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Abstract Dual-energy cone beam computed tomography (DE-CBCT) has been shown to provide more information and improve performance compared to a conventional single energy spectrum CBCT. Here we report a low-cost DE-CBCT by spectral filtration of a carbon nanotube x-ray source array. The x-ray photons from two focal spots were filtered respectively by a low and a high energy filter. Projection images were collected by alternatively activating the two beams while the source array and detector rotated around the object, and were processed by a one-step materials decomposition and reconstruction method. The performance of the DE-CBCT scanner was evaluated by imaging a water-equivalent plastic phantom with inserts containing known densities of calcium or iodine and an anthropomorphic head phantom with dental implants. A mean energy separation of 15.5 keV was achieved at acceptable dose rates and imaging time. Accurate materials quantification was obtained by materials decomposition. Metal artifacts were reduced in the virtual monoenergetic images synthesized at high energies. The results demonstrated the feasibility of high quality DE-CBCT imaging by spectral filtration without using either an energy sensitive detector or rapid high voltage switching.

The simultaneous administration of antibacterial treatment and acceleration of tissue regeneration are crucial for the effective healing of infected wounds. In this work, we developed a facile hydrogel (PCC hydrogel) through coordination and hydrogen interactions by polymerizing acrylamide monomers in the presence of carboxymethyl chitosan nanoparticles and copper ions. The prepared PCC hydrogel demonstrated effective bacterial capture from wound exudation and exhibited a potent bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Furthermore, slow release of copper ions from the hydrogel facilitated wound healing by promoting cell migration, collagen deposition and angiogenesis. Additionally, the PCC hydrogel possessed excellent biocompatibility and hemostatic properties. The practical effectiveness of PCC hydrogel in addressing bacterial infections and facilitating wound healing was verified using a mouse model of MRSA-induced wound infections. Overall, this work presents a simple yet efficient multifunctional hydrogel platform that integrates antibacterial activity, promotion of wound healing, and hemostasis for managing bacteria-associated wounds.

BackgroundNon-suicidal self-injury (NSSI) is a worldwide mental health problem that deserves thorough investigation. This study aims to explore the effect of parenting styles, attachment to parents, and self-compassion on the occurrence of non-suicidal self-injury (NSSI) behavior in adolescents and whether these factors influence their recovery motivation.MethodsA total of 132 adolescents who had engaged in NSSI within the last year and 72 adolescents who had never engaged in NSSI were recruited from the Shenzhen Kangning Hospital and from primary and secondary schools and communities. Differences in the Hamilton Depression Scale (HAMD), Inventory of Parent and Peer Attachment (IPPA), Egma Minn av. Bardndosnauppforstran (EMBU), and Self-Compassion Scale (SCS) of participants were compared. A binary logistic model was established to measure the odds ratios of these variables on the occurrence of NSSI. In the NSSI adolescent sample, separate binary logistic models were created with NSSI impulse inhibition, NSSI resistance activity, and NSSI recovery motivation as dependent variables and with parenting styles, attachment to parents, and self-compassion as independent variables.ResultsCompared with adolescents with no NSSI behavior, those who had engaged in NSSI within the past year had higher scores on the HAMD, as well as higher EMBU-negative father parental behavior (punishment, excessive interference, rejection, and overprotection), EMBU-negative mother parental behavior (excessive interference, rejection, and punishment), and SCS negative self-compassion scores. Moreover, adolescents with NSSI had lower EMBU-father emotional warmth, EMBU-mother emotional warmth, IPPA-attachment to father, IPPA-attachment to mother, and SCS positive self-compassion scores. Current depressive symptoms and maternal punishment are risk factors for NSSI in adolescents, while positive self-compassion was a protective factor. Positive self-compassion can positively predict NSSI impulse inhibition, NSSI resistance activity, and NSSI recovery motivation. However, we unexpectedly found that the father’s emotional warmth negatively predicts NSSI resistance activity.ConclusionThis study found that positive self-compassion has a significant impact on the prevention of and recovery from NSSI behavior in adolescents.

Abstract Objectives To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. Methods Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether‐filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI‐based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. Results The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. Conclusion Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Abstract Rice blast is a serious threat to the safe production of grain crops such as rice and wheat. Sporulation, appressorium formation, and invasive growth of Magnaporthe oryzae are the key stages of the development and spread of rice blast epidemics. M. oryzae is a hemibiotrophic fungus that undergoes changes in available carbon sources during the infection cycle. Lipid is a major storage for M. oryzae spores and a major carbon source used in glycerol synthesis and turgor pressure generation in appressoria. The formation of a dense cell wall melanin layer is necessary for an appressorium to produce turgor and to be pathogenic. The plant cell wall is an important carbon source during the infection stage of M. oryzae. Transcription factors regulate gene expression in fungi and are key intermediates between the reception of external environmental signals and the control of development and pathogenicity in M. oryzae. The disease cycle of M. oryzae is controlled by some key transcription factors, such as sporulation by Cos1 and Hox2, appressorium formation by Sfl1, Hox7, and Vrf1, invasive growth by Mst12 and Mig1, and resistance to host basal immunity by Ap1 and Atf1. This review focuses on describing the key transcription factors of M. oryzae that regulate sporulation, appressorium formation, invasive growth, lipid metabolism, carbohydrate metabolism, melanin synthesis, oxidative response, and host basal immunity, as well as the working mechanism of the transcription factors.

Abstract Multisource cone beam computed tomography CBCT (ms-CBCT) has been shown to overcome some of the inherent limitations of a conventional CBCT. The purpose of this study was to evaluate the accuracy of ms-CBCT for measuring the bone mineral density (BMD) of mandible and maxilla compared to the conventional CBCT. The values measured from a multi-detector CT (MDCT) were used as substitutes for the ground truth. An anthropomorphic adult skull and tissue equivalent head phantom and a homemade calibration phantom containing inserts with varying densities of calcium hydroxyapatite were imaged using the ms-CBCT, the ms-CBCT operating in the conventional single source CBCT mode, and two clinical CBCT scanners at similar imaging doses; and a clinical MDCT. The images of the anthropomorphic head phantom were reconstructed and registered, and the cortical and cancellous bones of the mandible and the maxilla were segmented. The measured CT Hounsfield Unit (HU) and Greyscale Value (GV) at multiple region-of-interests were converted to the BMD using scanner-specific calibration functions. The results from the various CBCT scanners were compared to that from the MDCT. Statistical analysis showed a significant improvement in the agreement between the ms-CBCT and MDCT compared to that between the CBCT and MDCT.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0–25% and 25–70%. Tumour proportion score distribution was as follows: tumour proportion score 5% in 10.6%. Combined positive score distribution was as follows: combined positive score 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (

Abstract Cone beam computed tomography (CBCT) is widely used in medical and dental imaging. Compared to a multidetector CT, it provides volumetric images with high isotropic resolution at a reduced radiation dose, cost and footprint without the need for patient translation. The current CBCT has several intrinsic limitations including reduced soft tissue contrast, inaccurate quantification of X-ray attenuation, image distortions and artefacts, which have limited its clinical applications primarily to imaging hard tissues and made quantitative analysis challenging. Here we report a multisource CBCT (ms-CBCT) which overcomes the shortcomings of the conventional CBCT by using multiple narrowly collimated and rapidly scanning X-ray beams from a carbon nanotube field emission source array. Phantom imaging studies show that, the ms-CBCT increases the accuracy of the Hounsfield unit values by 60%, eliminates the cone beam artefacts, extends the axial coverage, and improves the soft tissue contrast-to-noise ratio by 30–50%, compared to the CBCT configuration.

Abstract ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2. However, experimental structures are still missing to decipher its inhibition mechanism. Here, we present cryo-EM structures of apo ClC-2 and its complex with AK-42, both at 3.5 Å resolution. Residues S162, E205 and Y553 are involved in chloride binding and contribute to the ion selectivity. The side-chain of the gating glutamate E205 occupies the putative central chloride-binding site, indicating that our structure represents a closed state. Structural analysis, molecular dynamics and electrophysiological recordings identify key residues to interact with AK-42. Several AK-42 interacting residues are present in ClC-2 but not in other ClCs, providing a possible explanation for AK-42 specificity. Taken together, our results experimentally reveal the potential inhibition mechanism of ClC-2 inhibitor AK-42.

Abstract Most existing bioluminescence imaging methods can only visualize the location of engineered bacteria in vivo, generally precluding the imaging of natural bacteria. Herein, we leverage bacteria-specific ATP-binding cassette sugar transporters to internalize luciferase and luciferin by hitchhiking them on the unique carbon source of bacteria. Typically, the synthesized bioluminescent probes are made of glucose polymer (GP), luciferase, Cy5 and ICG-modified silicon nanoparticles and their substrates are made of GP and D-luciferin-modified silicon nanoparticles. Compared with bacteria with mutations in transporters, which hardly internalize the probes in vitro (i.e., ~2% of uptake rate), various bacteria could robustly engulf the probes with a high uptake rate of around 50%. Notably, the developed strategy enables ex vivo bioluminescence imaging of human vitreous containing ten species of pathogens collected from patients with bacterial endophthalmitis. By using this platform, we further differentiate bacterial and non-bacterial nephritis and colitis in mice, while their chemiluminescent counterparts are unable to distinguish them.

Pannexin 2 plays critical roles in many physiological processes but its mechanism remain unclear. Here, authors report the cryo-EM structure of human Panx2 in the open state and identify critical residues for its gating.

Abstract Objectives To compare tumor size measurements using CT and MRI in pancreatic cancer (PC) patients with neoadjuvant therapy (NAT). Methods This study included 125 histologically confirmed PC patients who underwent NAT. The tumor sizes from CT and MRI before and after NAT were compared by using Bland–Altman analyses and intraclass correlation coefficients (ICCs). Variations in tumor size estimates between MRI and CT in relationship to different factors, including NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0–2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analysed. The McNemar test was used to compare the efficacy of NAT evaluations based on the CT and MRI measurements according to RECIST 1.1 criteria. Results There was no significant difference between the median tumor sizes from CT and MRI before and after NAT (P = 0.44 and 0.39, respectively). There was excellent agreement in tumor size between MRI and CT, with mean size differences and limits of agreement (LOAs) of 1.5 [-9.6 to 12.7] mm and 0.9 [-12.6 to 14.5] mm before NAT (ICC, 0.93) and after NAT (ICC, 0.91), respectively. For all the investigated factors, there was good or excellent correlation (ICC, 0.76 to 0.95) for tumor sizes between CT and MRI. There was no significant difference in the efficacy evaluation of NAT between CT and MRI measurements (P = 1.0). Conclusion MRI and CT have similar performance in assessing PC tumor size before and after NAT.

BackgroundStudies on eye movements found that children with autism spectrum disorder (ASD) had abnormal gaze behavior to social stimuli. The current study aimed to investigate whether their eye movement patterns in relation to cartoon characters or real people could be useful in identifying ASD children.MethodsEye-tracking tests based on videos of cartoon characters and real people were performed for ASD and typically developing (TD) children aged between 12 and 60 months. A three-level hierarchical structure including participants, events, and areas of interest was used to arrange the data obtained from eye-tracking tests. Random forest was adopted as the feature selection tool and classifier, and the flattened vectors and diagnostic information were used as features and labels. A logistic regression was used to evaluate the impact of the most important features.ResultsA total of 161 children (117 ASD and 44 TD) with a mean age of 39.70 ± 12.27 months were recruited. The overall accuracy, precision, and recall of the model were 0.73, 0.73, and 0.75, respectively. Attention to human-related elements was positively related to the diagnosis of ASD, while fixation time for cartoons was negatively related to the diagnosis.ConclusionUsing eye-tracking techniques with machine learning algorithms might be promising for identifying ASD. The value of artificial faces, such as cartoon characters, in the field of ASD diagnosis and intervention is worth further exploring.

Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.

Purpose: Evaluation of the variabilities in apparent diffusion coefficient (ADC) measurements of the spleen (ADCspleen) and the paraspinal muscles (ADCmuscle) to identify the reference organ for normalizing the ADC from the abdominal diffusion weighted imaging (DWI). Methods: Two MRI scanners, with 314 abdominal exams on the GE and 929 on the Siemens system, were used for MRI examinations including DWI (b-values, 50 and 800 s/mm2). For a subset of 73 exams on the Siemens system a second exam was conducted. Four regions of interest (ROIs) in each exam were placed to measure the ADCspleen and the bilateral ADCmuscle. ADC variability between patients (on each scanner separately), ADC variability due to ROI placement between the two ROIs in each organ, and variability in the subset between the first and second exams were assessed. Results: The ADCspleen was more scattered and variable than the ADCmuscle in the comparability (n = 929 and 314 for two MRI scanners, respectively) and repeatability (n = 73) datasets. The Bland-Altmann bias and limits of agreement (LoAs) for the ADCspleen (ICC, 0.47; CV, 0.070) and ADCmuscle (ICC, 0.67; CV, 0.023) in the repeatability datasets (n = 73) were −0.1 (−25.7%–25.6%) and −0.3 (−8.8%–8.1%), respectively. For the Siemens system, the Bland-Altmann bias and LoAs for the ADCspleen (ICC, 0.72; CV, 0.061) and ADCmuscle (ICC, 0.53; CV, 0.030) in the comparability datasets (n = 929) were 2.1 (−20.0%–24.2%) and 0.7 (−10.0%–11.4%), respectively. Similar findings have been found in the GE system (n = 314). The CVs for the ADCmuscle measurements were lower than those of the ADCspleen both in the repeatability and the comparability analyses (all p

