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Abstract Background Along with the improvement of lung cancer screening implementation, the identification of interstitial lung abnormality (ILA) is increasing. Currently, there is a limited description of the oncogenic status and ILA subtypes among newly diagnosed non‐small cell lung cancer (NSCLC) patients with ILA in the Chinese population. This study aimed to investigate the prevalence, characteristics, oncogenic status and factors associated with overall survival (OS) among NSCLC patients with ILA. Methods A total of 765 newly diagnosed NSCLC cases at our hospital were reviewed and ILA was diagnosed according to the criteria of the Fleischner Society. The characteristics, clinical pathological features and OS of NSCLC patients with ILA were retrospectively analyzed. Results Of the 765 patients included in the study, 101 (13.2%) cases experienced ILA at the time of NSCLC diagnosis. Multivariate analysis revealed that ILA was more likely to be detected in NSCLC patients who were age ≥60 (OR 2.404, p = 0.001), male gender (OR 2.476, p = 0.004), and EGFR wild‐type (OR 2.035, p = 0.007). Additionally, according to the multivariate Cox model, the presence of ILA in NSCLC patients was significantly associated with a shorter OS period than those without ILA (751 days vs. 445 days, HR 0.6, p = 0.001). Following analysis, it was determined that OS in patients with usual interstitial pneumonia (UIP) was shorter than in those without UIP (HR 1.82, p = 0.037). Conclusion ILA is a common comorbidity among newly diagnosed NSCLC patients. We found that patients with EGFR wild‐type NSCLC were more likely to develop ILA. The presence of ILA, especially UIP, was significantly associated with poor NSCLC prognosis.

This study was conducted to investigate the effect of inoculation with Exiguobacterium profundum FELA1 isolated from traditional shrimp paste and koji on the taste, flavor characteristics, and bacterial community of rapidly fermented shrimp paste. E-nose and e-tongue results showed higher levels of alcohols, aldehydes, and ketones, enhanced umami and richness, and reduced bitterness and astringency in samples of shrimp paste inoculated with fermentation (p < 0.05). Eighty-two volatile compounds were determined using headspace solid-phase microextraction and gas chromatography–mass spectrometry (HS-SPEM-GC-MS). The contents of 3-methyl-1-butanol, phenylethanol, isovaleraldehyde, and 2-nonanone in the inoculated samples were significantly increased (p < 0.05), resulting in pleasant odors such as almond, floral, and fruity. High-throughput sequencing results showed that the addition of koji and FELA1 changed the composition and abundance of bacteria and reduced the abundance of harmful bacteria. Spearman’s correlation coefficient indicated that the alcohols, aldehydes, and ketones of the inoculated fermented samples showed a strong correlation (|ρ| > 0.6) with Virgibacillus and Exiguobacterium, which contributed to the formation of good flavor in the fast fermented shrimp paste. This study may offer new insights into the production of rapidly fermented shrimp paste with better taste and flavor.

Background Although computed tomography (CT)-defined emphysema is considered a predictor of lung cancer risk, it is not fully clear whether CT-defined emphysema is associated with the prognosis of lung cancer. We aimed to assess the clinical impact of CT-defined emphysema on the survival of lung cancer. Methods In the prospective cohort study of nonsmall cell lung cancer (NSCLC), the correlation between CT-defined emphysema and clinical variables was analysed. A multivariable Cox regression model was built to assess the association between CT-defined emphysema and overall survival (OS) for up to 8.8 years. The differences in survival analyses were derived by Kaplan–Meier analysis and log-rank testing. Low attenuation area (LAA%) was defined as the per cent of voxels below −950 HU. Results 854 patients were included and CT-defined emphysema was present in 300 (35.1%) at diagnosis. Epidermal growth factor receptor (EGFR) wild-type (OR 1.998; p17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; p=0.020). Conclusions CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.

