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We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.

Abstract To evaluate the safety and efficacy of combining EW-7197 with irreversible electroporation (IRE) for improving wound healing, 16 male Sprague–Dawley rats were randomly divided into four groups of four rats each after dorsal excisional wound induction: sham control group; oral administration of EW-7197 for 7 days group; one-time application of IRE group; and one-time application of IRE followed by oral administration of EW-7197 for 7 days group. Measurement of wound closure rate, laser Doppler scanning, histological staining (hematoxylin and eosin and Masson’s trichrome), and immunohistochemical analyses (Ki-67 and α-SMA) were performed to evaluate the efficacy. Fifteen of 16 rats survived throughout the study. Statistically significant differences in wound closure rates were observed between the combination therapy group and the other three groups (all P

Abstract Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 μs) were significantly increased compared to the short pulse duration-treated groups (100 μs) (all p

Abstract Eustachian tube balloon dilatation (ETBD) has shown promising results in the treatment of ET dysfunction (ETD); however, recurrent symptoms after ETBD frequently occur in patients with refractory ETD. The excessive pressure of balloon catheter during ETBD may induce the tissue hyperplasia and fibrotic changes around the injured mucosa. Sirolimus (SRL), an antiproliferative agent, inhibits tissue proliferation. An SRL-coated balloon catheter was fabricated using an ultrasonic spray coating technique with a coating solution composed of SRL, purified shellac, and vitamin E. This study aimed to investigate effectiveness of ETBD with a SRL-coated balloon catheter to prevent tissue proliferation in the rat ET after ETBD. In 21 Sprague–Dawley rats, the left ET was randomly divided into the control (drug-free ETBD; n = 9) and the SRL (n = 9) groups. All rats were sacrificed for histological examination immediately after and at 1 and 4 weeks after ETBD. Three rats were used to represent the normal ET. The SRL-coated ETBD significantly suppressed tissue proliferation caused by mechanical injuries compared with the control group. ETBD with SRL-coated balloon catheter was effective and safe to maintain ET luminal patency without tissue proliferation at the site of mechanical injuries for 4 weeks in a rat ET model.

Abstract COVID-19 caused by SARS-CoV-2 spread rapidly around the world, endangering the health of people globally. The SARS-CoV-2 spike protein initiates entry into target cells by binding to human angiotensin-converting enzyme 2 (ACE2). In this study, we developed DNA aptamers that specifically bind to the SARS-CoV-2 spike protein, thereby inhibiting its binding to ACE2. DNA aptamers are small nucleic acid fragments with random structures that selectively bind to various target molecules. We identified nine aptamers targeting the SARS-CoV-2 spike protein using the systematic evolution of ligands by exponential enrichment (SELEX) method and selected three optimal aptamers by comparing their binding affinities. Additionally, we confirmed that the DNA aptamers suppressed pro-inflammatory cytokines induced by the SARS-CoV-2 spike protein in ACE2-overexpressing HEK293 cells. Overall, the DNA aptamer developed in this study has the potential to bind to the SARS-CoV-2 spike protein and inhibit or block its interaction with ACE2. Thus, our DNA aptamers can be used as new biological tools for the prevention and diagnosis of SARS-CoV-2 infection.

Abstract Hair loss disorders such as androgenetic alopecia have caused serious disturbances to normal human life. Animal models play an important role in exploring pathogenesis of disease and evaluating new therapies. NIH hairless mice are a spontaneous hairless mouse discovered and bred in our laboratory. In this study, we resequenced the genomes of NIH normal mice and NIH hairless mice and obtained 3,575,560 high-quality, plausible SNP loci and 995,475 InDels. The Euclidean distance algorithm was used to assess the association of SNP loci with the hairless phenotype, at a threshold of 0.62. Two regions of chromosome 18 having the highest association with the phenotype contained 345 genes with a total length of 13.98 Mb. The same algorithm was used to assess the association of InDels with the hairless phenotype at a threshold of 0.54 and revealed a region of 25.45 Mb in length, containing 518 genes. The mutation candidate gene Lama3 (NM_010680.2: c.652C>T; NP_034810.1: p. Arg217Cys) was selected based on the results of functional gene analysis and mutation prediction screening. Lama3 (R217C) mutant mice were further constructed using CRISPR/Cas9 technology, and the relationship between Lama3 point mutations and the hairless phenotype were clarified by phenotypic observation. The results showed that male Lama3 point mutation mice started to lose hair on the 80th day after birth, and the hair loss area gradually expanded over time. H&E staining of skin sections showed that the point mutation mice had increased sebaceous glands in the dermis and missing hair follicle structure (i.e., typical symptoms of androgenetic alopecia). This study is a good extension of the current body of knowledge about the function of Lama3, and the constructed Lama3 (R217C) mutant mice may be a good animal model for studying androgenetic alopecia.

Abstract Breast cancer (BRCA) is known as the leading cause of death in women worldwide and has a poor prognosis. Traditional therapeutic strategies such as surgical resection, radiotherapy and chemotherapy can cause adverse reactions such as drug resistance. Immunotherapy, a new treatment approach with fewer side effects and stronger universality, can prolong the survival of BRCA patients and even achieve clinical cure. However, due to population heterogeneity and other reasons, there are still certain factors that limit the efficacy of immunotherapy. Therefore, the importance of finding new tumor immune biomarker cannot be emphasized enough. Studies have reported that LGALS2 was closely related to immunotherapy efficacy, however, it is unclear whether it can act as an immune checkpoint for BRCA immunotherapy. In the current study, changes in LGALS2 expression were analyzed in public datasets such as TCGA-BRCA. We found that LGALS2 expression was associated with immune infiltration, drug resistance and other characteristics of BRCA. Moreover, high LGALS2 expression was closely related to immunotherapy response, and was associated with methylation modifications and clinical resistance for the first time. These findings may help to elucidate the role of LGALS2 in BRCA for the development and clinical application of future immunotherapy strategies against BRCA.

