredictable stepwise reactions. Three indices (LPI, SHDI, PLAND) displayed minimal regularity to granularity changes. (3) The optimal long-term landscape analysis granularity for Lushui was identified as 100 m. (4) Before 1996, the city's landscape exhibited characteristics of aggregation, good connectivity, and minimal anthropogenic disturbance. However, post-1996, the landscape experienced disruptions, leading to an overall increase in fragmentation. The expansion of cultivated land and construction land due to urbanization has intensified landscape fragmentation. However, policies such as converting cropland to forest and planned ecological civilization initiatives have restored forest coverage and improved landscape cohesion and connectivity in Lushui City. This research offers vital insights for ecological planning and resource management in alpine valley watershed cities, deepening our grasp of landscape pattern evolution. [ABSTRACT FROM AUTHOR]

Background: The Helicobacter pylori epidemic in China accounts for up to a third of gastric cancers worldwide. We aim to monitor the temporal and spatial dynamics of H. pylori infection in both adults and children across China. Materials and Methods: We developed a surveillance system consisting of a data collection component that harnessed survey reports in natural populations and an analysis component that accounted for the differences in survey time and location, population age structure, and H. pylori detection method. System outputs were estimates of the prevalence of H. pylori in adults and children (aged ≤ 14 years) presented at three hierarchical levels (regional, provincial, and prefectural). Results: The overall prevalence of H. pylori infection declined sharply in adults (63.3%, 52.5%, 43.4%, and 38.7%) and less sharply in children (23.1%, 26.1%, 16.0%, and 15.7%) in 1983–1999, 2000–2009, 2010–2014, and 2015–2019, respectively. The changes were asynchronous across regions, with the most marked declines in the Northwest, the Hong Kong‐Macao‐Taiwan region, and the East. We estimated that 457.6 million adults and 44.5 million children have been infected with H. pylori, with cross‐province disparities in prevalence ranging from 24.3% to 69.3% among adults and 2.9% to 46.3% among children. In general, the risk level of gastric cancer increased as the prevalence of H. pylori increased. The correlation was statistically significant for both adult men (Spearman coefficient of correlation: 0.393, p = 0.0146) and women (0.470, p = 0.0029). Conclusions: The tracking system would be important for the continuous and stratified tracking of the Helicobacter pylori epidemic across China and can be used to furnish an evidence base for the formulation of tailored prevention strategies. [ABSTRACT FROM AUTHOR]

Background and Aim: Programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD‐L1 expression in advanced HCC patients treated with PD‐1/PD‐L1 inhibitors. Methods: A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD‐L1 status of HCC were included. Results: Eleven studies with 1,330 HCC patients treated with PD‐1/PD‐L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD‐L1‐positive patients compared with PD‐L1‐negative patients (OR, 1.86, 95% CI, 1.35–2.55). Similar results were observed in the anti‐PD‐1 treatment (p < 0.001) and anti‐PD‐1/PD‐L1 monotherapy (p < 0.001) subgroups. The pooled ORRs in the PD‐L1‐positive and PD‐L1‐negative groups were 26% (95% CI, 20%–32%) and 18% (95% CI, 13%–22%), respectively. For DCR, the pooled OR analysis showed no significant difference between PD‐L1‐positive patients and PD‐L1‐negative patients (66% [95% CI, 55%–76%] vs. 69% [95% CI, 62%–76%]; OR, 0.92, 95% CI, 0.59–1.44). The results were consistent across the drug target and combination treatment subgroups. Conclusion: Positive PD‐L1 expression is associated with a better ORR in advanced HCC patients treated with anti‐PD‐1/PD‐L1‐based therapies. This feature can help to identify HCC patients who will benefit most from PD‐1/PD‐L1 inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods: The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results: In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p < 0.001) were significantly correlated with RFS in the TCGA‐LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low‐risk and high‐risk subgroups by the predictive score. Compared with the low‐risk group, the high‐risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low‐risk patients with the G1‐G2 stage, the levels of infiltrated NK‐activated cells and NKG2D expression were both lower in the high‐risk patients. Conclusions: The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: The lack of precision biomarkers hinders the development of individualized immunotherapy for esophageal cancer (ESCA) patients. The activation of WNT signaling has proved to be associated with the primary resistance to immunotherapy. Therefore, our study aims to develop efficient biomarkers based on WNT signaling to guide ESCA immunotherapy. In the TCGA cohort with 196 cases and our BJCH cohort with 95 cases, we successfully constructed an IGFBP1hiWNT3Alo signature and validated its correlation with the poor prognosis of ESCA patients. Moreover, in 2 GEO cohorts with a total of 68 cases and our BJIM cohort with 21 cases, we verified that IGFBP1hiWNT3Alo ESCA patients had a good response and prognosis with immunotherapy. Our findings indicate that the IGFBP1hiWNT3Alo signature was a potential immunotherapeutic biomarker for ESCA. PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA. [ABSTRACT FROM AUTHOR]

