Anti-tumor effects of nanosecond pulsed electric fields in a murine model of pancreatic cancer.

Nanosecond Pulsed Electric Fields (nsPEFs) treatment has demonstrated anti-tumor effects on various cancer cell lines. However, the use of this treatment in pancreatic cancer is limited. This study demonstrated that nsPEFs treatment effectively suppressed the proliferation and metastasis of pancreatic cancer cells, while also inducing DNA damage. Meanwhile, animal experiments have shown that nsPEFs effectively suppressed the growth of pancreatic cancer, even in cases where the tumor volume exceeded 500-600 mm3 at the initiation of treatment. Notably, a single treatment session was found to significantly inhibit tumor growth, while also showing no adverse effects on the main organs of the mice. RNA sequencing and bioinformatics revealed that seven key genes (CDK1, CENPA, UBE2C, CCNB2, PLK1, CCNA2, and CCNB14) were significantly correlated with the overall survival rate of patients with pancreatic cancer. Through the application of the competing endogenous RNA (ceRNA) hypothesis, two miRNAs (has-let-7b-5p and hsa-miR-193b-3p) and four lncRNAs (MIR4435-2HG, ZNF436-AS1, LINC01089, and MIR4435-2HG) were identified as significantly impacting the overall survival of pancreatic cancer patients. We have effectively developed an mRNA-miRNA-lncRNA network that has the potential to stimulate further investigation into the underlying mechanisms of nsPEFs on pancreatic cancer.

Development of Hypoallergenic Derivatives of Cra a 1 with B Cell Epitope Deletion and T Cell Epitope Retention.

Tropomyosin was reported as an important allergen in Crassostrea angulata and designated as Cra a 1. The localization of the T cell epitopes and the reduction of the immunoreactivity of Cra a 1 are still lacking. In this study, four T cell epitopes were identified by using wild-type Cra a 1 (wtCra a 1)-immunized mouse splenocytes cultured with synthetic peptides. The immunoreactivity was maintained after chemical denaturation treatment, indicating that the linear epitope is an immunodominant epitope of wtCra a 1. Furthermore, the hypoallergenic derivative (mCra a 1) was developed by the deletion of linear B cell epitopes and retention of T cell epitopes. mCra a 1 could stimulate CD4+T cell proliferation and upregulate interleukin-10 secretion. Overall, basophil activation by mCra a 1 was low, but its ability to induce T cell proliferation was retained, suggesting that mCra a 1 may serve as a viable candidate for treating oyster allergy.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

A Combined Metabolome and Transcriptome Reveals the Lignin Metabolic Pathway during the Developmental Stages of Peel Coloration in the 'Xinyu' Pear.

Sand pear is the main cultivated pear species in China, and brown peel is a unique feature of sand pear. The formation of brown peel is related to the activity of the cork layer, of which lignin is an important component. The formation of brown peel is intimately associated with the biosynthesis and accumulation of lignin; however, the regulatory mechanism of lignin biosynthesis in pear peel remains unclear. In this study, we used a newly bred sand pear cultivar 'Xinyu' as the material to investigate the biosynthesis and accumulation of lignin at nine developmental stages using metabolomic and transcriptomic methods. Our results showed that the 30 days after flowering (DAF) to 50DAF were the key periods of lignin accumulation according to data analysis from the assays of lignin measurement, scanning electron microscope (SEM) observation, metabolomics, and transcriptomics. Through weighted gene co-expression network analysis (WGCNA), positively correlated modules with lignin were identified. A total of nine difference lignin components were identified and 148 differentially expressed genes (DEGs), including 10 structural genes (PAL1, C4H, two 4CL genes, HCT, CSE, two COMT genes, and two CCR genes) and MYB, NAC, ERF, and TCP transcription factor genes were involved in lignin metabolism. An analysis of RT-qPCR confirmed that these DEGs were involved in the biosynthesis and regulation of lignin. These findings further help us understand the mechanisms of lignin biosynthesis and provide a theoretical basis for peel color control and quality improvement in pear breeding and cultivation.

Spectrum Reconstruction Model Based on Multispectral Electrochromic Devices.