Abstract To explore the signal transmission mechanism of the arbuscular mycorrhizal network against root rot of Salvia miltiorrhiza. In this experiment, the arbuscular mycorrhizal hyphal network was established among Salvia miltiorrhiza plants, and a two plant three-compartment culture model was established. The root of the donor Salvia miltiorrhiza was inoculated with the pathogenic fungi Fusarium solani. The changes of hormone signals such as jasmonic acid and salicylic acid and the expression of related defense genes in the recipient Salvia miltiorrhiza plants in different periods were measured, to study the underground disease resistance signal transmission mechanism among medicinal plants. Salvia miltiorrhiza can transmit the signal of resistance to root rot through the jasmonic acid pathway; When plants suffer from disease stress, the content of JA increases significantly, and the increase of JA content will inhibit the content of SA in plants; The gene expression of PR-10 gene in the roots of Salvia miltiorrhiza with arbuscular mycorrhizal network infected by pathogenic fungi was 17.56 times higher than that inoculated only with pathogenic fungi; Changes in hormone content will also cause changes in the expression of related defense genes, such as SnRK2 is inhibited by ABA in the signal transduction pathway, while JA and ABA show antagonistic changes after inoculation of pathogenic fungi in Salvia miltiorrhiza, so JA may positively regulate the expression of SnRK2 gene. Plants can transmit signals through AM hyphal network after being stressed by the pathogen Fusarium solani. In the arbuscular mycorrhizal hyphal network, JA has important significance for the signal transmission of resistance to root rot and disease resistance of Salvia miltiorrhiza, which can make Salvia miltiorrhiza ready for stress resistance and improve the stress resistance of Salvia miltiorrhiza. This experiment is of great significance to further analyze the signal transmission mechanism of the arbuscular mycorrhizal hyphal network.

Abstract DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML). However, the mechanism underlying how DNA methylation regulates the differentiation of AML cells, including THP-1 is not fully elucidated. In this study, we report that UHRF1 or DNMT1 depletion enhances the phorbol-12-myristate-13-acetate (PMA)-induced differentiation of THP-1 cells. Transcriptome analysis and genome-wide methylation array results showed that depleting UHRF1 or DNMT1 induced changes that made THP-1 cells highly sensitive to PMA. Furthermore, knockdown of UHRF1 or DNMT1 impeded solid tumor formation in xenograft mouse model. These findings suggest that UHRF1 and DNMT1 play a pivotal role in regulating differentiation and proliferation of THP-1 cells and targeting these proteins may improve the efficiency of differentiation therapy in AML patients.

Abstract This study aimed to investigate the efficacy of a closed-cell self-expandable metallic stent (SEMS) with or without expanded-polytetrafluoroethylene (e-PTFE)-covering membrane in a porcine iliac artery model. Twelve Yorkshire domestic pigs were divided into a bare closed-cell SEMS (B-SEMS) group (n = 6) and covered closed-cell SEMS (C-SEMS) group (n = 6). Both closed-cell SEMSs were placed in the right or left iliac artery. Thrombogenicity score in the C-SEMS group was significantly higher than that in the B-SEMS group (p = 0.004) after 4 weeks. Angiographic findings of mean luminal diameters at 4 weeks follow-up did not differ significantly between B-SEMS and C-SEMS groups. Neointimal hyperplasia thickness as well as degree of inflammatory cell infiltration and collagen deposition in the C-SEMS group was significantly greater than that in the B-SEMS group (p

Abstract As a non-thermal ablation method, irreversible electroporation (IRE) has been widely investigated in the treatment of prostate cancer. However, no consensus has been achieved on the optimal parameters of IRE for prostate cancer. Since high voltage is known to carry risks of muscle contraction and patient discomfort, it is crucial to identify the minimum but effective and safer applied voltage to inhibit tumor growth. In this study, the effect of different applied voltages of IRE on prostate cancer was evaluated in BALB/c nude mice. Mathematical simulation and measurement of the actual ablation area revealed a larger ablation area at a higher voltage. In in vivo experiment, except for the three different voltages applied, all groups received identical electrical conditions: pulse number, 180 (20 groups × 9 pulses/group); pulse width, 100 µs; pulse interval, 2 ms; distance between the electrodes, 5 mm; and electrode exposure length, 15 mm. Whilst the tumor volume initially decreased in the 500 V (1000 V/cm) and 700 V (1400 V/cm) groups and subsequently increased, only a transient increase followed by a continuous decrease until the sacrifice was observed in the 900 V (1800 V/cm) group. This result demonstrated a lasting effect of a higher applied voltage on tumor growth inhibition. The histological, immunohistochemical, and western blot findings all confirmed IRE-induced apoptosis in the treatment groups. Taken together, 900 V seemed to be the minimum applied voltage required to reduce tumor growth, though subsequent studies are anticipated to further narrow the voltage intervals and lower the minimum voltage required for tumor inhibition.

