Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Following Neoadjuvant Immunochemotherapy in Resectable Stage III Non-Small Cell Lung Cancer Among Chinese Populations: A Multi-Center Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment but may pose greater technical challenges for surgery. This study aims to assess the feasibility and oncological effectiveness of video-assisted thoracoscopic surgery (VATS) for resectable stage III NSCLC after neoadjuvant immunochemotherapy. METHODS: Initial stage IIIA-IIIB NSCLC patients with neoadjuvant immunochemotherapy undergoing either VATS or open lobectomy at 6 medical centers during 2019-2023 were retrospectively identified. Perioperative outcomes and 2-year survival was analyzed. Propensity-score matching (PSM) was employed to balance patient baseline characteristics. RESULTS: Among the total 143 patients, PSM yielded 62 cases each for VATS and OPEN groups. Induction-related adverse events were comparable between the 2 groups. VATS showed a 14.5% conversion rate. Notably, VATS decreased numeric rating scales for postoperative pain, shortened chest tube duration (5[4-7] vs. 6[5-8] days, P = .021), reduced postoperative comorbidities (21.0% vs. 37.1%, P = .048), and dissected less N1 lymph nodes (5[4-6] vs. 7[5-9], P = .005) compared with thoracotomy. Even when converted, VATS achieves perioperative outcomes equivalent to thoracotomy. Additionally, over a median follow-up of 29.5 months, VATS and thoracotomy demonstrated comparable 2-year recurrence-free survival (77.20% vs. 73.73%, P = .640), overall survival (87.22% vs. 88.00%, P = .738), cumulative incidences of cancer-related death, and recurrence patterns. Subsequent subgroup comparisons and multivariate Cox analysis likewise revealed no statistical difference between VATS and thoracotomy. CONCLUSION: VATS is a viable and effective option for resectable stage III NSCLC patients following neoadjuvant immunochemotherapy, leading to decreased surgical-related pain, earlier chest tube removal, reduced postoperative complications, and similar survival outcomes compared to thoracotomy.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM: To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS: The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS: The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION: The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer.

BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.

Deep neural network with self-attention based automated determination system for treatment zone and peripheral steepened zone in Orthokeratology for adolescent myopia.

PURPOSE: The aim of this study is to develop an automatic model based on deep learning techniques for determining the Treatment Zone (TZ) and Peripheral Steepened Zone (PSZ) following Orthokeratology (OK) treatment. METHODS: A total of 1346 corneal topography maps were included in the study. A deep neural network based on the Segformer architecture was constructed to automatically detect TZ and PSZ. The model was optimized and trained multiple times, and the areas of TZ, PSZ, and TZ decentration were calculated based on the segmentation results. RESULTS: The mean Intersection over Union (mIoU) of the overall segmentation results of the model reached over 97% after multiple training with different optimization methods, and the IoU for the TZ and PSZ segmentation tasks were 98.08% and 94.54% in test set, respectively. Moreover, the model demonstrated high consistency with the expert annotation for the TZ segmentation, while a significant difference was found in the PSZ segmentation and expert annotation due to several interference factors. CONCLUSION: This study presents an efficient and repeatable system for clinical research, based on a deep neural network that accurately determines TZ and PSZ after OK treatment using the Segformer architecture. However, further deployment validation may be necessary.

Improvement of physicochemical properties, microstructure and stability of lotus root starch/xanthan gum stabilized emulsion by multi-frequency power ultrasound.

Multi-frequency power ultrasound was applied as an environmentally friendly technique to control the nanoparticles (LS/XG-NPs) embedded with lotus root starch/xanthan gum, with the aim of enhancing the stability of Pickering emulsions. The present investigation was centered on evaluating the impact of ultrasound technology on various aspects of the emulsions, encompassing their mean particle size, particle size distribution, zeta potential, microstructure, rheological characteristics, and environmental stability. The findings of this study indicate that ultrasonic treatment enhanced the adsorption of LS/XG-NP onto oil droplets surface, resulting in a reduction in their size. Additionally, ultrasonic treatment decreased the viscosity and Brownian motion rate of the emulsion stabilized by LS/XG-NP, leading to increased fluidity. Furthermore, the emulsion's thermal stability and resistance to environmental oxidation were significantly enhanced through ultrasonic treatment. The Pickering emulsions that were prepared using ultrasound demonstrated excellent resistance to acid, alkali (pH 2-8) and salt ions (50-300 mM NaCl) for a period of 30 days during storage. It was worth anticipating that ultrasound-assisted LS/XG-NPs could efficiently retard the volatilization of fishy odor components within fish oil. Taken together, the present research has evinced the efficacy of ultrasound in enhancing the stability of Pickering emulsions coated with LS/XG-NPs. These findings offer significant novel insights into the advancement of ultrasound-assisted Pickering emulsions that are stabilized with starch-based or biopolymeric materials.

