Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a ...testing panel and whether the result would affect clinical management.
We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018. All participants received germline testing for various hereditary cancer syndromes.
The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes was 7.8% (38/486), including 25 PVs in genes with high-risk CRC susceptibility (the minimal testing set) and 13 PVs in genes with moderate-risk CRC susceptibility or increased cancer risk other than CRC (the additional testing set). All the clinically relevant PVs were found in patients diagnosed under age 70 years. Among them, 11 patients would not have been diagnosed if testing reserved to present guidelines. Most (36/38) of the patients with PVs benefited from enhanced surveillance and tailored treatment. PVs in genes from the minimal testing set were found in all age groups, while patients carried PVs in genes from the additional testing set were older than 40 years.
Universal germline testing for cancer susceptibility genes should be recommended among all patients with CRC diagnosed under age 70 years. A broad panel including genes from the additional testing set might be considered for patients with CRC older than 40 years to clarify inheritance risks.
NCT03365986.
The important application of metal oxides (MOs) as a chemiresistive sensing material can be severely hampered by their poor selectivity towards analyte molecules that possess a similar sensing ...activity. In this work, a new metal oxide@metal-organic framework (MO@MOF) core-sheath nanowire array material was prepared. Using a post-synthetic modification of the pore size in the MOF sheath, the channel traffic of the analyte molecules with a similar sensing activity but different kinetic diameter was successfully modulated, which profoundly enhanced the selectivity of the MOs. As a result, the materials obtained showed the highest selective response to acetone in the presence of benzene in all the reported materials.
The channel traffic of gas molecules with a similar sensing activity was modulated in MO@MOF chemiresistors by modification of the pores of the MOF sheath.
In this Article, we present a series of cyclometalated iridium(III) polypyridine complexes of the formula Ir(N^C)2(N^N)(PF6) that showed dual emission under ambient conditions. The structures of ...the cyclometalating and diimine ligands were changed systematically to investigate the effects of the substituents on the dual-emission properties of the complexes. On the basis of the photophysical data, the high-energy (HE) and low-energy (LE) emission features of the complexes were assigned to triplet intraligand (3IL) and triplet charge-transfer (3CT) excited states, respectively. Time-dependent density functional theory (TD-DFT) calculations supported these assignments and indicated that the dual emission resulted from the interruption of the communication between the higher-lying 3IL and the lower-lying 3CT states by a triplet amine-to-ligand charge-transfer (3NLCT) state. Also, the avidin-binding properties of the biotin complexes were studied by emission titrations, and the results showed that the dual-emissive complexes can be utilized as ratiometric probes for avidin. Additionally, all the complexes exhibited efficient cellular uptake by live HeLa cells. The MTT and Annexin V assays confirmed that no cell death and early apoptosis occurred during the cell imaging experiments. Interestingly, laser-scanning confocal microscopy revealed that the complexes were selectively localized on the cell membrane, mitochondria, or both, depending on the nature of the substituents of the ligands. The results of this work will contribute to the future development of dual-emissive transition metal complexes as ratiometric probes and organelle-selective bioimaging reagents.
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IJS, KILJ, NUK, PNG, UL, UM
Saliva sampling is a non‐invasive method, and could be performed by donors themselves. However, there are few studies reporting biomarkers in saliva in the diagnosis of NPC. A total of 987 salivary ...samples were used in this study. First, EBV DNA methylation was profiled by capture sequencing in the discovery cohort (n = 36). Second, a q‐PCR based method was developed and five representative EBV DNA CpG sites (11 029 bp, 45 849 bp, 57 945 bp, 66 226 bp and 128 102 bp) were selected and quantified to obtain the methylated density in the validation cohort1 (n = 801). Third, a validation cohort2 (n = 108) was used to further verify the differences of EBV methylation in saliva. A significant increase of EBV methylation was found in NPC patients compared with controls. The methylated score of EBV genome obtained by capture sequencing could distinguish NPC from controls (sensitivity 90%, specificity 100%). Further, the methylated density of EBV DNA CpG sites revealed by q‐PCR showed a good diagnostic performance. The sensitivity and specificity of detecting a single CpG site (11 029 bp) could reach 75.4% and 99.7% in the validation cohort1, and 78.2% and 100% in the validation cohort2. Besides, the methylated density of the CpG site was found to decrease below the COV in NPC patients after therapy, and increase above the COV after recurrence. Our study provides an appealing alternative for the non‐invasive detection of NPC without clinical setting. It paves the way for conducting a home‐based large‐scale screening in the future.
