Two functional CC-NBS-LRR proteins from rye chromosome 6RS confer differential age-related powdery mildew resistance to wheat.

Rye (Secale cereale), a valuable relative of wheat, contains abundant powdery mildew resistance (Pm) genes. Using physical mapping, transcriptome sequencing, barley stripe mosaic virus-induced gene silencing, ethyl methane sulfonate mutagenesis, and stable transformation, we isolated and validated two coiled-coil, nucleotide-binding site and leucine-rich repeat (CC-NBS-LRR) alleles, PmTR1 and PmTR3, located on rye chromosome 6RS from different triticale lines. PmTR1 confers age-related resistance starting from the three-leaf stage, whereas its allele, PmTR3, confers typical all-stage resistance, which may be associated with their differential gene expression patterns. Overexpression in Nicotiana benthamiana showed that the CC, CC-NBS, and CC-LRR fragments of PMTR1 induce cell death, whereas in PMTR3 the CC and full-length fragments perform this function. Luciferase complementation imaging and pull-down assays revealed distinct interaction activities between the CC and NBS fragments. Our study elucidates two novel rye-derived Pm genes and their derivative germplasm resources and provides novel insights into the mechanism of age-related resistance, which can aid the improvement of resistance against wheat powdery mildew.

1D/2D core-shell structure Ni-Mo-S@NiFe LDH grown on nickel foam: a bifunctional electrocatalyst for efficient oxygen evolution and urea oxidation reactions.

The construction of bifunctional catalysts for the oxygen evolution reaction (OER) and urea oxidation reaction (UOR) is important for accelerating the development of the hydrogen economy. Herein, a novel three-dimensional core-shell heterostructure (Ni-Mo-S@NiFeLDH/NF) was prepared by vertically growing NiFe layered double hydroxide (NiFe LDH) nanosheets on nickel foam (NF)-supported arrays of Ni-Mo-S (Ni3S2, Ni0.96S, Mo2S3) nanorods via a hydrothermal-sulfide-hydrothermal process. Benefiting from the unique core-shell structure with numerous exposed active sites, the optimized Ni-Mo-S@NiFe LDH/NF shows excellent OER/UOR activity, with an overpotential of only 274 mV for OER to reach 100 mA cm-2 and 1.318 V for UOR to reach 10 mA cm-2. Moreover, the assembled Ni-Mo-S@NiFe LDH||Pt/C urea electrolytic system requires only 1.348 V to achieve 10 mA cm-2, as much as 159 mV lower than pure water electrolysis. This work provides an idea for researching NiFe LDH-based OER/UOR bifunctional catalysts.

Chlorogenic Acid Alleviates LPS-Induced Inflammation and Oxidative Stress by Modulating CD36/AMPK/PGC-1α in RAW264.7 Macrophages.

Chlorogenic acid (CGA) is a bioactive substance with anti-inflammatory activities. Clusters of CD36 have been suggested to be widely involved in inflammatory damage. However, the mechanism of CGA protecting against LPS-induced inflammation involving the CD36 regulation is unclear. Here, we demonstrated that CGA protected against LPS-induced cell death and decreased the production of ROS. Moreover, the SOD, CAT, and GSH-Px activities were also upregulated in CGA-treated cells during LPS stimulation. CGA reduced COX-2 and iNOS expression and IL-1ß, IL-6, and TNF-α secretion in LPS-stimulated RAW264.7 macrophages. In addition, CGA treatment widely involved in immune-related signaling pathways, including NF-κB signaling, NOD-like receptor signaling, and IL-17 signaling using transcriptomic analysis and CD36 also markedly reduced during CGA pretreatment in LPS-induced RAW264.7 cells. Furthermore, the CD36 inhibitor SSO attenuated inflammation and oxidative stress by enabling activation of the AMPK/PGC-1α cascade. These results indicate that CGA might provide benefits for the regulation of inflammatory diseases by modulating CD36/AMPK/PGC-1α to alleviate oxidative stress.