Abstract Several investigations on the feasibility of stent placement into the Eustachian tube (ET) are being conducted. However, stents optimized for the anatomical structure of the ET have not yet been developed. In this study, the efficacy and safety of a self-expandable metallic stent (SEMS) optimized for porcine ET morphology was investigated. Silicone was injected into a cadaveric porcine ET to analyze the ET morphology. The three-dimensional-reconstructed porcine ET phantom images obtained after a computed tomography scan were measured to determine the dimensions of the porcine ET. The SEMS was designed as a tapered structure on the basis of the morphological findings of the porcine ET. The tapered SEMS (T-SEMS) and conventional SEMS (C-SEMS) were placed into the porcine ET to compare the safety and efficacy of the two types of SEMSs. Stent-induced tissue hyperplasia in the T-SEMS group was significantly lower than that in the C-SEMS group (p

Abstract Endoluminal radiofrequency (RF) ablation has been widely used as a safe and effective treatment for Barrett’s esophagus. However, inadequate RF ablation may occur due to insufficient contact between the electrode and target tissues. Herein, a stent-based monopolar RF electrode (SE) was developed to evenly deliver RF energy to the inner wall of the rat esophagus. The optimal RF parameters were evaluated in the exposed rat esophagus. The temperature in the rat esophagus reached 70 ℃ in 89 s at 30 W, 59 s at 40 W, and 34 s at 50 W. The technical feasibility and efficacy of RF ablation using SE were evaluated based on changes in histological transformation and immunohistochemical parameters of tissues compared at immediately, 1 and 2 weeks after the procedure. The degrees of inflammatory cell infiltration, fibrotic changes, TUNEL, and HSP70 in the RF-ablated rat esophagus were significantly higher than compared with sham control (all p

Abstract Stent-grafts composed of expanded polytetrafluoroethylene (e-PTFE), polyethylene terephthalate (PET) and polyurethane (PU) are characterized by poor endothelialization, high modulus, and low compliance, leading to thrombosis and intimal hyperplasia. A composite synthetic/natural matrix is considered a promising alternative to conventional synthetic stent-grafts. This study aimed to investigate the efficacy of thermoplastic polyurethane (TPU) and gelatin (GL) blended nanofibers (NFs) covered stent-graft in the porcine iliac artery. Twelve pigs were randomly sacrificed 7 days (n = 6) and 28 days (n = 6) after stent-graft placement. The thrombogenicity score at 28 days was significantly increased compared at 7 days (p

Abstract This study evaluated dental caries detection ability between the Qraycam and Qraypen on the same dental caries lesions. A total of 178teeth from 61patients were imaged using Qraypen C®(QC) and Qraycam Pro®(QP) devices and evaluated using analysis software (QA2). Occlusal, secondary, and proximal dental caries were evaluated and scored according to International Caries Detection and Assessment System(ICDAS II) and X-ray criteria. Bland–Altman plots were used to compare quantitative light-induced fluorescence(QLF) parameters obtained from the different QLF devices. Sensitivity, specificity, and area under the receiver operating characteristic curve(AUROC) were calculated. The ΔFaver. of the QLF-parameters showed that the mean difference between the two different QLF devices was close to zero and that the ± 5 error value was included in the mean ± 1.96SD range for the detection of dental caries. The accuracies for diagnosing occlusal dental caries were 0.83–0.96 and 0.81–0.82 and the accuracies for diagnosing proximal dental caries were 0.52–0.62 and 0.52–0.71 for the QC and QP devices, respectively. In conclusion, the ΔFaver. obtained from the QP showed diagnostic value mainly for screening of demineralized teeth. For teeth selected through screening, the depth of the lesion must be precisely evaluated using additional QP and radiographic imaging.

Abstract Various preclinical studies with developed Eustachian tube (ET) stents are in progress but have not yet been clinically applied. ET stent is limited by stent-induced tissue hyperplasia in preclinical studies. The effectiveness of sirolimus-eluting cobalt–chrome alloy stent (SES) in suppressing stent-induced tissue hyperplasia after stent placement in the porcine ET model was investigated. Six pigs were divided into two groups (i.e., the control and the SES groups) with three pigs for each group. The control group received an uncoated cobalt–chrome alloy stent (n = 6), and the SES group received a sirolimus-eluting cobalt–chrome alloy stent (n = 6). All groups were sacrificed 4 weeks after stent placement. Stent placement was successful in all ETs without procedure-related complications. None of the stents was able to keep its round shape as original, and mucus accumulation was observed inside and around the stent in both groups. On histologic analysis, the tissue hyperplasia area and the thickness of submucosal fibrosis were significantly lower in the SES group than in the control group. SES seems to be effective in suppressing stent-induced tissue hyperplasia in porcine ET. However, further investigation was required to verify the optimal stent materials and antiproliferative drugs.

Abstract Eupafolin is a flavonoid that can be extracted from common sage. Previous studies have reported that Eupafolin has antioxidant, anti-inflammatory and anti-tumor properties. However, no studies have investigated the role of Eupafolin in breast cancer. Herein, we investigated the effect of Eupafolin on two human breast cancer cell lines, as well as its potential mechanism of action. Next, the data showed that proliferation, migration and invasion ability of breast cancer cells that were treated with Eupafolin was significantly reduced, while the apoptosis rate was significantly increased. In addition, Eupafolin treatment caused breast cancer cell proliferation to be blocked in the S phase. Moreover, Eupafolin significantly induced autophagy in breast cancer cells, with an increase in the expression of LC3B-II. PI3K/AKT, MAPKs and NF-κB pathways were significantly inhibited by Eupafolin treatment. Additionally, 3-MA (a blocker of autophagosome formation) significantly reduced Eupafolin-induced activation of LC3B-II in breast cancer cells. Furthermore, Eupafolin displayed good in vitro anti-angiogenic activity. Additionally, anti-breast cancer activity of Eupafolin was found to be partially mediated by Cav-1. Moreover, Eupafolin treatment significantly weakened carcinogenesis of MCF-7 cells in nude mice. Therefore, this data provides novel directions on the use of Eupafolin for treatment of breast cancer.