Reconstructing the visible spectra of real objects is critical to the spectral camouflage from emerging spectral imaging. Electrochromic materials exhibit unique superiority for this goal due to their subtractive color-mixing model and structural diversity. Herein, a simulation model is proposed and a method is developed to fabricate electrochromic devices for dynamically reproducing the visible spectrum of the natural leaf. Over 20 kinds of pH-dependent leuco dyes have been synthesized/prepared through molecular engineering and offered available spectra/bands to reconstruct the spectrum of the natural leaf. More importantly, the spectral variance between the device and leaf is optimized from an initial 98.9 to an ideal 10.3 through the simulation model, which means, the similarity increased nearly nine-fold. As a promising spectrum reconstruction approach, it will promote the development of smart photoelectric materials in adaptive camouflage, spectral display, high-end encryption, and anti-counterfeiting.

Biomimetic Exploration and Reflection on Switchable Coordination and Narrow-Band Electrofluorochromic Devices.

Electrofluorochromic (EFC) materials and devices with controllable fluorescence properties show great application potential in advanced anticounterfeiting, information storage and display. However, the low color purity caused by the broad emission spectra and underperforming switching time of the existing EFC materials limit their application. Through biomimetic exploration and the study of reversible electrochemical responsive coordination reactions, boron-nitrogen embedded polyaromatics (B,N-PAHs) with narrow-band emission and high color purity have been successfully integrated into EFC systems, which also help to better understand the role of boron in biological activity. The EFC device achieve good performance containing quenching efficiency greater than 90% within short switching time (ton: 0.6 s, toff: 2.4 s), and nearly no performance change after 200 cycles test. Three primary color (red, green, and blue) EFC devices are successfully prepared. In addition, new phenomena are obtained and discussed in this biomimetic exploration of related boron reactions. The success and harvest of this exploration are expected to provide new ideas for optimizing properties and broadening applications of EFC materials. Moreover, it may provide ideas and reference significance for further exploring and understanding the function of boron compounds in biological systems.

Detection of COVID-19 by quantitative analysis of carbonyl compounds in exhaled breath.

COVID-19 has caused a worldwide pandemic, creating an urgent need for early detection methods. Breath analysis has shown great potential as a non-invasive and rapid means for COVID-19 detection. The objective of this study is to detect patients infected with SARS-CoV-2 and even the possibility to screen between different SARS-CoV-2 variants by analysis of carbonyl compounds in breath. Carbonyl compounds in exhaled breath are metabolites related to inflammation and oxidative stress induced by diseases. This study included a cohort of COVID-19 positive and negative subjects confirmed by reverse transcription polymerase chain reaction between March and December 2021. Carbonyl compounds in exhaled breath were captured using a microfabricated silicon microreactor and analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). A total of 321 subjects were enrolled in this study. Of these, 141 (85 males, 60.3%) (mean ± SD age: 52 ± 15 years) were COVID-19 (55 during the alpha wave and 86 during the delta wave) positive and 180 (90 males, 50%) (mean ± SD age: 45 ± 15 years) were negative. Panels of a total of 34 ketones and aldehydes in all breath samples were identified for detection of COVID-19 positive patients. Logistic regression models indicated high accuracy/sensitivity/specificity for alpha wave (98.4%/96.4%/100%), for delta wave (88.3%/93.0%/84.6%) and for all COVID-19 positive patients (94.7%/90.1%/98.3%). The results indicate that COVID-19 positive patients can be detected by analysis of carbonyl compounds in exhaled breath. The technology for analysis of carbonyl compounds in exhaled breath has great potential for rapid screening and detection of COVID-19 and for other infectious respiratory diseases in future pandemics.

An electrochemically responsive B-O dynamic bond to switch photoluminescence of boron-nitrogen-doped polyaromatics.