The First Crested Duck Genome Reveals Clues to Genetic Compensation and Crest Cushion Formation.

The Chinese crested (CC) duck is a unique indigenous waterfowl breed, which has a crest cushion that affects its survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed that genes related to tissue repair, immune function, and tumors were under strong positive selection, indicating that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We also assembled a Chinese spot-billed (Csp-b) duck genome, and detected the structural variations (SVs) in the genome assemblies of three ducks (i.e., CC duck, Csp-b duck, and Peking duck). Functional analysis revealed that several SVs were related to the immune system of CC ducks, further strongly suggesting that genetic compensation in the anti-tumor and immune systems supports the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

Phosphoproteome Reveals Extracellular Regulated Protein Kinase Phosphorylation Mediated by Mitogen-Activated Protein Kinase Kinase-Regulating Granulosa Cell Apoptosis in Broody Geese.

Geese have strong brooding abilities, which severely affect their egg-laying performance. Phosphorylation is widely involved in regulating reproductive activities, but its role in goose brooding behavior is unclear. In this study, we investigated differences in the phosphoprotein composition of ovarian tissue between laying and brooding geese. Brooding geese exhibited ovarian and follicular atrophy, as well as significant oxidative stress and granulosa cell apoptosis. We identified 578 highly phosphorylated proteins and 281 lowly phosphorylated proteins, and a KEGG pathway analysis showed that these differentially phosphorylated proteins were mainly involved in cell apoptosis, adhesion junctions, and other signaling pathways related to goose brooding behavior. The extracellular regulated protein kinase (ERK)-B-Cell Lymphoma 2(BCL2) signaling pathway was identified as playing an important role in regulating cell apoptosis. The phosphorylation levels of ERK proteins were significantly lower in brooding geese than in laying geese, and the expression of mitogen-activated protein kinase kinase (MEK) was downregulated. Overexpression of MEK led to a significant increase in ERK phosphorylation and BCL2 transcription in H2O2-induced granulosa cells (p < 0.05), partially rescuing cell death. Conversely, granulosa cells receiving MEK siRNA exhibited the opposite trend. In conclusion, geese experience significant oxidative stress and granulosa cell apoptosis during brooding, with downregulated MEK expression, decreased phosphorylation of ERK protein, and inhibited expression of BCL2.

Artificial light at night, MRI-based measures of brain iron deposition and incidence of multiple mental disorders.

BACKGROUND: Epidemiologic evidence on whether iron accumulation in brain modified the association between artificial light at night (ALAN) and incident mental disorders is lacking. The authors aims to investigate modification of brain iron deposition on the associations of ALAN with multiple mental disorders in the middle-aged and older adults. METHODS: This prospective study used data from the UK Biobank. ALAN was drawn from satellite datasets. Susceptibility-weighted magnetic resonance imaging was used to ascertain iron content of each brain region. T2* signal loss was used as indices of iron deposition. The main outcomes are impacts of ALAN exposure on onset of wide spectrum of physician-diagnosed mental disorders, which was estimated by time-varying Cox proportional hazard model. The authors further conducted stratified analyses by levels of iron brain deposition to examine the potential modifying effects. RESULTS: Among 298,283 participants followed for a median of 10.91 years, higher ALAN exposure was associated with increased risk of mental disorders. An IQR (11.37 nW/cm2/sr) increase in annual levels of ALAN was associated with an HR of 1.050 (95 % CI: 1.034,1.066) for any mental disorder, 1.076 (95 % CI: 1.053,1.099) for substance use disorder, and 1.036 (95 % CI: 1.004,1.069) for depression disorder in fully adjusted models. The exposure-response curves showed steeper trends at lower ALAN levels and a plateau at higher exposures. The associations were stronger in participants with high iron deposition in left hippocampus, left accumbens and left pallidum. CONCLUSIONS: ALAN was associated with multiple mental disorders in the middle-aged and older adults, and the findings indicated stricter standards of ALAN is needed and targeted preventive measures are warranted, especially with high brain iron deposition.

