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Abstract We revisit anomalous phases related to large gauge transformations, such as the Witten anomaly. The latter, known to plague d = 4 Sp(k) theories, is well-understood in terms of π 4(Sp(k)) = ℤ2, but it also has an oblique relation to the instantons, labeled by π 3(G) = ℤ, via the fermion zero mode counting. We revisit this relation and point out how SU(N) theories escape an anomalous sign of the latter type, only thanks to the perturbative anomaly cancelation condition that restricts the chiral fermion spectrum. This leads to the question of what happens if the latter, more mundane anomaly is canceled by an inflow instead. After raising an open question about fractional D3 probe theories, we explore the simplest bottom-up model of such a kind, due to Witten and Yonekura, from which we find the relevant chiral theories to be free of such a disease despite the unrestricted chiral spectra. We close with a simple but often-overlooked observation about how fermionic zero modes enter physics differently between Euclidean and Lorentzian descriptions and point out a related issue in d = 3.

Abstract Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.

The rising demand for increased integration and higher power outputs poses a hidden risk to the long-term reliable operation of third-generation semiconductors. Thus, the power cycling test (PCT) is widely regarded as the utmost critical test for assessing the packaging reliability of power devices. In this work, low-thermal-resistance packaging design structures of SiC devices are introduced, encompassing planar packaging with dual heat dissipation, press-pack packaging, three-dimensional (3D) packaging, and hybrid packaging. PCT methods and their control strategies are summarized and discussed. Direct-current PCT is the focus of this review. The failure mechanisms of SiC devices under PCT are pointed out. The electrical and temperature-sensitive parameters adopted to monitor the aging of SiC devices are organized. The existing international standards for PCT are evaluated. Due to the lack of authoritative statements for SiC devices, it is difficult to achieve comparison research results without consistent preconditions. Furthermore, the lifetimes of the various packaging designs of the tested SiC devices under PCTs are statistically analyzed. Additionally, problems related to parameter monitoring and test equipment are also summarized. This review explores the broader landscape by delving into the current challenges and main trends in PCTs for SiC devices.

Abstract We generalize the idea of symmetry topological field theory (SymTFT) for subsystem symmetry. We propose the 2-foliated BF theory with level N in (3 + 1)d as subsystem SymTFT for subsystem ℤ N symmetry in (2 + 1)d. Focusing on N = 2, we investigate various topological boundaries. The subsystem Kramers-Wannier and Jordan-Wigner dualities can be viewed as boundary transformations of the subsystem SymTFT and are included in a larger duality web from the subsystem SL(2, ℤ 2) symmetry of the bulk foliated BF theory. Finally, we construct the condensation defects and twist defects of S-transformation in the subsystem SL(2, ℤ 2), from which the fusion rule of subsystem non-invertible operators can be recovered.

Abstract Background Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. Methods The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. Results Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. Conclusions Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.

Abstract Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical. Graphic Abstract

Background and aims: Bone marrow failure (BMF) is chronic benzene-induced hematotoxicity, which is associated with differential gene expression abnormality. Benzene-induced BMF is characterized by irreversible bone marrow depression. Despite extensive studies have been conducted, there is a lack of reliable, useful and simple diagnostic method for BMF. Previous studies have shown that the aberrant gene expression changes and reactive oxygen species production in bone marrow cells related to the development of BMF. Early detection of differentially expressed genes (DEGs) as potential biomarkers is important for diagnosis and treatment. However, the validation of effective biomarker through DEGs analysis in benzene-induced BMF still deserve to be clarified. This study aimed to identify target genes as potential biomarkers with benzene-induced BMF based on DEGs analysis. Methods: First, we developed a benzene-induced BMF mouse model and obtained the DEGs in bone marrow cells of benzene-exposed CD1 mice. Next, after obtaining the DEGs via RNA-Sequencing (RNA-seq) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also used, key genes associated with benzene-induced BMF were identified. Additionally, the key markers for benzene poisoning was evaluated using qRT-PCR technique. Results: We identified DEGs for further KEGG functional analysis. Ten statistically significantly (up or down) regulated genes, namely Mapk11, Foxo1, Lefty1, Ren1, Bank1, Fgf3, Cdc42ep2, Rasgrf1, P2rx7, and Shank3 were found mainly associated with mitogen-activated protein kinases (MAPK) oxidative stress pathway. Further analysis using qRT-PCR identified that eight statistically significant DEGs associated with signaling pathways such as MAPK. We found that the level of mRNA expression of Mapk11, Foxo1, Bank1, Lefty1, Ren1, P2rx7, and Fgf3 genes were increased and Cdc42ep2 gene was decreased in BMF mice compared to control mice. Additionally, we validated the eight candidate genes for potential biomarkers in peripheral blood mononuclear cells of benzene poisoning patients by qRT-PCR. Conclusion: Our results indicated that Mapk11 and Fgf3 were predominantly candidate genes linked to novel biomarkers for benzene hematotoxicity in human beings. Our study will provide new candidate genes as useful biomarkers involved in benzene-induced hematotoxicity.

