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Abstract Hepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via the TCGA and GEO databases and our clinical data, we found that its overexpression is associated with worse survival. The relevance of PNMA1 extends to immune factors such as M1 macrophages, CD8+ T cells, and immune checkpoints. Mechanistically, PNMA1 shapes a suppressive tumor microenvironment strongly linked to bile acid metabolism. It promotes tumor progression via immune inhibition and PI3K–AKT pathway activation. Notably, PNMA1 has emerged as a promising therapeutic target for tyrosine kinase inhibitors, as confirmed by reduced IC50 values and molecular docking. Experimental knockdown of PNMA1 hindered HepG2 cell proliferation and migration. Furthermore, PNMA1 is a pivotal HCC biomarker and therapeutic target with a focus on cancer progression, immune modulation, and bile acid metabolism.

Abstract Traffic sign poles are crucial components of the highway system, and their maintenance mainly relies on the subjective judgment of staff, which is low-efficiency and will lead to mistaken inspections. This paper proposes a convenient and effective method to monitor the health of sign poles by using a mobile phone. It is unknown whether a mobile phone can be used as a conventional acceleration sensor. Therefore, the performance of the mobile phone was initially tested to ensure its suitability for acquiring the acceleration data of the traffic sign pole. The results show that the acceleration sensor of mobile phones is high-performance and can be used as a traditional acceleration sensor under the similar sampling frequency. The mobile phone can measure the 1st, 2nd and 5th natural frequencies of the traffic sign pole. Although the 1st and 5th natural frequencies have a large error with simulation, the 2nd natural frequency is accurate and stable. The looseness of the base connection greatly impacts on the 2nd natural frequency, which can be used as a measure of the loose base connection. The 2nd natural frequency was measured for 21 times and found to conform to a normal distribution. The relationship between the 2nd natural frequency and base connection loosening was investigated, which fitted to the equation. The fitting result is good and can be used to predict the degree of sign pole base connection loosening. Therefore, the mobile phone based convenient health monitoring method for traffic sign poles is feasible.

Abstract Because China produces the most crayfish in the world, safe solutions must be improved to mitigate the risks of ongoing heavy metal stressors accumulation. This study aimed to use Saccharomyces cerevisiae as a bioremediation agent to counteract the harmful effect of cadmium (Cd) on crayfish (Procambarus clarkia). Our study used three concentrations of S. cerevisiae on crayfish feed to assess their Cd toxicity remediation effect by measuring total antioxidant capacity (TAC) and the biomarkers related to oxidative stress like malondialdehyde (MDA), protein carbonyl derivates (PCO), and DNA–protein crosslink (DPC). A graphite furnace atomic absorption spectroscopy device was used to determine Cd contents in crayfish. Furthermore, the mRNA expression levels of lysozyme (LSZ), metallothionein (MT), and prophenoloxidase (proPO) were evaluated before and following the addition of S. cerevisiae. The results indicated that S. cerevisae at 5% supplemented in fundamental feed exhibited the best removal effect, and Cd removal rates at days 4th, 8th, 12th, and 21st were 12, 19, 29.7, and 66.45%, respectively, which were significantly higher than the basal diet of crayfish. The addition of S. cerevisiae increased TAC levels. On the other hand, it decreased MDA, PCO, and DPC, which had risen due to Cd exposure. Furthermore, it increased the expression of proPO, which was reduced by Cd exposure, and decreased the expression of LSZ and MT, acting in the opposite direction of Cd exposure alone. These findings demonstrated that feeding S. cerevisiae effectively reduces the Cd from crayfish and could be used to develop Cd-free crayfish-based foods.

Abstract To evaluate myocardial strain in patients with different coronary artery disease-reporting and data system (CAD-RADS) levels using the computed tomography (CT) feature tracking technology and to investigate the relationship of myocardial strain with coronary artery calcium scores (CACs) and the degree of coronary artery stenosis. We prospectively enrolled 237 consecutive patients to undergo coronary CT angiography. The participants were divided into the following groups: control (n = 87), CAD-RADS 1 (n = 43), CAD-RADS 2 (n = 43), CAD-RADS 3 (n = 38), and CAD-RADS 4 and above (n = 26). Myocardial strains were analyzed by commercial software, and CACs and coronary stenosis were assessed on post-processing stations. Differences between multiple groups were analyzed using one-way analysis of variance or the Kruskal–Wallis test. Logistic regression were used to analyze the effects of dichotomous variables. As the CAD-RADS level increased, the global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) of the left ventricle based on CT gradually decreased. A significant correlation was observed between global myocardial strain and CACs (GRS: r = − 0.219, GCS: r = 0.189, GLS: r = 0.491; P