Function discovery of a non-ribosomal peptide synthetase-like encoding gene in the nematode-trapping fungus Arthrobotrys oligospora.

In this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.

Association of residual feed intake with intestinal microbiome and metabolome in laying period of ducks.

Introduction: Residual feed intake (RFI) is a indicator to evaluate animal feed. This experiment was explored to study the relationship between intestinal microbiome and metabolome of ducks with different residual feed intake during laying period. Methods: A total of 300 Shaoxing ducks aged 42 weeks were randomly selected and fed a diet of 60 d. At the end of the trial, 20 samples were selected according to the phenotype of RFI and divided into two groups (HRFI and LRFI). The cecal microbiota composition was explored by 16S ribosomal RNA gene sequencing and rectal metabolomics uses liquid chromatography-mass spectrometry (LC-MS) to identify the composition of metabolites in a non-targeted manner. Results: Results show feed intake and feed conversion ratio in the group HRFI were significantly higher than those in the group LRFI (p < 0.05). Chao1 indices were higher in the group LRFI than in the HRFI (p < 0.05), Shannon and Simpson indices were higher in the group LRFI than in the HRFI (p < 0.01). After linear discriminant analysis effect size (p < 0.05, LDA score > 3), Rikenellaceae, Rikenellaceae_RC9_gut_group, Lactobacillales and Ruminococcus_2, etc. were significantly enriched in the group LRFI at the genus level, while Prevotellaceae_NK3B31_group and Bacteria were significantly enriched in the group HRFI. After LC-MS analysis we found 338 metabolic difference products and 10 metabolic pathways, including the ABC transporter system, cysteine and methionine metabolism, arginine and proline metabolism, and vitamin B6 metabolism, were identified to be associated with the significantly differentially expressed between the groups LRFI and HRFI (p < 0.05). We hypothesize that the difference between ducks with different RFIs is mainly due to the fact that ducks with LRFI have more SCFAs-producing bacteria in their gut microorganisms, which regulate the RFI of animals. This process we found that Phascolarctobaterium and Anaerobiospirillum may provide energy for ABC transporter system by producing SCFAs, and regulate RFI to improve feed utilization efficiency. Discussion: These results revealed the relationship between microbiome and metabonomics in laying ducks with different RFI, and provided theoretical basis for further study on the relationship between them.

Population Structure and Selection Signatures of Domestication in Geese.

The goose is an economically important poultry species and was one of the first to be domesticated. However, studies on population genetic structures and domestication in goose are very limited. Here, we performed whole genome resequencing of geese from two wild ancestral populations, five Chinese domestic breeds, and four European domestic breeds. We found that Chinese domestic geese except Yili geese originated from a common ancestor and exhibited strong geographical distribution patterns and trait differentiation patterns, while the origin of European domestic geese was more complex, with two modern breeds having Chinese admixture. In both Chinese and European domestic geese, the identified selection signatures during domestication primarily involved the nervous system, immunity, and metabolism. Interestingly, genes related to vision, skeleton, and blood-O2 transport were also found to be under selection, indicating genetic adaptation to the captive environment. A forehead knob characterized by thickened skin and protruding bone is a unique trait of Chinese domestic geese. Interestingly, our population differentiation analysis followed by an extended genotype analysis in an additional population suggested that two intronic SNPs in EXT1, an osteochondroma-related gene, may plausibly be sites responsible for knob. Moreover, CSMD1 and LHCGR genes were found to be significantly associated with broodiness in Chinese domestic geese and European domestic geese, respectively. Our results have important implications for understanding the population structure and domestication of geese, and the selection signatures and variants identified in this study might be useful in genetic breeding for forehead knob and reproduction traits.