Abstract Background According to several studies, ROS1 rearrangement is associated with thrombotic risk in non-small cell lung cancer (NSCLC). However, there is no clear understanding of the predictors and prognostic impact of thromboembolic events (TEEs) in patients with advanced ROS1 rearrangement NSCLC. Methods A total of 47 newly diagnosed advanced NSCLC patients with ROS1 rearrangement from four Chinese hospitals were retrospectively included and were evaluated for TEEs incidence, characteristics, predictors, as well as response to therapies and overall survival (OS). Results Of the 47 enrolled patients, 23.4% (n = 11) patients developed TEEs. Among them, 7 of 11 patients (64%) developed pulmonary embolism (PE), and 5 patients (45%) experienced recurrent TEEs. In multivariate analysis, D-dimer was associated with the occurrence of TEEs in ROS1 rearranged NSCLC (HR 1.16, 95% CI 1.08–1.23, P

Abstract Background Patients with primary lung adenocarcinoma are at increased risk of venous thromboembolism (VTE). However, lung adenocarcinoma characteristics differ across histological subtypes. Therefore, we performed comprehensive analyses on the clinicopathological characteristics of lung adenocarcinoma and risk of VTE. Methods A total of 952 surgically resected lung adenocarcinoma cases were reviewed and classified according to criteria of the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS) /European Respiratory Society (ERS). The correlation between this classification and VTE risk was retrospectively analyzed. The risks of other clinicopathological features including pleural invasion, vascular invasion and associated surgical intervention risks were also assessed. Results Of the 952 patients, 100 (10.4%) cases experienced VTE events during the follow‐up period. Among those with VTE, 28 (28%) were found before surgery, 47 (47%) were found within 1 month after surgery, and 91 (91%) were found in hospital. Univariate analysis revealed that ages, extent of resection and presence of micropapillary features were predictive of VTE risk. Furthermore, multivariable analysis demonstrated that the presence of micropapillary features (subdistribution hazard ratio [SHR] 1.560, 95% CI: 1.043–2.330) and age >60 (SHR: 2.270, 95% CI:1.491–3.470) were associated with increased risk of VTE. After one year, the probability of developing VTE was 13.1% and 8.3% in patients with micropapillary features and those without, respectively. Conclusions VTE is a common complication for lung adenocarcinoma patients who undergo surgery, especially during the perioperative process and hospitalization. Presence of micropapillary subtype and age are positively associated with VTE risk.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk for lung cancer, but the underlying mechanisms driving malignant transformation remain largely unknown. This study aimed to identify differentially expressed genes (DEGs) distinguishing IPF and lung cancer from healthy individuals and common genes driving the transformation from healthy to IPF and lung cancer. Methods The gene expression data for IPF and non-small cell lung cancer (NSCLC) were retrieved from the Gene Expression Omnibus (GEO) database. The DEG signatures were identified via unsupervised two-way clustering (TWC) analysis, supervised support vector machine analysis, dimensional reduction, and mutual exclusivity analysis. Gene enrichment and pathway analyses were performed to identify common signaling pathways. The most significant signature genes in common among IPF and lung cancer were further verified by immunohistochemistry. Results The gene expression data from GSE24206 and GSE18842 were merged into a super array dataset comprising 86 patients with lung disorders (17 IPF and 46 NSCLC) and 51 healthy controls and measuring 23,494 unique genes. Seventy-nine signature DEGs were found among IPF and NSCLC. The peroxisome proliferator-activated receptor (PPAR) signaling pathway was the most enriched pathway associated with lung disorders, and matrix metalloproteinase-1 (MMP-1) in this pathway was mutually exclusive with several genes in IPF and NSCLC. Subsequent immunohistochemical analysis verified enhanced MMP1 expression in NSCLC associated with IPF. Conclusions For the first time, we defined common signature genes for IPF and NSCLC. The mutually exclusive sets of genes were potential drivers for IPF and NSCLC.