Abstract Successful ultrasound-guided supraclavicular block (SCB) requires the understanding of sonoanatomy and identification of the optimal view. Segmentation using a convolutional neural network (CNN) is limited in clearly determining the optimal view. The present study describes the development of a computer-aided diagnosis (CADx) system using a CNN that can determine the optimal view for complete SCB in real time. The aim of this study was the development of computer-aided diagnosis system that aid non-expert to determine the optimal view for complete supraclavicular block in real time. Ultrasound videos were retrospectively collected from 881 patients to develop the CADx system (600 to the training and validation set and 281 to the test set). The CADx system included classification and segmentation approaches, with Residual neural network (ResNet) and U-Net, respectively, applied as backbone networks. In the classification approach, an ablation study was performed to determine the optimal architecture and improve the performance of the model. In the segmentation approach, a cascade structure, in which U-Net is connected to ResNet, was implemented. The performance of the two approaches was evaluated based on a confusion matrix. Using the classification approach, ResNet34 and gated recurrent units with augmentation showed the highest performance, with average accuracy 0.901, precision 0.613, recall 0.757, f1-score 0.677 and AUROC 0.936. Using the segmentation approach, U-Net combined with ResNet34 and augmentation showed poorer performance than the classification approach. The CADx system described in this study showed high performance in determining the optimal view for SCB. This system could be expanded to include many anatomical regions and may have potential to aid clinicians in real-time settings. Trial registration The protocol was registered with the Clinical Trial Registry of Korea (KCT0005822, https://cris.nih.go.kr ).

Abstract Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants. Pathogenicity was defined according to the standards and guidelines of the American College of Medical Genetics and Genomics. We identified 33 rare variants predicted to be deleterious in 39 patients. The fasting [1.57(1.06–2.22) ng/ml] and postprandial C-peptide levels [2.8(1.75–4.46) ng/ml] of the patients with such WFS1 variations were lower than those of the patients without WFS1 variation [2.09(1.43–3.05) and 4.29(2.76–6.07) respectively, ng/ml]. Six (0.9%) patients carried pathogenic or likely pathogenic variants; they met the diagnostic criteria for WFS1-DM according to the latest guidelines, but typical phenotypes of Wolfram syndrome were seldom observed. They were diagnosed at an earlier age and usually presented with an absence of obesity, impaired beta cell function, and the need for insulin treatment. WFS1-DM is usually mistakenly diagnosed as type 2 diabetes, and genetic testing is helpful for individualized treatment.

Abstract CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.

Abstract The existing multi-person collaborative design scheme of Building Information Modeling (BIM) integrated with blockchain faces problems such as poor reliability of BIM drawing, inconsistent drawing information, redundant information, and inaccurate protection of copyright interests. This paper proposes a multi-person collaborative design model for BIM drawing that combines blockchain and InterPlanetary File System (IPFS). This model uses blockchain to store drawing design information to protect the copyright interests of designers and combines IPFS to ensure the reliability of drawing. A cycle division mechanism is designed to solve the problem of drawing information synchronization when multiple people collaborate in design. The Semantic Differential Transaction (SDT) method is used to achieve incremental update of drawing and reduce the information redundancy of the blockchain. Finally, a comparative analysis and validation evaluation of the scheme is carried out, and the usability of the scheme is illustrated with an illustrative example. The results show that: (1) proposed scheme is feasible for multi-person collaborative design; (2) proposed scheme can effectively ensure the reliability of drawing and reduce the redundancy of blockchain information, so as to achieve copyright protection for designers.

Abstract Ageing is co-regulated by genetic and environmental factors. Life on earth lives and evolves in a mild geomagnetic field. Yet, the biological effects of a moderate magnetic field on ageing and the underlying genetic mechanisms remain barely unknown. Here, we report that a moderate static magnetic field (SMF) extends the lifespan of Caenorhabditis elegans, a well-established model organism in ageing research. Consistently, the SMF-treated worms show improved motility and mitochondrial function when aged. We identified from the transcriptomic changes upon SMF treatment that the upregulation of three cytochrome P450 genes are required for SMF-induced longevity. Our findings thus reveal that proper SMF treatment could promote longevity through the well-conserved cytochrome P450 enzymes.