Dietary supplementation of coated sodium butyrate improves growth performance of laying ducks by regulating intestinal health and immunological performance.

Introduction: This study was conducted to assess the effects of dietary supplementation of coated sodium butyrate (CSB) on the growth performance, serum antioxidant, immune performance, and intestinal microbiota of laying ducks. Methods: A total of 120 48-week-old laying ducks were randomly divided into 2 treatment groups: the control group (group C fed a basal diet) and the CSB-treated group (group CSB fed the basal diet + 250 g/t of CSB). Each treatment consisted of 6 replicates, with 10 ducks per replicate, and the trial was conducted for 60 days. Results: Compared with the group C, the group CSB showed a significant increase in the laying rate (p<0.05) of the 53-56 week-old ducks. Additionally, the serum total antioxidant capacity, superoxide dismutase activity and immunoglobulin G level were significantly higher (p<0.05), while the serum malondialdehyde content and tumor necrosis factor (TNF)-a level were significantly lower (p<0.05) in the serum of the group CSB compared to the group C. Moreover, the expression of IL-1b and TNF-a in the spleen of the group CSB was significantly lower (p<0.05) compared to that of the group C. In addition, compared with the group C, the expression of Occludin in the ileum and the villus height in the jejunum were significantly higher in the group CSB (p<0.05). Furthermore, Chao1, Shannon, and Pielou-e indices were higher in the group CSB compared to the group C (p<0.05). The abundance of Bacteroidetes in the group CSB was lower than that in the group C (p<0.05), while the abundances of Firmicutes and Actinobacteria were higher in the group CSB compared to the group C (p<0.05). Conclusions: Our results suggest that the dietary supplementation of CSB can alleviate egg-laying stress in laying ducks by enhancing immunity and maintaining the intestinal health of the ducks.

Erratum to 'Evolution and genotypic characteristics of small cell lung cancer transformation in non-small cell lung carcinomas' [Journal of the National Cancer Center, 1 (2021), 4: 153-162].

[This corrects the article DOI: 10.1016/j.jncc.2021.11.001.].

A Novel Computational Framework for Predicting the Survival of Cancer Patients With PD-1/PD-L1 Checkpoint Blockade Therapy.

Background: Immune checkpoint inhibitors (ICIs) induce durable responses, but only a minority of patients achieve clinical benefits. The development of gene expression profiling of tumor transcriptomes has enabled identifying prognostic gene expression signatures and patient selection with targeted therapies. Methods: Immune exclusion score (IES) was built by elastic net-penalized Cox proportional hazards (PHs) model in the discovery cohort and validated via four independent cohorts. The survival differences between the two groups were compared using Kaplan-Meier analysis. Both GO and KEGG analyses were performed for functional annotation. CIBERSORTx was also performed to estimate the relative proportion of immune-cell types. Results: A fifteen-genes immune exclusion score (IES) was developed in the discovery cohort of 65 patients treated with anti-PD-(L)1 therapy. The ROC efficiencies of 1- and 3- year prognosis were 0.842 and 0.82, respectively. Patients with low IES showed a longer PFS (p=0.003) and better response rate (ORR: 43.8% vs 18.2%, p=0.03). We found that patients with low IES enriched with high expression of immune eliminated cell genes, such as CD8+ T cells, CD4+ T cells, NK cells and B cells. IES was positively correlated with other immune exclusion signatures. Furthermore, IES was successfully validated in four independent cohorts (Riaz's SKCM, Liu's SKCM, Nathanson's SKCM and Braun's ccRCC, n = 367). IES was also negatively correlated with T cell-inflamed signature and independent of TMB. Conclusions: This novel IES model encompassing immune-related biomarkers might serve as a promising tool for the prognostic prediction of immunotherapy.

Construction and validation of an immunoediting-based optimized neoantigen load (ioTNL) model to predict the response and prognosis of immune checkpoint therapy in various cancers.