Lambert‐Eaton myasthenic syndrome (LEMS) is a rare disease characterized by involvement of the neuromuscular junction. Most cases have an underlying malignancy, especially small‐cell lung cancer (SCLC), while adenocarcinoma is less common. Here, we report a rare case of metastatic lung adenocarcinoma complicated with LEMS. In this case, L858R mutation was detected in the 21st exon of the EGFR gene. First‐line treatment with gefitinib was given, and the patient has survived for more than six years. Early diagnosis of LEMS and timely and effective treatment can result in a good prognosis. We also searched for “lung cancer”, or “carcinoma of lung”, or “adenocarcinoma of lung”, or “Lambert‐Eaton myasthenic syndrome” in PubMed until 1 December 2019. Seven cases of lung adenocarcinoma complicated with LEMS were found, most of which had a poor prognosis. Key points This article reports a rare case of metastatic lung adenocarcinoma with EGFR mutation, complicated with LEMS. Gefitinib was given as first‐line treatment, and resulted in a good prognosis.

Abstract Background Preclinical data suggest that oncogene (EGFR and KRAS) events regulate tumor procoagulant activity. However, few studies have prospectively investigated the clinical relevance between the presence of EGFR or KRAS mutations and occurrence of venous thromboembolism(VTE) in patients with non-small cell lung cancer (NSCLC). Methods A total of 605 Chinese patients with newly diagnosed NSCLC were included and were followed for a maximum period of 4.5 years. EGFR and KRAS mutations were determined by amplification refractory mutation system polymerase chain reaction method at inclusion. The main outcome was objectively confirmed VTE. Results Of the 605 patients, 40.3% (244) had EGFR mutations and 10.2% (62) of patients had KRAS mutations. In multivariable analysis including age, sex, tumor histology, tumor stage, performance status, EGFR and KRAS status, EGFR wild-type (sub-distribution hazard ratio 1.81, 95% confidence interval 1.07–3.07) were associated with the increased risk of VTE. In competing risk analysis, the probability of developing VTE was 8.3% in those with and 13.2% in those without EGFR mutations after 1 year; after 2 years, the corresponding risks were 9.7 and 15.5% (Gray test P = 0.047). Conclusions EGFR mutations have a negative association with the risk of VTE in Chinese patients with NSCLC.

ObjectiveNetherton syndrome (NS) is a rare hereditary dermatosis, and the correlation between genotype and phenotype in this disease warrants further investigation. This study aimed to explore the genotype-phenotype correlation in NS.MethodsWe collect cases from our clinic and relevant literature. After rigorous screening, we included 162 patients with NS-associated symptoms and SPINK5 mutations. We characterized the distribution and mutation types of allele variants. Logistic regression was employed to analyze the correlation between the location of these variants and phenotypes. Additionally, the association between the homozygous condition of variants and death during infancy was analyzed using the Chi-square test.ResultsAmong 162 patients, we identified 324 allele variants, comprising 75 different mutations. Of these, 73 patients carried heterozygous variants, while 89 patients had homozygous variants. We observed that patients with variants or homozygous variants located in the 5′ half of the gene were more likely to experience failure to thrive (P < 0.05). Similarly, variants or homozygous variants located outside DomainR-5 were also associated with an increased risk of failure to thrive (P < 0.05). Furthermore, variants in domain regions were significantly correlated with the presence of ichthyosis linearis circumflexa (P < 0.01). Patients with homozygous fatal variants (c.153delT, c.1431-12G>A, c.1111C>T, c. 1887 + 1G>A, and c. 995delT) had a higher likelihood of mortality during infancy (P < 0.001).ConclusionOur study provides valuable insights into the genotype-phenotype correlation in Netherton syndrome, enhancing our understanding of the disease and potentially informing the development of future therapeutic approaches.