A circRNA-based ceRNA network shows its diagnostic value in non-small-cell lung cancer.

BACKGROUND: Numerous studies have reported the vital roles of circular RNA (circRNA)-based competitive endogenous RNA (ceRNA) regulatory networks in cancers. Here, we established a non-small-cell lung cancer (NSCLC)-related circRNA-miRNA-mRNA axis and estimated its diagnostic value in NSCLC. METHODS: The circ_0061235-miR-3180-5p-PPM1L axis was constructed by small RNA deep sequencing, bioinformatics databases, and preliminary testing. The serum levels of the selected circ_0061235, miR-3180-5p, and PPM1L were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic power. RESULTS: The levels of circ_0061235, miR-3180-5p, and PPM1L showed close correlations according to the ceRNA regulation rule. They were significantly dysregulated in NSCLC and showed the diagnostic ability to discriminate between healthy and NSCLC, and remarkably, between benign lung tumors and NSCLC. Additionally, the down-regulated levels of hsa_circ_0061235, the up-regulated levels of miR-3180-5p, and the decreased levels of PPM1L were correlated to more aggressive features of NSCLC, such as lymph node metastasis, distant metastasis, and higher stages. Intriguingly, compared to the single circ_0061235, miR-3180-5p, PPM1L, and traditional tumor markers, the diverse combinations of circ_0061235, miR-3180-5p, and PPM1L showed much higher sensitivity and specificity to differentiate greater or lesser severity of NSCLC. GO annotation and KEGG pathway analyses revealed the underlying role of the circ_0061235-miR-3180-5p-PPM1L axis in NSCLC. CONCLUSIONS: We established a specific circRNA-miRNA-mRNA network with higher sensitivity and specificity to diagnose NSCLC, particularly more aggressive NSCLC, providing a new strategy for further developing tumor biomarkers.

Ultrasonic and homogenization: An overview of the preparation of an edible protein-polysaccharide complex emulsion.

Emulsion systems are extensively utilized in the food industry, including dairy products, such as ice cream and salad dressing, as well as meat products, beverages, sauces, and mayonnaise. Meanwhile, diverse advanced technologies have been developed for emulsion preparation. Compared with other techniques, high-intensity ultrasound (HIUS) and high-pressure homogenization (HPH) are two emerging emulsification methods that are cost-effective, green, and environmentally friendly and have gained significant attention. HIUS-induced acoustic cavitation helps in efficiently disrupting the oil droplets, which effectively produces a stable emulsion. HPH-induced shear stress, turbulence, and cavitation lead to droplet disruption, altering protein structure and functional aspects of food. The key distinctions among emulsification devices are covered in this review, as are the mechanisms of the HIUS and HPH emulsification processes. Furthermore, the preparation of emulsions including natural polymers (e.g., proteins-polysaccharides, and their complexes), has also been discussed in this review. Moreover, the review put forward to the future HIUS and HPH emulsification trends and challenges. HIUS and HPH can prepare much emulsifier-stable food emulsions, (e.g., proteins, polysaccharides, and protein-polysaccharide complexes). Appropriate HIUS and HPH treatment can improve emulsions' rheological and emulsifying properties and reduce the emulsions droplets' size. HIUS and HPH are suitable methods for developing protein-polysaccharide forming stable emulsions. Despite the numerous studies conducted on ultrasonic and homogenization-induced emulsifying properties available in recent literature, this review specifically focuses on summarizing the significant progress made in utilizing biopolymer-based protein-polysaccharide complex particles, which can provide valuable insights for designing new, sustainable, clean-label, and improved eco-friendly colloidal systems for food emulsion. PRACTICAL APPLICATION: Utilizing complex particle-stabilized emulsions is a promising approach towards developing safer, healthier, and more sustainable food products that meet legal requirements and industrial standards. Moreover, the is an increasing need of concentrated emulsions stabilized by biopolymer complex particles, which have been increasingly recognized for their potential health benefits in protecting against lifestyle-related diseases by the scientific community, industries, and consumers.