BackgroundArterial Velocity-pulse Index (AVI) and Arterial Pressure-volume Index (API), measured by a brachial cuff, have been demonstrated to be indicative of arterial stiffness and correlated with the risk of cardiovascular events. However, the threshold values of AVI and API for screening increased arterial stiffness in the general population are yet to be established.MethodsThe study involved 860 subjects who underwent general physical examinations (M/F = 422/438, age 53.4 ± 12.7 years) and were considered to represent the general population in China. In addition to the measurements of AVI, API and brachial-ankle pulse wave velocity (baPWV), demographic information, arterial blood pressures, and data from blood and urine tests were collected. The threshold values of AVI and API were determined by receiver operating characteristic (ROC) analyses and covariate-adjusted ROC (AROC) analyses against baPWV, whose threshold for diagnosing high arterial stiffness was set at 18 m/s. Additional statistical analyses were performed to examine the correlations among AVI, API and baPWV and their correlations with other bio-indices.ResultsThe area under the curve (AUC) values in ROC analysis for the diagnosis with AVI/API were 0.745/0.819, 0.788/0.837, and 0.772/0.825 (95% CI) in males, females, and all subjects, respectively. Setting the threshold values of AVI and API to 21 and 27 resulted in optimal diagnosis performance in the total cohort, whereas the threshold values should be increased to 24 and 29, respectively, in order to improve the accuracy of diagnosis in the female group. The AROC analyses revealed that the threshold values of AVI and API increased markedly with age and pulse pressure (PP), respectively.ConclusionsWith appropriate threshold values, AVI and API can be used to perform preliminary screening for individuals with increased arterial stiffness in the general population. On the other hand, the results of the AROC analyses imply that using threshold values adjusted for confounding factors may facilitate the refinement of diagnosis. Given the fact that the study is a cross-sectional one carried out in a single center, future multi-center or follow-up studies are required to further confirm the findings or examine the value of the threshold values for predicting cardiovascular events.

The current tumour-node-metastasis staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer. Herein, the authors propose a pathomics signature that was derived from multiple features of haematoxylin and eosin-stained slides.

Different blood-brain barrier permeable systems, such as bacteria loaded with chemotherapy, have been proposed to treat glioblastoma. Here, the authors generate bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles to eliminate bacteria-infected glioblastoma cells and induce an anti-tumour immune response upon photothermal therapy.

Background: Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI. Materials and methods: In an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT2FLAIR-MZFI) sequence. Results: The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p

Abstract Purpose Emerging evidence shows that immune checkpoint inhibitors lead to durable responses in a variety of cancers, including nasopharyngeal carcinoma (NPC), however, combination approaches (i.e., stereotactic body radiation therapy, SBRT) are required to extend this benefit beyond a subset of patients. This study retrospectively evaluated eight recurrent/metastatic NPC patients, to investigate how radiation could potentiate PD-1 checkpoint inhibition therapy. Methods Between September 2016 and July 2017, eight consecutive cases with histologically confirmed PDL1-positive status, for which prior standard therapy had been ineffective (five patients), were treated at our institution and Macao Clinics and two patients had disease progression within 6 months of completion of definitive chemoradiation, or one patient refused to receive chemoradiotherapy. All received PD-1 inhibitors first, seven of them accepted SBRT with an unmodified PD-1 inhibitors regimen after first evaluation as they were unresponsive to PD-1 inhibitors alone. Treatment was discontinued as long as patients were experiencing a clinical benefit in the opinion of the physicians and at least five cycles were given before stoppage. Results Median follow-up time was 56.7 months. The confirmed objective response rate based on RECIST-v1.1 at first evaluation was 12.5% (1/8). For the seven cases who received SBRT, six of them experience an objective response (6/7, 85.7%) after SBRT. Only one patient showed rapid progress and die within 95 days after the initiation of SBRT intervention. Three patients who did not have all lesions exposed to irradiation were available to evaluate the incidence of an abscopal effect, however, it did not occur as expected. Median PFS and OS for the seven patients were 8.0 and 30.8 months after SBRT intervention, respectively. Two-year OS as indicated was 71.0%. Conclusions PD-1 inhibitors combined with SBRT demonstrated promising antitumor activity in patients with PD-L1 positive RM-NPC. Patients may benefit from continue immunotherapy beyond disease progression when SBRT was introduced.

Summary: The tumor, nodes and metastasis (TNM) classification system provides useful but incomplete prognostic information and lacks the assessment of the tumor microenvironment (TME). Collagen, the main component of the TME extracellular matrix, plays a nonnegligible role in tumor invasion and metastasis. In this cohort study, we aimed to develop and validate a TME collagen signature (CSTME) for prognostic prediction of stage II/III colorectal cancer (CRC) and to compare the prognostic values of “TNM stage + CSTME” with that of TNM stage alone. Results indicated that the CSTME was an independent prognostic risk factor for stage II/III CRC (hazard ratio: 2.939, 95% CI: 2.180–3.962, p

PurposeTo evaluate the diagnostic performance of radiomics model based on fully automatic segmentation of pancreatic tumors from non-enhanced magnetic resonance imaging (MRI) for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).Materials and methodsIn this retrospective study, patients with surgically resected histopathologically confirmed PASC and PDAC who underwent MRI scans between January 2011 and December 2020 were included in the study. Multivariable logistic regression analysis was conducted to develop a clinical and radiomics model based on non-enhanced T1-weighted and T2-weighted images. The model performances were determined based on their discrimination and clinical utility. Kaplan-Meier and log-rank tests were used for survival analysis.ResultsA total of 510 consecutive patients including 387 patients (age: 61 ± 9 years; range: 28–86 years; 250 males) with PDAC and 123 patients (age: 62 ± 10 years; range: 36–84 years; 78 males) with PASC were included in the study. All patients were split into training (n=382) and validation (n=128) sets according to time. The radiomics model showed good discrimination in the validation (AUC, 0.87) set and outperformed the MRI model (validation set AUC, 0.80) and the ring-enhancement (validation set AUC, 0.74).ConclusionsThe radiomics model based on non-enhanced MRI outperformed the MRI model and ring-enhancement to differentiate PASC from PDAC; it can, thus, provide important information for decision-making towards precise management and treatment of PASC.

