Value of the Air Bronchogram Sign and Other Computed Tomography Findings in the Early Diagnosis of Lung Adenocarcinoma.

OBJECTIVES: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD). METHOD: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed. RESULTS: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU. CONCLUSIONS: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded.

Genetic advances in Meniere Disease.

Meniere Disease (MD) is an idiopathic inner ear disease with complex etiology and pathogenesis, which is still unclear. With the development in gene analysis technology, the genetic research of MD has attracted extensive attention, resulting in a large number of studies on the research of the relationship between human genes and MD. This paper aims to review the studies on this topic in recent years. The studies mainly focused on the genetics of familial MD and the correlation between MD and potentially related functional genes. The results of these studies have demonstrated the complexity and diversity of the pathogenesis of MD with both genetic and epigenetic alterations, suggesting that MD might be related to inflammation, immunity, aqua and ion balance in the lymphatic fluid, virus infection, metabolism, and abnormal function of nerve conduction. The finding of rare mutations in TECTA, MYO7A and OTOG genes and other genes such as CDH23, PCDH15 and ADGRV1 in the same families suggest that the integrity of the stereocilia and their interaction with the tectorial and otolithic membranes could be involved in the pathophysiology of familial MD.

BEZ235 reduction of cisplatin resistance on wild-type EGFR non-small cell lung cancer cells.

Cisplatin, as a first-line chemotherapy drug for advanced wild-type epidermal growth factor receptor (wtEGFR) non-small cell lung cancer (NSCLC), often loses effectiveness because of acquired drug resistance. We found that ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) of DNA repair kinases and signal transduction molecules, protein kinase B (AKT)/target mammalian target of rapamycin (mTOR), were significantly phosphorylated in cisplatin-resistant wtEGFR NSCLC cell lines (H358R and A549R) than in their parental cells. Also, BEZ235 (dual phosphatidylinositol-3-kinase (PI3K)/mTOR inhibitor) significantly decreased the phosphorylation levels of these kinases/proteins, as detected by Western blot analysis. In H358R and A549R cells, the results of indirect immunofluorescence, single-cell gel electrophoresis, flow cytometry, methylthiazolyldiphenyl-tetrazolium bromide, clone formation assay, and scratch healing experiment showed that BEZ235 enhanced cisplatin-induced DNA damage and cell apoptosis, and effectively inhibited cellular proliferation/migration when combined with cisplatin. The data indicated that the abnormal activation of ATM/ATR/DNA-PKcs kinases and AKT/mTOR pathway might induce wtEGFR NSCLC cell resistance to cisplatin. The effects of the combination of BEZ235 and cisplatin suggested that BEZ235 should be considered as a combination therapy for patients with cisplatin-resistant wtEGFR NSCLC.

An APETALA2/ethylene responsive factor transcription factor GmCRF4a regulates plant height and auxin biosynthesis in soybean.

Plant height is one of the key agronomic traits affecting soybean yield. The cytokinin response factors (CRFs), as a branch of the APETALA2/ethylene responsive factor (AP2/ERF) super gene family, have been reported to play important roles in regulating plant growth and development. However, their functions in soybean remain unknown. This study characterized a soybean CRF gene named GmCRF4a by comparing the performance of the homozygous Gmcrf4a-1 mutant, GmCRF4a overexpression (OX) and co-silencing (CS) lines. Phenotypic analysis showed that overexpression of GmCRF4a resulted in taller hypocotyls and epicotyls, more main stem nodes, and higher plant height. While down-regulation of GmCRF4a conferred shorter hypocotyls and epicotyls, as well as a reduction in plant height. The histological analysis results demonstrated that GmCRF4a promotes epicotyl elongation primarily by increasing cell length. Furthermore, GmCRF4a is required for the expression of GmYUCs genes to elevate endogenous auxin levels, which may subsequently enhance stem elongation. Taken together, these observations describe a novel regulatory mechanism in soybean, and provide the basis for elucidating the function of GmCRF4a in auxin biosynthesis pathway and plant heigh regulation in plants.

Clinical and drug resistance characteristics of Providencia stuartii infections in 76 patients.