Eicosapentaenoic acid supplementation modulates the osteoblast/osteoclast balance in inflammatory environments and protects against estrogen deficiency-induced bone loss in mice.

BACKGROUND: An imbalance of osteoblasts (OBs) and osteoclasts (OCs) in a chronic inflammatory microenvironment is an important pathological factor leading to osteoporosis. Eicosapentaenoic acid (EPA) has been shown to suppress inflammation in macrophages and adipocytes. However, the effect of EPA on OBs and OCs has yet to be fully elucidated. AIMS: We explored the roles of EPA in the differentiation of OBs and OCs, as well as the coupling between OBs and OCs in an inflammatory microenvironment. The effects of EPA on estrogen deficiency-induced osteoporosis were also evaluated. METHODS: Mouse bone marrow mesenchymal stem cells (mBMSCs) and mouse bone marrow-derived macrophages (mBMMs) were used for in vitro OBs and OCs differentiation. TNF-α was used to create an inflammatory microenvironment. We examined the effects of EPA on osteoblastogenesis in the absence or presence of TNF-α and collect OBs' culture medium as the conditioned medium (CM). Then we examined the effects of EPA and CM on RANKL-induced osteoclastogenesis. The in vivo effects of EPA were determined using an ovariectomized (OVX) mouse model treated with EPA or vehicle. RESULTS: High-dose EPA was shown to promote osteoblastogenesis in an inflammatory environment in vitro, as well as upregulate expression of OBs-specific proteins and genes. ARS and ALP staining also showed that high-dose EPA-treated groups restored mBMSCs' impaired osteogenic capacity caused by TNFa. Mechanistically, EPA suppressed the NF-κB pathway activated by TNF-α in mBMSCs and rescued TNF-α-mediated inhibition of osteoblastogenesis. EPA was also shown to inhibit expression of RANKL and decrease the RANKL/OPG ratio in OBs in an inflammatory environment. CM from TNF-α-stimulated OBs promoted osteoclastogenesis of mBMMs; EPA-treated CM prevented this. In the OVX mouse model, EPA supplementation prevented bone loss in an estrogen deficiency-induced inflammatory environment. CONCLUSIONS: EPA was demonstrated for the first time to restore mBMSCs' impaired osteogenic capacity caused by TNFa-induced inflammation and rescue the OBs/OCs balance via regulation of RANKL and OPG expression in OBs. EPA showed a remarkable ability to prevent bone loss in OVX mice, suggesting a potential application of EPA in postmenopausal osteoporosis.

Whole Blood-Derived circUSP10 Acts as a Diagnostic Biomarker in Patients With Early-Stage Non-Small-Cell Lung Cancer.

Accumulating evidence has indicated that differentially expressed noncoding circular RNAs (circRNAs) play essential roles in the occurrence and development of various types of cancer. Here, we aimed to identify and explore the diagnostic value of hsa_circ_0003026 (named circUSP10) in patients with early non-small-cell lung cancer (NSCLC). The differentially expressed circRNAs were screened from the microarray-based assay of human NSCLC tissues and their corresponding noncancerous tissues, and the candidate circRNAs were further verified in patients with NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Circulating circUSP10 was isolated from whole blood of healthy people and patients with NSCLC and was detected by RT-qPCR. In addition, the diagnostic value of circUSP10 in early NSCLC was evaluated by receiver operating characteristic (ROC) curve analysis. We found that circUSP10 was upregulated in tumor tissues from patients with early NSCLC and associated with tumor size and tumor-node-metastasis (TNM) stage. Importantly, circUSP10 was obviously upregulated in the whole blood of patients with NSCLC. Additionally, whole blood-derived circUSP10 showed good diagnostic performance for screening early NSCLC and was relatively stable in blood under adverse conditions. These findings demonstrate that circUSP10 may act as a novel biomarker for the diagnosis of early-stage NSCLC, suggesting the potential of circUSP10 in RNA-based therapy for cancer.

