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Abstract To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as “group A”) and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as “group B”). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.

miR-SNP is a type of functional single nucleotide polymorphism (SNP) that affects the regulatory functions of miRNA genes, miRNA binding sites, or components of miRNA biogenesis. This study aimed to explore the relationship between miRNA gene polymorphisms that regulate the kininogen L protein and schizophrenia (SCZ). Bioinformatics methods predicted miRNA gene polymorphism sites regulating the kininogen L protein. The polymorphisms of rs56103835, rs6513496, rs651349, and rs2986407 were detected using imLDR multiple SNP typing technologies in 513 SCZ patients and 509 controls. The association of miR-SNP variations with SCZ susceptibility and symptoms was evaluated using SNPstat to determine the optimal inheritance model. Generalized multifactor dimensionality reduction (GMDR) analysis and logistic regression were used to calculate miR-SNP interactions. The association between hsa-miR-323b-rs56103835 and SCZ was statistically significant under the dominant model. The result of gene-gene interaction showed that the three-factor model (rs56103835 / rs2986407 / rs2155248) was the best, but it could not be considered significantly related to SCZ. Additionally, SCZ patients with the CC or CT genotype on rs2986407 were more likely to experience auditory hallucinations than those with the TT genotype. Our data revealed that the mutation of hsa-miR-323b-rs56103835 from C to T was associated with susceptibility to SCZ. The mutation of hsa-miR-1343-rs2986407 from T to C increases the risk of auditory hallucinations in SCZ patients.

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non‐small‐cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. Method In this study, we developed and validated a next‐generation sequencing panel targeting 101 cancer‐related genes (101‐test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101‐test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. Results The 101‐test demonstrated a LOD of 0.38% for single‐nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by‐variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor‐only and tumor‐normal analyses. In a real‐world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. Conclusion The ctDNA‐based 101‐test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue‐based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

Abstract The polar oceans play a vital role in regulating atmospheric CO2 concentrations (pCO2) during the Pleistocene glacial cycles. However, despite being the largest modern reservoir of respired carbon, the impact of the subarctic Pacific remains poorly understood due to limited records. Here, we present high-resolution, 230Th-normalized export productivity records from the subarctic northwestern Pacific covering the last five glacial cycles. Our records display pronounced, glacial-interglacial cyclicity superimposed with precessional-driven variability, with warm interglacial climate and high boreal summer insolation providing favorable conditions to sustain upwelling of nutrient-rich subsurface waters and hence increased export productivity. Our transient model simulations consistently show that ice sheets and to a lesser degree, precession are the main drivers that control the strength and latitudinal position of the westerlies. Enhanced upwelling of nutrient/carbon-rich water caused by the intensification and poleward migration of the northern westerlies during warmer climate intervals would have led to the release of previously sequestered CO2 from the subarctic Pacific to the atmosphere. Our results also highlight the significant role of the subarctic Pacific in modulating pCO2 changes during the Pleistocene climate cycles, especially on precession timescale ( ~ 20 kyr).

BackgroundLung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer.MethodsTumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms.Resultsthe microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively.ConclusionNanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.

Alzheimer’s disease (AD) is a condition in the brain that is marked by a gradual and ongoing reduction in memory, thought, and the ability to perform simple tasks. AD has a poor prognosis but no cure yet. Therefore, the need for novel models to study its pathogenesis and therapeutic strategies is evident, as the brain poorly recovers after injury and neurodegenerative diseases and can neither replace dead neurons nor reinnervate target structures. Recently, mesenchymal stem cells (MSCs), particularly those from the human olfactory mucous membrane referred to as the olfactory ecto-MSCs (OE-MSCs), have emerged as a potential avenue to explore in modeling AD and developing therapeutics for the disease due to their lifelong regeneration potency and facile accessibility. This review provides a comprehensive summary of the current literature on isolating OE-MSCs and delves into whether they could be reliable models for studying AD pathogenesis. It also explores whether healthy individual-derived OE-MSCs could be therapeutic agents for the disease. Despite being a promising tool in modeling and developing therapies for AD, some significant issues remain, which are also discussed in the review.

