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.

Ti4+ functionalized zirconium metal-organic frameworks with polymer brushes for specific identification of phosphopeptides in human serum and skimmed milk.

In the present study, click chemistry and Schiff base reactions were simultaneously applied to prepare polymer brush (PEG)-functionalized MOF materials (UiO-66-NH2) and immobilized with Ti4+ (MOF-Brush-THBA-Ti4+) for phosphopeptide analysis. The material has a detection limit of 0.5 fmol, a selectivity of 2000:1, and a loading capacity of 133 mg/g for phosphopeptides. It also demonstrated great repeatability (10 cycles) and recovery rate (96.7 ± 1.4%). During the analysis of bio-samples, 4 specific phosphopeptides were identified in endogenous breast cancer serum, while 11 phosphopeptides were identified in skimmed milk. Moreover, 47 phosphopeptides correlated with 29 phosphorylated proteins were selectively identified from normal control serum, and 66 phosphopeptides correlated with 26 phosphorylated proteins were identified from breast cancer serum. Further analysis of gene ontology (GO) revealed that the detected phosphorylated proteins associated with breast cancer included positive regulation of receptor-mediated endocytosis, proteolysis, extracellular exosome, heparin binding, and chaperone binding. These findings suggest that these associated pathways might contribute to the etiology of breast cancer. Overall, this application exhibits enormous potential in the identification of phosphorylated peptides within bio-samples.

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.

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.

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.

Iodine Immobilized Metal-Organic Framework for NIR-Triggered Antibacterial Therapy on Orthopedic Implants.

Iodine has been known as an effective disinfectant with broad-spectrum antimicrobial potency yet without drug resistance risk when used in clinic. However, the exploration of iodine for antibacterial therapy in orthopedics remains sparse due to its volatile nature and poor solubility. Herein, leveraging the superior absorption capability of metal-organic frameworks (MOFs) and their inherent photocatalytic properties, iodine-loaded MOF surface is presented to realize responsive iodine release along with intracellular reactive oxygen species(ROS) oxidation under near-infrared (NIR) exposure to achieve synergistic antibacterial effect. Iodine is successfully loaded using vapor deposition process onto zeolitic imidazolate framework-8(ZIF-8), which is immobilized onto micro arc oxidized titanium via a hydrothermal approach. The combination of NIR-triggered iodine release and ZIF-8 mediated ROS oxidative stress substantially augments the antibacterial efficacy of this approach both in vitro and in vivo. Furthermore, this composite coating also supported osteogenic differentiation of bone marrow stromal cells, as well as improved osseointegration of coated implants using an intramedullary rat model, suggesting improvement of antibacterial efficacy does not impair osteogenic potential of the implants. Altogether, immobilization of iodine via MOF on orthopedic implants with synergistic antibacterial effect can be a promising strategy to combat bacterial infections.

lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/ß-catenin signaling.

BACKGROUND: MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown. METHODS: RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment. RESULTS: We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/ß-catenin signaling. CONCLUSIONS: These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.

Identification and functional analysis of long non-coding RNAs in the synovial membrane of osteoarthritis patients.

Osteoarthritis (OA), the most common chronic joint disease in the elderly, has become a significant economic burden for families and societies worldwide. Although treatments are continually improving, current drugs only target joint pain, with no effective therapies modifying OA progression. Long noncoding RNAs (lncRNAs), which have received increasing attention in recent years, are abnormally expressed in OA cartilage. In the present study, weighted coexpression network analysis (WGCNA) was applied to identify modules related to certain OA clinical traits. In total, 4404 coding genes and 161 lncRNAs were differentially expressed based on two OA expression profile data sets and normal control samples. Subsequently, 11 independent modules were acquired, and the green module, with a total of 49 hub genes, was identified as the most relevant to OA. These hub genes were validated using the GSE12021 data set. There was only one lncRNA among the hub genes, namely, NONHSAG034351. Thus, we further explored the function of NONHSAG034351-related genes in the network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that NONHSAG034351-associated genes are involved in the response to lipopolysaccharide, angiogenesis, tumour necrosis factor (TNF) signalling, and mitogen-activated protein kinase (MAPK) signalling pathways. In conclusion, we identified modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub-lncRNA, was downregulated in OA synovial tissue and might play a significant role in the pathological progression of this disease. Our findings have important clinical implications and could provide novel biomarkers that indicate the molecular mechanisms of OA and act as potential therapeutic targets. SIGNIFICANCE OF THIS STUDY: Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in osteoarthritis (OA), which is the most common chronic joint disease among the elderly. In the present study, we report the expression profiles of lncRNAs in OA and the identification of modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub-lncRNA identified to be downregulated in the synovial tissue of OA patients, might play a significant role in the pathological progression of OA. Furthermore, our findings provide novel biomarkers associated with the molecular mechanisms underlying OA pathogenesis, thus implying potential therapeutic targets with important clinical implications.