The mtDNA fragments within exosomes might be novel diagnostic biomarkers of non-small cell lung cancer.

BACKGROUND: A portion of circulating mtDNAs is encapsulated in exosomes, but their contribution to cancers is rarely studied. We aim to investigate the diagnostic potential of exosomal mtDNA content for non-small cell lung cancer (NSCLC). METHODS: Exosomes were isolated from plasma and identified by western blot, scanning electron microscopy, and particle size analysis. The plasma and plasma exosomal mtDNA fragment levels (mtDNA79, mtDNA230, and MTATP8) in healthy, pneumonia, benign lung tumors, and NSCLC were quantified by qPCR. Statistical analyses were performed to compare the levels of mtDNA fragments in different subgroups. ROC analyses were used to evaluate mtDNA fragments' diagnostic sensitivity and specificity. RESULTS: We found that plasma mtDNAs were partially present in exosomes. Both plasma and exosomal mtDNA fragments (mtDNA79, mtDNA230, and MTATP8) were increased in NSCLC, particularly more malignant NSCLC. Compared to plasma mtDNAs and traditional tumor markers, exosomal mtDNAs are more closely associated with aggressive features of NSCLC, like bigger tumor sizes, advanced stages, lymph node metastasis, and distant metastasis, showing higher sensitivity and specificity to diagnose NSCLC. CONCLUSIONS: Changed contents of plasma and plasma exosomal mtDNAs show great potential to diagnose NSCLC, and exosomal mtDNAs might be promising biomarkers for more aggressive NSCLC.

Prognostic impact of tumor spread through air spaces for T2aN0 stage IB non-small cell lung cancer.

BACKGROUND: Spread through air spaces (STAS) is a pattern of invasion recently identified in non-small cell lung cancer (NSCLC), with a poor prognosis. However, the predictive impact of STAS in stage IB NSCLC is not well understood. This investigation aims to assess the prognostic influence of STAS in stage IB NSCLC. METHODS: We reviewed 130 resected stage IB NSCLC between 2010 and 2015. Beyond the central tumor edge, lung parenchymal air gaps containing cancer cells were identified as STAS. In order to estimate recurrence-free survival (RFS) and overall survival (OS), Cox models and Kaplan-Meier techniques were utilized. Logistic regression analysis was employed to define the factors influencing STAS. RESULTS: Of 130 patients, 72 (55.4%) had STAS. STAS was a significant prognosticator. Kaplan-Meier method showed that STAS-positive patients had a significantly lower OS and RFS than STAS-negative patients (5-year OS, 66.5% vs. 90.4%, p = 0.02; 5-year RFS, 59.5% vs. 89.7%, p = 0.004) In a semiquantitative assessment, the RFS and OS were shorter in survival analysis when STAS increased (5-year RFS, 89.7%, no STAS, 61.8%, low STAS, 57.2%, high STAS, p = 0.013; 5-year OS, 90.4%, no STAS, 78.3%, low STAS, 57.2%, high STAS, p = 0.002). The association between STAS and poor differentiation, adenocarcinoma, and vascular invasion (p value was <0.001, 0.047, and 0.041, respectively) was statistically significant. CONCLUSIONS: The STAS is an aggressive pathological feature. RFS and OS could be significantly reduced by STAS, while it also serves as an independent predictor.

Peripheral Blood-Derived CircVPS35L as a Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer.

