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Local recurrence and distant metastasis of non-small cell lung cancer (NSCLC) caused by immune escape is one of the root causes of treatment difficulties. We aim to investigate the mechanism of immune escape in NSCLC. NSCLC tissues were collected. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion ability was measured by Transwell assay. The expressions of E-cadherin, N-cadherin and PD-L1 were detected by Western blot. NSCLC cells were co-cultured with CD8+ T cells to simulate tumor microenvironment in vitro. The proportion of CD8+ T cells and apoptosis were detected by flow cytometry. Dual-luciferase reporter gene assay confirmed the targeting relationship of circDENND2D and STK11. The expressions of circDENND2D and STK1 were down-regulated, while miR-130b-3p expression was up-regulated in NSCLC tissues. Overexpression of circDENND2D or STK11 inhibited NSCLC cells proliferation, migration and invasion, and attenuated the immune escape of NSCLC cells. CircDENND2D targeted miR-130b-3p to competitively promote STK11 expression. STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy, represented by immune checkpoint inhibitors, has made significant progress in the treatment of cancer. Numerous studies have demonstrated that antitumor therapies targeting cell death exhibit synergistic effects with immunotherapy. Disulfidptosis is a recently discovered form of cell death, and its potential influence on immunotherapy, similar to other regulated cell death processes, requires further investigation. The prognostic value of disulfidptosis in breast cancer and its role in the immune microenvironment has not been investigated. Methods: High dimensional weighted gene coexpression network analysis (hdWGCNA) and Weighted co-expression network analysis (WGCNA) methods were employed to integrate breast cancer single-cell sequencing data and bulk RNA data. These analyses aimed to identify genes associated with disulfidptosis in breast cancer. Risk assessment signature was constructed using Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses. Results: In this study, we constructed a risk signature by disulfidptosis-related genes to predict overall survival and immunotherapy response in BRCA patients. The risk signature demonstrated robust prognostic power and accurately predicted survival compared to traditional clinicopathological features. It also effectively predicted the response to immunotherapy in patients with breast cancer. Through cell communication analysis in additional single-cell sequencing data, we identified TNFRSF14 as a key regulatory gene. Combining TNFRSF14 targeting and immune checkpoint inhibition to induce disulfidptosis in tumor cells could potentially suppress tumor proliferation and enhance survival in patients with BRCA. [ABSTRACT FROM AUTHOR]

Locillomycins are cyclic lipononapeptides assembled by a nonlinear hexamodular NRPS and have strong antibacterial activity. In this study, we genetically engineered Bacillus velezensis FZB42 as a surrogate host for the heterologous expression of the loc gene cluster for locillomycins. The fosmid N13 containing whole loc gene cluster was screened from the B. velezensis 916 genomic library. Subsequently, a spectinomycin resistance cassette, and the cassette fused with an IPTG inducible promoter Pspac, was introduced in the fosmid N13 using λ Red recombination system, respectively. The resulting fosmids, designated N13+Spec and N13+PSSpec, were used for the transformation of B. velezensis FZB42 to obtain derivative strains FZBNPLOC and FZBPSLOC. RT-PCR and qRT-PCR results revealed the efficient heterologous expression of the loc gene cluster in both derivative strains. Particularly, there was positive correlation between the derivative FZBPSLOC strain and the enhanced production of locillomycins upon addition of the inducer IPTG with the highest production of locillomycins at 15-fold more than that of B. velezensis 916. This overproduction of locillomycins was also related to the enhancement of antibacterial activity against methicillin-resistant Staphylococcus aureus, and exhibited moderate changes in its hemolytic activity. Together our findings demonstrate that the nonlinear hexamodular NRPS, encoded by the loc gene cluster from B. velezensis 916, is sufficient for the biosynthesis of cyclic lipononapeptide locillomycins in the surrogate host B. velezensis FZB42. Moreover, the FZBPSLOC strain will also be useful for further development of novel locillomycins derivatives with improved antibacterial activity. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study. Methods: Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups. Results: Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p < 0.001). PGRN and activin A levels were significantly negatively correlated with carbon monoxide diffusion capacity r = − 0.857 (p < 0.001) and r = − 0.757 (p < 0.001). Conclusion: Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF. [ABSTRACT FROM AUTHOR]