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups. [ABSTRACT FROM AUTHOR]

Background: Repeat hepatectomy is an important treatment for patients with repeat recurrent hepatocellular carcinoma (HCC). Methods: This study was a multicenter retrospective analysis of 1,135 patients who underwent primary curative liver resection for HCC. One hundred recurrent patients with second hepatectomy were included to develop a nomogram to predict the risk of post-recurrence survival (PRS). Thirty-eight patients in another institution were used to externally validate the nomogram. Univariate and multivariate Cox regression analyses were used to identify independent risk factors of PRS. Discrimination, calibration, and the Kaplan–Meier curves were used to evaluate the model performance. Results: The nomogram was based on variables associated with PRS after HCC recurrence, including the tumor, node, and metastasis (TNM) stage; albumin and aspartate aminotransferase levels at recurrence; tumor size, site, differentiation of recurrences; and time to recurrence (TTR). The discriminative ability of the nomogram, as indicated by the C statistics (0.758 and 0.811 for training cohort and external validation cohorts, respectively), was shown, which was better than that of the TNM staging system (0.609 and 0.609, respectively). The calibration curves showed ideal agreement between the prediction and the real observations. The area under the curves (AUCs) of the training cohort and external validation cohorts were 0.843 and 0.890, respectively. The Kaplan–Meier curve of the established nomogram also performed better than those of both the TNM and the BCLC staging systems. Conclusions: We constructed a nomogram to predict PRS in patients with repeat hepatectomy (RH) after repeat recurrence of HCC. [ABSTRACT FROM AUTHOR]

The crosstalk between the estrogen receptor (ER) and NF-κB signalling pathways has merged in vertebrates and plays a key role in the control of genes involved in inflammation, cell proliferation and apoptosis. However, such crosstalk between the endocrine and immune systems needs to be explored in lower invertebrates. In this study, we identified a 2856-bp homologue of the estrogen receptor from Hong Kong oyster (Ch ER), containing a 5′ untranslated region (UTR) of 234 bp, a 3' UTR of 387 bp, and an open reading frame (ORF) of 2235 bp. We observed that overexpression of Ch ER suppressed Ch Rel-dependent NF-kappaB (NF-κB) activation in the HEK293T (human embryonic kidney 293T) cell line, and depletion of Ch ER in vivo resulted in upregulation of two NF-κB-responsive marker genes, namely, TNF-α and IL-17 , which confirmed its potential role in controlling NF-κB signalling. Furthermore, an EMSA (electrophoretic mobility shift assay) showed that Ch ER could negatively regulate the binding of Ch Rel to NF-κB probe-responsive elements. Serial domain requirement analysis showed that both region C (DNA-binding domain) and region E (ligand-binding domain) of Ch ER were essential for mediating the crosstalk underlying Ch ER-dependent NF-κB suppression. In conclusion, we demonstrate for the first time the negative regulatory role of the ER in NF-κB signalling in oysters, strongly indicating the presence of complex crosstalk between the endocrine and immune systems in lower marine molluscs. ● A gene from Crassostrea Hongkongensis encoding estrogen receptor (ER) was identified. ● Ch ER suppressed the Ch Rel-dependent NF-κB activation. ● Region C (DNA binding domain) and region E (ligand binding domain) of Ch ER are essential to mediate the crosstalk underlying Ch ER-dependent NF-κB suppression [ABSTRACT FROM AUTHOR]