INTRODUCTION: Circular RNAs (circRNAs) are dysregulated in cancers and are stably expressed in body fluids such as blood. We therefore identified and evaluated the clinical value of a newly found circRNA VPS35L (circVPS35L) as a biomarker for the diagnosis of non-small cell lung cancer (NSCLC). METHODS: Reverse-transcription quantitative PCR (RT-qPCR) was used to determine the expression levels of circVPS35L in tissues, whole blood, and cell lines. The actinomycin D assay and RNase R treatment were utilized to determine the stability of circVPS35L. Receiver operating characteristic (ROC) curve analysis was conducted to predict the diagnostic value of blood-derived circVPS35L in NSCLC. RESULTS: CircVPS35L was found to be downregulated in NSCLC tissues and cell lines. Interestingly, circVPS35L expression was significantly correlated with tumor size (p = 0.0269), histology type (p < 0.0001), and TNM stage (p = 0.0437). Importantly, circVPS35L was poorly expressed in peripheral blood of NSCLC patients when compared with healthy controls and patients with benign lung disease. ROC analysis revealed a higher diagnostic value of circVPS35L than the three conventional tumor markers (CYFR21-1, NSE, and CEA) in patients with NSCLC. Moreover, circVPS35L was highly stable in peripheral blood when exposed to undesirable conditions. CONCLUSION: These findings demonstrate that circVPS35L has great potential as a novel biomarker for the diagnosis of NSCLC and can be used to distinguish NSCLC from benign lung disease.

The diagnostic potential of a circRNA-miRNA network in non-small cell lung cancer.

Increasing studies demonstrate the significant contributions of circRNA-related competitive endogenous RNA (ceRNA) regulatory networks to tumorigenesis and cancer progression. Here, we aimed to construct a non-small cell lung cancer (NSCLC)-specific circRNA-miRNA network and evaluate its diagnostic potential in NSCLC. MiRNA deep sequencing was performed to screen differentially-expressed serum miRNAs in NSCLC. Four bioinformatics databases (TargetScan, miRanda, starBase, and RNAhybrid) were used to analyze the integrated circRNA-miRNA interaction network. The circRNA-miRNA network, including hsa-miR-4482-3p, hsa-miR-146a-3p, hsa_circ_0008167 and hsa_circ_0003317 was constructed based on their interactions and preliminary testing in NSCLC cells. The relative levels of the selected non-coding RNAs (ncRNAs) were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) in the healthy, pneumonia, benign lung tumor and NSCLC cohorts. The diagnostic power of the circRNA-miRNA network was evaluated using receiver operating characteristic (ROC) analyses. The serum levels of hsa-miR-4482-3p, hsa-miR-146a-3p, hsa_circ_0008167, and hsa_circ_0003317 were dysregulated in NSCLC. The combination of the four ncRNAs showed the highest diagnostic value to discriminate between benign lung tumors and NSCLC. Additionally, the upregulated levels of hsa_circ_0008167 were correlated to more aggressive features of NSCLC, such as lymph node metastasis, distant metastasis, and higher stage. Furthermore, the combination of hsa_circ_0008167 + hsa-miR-4482-3p, and hsa_circ_0008167 + hsa-miR-4482-3p + hsa-miR-146a-3p had the greatest diagnostic power to differentiate between lymph node +/- metastases and higher/lower stages, respectively, compared to circRNAs or miRNAs alone, and traditional tumor markers. In conclusion, we identified a specific circRNA-miRNA network with higher sensitivity and specificity to diagnose NSCLC, thereby providing a new strategy for further development of ceRNA-related tumor markers in other cancers. KEY MESSAGES: Serum miR-4482-3p, miR-146a-3p, circ_0008167 and circ_0003317 are dysregulated in NSCLC. Higher levels of serum circ_0008167 are associated with more malignant NSCLC. Multiple combinations of circRNAs and miRNAs show higher value to diagnose NSCLC.

Global, regional, and national burden of chronic respiratory diseases and associated risk factors, 1990-2019: Results from the Global Burden of Disease Study 2019.