Astrocytoma is a common brain tumor that can occur in any part of the central nervous system. This tumor is extremely harmful to patients, and there are no clear studies on the risk factors for astrocytoma of the brain. This study was conducted based on the SEER database to determine the risk factors affecting the survival of patients with astrocytoma of the brain. Patients diagnosed with brain astrocytoma in the SEER database from 2004 to 2015 were screened by inclusion exclusion criteria. Final screened brain astrocytoma patients were classified into low grade and high grade according to WHO classification. The risk factors affecting the survival of patients with low-grade and high-grade brain astrocytoma were analyzed by univariate Kaplan–Meier curves and log-rank tests, individually. Secondly, the data were randomly divided into training set and validation set according to the ratio of 7:3, and the training set data were analyzed by univariate and multivariate Cox regression, and the risk factors affecting the survival of patients were screened and nomogram was established to predict the survival rates of patients at 3 years and 5 years. The area under the ROC curve (AUC value), C-index, and Calibration curve are used to evaluate the sensitivity and calibration of the model. Univariate Kaplan–Meier survival curve and log-rank test showed that the risk factors affecting the prognosis of patients with low-grade astrocytoma included Age, Primary site, Tumor histological type, Grade, Tumor size, Extension, Surgery, Radiation, Chemotherapy and Tumor number; risk factors affecting the prognosis of patients with high-grade astrocytoma include Age, Primary site, Tumor histological type, Tumor size, Extension, Laterality, Surgery, Radiation, Chemotherapy and Tumor number. Through Cox regression, independent risk factors of patients with two grades were screened separately, and nomograms of risk factors for low-grade and high-grade astrocytoma were successfully established to predict the survival rate of patients at 3 and 5 years. The AUC values of low-grade astrocytoma training set patients were 0.829 and 0.801, and the C-index was 0.818 (95% CI 0.779, 0.857). The AUC values of patients in the validation set were 0.902, 0.829, and the C-index was 0.774 (95% CI 0.758, 0.790), respectively. The AUC values of high-grade astrocytoma training set patients were 0.814 and 0.806, the C-index was 0.774 (95% CI 0.758, 0.790), the AUC values of patients in the validation set were 0.802 and 0.823, and the C-index was 0.766 (95% CI 0.752, 0.780), respectively, and the calibration curves of the two levels of training set and validation set were well fitted. This study used data from the SEER database to identify risk factors affecting the survival prognosis of patients with brain astrocytoma, which can provide some guidance for clinicians. [ABSTRACT FROM AUTHOR]

Photosynthesis of carbohydrates is the primary source of grain yield in wheat. Photosynthetic organs, especially flag leaves and awns play important roles in wheat growth and development. Genetic analysis of flag leaf posture, size and shape and presence/absence of awns was conducted using a set of 269 recombinant inbred lines (RILs) derived from Yanda1817 × Beinong6. Six agronomic traits comprising flag leaf angle (FLAN), flag leaf width (FLW), flag leaf length (FLL), the ratio of length/width of flag leaf (FLR), flag leaf area (FLA) and presence/absence of awns were evaluated in Shijiazhuang (2011, 2012 and 2013) and Beijing (2012). Using the available high-density single nucleotide polymorphism and simple sequence repeats (SSR) genetic linkage map, a total of 61 putative quantitative trait loci (QTL) for FLAN, FLW, FLL, FLR and FLA were detected on 16 of the 21 wheat chromosomes excluding 1D, 4B, 5D, 6A and 7A, with single QTL in different environments explaining 2.49-42.41 % of the phenotypic variation. Among the identified QTL, 17 were for FLAN, 11 for FLW, seven for FLL, 13 for FLR and 13 for FLA. Twenty-five (41 %) QTL were detected in at least two environments, while four QTL for FLW were detected in all environments. Thirty QTL were associated with higher number of flag leaf traits originated from Yanda1817 alleles, whereas the remaining 31 QTL were derived from Beinong6. In addition, pleiotropic effects were detected for QTL on chromosomes 2D, 3B, 4A, 4D, 5A, 5B, 6B, 6D and 7D that could serve as target regions for fine mapping and marker-assisted selection in wheat breeding programs. Genetic analysis revealed that the presence/absence of awns in the RIL population is controlled by the awn-inhibitor gene B1 linked to SSR marker Xgwm291 on the long arm of chromosome 5A. Our results also suggest that physiological traits FLL, FLW and FLA were significantly and positively correlated to spike length (SL), grain weight per spike and grain number per spike. FLR was significantly and positively related to SL but negatively related to grain width and grain thickness (GT). In addition, the awn trait was strongly and positively correlated to thousand grain weight, grain length and GT. [ABSTRACT FROM AUTHOR]

