The Effect of Heparin and Other Exogenous Glycosaminoglycans (GAGs) in Reducing IL-1ß-Induced Pro-Inflammatory Cytokine IL-8 and IL-6 mRNA Expression and the Potential Role for Reducing Inflammation.

Glycosaminoglycans (GAGs) are long linear polysaccharides found in every mammalian tissue. Previously thought only to be involved in cellular structure or hydration, GAGs are now known to be involved in cell signaling and protein modulation in cellular adhesion, growth, proliferation, and anti-coagulation. In this study, we showed that GAGs have an inhibitory effect on the IL-1ß-stimulated mRNA expression of IL-6 and IL-8. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), chondroitin (p < 0.049), dermatan (p < 0.0027), and hyaluronan (p < 0.0005) significantly reduced the IL-1ß-induced IL-8 mRNA expression in HeLa cells. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), and dermatan (p < 0.0027) also significantly reduced IL-1ß-induced IL-6 mRNA expression in HeLa cells, but exogenous chondroitin and hyaluronan had no significant effect. The exogenous GAGs may reduce the transcription of these inflammatory cytokines through binding to TILRR, a co-receptor of IL-1R1, and block/reduce the interactions of TILRR with IL-1R1.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

The role of computed tomography features in assessing response to neoadjuvant chemotherapy in locally advanced gastric cancer.

OBJECTIVE: To compare the computed tomography (CT) images of patients with locally advanced gastric cancer (GC) before and after neoadjuvant chemotherapy (NAC) in order to identify CT features that could predict pathological response to NAC. METHODS: We included patients with locally advanced GC who underwent gastrectomy after NAC from September 2016 to September 2021. We retrieved and collected the patients' clinicopathological characteristics and CT images before and after NAC. We analyzed CT features that could differentiate responders from non-responders and established a logistic regression equation based on these features. RESULTS: We included 97 patients (69 [71.1%] men; median [range] age, 60 [26-75] years) in this study, including 66 (68.0%) responders and 31 (32.0%) non-responders. No clinicopathological variable prior to treatment was significantly associated with pathological response. Out of 16 features, three features (ratio of tumor thickness reduction, ratio of reduction of primary tumor attenuation in arterial phase, and ratio of reduction of largest lymph node attenuation in venous phase) on logistic regression analysis were used to establish a regression equation that demonstrated good discrimination performance in predicting pathological response (area under receiver operating characteristic curve 0.955; 95% CI, 0.911-0.998). CONCLUSION: Logistic regression equation based on three CT features can help predict the pathological response of patients with locally advanced GC to NAC.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Three-dimensional patterning of MoS2 with ultrafast laser.

Transition metal chalcogenides, a special two-dimensional (2D) material emerged in recent years, possess unique optoelectronic properties and have been used to fabricate various optoelectronic devices. While it is essential to manufacture multifunctional devices with complex nanostructures for practical applications, 2D material devices present a tendency toward miniaturization. However, the controllable fabrication of complex nanostructures on 2D materials remains a challenge. Herein, we propose a method to create designed three-dimensional (3D) patterns on the MoS2 surface by modulating the interaction between an ultrafast laser and MoS2. Three different nanostructures, including flat, bulge, and craters, can be fabricated through laser-induced surface morphology transformation, which is related to thermal diffusion, oxidation, and ablation processes. The MoS2 field effect transistor is fabricated by ultrafast laser excitation which exhibits enhanced electrical properties. This study provides a promising strategy for 3D pattern fabrication, which is helpful for the development of multifunctional microdevices.

Dual-Energy CT Deep Learning Radiomics to Predict Macrotrabecular-Massive Hepatocellular Carcinoma.