Background: The burden of chronic respiratory diseases has changed over the three decades. This study aims to describe the spatiotemporal trends of prevalence, mortality, and disability-adjusted life years (DALY) due to chronic respiratory diseases (CRDs) worldwide during 1990-2019 using data from the Global Burden of Disease Study 2019 (GBD 2019). Methods: The prevalence, mortality, and DALY attributable to CRDs and risk factors from 1990 to 2019 were estimated. We also assessed the driving factors and potentiality for improvement with decomposition and frontier analyses, respectively. Results: In 2019, 454.56 [95% uncertainty interval (UI): 417.35-499.14] million individuals worldwide had a CRD, showing a 39·8% increase compared with 1990. Deaths due to CRDs were 3.97 (95%UI: 3.58-4.30) million, and DALY in 2019 was 103.53 (95%UI: 94.79-112.27) million. Declines by average annual percent change (AAPC) were observed in age-standardized prevalence rates (ASPR) (0.64% decrease), age-standardized mortality rates (ASMR) (1.92%), and age-standardized DALY rates (ASDR) (1.72%) globally and in 5 socio-demographic index (SDI) regions. Decomposition analyses represented that the increase in overall CRDs DALY was driven by aging and population growth. However, chronic obstructive pulmonary disease (COPD) was the leading driver of increased DALY worldwide. Frontier analyses witnessed significant improvement opportunities at all levels of the development spectrum. Smoking remained a leading risk factor (RF) for mortality and DALY, although it showed a downward trend. Air pollution, a growing factor especially in relatively low SDI regions, deserves our attention. Conclusion: Our study clarified that CRDs remain the leading causes of prevalence, mortality, and DALY worldwide, with growth in absolute numbers but declines in several age-standardized estimators since 1990. The estimated contribution of risk factors to mortality and DALY demands the need for urgent measures to improve them. Systematic review registration: http://ghdx.healthdata.org/gbd-results-tool.

Emerging role of long non-coding RNA JPX in malignant processes and potential applications in cancers.

ABSTRACT: Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.

Pickering emulsion: A multi-scale stabilization mechanism based on modified lotus root starch/xanthan gum nanoparticles.

New Pickering emulsion stabilizer LS/XG-NPs (Lotus root starch/xanthan gum nanoparticles) was prepared via autoclaving-cooling method followed by combination with XG. The LS/XG-NPs showed uniform and stable particles with particle size <500 nm, PDI <30, and zeta potential 30-40. The autoclaving-cooling treatment completely changed the crystalline form (from A-type to B-type) and structure of starch; hydrogen bonding and electrostatic interactions were proved to be existed between starch and XG in LS/XG-NPs. The addition of XG increased the contact angle of LS/XG-NPs from 58.79° to 85.42°. In the prepared Pickering emulsion, the LS/XG-NPs adsorbed well on the oil droplets surface, forming a three-dimensional gel network with evenly distributed oil droplets. The Pickering emulsion prepared with LS/XG-NPs showed excellent storage stability and auto-oxidation resistance; the EPA + DHA content in the emulsion remained at 92.46 % after 5 d of storage. The results of this study suggest that LS/XG-NPs have the potential to be food-grade Pickering emulsifiers that not only stabilize emulsions but also prevent emulsion oils from oxidizing.

Clinical and Imaging Characteristics of Primary Severe Community-Acquired Pneumonia Caused by Hypervirulent Klebsiella Pneumoniae.

BACKGROUND: To investigate the CT imaging features and microbial phenotypes of primary severe community-acquired pneumonia caused by hypervirulent Klebsiella pneumoniae (hvKp). METHODS: Patients diagnosed with primary hvKp pneumonia were included, and their clinical data were analyzed, including the baseline characteristics and CT imaging results. After hypermucoviscosity phenotyping, the strains, serological types, and virulence genes of hvKp were identified using multiplex PCR. RESULTS: Twelve patients with primary hvKp pneumonia were included (11 males, 1 female). All patients were infected via respiratory tract inhalation. Ten patients were long-term drinkers. Four patients (33.3%), who were long-term alcohol abusers, died within 30 days after diagnosis. No extrapulmonary metastatic infection was found in any patient. The imaging of lung lesions at the early disease stage exhibited an extensive consolidation in the lungs. As the disease progressed, the most common imaging features were pleural effusion (9/12), cavitation and necrosis (8/12), and pneumothorax (3/12). The serological typing of the capsular polysaccharides on hvKp strains were K1 (6/12) and K2 (6/12). Furthermore, the virulence genotyping showed rmpA (11/12), magA (11/12), ureA (12/12), mrkD (12/12), fim-1 (12/12), wabG (12/12), ybtS (12/12), and iucB (11/12). CONCLUSIONS: Primary severe community-acquired hvKp-associated pneumonia is more common in men, especially those with a long-term history of alcohol consumption. CT scanning at the early disease stage mostly showed extensive pulmonary consolidation, which was prone to be combined with cavitation, necrosis, and pleural effusion. K1 and K2 serotypes were identified among the hvKp strains, which were not prone to form extrapulmonary metastasis via the bloodstream.