The endoplasmic reticulum (ER) acts as the starting point of the secretory pathway, where approximately one-third of the proteins are correctly folded and modified, loaded into vesicles, and transported to the Golgi for further processing and modification. In this process, COPII vesicles are responsible for transporting cargo proteins from the ER to the Golgi. Here, we identified the inner shell subunit of COPII vesicles (MoSec24B) and explored the importance of MoSec24B in the rice blast fungus. The targeted disruption of MoSec24B led to decreased growth, reduced conidiation, restricted glycogen and lipids utilization, sensitivity to the cell wall and hypertonic stress, the failure of septin-mediated repolarization of appressorium, impaired appressorium turgor pressure, and decreased ability to infect, which resulted in reduced pathogenicity to the host plant. Furthermore, MoSec24B functions in the three mitogen-activated protein kinase (MAPK) signaling pathways by acting with MoMst50. Deletion of MoSec24B caused reduced lipidation of MoAtg8, accelerated degradation of exogenously introduced GFP-MoAtg8, and increased lipidation of MoAtg8 upon treatment with a late inhibitor of autophagy (BafA1), suggesting that MoSec24B regulates the fusion of late autophagosomes with vacuoles. Together, these results suggest that MoSec24B exerts a significant role in fungal development, the pathogenesis of filamentous fungi and autophagy.

A multi-scale encoder algorithm is proposed for image edge detection, which takes the auto-encoder as basic backbone structure. Three auto-encoders, each is responsible for processing an image of one scale, are organized together to perform image-to-image prediction by combining all multi-scale convolutional features. Taking the advantage of the multi-scale strategy and self-attention mechanism, the algorithm detects image edges from coarse to fine gradually, and succeeds in detecting edges missed easily in other works. Two types of skip connections designed in the model structure. One is connected between encoder and decoder within an auto-encoder, worked as the residual function, the other is between auto-encoders, providing multi-scale knowledge about the edges. The loss function is composed of cross-entropy function and Dice coefficient term which is used to handle imbalanced training data. Experimental results evaluated from BSDS500 and BIPED datasets show the algorithm achieves scores of 0.847, 0.858, 0.884 on ODS, OIS, AP indices and output high-quality edges.

Abstract Purpose To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in pancreatic ductal adenocarcinoma (PDAC). Materials and methods In this retrospective study, 225 patients with surgically resected, pathologically confirmed PDAC underwent multislice computed tomography (MSCT) between January 2014 and January 2017. Radiomics features were extracted from arterial CT scans. The least absolute shrinkage and selection operator method was used to select the features. Multivariable logistic regression analysis was used to develop the predictive model, and a radiomics nomogram was built and internally validated in 45 consecutive patients with PDAC between February 2017 and December 2017. The performance of the nomogram was assessed in the training and validation cohort. Finally, the clinical usefulness of the nomogram was estimated using decision curve analysis (DCA). Results The radiomics signature, which consisted of 13 selected features of the arterial phase, was significantly associated with LN status (p

Abstract Background Diabetic peripheral neuropathy (DPN) is the most common chronic neurological complication. It is the main cause of disability in diabetes mellitus (DM) patients and seriously affects the quality of life of patients. Pharmacological treatments always associate with limited efficacy and adverse effects. Moxibustion has been recommended to treat DPN as an adjuvant therapy to conventional medical treatment to accelerate alleviation of the symptoms of DPN. 10.6-μm laser moxibustion (LM), whose wavelength is close to the peak of infrared radiation spectrum of the traditional moxibustion as well as human acupoints, produces the thermal effect similar with moxibustion but with no smoke or smell. The purpose of this sham controlled clinical trial is to determine the effect and safety of 10.6-μm LM as adjuvant therapy in patients with DPN. Methods This is a protocol for a randomized, double-blind, sham-controlled trial. One hundred fourteen patients meeting the inclusion and exclusion criteria will be recruited and randomly assigned to the LM group or the sham LM group with a 1:1 allocation ratio. Patients in both groups will receive a basic integrated treatment of Chinese and Western medicine and a total of 12 sessions of true or sham LM treatments over 4 weeks with 3 sessions a week. The primary outcome is nerve conduction velocity (NCV), and the secondary outcomes include Michigan Neuropathy Screening Instrument (MNSI) scores, Diabetes-Specific Quality of Life (DSQL) scores, blood rheology parameters, and assessments of safety and blinding. Outcome measures will be collected at baseline, 2 weeks after treatment, the end of LM treatments (4 weeks), and 4, 8 weeks after the end of LM treatment (8, 12weeks). Discussion This study will be conducted to compare the efficacy of LM versus sham LM combined with medical treatment. 10.6-μm LM may alleviate symptoms, improve quality of life, and reduce the dosage of drugs as well as avoid causing serious side effects. Trial registration Chinese Clinical Trial Registry ChiCTR2000029329 . Registered on 25 January 2020.

Chromatin regulators (CRs) regulate the gene transcription process through combinatorial patterns, which currently remain obscure for pan-cancer. This study identified the interaction of CRs and constructed CR-CR interaction networks across five tumor cell lines. The global interaction analysis revealed that CRs tend to function in synergistically. In addition, common and specific CRs in interaction networks were identified, and the epigenetic processes of these CRs in regulating gene transcription were analyzed. Common CRs have conserved binding sites but cooperate with different partners in multiple tumor cell lines. They also participate in gene transcription regulation, through mediation of different histone modifications (HMs). Specific CRs, ATF2 and PRDM10 were found to distinguish liver cancer samples with different prognosis. PRDM10 participates in gene transcription regulation, by exertion of influence on the DNA methylation level of liver cancer. Through analysis of the edges in the CR-CR interaction networks, it was found EP300-TAF1 has genome-wide distinct signaling patterns, which exhibit different effects on downstream targets. This analysis provides novel insights for the understanding of synergistic mechanism of CRs function, as controllers of gene transcription across cancer types.