Background It is unknown whether the additional information provided by multiparametric dual-energy CT (DECT) could improve the noninvasive diagnosis of the aggressive macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC). Purpose To evaluate the diagnostic performance of dual-phase contrast-enhanced multiparametric DECT for predicting MTM HCC. Materials and Methods Patients with histopathologic examination-confirmed HCC who underwent contrast-enhanced DECT between June 2019 and June 2022 were retrospectively recruited from three independent centers (center 1, training and internal test data set; centers 2 and 3, external test data set). Radiologic features were visually analyzed and combined with clinical information to establish a clinical-radiologic model. Deep learning (DL) radiomics models were based on DL features and handcrafted features extracted from virtual monoenergetic images and material composition images on dual phase using binary least absolute shrinkage and selection operators. A DL radiomics nomogram was developed using multivariable logistic regression analysis. Model performance was evaluated with the area under the receiver operating characteristic curve (AUC), and the log-rank test was used to analyze recurrence-free survival. Results A total of 262 patients were included (mean age, 54 years ± 12 [SD]; 225 men [86%]; training data set, n = 146 [56%]; internal test data set, n = 35 [13%]; external test data set, n = 81 [31%]). The DL radiomics nomogram better predicted MTM than the clinical-radiologic model (AUC = 0.91 vs 0.77, respectively, for the training set [P < .001], 0.87 vs 0.72 for the internal test data set [P = .04], and 0.89 vs 0.79 for the external test data set [P = .02]), with similar sensitivity (80% vs 87%, respectively; P = .63) and higher specificity (90% vs 63%; P < .001) in the external test data set. The predicted positive MTM groups based on the DL radiomics nomogram had shorter recurrence-free survival than predicted negative MTM groups in all three data sets (training data set, P = .04; internal test data set, P = .01; and external test data set, P = .03). Conclusion A DL radiomics nomogram derived from multiparametric DECT accurately predicted the MTM subtype in patients with HCC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chu and Fishman in this issue.

Preoperative diagnosis of metastatic lymph nodes by CT-histopathologic matching analysis in gastric adenocarcinoma using dual-layer spectral detector CT.

OBJECTIVES: There still remain challenges to accurate diagnosis of lymph node (LN) involvement in gastric cancer (GC) on conventional CT. This study evaluated the quantitative data derived from dual-layer spectral detector CT (DLCT) for preoperative diagnosis of metastatic LNs compared to conventional CT images. METHODS: Patients with adenocarcinoma scheduled for gastrectomy were enrolled in this prospective study from July, 2021, to February, 2022. Regional LNs were labeled on preoperative DLCT. The LNs were located and matched using carbon nanoparticle solution during surgery according to their locations and anatomic landmarks on preoperative images. The matched LNs were randomly split into training and validation cohorts in a ratio of 2:1. The DLCT quantitative parameters in the training cohort were investigated using logistic regression models to identify independent predictors of metastatic LNs, and these predictors were subsequently applied to the validation cohort. Receiver operating characteristic curves were compared between the DLCT parameters and conventional CT images. RESULTS: Fifty-five patients were included in the study, with 267 successfully matched LNs (90 metastatic, 177 nonmetastatic). Independent predictors included arterial phase CT attenuation on 70-keV images, venous phase electron density, and clustered feature. These combination predictors had areas under the curve (AUC) of 0.855 and 0.907 in the training and validation cohorts, respectively. Compared to conventional CT criteria alone, the model had higher AUC and accuracy (0.741 vs. 0.907, 75.28% vs. 87.64%; p < 0.01) for LN diagnosis. CONCLUSION: Incorporating DLCT parameters improved preoperative diagnosis of LN metastasis in GC, increasing the accuracy of clinical N stage. CLINICAL RELEVANCE STATEMENT: Compared to conventional CT criteria, quantitative parameters from dual-layer spectral detector CT showed higher diagnostic efficacy for the preoperative diagnosis of lymph node metastases in gastric cancer, increasing the accuracy of clinical N stage. KEY POINTS: • Quantitative parameters from dual-layer spectral detector CT are useful for the preoperative diagnosis of lymph node metastases in gastric adenocarcinoma, increasing the accuracy of clinical N stage. • The values for metastatic lymph nodes are higher than those of nonmetastatic ones. The arterial phase of CT attenuation on 70-keV images, venous phase of electron density, and clustered feature independently predicted lymph node metastases. • Prediction model had area under the curve of 0.907, sensitivity of 81.82%, specificity of 91.07%, and accuracy of 87.64% for the preoperative diagnosis of lymph node metastasis.