Anaplastic thyroid carcinoma is one of the highly fatal cancers and poses a serious threat to human health. Ferroptosis has been widely studied and proved to have an important role in tumor suppression, providing new avenues for cancer therapy; glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase(TXNRD1) are important regulatory targets in ferroptosis.Warburg effect is one of the important energy sources for cancer hypermetabolism, and pyruvate kinase isoenzyme 2 (PKM2) is a key metabolism enzyme that is important in this effect. Shikonin(SKN) is a Chinese herb that has been extensively studied for its anti-tumor ability. The aim of this study was to investigate the mechanism of anti-tumor effect of SKN in ATC cells and to elucidate the role played by ferroptosis and glycolysis in this inhibitory mechanism. The effects of SKN in ATC cell lines CAL-62 and 8505C cells were detected by flow cytometry, Western blotting,real-time quantitative PCR and a fluorescent probe for reactive oxygen species (ROS) to detect changes in intracellular ROS positivity; glucose and lactate assay kits to detect the levels of the raw material of glucose metabolism, glucose (GLU), and the product of glucose metabolism, lactate (LD); and the establishment of the BALB/C nude mice subcutaneous tumor model to analyse the inhibitory effect of SKN on ATC in vivo. The present study demonstrated that SKN inhibits the expression of NF-κB,GPX4,TXNRD1,PKM2,GLUT1.SKN inhibits ATC cell growth by down-regulating the occurrence of intracellular ferroptosis and inhibiting glycolysis in ATC cells.

Background: The effect of combined radiation and chemotherapy (combination therapy) versus monotherapy on anaplastic thyroid carcinoma (ATC) has not yet been clear. Methods: We identified 516 ATC patients during 2010–2015 from the Surveillance, Epidemiology and End Results (SEER) database and evaluated their survival outcome using the Kaplan-Meier method, Cox regression analysis and propensity score matching (PSM) technique. Results: The median overall survival (OS) among the entire cohort was 3 months (95 % confidence interval [CI], 2.58–3.42 months), and the 6- and 12-month OS rates were 29 % (95 % CI, 25.01%–32.88 %) and 13 % (95 % CI, 10.60%–16.58 %), respectively. Multivariable analysis demonstrated that ATC patients not receiving radiotherapy or chemotherapy were unquestionably associated with worse OS (hazard ratio [HR] 3.000, 95 % CI, 2.390–3.764) and cancer-specific survival (CSS) (HR = 3.107, 95 % CI, 2.388–4.043), compared with those receiving combination therapy. However, combination therapy did not predict better prognosis compared with monotherapy (all P > 0.05). After PSM, the median OS and CSS were also not significantly improved in patients undergoing chemoradiotherapy versus chemotherapy alone (OS, P = 0.382; CSS, P = 0.420) or radiotherapy alone (OS, P = 0.065; CSS, P = 0.251). Conclusion: Combination therapy, compared to monotherapy, does not have the expected improvement in survival beyond the benefits achievable with each single-modality treatment, necessitating further prospective research to tailor its treatment management.

Abstract Background Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. Methods High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. Results High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. Conclusions Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

Abstract Microbial cement, known for its superior fluidity, stable crystal formation, and strong bond with concrete, is an effective solution in fixing defects such as voids that appear due to insufficient grouting in the joints of precast concrete components. To evaluate the mechanical properties of rebar anchored with microbial cement grout, three pull-out tests were designed, taking into account parameters such as calcium source concentration, the filler in borehole voids, and the shape of the rebar. The results indicate that specimens with a higher concentration of calcium source require fewer grouting cycles, but the pull-out bearing capacity of the anchored rebar is lower. However, the introduction of quartz sand as a filler in the borehole voids results in a significant increase in the pull-out bearing capacity of the rebar compared to specimens without filler. Among these, the specimens with a medium particle size of 0.5 ~ 1 mm (1/4δ ~ 1/2δ, the gap of δ = 2 mm between the steel bars and hole wall) have the highest pull-out bearing capacity. In comparing rebar shapes, ribbed rebar slightly outperforms smooth round rebar in terms of pull-out bearing capacity. Based on the experimental results analysis, the anchoring mechanism of microbial cement grouting on reinforcement has been elucidated.

Summary: Range-limited endemic species, often labeled as endangered due to their low adaptability to climate change, exhibit unclear evolutionary mechanisms influencing their distribution. This study explores the relationship between leaf length, maximum height, and seed diameter and their linkage to phylogeny and climate in the macroecology of 1,370 woody endemics. Using Bayesian analytical method that allows partitioning phylogenetic and environmental variances and covariance, we revealed moderate to high phylogenetic signals in these traits, indicating evolutionary constraints potentially impacting climate change adaptability. The study uncovered a phylogenetically conserved coordination between height and leaf length which showed to be independent of macroecological patterns of temperature and precipitation. These findings emphasize the role of phylogenetic ancestry in shaping the distribution of woody endemics, highlighting the need for prioritized in-situ conservation and providing insights for ex situ conservation strategies.