BACKGROUND: Only a minority of patients clinically benefit from immune checkpoint therapy. Tumor clones with neoantigens have immunogenicity; therefore, they are eliminated by T-cell-mediated immune editing. Identifying neoantigen clones with the ability to induce immune elimination may better predict the clinical outcome of immunotherapy. METHODS: We developed ioTNL model, which indicates the immunoediting-based optimized tumor neoantigen load, by identifying tumor clones that could induce immune elimination. Data of more than two hundred patients from our patient pool and previously reported studies who underwent anti-PD-(L)1 therapy were collected to validate the prediction performance of ioTNL model. Clonal architectures, immune editing scores and ioTNL scores were identified. The association between the response as well as prognosis and the ioTNL were evaluated. Panel sequencing of genes from 2,469 patients within 20 cancer types was performed to profile the landscape of immunoediting. RESULTS: As expected, the ioTNL score could predict the response in patients who underwent immune checkpoint inhibitor (ICI) immunotherapy for various cancers, including non-small cell lung cancer (NSCLC; p = 0.0066), skin cutaneous melanoma (SKCM; p = 0.026) and nasopharyngeal carcinoma (NPC; p = 0.0025). Patients with a high ioTNL score demonstrated longer survival than those with a low score. We verified the ioTNL on our cohort through panel sequencing and found that the ioTNL was associated with the response (p = 0.025) and prognosis (p = 0.00082) in anti-PD-(L)1 monotherapy. In addition, we found that the immune editing score correlated with the tumor mutation burden (TMB) and the objective response rate of immunotherapy. CONCLUSIONS: Identifying neoantigen clones with the ability to induce immune elimination would better predict the efficacy of immunotherapy. We have proved that the reliable method of ioTNL can be applied to whole-exome sequencing (WES) and panel data and would have a broad application in precision diagnosis in immunotherapy.

SDK1-ALK Fusion in a Lung Adenocarcinoma Patient With Excellent Response to ALK Inhibitor Treatment: A Case Report.

Background: Rearrangements of Anaplastic lymphoma kinase (ALK) have been discovered as a novel driver mutation in patients with non-small-cell lung cancer (NSCLC). Patients' responses to ALK tyrosine kinase inhibitors (TKIs) may vary depending on the variations of ALK rearrangements they have. It is imperative for clinicians to identify druggable ALK fusions in routine practice. Case Presentation: In this study, we discovered a rare ALK rearrangement type (SDK1-ALK) in a Chinese lung adenocarcinoma patient who responded well to ALK inhibitor SAF-189s. The positive expression of ALK in lung biopsy tissue was verified by IHC analysis. A new SDK1-ALK fusion was discovered using NGS. The patient was treated with SAF-189s (160 mg per day) as a first-line therapy and went into continuous remission, with a 12 months progression-free survival at the last follow-up. Conclusion: This is the first case of SDK1-ALK fusion with an excellent response to an ALK inhibitor, which will provide better understanding of ALK-TKI applications for NSCLC patients with ALK fusion in the future.

Identification of a prognostic immune-related signature for small cell lung cancer.

PURPOSE: As a subgroup of lung cancer, small cell lung cancer (SCLC) is characterized by a short tumor doubling time, high rates of early occurred distant cancer spread, and poor outcomes. Despite its exquisite sensitivity to chemotherapy and radiotherapy, acquired drug resistance and tumor progression are typical. This study aimed to develop a robust signature based on immune-related genes to predict the outcome of patients with SCLC. METHODS: The expression data of 77 SCLC patients from George's cohort were divided into training set and testing set, and 1534 immune-related genes from ImmPort database were used to generate and validate the signature. Cox proportional hazards and the Kaplan-Meier analysis were used for developing and testing the prognostic signature. Single-sample gene set enrichment analysis was used to determine immune cell infiltration phenotypes. RESULTS: A 10-gene model comprising NR3C1, NR1D2, TANK, ARAF, HDGF, INHBE, LRSAM1, PLXNA1, PML, and SP1 with the highest frequency after 1000 interactions, was chosen to construct immune-related signature. This signature showed robust predictive value for SCLC patients' survival in both training and testing sets. This signature was weakly associated with the clinic pathological values like TNM stage. Furthermore, patients with low risk presented with activation of immune signal pathways, and specific immune cell infiltration with high levels of CD56bright NK cells but low levels of CD8+ T cells, mast cells, and helper T cells. CONCLUSION: The present study developed immune-related signature that may help predict the prognosis of SCLC patients, which reflects an unappreciated level of heterogeneity of immunophenotype associated with diverse prognosis for specific subsets in this highly lethal cancer type.