Correction: Luo, M. Natural Immunity against HIV-1: Progression of Understanding after Association Studies. Viruses 2022, 14, 1243.

The author wishes to make the following corrections to this paper [...].

Laser Induced Coffee-Ring Structure through Solid-Liquid Transition for Color Printing.

Metallic micro/nano structures with special physicochemical properties have undergone rapid development owing to their broad applications in micromachines and microdevices. Ultrafast laser processing is generally accepted as an effective technology for functional structures manufacture, however, the controllable fabrication of specific metallic micro/nano structures remains a challenge. Here, this work proposes a novel strategy of laser induced transient solid-liquid transition to fabricate unique structures. Through modulating the transient state of metal from solid to liquid phase using the initial pulse excitation, the subsequent ultrafast pulse-induced recoil pressure can suppress the plasma emission and removal of liquid phase metals, resulting in the controllable fabrication of coffee-ring structures. The solid-liquid transition dynamics, which related with the transient reflectivity and plasma intensity, are revealed by established two temperature model coupled with molecular dynamics model. The coffee-ring structure exhibits tunable structure color owing to various optical response, which can be used for color printing with large scale and high resolution. This work provides a promising strategy for fabricating functional micro/nano structures, which can greatly broaden the potential applications.

Percutaneous ablation of liver metastases from colorectal cancer: a comparison between the outcomes of ultrasound guidance and CT guidance using propensity score matching.

PURPOSE: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). METHODS: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients' initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)-free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. RESULTS: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). CONCLUSION: For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Supine magnetic resonance image registration for breast surgery: insights on material mechanics.

Purpose: Breast conserving surgery (BCS) is a common procedure for early-stage breast cancer patients. Supine preoperative magnetic resonance (MR) breast imaging for visualizing tumor location and extent, while not standard for procedural guidance, is being explored since it more closely represents the surgical presentation compared to conventional diagnostic imaging positions. Despite this preoperative imaging position, deformation is still present between the supine imaging and surgical state. As a result, a fast and accurate image-to-physical registration approach is needed to realize image-guided breast surgery. Approach: In this study, three registration methods were investigated on healthy volunteers' breasts ( n = 11 ) with the supine arm-down position simulating preoperative imaging and supine arm-up position simulating intraoperative presentation. The registration methods included (1) point-based rigid registration using synthetic fiducials, (2) nonrigid biomechanical model-based registration using sparse data, and (3) a data-dense three-dimensional diffeomorphic image-based registration from the Advanced Normalization Tools (ANTs) repository. Additionally, deformation metrics (volume change and anisotropy) were calculated from the ANTs deformation field to better understand breast material mechanics. Results: The average target registration errors (TRE) were 10.4 ± 2.3 , 6.4 ± 1.5 , and 2.8 ± 1.3 mm (mean ± standard deviation) and the average fiducial registration errors (FRE) were 7.8 ± 1.7 , 2.5 ± 1.1 , and 3.1 ± 1.1 mm for the point-based rigid, nonrigid biomechanical, and ANTs registrations, respectively. The mechanics-based deformation metrics revealed an overall anisotropic tissue behavior and a statistically significant difference in volume change between glandular and adipose tissue, suggesting that nonrigid modeling methods may be improved by incorporating material heterogeneity and anisotropy. Conclusions: Overall, registration accuracy significantly improved with increasingly flexible and data-dense registration methods. Analysis of these outcomes may inform the future development of image guidance systems for lumpectomy procedures.

NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population.

Background: We examined associations between NFκB1 polymorphisms and influenza A (H1N1) clinical outcomes in Canadian. Methods: A total of thirty-six Caucasian patients admitted to the intensive care unit (ICU) in hospitals in Canada were recruited during the 2009 H1N1 pandemic. Genomic DNA was extracted from the whole blood samples. The NFkB1 gene was targeted for genotyping using next-generation sequencing technology­Roche 454. Results: A total of 136 single nucleotide polymorphisms (SNPs) were discovered within the NFκB1 gene. Among them, 63 SNPs were significantly enriched in patients admitted in the ICU (p < 0.05) compared with the British Caucasian population in the 1000 Genomes study. These enriched SNPs are mainly intron variants, and only two are exon SNPs from the non-transcribing portion of the NFκB1 gene. Conclusions: Genetic variations in the NFκB1 gene could influence clinical outcomes of pandemic H1N1 infections. Our findings showed that sequence variations of the NFκB1 gene might influence patient response to influenza infection.