What's new?
While various Epstein‐Barr virus (EBV)‐related biomarkers have been established as potential screening biomarkers for nasopharyngeal carcinoma, most of them rely on blood or nasopharyngeal swab samples. Using saliva samples, this study found a significant increase in EBV DNA methylation in nasopharyngeal carcinoma patients compared to controls. Detection at a single CpG site could reach a sensitivity of 75.8% and specificity of 99.7%. The methylated density of the CpG site was found to decrease below the cut‐off value after therapy and increase above the cut‐off value after recurrence. This study potentially provides a non‐invasive alternative for the detection of nasopharyngeal carcinoma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Plant height and branch number are essential components of rapeseed plant architecture and are directly correlated with its yield. Presently, improvement of plant architecture is a major ...challenge in rapeseed breeding. In this study, we first verified that the two rapeseed BnaMAX1 genes had redundant functions resembling those of Arabidopsis MAX1, which regulates plant height and axillary bud outgrowth. Therefore, we designed two sgRNAs to edit these BnaMAX1 homologs using the CRISPR/Cas9 system. The T0 plants were edited very efficiently (56.30%–67.38%) at the BnaMAX1 target sites resulting in homozygous, heterozygous, bi‐allelic and chimeric mutations. Transmission tests revealed that the mutations were passed on to the T1 and T2 progeny. We also obtained transgene‐free lines created by the CRISPR/Cas9 editing, and no mutations were detected in potential off‐target sites. Notably, simultaneous knockout of all four BnaMAX1 alleles resulted in semi‐dwarf and increased branching phenotypes with more siliques, contributing to increased yield per plant relative to wild type. Therefore, these semi‐dwarf and increased branching characteristics have the potential to help construct a rapeseed ideotype. Significantly, the editing resources obtained in our study provide desirable germplasm for further breeding of high yield in rapeseed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
In the context of the COVID‐19 pandemic, cases of adverse skin reactions related to the wearing of masks have been observed.
Objectives
To analyze the short‐term effects of N95 respirators ...and medical masks, respectively, on skin physiological properties and to report adverse skin reactions caused by the protective equipment.
Methods
This study used a randomized crossover design with repeated measurements. Twenty healthy Chinese volunteers were recruited. Skin parameters were measured on areas covered by the respective masks and on uncovered skin 2 and 4 hours after donning, and 0.5 and 1 hour after removing the masks, including skin hydration, transepidermal water loss (TEWL), erythema, pH, and sebum secretion. Adverse reactions were clinically assessed, and perceived discomfort and non‐compliance measured.
Results
Skin hydration, TEWL, and pH increased significantly with wearing the protective equipment. Erythema values increased from baseline. Sebum secretion increased both on the covered and uncovered skin with equipment‐wearing. There was no significant difference in physiological values between the two types of equipment. More adverse reactions were reported following a N95 mask use than the use of a medical mask, with a higher score of discomfort and non‐compliance.
Conclusions
This study demonstrates that skin biophysical characters change as a result of wearing a mask or respirator. N95 respirators were associated with more skin reactions than medical masks.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Detecting EBV DNA load in nasopharyngeal (NP) brushing samples for the diagnosis of nasopharyngeal carcinoma (NPC) has attracted widespread attentions. Currently, NP brush sampling mostly relies on ...endoscopic guidance, and there are few reports on diagnostic markers suitable for nonguided conditions (blind brush sampling), which is of great significance for extending its application. One hundred seventy nasopharyngeal brushing samples were taken from 98 NPC patients and 72 non‐NPC controls under the guidance of endoscope, and 305 blind brushing samples were taken without endoscopic guidance from 164 NPC patients and 141 non‐NPC controls (divided into discovery and validation sets). Among these, 38 cases of NPC underwent both endoscopy‐guided NP brushing and blind brushing. EBV DNA load targeting BamHI‐W region and EBV DNA methylation targeting 11029 bp CpG site located at Cp‐promoter region were detected by quantitative polymerase chain reaction (q‐PCR). EBV DNA load showed good classification accuracy for NPC in endoscopy‐guided brushing samples (AUC = 0.984). However, in blind bushing samples, the diagnostic performance was greatly reduced (AUC = 0.865). Unlike EBV DNA load, the accuracy of EBV DNA methylation was less affected by brush sampling methods, whether in endoscopy‐guided brushing (AUC = 0.923) or blind brushing (AUC = 0.928 in discovery set and AUC = 0.902 in validation set). Importantly, EBV DNA methylation achieved a better diagnostic accuracy than EBV DNA load in blind brushing samples. Overall, detection of EBV DNA methylation with blind brush sampling shows great potential in the diagnosis of NPC and may facilitate its use in nonclinical screening of NPC.