In fungi, the methylcitrate cycle converts cytotoxic propionyl-coenzyme A (CoA) to pyruvate, which enters gluconeogenesis. The glyoxylate cycle converts acetyl-CoA to succinate, which enters gluconeogenesis. The tricarboxylic acid cycle is a central carbon metabolic pathway that connects the methylcitrate cycle, the glyoxylate cycle, and other metabolisms for lipids, carbohydrates, and amino acids. Fungal citrate synthase and 2-methylcitrate synthase as well as isocitrate lyase and 2-methylisocitrate lyase, each evolved from a common ancestral protein. Impairment of the methylcitrate cycle leads to the accumulation of toxic intermediates such as propionyl-CoA, 2-methylcitrate, and 2-methylisocitrate in fungal cells, which in turn inhibits the activity of many enzymes such as dehydrogenases and remodels cellular carbon metabolic processes. The methylcitrate cycle and the glyoxylate cycle synergistically regulate carbon source utilization as well as fungal growth, development, and pathogenic process in pathogenic fungi.

Abstract We report a novel method to profile intrcellular oxygen concentration (icO2) during in vitro mammalian oocyte and preimplantation embryo development using a commercially available multimodal phosphorescent nanosensor (MM2). Abattoir-derived bovine oocytes and embryos were incubated with MM2 in vitro. A series of inhibitors were applied during live-cell multiphoton imaging to record changes in icO2 associated with mitochondrial processes. The uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) uncouples mitochondrial oxygen consumption to its maximum, while antimycin inhibits complex III to ablate mitochondrial oxygen consumption. Increasing oxygen consumption was expected to reduce icO2 and decreasing oxygen consumption to increase icO2. Use of these inhibitors quantifies how much oxygen is consumed at basal in comparison to the upper and lower limits of mitochondrial function. icO2 measurements were compared to mitochondrial DNA copy number analysed by qPCR. Antimycin treatment increased icO2 for all stages tested, suggesting significant mitochondrial oxygen consumption at basal. icO2 of oocytes and preimplantation embryos were unaffected by FCCP treatment. Inner cell mass icO2 was lower than trophectoderm, perhaps reflecting limitations of diffusion. Mitochondrial DNA copy numbers were similar between stages in the range 0.9–4 × 106 copies and did not correlate with icO2. These results validate the MM2 probe as a sensitive, non-toxic probe of intracellular oxygen concentration in mammalian oocytes and preimplantation embryos.

BackgroundPrevious studies have established a strong association between depression and suicidal behaviors, yet the relationship between anxiety and suicidal behaviors remains unclear. This study examines whether anxiety and depression are independent risk factors for suicidal behaviors in medical college students, and further, whether anxiety may increase the greater risk of suicidal behaviors (SB) in participants with depression.MethodsThis cross-sectional study was conducted among 4,882 medical students. Demographic information, anxiety, and depression data were collected using online questionnaires or through a widely used social media app named WeChat.ResultsAnxiety and depression were independent risk factors for suicidal behaviors, and levels of risk correlated positively with the severity of both anxiety and depressive symptoms. A dose–response relationship was identified between the severity of anxiety and the risk of SB, as well as the severity of depression and SB. Furthermore, anxiety increased the risk of suicidal behaviors in participants with depression, with a dose–response relationship between the severity of anxiety symptoms and the risk of SB.ConclusionThe findings highlight the importance of screening for anxiety and depressive symptoms in medical college students, as well as reducing anxiety in addition to depressive symptoms in treatment. This study provides valuable data as a reference for clinicians for suicide risk assessments.

The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2–MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.

ABSTRACT Rice blast disease caused by Magnaporthe oryzae is a serious threat to global grain yield and food security. Cti6 is a nuclear protein containing a plant homeodomain (PHD) that is involved in transcriptional regulation in Saccharomyces cerevisiae. The biological function of its homologous protein in M. oryzae has been elusive. Here, we report Clp1 with a PHD domain in M. oryzae, a homologous protein of the yeast Cti6. Clp1 was mainly located in the nucleus and partly in the vesicles. Clp1 colocalized and interacted with the autophagy-related proteins Atg5, Atg7, Atg16, Atg24, and Atg28 at preautophagosomal structures (PAS) and autophagosomes, and the loss of Clp1 increased the fungal background autophagy level. Δclp1 displayed reduced hyphal growth and hyperbranching, abnormal fungal morphology (including colony, spore, and appressorium), hindered appressorial glycogen metabolism and turgor production, weakened plant infection, and decreased virulence. The PHD is indispensable for the function of Clp1. Therefore, this study revealed that Clp1 regulates development and pathogenicity by maintaining autophagy homeostasis and affecting gene transcription in M. oryzae. IMPORTANCE The fungal pathogen Magnaporthe oryzae causes serious diseases of grasses such as rice and wheat. Autophagy plays an indispensable role in the pathogenic process of M. oryzae. Here, we report a Cti6-like protein, Clp1, that is involved in fungal development and infection of plants through controlling autophagy homeostasis in the cytoplasm and gene transcription in the nucleus in M. oryzae. This study will help us to understand an elaborated molecular mechanism of autophagy, gene transcription, and virulence in the rice blast fungus.

Abstract Background To explore the diagnostic value of three different measurement approaches in differentiating T1a–T1b from T2 gastric cancer (GC) lesions. Methods A total of 95 consecutive patients with T1a–T2 stage of GC who performed preoperative MRI were retrospectively enrolled between January 2017 and November 2020. The parameters MRI T stage (subjective evaluation), thickness, maximum area and volume of the lesions were evaluated by two radiologists. Specific indicators including AUC, optimal cutoff, sensitivity, specificity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV) and negative predictive value (NPV) of MRI T stage, thickness, maximum area and volume for differentiating T1a–T1b from T2 stage lesions were calculated. The ROC curves were compared by the Delong test. Decision curve analysis (DCA) was used to evaluate the clinical benefit. Results The ROC curves for thickness (AUC = 0.926), maximum area (AUC = 0.902) and volume (AUC = 0.897) were all significantly better than those of the MRI T stage (AUC = 0.807) in differentiating T1a–T1b from T2 lesions, with p values of 0.004, 0.034 and 0.041, respectively. The values corresponding to the thickness (including AUC, sensitivity, specificity, accuracy, PPV, NPV, PLR and NLR) were all higher than those corresponding to the MRI T stage, maximum area and volume. The DCA curves indicated that the parameter thickness could provide the highest clinical benefit if the threshold probability was above 35%. Conclusions Thickness may provide an efficient approach to rapidly distinguish T1a–T1b from T2 stage GC lesions.

