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Abstract Aims Hepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level. Method In addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and immunohistochemistry (IHC) of HBsAg were performed in tissues from 131 HBsAg-positive HCC patients undergoing liver resection. Serum α-fetoprotein together with basic biochemical and immunological parameter was also measured. Results Overall, the ISH of HBV DNA and IHC of HBsAg showed 31.3% and 92.9% positive rate respectively (p

BackgroundAngiogenesis is a major promotor of tumor progression and metastasis in gastric adenocarcinoma (STAD). We aimed to develop a novel lncRNA gene signature by identifying angiogenesis-related genes to better predict prognosis in STAD patients.MethodsThe expression profiles of angiogenesis-related mRNA and lncRNA genes were collected from The Cancer Genome Atlas (TCGA). Then, the “limma” package was used to identify differentially expressed genes (DEGs). The expression profiles of angiogenesis-related genes were clustered by consumusclusterplus. The Pearson correlation coefficient was further used to identify lncRNAs coexpressed with angiogenesis-related clustere genes. We used Lasso Cox regression analysis to construct the angiogenesis-related lncRNAs signature. Furthermore, the diagnostic accuracy of the prognostic risk signature were validated by the TCGA training set, internal test sets and external test set. We used multifactor Cox analysis to determine that the risk score is an independent prognostic factor different from clinical characteristics. Nomogram has been used to quantitatively determine personal risk in a clinical environment. The ssGSEA method or GSE176307 data were used to evaluate the infiltration state of immune cells or predictive ability for the benefit of immunotherapy by angiogenesis-related lncRNAs signature. Finally, the expression and function of these signature genes were explored by RT–PCR and colony formation assays.ResultsAmong angiogenesis-related genes clusters, the stable number of clusters was 2. A total of 289 DEGs were identified and 116 lncRNAs were screened to have a significant coexpression relationship with angiogenic DEGs (P value0.5). A six-gene signature comprising LINC01579, LINC01094, RP11.497E19.1, AC093850.2, RP11.613D13.8, and RP11.384P7.7 was constructed by Lasso Cox regression analysis. The multifactor Cox analysis and Nomogram results showed that our angiogenesis-related lncRNAs signature has good predictive ability for some different clinical factors. For immune, angiogenesis-related lncRNAs signature had the ability to efficiently predict infiltration state of 23 immune cells and immunotherapy. The qPCR analysis showed that the expression levels of the six lncRNA signature genes were all higher in gastric adenocarcinoma tissues than in adjacent tissues. The functional experiment results indicated that downregulation of the expression of these six lncRNA signature genes suppressed the proliferation of ASG and MKN45 cells.ConclusionSix angiogenesis-related genes were identified and integrated into a novel risk signature that can effectively assess prognosis and provide potential therapeutic targets for STAD patients.

Advanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigate prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in an in vivo murine model. We observe an expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients. Moreover, transformed epithelial cells and associated fibroblasts create a microenvironment conducive to pro-tumorigenic immune infiltration, which is partially androgen responsive. Androgen-independent prostate cancer leads to significant diversification of intermediate luminal cell populations characterized by a range of androgen signaling activity, which is inversely correlated with proliferation and mRNA translation. Accordingly, distinct epithelial populations are exquisitely sensitive to translation inhibition, which leads to epithelial cell death, loss of pro-tumorigenic signaling, and decreased tumor heterogeneity. Our findings reveal a complex tumor environment largely dominated by castration-resistant luminal cells and immunosuppressive infiltrates.