Key message: By applying comparative genomics analyses, a high-density genetic linkage map narrowed the powdery mildew resistance gene Pm41 originating from wild emmer in a sub-centimorgan genetic interval. Abstract: Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici, results in large yield losses worldwide. A high-density genetic linkage map of the powdery mildew resistance gene Pm41, originating from wild emmer ( Triticum turgidum var. dicoccoides) and previously mapped to the distal region of chromosome 3BL bin 0.63-1.00, was constructed using an F recombinant inbred line population derived from a cross of durum wheat cultivar Langdon and wild emmer accession IW2. By applying comparative genomics analyses, 19 polymorphic sequence-tagged site markers were developed and integrated into the Pm41 genetic linkage map. Ultimately, Pm41 was mapped in a 0.6 cM genetic interval flanked by markers XWGGC1505 and XWGGC1507, which correspond to 11.7, 19.2, and 24.9 kb orthologous genomic regions in Brachypodium, rice, and sorghum, respectively. The XWGGC1506 marker co-segregated with Pm41 and could be served as a starting point for chromosome landing and map-based cloning as well as marker-assisted selection of Pm41. Detailed comparative genomics analysis of the markers flanking the Pm41 locus in wheat and the putative orthologous genes in Brachypodium, rice, and sorghum suggests that the gene order is highly conserved between rice and sorghum. However, intra-chromosome inversions and re-arrangements are evident in the wheat and Brachypodium genomic regions, and gene duplications are also present in the orthologous genomic regions of Pm41 in wheat, indicating that the Brachypodium gene model can provide more useful information for wheat marker development. [ABSTRACT FROM AUTHOR]

Key message: Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars. [ABSTRACT FROM AUTHOR]

Key message: A new spot blotch (Bipolaris sorokiniana) resistance gene Sb4 was mapped in a genomic interval of 1.34 Mb on wheat chromosome 4BL. Spot blotch, caused by Bipolaris sorokiniana, has emerged as a serious concern for cultivation of wheat in warmer and humid regions of the world, which results in substantial yield losses and descends with quality. In this study, we identified and mapped a spot blotch resistance gene, designated as Sb4, against B. sorokiniana in wheat. Bulked segregant RNA-Seq (BSR-Seq) analysis and single-nucleotide polymorphism mapping showed that Sb4 is located on the long arm of chromosome 4B. A genetic linkage map of Sb4 was constructed using an F4 mapping population developed from the cross between 'GY17' and 'Zhongyu1211,' and Sb4 was delimited in a 7.14-cM genetic region on 4BL between markers B6811 and B6901. Using the Chinese Spring reference sequences of chromosome arm 4BL, 13 new polymorphic markers were developed. Finally, Sb4 was mapped in a 1.19-cM genetic interval corresponding to a 1.34-Mb physical genomic region of Chinese Spring chromosome 4BL containing 21 predicted genes. This study provides a foundational step for further cloning of Sb4 using a map-based approach. [ABSTRACT FROM AUTHOR]