Chiral Majorana fermions in two-dimensional square lattice antiferromagnet with proximity-induced superconductivity.

Combination of proximity-induced superconductivity and ferromagnetic exchange field in a two-dimensional square-lattice antiferromagnet with spin-orbit coupling and nonsymmorphic symmetry can induce a topological superconductor phase with chiral Majorana edge states. The lattice model of the Bogoliubov-de Gennes (BdG) Hamiltonian was applied to study the phase diagram of bulks and chiral Majorana edge states in nanoribbons. By numerically studying the phase diagram, we found that the non-uniformity of either the superconducting pairing parameters or the exchange field at the two sublattices is necessary to induce a topological superconductor phase with chiral Majorana edge states. The BdG Chern number of certain topological superconductor phases is ±1 or ±3, such that the corresponding nanoribbons have one or three pairs of chiral Majorana edge states, respectively.

Magnetic resonance imaging features of intrahepatic extramedullary hematopoiesis: Three case reports.

BACKGROUND: Extramedullary hematopoiesis rarely occurs within the liver alone, and is easily misdiagnosed. The radiological literature on this disease is exclusively case reports. There is a paucity of literature on the role of magnetic resonance imaging (MRI). The most common imaging modalities used are computed tomography and ultrasound. This report aims to provide more data on the appearance of extramedullary hematopoiesis using MRI to help radiologists establish the diagnosis. CASE SUMMARY: Three patients (one male and two females) were incidentally found to have a hepatic mass or nodule, without hepatomegaly or splenomegaly. Laboratory tests including liver function, serum hepatic tumor markers, and hepatitis serologic markers were normal. On MRI scans, all lesions showed lower signal intensity on in-phase images than on out-phase images. One case showed changes in signal intensity on T2 weighted images (WI) and diffusion WI, which shifted from hyperintensity to hypointensity with size enlargement between two rounds of imaging examination. These lesions exhibited different enhancement patterns on dynamic contrast enhancement series. CONCLUSION: The MRI signal change and in-/out-phase image might provide useful information and help radiologists establish the diagnosis of intrahepatic extramedullary hematopoiesis.

Natural Immunity against HIV-1: Progression of Understanding after Association Studies.

Natural immunity against HIV has been observed in many individuals in the world. Among them, a group of female sex workers enrolled in the Pumwani sex worker cohort remained HIV uninfected for more than 30 years despite high-risk sex work. Many studies have been carried out to understand this natural immunity to HIV in the hope to develop effective vaccines and preventions. This review focuses on two such examples. These studies started from identifying immunogenetic or genetic associations with resistance to HIV acquisition, and followed up with an in-depth investigation to understand the biological relevance of the correlations of protection, and to develop and test novel vaccines and preventions.

Concurrent Improvement in Maize Grain Yield and Nitrogen Use Efficiency by Enhancing Inherent Soil Productivity.

Quantifying the relationships of maize yield and nitrogen use efficiency (NUE) to inherent soil productivity (ISP) could provide a theoretical basis for implementing strategies that concurrently narrow the yield gap, increase NUE, and improve soil quality. A field study under irrigation conditions was conducted at five locations with large differences in ISP (estimated by maize grain yield without using fertilizers) across various ecological regions in Inner Mongolia, China. Our results showed that the changes in maize yield and nitrogen partial factor productivity (PFPN) to ISP followed a linear-plateau model, with a common inflection point. When ISP was below 8.0 t ha-1, maize yield and PFPN were stagnating at a low level, due to a trade-off between the contribution of soil and chemical fertilizers to yield. When ISP exceeded 8.0 t ha-1, the contribution rate of soil to yield stabilized at 80%, resulting in a simultaneous increase in maize yield by 1.2 t ha-1 and PFPN by 4.6 kg kg-1, for increasing ISP at each t ha-1. Our results indicated that while keeping other management strategies unchanged, to increase maize yield and PFPN by 15% or further 30%, it is necessary to increase ISP to 9.3 and 10.4 t ha-1, respectively. In this scenario, N input will be reduced by 33.5 and 47.5%, and apparent N losses will be reduced by 11.7 and 21.5%, respectively. Therefore, enhancing ISP could lead to a simultaneous improvement in yield and NUE as well as strongly support the green development of maize production.