Abstract Anchoring miniscrews used for a tissue bone borne maxillary expander (C-expander) can fail if they contact tooth roots or perforate the maxillary sinus. Cone beam computed tomography images were reviewed retrospectively to evaluate the geometric factors of miniscrew placement in the palate that contribute to root proximity (RP) and sinus perforation (SP), and to investigate the differences of miniscrew placement depth (PD) and placement angle (PA) among the groups in each variable from 340 anchoring miniscrews on 70 patients whose C-expanders showed sufficient stability after palatal expansion for orthodontic treatment. Two types of miniscrews were used: a self-tapping miniscrew with 1.8 mm-in-diameter, and a self-drilling miniscrew with 1.6 mm-in-diameter. While the self-tapping larger diameter miniscrew influenced root proximity significantly, the screw location and PD affected the rate of sinus perforation. PA was significantly different between the right and left sides of the palate. The results of this study confirmed that root proximity and sinus perforation of anchoring miniscrews in a tissue bone borne palatal expander occurred due to certain risk factors, even when the palates were expanded successfully. Knowledge of these factors can help the clinician place miniscrews with less risk of root proximity or sinus perforation.

Abstract The exposure of the prostate to high electric field strength during irreversible electroporation (IRE) has been extensively investigated. Multiple monopolar electrodes, however, have risks of organ piercing and bleeding when placing electrodes. A novel bipolar electrode made of pure platinum and stainless steel was developed for prostate cancer ablation. Voltages of 500 and 700 V were applied to the beagle prostate with this electrode to evaluate ablated tissues and their characteristics. IRE procedures were technically successful in all dogs without procedure-related complications. The current that flowed through the anode and cathode while applying 500 and 700 V were 1.75 ± 0.25 A and 2.22 ± 0.35 A, respectively. TUNEL assays showed that the estimated ablated areas when applying 500 and 700 V were 0.78 cm2 and 1.21 cm2, respectively. The minimum electric field strength threshold required for induction of IRE was 800 V/cm. The platinum electrode was resistant to corrosion. The IRE procedure for beagle prostates using a single bipolar electrode was technically feasible and safe. The novel bipolar electrode has great potential for treating human prostate cancer with fewer IRE-related complications.

Abstract Some craniofacial diseases or anatomical variations are found in radiographic images taken for other purposes. These incidental findings (IFs) can be detected in orthodontic patients, as various radiographs are required for orthodontic diagnosis. The radiographic data of 1020-orthodontic patients were interpreted to evaluate the rates of IFs in three-dimensional (3D) cone-beam-computed tomography (CBCT) with a large field of view (FOV) and investigate the effectiveness and accuracy of two-dimensional (2D) radiographs for detecting IFs compared to CBCT. Prevalence and accuracy in five areas was measured for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The accuracies of various 2D-radiograph were compared through a proportion test. A total of 709-cases (69.5%) of 1020-subjects showed one or more IFs in CBCT images. Nasal cavity was the most affected area. Based on the CBCT images as a gold standard, different accuracies of various 2D-radiographs were observed in each area of the findings. The highest accuracy was confirmed in soft tissue calcifications with comprehensive radiographs. For detecting nasal septum deviations, postero-anterior cephalograms were the most accurate 2D radiograph. In cases the IFs were not determined because of its ambiguity in 2D radiographs, considering them as an absence of findings increased the accuracy.

Abstract Zika virus (ZIKV) has emerged as a serious health threat in the Americas and the Caribbean. ZIKV is transmitted by the bite of an infected mosquito, sexual contact, and blood transfusion. ZIKV can also be transmitted to the developing fetus in utero, in some cases resulting in spontaneous abortion, fetal brain abnormalities, and microcephaly. In adults, ZIKV infection has been correlated with Guillain–Barre syndrome. Despite the public health threat posed by ZIKV, neither a vaccine nor antiviral drugs for use in humans are currently available. We have identified an amphibian host defense peptide, Yodha, which has potent virucidal activity against ZIKV. It acts directly on the virus and destroys Zika virus particles within 5 min of exposure. The Yodha peptide was effective against the Asian, African, and South American Zika virus strains and has the potential to be developed as an antiviral therapeutic in the fight against Zika virus. The peptide was also effective against all four dengue virus serotypes. Thus, Yodha peptide could potentially be developed as a pan-therapeutic for Zika and dengue viruses.

Abstract Photoacoustic microscopy (PAM) capitalizes on the optical absorption of blood hemoglobin to enable label-free high-contrast imaging of the cerebral microvasculature in vivo. Although time-resolved ultrasonic detection equips PAM with depth-sectioning capability, most of the data at depths are often obscured by acoustic reverberant artifacts from superficial cortical layers and thus unusable. In this paper, we present a first-of-a-kind dictionary learning algorithm to remove the reverberant signal while preserving underlying microvascular anatomy. This algorithm was validated in vitro, using dyed beads embedded in an optically transparent polydimethylsiloxane phantom. Subsequently, we demonstrated in the live mouse brain that the algorithm can suppress reverberant artifacts by 21.0 ± 5.4 dB, enabling depth-resolved PAM up to 500 µm from the brain surface.

Abstract Microvascular endothelial cell heterogeneity and its relationship to hemodynamics remains poorly understood due to a lack of sufficient methods to examine these parameters in vivo at high resolution throughout an angiogenic network. The availability of surrogate markers for functional vascular proteins, such as green fluorescent protein, enables expression in individual cells to be followed over time using confocal microscopy, while photoacoustic microscopy enables dynamic measurement of blood flow across the network with capillary-level resolution. We combined these two non-invasive imaging modalities in order to spatially and temporally analyze biochemical and biomechanical drivers of angiogenesis in murine corneal neovessels. By stimulating corneal angiogenesis with an alkali burn in Tie2-GFP fluorescent-reporter mice, we evaluated how onset of blood flow and surgically-altered blood flow affects Tie2-GFP expression. Our study establishes a novel platform for analyzing heterogeneous blood flow and fluorescent reporter protein expression across a dynamic microvascular network in an adult mammal.