The specificity protein 3 (SP3) gene in ducks (Anas platyrhynchos): cloning, characterization and expression during viral infection.

Specificity Protein 3 (SP3) is a newly identified regulator of tumor growth and invasiveness in humans. In this study, we identified and characterized the function of duck SP3 (duSP3). The full-length cDNA sequence of the duSP3 gene was cloned via rapid amplification of cDNA ends. It contained 2468 nucleotides, including a 111 base pair (bp) 5'-untranslated region (UTR), 215 bp 3'-UTR, and 2142 bp open reading frame (ORF), which encoded a 713 amino acid (AA) strongly conserved with Avian SP3. Tissue specificity analysis demonstrated that duSP3 was constitutively expressed in the eight tissues tested: liver, spleen, lung, heart, kidney, thymus, breast, and leg; and low expression levels were observed in all tissues, except the spleen and thymus. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that duSP3 expression rapidly increased in vitro after stimulation with both the hepatitis virus (DHV-1) and polyriboinosinic polyribocytidylic acid (poly(I:C)). However, the expression under these treatments varied in kidney and liver tissues; in the liver, duSP3 increased significantly at 36 h after the DHV-1 treatment and peaked at 72 h after poly(I:C) stimulation. These results suggested that SP3 may play a positive role in immune responses against viral infections in ducks.

HLA loss of heterozygosity-mediated discordant responses to immune checkpoint blockade in squamous cell lung cancer with renal metastasis.

Despite the significant success of immune checkpoint blockade therapy in advanced non-small-cell lung cancer compared with chemotherapy, efficacy varies greatly across patients, and acquired resistance frequently occurs. In particular, during immunotherapy, the dynamic changes in molecular events have not been characterized. The authors report a case of squamous cell lung carcinoma with renal metastasis, treated with pembrolizumab, in which the primary tumor and rare renal metastases showed different responses. Using whole-exome sequencing, the authors found loss of heterogeneity in HLA genes in all tumors and high levels of intratumor heterogeneity in metastases. The increased levels of HLA loss led to therapy resistance during tumor evolution. In addition to tumor mutational burden and PD-L1, HLA loss of heterozygosity and intratumor heterogeneity should be taken into consideration during immunotherapy.

Evolution and genotypic characteristics of small cell lung cancer transformation in non-small cell lung carcinomas.

Background: Small cell lung cancer (SCLC) transformation had previously been reported mainly in epidermal growth factor receptor (EGFR) mutant adenocarcinoma. However, the underlying genomic profile remains unclear. Our study aimed to find the evolution and genotypic characteristic of SCLC transformation. Methods: Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer (NSCLC) patients were included. Whole exome sequencing (WES) of both primary and transformed re-biopsy lesions was conducted on 12 patients. Clinical characteristics were analyzed using R software (v.3.6.1). Results: Our study included 31 patients, of whom, three had lung squamous cell carcinoma, 6 patients did not carry EGFR mutations, and 30 patients received chemotherapy for SCLCs. The disease control rate (DCR) was 96.7%, and the median progression-free survival (PFS) was 4.03 months. The median time to transformation was 33.07 months, and the median overall survival (OS) was 62.08 months. Somatic mutation analysis showed that besides TP53, RB1, and EGFR, there was a high occurrence of mutations to CSMD3 and ADAMTS19, especially in the EGFR-wild type (EGFR-wt) group. Concerning mutational signature, the EGFR-mutant (EGFR-mut) transformed group favored an apolipoprotein B (APOBEC) mRNA editing catalytic polypeptide-like-associated mutation pattern (P = 0.16). DNA damage repair (DDR)-related signatures were significantly enriched in the EGFR-wt transformed group (P = 0.034). Additionally, clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree. Transformed SCLCs are not sensitive to immunotherapy, possibly due to increased tumor heterogeneity. Conclusions: Our results indicate that the EGFR-wt patients could also transform to SCLCs, but they have different genetic features with EGFR-mut patients. SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.