A simple protocol for the sulfur-promoted conversion of aromatic aldehydes to aromatic nitriles has been developed. This strategy enables the one-pot conversion of inexpensive and readily available aromatic aldehydes into highly valuable aromatic nitriles using a cheap inorganic ammonium salt as the nitrogen source in the absence of metals. Significantly, a broad scope of substrates was explored using this strategy, and various groups, including alkyl, alkoxyl, alkylthiol, hydroxyl, amino, aryl, alkenyl, cyano, carboxyl, and borate ester groups were tolerated, and good to excellent yields were achieved in most cases. Additionally, polycyclic aromatic aldehydes and heteroaromatic aldehydes also could be converted to the corre-sponding nitriles with satisfactory yields. This method can be utilized as a powerful tool for the cyanation of complex molecules.

Abstract Free chlorine is one of the key water quality parameters in tap water. However, a free chlorine sensor with the characteristics of batch processing, durability, antibiofouling/antiorganic passivation and in situ monitoring of free chlorine in tap water continues to be a challenging issue. In this paper, a novel silicon-based electrochemical sensor for free chlorine that can self-clean and be mass produced via microfabrication technique/MEMS (Micro-Electro-Mechanical System) is proposed. A liquid-conjugated Ag/AgCl reference electrode is fabricated, and electrochemically stable BDD/Pt is employed as the working/counter electrode to verify the effectiveness of the as-fabricated sensor for free chlorine detection. The sensor demonstrates an acceptable limit of detection (0.056 mg/L) and desirable linearity (R 2 = 0.998). Particularly, at a potential of +2.5 V, hydroxyl radicals are generated on the BBD electrode by electrolyzing water, which then remove the organic matter attached to the surface of the sensor though an electrochemical digestion process. The performance of the fouled sensor recovers from 50.2 to 94.1% compared with the initial state after self-cleaning for 30 min. In addition, by employing the MEMS technique, favorable response consistency and high reproducibility (RSD

A 22-year-old male presented with a pimple on the left neck for three years. Physical examination revealed a demarcated pink papule in 0.2 cm of diameter on the left neck, with central eruption, but no extrusion. Dermoscopic examination revealed pink background under nonpolar light, with central eruption, while under polar light, a pink background with central eruption, surrounded by white structureless area and dilated blood vessels. Histopathological examination showed a cyst and lumens which were lined with pseudostratified ciliated columnar epithelium. Epidermal polypoid projection, mucous cells in the dermis and lymphocytic infiltration around the lumens were evident. The epidermis exhibited transition of some squamous epithelial tissue to stratified columnar epithelium tissue. Diagnosis was bronchogenic cysts. After surgical excision, no recurrence was observed during a 3-month follow-up.

Abstract The Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve, which is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is rich in protein, amino acids, and microelements. The genome of C. fluminea has not yet been characterized; therefore, genome-assisted breeding and improvements cannot yet be implemented. In this work, we present a de novo chromosome-scale genome assembly of C. fluminea using PacBio and Hi-C sequencing technologies. The assembled genome comprised 4728 contigs, with a contig N50 of 521.06 Kb, and 1,215 scaffolds with a scaffold N50 of 70.62 Mb. More than 1.51 Gb (99.17%) of genomic sequences were anchored to 18 chromosomes, of which 1.40 Gb (92.81%) of genomic sequences were ordered and oriented. The genome contains 38,841 coding genes, 32,591 (83.91%) of which were annotated in at least one functional database. Compared with related species, C. fluminea had 851 expanded gene families and 191 contracted gene families. The phylogenetic tree showed that C. fluminea diverged from Ruditapes philippinarum, ~ 228.89 million years ago (Mya), and the genomes of C. fluminea and R. philippinarum shared 244 syntenic blocks. Additionally, we identified 2 MITF members and 99 NLRP members in C. fluminea genome. The high-quality and chromosomal Asian Clam genome will be a valuable resource for a range of development and breeding studies of C. fluminea in future research.