Abstract We evaluated pulmonary sequelae in COVID-19 survivors by quantitative inspiratory–expiratory chest CT (QCT) and explored abnormal pulmonary diffusion risk factors at the 6-month follow-up. This retrospective study enrolled 205 COVID-19 survivors with baseline CT data and QCT scans at 6-month follow-up. Patients without follow-up pulmonary function tests were excluded. All subjects were divided into group 1 (carbon monoxide diffusion capacity [DLCO] 75%). Data was analyzed by two-sample t-test, Spearman test, etc. 29% survivors showed air trapping by follow-up QCT. Semiquantitative CT score and QCT parameter of air trapping in group 1 were significantly greater than group 2 (p

Abstract Bullous pemphigoid (BP), the most frequent blistering dermatosis in the elderly, is associated with increased mortality. The severity of BP can be assessed by detecting the anti-BP180 immunoglobulin G (IgG) concentration, but the lab test is not available in many community clinics. BP patients are usually in a hypercoagulable state with increased levels of D-dimer and fibrin degradation products (FDPs). We aimed to evaluate the use of D-dimer and FDPs in assessing BP severity. We compared the levels of plasma D-dimer, plasma FDPs, eosinophil counts, eosinophil cationic protein, and serum anti-BP180 IgG concentration between 48 typical BP patients and 33 Herpes zoster (HZ) patients (control group). Correlational analyses were conducted to determine the relationships between the lab values and common BP severity markers. The plasma D-dimer and FDP levels were higher in BP patients than in HZ controls (D-dimer: 3297 ± 2517 µg/L vs. 569.70 ± 412.40 µg/L; FDP: 9.74 ± 5.88 mg/L vs. 2.02 ± 1.69 mg/L, respectively, P

Abstract In this study, we aimed to propose a novel diabetes index for the risk classification based on machine learning techniques with a high accuracy for diabetes mellitus. Upon analyzing their demographic and biochemical data, we classified the 2013–16 Korea National Health and Nutrition Examination Survey (KNHANES), the 2017–18 KNHANES, and the Korean Genome and Epidemiology Study (KoGES), as the derivation, internal validation, and external validation sets, respectively. We constructed a new diabetes index using logistic regression (LR) and calculated the probability of diabetes in the validation sets. We used the area under the receiver operating characteristic curve (AUROC) and Cox regression analysis to measure the performance of the internal and external validation sets, respectively. We constructed a gender-specific diabetes prediction model, having a resultant AUROC of 0.93 and 0.94 for men and women, respectively. Based on this probability, we classified participants into five groups and analyzed cumulative incidence from the KoGES dataset. Group 5 demonstrated significantly worse outcomes than those in other groups. Our novel model for predicting diabetes, based on two large-scale population-based cohort studies, showed high sensitivity and selectivity. Therefore, our diabetes index can be used to classify individuals at high risk of diabetes.

Abstract Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type composition, satellite cell and myonuclei content, signaling pathways involved in muscle protein synthesis, and myogenic regulatory factors. The gastrocnemius muscle weight and fiber cross-sectional area of the stretched side was found greater compared with that of the unstretched side. Passive repetitive stretching increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1.The phosphorylation level of p70S6K significantly increased in the stretched muscles, whereas of Akt and 4E-BP1 remained unchanged, compared to the unstretched side. The Pax7+ cells and myonuclei content did not differ between the stretched and unstretched muscles. These findings suggest that the hypertrophic or suppressed atrophic observation in the stretched muscles are mainly attributable to the protein turnover provoked by stretching. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.

Abstract The aim of this study was to identify the relationships of epidermal growth factor receptor (EGFR) mutations and anaplastic large-cell lymphoma kinase (ALK) status with CT characteristics in adenocarcinoma using the largest patient cohort to date. In this study, preoperative chest CT findings prior to treatment were retrospectively evaluated in 827 surgically resected lung adenocarcinomas. All patients were tested for EGFR mutations and ALK status. EGFR mutations were found in 489 (59.1%) patients, and ALK positivity was found in 57 (7.0%). By logistic regression, the most significant independent prognostic factors of EGFR effective mutations were female sex, nonsmoker status, GGO air bronchograms and pleural retraction. For EGFR mutation prediction, receiver operating characteristic (ROC) curves yielded areas under the curve (AUCs) of 0.682 and 0.758 for clinical only or combined CT features, respectively, with a significant difference (p