Current remote collaborative systems in manufacturing are mainly based on video-conferencing technology. Their primary aim is to transmit manufacturing process knowledge between remote experts and local workers. However, it does not provide the experts with the same hands-on experience as when synergistically working on site in person. The mixed reality (MR) and increasing networking performances have the capacity to enhance the experience and communication between collaborators in geographically distributed locations. In this paper, therefore, we propose a new gesture-based remote collaborative platform using MR technology that enables a remote expert to collaborate with local workers on physical tasks. Besides, we concentrate on collaborative remote assembly as an illustrative use case. The key advantage compared to other remote collaborative MR interfaces is that it projects the remote expert's gestures into the real worksite to improve the performance, co-presence awareness, and user collaboration experience. We aim to study the effects of sharing the remote expert's gestures in remote collaboration using a projector-based MR system in manufacturing. Furthermore, we show the capabilities of our framework on a prototype consisting of a VR HMD, Leap Motion, and a projector. The prototype system was evaluated with a pilot study comparing with the POINTER (adding AR annotations on the task space view through the mouse), which is the most popular method used to augment remote collaboration at present. The assessment adopts the following aspects: the performance, user's satisfaction, and the user-perceived collaboration quality in terms of the interaction and cooperation. Our results demonstrate a clear difference between the POINTER and 2.5DHANDS interface in the performance time. Additionally, the 2.5DHANDS interface was statistically significantly higher than the POINTER interface in terms of the awareness of user's attention, manipulation, self-confidence, and co-presence. [ABSTRACT FROM AUTHOR]

Key message: We isolated a novel allele associated with grain length and grain weight in wheat, TaGL3-5A-G. The TaGL3-5A-G allele frequency is low in wheat, so it has potential for breeding. Selection of large-grain wheat showing big grain sink potential and strong sink activity is becoming an important objective in breeding programs. Here, we cloned a wheat TaGL3-5A gene that was orthologous to rice GL3 and was phylogenetically clustered with both monocot PPKL1 and its expression pattern was similar to grain size change at early and middle stages of seed development. The isolated TaGL3-5A genomic sequence was 10,227 bp long and included 21 exons and 20 introns. Alignment of the TaGL3-5A sequences in Beinong 6 and Yanda 1817 showed a G/A substitution in the 11th exon (position 5946) that would lead to an amino acid change (Met/Ile). Subsequently, a KASP marker was designed based on this SNP. Genotyping of RILs showed that TaGL3-5A was located on the wheat 5AL chromosome and was colocated with a significant grain length QTL in three independent environments and mean value. Association analysis revealed that the TaGL3-5A-G allele was significantly correlated with longer grains and higher thousand-kernel weight. Haplotype association analysis indicated that TaGL3-5A-G could enhance grain traits in combination with TaGS5-3A and TaGW2-6B. The frequency of TaGL3-5A-G was higher in modern cultivars than in landraces but was still low in major Chinese wheat production areas. Additionally, the frequency of the TaGL3-5A-G allele in hexaploid wheat was slightly lower than in Triticum dicoccoides and much lower than in Triticum turgidum. Hence, T. dicoccoides and T. turgidum represent valuable resources for transferring the TaGL3-5A-G allele into common wheat, which should lead to longer grain length. [ABSTRACT FROM AUTHOR]

Key message : A stripe rust resistance gene YrZH22 was mapped by combined BSR-Seq and comparative genomics analyses to a 5.92 centimorgan (cM) genetic interval spanning a 4 Mb physical genomic region on wheat chromosome 4BL1. Abstract: Stripe rust, caused by Puccinia striiformis f. sp. tritici (PST), is one of the most destructive diseases of wheat and severely threatens wheat production worldwide. The widely grown Chinese wheat cultivar Zhoumai 22 is highly resistant to the current prevailing PST race CYR34 (V26). Genetic analysis of F and F recombinant inbred line (RIL) populations indicated that adult-plant stripe rust resistance in Zhoumai 22 is controlled by a single gene, temporarily designated YrZH22. By applying bulked segregant RNA-Seq (BSR-Seq), 7 SNP markers were developed and SNP mapping showed that YrZH22 is located between markers WGGB105 and WGGB112 on chromosome arm 4BL. The corresponding genomic regions of the Chinese Spring 4BL genome assembly and physical map of Aegilops tauschii 4DL were selected for comparative genomics analyses to develop nine new polymorphic markers that were used to construct a high-resolution genetic linkage map of YrZH22. YrZH22 was delimited in a 5.92 cM genetic interval between markers WGGB133 and WGGB146, corresponding to 4.1 Mb genomic interval in Chinese Spring 4BL and a 2.2 Mb orthologous genomic region in Ae. tauschii 4DL. The genetic linkage map of YrZH22 will be valuable for fine mapping and positional cloning of YrZH22, and can be used for marker-assisted selection in wheat breeding. [ABSTRACT FROM AUTHOR]