Quercetin is a flavanol beneficial in reducing fat, promoting muscle growth, and Anti-oxidation. To study its effects in freshwater fish, the full-length cDNA of the follistatin (FST) and myostatin (MSTN) genes of the dark sleeper Odontobutis potamophila were cloned for the first time. Juvenile individual O. potamophila was exposed to quercetin at one of four concentrations (0, 2.5, 5, and 10 mg/L) for 21 days. The expression level of MSTN which inhibits muscle growth in the quercetin solution was lower than in the unexposed control group. The genes that promote muscle growth are in TGF-β superfamily like FST, TGF-β1 (transforming growth factor-beta 1), and Myogenic regulatory factors (MRFs) like Myf5 (myogenic factor 5), MyoD (myogenic differentiation), MyoG (myogenin), were higher than in the control group. Apolipoprotein and growth hormone receptor transcription levels in the quercetin-treated fish were significantly lower than in the control group. The concentrations of triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the muscle tissue decreased, and the lipid-lowering function of quercetin was also demonstrated at the biochemical level. In this study, we analyzed the mRNA levels of AKT, Keap1 (kelch-like ECH-associated protein 1), Nrf2 (NF-E2-related factor 2) oxidation-related genes in the Nrf2/ARE antioxidant pathway, and Malondialdehyde (MDA), catalase (CAT) activity and glutathione (GSH) content in the hepatopancreas of O. potamophila after quercetin treatment, the mRNA expression of AKT, Nrf2 and CAT activity and GSH content are higher than in the control group. Quercetin enhances antioxidant properties and positively affects muscle growth. The results showed that quercetin has no significant effects on the growth performance of O. potamophila, but is effective in increasing muscle growth rate and lowering muscle fat content.

The freshwater gammarid Grandidierella taihuensis is an important composition of benthic community. In this study, the complete mitogenome sequences of G. taihuensis are determined using next-generation and PacBio long-read sequencing. The mitogenome of G. taihuensis is 15,099 bp in size, and consisted of 13 protein-coding genes, two ribosomal RNA genes, 22 tRNA genes, and a putative control region. Gene arrangement is as same as that of G. rubroantennata. The base composition of the entire mitogenome showed a conspicuous A + T bias of 69.4%. The mitogenome data produced in this study provides a useful resource for future evolutionary and ecological studies.

Flavonoids have antimicrobial and anti-oxidation properties. The effects of the flavonoid quercetin on the intestinal microflora of freshwater dark sleeper Odontobutis potamophila were tested for the first time. Odontobutis potamophila juveniles were treated with quercetin for 21 days at one of three concentrations (2.5, 5.0, or 10.0 mg/L) and compared with a control group that was not treated with quercetin. Quercetin improved the stability of the intestinal flora in O. potamophila and the probiotic bacteria Bacillus spp. and Lactobacillus spp. increased in species abundance after the low concentration quercetin treatments. Furthermore, the abundance of pathogenic bacteria Plesiomonas spp., Aeromonas spp., and Shewanella spp. decreased after the fish had been exposed to quercetin. Activity of hepatic antioxidant enzymes (superoxide dismutase, SOD), (glutathione S-transferase, GST), (glutathione peroxidase, GSH-Px), and (total antioxidant capacity, T-AOC) increased in the livers of O. potamophila treated with quercetin, thereby increasing their hepatic antioxidant capacity and their ability to scavenge free radicals.

Netherton syndrome (NS) is a rare, autosomal recessive hereditary skin disease caused by mutations in SPINK5 gene, characterized with severe skin barrier damage. A human induced pluripotent stem cell (iPSC) line has been established with electroporation method from urine-derived cells of a NS patient carrying a compound heterozygous mutation c.2260A > T (p.K754X) and c.2423C > T(p.T808I) in SPINK5 gene. This iPSC line may serve as a valuable model for the research of pathogenesis of NS, and the mechanisms and therapeutics for skin barrier damage.