Abstract Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

Abstract Traffic-related air pollution particulate matter 2.5 (TRAPM2.5), is involved in chronic obstructive pulmonary disease (COPD), which is characterized by airway inflammation. Specifically, these harmful particles or gases can increase chronic airway inflammation. Some recent studies have shown that lncRNAs are closely related to COPD and participate in the regulation of airway inflammation. However, the precise mechanisms remain unknown. In the present study, we investigated the effect of TRAPM2.5 on airway inflammation in human bronchial epithelial cells (HBECs) and the underlying mechanisms mediated by a lncRNA. After exposure to TRAPM2.5, the novel lncRNA RP11-86H7.1 was markedly upregulated in HBECs. Functional assays indicated that the lncRNA RP11-86H7.1 was required for the TRAPM2.5-induced expression of inflammatory factors in HBECs. A mechanistic study demonstrated that lncRNA RP11-86H7.1 might participate in TRAPM2.5-induced inflammatory responses by activating the NF-κB signaling pathway. Moreover, the lncRNA RP11-86H7.1 can promote the inflammatory response by acting as a competing endogenous RNA of miR-9-5p, reversing the inhibitory effect of its target gene NFKB1, and sustaining NF-κB activation. In summary, our study elucidates the pro-inflammatory roles of the lncRNA RP11-86H7.1–miR-9-5p–NFKB1 regulatory network in airway inflammation induced by TRAPM2.5 and indicates that the components of this network might serve as novel diagnostic biomarkers and potential therapeutic targets.

Abstract Screening for possible development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is essential for risk prediction and early therapy. This study reported a novel model comprised of routine laboratory variables for predicting HCC from CHB. A retrospective study was performed among 463 participants. alpha-fetoprotein (AFP), platelet and alanine aminotransferase (ALT) ratio (APAR) was constructed to differentiate HCC from CHB or non-cancer with area under the receiver operating characteristic curves (AUC) of 0.815 and 0.868 in the training set, 0.831 and 0.861 in the validation set, respectively. In participants with low or normal AFP (

Abstract The black-necked crane (Grus nigricollis) is the only alpine crane species and is endemic to the Tibetan Plateau. The breeding habitats of this species are poorly understood, which greatly hampers practical research and conservation work. Using machine learning methods and the best-available data from our 7,000-kilometer mega-transect survey and open access data, we built the first species distribution model (SDM) to analyze the black-necked crane’s breeding habitats. Our model showed that current conservation gaps account for 26.7% of its predicted breeding habitats. Specifically, the northern parts of the Hengduan Mountains and the southeastern Tibet Valley, the northern side of the middle Kunlun Mountains, parts of the Pamir Plateau, the northern Pakistan Highlands and the western Hindu Kush should be considered as its main potential breeding areas. Additionally, our model suggested that the crane prefers to breed in alpine meadows at an elevation over 2,800 m, a maximum temperature of the warmest month below 20.5 °C, and a temperature seasonality above 7,800 units. The identified conservation gaps and potential breeding areas can aid in clearly prioritizing future conservation and research, but more attention and study should be directed to the unassessed Western Development of China to secure this endangered crane lineage and other wildlife on the Tibetan Plateau.

Abstract Air quality around the globe is declining and public health is seriously threatened by indoor air pollution. Typically, indoor air pollutants are composed of a series of volatile organic compounds (VOCs) that are generally harmful to the human body, especially VOCs with low molecular weights (less than 100 Da). Moreover, in some situations, more than one type of VOC is present; thus, a device that can detect one or more VOCs simultaneously would be most beneficial. Here, we synthesized a sensor array with 4 units to detect 4 VOCs: acetone (unit 1), benzene (unit 2), methanol (unit 3) and formaldehyde (unit 4) simultaneously. All units were simultaneously exposed to 2.5 ppm of all four VOCs. The sensitivity of unit 1 was 14.67 for acetone and less than 2.54 for the other VOCs. The sensitivities of units 2, 3 and 4 to benzene, methanol and formaldehyde were 2 18.64, 20.98 and 17.26, respectively, and less than 4.01 for the other VOCs. These results indicated that the sensor array exhibited good selectivity and could be used for the real-time monitoring of indoor air quality. Thus, this device will be useful in situations requiring the simultaneous detection of multiple VOCs.

Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants. Pathogenicity was defined according to the standards and guidelines of the American College of Medical Genetics and Genomics. We identified 33 rare variants predicted to be deleterious in 39 patients. The fasting [1.57(1.06–2.22) ng/ml] and postprandial C-peptide levels [2.8(1.75–4.46) ng/ml] of the patients with such WFS1 variations were lower than those of the patients without WFS1 variation [2.09(1.43–3.05) and 4.29(2.76–6.07) respectively, ng/ml]. Six (0.9%) patients carried pathogenic or likely pathogenic variants; they met the diagnostic criteria for WFS1-DM according to the latest guidelines, but typical phenotypes of Wolfram syndrome were seldom observed. They were diagnosed at an earlier age and usually presented with an absence of obesity, impaired beta cell function, and the need for insulin treatment. WFS1-DM is usually mistakenly diagnosed as type 2 diabetes, and genetic testing is helpful for individualized treatment. [ABSTRACT FROM AUTHOR]