Objective: This study focused on fresh-keeping technology with quality control as the main factor. Methods: The respiratory climacteric Zaoshengxinshui pear was used as material, after being fumigated with 3.24 μL/L of 1-MCP, then was stored at （10±1） ℃. The fruits stored at （10±1） ℃ and （1±1） ℃ without any treatment were used as control 1 （CK1） and control 2 （CK2）. The respiration intensity, ethylene release rate, firmness, soluble solid content, peel chromatism, core browning index, weight loss rate and decay rate of fruits during postharvest storage were measured and investigated, and the correlation was analyzed. Results: Compared with CK1, （10±1） ℃ combined with 1-MCP treatment could inhibit the ethylene release rate and respiratory intensity of fruit, delay its peak, but the inhibition effect on respiration intensity and ethylene release rate were still significantly lower than that of CK2. It can maintain high soluble solid content, reduce fruit water loss, delay fruit decay and browning, maintain the green peel （absolute value of a* was high, h° was high）. During the whole storage time, the peel hardness, pulp hardness, fruit brittleness and pulp compactness of fruits treated with （10±1） ℃ combined with 1-MCP were significantly higher than those of CK1. However, the retention effect of CK2 on fruit parenchyma was still higher than of （10±1） ℃ combined with 1-MCP; except respiration intensity, ethylene release rate and brown heart index, there were different degrees of correlation among other indexes. Conclusion: The safe storage period of （10±1） ℃ combined with 3.24 μL/L 1-MCP fumigation can reach 103 days, and the soluble solids are stable at about 12%. Therefore, it can better maintain the. inherent flavor and color of the fruit, which can be used as one of the fresh-keeping technologies instead of single low-temperature storage.

Objective: In order to study the correlation between fruit firmness, total soluble solids, red and green color, sensory scores of fresh yellow peaches, a prediction model of safe storage period of yellow peach was established to realize early warning and prediction of fruits quality. Methods: Solute Jinxiu peach was used as test material,firmness with skin, firmness without skin, fruit color difference,soluble solid contentand other indexes of the fruits in storage in three picking periods were measured, and sensory scores were made in four modules: fruit texture, color, flavor and aroma. The correlation analysis and time series analysis techniques were used to evaluate and establish a mathematical prediction model. Results: The best cluster number determined by contour curve is 4, which mainly showed the differences of fruit firmness, red-green color and soluble solids content, itwas consistent with the three module features of texture, color and flavor that consumers paid attention to.There is strong collinearity among sensory scores of the three modules of fruit firmness, color and flavor. Storage time is negatively correlated with fruit with skin and firmness without skin, and positively correlated with fruit red-green color difference.The red-green color of fruit is negatively correlated with fruit with skin and firmness without skin, which can be used as one of the characterization factors for nondestructive testing of firmness. Conclusion: At a temperature of （10.0±0.5） ℃ and a relative humidity of 80%~85%,a nonlinear prediction model of fruit with skin and firmness without skin was established: f[T.(a,k,b)]=a×exp(k×T)+b; The linear prediction model of red-green color of fruit was established: f(x)=kx+b. The verification results show that the prediction error of the above two prediction models is low （R2＞0.9, average error＜0.2）.

This study aimed to investigate ultrasound features of arteriovenous fistula stenosis and their relationship with primary patency after percutaneous transluminal angioplasty (post-intervention primary patency) and compare this classification with that using lesion location. Hemodialysis patients who underwent ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis from July 2020 to December 2021 were retrospectively evaluated. Lesions (excluding inflow arteries) were categorized into five groups based on ultrasound features, and the clinical characteristics and risk factors affecting the post-intervention primary patency of the arteriovenous fistula were analyzed. Among 185 patients, 100 (54.05%), 36 (19.46%), 22 (11.89%), 11 (5.95%), and 16 (8.65%) were classified into the intima-dominant, non-intima-dominant, valve obstruction, vascular calcification, and mixed groups, respectively. The dialysis duration and arteriovenous fistula use time were the highest in the vascular calcification group at 86 (interquartile range: 49–140) and 77 (interquartile range: 49–110) months, respectively. Diabetes mellitus was most common in the intima-dominant group (42.0%). In Kaplan–Meier and univariate Cox analysis, type III lesion location (stenosis in the venous confluence site) was associated with the lower post-intervention primary patency. In the multivariate Cox analysis, percutaneous transluminal angioplasty times (the number of times patients were treated with percutaneous transluminal angioplasty for arteriovenous fistula stenosis dysfunction), vascular calcification, calcification at the lesion site requiring percutaneous transluminal angioplasty, and serum parathyroid hormone levels were independent risk factors for post-intervention primary patency. Ultrasound features showed that calcification of the arteriovenous fistula was detrimental to the post-intervention primary patency of arteriovenous fistula. [ABSTRACT FROM AUTHOR]