A finite-time control strategy is proposed to solve the problem of position tracking control for a permanent magnet synchronous motor servo system. It can guarantee that the motor's desired position can be tracked in a finite time. Firstly, for the d-axis voltage, a first-order finite-time controller is designed based on the vector control principle. Then, for the q-axis voltage, based on a radial basis function (RBF) neural network, an integral high-order terminal sliding mode controller is designed. Theoretical analysis shows that under the proposed controller, the desired position can be tracked by the motor position in a finite time. Simulation results are given to show that the proposed control method has a strong anti-disturbance ability and a fast convergence performance. [ABSTRACT FROM AUTHOR]

NEMO (NF-κB essential modulator) is one of the important regulatory subunits of the IκB kinase (IκK) complex that controls the activation of the NF-κB signaling pathway. Here, we have identified the homolog of NEMO from the pacific oyster Crassostrea gigas. Cg NEMO harbors the conserved the IκK binding region, NEMO ubiquitin binding domain and Zinc finger domain. In terms of tissue distribution, Cg NEMO is expressed in various tissues with an observed highest expression in the hemocytes. Furthermore, infection by two related Vibrio strains significantly increased Cg NEMO expression in the hemocytes. Cell culture based luciferase reporter assays showed that Cg NEMO activates the NF-κB reporter in a dose-pendent manner. Moreover, Cg NEMO was also found to counter the IkB-dependent inhibitory effect on NF-κB activation, providing a plausible mechanism of NF-κB activation by Cg NEMO. Meanwhile, site-directed mutagenesis demonstrated that the putative ubiquitination site K535 is required for the activation of NF-κB, implying that ubiquitination of NEMO may be involved in regulating its activity. Finally, RNAi mediated knockdown of Cg NEMO in vivo significantly compromised the bacterial induction of key cytokines TNF-α and IL-17, strongly suggesting a role for Cg NEMO in acute immune defense in oyster. In conclusion, this study provides new insights into our understanding about the evolution of NEMO mediated NF-κB activation and the induction of cytokine. Our findings may provide valuable information about diseases control and management in oyster aquaculture. [ABSTRACT FROM AUTHOR]

In vertebrates, embryonic hematopoietic stem and progenitor cells (HSPCs) are derived from a subset of endothelial cells, the hemogenic endothelium (HE), through the endothelial-to-hematopoietic transition (EHT). Notch signaling is essential for HSPC development during embryogenesis across vertebrates. However, whether and how it regulates EHT remains unclear. Here, we show that G protein-coupled receptor 183 (Gpr183) signaling serves as an indispensable switch for HSPC emergence by repressing Notch signaling before the onset of EHT. Inhibition of Gpr183 significantly upregulates Notch signaling and abolishes HSPC emergence. Upon activation by its ligand 7α-25-OHC, Gpr183 recruits β-arrestin1 and the E3 ligase Nedd4 to degrade Notch1 in specified HE cells and then facilitates the subsequent EHT. Importantly, 7α-25-OHC stimulation promotes HSPC emergence in vivo and in vitro, providing an attractive strategy for enhancing the in vitro generation of functional HSPCs. [ABSTRACT FROM AUTHOR]