Boron-doped polycyclic aromatic hydrocarbons exhibit excellent optical properties, and regulating their photophysical processes is a powerful strategy to understand the luminescence mechanism and develop new materials and applications. Herein, an electrochemically responsive B-O dynamic coordination bond is proposed, and used to regulate the photophysical processes of boron-nitrogen-doped polyaromatic hydrocarbons. The formation of the B-O coordination bond under a suitable voltage is confirmed by experiments and theoretical calculations, and B-O coordination bond can be broken back to the initial state under opposite voltage. The whole process is accompanied by reversible changes in photophysical properties. Further, electrofluorochromic devices are successfully prepared based on the above electrochemically responsive coordination bond. The success and harvest of this exploration are beneficial to understand the luminescence mechanism of boron-nitrogen-doped polyaromatic hydrocarbons, and provide ideas for design of dynamic covalent bonds and broaden material types and applications.

Cesium ion-guided detection of trichloroethylene in air.

Whereas the close associations of cesium ion with organochlorine compounds have been previously documented, the present report is the first attempt to exploit these interactions to create a trichloroethylene (TCE)-selective sensor. Gold monolayer-protected clusters peripherally functionalized with Cs+ ions were used to prepare a chemiresistance film on MEMS-fabricated interdigitated electrodes. Vapor sensing properties of the cesium-rich chemiresistor were determined using a panel of chlorinated hydrocarbons including TCE as well as polar and non-polar VOCs for comparison. The sensor was selective and highly sensitive toward VOCs containing a 1,2-dichloro group at concentrations as low as 0.1 ppm. The results suggest the key interaction contributing to sensor response is a bidentate, metallocycle-like coordination of the 1,2-dichloro group to the cesium cations at the sensor surface.

A comprehensive meta-analysis and systematic review of breath analysis in detection of COVID-19 through Volatile organic compounds.

BACKGROUND: The COVID-19 pandemic had profound global impacts on daily lives, economic stability, and healthcare systems. Diagnosis of COVID-19 infection via RT-PCR was crucial in reducing spread of disease and informing treatment management. While RT-PCR is a key diagnostic test, there is room for improvement in the development of diagnostic criteria. Identification of volatile organic compounds (VOCs) in exhaled breath provides a fast, reliable, and economically favorable alternative for disease detection. METHODS: This meta-analysis analyzed the diagnostic performance of VOC-based breath analysis in detection of COVID-19 infection. A systematic review of twenty-nine papers using the grading criteria from Newcastle-Ottawa Scale (NOS) and PRISMA guidelines was conducted. RESULTS: The cumulative results showed a sensitivity of 0.92 (95 % CI, 90 %-95 %) and a specificity of 0.90 (95 % CI 87 %-93 %). Subgroup analysis by variant demonstrated strong sensitivity to the original strain compared to the Omicron and Delta variant in detection of SARS-CoV-2 infection. An additional subgroup analysis of detection methods showed eNose technology had the highest sensitivity when compared to GC-MS, GC-IMS, and high sensitivity-MS. CONCLUSION: Overall, these results support the use of breath analysis as a new detection method of COVID-19 infection.

Sustainable, low-cost, high-contrast electrochromic displays via host-guest interactions.

Electrochromic (EC) displays with electronically regulating the transmittance of solar radiation offer the opportunity to increase the energy efficiency of the building and electronic products and improve the comfort and lifestyle of people. Despite the unique merit and vast application potential of EC technologies, long-awaited EC windows and related visual content displays have not been fully commercialized due to unsatisfactory production cost, durability, color, and complex fabrication processes. Here we develop a unique EC strategy and system based on the natural host and guest interactions to address the above issues. A completely reusable and sustainable EC device has been fabricated with potential advantages of extremely low cost, ideal user-/environment friendly property, and excellent optical modulation, which is benefited from the extracted biomass EC materials and reusable transparent electrodes involved in the system. The as-prepared EC window and nonemissive transparent display also show comprehensively excellent properties: high transmittance change (>85%), broad spectra modulation covering Ultraviolet (UV), Visible (Vis) to Infrared (IR) ranges, high durability (no attenuation under UV radiation for more than 1.5 mo), low open voltage (0.9 V), excellent reusability (>1,200 cycles) of the device's key components and reversibility (>4,000 cycles) with a large transmittance change, and pleasant multicolor. It is anticipated that unconventional exploration and design principles of dynamic host-guest interactions can provide unique insight into different energy-saving and sustainable optoelectronic applications.

Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Genome-wide identification, subcellular localization, and expression analysis of the phosphatidyl ethanolamine-binding protein family reveals the candidates involved in flowering and yield regulation of Tartary buckwheat (Fagopyrum tataricum).