Abstract Background To explore the usefulness of analyzing histograms and textures of apparent diffusion coefficient (ADC) maps and T2-weighted (T2W) images to differentiate prostatic cancer (PCa) from benign prostatic hyperplasia (BPH) using histopathology as the reference. Methods Ninety patients with PCa and 112 patients with BPH were included in this retrospective study. Differences in whole-lesion histograms and texture parameters of ADC maps and T2W images between PCa and BPH patients were evaluated using the independent samples t-test. The diagnostic performance of ADC maps and T2W images in being able to differentiate PCa from BPH was assessed using receiver operating characteristic (ROC) curves. Results The mean, median, 5th, and 95th percentiles of ADC values in images from PCa patients were significantly lower than those from BPH patients (p

The rice blast fungus Magnaporthe oryzae spores differentiate and mature into functional appressoria by sensing the host surface signals. Environmental stimuli are transduced into cells through internalization during appressorium formation, such as in the cAMP-PKA pathway. Here, we describe a novel contribution to how appressoria mature on the surface of a leaf, and its connection to endosomes and the cAMP-PKA pathway. An appressorium membrane-specific protein, Pams1, is required for maintaining endosomal structure, appressorium maturation, and virulence in M. oryzae. During appressorium development, Pams1 was translocated from the cell membrane to the endosomal membrane. Deletion of PAMS1 led to the formation of two types of abnormal appressoria after 8 h post inoculation (hpi): melanized type I had a reduced virulence, while pale type II was dead. Before 8 hpi, Δpams1 formed appressoria that were similar to those of the wild type. After 8 hpi, the appressoria of Δpams1 was differentiated into two types: (1) the cell walls of type I appressoria were melanized, endosomes were larger, and had a different distribution from the wild type and (2) Type II appressoria gradually stopped melanization and began to die. The organelles, including the nucleus, endosomes, mitochondria, and endoplasmic reticula, were degraded, leaving only autophagic body-like vesicles in type II appressoria. The addition of exogenous cAMP to Δpams1 led to the formation of a greater proportion of type I appressoria and a smaller proportion of type II appressoria. Thus, defects in endosomal structure and the cAMP-PKA pathway are among the causes of the defective appressorium maturation and virulence of Δpams1.

Human tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the synthesis of serotonin. Its dysfunction has been implicated in various psychiatric disorders such as depression, autism, and bipolar disorder. TPH2 is typically decreased in stability and catalytic activity in patients; thus, screening of molecules capable of binding and stabilizing the structure of TPH2 in activated conformation is desired for drug development in mental disorder treatment. Here, we solved the 3.0 Å cryo-EM structure of the TPH2 tetramer. Then, based on the structure, we conducted allosteric site prediction and small-molecule activator screening to the obtained cavity. ZINC000068568685 was successfully selected as the best candidate with highest binding affinity. To better understand the driving forces and binding stability of the complex, we performed molecular dynamics simulation, which indicates that ZINC000068568685 has great potential to stabilize the folding of the TPH2 tetramer to facilitate its activity. The research might shed light on the development of novel drugs targeting TPH2 for the treatment of psychological disorders.

Genetic variation has been shown to affect tumor growth and progression, and the temperature at different latitudes may promote the evolution of genetic variation. Geographical data with latitudinal information is of importance to understand the interplay between genetic variants and environmental influence, such as the temperature, in gastric cancer (GC). In this study, we classified the GC samples from The Cancer Genome Atlas database into two groups based on the latitudinal information of patients and found that GC samples with low-latitude had better clinical outcomes. Further analyses revealed significant differences in other clinical factors such as disease stage and grade between high and low latitudes GC samples. Then, we analyzed the genomic and transcriptomic differences between the two groups. Furthermore, we evaluated the activity score of metabolic pathways and infiltrating immune cells in GC samples with different latitudes using the single-sample gene set enrichment analysis algorithm. These results showed that GC samples at low-latitude had lower tumor mutation burden and subclones as well as higher DNA repair activities. Meanwhile, we found that most immune cells were associated with the prognosis of low-latitude GC patients. At last, we constructed and validated an immune-related prognostic model to evaluate the prognosis of GC samples at different latitudes. This study has provided a further understanding of the geographical contribution to GC at the multiomic level and may benefit the individualized treatment of GC patients at different latitudes.

ObjectiveTo develop and validate a multimodal MRI-based radiomics nomogram for predicting clinically significant prostate cancer (CS-PCa).MethodsPatients who underwent radical prostatectomy with pre-biopsy prostate MRI in three different centers were assessed retrospectively. Totally 141 and 60 cases were included in the training and test sets in cohort 1, respectively. Then, 66 and 122 cases were enrolled in cohorts 2 and 3, as external validation sets 1 and 2, respectively. Two different manual segmentation methods were established, including lesion segmentation and whole prostate segmentation on T2WI and DWI scans, respectively. Radiomics features were obtained from the different segmentation methods and selected to construct a radiomics signature. The final nomogram was employed for assessing CS-PCa, combining radiomics signature and PI-RADS. Diagnostic performance was determined by receiver operating characteristic (ROC) curve analysis, net reclassification improvement (NRI) and decision curve analysis (DCA).ResultsTen features associated with CS-PCa were selected from the model integrating whole prostate (T2WI) + lesion (DWI) for radiomics signature development. The nomogram that combined the radiomics signature with PI-RADS outperformed the subjective evaluation alone according to ROC analysis in all datasets (all p

Abstract Background Intracranial artery dissection (IAD) often causes headache and cerebral vascular ischemic events. The imaging characteristics of IAD remain unclear. This study aims to characterize the appearance of culprit and non-culprit IAD using high-resolution cardiovascular magnetic resonance imaging (hrCMR) and quantify the incremental value of hrCMR in identifying higher risk lesions. Methods Imaging data from patients who underwent intervention examination or treatment using digital subtraction angiography (DSA) and hrCMR using a 3 T CMR system within 30 days after the onset of neurological symptoms were collected. The CMR protocol included diffusion-weighted imaging (DWI), black blood T1-, T2- and contrast-enhanced T1-weighted sequences. Lesions were classified as culprit and non-culprit according to imaging findings and patient clinical presentations. Univariate and multivariate analyses were performed to assess the difference between culprit and non-culprit lesions and complementary value of hrCMR in identifying higher risk lesions. Results In total, 75 patients were included in this study. According to the morphology, lesions could be classified into five types: Type I, classical dissection (n = 50); Type II, fusiform aneurysm (n = 1); Type III, long dissected aneurysm (n = 3); Type IV, dolichoectatic dissecting aneurysm (n = 9) and Type V, saccular aneurysm (n = 12). Regression analyses showed that age and hypertension were both associated with culprit lesions (age: OR, 0.83; 95% CI 0.75–0.92; p