A novel circulating miRNA-based signature for the early diagnosis and prognosis prediction of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a significant public health issue worldwide. The aim of our study was to develop a serum miRNA-based molecular signature for the early detection and prognosis prediction of NSCLC. METHODS: The significantly altered circulating miRNAs were profiled in GSE24709. The top ten upregulated miRNAs were miR-432, miR-942, miR-29c-5p, miR-601, miR-613, miR-520d-3p, miR-1261, miR-132-5p, miR-302b, and miR-154-5p, while the top ten downregulated miRNAs were miR-562, miR-18b, miR-9-3p, miR-154-3p, miR-20b, miR-18a, miR-487a, miR-20a, miR-103, and miR-144. Then, the top four upregulated serum miRNAs (miR-432, miR-942, miR-29c-5p, and miR-601) were validated by real-time quantitative PCR. The clinical significance of two candidate serum miRNAs, miR-942 and miR-601, was further explored. RESULTS: Our results showed that the expression levels of serum miR-942 and serum miR-601 were significantly upregulated in NSCLC. In addition, serum miR-942 and serum miR-601 showed better performance than CEA, CYFRA21-1, and SCCA for early diagnosis of NSCLC. Combining serum miR-942 and serum miR-601 enhanced the efficacy of detecting early-stage NSCLC. Moreover, high serum miR-942 and serum miR-601 were both associated with adverse clinical variables and poor survival. The NSCLC patients with simultaneously high serum miR-942 and serum miR-601 suffered worst clinical outcome, while those with simultaneously low serum miR-942 and serum miR-601 had most favorable outcome. The multivariate analysis showed that serum miR-942 and serum miR-601 were independent prognostic factors for NSCLC. CONCLUSIONS: Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.

Combined antisclerostin antibody and parathyroid hormone (1-34) synergistically enhance the healing of bone defects in ovariectomized rats.

Osteoporotic bones heal more slowly and ineffectively than normal bones. A combination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1-34 (PTH 1-34) may improve healing. A standard osteoporotic rat model was established 12 weeks after bilateral ovarian resection (OVX). Bone defects were created in the right femora of 80 rats, which were randomly divided into 4 groups: control, Scl-Ab (25 mg/kg twice weekly), PTH (60 µg/kg of PTH 1-34 three times a week) and PTH plus Scl-Ab. After 12 weeks of treatment the rats were sacrificed and blood and the distal femora were harvested for biochemical evaluation, histology, microcomputed tomography and biomechanical testing. Compared to the control group, monotherapy and combination therapy with PTH and/or Scl-Ab promoted the formation of new bone, enhanced maximum femoral loading and increased the levels of procollagen type I N­terminal propeptide (PINP) and osteocalcin. The administration of PTH + Scl-Ab maximally enhanced bone defect healing. Combination treatment was better than either treatment alone, indicating a synergistic effect.

Knockdown of lncRNA NEAT1 inhibits Th17/CD4+ T cell differentiation through reducing the STAT3 protein level.

CD4+ T cells differentiated into Th17 cells are a main cause for occurrence and development of rheumatoid arthritis (RA). This study aims to define the role of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) and its downstream molecule in Th17 cell differentiation. Determination of lncRNA NEAT1 expression in the peripheral blood mononuclear cells (PBMCs) of patients with RA and in Th17 cells induced differentiation in vitro used quantitative real-time polymerase chain reaction. Lentivirus-constructed short hairpin RNA interference for NEAT1 (Lenti-siRNA-NEAT1) was pretransfected into CD4+ T cells before inducing treatment of Th17 cell differentiation. NEAT1 targets STAT3 protein was proved by RNA pull down. Lenti-siRNA-NEAT1 was injected into the joint of the mice arthritis model to verify the function of NEAT1 knockdown. Our results showed that NEAT1 is significantly upregulated in the PBMCs of RA patients, as well as in Th17 cells in vitro induced from CD4+ T cells. The knockdown of NEAT1 restrains CD4+ T cells differentiate into Th17 cells. STAT3 protein, a critical molecule for Th17 cell differentiation, is a downstream molecule for NEAT and its cellular level can be positively targeted and regulated by NEAT via reducing the ubiquitination level. Moreover, the cotreatment of NEAT1 knockdown and STAT3 overexpression promotes Th17 cell differentiation compared with NEAT1 knockdown alone. Knockdown of Th17 by in vivo injection of lenti-siRNA-NEAT1 relieves arthritis degree in II type collagen induced mice arthritis model. These data concluded that NEAT1 is auxo-active molecule for CD4+ T cells differentiating into Th17 cells and knockdown of NEAT1 positively inhibits Th17/CD4+ T cell differentiation through reducing the STAT3 protein level.

Comparison of sinus tarsi approach versus extensile lateral approach for displaced intra-articular calcaneal fractures Sanders type IV.