The Regulators of Complement Activation (RCA) gene cluster comprises several tandemly arranged genes with shared functions within the immune system. RCA members, such as complement receptor 2 (CR2), are well-established susceptibility genes in complex autoimmune diseases. Altered expression of RCA genes has been demonstrated at both the functional and genetic level, but the mechanisms underlying their regulation are not fully characterised. We aimed to investigate the structural organisation of the RCA gene cluster to identify key regulatory elements that influence the expression of CR2 and other genes in this immunomodulatory region. Using 4C, we captured extensive CTCF-mediated chromatin looping across the RCA gene cluster in B cells and showed these were organised into two topologically associated domains (TADs). Interestingly, an inter-TAD boundary was located within the CR1 gene at a well-characterised segmental duplication. Additionally, we mapped numerous gene-gene and gene-enhancer interactions across the region, revealing extensive co-regulation. Importantly, we identified an intergenic enhancer and functionally demonstrated this element upregulates two RCA members (CR2 and CD55) in B cells. We have uncovered novel, long-range mechanisms whereby autoimmune disease susceptibility may be influenced by genetic variants, thus highlighting the important contribution of chromatin topology to gene regulation and complex genetic disease.

Abstract Targeting cell division by chemotherapy is a highly effective strategy to treat a wide range of cancers. However, there are limitations of many standard-of-care chemotherapies: undesirable drug toxicity, side-effects, resistance and high cost. New small molecules which kill a wide range of cancer subtypes, with good therapeutic window in vivo, have the potential to complement the current arsenal of anti-cancer agents and deliver improved safety profiles for cancer patients. We describe results with a new anti-cancer small molecule, WEHI-7326, which causes cell cycle arrest in G2/M, cell death in vitro, and displays efficacious anti-tumor activity in vivo. WEHI-7326 induces cell death in a broad range of cancer cell lines, including taxane-resistant cells, and inhibits growth of human colon, brain, lung, prostate and breast tumors in mice xenografts. Importantly, the compound elicits tumor responses as a single agent in patient-derived xenografts of clinically aggressive, treatment-refractory neuroblastoma, breast, lung and ovarian cancer. In combination with standard-of-care, WEHI-7326 induces a remarkable complete response in a mouse model of high-risk neuroblastoma. WEHI-7326 is mechanistically distinct from known microtubule-targeting agents and blocks cells early in mitosis to inhibit cell division, ultimately leading to apoptotic cell death. The compound is simple to produce and possesses favorable pharmacokinetic and toxicity profiles in rodents. It represents a novel class of anti-cancer therapeutics with excellent potential for further development due to the ease of synthesis, simple formulation, moderate side effects and potent in vivo activity. WEHI-7326 has the potential to complement current frontline anti-cancer drugs and to overcome drug resistance in a wide range of cancers.

Theft is an inevitable problem in the context of urbanization and poses a challenge to people’s lives and social stability. The study of theft and criminal behavior using spatiotemporal, big, demographic, and neighborhood data is important for guiding security prevention and control. In this study, we analyzed the theft frequency and location characteristics of the study area through mathematical statistics and hot spot analysis methods to discover the spatiotemporal divergence characteristics of theft in the study area during the pre-COVID-19 and COVID-19 periods. We detected the spatial variation pattern of the regression coefficients of the local areas of thefts in Haining City by modeling the influencing factors using the geographically weighted regression (GWR) analysis method. The results explained the relationship between theft and the influencing factors and showed that the regression coefficients had both positive and negative values in the pre-COVID-19 and COVID-19 periods, indicating that the spatial distribution of theft in urban areas of Haining City was not smooth. Factors related to life and work indicated densely populated areas had increased theft, and theft was negatively correlated with factors related to COVID-19. The other influencing factors were different in terms of their spatial distributions. Therefore, in terms of police prevention and control, video surveillance and police patrols need to be deployed in a focused manner to increase their inhibiting effect on theft according to the different effects of influencing factors during the pre-COVID-19 and COVID-19 periods.