Abstract Background BRAFV600E is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including proliferation, metastasis and immune‐escape. BRAFV600E‐mutated papillary thyroid cancer (PTC) also displays greatly reduced expression of thyroid differentiation markers, thus tendency to radioactive iodine (RAI) refractory and poor prognosis. Therefore, understanding the molecular mechanisms and main oncogenic events underlying BRAFV600E will guide future therapy development. Methods Bioinformatics and clinical specimen analyses, genetic manipulation of BRAFV600E‐induced PTC model, functional and mechanism exploration guided with transcriptomic screening, as well as systematic rescue experiments were applied to investigate miR‐31 function within BRAFV600E‐induced thyroid cancer development. Besides, nanoparticles carrying miR‐31 antagomirs were testified to alleviate 131I iodide therapy on PTC models. Results We identify miR‐31 as a significantly increased onco‐miR in BRAFV600E‐associated PTC that promotes tumour progression, metastasis and RAI refractoriness via sustained Wnt/β‐catenin signalling. Mechanistically, highly activated BRAF/MAPK pathway induces miR‐31 expression via c‐Jun‐mediated transcriptional regulation across in vitro and transgenic mouse models. MiR‐31 in turn facilitates β‐catenin stabilisation via directly repressing tumour suppressors CEBPA and DACH1, which direct the expression of multiple essential Wnt/β‐catenin pathway inhibitors. Genetic functional assays showed that thyroid‐specific knockout of miR‐31 inhibited BRAFV600E‐induced PTC progression, and strikingly, enhanced expression of sodium‐iodide symporter and other thyroid differentiation markers, thus promoted 131I uptake. Nanoparticle‐mediated application of anti‐miR‐31 antagomirs markedly elevated radio‐sensitivity of BRAFV600E‐induced PTC tumours to 131I therapy, and efficiently suppressed tumour progression in the pre‐clinical mouse model. Conclusions Our findings elucidate a novel BRAF/MAPK‐miR‐31‐Wnt/β‐catenin regulatory mechanism underlying clinically BRAFV600E‐associated DTC tumourigenesis and dedifferentiation, also highlight a potential adjuvant therapeutic strategy for advanced DTC.

PurposeTo investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves’ disease (GD) and to further assess predictive value of changes in early stage retrospectively.MethodsWe studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered.ResultsThe levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05).ConclusionBTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Abstract Background The effects of obesity and diabetes on the clinical outcomes of differentiated thyroid cancer (DTC) remain unclear. Objectives To explore the association between obesity and diabetes with pathological features and therapeutic response of DTC. Methods Patients were categorized based on body mass index (BMI) and glycemic status. Compare the correlation between BMI and glycemic status with pathological features and therapeutic response of DTC. To analyze the independent risk factors for the aggressiveness of DTC. Results The proportion of patients with bilateral tumors was higher in the overweight, obese and diabetes group (P = 0.001, 0.045). The overweight group demonstrated a higher TNM stage (P = 0.004), while the T and TNM stages were higher in the diabetes group (P = 0.032, 0.000). The probability of distant metastasis increases by 37.4% for each unit of BMI increase (odds ratio (OR) = 1.374, CI 95% 1.061–1.778, P

Abstract Given a two-dimensional bosonic theory with a non-anomalous ℤ2 symmetry, the orbifolding and fermionization can be understood holographically using three-dimensional BF theory with level 2. From a Hamiltonian perspective, the information of dualities is encoded in a topological boundary state which is defined as an eigenstate of certain Wilson loop operators (anyons) in the bulk. We generalize this story to two-dimensional theories with non-anomalous ℤ N symmetry, focusing on parafermionization. We find the generic operators defining different topological boundary states including orbifolding and parafermionization with ℤ N or subgroups of ℤ N , and discuss their algebraic properties as well as the ℤ N duality web.

Abstract Background Silicosis is an important occupational disease caused by inhalation of free silica and is characterized by persistent pulmonary inflammation, subsequent fibrosis and lung dysfunction. Until now, there has been no effective treatment for the disease due to the complexity of pathogenesis. Fermented cordyceps powder (FCP) has a similar effect to natural cordyceps in tonifying the lung and kidney. It has started to be used in the adjuvant treatment of silicosis. This work aimed to verify the protective effects of FCP against silicosis, and to explore the related mechanism. Methods Wistar rats were randomly divided into four groups including the saline-instilled group, the silica-exposed group, the silica + FCP (300 mg/kg) group and the silica + FCP (600 mg/kg) group. Silicosis rat models were constructed by intratracheal instillation of silica (50 mg). Rats in the FCP intervention groups received the corresponding dose of FCP daily by intragastric gavage. Rats were sacrificed on days 7, 28 and 56 after treatment, then samples were collected for further analysis. Results FCP intervention reduced the infiltration of inflammatory cells and the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) at days 7, 28, 56, and decreased the expression of collagen, α-smooth muscle actin (α-SMA) and fibronectin (FN) at days 28 and 56 in the lung of silicosis rats. FCP also decreased the immune response of Th1 and Th17 at days 7, 28, 56 and inhibited the enhancement of the Th2 response at day 56. Conclusions FCP intervention could alleviate silica-induced pulmonary inflammation and fibrosis, the protective effect may be achieved by reducing Th1 and Th17 immune responses and inhibiting the enhancement of the Th2 response.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. Results: A cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. Conclusion: The proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