Key message: Spot blotch disease resistance gene Sb3 was mapped to a 0.15 centimorgan (cM) genetic interval spanning a 602 kb physical genomic region on chromosome 3BS. Abstract: Wheat spot blotch disease, caused by B. sorokiniana, is a devastating disease that can cause severe yield losses. Although inoculum levels can be reduced by planting disease-free seed, treatment of plants with fungicides and crop rotation, genetic resistance is likely to be a robust, economical and environmentally friendly tool in the control of spot blotch. The winter wheat line 621-7-1 confers immune resistance against B. sorokiniana. Genetic analysis indicates that the spot blotch resistance of 621-7-1 is controlled by a single dominant gene, provisionally designated Sb3. Bulked segregant analysis (BSA) and simple sequence repeat (SSR) mapping showed that Sb3 is located on chromosome arm 3BS linked with markers Xbarc133 and Xbarc147. Seven and twelve new polymorphic markers were developed from the Chinese Spring 3BS shotgun survey sequence contigs and 3BS reference sequences, respectively. Finally, Sb3 was mapped in a 0.15 cM genetic interval spanning a 602 kb physical genomic region of Chinese Spring chromosome 3BS. The genetic and physical maps of Sb3 provide a framework for map-based cloning and marker-assisted selection (MAS) of the spot blotch resistance. [ABSTRACT FROM AUTHOR]

Key message: A powdery mildew resistance gene MlHLT derived from a Chinese wheat landrace maps within a 3.6 centimorgan (cM) genetic interval spanning a 13.4 megabase (Mb) physical genomic region on chromosome 1DS. Abstract: Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici ( Bgt) is a devastating disease that can cause severe yield losses. Chinese wheat landrace Hulutou confers nearly immune resistance against prevailing Bgt isolate E09 in Beijing. Genetic analysis indicate that the powdery mildew resistance of Hulutou is controlled by a single dominant gene, provisionally designated MlHLT. Bulked segregant analysis(BSA) and simple sequence repeat (SSR) mapping showed that MlHLT is located on chromosome arm 1DS between markers Xgwm337 and Xcfd83/ Xcfd72. By applying comparative genomics analysis, collinearity genomic regions of the MlHLT locus on Aegilops tauschii chromosome 1DS were identified in Brachypodium distachyon chromosome 2, rice chromosome 5 and sorghum chromosome 9, respectively. Three new polymorphic markers were developed using the draft genome sequences and the extended single nucleotide polymorphism (SNP) marker sequences of Ae. tauschii accession AL8/78, as well as the Triticum aestivum cv. Chinese Spring 454 contig sequences and the International Wheat Genome Sequencing Consortium (IWGSC) survey sequences. MlHLT mapped into a 3.6 cM genetic interval spanning 13.4 Mb physical genomic region containing seven contigs (ctg220, ctg4623, ctg1063, ctg5929, ctg3163, ctg699 and ctg1065) on 1DS that has synteny with a 369.8 kb genomic region in Brachypodium, a 380.8 kb genomic region in rice and a 298.4 kb genomic region in sorghum. The genetic and physical maps of MlHLT provide framework for map-based cloning and marker-assisted selection (MAS) of the powdery mildew resistance gene MlHLT in Hulutou. [ABSTRACT FROM AUTHOR]