Background: PEBP (phosphatidyl ethanolamine-binding protein) is widely found in eukaryotes including plants, animals and microorganisms. In plants, the PEBP family plays vital roles in regulating flowering time and morphogenesis and is highly associated to agronomic traits and yields of crops, which has been identified and characterized in many plant species but not well studied in Tartary buckwheat (Fagopyrum tataricum Gaertn.), an important coarse food grain with medicinal value. Methods: Genome-wide analysis of FtPEBP gene family members in Tartary buckwheat was performed using bioinformatic tools. Subcellular localization analysis was performed by confocal microscopy. The expression levels of these genes in leaf and inflorescence samples were analyzed using qRT-PCR. Results: Fourteen Fagopyrum tataricum PEBP (FtPEBP) genes were identified and divided into three sub-clades according to their phylogenetic relationships. Subcellular localization analysis of the FtPEBP proteins in tobacco leaves indicated that FT- and TFL-GFP fusion proteins were localized in both the nucleus and cytoplasm. Gene structure analysis showed that most FtPEBP genes contain four exons and three introns. FtPEBP genes are unevenly distributed in Tartary buckwheat chromosomes. Three tandem repeats were found among FtFT5/FtFT6, FtMFT1/FtMFT2 and FtTFL4/FtTFL5. Five orthologous gene pairs were detected between F. tataricum and F. esculentum. Seven light-responsive, nine hormone-related and four stress-responsive elements were detected in FtPEBPs promoters. We used real-time PCR to investigate the expression levels of FtPEBPs among two flowering-type cultivars at floral transition time. We found FtFT1/FtFT3 were highly expressed in leaf and young inflorescence of early-flowering type, whereas they were expressed at very low levels in late-flowering type cultivars. Thus, we deduced that FtFT1/FtFT3 may be positive regulators for flowering and yield of Tartary buckwheat. These results lay an important foundation for further studies on the functions of FtPEBP genes which may be utilized for yield improvement.

Efficient biosynthesis of prunin in methanol cosolvent system by an organic solvent-tolerant α-L-rhamnosidase from Spirochaeta thermophila.

Prunin of desirable bioactivity and bioavailability can be transformed from plant-derived naringin by the key enzyme α-L-rhamnosidase. However, the production was limited by unsatisfactory properties of α-L-rhamnosidase such as thermostability and organic solvent tolerance. In this study, biochemical characteristics, and hydrolysis capacity of a novel α-L-rhamnosidase from Spirochaeta thermophila (St-Rha) were investigated, which was the first characterized α-L-rhamnosidase for Spirochaeta genus. St-Rha showed a higher substrate specificity towards naringin and exhibited excellent thermostability and methanol tolerance. The Km of St-Rha in the methanol cosolvent system was decreased 7.2-fold comparing that in the aqueous phase system, while kcat/Km value of St-Rha was enhanced 9.3-fold. Meanwhile, a preliminary conformational study was implemented through comparative molecular dynamics simulation analysis to explore the mechanism underlying the methanol tolerance of St-Rha for the first time. Furthermore, the catalytic ability of St-Rha for prunin preparation in the 20% methanol cosolvent system was explored, and 200 g/L naringin was transformed into 125.5 g/L prunin for 24 h reaction with a corresponding space-time yield of 5.2 g/L/h. These results indicated that St-Rha was a novel α-L-rhamnosidase suitable for hydrolyzing naringin in the methanol cosolvent system and provided a better alternative for improving the efficient production yield of prunin.

Prediction of pathological complete response of breast cancer patients who received neoadjuvant chemotherapy with a nomogram based on clinicopathologic variables, ultrasound, and MRI.

OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.

Comparison of effects of tamoxifen and Toremifene on hepatic function and serum lipids in breast cancer patients during adjuvant endocrine therapy.