Equiatomic high-entropy alloys (HEAs) fabricated by additive manufacturing (AM) have gained increasing attention since they present superior mechanical properties over their counterparts made by traditional synthesis routes. However, few studies have investigated AM of non-equiatomic HEAs, although this type of HEAs showing excellent mechanical properties. In this paper, we additively manufactured a novel non-equiatomic FeCoCrNi HEA via in-situ alloying 316L stainless steel and CrCoNi medium-entropy alloy. Besides the fine grain size (9 μm) and high dislocation density (3.8 × 1014 m−2), we observed unexpected high-intensity of hybrid crystal-amorphous precipitates, which have never been reported in NiCoCr-based alloys made by AM. These unique microstructures led to exceptional combination of strength (561 MPa) and elongation (41 %) exceeding those of additively manufactured equiatomic FeCoCrNi HEAs. Our observation from EBSD, TEM and atomistic simulations reveals a group of deformation mechanisms of stacking faults, deformation twins, TB-dislocation and dislocation-precipitates interactions. Our findings not only provide new insights into AM of non-equiatomic HEAs via in situ alloying, also shed lights on understanding the microstructure-properties relationship of non-equiatomic HEAs fabricated by AM.

Abstract Background Evidence showed that N6-methyladenosine (m6A) is strongly associated with male germline development. However, the role of m6A methylation on circRNAs in amphibians remains unknown. In this study, we conducted m6A sequencing analysis to explore the m6A transcriptome-wide profile of circRNAs in testis tissues of Xenopus laevis (X. laevis) with and without treatment with 100 µg/L atrazine (AZ). Results The analysis showed that m6A modification of circRNAs enriched in sense overlapping in testes of X. laevis. We identified the differential m6A modification sites within circRNAs in testes of AZ-exposed X. laevis and compared that with animals from control group. The results showed that a total of 1507 methylated m6A sites was induced by AZ (760 up-methylated and 747 down-methylated). The cross-analysis exhibited a negative correlation of differentially methylated m6A peaks and circRNAs expression level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that 20 key pathways may be involved in the mechanism of testis damage of AZ-exposed X. laevis. Conclusions These findings indicated that differentially m6A-methylated circRNAs may play important roles in abnormal testis development of AZ-exposed X. laevis. This study is the first report about a map of m6A modification of circRNAs in male X. laevis and provides a basis for further studying on the function and mechanism of m6A methylation of circRNAs in the testis development of amphibian.

Abstract Background This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. Methods We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named “YOLO” to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). Results Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value

Abstract Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed. Graphical Abstract

Exposure to toluene diisocyanate (TDI) can cause pulmonary diseases such as asthma. Inhibition of high mobility group box 1 protein (HMGB1) has been found to be protective against the toxic effects of TDI on human bronchial epithelial (HBE) cells. Here, we evaluated the in vivo positive roles of HMGB1 in the TDI-caused asthma mice and explored its underlying mechanisms in HBE cells. We found that suppression of HMGB1 obviously alleviated airway inflammation, airway hyperresponsiveness, and airway remodeling in the lung tissue of the asthma mice. The in vitro results showed that inhibition of HMGB1 ameliorated TDI-induced reactive oxygen species (ROS) release, inflammatory response, and activation of autophagy in HBE cells. At the molecular level, inhibition of HMGB1 decreased the expressions of HMGB1, Toll-like receptor 4, Vimentin and matrix metalloproteinase-9 proteins, activated NF-κB and NOD-like receptor protein 3 (NLRP3) inflammasome, and increased E-cadherin expression. Importantly, activation of autophagy could lead to the overactivation of NLRP3 inflammasome in TDI-induced asthma. These results suggest that inhibition of HMGB1 can alleviate TDI-induced asthma through ROS/AMPK/autophagy pathways, which may provide valuable evidence for the pathogenesis and therapeutic targets of TDI-induced asthma.

Background: Whether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC. Methods: The ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis. HMDB was searched to identify potential differential metabolites and final metabolic pathway analysis was performed by MetaboAnalyst 5.0. We analyzed the differential metabolites diagnostic accuracy through receiver operating characteristic (ROC) curves analysis. Results: Seven different metabolites were screened from HT group and NC group, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine. Logistic regression model combined with ROC analysis of these 7 biomarkers had good discriminability for PTC (area under operating characteristic curve of HT group and NC group were 0.867 and 0.973, respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. Conclusions: The metabolic profiles of the NC and HT groups had important similarities and differences in PTC. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

Abstract Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

Wildfires in transmission line passages are a severe threat to power security. Two wildfire detection models, which are based on the YOLOv5, are proposed in this paper. Due to the limited computing power of embedded terminals, the proposed models simplify the network structure of YOLOv5. Specifically, one is that only the overall structure of the neck and head parts in the original network structure is simplified, and the second method is based on the first method to delete the modules of backbone, which greatly reduces the number of parameters of the model. The experimental results show that the proposed lightweight models can achieve real-time monitoring in embedded devices while the accuracy and recall remain high.