Abstract Drug repositioning strategies have improved substantially in recent years. At present, two advances are poised to facilitate new strategies. First, the LINCS project can provide rich transcriptome data that reflect the responses of cells upon exposure to various drugs. Second, machine learning algorithms have been applied successfully in biomedical research. In this paper, we developed a systematic method to discover novel indications for existing drugs by approaching drug repositioning as a multi-label classification task and used a Softmax regression model to predict previously unrecognized therapeutic properties of drugs based on LINCS transcriptome data. This approach to complete the said task has not been achieved in previous studies. By performing in silico comparison, we demonstrated that the proposed Softmax method showed markedly superior performance over those of other methods. Once fully trained, the method showed a training accuracy exceeding 80% and a validation accuracy of approximately 70%. We generated a highly credible set of 98 drugs with high potential to be repositioned for novel therapeutic purposes. Our case studies included zonisamide and brinzolamide, which were originally developed to treat indications of the nervous system and sensory organs, respectively. Both drugs were repurposed to the cardiovascular category.

Abstract Our previous study indicated that interleukin (IL)-37 is involved in atherosclerosis. In the present study, Anterior tibial arteries were collected from diabetes patients and controls. A histopathological analysis showed that IL-37 was over-expressed in human atherosclerotic plaques. Many types of cells including macrophages, vascular smooth muscle cells (VSMCs), endothelial cells and T lymphocyte expressed IL-37 in human atherosclerotic plaques. ApoE−/− mice were divided into a control group and a recombinant human IL-37-treated group. The IL-37 treatment resulted in a significant decrease in macrophages and CD4+ T lymphocytes and a substantial increase in VSMCs and collagen in atherosclerotic plaques, resulting in a reduction in atherosclerotic plaque size. Furthermore, the IL-37 treatment modulated the CD4+ T lymphocyte activity, including a decrease in T helper cell type 1 (Th1) and Th17 cells and an increase in regulatory T (Treg) cells, and inhibited the maturity of dendritic cells both in vivo and in vitro. In addition, treatment with anti-IL-10 receptor monoclonal antibody abrogated the anti-atherosclerotic effects of IL-37. These data suggest that exogenous IL-37 ameliorates atherosclerosis via inducing the Treg response. IL-37 may be a novel therapeutic to prevent and treat atherosclerotic disease.

In order to ensure the filling integrity of complex counter-gravity casting and improve metallurgical quality, it is necessary to shorten the filling time while avoiding air entrainments. To address this contradiction, a novel nonlinear pressurization method was proposed in this study. Through systematically analyzing the relationship between critical gating velocity and stable filling height, a criterion for iterative calculation of nonlinear pressurization curve was established, and an empirical expression between nonlinear pressurizing speed and the filling height was obtained. Based on the empirical expression, a nonlinear pressurization curve can be designed according to the casting structures and initial pressurizing speeds. The above nonlinear pressure curve design method was validated through water filling experiments. It was proved that the nonlinear pressure curve can shorten the filling time while avoiding air entrainments. It provides important processing control method for improving the low-pressure casting performance of complex castings., (© 2024. The Author(s).)

The aim of this paper is to explore whether and how urban road transport (URT) development affects haze pollution. One of the innovations of this paper is that URT development is measured by road accessibility with novel digital elevation model datasets, which have been used by few scholars. The endogenous problem caused by revere causality issue in the relationship between URT development and haze pollution is also considered. Based on the panel data of prefecture-level cities of Yangtze River Delta (YRD) region in China from 2011 to 2018, this paper uses long-lagged values of URT development as the instrumental variable, employing the two-stage least squares (2SLS) method. The study shows that URT development leads to an increase of haze pollution. Moreover, mechanism tests based on moderating and mediating models support the finding that decreasing haze pollution resulted from better connection effects, while rising agglomeration effects tend to bring about increasing haze pollution, and the latter effect is larger in magnitude than the former. Current URT development may have long-term negative consequences for livability of YRD cities, and urban decision makers should reconsider the effectiveness of the current road transport investment and construction., (© 2024. The Author(s).)

This paper introduces the efficient medical-images-aimed segment anything model (EMedSAM), addressing the high computational demands and limited adaptability of using SAM for medical image segmentation tasks. We present a novel, compact image encoder, DD-TinyViT, designed to enhance segmentation efficiency through an innovative parameter tuning method called med-adapter. The lightweight DD-TinyViT encoder is derived from the well-known ViT-H using a decoupled distillation approach.The segmentation and recognition capabilities of EMedSAM for specific structures are improved by med-adapter, which dynamically adjusts the model parameters specifically for medical imaging. We conducted extensive testing on EMedSAM using the public FLARE 2022 dataset and datasets from the First Hospital of Zhejiang University School of Medicine. The results demonstrate that our model outperforms existing state-of-the-art models in both multi-organ and lung segmentation tasks., (© 2024. The Author(s).)

Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a deadly disease worldwide. The relationship between HF and cancer remains poorly understood. The Gene Expression Omnibus database was used to download the RNA sequencing data of 356 patients with hypertrophic cardiomyopathy-induced HF and non-HF. A co-expression network was established through the weighted correlation network analysis (WGCNA) to identify hub genes of HF and cancer. Cox risk analysis was performed to predict the prognostic risks of HF hub genes in pan-cancer. HF was linked to immune response pathway by the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A positive correlation was observed between the expression levels of 4 hub genes and the infiltration of CD8 + T-cells in pan-cancer. 4 hub genes were identified as beneficial prognostic factors in several cancers. Western blotting and real-time polymerase chain reaction validated the high expression of GZMM, NKG7, and ZAP70 in both mice and patients with HF compared to control groups. Our study highlights the shared immune pathogenesis of HF and cancer and provides valuable insights for developing novel therapeutic strategies, offering new opportunities for improving the management and treatment outcomes of both HF and cancer., (© 2024. The Author(s).)

Normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) in lung cancer patients with stereotactic body radiation therapy (SBRT), which based on dosimetric data from treatment planning, are limited to patients who have already received radiation therapy (RT). This study aims to identify a novel predictive factor for lung dose distribution and RP probability before devising actionable SBRT plans for lung cancer patients. A comprehensive correlation analysis was performed on the clinical and dose parameters of lung cancer patients who underwent SBRT. Linear regression models were utilized to analyze the dosimetric data of lungs. The performance of the regression models was evaluated using mean squared error (MSE) and the coefficient of determination (R 2 ). Correlational analysis revealed that most clinical data exhibited weak correlations with dosimetric data. However, nearly all dosimetric variables showed "strong" or "very strong" correlations with each other, particularly concerning the mean dose of the ipsilateral lung (MI) and the other dosimetric parameters. Further study verified that the lung tumor ratio (LTR) was a significant predictor for MI, which could predict the incidence of RP. As a result, LTR can predict the probability of RP without the need to design an elaborate treatment plan. This study, as the first to offer a comprehensive correlation analysis of dose parameters, explored the specific relationships among them. Significantly, it identified LTR as a novel predictor for both dose parameters and the incidence of RP, without the need to design an elaborate treatment plan., (© 2024. The Author(s).)

Psoriasis, a chronic inflammatory skin disorder, is associated with comorbidities such as acute myocardial infarction (AMI). However, the molecular mechanisms connecting these conditions are unclear. In this study, we conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes and hub genes associated with both psoriasis and AMI. Our findings emphasize the involvement of immune-related pathways in the pathogenesis of both conditions. Furthermore, we investigated the expression levels of hub genes in AMI patients and myocardial infarction (MI) mice. ELISA measurements revealed significantly higher levels of CXCL8, IL1B, S100A9, and S100A12 in the serum of AMI patients compared to normal individuals. Immunohistochemical staining of heart tissue from MI mice showed a progressive increase in the expression of CXCL8 and IL-1B as MI advanced, while S100A9 exhibited high expression at day 3 post-MI. mRNA expression analysis validated these findings. Additionally, we explored the skin lesions of psoriasis patients and found significantly higher expression of CXCL8, IL-1B, S100A9, and S100A12 in the affected skin areas compared to unaffected regions. These results highlight the consistent upregulation of hub genes in both AMI and psoriasis patients, as well as in myocardial infarction mice, underscoring their potential as reliable markers for disease diagnosis. Moreover, molecular docking simulations revealed potential interactions between simvastatin and key target proteins, suggesting a potential therapeutic avenue. Overall, our study uncovers shared molecular signatures and potential therapeutic targets, providing a foundation for future investigations targeting common pathways in psoriasis and AMI., (© 2024. The Author(s).)

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells., (© 2024. The Author(s).)

In order to extract more important morphological features of neuron images and achieve accurate classification of the neuron type, a method is proposed that uses Sugeno fuzzy integral integration of three optimized deep learning models, namely AlexNet, VGG11_bn, and ResNet-50. Firstly, using the pre-trained model of AlexNet and the output layer is fine-tuned to improve the model's performance. Secondly, in the VGG11_bn network, Global Average Pooling (GAP) is adopted to replace the traditional fully connected layer to reduce the number of parameters. Additionally, the generalization ability of the model is improved by transfer learning. Thirdly, the SE(squeeze and excitation) module is added to the ResNet-50 variant ResNeXt-50 to adjust the channel weight and capture the key information of the input data. The GELU activation function is used to better fit the data distribution. Finally, Sugeno fuzzy integral is used to fuse the output of each model to get the final classification result. The experimental results showed that on the Img_raw, Img_resample and Img_XYalign dataset, the accuracy of 4-category classification reached 98.04%, 91.75% and 93.13%, respectively, and the accuracy of 12-category classification reached 97.82%, 85.68% and 87.60%, respectively. The proposed method has good classification performance in the morphological classification of neurons., (© 2024. The Author(s).)

Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes-SLC7A11, LRPPRC, NDUFS1, and CD2AP-were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier., (© 2024. The Author(s).)

This study utilized arterial spin labeling-magnetic resonance imaging (ASL-MRI) to explore the developmental trajectory of brain activity associated with attention deficit hyperactivity disorder (ADHD). Pulsed arterial spin labeling (ASL) data were acquired from 157 children with ADHD and 109 children in a control group, all aged 6-12 years old. Participants were categorized into the age groups of 6-7, 8-9, and 10-12, after which comparisons were performed between each age group for ASL analysis of cerebral blood flow (CBF). In total, the ADHD group exhibited significantly lower CBF in the left superior temporal gyrus and right middle frontal gyrus regions than the control group. Further analysis revealed: (1) The comparison between the ADHD group (N = 70) aged 6-7 and the age-matched control group (N = 33) showed no statistically significant difference between. (2) However, compared with the control group aged 8-9 (N = 39), the ADHD group of the same age (N = 53) showed significantly lower CBF in the left postcentral gyrus and left middle frontal gyrus regions. (3) Further, the ADHD group aged 10-12 (N = 34) demonstrated significantly lower CBF in the left superior occipital region than the age-matched control group (N = 37). These age-specific differences suggest variations in ADHD-related domains during brain development post age 6-7., (© 2024. The Author(s).)