Effects of Culture Mechanism of Cinnamomum kanehirae and C. camphora on the Expression of Genes Related to Terpene Biosynthesis in Antrodia cinnamomea.

The rare edible and medicinal fungus Antrodia cinnamomea has a substantial potential for development. In this study, Illumina HiSeq 2000 was used to sequence its transcriptome. The results were assembled de novo, and 66,589 unigenes with an N50 of 4413 bp were obtained. Compared with public databases, 6,061, 3,257, and 2,807 unigenes were annotated to the Non-Redundant, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The genes related to terpene biosynthesis in the mycelia of A. cinnamomea were analyzed, and acetyl CoA synthase (ACS2 and ACS4), hydroxymethylglutaryl CoA reductase (HMGR), farnesyl transferase (FTase), and squalene synthase (SQS) were found to be upregulated in XZJ (twig of C. camphora) and NZJ (twig of C. kanehirae). Moreover, ACS5 and 2,3-oxidized squalene cyclase (OCS) were highly expressed in NZJ, while heme IX farnesyl transferase (IX-FIT) and ACS3 were significantly expressed in XZJ. The differential expression of ACS1, ACS2, HMGR, IX-FIT, SQS, and OCS was confirmed by real-time quantitative reverse transcription PCR. This study provides a new concept for the additional exploration of the molecular regulatory mechanism of terpenoid biosynthesis and data for the biotechnology of terpenoid production.

Toll-like Interleukin -1 Receptor Regulator (TILRR) Protein, a Major Modulator of Inflammation, is Expressed in Normal Human and Macaque Tissues and PBMCs.

Purpose: TILRR is a modulator of genes in the NF-κB inflammation pathway. It regulates inflammation-responsive genes, the secretion of inflammatory mediators, and the migration of immune cells. Because inflammation drives the pathogenesis of many infectious and inflammatory diseases, it is important to know the expression of TILRR protein in tissues and cells. This study examined TILRR protein expression in healthy adult human and macaques' tissues and PBMCs (peripheral blood mononuclear cells). Methods and Results: Tissues (trachea, lungs, stomach, small intestine [ileum], cecum, colon, rectum, vagina, cervix, uterus, and penis) and PBMCs from humans and macaques were lysed in RIPA (radioimmunoprecipitation assay) lysis buffer. The TILRR protein was examined by fluorescent Western blot analysis. The relative fluorescence units (rfu) of TILRR protein expression were quantified by Image Studio software (LI-COR). The results showed that adult healthy female (n=1) rectal and cervicovaginal tissues expressed a higher level of TILRR protein than the other tissues (trachea, lungs, stomach, small intestine [ileum], cecum, colon, uterus, and penis) examined. Like humans, the lungs, colon, and rectal tissues of healthy adult female cynomolgus monkeys (Macaca fascicularis) (n=2) expressed the TILRR protein. In addition, PBMCs of healthy adult women (n=4), adult female cynomolgus monkeys (Macaca fascicularis) (n=4), and adult male and female rhesus monkeys (Macaca mulatta) (n=4) showed a similar expression level of TILRR protein (p= 0.2858). TILRR protein was not detected in most of the human cell lines examined, except in Jurkat cells. Conclusion: Our study for the first time showed that TILRR protein is expressed in healthy adult human and monkey tissues and PBMCs. The TILRR protein in these tissues and PBMCs may play a role in the inflammatory response of these tissues and cells in response to infectious pathogens.