Abstract Tree architectural attributes demonstrate a significant association with fruit yield. Yellowhorn is the future bioenergy tree in China; however, the species suffers from high reproductive energy and exceedingly low reproductive output. To optimize yellowhorn management and pinpoint priority trees featuring optimal architecture, we employed machine learning modeling to develop high fruit yielding predictive models using five yield indicators (dependent variables: FrW, SeW, ShW, FrW, and SeN) and five tree characteristics (independent variables: CA, TH, DGL, HLC, and MBN) of yellowhorn. Results showed that trees characterized by a substantial canopy area (>1.70 m2) and a large diameter at ground level (>3.71 cm) have been found to yield a higher fruit production. However, increased tree height does not invariably correlate with an elevated yield. Effective selection of high‐yielding individuals can be accomplished by restricting tree height within the range of 192–232.4 cm. This approach emphasizes the importance of integrating considerations of tree architecture into forestry management practices. Such integration can bolster productivity, thereby contributing to both the sustainability and economic viability of yellowhorn forests.

Two Mn2+ coordination polymers (CPs) with the scientific terms of {[Mn(TTPA)·(H2O)2]·H2O}n (1) and {[Mn(TTPA)·(H2TTPA)]·2DMSO}n (2) were favorably created on the basis of multidentate linking organic ligand 2,5-bis-(1,2,4-triazol-1-yl)-terephthalic acid (H2TTPA) in the conditions of solvent-presupposed thermal reaction. To measure the influence of two Mn2+ coordination polymers with novel structures, the ELISA assay and real-time RT-PCR assay were conducted in this present research. First of all, the ELISA assay was conducted to measure the content of inflammatory cytokines released into the hippocampal tissue. In addition to this, the relative expression of the TAU protein in the brain was further determined with real-time RT-PCR assay.

Abstract We study the Seberg-Witten geometry of 5d N $$ \mathcal{N} $$ = 1 pure Yang-Mills theories compactified on a circle. The concept of the holonomy saddle implies that there are multiple 4d limits of interacting Seiberg-Witten theories from a single 5d theory, and we explore this in the simplest case of pure SU(N) theories. The compactification leads to N copies of locally indistinguishable 4d pure SU(N) Seiberg-Witten theories in the infrared, glued together in a manner dictated by the Chern-Simons level. We show how this picture naturally builds the 5d BPS quivers which agree with the D0 probe dynamics previously proposed via the geometrically engineered local Calabi-Yau. We work out various SU(2) and SU(3) examples through a detailed look at the respective spectral curves. We also note a special ℤ2N feature of SU(N) N spectral curves and the resulting BPS quivers, with emphasis on how the 4d holonomy saddles are affected.

Abstract Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors. Graphical Abstract

In recent years, UAV aerial survey technology has been widely used in the field of geological disaster prevention, especially in the emergency disposal of abrupt geological hazard. Image free UAV aerial survey technology can quickly obtain surveying and mapping data. Compared with traditional aerial survey methods, it greatly saves time cost and labor cost. In this paper, the DJI Phantom 4 RTK UAV is used to acquire and process the image free aerial survey data of landslide and debris flow disaster in Lijie North Hill landslide-debris flow disaster in Zhouqu County, Gansu Province. According to the aerial survey results, the relevant parameters such as landslide morphological characteristics and debris flow gully characteristics are quickly obtained, the signs of landslide deformation are analyzed, and the field survey data are used to evaluate and analyze the accuracy of image free aerial survey.The results show that the deformation signs, morphological characteristics and debris flow gully characteristics of landslide are consistent with the field, and the accuracy of verification points meets the data production specification of low altitude digital aerial photogrammetry (GH/Z 3003—2010). The result data can be used for the analysis of deformation characteristics of disaster body, rapid extraction of geometric parameters, and auxiliary analysis and evaluation of danger and disaster, It has a certain reference significance for the rapid acquisition of UAV mapping data in the emergency disposal of abrupt geological hazard.

Abstract We study the infrared physics of 5d N $$ \mathcal{N} $$ = 1 Yang-Mills theories compactified on S 1 $$ {\mathbbm{S}}^1 $$ , with a view toward 4d and 5d limits. Global structures of the simplest Coulombic moduli spaces are outlined, with an emphasis on how multiple planar 4d Seiberg-Witten geometries are embedded in the cigar geometry of a single 5d theory on S 1 $$ {\mathbbm{S}}^1 $$ . The Coulomb phase boundaries in the decompactification limit are given particular attention and related to how the wall-crossings by 5d BPS particles turn off. On the other hand, the elliptic genera of magnetic BPS strings do wall-cross and retain the memory of 4d wall-crossings, which we review with the example of dP2 theory. Along the way, we also offer a general field theory proof of the odd shift of electric charge on Sp(k)π instanton solitons, previously observed via geometric engineering for low-rank supersymmetric theories.