OBJECTIVES: To investigate the clinical and drug resistance characteristics of Providencia stuartii infections in the Huainan region of Anhui and provide a reference for the clinical selection of antimicrobial agents. METHODS: This single-center retrospective analysis included 76 patients with P. stuartii infection in Huainan during the period from October 2018 to March 2020. The hospital department in which the patients were treated and the drug susceptibility characteristics of the P. stuartii isolates were recorded. RESULTS: Among the 76 patients, the lung was the most common site of infection, and intensive care unit was the main hospital department. Extended spectrum beta-lactamase screening revealed expression by all 76 isolates of P. stuartii. Of the 76 isolates, 92.1% exhibited multiple drug resistance or extensive drug resistance. P. stuartii isolates were sensitive to cefepime and imipenem, but not to other beta-lactam antibiotics. Twenty isolates were resistant to all 21 types of antibiotics. Of the 20 patients infected with extensively drug-resistant isolates, nine (45%) died. CONCLUSIONS: Drug resistance is increasing in P. stuartii. The antimicrobial agent imipenem may be effective for treatment of P. stuartii infections. Fluoroquinolones, aminoglycosides, and fourth-generation cephalosporins are suitable options for antibiotic therapy.

Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells.

PURPOSE: The usual first-line strategy of wild-type EGFR (wtEGFR) non-small cell lung cancer (NSCLC) remains cisplatin-based chemotherapy. However, cisplatin often loses effectiveness because most tumors acquire drug resistance over time. As EGFR is the most important pro-survival/proliferation signal receptor in NSCLC cells, we aimed at investigating whether cisplatin resistance is related to EGFR activation and further evaluating the combined effects of cisplatin/gefitinib (EGFR-tyrosine kinase inhibitor, EGFR-TKI) on cisplatin-resistant wtEGFR NSCLC cells. MATERIALS AND METHODS: EGFR activation was analysed in parental and cisplatin-resistant wtEGFR NSCLC cell lines (H358 and H358R, A549 and A549R). Cellular proliferation and apoptosis of H358R/A549R cells treated with cisplatin or gefitinib, alone or in combination were investigated, and the related effector protein was detected by western blot analysis. Anti-tumor effect of two drugs combined was evaluated in animal models of H358R xenografts in vivo. RESULTS: EGFR was significantly phosphorylated in cisplatin-resistant wtEGFR NSCLC cells H358R and A549R than their parental cells. In H358R and A549R cells, anti-proliferative ability of gefitinib was further improved, and gefitinib combined with cisplatin enhanced inhibition of cellular survive/proliferation, and promotion of apoptosis in vitro. The combined effects were also associated with the inhibition of EGFR downstream effector proteins. Similarly, in vivo, gefitinib and cisplatin in combination significantly inhibited tumor growth of H358R xenografts. CONCLUSION: Abnormal activation of EGFR may induce wtEGFR NSCLC cell resistance to cisplatin. The combined effects of cisplatin/gefitinib suggest that gefitinib, as a combination therapy for patients with cisplatin-resistant wtEGFR NSCLC should be considered.

BEZ235 increases sorafenib inhibition of hepatocellular carcinoma cells by suppressing the PI3K/AKT/mTOR pathway.

BACKGROUND: Sorafenib is an oral multi-kinase inhibitor that inhibits hepatocellular carcinoma (HCC) via the Ras/Raf/MAPK pathway. However, sorafenib loses effectiveness because most tumors acquire drug resistance over time. As the PI3K/AKT/mTOR signaling pathway is also activated abnormally in HCC, we evaluated the effect of sorafenib, in combination with a dual PI3K/mTOR inhibitor, BEZ235, on HCC cell proliferation and survival in vitro. MATERIALS AND METHODS: Biological phenotypes were analysed in HCC cell lines, parental and sorafenib-resistant HepG2 cells (HepG2 and HepG2R), treated with sorafenib or BEZ235, alone or in combination. HCC cellular proliferation and apoptosis were investigated, and perturbations of the Ras/Raf/MAPK and PI3K/AKT/mTOR signaling/survival pathways were evaluated by western blot analysis. RESULTS: BEZ235 enhanced sorafenib inhibition of cellular proliferation, migration, and promotion of apoptosis in HepG2 and HepG2R cells. The combined effects were associated with inhibition of phosphorylation of AKT, mTOR and S6K in the PI3K/AKT/mTOR pathway, whereas the combination of sorafenib and BEZ235 did not significantly alter the Ras/Raf/MAPK pathway compared with the effect of sorafenib alone. CONCLUSION: Sorafenib/BEZ235 combination has potent anti-HCC cell activity. This anti-tumor activity is most likely multi-factorial, mainly involving PI3K down-regulation and AKT, mTOR and S6K dephosphorylation. Combined inhibition of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways enhances sorafenib inhibition of HCC. The results of these in vitro studies suggest that trials of combined sorafenib and BEZ235 in the treatment of HCC should be considered.