Abstract Backgrounds Associations between attention deficit hyperactivity disorder (ADHD) subtypes and suicidal behaviors remains unclear. The current study explored the prevalence of suicidal behaviors, and its association with ADHD among Chinese medical students. Methods Five thousand six hundred ninety-three medical college students participated. Symptoms of suicidal behaviors, ADHD, anxiety, depression, tobacco and alcohol use were assessed using online questionnaires. Results The prevalence of lifetime suicidal ideation, suicide plans, and suicide attempts among medical college students were 27.5, 7.9 and 14.8% respectively. Participants with ADHD predominantly inattentive type (ADHD-I) had more than fivefold increased odds of suicidal behaviors, the adjusted odds ratios (ORs) of ADHD-I and ADHD combined type (ADHD-C) remained significant after controlling for confounding factors. Conclusions ADHD is associated with high risk of suicidal behaviors. ADHD-I and ADHD-C were strongly associated with suicidal behaviors independent of comorbidities. The finding suggests the importance of addressing ADHD symptoms in suicide prevention.

Abstract Background ASPECTS scoring method varies, but which one is most suitable for predicting the prognosis still unclear. We aimed to evaluate the diagnostic performance of Automated (Auto)-, noncontrast CT (NCCT)- and CT perfusion (CTP) -ASPECTS for early ischemic changes (EICs) in acute ischemic stroke patients with large vessel occlusion (LVO) and to explore which scoring method is most suitable for predicting the clinical outcome. Methods Eighty-one patients with anterior circulation LVO were retrospectively enrolled and grouped as having a good (0–2) or poor (3–6) clinical outcome using a 90-day modified Rankin Scale score. Clinical characteristics and perfusion parameters were compared between the patients with good and poor outcomes. Differences in scores obtained with the three scoring methods were assessed. Diagnosis performance and receiver operating characteristic (ROC) curves were used to evaluate the value of the three ordinal or dichotomized ASPECTS methods for predicting the clinical outcome. Results Sixty-three patients were finally included, with 36 (57.1%) patients having good clinical outcome. Significant differences were observed in the ordinal or dichotomized Auto-, NCCT- and CTP-ASPECTS between the patients with good and poor clinical outcomes (all p 0.05). Conclusions The CTP-ASPECTS is superior to the Auto- and NCCT-ASPECTS in detecting EICs in LVO. CTP-ASPECTS with a cutoff value of 6 is a good predictor of the clinical outcome at 90-day follow-up.

The green supplier selection (GSS) is a significant part in green supply chain management (GSCM). Choosing optimal green supplier can not only realize the sustainable development of enterprises, but also maximize the utilization rate of resources and diminish the negative effect of environmental issues, which conforms to the theme of green development. As a multiple attribute group decision-making (MAGDM) issue, selecting optimal green supplier is of vital important to enterprises. However, how to select the optimal supplier for enterprises is a great challenge. To handle this issue, a novel picture fuzzy COPRAS (COmplex PRoportional Assessment) method is devised. First, some necessary theories related to picture fuzzy sets (PFSs) are briefly reviewed. In addition, a method called CRITIC (Criteria Importance Though Intercrieria Correlation) is utilized to calculate criteria’s weights. Afterwards, the conventional COPRAS method is extended to the PFSs to calculate each alternative’s utility degree. At last, the designed method is exacted to an application which is related to GSS and there also conduct some comparative analysis to demonstrate the designed method’s superiority. The final results show that the proposed model can be utilized to decide the optimum green supplier.

DNA repair mechanisms have been proven to be essential for cells, and abnormalities in DNA repair could cause various diseases, such as cancer. However, the diversity and complexity of DNA repair mechanisms obscure the functions of DNA repair in cancers. In addition, the relationships between DNA repair, the tumor mutational burden (TMB), and immune infiltration are still ambiguous. In the present study, we evaluated the prognostic values of various types of DNA repair mechanisms and found that double-strand break repair through single-strand annealing (SSA) and nonhomologous end-joining (NHEJ) was the most prognostic DNA repair processes in gastric cancer (GC) patients. Based on the activity of these two approaches and expression profiles, we constructed a HR-LR model, which could accurately divide patients into high-risk and low-risk groups with different probabilities of survival and recurrence. Similarly, we also constructed a cancer-normal model to estimate whether an individual had GC or normal health status. The prognostic value of the HR-LR model and the accuracy of the cancer-normal model were validated in several independent datasets. Notably, low-risk samples, which had higher SSA and NHEJ activities, had more somatic mutations and less immune infiltration. Furthermore, the analysis found that low-risk samples had higher and lower methylation levels in CpG islands (CGIs) and open sea regions respectively, and had higher expression levels of programmed death-ligand 1 (PD-L1) and lower methylation levels in the promoter of the gene encoding PD-L1. Moreover, low-risk samples were characterized primarily by higher levels of CD4+ memory T cells, CD8+ naive T cells, and CD8+ TEM cells than those in high-risk samples. Finally, we proposed a decision tree and nomogram to help predict the clinical outcome of an individual. These results provide an improved understanding of the complexity of DNA repair, the TMB, and immune infiltration in GC, and present an accurate prognostic model for use in GC patients.

The culprit of rice blast, Magnaporthe oryzae, is a filamentous fungus that seriously affects the yield and quality of rice worldwide. MoIst1, a subunit of ESCRT-III, is involved in identified ubiquitinated proteins and transports them into the intraluminal vesicles of multivesicular bodies (MVBs) for degradation in lysosomes. Here, we identify and characterize MoIst1 in M. oryzae. Disruption of MoIst1 leads to a significant decrease in sporulation and formation of appressoria, defects in response to oxidative stress, cell wall stress, hyperosmotic stress, and reduced pathogenicity. Deletion of MoIst1 also caused the decreased Pmk1 phosphorylation levels, appressorium formation, the delayed translocation and degradation of lipid droplets and glycogen, resulting in a decreased appressorium turgor. In addition, deletion of MoIst1 leads to an abnormal autophagy. In summary, our results indicate that MoIst1 is involved in sporulation, appressorium development, plant penetration, pathogenicity, and autophagy in M. oryzae.