Abstract Background Silicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis. Although great effort has been made to understand the pathogenesis of the disease, molecular mechanism underlying silicosis is not fully elucidated. This study was aimed to explore proteomic and transcriptomic changes in rat model of silicosis. Methods Twenty male Wistar rats were randomly divided into two groups with 10 rats in each group. Rats in the model group were intratracheally instilled with 50 mg/mL silicon dioxide (1 mL per rat) and rats in the control group were treated with 1.0 mL saline (1 mL per rat). Twenty-eight days later, transcriptomic analysis by microarray and tandem mass tags (TMT)-based proteomic analysis were performed to reveal the expression of mRNAs and proteins in lung tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze the altered genes and proteins. The integrated analysis was performed between transcriptome and proteome. The data were further verified by RT-qPCR and parallel reaction monitoring (PRM). Results In total, 1769 differentially expressed genes (DEGs) and 650 differentially expressed proteins (DEPs) were identified between the silicosis model and control groups. The integrated analysis showed 250 DEPs were correlated to the corresponding DEGs (cor-DEPs-DEGs), which were mainly enriched in phagosome, leukocyte transendothelial migration, complement and coagulation cascades and cellular adhesion molecule (CAM). These pathways are interrelated and converged at common points to produce an effect. GM2a, CHI3L1, LCN2 and GNAI1 are involved in the extracellular matrix (ECM) and inflammation contributing to fibrosis. Conclusion Our comprehensive transcriptome and proteome data provide new insights into the mechanisms of silicosis and helpful information for more targeted prevention and treatment of silicosis.

Abstract Background Increasing evidence suggested N6-methyladenosine (m6A) modification is crucial for male germline development. However, m6A modification of lncRNAs gains a little attention in amphibians in recent years. Xenopus laevis (X. laevis) was chosen to be an ideal model organism for testing environmental endocrine disrupting chemicals (EDCs) exposure and resultant effects. Atrazine (AZ) as an endocrine disrupt can effect development of testis in amphibians. Our previous study revealed that m6A is a highly conserved modification across the species. Results The results of m6A sequences showed that m6A-methylated lncRNAs enriched in intergenic region in testes of X. laevis. We further examined the differential expression of lncRNAs m6A sites in testes of AZ-exposed and compared with that in animals from control group. The results indicated that up to 198 differentially methylated m6A sites were detected within 188 lncRNAs, in which 89 significantly up-methylated sites and 109 significantly down-methylated sites. Data from KEGG pathway analysis indicated that AZ-affected lncRNAs m6A sites were mainly involved in 10 pathways in which 3 mutual pathways were found in the result of differentially m6A-methylated mRNAs. Conclusions These findings suggested that differentially m6A-methylated lncRNAs and these 3 pathways may act on regulatory roles in abnormal testis development of AZ-exposed X. laevis. This study for the first time provides insights into the profile of lncRNAs m6A modifications in amphibian species.

Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.

Abstract Background The digital cadmium–zinc–telluride (CZT)-based SPECT system has many advantages, including better spatial and energy resolution. However, the impacts of different acquisition and reconstruction parameters on CZT SPECT quantification might still need to be validated. This study aimed to evaluate the impacts of acquisition parameters (the main energy window and acquisition time per frame) and reconstruction parameters (the number of iterations, subsets in iterative reconstruction, post-filter, and image correction methods) on the technetium quantification of CZT SPECT/CT. Methods A phantom (PET NEMA/IEC image quality, USA) was filled with four target-to-background (T/B) ratios (32:1, 16:1, 8:1, and 4:1) of technetium. Mean uptake values (the calculated mean concentrations for spheres) were measured to evaluate the recovery coefficient (RC) changes under different acquisition and reconstruction parameters. The corresponding standard deviations of mean uptake values were also measured to evaluate the quantification error. Image quality was evaluated using the National Electrical Manufacturers Association (NEMA) NU 2–2012 standard. Results For all T/B ratios, significant correlations were found between iterations and RCs (r = 0.62–0.96 for 1–35 iterations, r = 0.94–0.99 for 35–90 iterations) as well as between the full width at half maximum (FWHM) of the Gaussian filter and RCs (r = − 0.86 to − 1.00, all P values 0.05) were found between the 15% and 20% energy windows except for the 32:1 T/B ratio (P value = 0.023) or between the 10 s/frame and 120 s/frame acquisition times except for the 4:1 T/B ratio (P value = 0.015) in terms of RCs. Conclusions CZT-SPECT/CT of technetium resulted in good quantification accuracy. The favourable acquisition parameters might be a 15% energy window and 40 s/frame of acquisition time. The favourable reconstruction parameters might be 35 iterations, 20 subsets, the AC + SC + RR correction combination, and no filter.

BackgroundPopulation-based estimates of the incidence and prognosis of bone metastases (BM) stratified by histologic subtype at diagnosis of thyroid cancer are limited.MethodsUsing multivariable logistic and Cox regression analyses, we identified risk factors for BM and investigated the prognostic survival of BM patients between 2010 and 2015 via the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong 64,083 eligible patients, a total of 347 patients with BM at the time of diagnosis were identified, representing 0.5% of the entire cohort but 32.4% of the subset with metastases. BM incidence was highest (11.6%) in anaplastic thyroid cancer (ATC), which, nevertheless, was highest (61.5%) in follicular thyroid cancer (FTC) among the subset with metastases. The median overall survival among BM patients was 40.0 months, and 1-, 3-, and 5-year survival rates were 65.2%, 51.3%, and 38.7%, respectively. Compared with papillary thyroid cancer (PTC), FTC (aOR, 6.33; 95% CI, 4.72–8.48), medullary thyroid cancer (MTC) (aOR, 6.04, 95% CI, 4.09–8.92), and ATC (aOR, 6.21; 95% CI, 4.20–9.18) significantly increased the risk of developing BM. However, only ATC (aHR, 6.07; 95% CI, 3.83–9.60) was independently associated with worse survival in multivariable analysis. Additionally, patients with BM alone (56.5%) displayed the longest median survival (66.0 months), compared with those complicated with one extraskeletal metastatic site (lung, brain, or liver) (35.2%; 14.0 months) and two or three sites (8.3%; 6.0 months). The former 5-year overall survival rate was 52.6%, which, however, drastically declined to 23.0% in patients with one extraskeletal metastatic site and 9.1% with two or three sites.ConclusionCloser bone surveillance should be required for patients with FTC, MTC, and ATC, and extraskeletal metastases at initial diagnosis frequently predict a poorer prognosis.

ObjectivesAnaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC.Methods131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels.ResultsThe synthesized nanoparticles had a suitable size (25–45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4–6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser.ConclusionsIn summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.

Abstract Background Exposure to respirable crystalline silica (RCS) can induce accelerated silicosis (AS), a form of silicosis that is more progressive and severe form of silicosis. In this project we aimed to assess processes of silicosis in rats exposed to RCS with focus on the regulation of long noncoding RNAs (lncRNAs). Results The results showed that RCS induced acute inflammatory response as indicated by the appearance of inflammatory cells in the lung from the first day and peaked on day 7 of exposure. The fibroblasts appeared along with the inflammatory cells decreasing gradually on day 14. Extensive fibrosis appeared in the lung tissue, and silicon nodules were getting larger on day 28. Interestingly, the number of altered lncRNAs increased with the exposure time with 193, 424, 455, 421 and 682 lncRNAs on day 1, 7, 14, 21, and 28 after exposure, respectively. We obtained 285 lncRNAs with five significant temporal expression patterns whose expressions might correlate with severity of silicosis. KEGG analysis showed that lncRNAs from short time-series expression miner (STEM)-derived data mainly involved in 17 pathways such as complement and coagulation cascades. Conclusions The differential expression profiles of lncRNAs may be potential biomarkers in silicosis through modulating expressions of their relevant genes in lungs of rat and thus warrant further investigation.

PurposeTo assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively.MethodsWe studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC.ResultsIn TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively.ConclusionsFor TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.

Purpose Compelling evidence suggests that nanoparticles (NPs) play a crucial role in cancer therapy. NPs templated with human serum albumin (HSA) has good retention in tumors. Manganese dioxide (MnO 2 ) has been used to enhance the effect of radiotherapy. In this study, synthesized NPs using HSA-MnO 2 labeled 131 I to perform both imaging and therapy for anaplastic thyroid carcinoma (ATC). Method HSA-MnO 2 was synthesized via HSA using a simple biomineralization method, and then labeled with Na 131 I by the chloramine T method. The cytotoxicity and biosafety of HSA-MnO 2 were evaluated by the MTT test. The proliferation-inhibiting effect of HSA-MnO 2 - 131 I was evaluated in papillary thyroid cancer cell lines (K1, BCPAP, and KTC) and anaplastic thyroid carcinoma cell lines (Cal62, THJ16T, and ARO). For further translational application in medicine, we established a model of transplantable subcutaneously tumors in BALB\c-nu mice to assess the anti-tumor effect of HSA-MnO 2 - 131 I. The imaging effects of NPs were evaluated by MRI and SPECT/CT. Results The MTT test proved that the HSA-MnO 2 had low toxicity. HSA-MnO 2 - 131 I significantly inhibited the proliferation of PTC and ATC cell lines. In addition, the results unveiled that HSA-MnO 2 - 131 I exhibited dual-modality MR/SPECT imaging for thyroid cancer visualization. In particular, HSA-MnO 2 - 131 I had an enhanced T1 signal in MR. Using SPECT/CT, we observed that HSA-MnO 2 - 131 I had good retention in tumor tissue, which was helpful for the diagnosis and treatment of tumor. In vivo assays indicated that the NPs led to a reduction in radioresistance in the tumor hypoxic microenvironment. Conclusion The nanomaterial had a simple synthesis method, good water solubility and biosafety, and good retention in tumor tissue. Hence, it could be used for SPECT/CT and MR dual mode imaging and therapy with radioiodine of tumor cells. The experimental results provided a feasible solution for combining radiotherapy and dual-model imaging by NPs for cancer diagnosis and treatment.

Abstract It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.

Every day social multimedia applications generate millions of images. To handle such huge amount of images, an optimal solution is using the public cloud, since it has powerful storage capability. Images usually contain a wealth of sensitive information, therefore social service providers need not only to provide services such as retrieval and sharing but also to protect the privacies of the images. In this paper, we propose a privacy-preserving scheme for content-based image retrieval and sharing in social multimedia applications. First, the users extract visual features from the images, and perform locality-sensitive hashing functions on visual features to generate image profile vectors. We then model the retrieval on the images as the equality search on the image profile vectors. To enable accurate and efficient retrieval, we design the secure index structure based on cuckoo hashing, which has constant lookup time. To meet the requirements of dynamic image updating, we enrich our service with image insertion and deletion. In order to reduce the key management overhead and the access control overhead in social applications, we process keys using secret sharing techniques to enable the users holding similar images to query and decrypt images independently. Finally we implement the prototype of the proposed scheme, and perform experiments over encrypted image databases.