It is increasingly appreciated that neuroendocrine-immune interactions hold the key to understand the complex immune system. In this study, we explored the role of a reproductive regulation-related hormone, GnRH, in the regulation of immunity in Hong Kong oysters. We found that vibrio bacterial strains injection increased the expression of Ch GnRH. Moreover, Ch GnRH neuropeptide promotes the phagocytic ability and bacterial clearance effect of hemocytes which regarded to be the central immune organ. The content of cAMP after incubation with Ch GnRH peptide was increased, which could be blocked by adenylyl cyclase inhibitor SQ 22,536. Furthermore, the stimulated effect of Ch GnRH peptide on the phagocytosis and bacterial clearance was also blocked by SQ 22,536, H89 and enzastaurin, strongly demonstrating that cAMP dependent PKA and PKC signaling pathway was involved in Ch GnRH mediated immune regulation. In conclusion, this study confirms the presence of neuroendocrine-immune regulatory system in marine invertebrates, which contributes to understand the complexity of oyster immune defense system. • A gene from Crassostrea Hongkongensis encoding GnRH was identified. • Ch GnRH promotes the phagocytic ability and bacterial clearance effect of hemocytes. • cAMP dependent PKA and PKC signaling pathway was involved in Ch GnRH mediated immune regulation. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA's (mtDNA) haplogroups and SNPs were associated with the risk of different cancer. However, there is no evidence that the same haplogroup or mitochondrial SNP (mtSNP) exhibits the pleiotropic effect on multiple cancers., Methods: We recruited 2,489 participants, including patients with colorectal, hepatocellular, lung, ovarian, bladder, breast, pancreatic, and renal cell carcinoma. In addition, 715 healthy individuals from Northern China served as controls. Next, cross-tumor analysis was performed to determine whether mtDNA variation is associated with multiple cancers., Results: Our results revealed a significant decrease in the occurrence risk of multiple cancers among individuals belonging to haplogroup A [OR = 0.553, 95% confidence interval (CI) = 0.375-0.815, P = 0.003]. Furthermore, we identified 11 mtSNPs associated with multiple cancers and divided the population into high-risk and low-risk groups. Low-risk groups showed a significantly reduced risk of occurrence compared with high-risk groups (OR = 0.614, 95% CI = 0.507-0.744, P < 0.001). Furthermore, using interaction analysis, we identified a special group of individuals belonging to haplogroup A/M7 and the low-risk population, who exhibit a lower risk of multiple cancers compared with other populations (OR = 0.195, 95% CI = 0.106-0.359, P < 0.001). Finally, gene set enrichment analysis confirmed that haplogroup A/M7 patients had lower expression levels of cancer-related pathway genes compared with haplogroup D patients., Conclusions: We found that specific mtDNA haplogroups and mtSNPs may play a role in predicting multiple cancer predisposition in Chinese populations., Impact: This may provide a potential tool for early screening in clinical settings for individuals in the Chinese population., (©2024 American Association for Cancer Research.)

Purpose: The study aimed to explore the role of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elder women with early-stage breast cancer (BC)., Methods: BC patients with 70-79 years of age, stage T1-2N0-1M0, undergoing BCS were screened in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The clinicopathological characteristics were balanced with propensity-score matching (PSM) method. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of adjuvant RT on BC patients., Results: Ultimately, 12,310 patients treated with adjuvant RT and 4837 patients treated with no RT, were involved in the analysis. Overall, patients treated with adjuvant RT was associated with a better breast cancer-specific survival (BCSS) (HR: 1.980 [1.596- 2.456], P < 0.001) and overall survival (OS) (HR: 2.214 [1.966- 2.494], P < 0.001) than those who did not undergo RT. After 1:1 PSM, adjuvant RT still performed advantage in both BCSS (HR: 1.918 [1.439- 2.557], P < 0.001) and OS (HR: 2.235 [1.904- 2.624], P < 0.001). In the multivariate COX analysis of BCSS, widowed, divorced and separated patients, tumor grade III, T2 stage, N1 stage, no RT, molecular subtypes with luminal B and triple negative were associated with a shorter BCSS (P < 0.05). In the multivariate COX analysis of OS, age ≥74 years, widowed, divorced and separated patients, tumor grade II/III, T2 stage, no RT, no chemotherapy, molecular subtypes with triple negative were associated with a shorter OS (P < 0.05). Furthermore, the advantages of adjuvant RT were observed in all subgroup analysis., Conclusion: Adjuvant RT after BCS can improve both BCSS and OS in elderly patients with early-stage BC. Additionally, all subgroups analysis-derived BCSS and OS were in support of RT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Shi, Chen, Chen and Hao.)

Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.