Abstract Background This study is aimed to explore the factors influencing the visualization of the anterior peritoneal reflection (APR) and evaluated the feasibility of measuring the distance from the anal verge to APR (AV-APR), the tumor height on MRI and the accuracy of determining the tumor location with regard to APR. Methods We retrospectively analyzed 110 patients with rectal cancer. A univariate and multivariate logistic regression was performed to identify the independent factors (age, sex, T stage, the degree of bladder filling, pelvic effusion, intraoperative tumor location, BMI, uterine orientation, the distance from seminal vesicle/uterus to rectum) associated with the visualization of the APR on MRI. The nomogram diagram and receiver operating characteristic curve (ROC curve) were established. Intraclass correlation coefficient (ICC) was used to evaluate the consistency of the distance of AV-APR. The Pearson correlation coefficient was used to characterize the agreement between measurements of the tumor height by colonoscopy and MRI. The Kappa statistics was used to evaluate the value of MRI in the diagnosis of the tumor location with regard to the APR. Results Multivariate logistic regression showed that BMI (P = 0.031, odds ratio, OR = 1.197), pelvic effusion (P = 0.020, OR = 7.107) and the distance from seminal vesicle/uterus to the rectum (P = 0.001, OR = 3.622) were correlated with the visualization of APR. The cut-off point of BMI and the distance from seminal vesicle/uterus to the rectum is 25.845 kg/m2 and 1.15 cm. The area under curve (AUC) (95% Confidence Interval, 95% CI) of the combined model is 0.840 (0.750–0.930). The favorable calibration of the nomogram showed a non-significant Hosmer–Lemeshow test statistic (P = 0.195). The ICC value (95% CI) of the distance of AV-APR measured by two radiologists was 0.981 (0.969–0.989). The height measured by MRI and colonoscopy were correlated with each other (r = 0.699, P

Abstract Background To validate and compare various MRI-based radiomics models to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal cancer. Methods A total of 80 patients with locally advanced rectal cancer (LARC) who underwent surgical resection after nCRT were enrolled retrospectively. Rectal MR images were scanned pre- and post-nCRT. The radiomics features were extracted from T2-weighted images, then reduced separately by least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA). Four classifiers of Logistic Regression, Random Forest (RF), Decision Tree and K-nearest neighbor (KNN) models were constructed to assess the tumor regression grade (TRG) and pathologic complete response (pCR), respectively. The diagnostic performances of models were determined with leave-one-out cross-validation by generating receiver operating characteristic curves and decision curve analysis. Results Three features related to the TRG and 11 features related to the pCR were obtained by LASSO. Top five principal components representing a cumulative contribution of 80% to overall features were selected by PCA. For TRG, the area under the curve (AUC) of RF model was 0.943 for LASSO and 0.930 for PCA, higher than other models (P

Gastric cancer can metastasise to the peritoneal cavity; predicting in which patients this will occur is important for clinical management of the disease. Here, the authors use multi-photon imaging to derive a collagen signature of the primary cancer that allows the prediction of metastasis.

The rice blast pathogen, Magnaporthe oryzae, spreads through spores and invades rice through appressoria. Melanin is necessary for an appressorium to penetrate plant cells, but there are many unknown aspects of its role in fungal conidiation. In this study, we confirmed that melanin promotes spore production in M. oryzae, and that this effect is related to the background melanin content of wild-type strains. In the wild-type 70-15 strain with low melanin content of aerial hyphae, increased melanin synthesis promoted sporulation. In contrast, increased melanin synthesis in the wild-type Guy11 strain, which has higher melanin content, did not promote sporulation. The transcription factor Cnf1 (conidial production negative regulatory factor 1), which negatively regulates melanin synthesis, has opposite effects in conidiophore differentiation of Guy11 and 70-15. Deletion of CNF1 did not abolish the defects of Δcos1 and Δhox2 (where COS1/conidiophore stalk-less 1 or HOX2/homeodomain protein 2 was deleted) in conidiation, while increased the conidiation of Δgcc1 and Δgcf3 (where GCC1/growth, conidiation and cell wall regulatory factor 1, or GCF3/growth and conidiation regulatory factor 3 was deleted). Pig1 (pigment of Magnaporthe 1) regulates the melanin synthesis of hyphae but not of conidiophores, spores, or appressoria. Deletion of the same gene in different wild-type strains can lead to different phenotypes, partly because of differences in melanin content between fungal strains. Overall, this study reveals the functional diversity and complexity of melanin in different M. oryzae strains.

Cone beam computed tomography (CBCT) is now widely used in dentistry and growing areas of medical imaging. The presence of strong metal artifacts is however a major concern of using CBCT especially in dentistry due to the presence of highly attenuating dental restorations, fixed appliances, and implants. Virtual monoenergetic images (VMIs) synthesized from dual energy CT (DECT) datasets are known to reduce metal artifacts. Although several techniques exist for DECT imaging, they in general come with significantly increased equipment cost and not available in dental clinics. The objectives of this study were to investigate the feasibility of developing a low-cost dual energy CBCT (DE-CBCT) by retrofitting a regular CBCT scanner with a carbon nanotube (CNT) x-ray source with dual focal spots and corresponding low-energy (LE) and high-energy (HE) spectral filters. A testbed with a CNT field emission x-ray source (NuRay Technology, Chang Zhou, China), a flat panel detector (Teledyne, Waterloo, Canada), and a rotating object stage was used for this feasibility study. Two distinct polychromatic x-ray spectra with the mean photon energies of 66.7keV and 86.3keV were produced at a fixed 120kVp x-ray tube voltage by using Al+Au and Al+Sn foils as the respective LE and HE filters attached to the exist window of the x-ray source. The HE filter attenuated the x-ray photons more than the LE filter. The calculated post-object air kerma rate of the HE beam was 31.7% of the LE beam. An anthropomorphic head phantom (RANDO, Nuclear Associates, Hicksville, NY) with metal beads was imaged using the testbed and the images were reconstructed using an iterative volumetric CT reconstruction algorithm. The VMIs were synthesized using an image-domain basis materials decomposition method with energy ranging from 30 to 150keV. The results were compared to the reconstructed images from a single energy clinical dental CBCT scanner (CS9300, Carestream Dental, Atlanta, GA). A significant reduction of the metal artifacts was observed in the VMI images synthesized at high energies compared to those from the same object imaged by the clinical dental CBCT scanner. The ability of the CNT x-ray source to generate the output needed to compensate the reduction of photon flux due to attenuation from the spectral filters and to maintain the CT imaging time was evaluated. The results demonstrated the feasibility of DE-CBCT imaging using the proposed approach. Metal artifact reduction was achieved in VMIs synthesized. The x-ray output needed for the proposed DE-CBCT can be generated by a fixed-anode CNT x-ray source.