QTL architecture of vine growth habit and gibberellin oxidase gene diversity in wild soybean (Glycine soja).

Vine growth habit (VGH) is a beneficial phenotype in many wild plants, and is considered an important domesticated-related trait in soybean. However, its genetic basis remains largely unclear. Hence, in the present study we used an integrated strategy combining linkage mapping and population genome diversity analyses to reveal the genetics of VGH in soybean. In this regard, two recombinant inbred line (RIL) populations derived by crossing a common wild soybean genotype (PI342618B) with two cultivated lines viz., NN 86-4 and NN 493-1 were used to map quantitative trait loci (QTL) for VGH. Here, we identified seven and five QTLs at flowering stage (R1) and maturity stage (R8), respectively, and among them qVGH-18-1, qVGH-18-2, qVGH-19-3, qVGH-19-4 were identified as major loci (R2 > 10% and detection time ≥2). However, qVGH-18-2 was considered as a main QTL for VGH being consistently identified in both RIL populations as well as all growth stages and cropping years. Out of all the annotated genes within qVGH-18-2, Glyma18g06870 was identified as the candidate gene and named as VGH1, which was a gibberellin oxidase (GAox) belongs to 2-oxoglutarate-dependent dioxygenase (2- ODD). Interestingly, there was one member of 2-ODD/GAox in qVGH-18-1 and qVGH-19-4 named as VGH2 and VGH3, respectively. Moreover, from sequencing data analysis VGH1 and three other GAox genes were found significantly divergent between vine and erect soybean with FST value larger than 0.25. Hence, GAox was assumed to play a major role in governing inheritance of VGH in soybean. Therefore, elucidating the genetic mechanism of GAox is very useful for exploring VGH and other stem traits, as well as genetic improvement of plant type in soybean.

IL-22 Up-Regulates ß-Defensin-2 Expression in Human Alveolar Epithelium via STAT3 but Not NF-κB Signaling Pathway.

Human ß-defensin-2(HBD-2) is one of the two major vertebrate antimicrobial peptide families (α and ß), which is highly expressed by proinflammatory induction in the lung and exhibit broad-spectrum antimicrobial activity. We observed that IL-22 receptors high expressed on the membrane of A549 cells; HBD-2 mRNA was expressed in a time- and concentration-dependent manners in A549 cells when treated with IL-22; further studies demonstrated that HBD-2 expression was attenuated by AG490, but to JSH-23, inhibitors of p-STAT3 DNA binding and NF-κB/p65 subunit nuclear translocation, respectively. These results support that IL-22-mediated signalling pathway of HBD-2 gene expression involved STAT3 but not NF-κB in human alveolar epithelium. These findings provide a new insight into how IL-22 may play an important link between innate and adaptive immunity, thereby anti-infection locally in the alveolar epithelium.

Genome-wide identification and transcription analysis of soybean carotenoid oxygenase genes during abiotic stress treatments.

Carotenoid oxygenase is a key enzyme in carotenoid metabolism leading to the synthesis of two phytohormones, abscisic acid (ABA) and strigolactone, as well as norisoprenoids. Few studies have analyzed inter-relationship of the metabolic networks of these three substances. In this present paper, soybean carotenoid oxygenase genes were identified to reveal their phylogenetic relationships, and the transcriptional response of these genes to four abiotic stresses (NaCl, PEG, high and low temperature) and ABA treatment were investigated to characterize their potential roles in plant resistance. Positive selection was found in the branches of carotenoid cleavage dioxygenase (CCD1), CCD8 and NCED (9-cis-epoxycarotenoid oxygenase), indicating an adaptive evolution in these clades. In soybean eight carotenoid oxygenase genes were identified. The transcriptional responses of almost all of them under stress and ABA conditions were significantly altered when assessed by quantitative polymerase chain reaction. Notably, CCD1 and CCD4, previously known as the key genes in norisoprenoids metabolism, showed especially strong responses to the abiotic stresses and ABA treatment. Furthermore, transcription levels of CCD7 and CCD8, key genes for the strigolactone pathway, highly increased during ABA treatment providing further evidence that ABA is involved in regulating strigolactone metabolism. All of the carotenoid oxygenase genes in soybean are involved in plant abiotic stress physiology, and ABA is presumed to be a core regulatory substance. These findings provide some insights into the mechanisms that underlie the regulation of tolerance response to abiotic stresses in soybean.