Tumor-infiltrating immune cells greatly participate in regulating tumorigenesis and metastasis of hepatocellular carcinoma (HCC). Natural killer cell, as an important role of innate immunity, plays an indispensable role in antitumor immunity and regulate tumor development. In this study, we firstly identified 251 NK cell marker genes of HCC based on single-cell RNA sequencing data. Subsequently, an NK cell marker genes-related prognostic signature (NKPS) was developed in the cancer genome atlas (TCGA) cohort for risk stratification and prognosis prediction. The predictive value of the NKPS in prognosis was well validated in different clinical subgroups and three external datasets (ICGC-LIHC cohort, GSE14520 cohort and Guilin cohort). Moreover, multivariate analysis revealed the independent prognostic value of NKPS for OS in HCC. Further functional analysis indicated the NKPS was associated with basic cellular processes, that may contribute to the development and progression of HCC. Thereafter, immune characteristics as well as the therapeutic benefits in NKPS risk score-defined subgroups were analyzed. Patients with low-risk score exhibited immune-active status, manifested as higher immune scores, more infiltration of CD8+ T cells and macrophage M1, and higher T-cell receptor (TCR) richness and diversity. Remarkably, the NKPS was negatively correlated with immunotherapy response-related signatures. In addition, the low-risk group exhibited significantly improved therapeutic benefits, either from immunotherapy or traditional chemotherapy and target therapy. Overall, the NKPS showed an excellent predictive value for prognosis and therapeutic responses for HCC, which might also provide novel insights into better HCC management strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, She, Ren, Zhao, Chen and Chen.)

Background: Previous studies confirmed that most neoantigens predicted by algorithms do not work in clinical practice, and experimental validations remain indispensable for confirming immunogenic neoantigens. In this study, we identified the potential neoantigens with tetramer staining, and established the Co-HA system, a single-plasmid system coexpressing patient human leukocyte antigen (HLA) and antigen, to detect the immunogenicity of neoantigens and verify new dominant hepatocellular carcinoma (HCC) neoantigens., Methods: First, we enrolled 14 patients with HCC for next-generation sequencing for variation calling and predicting potential neoantigens. Then, the Co-HA system was established. To test the feasibility of the system, we constructed target cells coexpressing HLA-A*11:01 and the reported KRAS G12D neoantigen as well as specific T-cell receptor (TCR)-T cells. The specific cytotoxicity generated by this neoantigen was shown using the Co-HA system. Moreover, potential HCC-dominant neoantigens were screened out by tetramer staining and validated by the Co-HA system using methods including flow cytometry, enzyme-linked immunospot assay and ELISA. Finally, antitumor test in mouse mode and TCR sequencing were performed to further evaluate the dominant neoantigen., Results: First, 2875 somatic mutations in 14 patients with HCC were identified. The main base substitutions were C>T/G>A transitions, and the main mutational signatures were 4, 1 and 16. The high-frequency mutated genes included HMCN1 , TTN and TP53 . Then, 541 potential neoantigens were predicted. Importantly, 19 of the 23 potential neoantigens in tumor tissues also existed in portal vein tumor thrombi. Moreover, 37 predicted neoantigens restricted by HLA-A*11:01, HLA-A*24:02 or HLA-A*02:01 were performed by tetramer staining to screen out potential HCC-dominant neoantigens. HLA-A*24:02-restricted epitope 5'-FYAFSCYYDL-3' and HLA-A*02:01-restricted epitope 5'-WVWCMSPTI-3' demonstrated strong immunogenicity in HCC, as verified by the Co-HA system. Finally, the antitumor efficacy of 5'-FYAFSCYYDL-3'-specific T cells was verified in the B-NDG- B2m tm1 Fcrn tm1(mB2m) mouse and their specific TCRs were successfully identified., Conclusion: We found the dominant neoantigens with high immunogenicity in HCC, which were verified with the Co-HA system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Abscisic acid (ABA) is an important sesquiterpene compound that regulates the stress resistance of plants. Botrytis cinerea can synthesize ABA via the mevalonic acid pathway. To identify the functional genes that are involved in the biosynthesis of ABA, we performed insertion mutagenesis into B. cinerea TB-31., Methods: We obtained the ABA-reduced mutant E154 by insertion mutagenesis, and we identified the insertion site was located upstream of the gene bcfrp1 by Thermal asymmetric interlaced PCR. We performed a detailed phenotypic characterization of the bcfrp1 knockout and complementation mutants in TB-31. Furthermore, transcriptome and proteome analyses were conducted to explore how bcfrp1 affects the level of the ABA biosynthesis., Results: The bcfrp1 gene encodes an F-box protein. The phenotypic results confirmed the positive contribution of bcfrp1 to the biosynthesis of ABA and growth. Between TB-31 and ΔBcfrp1, we obtained 4,128 and 1,073 differentially expressed genes and proteins, respectively. The impaired ABA biosynthesis in the ΔBcfrp1 mutants was primarily affected by the different levels of expression of the ABA biosynthetic gene cluster and the genes involved in the mevalonic acid pathway. In addition, we further characterized the differentially expressed genes and proteins that participated in the growth, secondary metabolism, and signal transduction in B. cinerea based on the transcriptome and proteome data., Discussion: This research based on the transcriptome and proteome analyses to display the changes after the deletion of bcfrp1 in B. cinerea TB-31, will help us to explore the molecular mechanism of ABA biosynthesis in B. cinerea ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Shu, Wei, Luo, Yang, Li and Tan.)