Effects of immunopotentiators on biochemical parameters, proinflammatory cytokine, and nonspecific immune responses in Shaoxing ducklings.

Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, misuse of antibiotics imperils the development of animal husbandry and human health all over the world, and it is important to find reliable alternatives to antibiotics to reduce the use of antibiotics. In this study, 22 potential immunopotentiators were screened on the levels of apoptosis and inflammatory factor in duck embryo fibroblast cells (DEFs). The results indicated that interferon (IFN)-ß and tumor necrosis factor-α gene transcriptions were significantly upregulated, while interleukin (IL)-2 and Bcl2 mRNA levels were significantly decreased during 22 immunopotentiators treatment. Besides, the expression level of IL-1ß mRNA showed significant increase during dihydromyricetin, chlorogenic acid, naringin, imiquimod, thymopentin, ß-D-Glucan, astragalus polysacharin, astragalus saponin I, astragalus flavone, curcumin, CpG-DNA-2, and LPS treatment. And the level of caspase 3 protein was significantly upregulated with treating chlorogenic acid, ß-D-Glucan, astragalus polysacharin, astragalus flavone, curcumin, CpG-DNA-2, chicken IgG, LPS, and poly(I:C). These results indicated that chlorogenic acid, ß-D-Glucan, astragalus flavone, CpG-DNA-2, and chicken IgG have the positive immune regulation effects on duck DEFs. Thus, the 5 immunopotentiators were chosen to further verify their immunomodulatory function in vivo. The results showed that the activity of serum AST was significantly downregulated during all immunopotentiators treatments excepting for ß-D-Glucan, and the activities of serum IL12p40, IL-1ß, IFN-α, and IFN-ß were significantly increased compared with the control group. Five immunopotentiators also induced the duck's pattern recognition receptors and inflammatory factor gene expression. In addition, 5 immunopotentiators could facilitate the contents of serum caspase 3, iNOSm and COX2 and reduce the Bcl2. These results suggested that these 5 immunopotentiators could enhance duck innate immune responses. Taken together, our study not only screened out 5 kinds of duck innate immune immunopotentiators but also initially clarified their underlying mechanism of action, which provide a new insight for the development of efficient approaches to prevent the duck disease from pathogen infections.

Lung adenocarcinoma harboring rare epidermal growth factor receptor L858R and V834L mutations treated with icotinib: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations. However, patients with rare, even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors, which bring uncertainty to clinical treatment. CASE SUMMARY: A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain. Chest computed tomography revealed lung space-occupying lesions and multiple lymphadenectasis. Bronchoscopy and pathology suggested lung adenocarcinoma. Compound variation of EGFR gene (exon 21 L858R/V834L) was detected in both tissue and circulating tumor deoxyribonucleic acid samples. As a result of next-generation sequencing and her family's wishes, the patient was given oral treatment with icotinib hydrochloride (125 mg/d, tid) from March 21, 2019 and has achieved stable disease for the last 1 year. CONCLUSION: Non-small cell lung adenocarcinoma with EGFR L858R/V834L was treated successfully with icotinib, and it may be a new medication treatment option.