Objective The randomized controlled trail was carried out to investigate the influence of statin pre-treatment on clinical efficacy of carotid artery stenting (CAS).Methods 160 eligible patients were randomly divided into statin group (n = 82) and control group (n = 78). The patients in statin group received 40 mg atorvastatin daily 7 days before operation. Major endpoints included transient ischemic attack (TIA), stroke, death, myocardial infarction (MI), and other cardiac adverse events within 30 days after CAS.Results Preoperative baseline information was similar between the statin and control groups (p > 0.05 for all). Within 48 h after operation, the occurrence rate of CIN (3.66% vs 8.97%, p = .019) and new infarction (4.88% vs. 14.10%, p = .045) were significantly lower in statin group than in control group. 30 days after CAS, the incidences of TIA (12.20% vs. 26.92%, p = .018), ischemic stroke (6.10% vs. 16.67%, p = .034), and other cardiac complications (7.32% vs. 19.23%, p = .026) were also significantly lower in statin group, than in the control group. Multiple analysis demonstrated that statin use exerted protective effect against ischemic stroke (OR = 0.038, 95% CI = 0.003–0.543, p = .016) and other cardiac complications (OR = 0.208, 95%CI = 0.063–0.694, p = .011).Conclusion Pre-treatment with statin is an effective and safe strategy to prevent from perioperative complications and to improve postoperative outcomes in patients undergoing CAS.

Abstract Background The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. Methods The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18–80 years old, in stable CKD stages 4–5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. Discussion This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. Trial registration The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

Long-term exposure to crystalline silica particles leads to silicosis characterized by persistent inflammation and progressive fibrosis in the lung. So far, there is no specific treatment to cure the disease other than supportive care. In this study, we examined the effects of metformin, a prescribed drug for type || diabetes on silicosis and explored the possible mechanisms in an established rat silicosis model in vivo, and an in vitro co-cultured model containing human macrophages cells (THP-1) and human bronchial epithelial cells (HBEC). Our results showed that metformin significantly alleviated the inflammation and fibrosis of lung tissues of rats exposed to silica particles. Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat lung tissue and HBEC culture supernatant. The protein levels of Vimentin and α-smooth muscle actin (α-SMA) were significantly decreased by metfomin while expression level of E-cadherin (E-Cad) increased. Besides, metformin increased the expression levels of phosphorylated adenosine 5′-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.

Recent studies by one of the present authors along with his collaborators in [1–4] show that there exist the so-called open string pair production for a possible simplest system of two Dp branes, placed parallel at a separation and with each carrying different electric flux, in Type II superstring theories. Further this pair production can be greatly enhanced when a magnetic flux, sharing no common field strength index with the electric one, is added, implying then p≥3. Given this, one may wonder if further enhancement can be achieved by adding more magnetic flux(es) in a similar fashion. In this paper, we explore this possibility. It turns out that adding more such magnetic flux diminishes rather than enhances the pair production rate. This actually implies that the largest enhancement occurs at p=3 when the same realistic electric and magnetic fluxes are applied for all p≥3. Curiously one of D3 branes may be our own world and if so, the enhancement gives a possible opportunity to detect the pair production, therefore to test the underlying string theories.

Abstract Background Reliable information on the distribution of target species and influencing environmental factors is essential for effective conservation management. However, ecologists have often derived data from costly field surveys. The Swan Goose (Anser cygnoides), a vulnerable Anatidae species, winters almost exclusively in China’s Yangtze River floodplain, but wintering numbers have been steadily decreasing. To better safeguard this unique species, modern modeling approaches can be used to quantify and predict its suitable wintering habitat. Specifically, a potential wintering distribution map of this species is critically important. Methods This study used the maximum entropy approach to model a distribution map of this species. In total, data from 97 up-to-date sites were extracted from 1263 survey sites (excluding duplicate data). After eliminating spatial autocorrelation, 11 environmental variables, including factors related to climate, land structure, vegetation, and anthropogenic activities, were used for model prediction. Results The prediction distribution map shows that the population has concentrated mainly in the boundary area of Anhui, Hubei, and Jiangxi provinces, especially along the Yangtze River. Modeling results suggest that areas within the middle and lower Yangtze River floodplain, such as those in Hunan and Hubei provinces and the eastern coastal area of Zhejiang Province, demonstrate a potential level of “medium” suitability for this species to winter. Conclusions Results from this study provide fundamental information for the restoration and management of the Swan Goose. Our “visualized” potential distribution map can assist in planning optimal conservation strategies, and consequently may help to increase the number of wintering populations in China.

Background/Aims: Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. Results: Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (P = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, I2 = 25%) and an increase of IL-6 in 3 studies with 134 subjects (P = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, I2 = 0%) in the probiotics groups. Analysis of serum creatinine (P = 0.47), blood urine nitrogen (P = 0.73), CRP (P = 0.55) and Hb (P = 0.49) yielded insignificant difference. Conclusion: Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.