What's new?
Detection of Epstein‐Barr virus (EBV) DNA load in nasopharyngeal (NP) brush samples is a promising diagnostic tool for nasopharyngeal carcinoma (NPC). Brush sampling, however, typically requires endoscopic guidance, whereas blind brushing, without endoscopy, could facilitate the use of brush sampling for NPC detection. Here, the authors compared methylation markers against EBV DNA load for NPC diagnosis in endoscopy‐guided and nonguided brush samples. Under blind brushing conditions, a qPCR‐based method for detecting EBV DNA methylation outperformed EBV DNA load detection for NPC diagnosis. Blind brushing, combined with EBV DNA methylation detection, could have significant advantages for NPC diagnosis in nonclinical settings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This paper attempts to uncover one possible method for the IMR (indoor mobile robot) to perform indoor exploration associated with SLAM (simultaneous localization and mapping) using LiDAR. ...Specifically, the IMR is required to construct a map when it has landed on an unexplored floor of a building. We had implemented the e-SLAM (exploration-based SLAM) using the coordinate transformation and the navigation prediction techniques to achieve that purpose in the engineering school building which consists of many 100-m
labs, corridors, elevator waiting space and the lobby. We first derive the LiDAR mesh for the orthogonal walls and filter out the static furniture and dynamic humans in the same space as the IMR. Then, we define the LiDAR pose frame including the translation and rotation from the orthogonal walls. According to the MSC (most significant corner) obtained from the intersection of the orthogonal walls, we calculate the displacement of the IMR. The orientation of the IMR is calculated from the alignment of orthogonal walls in the consecutive LiDAR pose frames, which is also assisted by the LQE (linear quadratic estimation) method. All the computation can be done in a single processor machine in real-time. The e-SLAM technique leads to a potential for the in-house service robot to start operation without having pre-scan LiDAR maps, which can save the installation time of the service robot. In this study, we use only the LiDAR and compared our result with the IMU to verify the consistency between the two navigation sensors in the experiments. The scenario of the experiment consists of rooms, corridors, elevators, and the lobby, which is common to most office buildings.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Increasing ethanol demand and public concerns about environmental protection promote the production of lignocellulosic bioethanol. Compared to that of starch- and sugar-based bioethanol production, ...the production of lignocellulosic bioethanol is water-intensive. A large amount of water is consumed during pretreatment, detoxification, saccharification, and fermentation. Water is a limited resource, and very high water consumption limits the industrial production of lignocellulosic bioethanol and decreases its environmental feasibility. In this review, we focused on the potential for reducing water consumption during the production of lignocellulosic bioethanol by performing pretreatment and fermentation at high solid loading, omitting water washing after pretreatment, and recycling wastewater by integrating bioethanol production and anaerobic digestion. In addition, the feasibility of these approaches and their research progress were discussed. This comprehensive review is expected to draw attention to water competition between bioethanol production and human use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ascomycete Fusarium graminearum is a destructive fungal pathogen of wheat (Triticum aestivum). To better understand how this pathogen proliferates within the host plant, we tracked pathogen ...growth inside wheat coleoptiles and then examined pathogen gene expression inside wheat coleoptiles at 16, 40, and 64 h after inoculation (HAI) using laser capture microdissection and microarray analysis. We identified 344 genes that were preferentially expressed during invasive growth in planta. Gene expression profiles for 134 putative plant cell wall-degrading enzyme genes suggest that there was limited cell wall degradation at 16 HAI and extensive degradation at 64 HAI. Expression profiles for genes encoding reactive oxygen species (ROS)-related enzymes suggest that F. graminearum primarily scavenges extracellular ROS before a later burst of extracellular ROS is produced by F. graminearum enzymes. Expression patterns of genes involved in primary metabolic pathways suggest that F. graminearum relies on the glyoxylate cycle at an early stage of plant infection. A secondary metabolite biosynthesis gene cluster was specifically induced at 64 HAI and was required for virulence. Our results indicate that F. graminearum initiates infection of coleoptiles using covert penetration strategies and switches to overt cellular destruction of tissues at an advanced stage of infection.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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