Background: There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancer-specific survival (ECSS) in patients with stage I-III UESCC., Methods: Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts., Results: A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival., Conclusions: Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system., Competing Interests: Conflicts of Interest:All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4577/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Artemisia pollen is the major cause of seasonal allergic respiratory diseases in the northern hemisphere. About 28.57% of Artemisia allergic patients' IgE can recognize ArtCaM, a novel allergenic calmodulin from Artemisia identified in this study. These patients exhibited stronger allergic reactions and a longer duration of allergic symptoms. However, the signaling mechanism that triggers these allergic reactions is not fully understood. In this study, we found that extracellular ArtCaM directly induces the maturation of human dendritic cells (DCs), which is attributed to a series of Ca 2+ relevant cascades, including Ca 2+ /NFAT/CaMKs. ArtCaM alone induces inflammatory response toward Th1, Th17, and Treg. Interestingly, a combination of ArtCaM and anti-ArtCaM IgE led to Th2 polarization. The putative mechanism is that anti-ArtCaM IgE partially blocks the ArtCaM-induced ERK signal, but does not affect Ca 2+ -dependent cascades. The crosstalk between ERK and Ca 2+ signal primes DCs maturation and Th2 polarization. In summary, ArtCaM related to clinical symptoms when combined with anti-ArtCaM IgE, could be a novel allergen to activate DCs and promote Th2 polarization. Such findings provide mechanistic insights into Th2 polarization in allergic sensitization and pave the way for novel preventive and therapeutic strategies for efficient management of such pollen allergic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Hu, Chen, Ding, Wang, Wang, Chi, Li, Li and Li.)

Purpose: Microvascular invasion (MVI) impairs long-term prognosis of patients with hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict MVI and patients' prognosis based on radiomic features of contrast-enhanced CT (CECT)., Patients and Methods: HCC patients who underwent curative resection were enrolled. The radiomic features were extracted from the region of tumor, and the optimal MVI-related radiomic features were selected and applied to construct radiomic signature (Rad-score). The prediction models were created according to the logistic regression and evaluated. Biomarkers were analyzed via q-PCR from randomly selected HCC patients. Correlations between biomarkers and radiomic signature were analyzed., Results: A total of 421 HCC patients were enrolled. A total of 1962 radiomic features were extracted from the region of tumor, and the 11 optimal MVI-related radiomic features showed a favor predictive ability with area under the curves (AUCs) of 0.796 and 0.810 in training and validation cohorts, respectively. Aspartate aminotransferase (AST), tumor number, alpha-fetoprotein (AFP) level, and radiomics signature were independent risk factors of MVI. The four factors were integrated into the novel nomogram, named as CRM, with AUCs of 0.767 in training cohort and 0.793 in validation cohort for predicting MVI, best among radiomics signature alone and clinical model. The nomogram was well-calibrated with favorable clinical value demonstrated by decision curve analysis and can divide patients into high- or low-risk subgroups of recurrence and mortality. In addition, gene BCAT1, DTGCU2, DOCK3 were analyzed via q-PCR and serum AFP were identified as having significant association with radiomics signature., Conclusion: The novel nomogram demonstrated good performance in preoperatively predicting the probability of MVI, which might guide clinical decision., Competing Interests: The authors have no conflicts of interest for this work., (© 2022 Xu et al.)