The natriuretic peptide system (NPS) and renin-angiotensin-aldosterone system (RAAS) function oppositely at multiple levels. While it has long been suspected that angiotensin II (ANGII) may directly suppress NPS activity, no clear evidence to date supports this notion. This study was designed to systematically investigate ANGII–NPS interaction in humans, in vivo, and in vitro. Circulating atrial, b-type, and c-type natriuretic peptides (ANP, BNP, CNP), cyclic guanosine monophosphate (cGMP), and ANGII were simultaneously investigated in 128 human subjects. Prompted hypothesis was validated in vivo to determine the influence of ANGII on ANP actions. The underlying mechanisms were further explored via in vitro approaches. In humans, ANGII demonstrated an inverse relationship with ANP, BNP, and cGMP. In regression models predicting cGMP, adding ANGII levels and the interaction term between ANGII and natriuretic peptides increased the predictive accuracy of the base models constructed with either ANP or BNP, but not CNP. Importantly, stratified correlation analysis further revealed a positive association between cGMP and ANP or BNP only in subjects with low, but not high, ANGII levels. In rats, co-infusion of ANGII even at a physiological dose attenuated cGMP generation mediated by ANP infusion. In vitro, we found the suppressive effect of ANGII on ANP-stimulated cGMP requires the presence of ANGII type-1 (AT1) receptor and mechanistically involves protein kinase C (PKC), as this suppression can be substantially rescued by either valsartan (AT1 blocker) or Go6983 (PKC inhibitor). Using surface plasmon resonance (SPR), we showed ANGII has low binding affinity to the guanylyl cyclase A (GC-A) receptor compared to ANP or BNP. Our study reveals ANGII is a natural suppressor for the cGMP-generating action of GC-A via AT1/PKC dependent manner and highlights the importance of dual-targeting RAAS and NPS in maximizing beneficial properties of natriuretic peptides in cardiovascular protection.

To improve the radiation resistance of Yb-doped fiber lasers, we investigate the influence of pre-radiation and photo-bleaching on the gamma-radiated laser’s performance. When the gamma radiation dose is within 10 krad(Si) with a radiation dose rate less than 0.4 rad(Si)/s, compared to the output power of a non-pre-radiated Yb-doped fiber laser, the pre-radiation technique could enhance the radiation resistance against gamma-ray. However, the mode instability threshold was decreased, which was caused by the cumulated radiation-induced attenuation of pre-radiation and radiation. Based on an electronic probe micro-analyzer, the Yb-doped active fiber was Yb-doped aluminophosphosilicate ternary fiber; therefore, the radiated defects were mainly hole-related defects. A laser diode centered at 532 nm was chosen as the photo-bleaching laser source, which could recover 45.2% of the radiated-induced attenuation and increase the mode instability threshold. This work demonstrates the influence of pre-radiation and photo-bleaching on the radiation resistance against the gamma-ray of Yb-doped fiber lasers, which are of significance in the design and fabrication of related fiber lasers.

The task of question matching/retrieval focuses on determining whether two questions are semantically equivalent. It has garnered significant attention in the field of natural language processing (NLP) due to its commercial value. While neural network models have made great strides and achieved human-level accuracy, they still face challenges when handling complex scenarios. In this paper, we delve into the utilization of different specializations encoded in different layers of large-scale pre-trained language models (PTMs). We propose a novel attention-based model called ERNIE-ATT that effectively integrates the diverse levels of semantics acquired by PTMs, thereby enhancing robustness. Experimental evaluations on two challenging datasets showcase the superior performance of our proposed model. It outperforms not only traditional models that do not use PTMs but also exhibits a significant improvement over strong PTM-based models. These findings demonstrate the effectiveness of our approach in enhancing the robustness of question matching/retrieval systems. [ABSTRACT FROM AUTHOR]

Plant cell walls are largely composed of polysaccharide polymers, including cellulose, hemicelluloses (xyloglucan, xylan, mannan, and mixed-linkage β-1,3/1,4-glucan), and pectins. Among these cell wall polysaccharides, xyloglucan, xylan, mannan, and pectins are often O-acetylated, and polysaccharide O-acetylation plays important roles in cell wall assembly and disease resistance. Genetic and biochemical analyses have implicated the involvement of three groups of proteins in plant cell wall polysaccharide O-acetylation: trichome birefringence-like (TBL)/domain of unknown function 231 (DUF231), reduced wall acetylation (RWA), and altered xyloglucan 9 (AXY9). Although the exact roles of RWAs and AXY9 are yet to be identified, members of the TBL/DUF231 family have been found to be O-acetyltransferases responsible for the O-acetylation of xyloglucan, xylan, mannan, and pectins. Here, we provide a comprehensive overview of the occurrence of O-acetylated cell wall polysaccharides, the biochemical properties, structural features, and evolution of cell wall polysaccharide O-acetyltransferases, and the potential biotechnological applications of manipulations of cell wall polysaccharide acetylation. Further in-depth studies of the biochemical mechanisms of cell wall polysaccharide O-acetylation will not only enrich our understanding of cell wall biology, but also have important implications in engineering plants with increased disease resistance and reduced recalcitrance for biofuel production. [ABSTRACT FROM AUTHOR]