Potentially toxic metal(loid) assessment of tea and tea garden soil is a vital guarantee of tea safety and is very necessary. This study analyzed the distribution of seven potentially toxic metal(loid)s in different organs of the tea plants and soil at various depths in the Yangai tea farm of Guiyang City, Guizhou Province, China. Although soil potentially toxic metal(loid) in the study area is safe, there should be attention to the health risks of Cu, Ni, As, and Pb in the later stages of tea garden management. Soil As and Pb are primarily from anthropogenic sources, soil Zn is mainly affected by natural sources and human activities, and soil with other potentially toxic metal(loid) is predominantly from natural sources. Tea plants might be the enrichment of Zn and the exclusion or tolerance of As, Cu, Ni, and Pb. The tea plant has a strong ability for absorbing Cd and preferentially storing it in its roots, stems, and mature leaves. Although the Cd and other potentially toxic metal(loid)s content of tea in Guizhou Province is generally within the range of edible safety, with the increase of tea planting years, it is essential to take corresponding measures to prevent the potential health risks of Cd and other potentially toxic metal(loid)s in tea., (© 2024. The Author(s).)

Investigating surfactant effects on the floatability of Wiser bituminous coal holds significant importance in improving coal cleanliness and utilization value. Using density functional theory and molecular dynamics simulation methods, this study constructed models of Wiser bituminous coal and examined the impact of different surfactants, including the anionic surfactant sodium dodecyl benzene sulfonate, the cationic surfactant hexadecyl trimethyl ammonium bromide (CTAB), and the non-ionic surfactant fatty alcohol ethoxylated ether. The focus was on investigating the charge distribution characteristics of these molecules and the modifying effect of binary surfactants on the hydrophobicity of bituminous coal. Results revealed that the maximum electrostatic potential was concentrated near oxygen/nitrogen/sulfur-containing functional groups like sulfonic acid groups, quaternary ammonium cations, ethylene oxide, hydroxyl groups, carboxyl groups, and sulfur bonds. These functional groups exhibited a propensity for accepting/delivering electrons to form hydrogen bonds. Among the surfactants tested, CTAB revealed the slightest difference in frontier orbital energy, measuring 3.187 eV, thereby demonstrating a superior trapping ability compared with the other two surfactants. Adsorption reactions within the system were determined to be spontaneous, with over 60% of the interaction force attributed to electrostatic forces. Moreover, the repulsive force magnitude with water molecules followed the trend: sulfonate group (2.20 Å) < ethylene oxide (2.43 Å) < quaternary ammonium cation (2.57 Å), indicating more excellent water repellency of CTAB. Findings showed that CTAE binary surfactants proved most effective in modifying the hydrophobicity of bituminous coal. This study offers valuable insights into reducing waste, pollution, and resource wastage., (© 2024. The Author(s).)

Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA + H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ., (© 2024. The Author(s).)

Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between  ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a "Trojan horse" to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors., (© 2024. The Author(s).)

The agonist-antagonist myoneural interface (AMI) is an amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects conducted by Srinivasan et al. (2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this study on resting state functional magnetic resonance imaging in AMI subjects, we compared functional connectivity in patients with transtibial AMI (n = 12) and traditional (n = 7) amputations (TA). To test our hypothesis that we would find significant neurophysiological differences between AMI and TA subjects, we performed a whole-brain exploratory analysis to identify a seed region; namely, we conducted ANOVA, followed by t-test statistics to locate a seed in the salience network. Then, we implemented a seed-based connectivity analysis to gather cluster-level inferences contrasting our subject groups. We show evidence supporting our hypothesis that the AMI surgery induces functional network reorganization resulting in a neural configuration that significantly differs from the neural configuration after TA surgery. AMI subjects show significantly less coupling with regions functionally dedicated to selecting where to focus attention when it comes to salient stimuli. Our findings provide researchers and clinicians with a critical mechanistic understanding of the effect of AMI amputation on brain networks at rest, which has promising implications for improved neurorehabilitation and prosthetic control., (© 2024. The Author(s).)

Topographic Rossby waves (TRWs) dominate the low-frequency variability of deep ocean currents and play a crucial role in energy exchange and material mixing. On the continental slope of the southwestern South China Sea, a deep-water mooring was deployed to observe TRWs for a period of ~ 40 days. The TRWs, with a wavelength of 109 km, account for 41.3% of the subinertial variations. A ray-tracing model was applied to investigate the propagation and energy source. The results showed that the TRWs propagated from the northeast of the mooring location and were most likely caused by the mesoscale eddy disturbances off the Vietnam coast. This study provides a new perspective on examining the impact of mesoscale eddies off Vietnam on abyssal currents., (© 2024. The Author(s).)

Breast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth retardation and chemotherapy sensitivity in tumor cells. We investigated whether D-arabinose has capability to restrict the proliferation of tumor cells and its mechanism. Here, we report that D-arabinose induced cytotoxicity is modulated by autophagy and p38 MAPK signaling pathway in breast cancer cell lines. The proliferation of cells was evaluated by CCK-8 and Colony formation assay. The distribution of cells in cell cycle phases was analyzed by flow cytometry. Cell cycle, autophagy and MAPK signaling related proteins were detected by western blotting. Mouse xenograft model was used to evaluate the efficacy of D-arabinose in vivo. The proliferation of cells was dramatically inhibited by D-arabinose exposure in a dose-dependent manner, which was relevant to cell cycle arrest, as demonstrated by G2/M cell cycle restriction and ectopic expression of cell cycle related proteins. Mechanistically, we further identified that D-arabinose is positively associated with autophagy and the activation of the p38 MAPK signaling in breast cancer. In contrast, 3-Ma or SB203580, the inhibitor of autophagy or p38 MAPK, reversed the efficacy of D-arabinose. Additionally, D-arabinose in vivo treatment could significantly inhibit xenograft growth of breast cancer cells. Our findings were the first to reveal that D-arabinose triggered cell cycle arrest by inducing autophagy through the activation of p38 MAPK signaling pathway in breast cancer cells., (© 2024. The Author(s).)