PURPOSE: Displaced intra-articular calcaneus fractures Sanders type IV(DIACFS IV) can result in an unsatisfactory prognosis and a high complication rate. Our investigation intends to compare the outcomes of DIACFS IV treated by open reduction and internal fixation (ORIF) via sinus tarsi approach (STA) with these via extensile lateral approach (ELA). METHODS: Sixty-nine patients (82 ft) with DIACFS IV who were treated with ORIF (29 in STA group and 40 in ELA group) were retrospectively assessed. Median follow-up was 50 months in two groups. Radiographic results were reviewed pre-operatively and post-operatively, and relative complications were collected. Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analog scale (VAS). RESULTS: The wound-healing complication rate was 14.28% in STA group and 34.04% in ELA group (p = .043), and overall complication rate was 54% and 77% (p = .056), respectively. Seven cases of sural nerve injury only occurred in ELA group. The post-operative radiographs of the calcaneus (Böhler's angle, height, width, and length) were significantly different from those measured pre-operatively in each group. And these data were parallel between the two groups. In STA and ELA groups, the average AOFAS was 75.45 versus 72.44 (p = .496), and the mean VAS was 23.95 versus 30.93 (p = .088), respectively. CONCLUSION: Similar clinical and radiographic outcomes are achieved between STA and ELA. And STA has a lower incidence of wound healing complication and sural nerve injury. Therefore, ORIF via STA can be a considerable management for DIACFS IV.

CRISPR/Cas9-mediated noncoding RNA editing in human cancers.

Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.

Does Timing of Surgery Affect Treatment of the Terrible Triad of the Elbow?

BACKGROUND This study investigated the influence of surgical timing on the treatment of terrible triad of the elbow (TTE). MATERIAL AND METHODS After exclusion, 63 patients were enrolled in this study: 20 patients were classified into the emergency group (group A, within 24 h after injury), 26 into the early surgery group (group B, from 4 to 14 days after injury), and 17 into the delayed surgery group (group C, more than 14 days after injury). All patients underwent the same approach, and elbow motion and complication rates were recorded and compared. RESULTS Fifty-eight patients were followed up (mean 20.5±1.9 months), and 5 patients had lost partial final data. At 1 month after the operation, elbow motion in group A was higher than in group B and group C (P<0.01); however, 3 or more months later, there was no distinct difference between group A and group B (P>0.05), while both group A and group B showed better outcomes than group C at all time points (P<0.05). Moreover, group A and group B had better higher elbow motion, MEPS, excellent and good rate than group C at the final clinical visit (all P<0.05). No postoperative pain or complication rate differences were found among the 3 groups except for elbow stiffness (2 in group A, 3 in group B, and 7 in group C) (P<0.05) which required reoperation to enhance elbow function. CONCLUSIONS Emergency or early operation for TTE patients were more effective than delayed operation.

Long and short noncoding RNAs in lung cancer precision medicine: Opportunities and challenges.

The long and short noncoding RNAs have been involved in the molecular diagnosis, targeted therapy, and predicting prognosis of lung cancer. Utilizing noncoding RNAs as biomarkers and systemic RNA interference as an innovative therapeutic strategy has an immense likelihood to generate novel concepts in precision oncology. Targeting of RNA interference payloads such as small interfering RNAs, microRNA mimetic, or anti-microRNA (antagomirs) into specific cell types has achieved initial success. The clinical trials of noncoding RNA-based therapies are on the way with some positive results. Many attempts are done for developing novel noncoding RNA delivery strategies that could overcome systemic or local barriers. Furthermore, it precipitates concerted efforts to define the molecular subtypes of lung cancer, characterize the genomic landscape of lung cancer subtypes, identify novel therapeutic targets, and reveal mechanisms of sensitivity and resistance to targeted therapies. These efforts contribute a visible effect now in lung cancer precision medicine: patients receive molecular testing to determine whether their tumor harbors an actionable come resistance to the first-generation drugs are in clinical trials, and drugs targeting the immune system are showing activity in patients. This extraordinary promise is tempered by the sobering fact that even the newest treatments for metastatic disease are rarely curative and are effective only in a small fraction of all patients. Thus, ongoing and future efforts to find new vulnerabilities of lung cancers unravel the complexity of drug resistance, increase the efficacy of immunotherapies, and perform biomarker-driven clinical trials are necessary to improve the outcome of lung cancer patients.

Direction-of-Arrival Estimation with Coarray ESPRIT for Coprime Array.

A coprime array is capable of achieving more degrees-of-freedom for direction-of-arrival (DOA) estimation than a uniform linear array when utilizing the same number of sensors. However, existing algorithms exploiting coprime array usually adopt predefined spatial sampling grids for optimization problem design or include spectrum peak search process for DOA estimation, resulting in the contradiction between estimation performance and computational complexity. To address this problem, we introduce the Estimation of Signal Parameters via Rotational Invariance Techniques (ESPRIT) to the coprime coarray domain, and propose a novel coarray ESPRIT-based DOA estimation algorithm to efficiently retrieve the off-grid DOAs. Specifically, the coprime coarray statistics are derived according to the received signals from a coprime array to ensure the degrees-of-freedom (DOF) superiority, where a pair of shift invariant uniform linear subarrays is extracted. The rotational invariance of the signal subspaces corresponding to the underlying subarrays is then investigated based on the coprime coarray covariance matrix, and the incorporation of ESPRIT in the coarray domain makes it feasible to formulate the closed-form solution for DOA estimation. Theoretical analyses and simulation results verify the efficiency and the effectiveness of the proposed DOA estimation algorithm.

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.

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.

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.

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.