Objective: This paper aimed to explore the effects of radiotherapy after thoracic and laparoscopic surgery (TLS) in patients with esophageal cancer and on their prognoses., Methods: Altogether 118 patients with esophageal cancer diagnosed in our hospital were recruited as the study cohort and randomly divided into a postoperative radiotherapy group (59 cases) and a postoperative chemotherapy group (59 cases). All the patients were treated with TLS. In addition to the TLS, the patients in the postoperative radiotherapy group underwent radiotherapy, and the patients in the postoperative chemotherapy group were administered cisplatin and 5-fluorouracil (PF) chemotherapy. Before the treatment and at 6 months after the treatment, the serum carbohydrate antigen 199 (CA199), carbohydrate antigen 153 (CA153), and carcinoembryonic antigen (CEA) levels were measured using immunity transmission turbidity (ITT). The expression levels of Bax and Bcl-2 in the peripheral blood mononuclear cells (PBMCs) were measured using Western blot (WB). The CD4 + , CD8 + and CD3 + levels in the peripheral venous blood were measured using a flow cytometer. The two groups were compared in terms of their effective treatment rates, their incidences of complications, and their postoperative survival rates., Results: After the treatment, the serum CEA, CA153, and CA199 levels in the postoperative radiotherapy group were significantly lower than they were in the postoperative chemotherapy group (P<0.05). After the treatment, the expression level of Bcl-2 was significantly lower in the postoperative radiotherapy group, but the Bax expression level was significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, there were no statistically significant differences in the CD4 + , CD3 + or CD8 + levels between the two groups (P>0.05). After the treatment, the overall response rate (ORR) and the total incidence of adverse reactions were significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, the 1-year, 3-year, and 5-year survival rates were significantly elevated in the postoperative radiotherapy group (P<0.05)., Conclusion: Compared with the esophageal cancer patients treated with chemotherapy after TLS, the serum CA153, CA199, and CEA levels were significantly improved in the patients treated with radiotherapy. The Bcl-2 and Bax levels in the PBMCs tended close to normal. Therefore, undergoing radiotherapy after TLS is markedly effective in prolonging patients' survival times and improving their prognoses., Competing Interests: None., (AJTR Copyright © 2021.)

At the end of 2019, an outbreak of pneumonia took place caused by a new coronavirus (SARS-CoV-2 virus), named coronavirus disease 2019 (COVID-19). A series of strict prevention and control measures were then implemented to reduce the spread of the epidemic. Influenza, another respiratory tract virus, may also respond to these measures. To assess the impact of these measures, we used the total number of passengers movement in mainland China from 2018 to 2020 and daily number of railway passenger flow during the 2020 Spring Festival travel rush to reflect the population movement and to analyze newly and cumulatively confirmed COVID-19 and influenza cases. We found that implementing the series of measures against COVID-19 mitigated both COVID-19 and influenza epidemics in China. Prevention and control measures for COVID-19 might be used to control respiratory tract infections to reduce the national health economic burden caused by these pathogens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stem cells (HSCs) are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to-hematopoietic transition (EHT). Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DL1-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 (E10.5) Tie2(+) cells remarkably. Then, the immunophenotypically defined endothelial cells were harvested by a combination of surface markers (Flk1(+)CD31(+)CD41(-)CD45(-)Ter119(-)) from the caudal half of E10.0-E11.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co-cultures led to long-term, high-level, multi-lineage, and multi-organ hematopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at E10.5, and a significant increase was detected at E11.0, which suggests a temporally specific regulation. Taken together, for the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research., (Copyright © 2013. Published by Elsevier Ltd.)

In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be the sole location for intraembryonic emergence of hematopoietic stem cells (HSCs). Here we report that, in parallel to the AGM region, the E10.5-E11.5 mouse head harbors bona fide HSCs, as defined by long-term, high-level, multilineage reconstitution and self-renewal capacity in adult recipients, before HSCs enter the circulation. The presence of hemogenesis in the midgestation head is indicated by the appearance of intravascular cluster cells and the blood-forming capacity of a sorted endothelial cell population. In addition, lineage tracing via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of head endothelium. Most importantly, a spatially restricted lineage labeling system reveals the physiological contribution of cerebrovascular endothelium to postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse embryonic head is a previously unappreciated site for HSC emergence within the developing embryo., (Copyright © 2012 Elsevier Inc. All rights reserved.)