Due to the BCS theory, hydrogen, the lightest element, would be the prospect of room-temperature superconductor after metallization, but because of the difficulty of the hydrogen metallization, the theory about hydrogen pre-compression was proposed that the hydrogen-rich compounds could be a great option for the high T c superconductors. The superior properties of TmH 6 , YbH 6 and LuH 6 indicated the magnificent potential of heavy rare earth elements for low-pressure stability. Here, we designed XTmH 12 (X = Y, Yb, Lu, and La) to obtain higher T c while maintaining low pressure stability. Most prominently, YbTmH 12 can stabilize at a pressure of 60 GPa. Compared with binary TmH 6 hydride, its T c was increased to 48 K. The results provide an effective method for the rational design of moderate pressure stabilized hydride superconductors., (© 2024. The Author(s).)

Myocardial infarction (MI) is the leading cause of premature death. The death of cardiomyocytes (CMs) and the dysfunction of the remaining viable CMs are the main pathological factors contributing to heart failure (HF) following MI. This study aims to determine the transcriptional profile of CMs and investigate the heterogeneity among CMs under hypoxic conditions. Single-cell atlases of the heart in both the sham and MI groups were developed using single-cell data (GSE214611) downloaded from Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). The heterogeneity among CMs was explored through various analyses including enrichment, pseudo time, and intercellular communication analysis. The marker gene of C5 was identified using differential expression analysis (DEA). Real-time polymerase chain reaction (RT-PCR), bulk RNA-sequencing dataset analysis, western blotting, immunohistochemical and immunofluorescence staining, Mito-Tracker staining, TUNEL staining, and flow cytometry analysis were conducted to validate the impact of the marker gene on mitochondrial function and cell apoptosis of CMs under hypoxic conditions. We identified a cell subcluster named C5 that exhibited a close association with mitochondrial malfunction and cellular apoptosis characteristics, and identified Slc25a4 as a significant biomarker of C5. Furthermore, our findings indicated that the expression of Slc25a4 was increased in failing hearts, and the downregulation of Slc25a4 improved mitochondrial function and reduced cell apoptosis. Our study significantly identified a distinct subcluster of CMs that exhibited strong associations with ventricular remodeling following MI. Slc25a4 served as the hub gene for C5, highlighting its significant potential as a novel therapeutic target for MI., (© 2024. The Author(s).)

Accurate labeling of lung nodules in computed tomography (CT) images is crucial in early lung cancer diagnosis and before nodule resection surgery. However, the irregular shape of lung nodules in CT images and the complex lung environment make it much more challenging to segment lung nodules accurately. On this basis, we propose an improved V-Net segmentation method based on pixel threshold separation and attention mechanism for lung nodules. This method first offers a data augment strategy to solve the problem of insufficient samples in 3D medical datasets. In addition, we integrate the feature extraction module based on pixel threshold separation into the model to enhance the feature extraction ability under different thresholds on the one hand. On the other hand, the model introduces channel and spatial attention modules to make the model pay more attention to important semantic information and improve its generalization ability and accuracy. Experiments show that the Dice similarity coefficients of the improved model on the public datasets LUNA16 and LNDb are 94.9% and 81.1% respectively, and the sensitivities reach 92.7% and 76.9% respectively. which is superior to most existing UNet architecture models and comparable to the manual level segmentation results by medical technologists., (© 2024. The Author(s).)

Deep clustering has been widely applicated in various fields, including natural image and language processing. However, when it is applied to hyperspectral image (HSI) processing, it encounters challenges due to high dimensionality of HSI and complex spatial-spectral characteristics. This study introduces a kind of deep clustering model specifically tailed for HSI analysis. To address the high dimensionality issue, redundant dimension of HSI is firstly eliminated by combining principal component analysis (PCA) with t-distributed stochastic neighbor embedding (t-SNE). The reduced dataset is then input into a three-dimensional attention convolutional autoencoder (3D-ACAE) to extract essential spatial-spectral features. The 3D-ACAE uses spatial-spectral attention mechanism to enhance captured features. Finally, these enhanced features pass through an embedding layer to create a compact data-representation, and the compact data-representation is divided into distinct clusters by clustering layer. Experimental results on three publicly available datasets validate the superiority of the proposed model for HSI analysis., (© 2024. The Author(s).)

Benzopyrene (B[a]P) is a well-known carcinogen that can induce chronic inflammation and fibrosis in the liver, leading to liver disease upon chronic exposure. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis of publicly available gene expression profiles, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer. Furthermore, network analysis revealed hub genes and protein-protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Notably, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we conducted qPCR analysis on cell lines and NASH mouse liver tissues and performed immunohistochemistry labeling in mouse and human HCC liver sections. These findings provide crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity, shedding light on the pathogenesis of B[a]P-associated NASH and HCC. Moreover, our study suggests that HSPA1A and PPARGC1A could serve as promising therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes., (© 2023. The Author(s).)

The interspecific responses to alarm signals may be based on unlearned mechanisms but research is often constrained by the difficulties in differentiating between unlearned and learned responses in natural situations. In a field study of two Paridae species, Parus minor and Sittiparus varius, who originated from a common ancestor 8 million years ago, we found a considerable degree of between-species overlap in acoustic properties of referential snake-alarm calls. Playback of these calls triggered unlearned adaptive fledging behavior in conspecific and heterospecific naive nestlings, suggesting a between-species overlap in the hypothetical unlearned neural templates involved in nestlings' reactions to alarm calls in both species. This suggests that similar calls and similar unlearned sensitivity might have been present in the common ancestor of the two species, and possibly in the ancestor of the whole family Paridae that originated 10-15 million years ago in Asian regions rich in snakes., (© 2023. The Author(s).)