Background: Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. Objective: This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto‐basal ganglia loops, in ToM. Methods: Thirty‐four patients with idiopathic PD (15 women, aged 62.2 ± 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. Results: DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (≥0.157) or cognitive decline (Montreal Cognitive Assessment < 26). Conclusions: The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Grass xylan consists of a linear chain of β-1,4-linked xylosyl residues that often form domains substituted only with either arabinofuranose (Ara f) or glucuronic acid (GlcA)/methylglucuronic acid (MeGlcA) residues, and it lacks the unique reducing end tetrasaccharide sequence found in dicot xylan. The mechanism of how grass xylan backbone elongation is initiated and how its distinctive substitution pattern is determined remains elusive. Here, we performed biochemical characterization of rice xylan biosynthetic enzymes, including xylan synthases, glucuronyltransferases and methyltransferases. Activity assays of rice xylan synthases demonstrated that they required short xylooligomers as acceptors for their activities. While rice xylan glucuronyltransferases effectively glucuronidated unsubstituted xylohexaose acceptors, they transferred little GlcA residues onto (Ara f)-substituted xylohexaoses and rice xylan 3- O -arabinosyltransferase could not arabinosylate GlcA-substituted xylohexaoses, indicating that their intrinsic biochemical properties may contribute to the distinctive substitution patterns of rice xylan. In addition, we found that rice xylan methyltransferase exhibited a low substrate binding affinity, which may explain the partial GlcA methylation in rice xylan. Furthermore, immunolocalization of xylan in xylem cells of both rice and Arabidopsis showed that it was deposited together with cellulose in secondary walls without forming xylan-rich nanodomains. Together, our findings provide new insights into the biochemical mechanisms underlying xylan backbone elongation and substitutions in grass species. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, hepatocellular carcinoma (HCC) is widely diagnosed by using MRI, however, whether the imaging features are affected by hepatic steatosis (HS) is still unknown. Purpose: To investigate and compare the differences in HCC related imaging features between with‐ and without‐HS groups, and to further determine whether HS affects the diagnosis accuracy of Liver Imaging Reporting and Data System (LI‐RADS) v2018 of HCC in MRI. Study Type: Prospective. Subjects: One hundred and seventy‐one patients (mean age, 52 ± 11 years; range, 26–83 years) including 137 men and 34 women. Field Strength/Sequence: 3.0 T, gradient echo (GRE). Assessment: Subjects were classified as HS and non‐HS groups according to MRI‐proton density fat‐fraction (PDFF). HS was defined as MRI‐PDFF >5.6%. Three radiologists accessed HCC features and assigned LI‐RADS categories in MRI independently based on LI‐RADS v2018. Frequencies of HCC major features and LR categorization assignment between the two groups as well as interobserver agreement between the two radiologists were assessed. Statistical Tests: Unpaired t‐test, Chi‐square test, Fisher's exact test, kappa statistic, intraclass correlation coefficient (ICC). A two‐sided P value <0.05 was considered as statistically significant. Results: Major features including arterial hyperenhancement (APHE), enhancing "capsule" and nonperipheral "washout" observed between HS and non‐HS groups were not significantly different (78.95% vs.78.62%, P = 0.866; 57.89% vs.52.98%, P = 0.483; and 75% vs.81.46%, P = 0.257, respectively), and the assessment of observation size showed a borderline difference (P = 0.059). No significant difference in LR‐5 assignment between the two groups (69.74% vs. 72.85% for reader 1, P = 0.641; 71.05% vs. 72.19% for reader 2, P = 0.877). Interobserver agreement between the two radiologists showed almost perfect in LR‐5 assignment (κ = 0.869) and size observation (ICC = 0.997). Data Conclusion: The diagnosis of HCC based on LI‐RADS v2018 in MRI is of comparable performance regardless of HS, in which there is no significant difference in either the major imaging features or LR categorization. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p< 0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation. [ABSTRACT FROM AUTHOR]