To investigate the effects of tamoxifen (TAM) and toremifene (TOR) on hepatic function and serum lipid levels in breast cancer patients receiving adjuvant endocrine therapy. The clinical data of 597 early breast cancer patients treated at the First Affiliated Hospital of Nanjing Medical University between January 2016 and December 2022 were collected. All the patients received standard adjuvant endocrine therapy with TAM or TOR after chemotherapy. Hepatic function and serum lipid data of all patients before and at 6 months and 1, 2, and 3 years after the treatment were collected retrospectively and analyzed statistically. There: no negative effect on hepatic function was observed in patients treated with either TAM or TOR. The triglyceride levels in both groups increased during treatment, and the effect of TAM on improving total cholesterol levels was stronger. Total cholesterol levels were not affected by time or treatment regimen. The low-density lipoprotein cholesterol levels decreased in both groups, and the effect was similar between groups. TAM can decrease the high-density lipoprotein cholesterol levels, whereas TOR can increase the high-density lipoprotein cholesterol levels, and there was a significant difference between groups. In the postoperative adjuvant endocrine therapy, TOR and TAM will not negatively impact the hepatic function of breast cancer patients, and TOR is better than TAM in the management of serum lipids; therefore, it may be a better choice for clinical medication.

[Efficacy of bronchoalveolar lavage combined with prone positioning in children with Mycoplasma pneumoniae pneumonia and atelectasis: a prospective randomized controlled study]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—è”åˆä¿¯å§ä½æ²»ç–—å„¿ç«¥è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žä¼´è‚ºä¸å¼ ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with Mycoplasma pneumoniae pneumonia (MPP) and atelectasis and its effect on pulmonary function. METHODS: A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023. The children were randomly divided into a treatment group and a control group, with 47 children in each group. The children in the treatment group were given conventional treatment, BAL, and prone positioning, and those in the control group were given conventional treatment and BAL. The two groups were compared in terms of fever, pulmonary signs, length of hospital stay, lung recruitment, and improvement in pulmonary function. RESULTS: Compared with the control group, the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization, on the day of discharge, and at 1 week after discharge (P<0.05). Compared with the control group, the treatment group had significantly higher levels of forced vital capacity (FVC) as a percentage of the predicted value, forced expiratory volume (FEV) in 1 second as a percentage of the predicted value, ratio of FEV in 1 second to FVC, forced expiratory flow at 50% of FVC as a percentage of the predicted value, forced expiratory flow at 75% of FVC as a percentage of the predicted value, and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge (P<0.05). There was no significant difference in the time for body temperature to return to normal between the two groups (P>0.05). CONCLUSIONS: In the treatment of children with MPP and atelectasis, BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.

Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION: Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath.

BACKGROUND: Pathophysiological conditions underlying pulmonary fibrosis remain poorly understood. Exhaled breath volatile organic compounds (VOCs) have shown promise for lung disease diagnosis and classification. In particular, carbonyls are a byproduct of oxidative stress, associated with fibrosis in the lungs. To explore the potential of exhaled carbonyl VOCs to reflect underlying pathophysiological conditions in pulmonary fibrosis, this proof-of-concept study tested the hypothesis that volatile and low abundance carbonyl compounds could be linked to diagnosis and associated disease severity. METHODS: Exhaled breath samples were collected from outpatients with a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) or Connective Tissue related Interstitial Lung Disease (CTD-ILD) with stable lung function for 3 months before enrollment, as measured by pulmonary function testing (PFT) DLCO (%), FVC (%) and FEV1 (%). A novel microreactor was used to capture carbonyl compounds in the breath as direct output products. A machine learning workflow was implemented with the captured carbonyl compounds as input features for classification of diagnosis and disease severity based on PFT (DLCO and FVC normal/mild vs. moderate/severe; FEV1 normal/mild/moderate vs. moderately severe/severe). RESULTS: The proposed approach classified diagnosis with AUROC=0.877 ± 0.047 in the validation subsets. The AUROC was 0.820 ± 0.064, 0.898 ± 0.040, and 0.873 ± 0.051 for disease severity based on DLCO, FEV1, and FVC measurements, respectively. Eleven key carbonyl VOCs were identified with the potential to differentiate diagnosis and to classify severity. CONCLUSIONS: Exhaled breath carbonyl compounds can be linked to pulmonary function and fibrotic ILD diagnosis, moving towards improved pathophysiological understanding of pulmonary fibrosis.