Ischemic stroke is a life-threatening condition that also frequently results in long-term disability. Currently, intravenous thrombolysis with tissue plasminogen activator and mechanical thrombectomy is the most popular treatment. However, the narrow time window and related complications limit the treatment benefits. Exosomes have recently emerged as ideal therapeutic candidates for ischemic stroke with the ability to pass through the blood_brain barrier and mediate intercellular communication, in addition, exosomes and their contents can be bioengineered to implement targeted delivery. In the last two decades, exosomes and exosomal noncoding RNAs have been found to be involved in the pathophysiological progression of ischemic stroke, including atherosclerosis, apoptosis, inflammation, oxidative stress, and neurovascular remodeling. In this review, we describe the latest progress regarding the role of exosomal long noncoding RNAs and circular RNAs in the occurrence, progression, and recovery of ischemic stroke. Exploration of exosomal noncoding RNAs and their correlated effects in ischemic stroke may facilitate accurate diagnosis, and they may serve as new therapeutic targets for the disease.

In this study, we present the complete mitogenome and a phylogenetic analysis of Callionymus olidus, determined by long PCR and primer walking methods. The complete mitochondrial genome is a circular molecule of 16,491 bp in length and contains the same set of 37 mitochondrial genes (13 protein-coding genes, 2 ribosomal RNA (rRNA), 22 transfer RNA (tRNA)), and a control region as other bony fishes. The base composition of the entire mitogenome showed a slight excess of AT bias. The entire mitogenome data produced in this study provides the genomic resources available for future evolutionary studies.

Characterization of flow behaviors is one of the most challenging problems in a gas-liquid flow system. In this paper, correlation dimension, a chaotic characteristic indicator, was introduced to characterize the gas-liquid two-phase flow behaviors by using the fluctuating pressure induced by a bluff body. An artificial neural network was trained to help select suitable flow parameters that were combined with correlation dimension to construct a novel gas-liquid flow pattern map, which was able to distinguish between the bubble, bubble/plug transitional, plug, slug, and annular flows with reasonable accuracy. Furthermore, a quantitative correlation with the form of ug = AD2BuC was established by the universal fitting and the pattern-specific fitting with the coefficients of determination R2 approaching to 1. In view of the simplicity and the convenience of vortex generation and pressure measurement, the correlation dimension-based method provides an effective and practical idea to gas-liquid two-phase flows study.

To improve bus passengers’ degree of comfort, it is necessary to determine the real-time crowd coefficient in the bus. With this concern, this paper employed the RBF Neural Networks approach to predict the number of passengers in the bus based on historical data. To minimize the impact of the randomness of passenger flow on the determination of bus crowd coefficient, a cloud model-based bus crowd coefficient identification method was proposed. This paper first selected the performance measurements for determining bus crowd coefficient and calculated the digital characteristics of the cloud model based on the boundary values of the selected performance measures under six Levels-of-Service (LOSs). Then the subclouds obtained under the six LOSs were synthesized into a standard cloud. According to the predicted number of passengers in the bus, the passenger density and loading frequency were calculated, which were imported into the cloud generator to set up the bus crowd coefficient identification model. By calculating the crowd degrees of identification cloud and template cloud at each site, this paper determined the crowed coefficient of each bus station. Finally, this paper took the bus line No. 10 in Dalian city as case study to verify the proposed model. It was found that the crowd coefficients of the selected route ranged from 60.265 to 109.825, and the corresponding LOSs ranged between C and F. The method of discriminating bus crowding coefficient can not only effectively determine the congestion coefficient, but also effectively avoid the fuzziness and randomness of the crowding coefficient judgment in the bus, which has strong theoretical and practical significance.

Corbicula fluminea is an important aquatic commercial species in China. In this study, we present the complete mitogenome and a phylogenetic analysis of C. fluminea, determined using next-generation and PacBio long read sequencing. The mitogenome of C. fluminea is 17,423 bp in size, including 13 protein-coding genes, two ribosomal RNA genes, 22 tRNA genes, and a putative control region, all located on the same strand. The base composition of the entire mitogenome showed a conspicuous A + T bias of 70.5 %. The entire mitogenome data produced in this study provides the genomic resources available for future evolutionary studies.