High-localition loess landslide has the characteristics of high potential energy, suddenness, concealment, rapid sliding speed, wide threat range, and strong destructive impact capacity. The main forms of damage are destruction and burial, making them a difficult problem for disaster prevention, reduction, and engineering governance in loess areas. Different landform types, stratum lithology, hydrogeological conditions and tectonics have essential differences in landslide formation. Based on typical examples of high-altitude loess landslides in Renda Town, Jingning County, Pingliang City and Dagou, Maiji District, Tianshui City, a systematic study was conducted through technical means such as engineering geological mapping, engineering geological exploration, and high-precision drone aerial surveys from the aspects of spatial distribution, landslide characteristics, causes, motion mechanisms, and disaster characteristics. The results showed that according to the classification of terrain and topography, high-localition loess landslide can be divided into slope type and valley type. Among them, the landslide in Renda Town, Jingning County, Pingliang City belongs to the slope type, moving in the form of “soil waves” , with the same periodicity and continuity as the landslide initiation in terms of movement time. The movement speed is rapid, and the movement sequence is as follows: the sliding body separates from the parent body, the soil slides, and the soil accumulates. The Dagou in Maiji District, Tianshui City belongs to a valley type and moves in the form of mud flow. The sliding of landslides and the initiation of accumulation bodies have a certain lag in time, and the speed is relatively slow compared to the former. The movement sequence is as follows: the sliding body separates from the parent body → soil accumulation → soil sliding → sedimentation, and its movement and accumulation characteristics are basically similar to those of viscous debris flows.

Abstract Objective Our study was conducted aimed at investigating the potential correlation between cerebral microangiopathy and autonomic nervous dysfunction. Methods We initially included 164 hospitalized patients with cerebral microangiopathy at our hospital from November 2019 to January 2021. Based on the inclusion and exclusion criteria, a final total of 162 patients with cerebral microangiopathy were selected. According to the patient's Autonomic Symptom Profile (ASP) score, patients with a score greater than 22 were categorized into a group with concomitant autonomic dysfunction (71 cases, combined group), while those with a score below 22 were categorized into a group of isolated cerebral microangiopathy (83 cases, cerebral microangiopathy group). The general data and laboratory examination results of the two groups were analyzed, and Pearson correlation analysis was performed to evaluate the correlation between cerebral microangiopathy and autonomic dysfunction, as well as the influencing factors of cerebral microangiopathy patients combined with autonomic dysfunction. Results There were no significant differences between the two groups in terms of sex, BMI, smoking, drinking, family dementia history, diabetes, hypothyroidism, carotid atherosclerosis, obstructive sleep apnea hypopnea syndrome, hyperuricemia, hyperlipidemia, chronic obstructive pulmonary disease, Hamilton Anxiety Scale score, Hamilton Depression Scale score, 24‐h mean systolic blood pressure (SBP), 24‐h mean diastolic blood pressure DBP, daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure, nighttime mean systolic blood pressure (nSBP), nighttime mean diastolic blood pressure, 24‐h systolic blood pressure standard deviation (SBPSD), 24‐h diastolic blood pressure standard deviation, daytime diastolic blood pressure standard deviation, nighttime diastolic blood pressure standard deviation (nDBPSD), nDBPSD (p > .05). However, significant differences were observed between the two groups regarding age, history of coronary heart disease, hypertension, leukoaraiosis, cognitive function, ASP score, SSR, 24‐h SBPSD, daytime systolic blood pressure standard deviation (dSBPSD), nighttime systolic blood pressure standard deviation (nSBPSD), standard deviation of RR interval (SDNN), root mean square value of successive RR interval difference (RMSSD), high‐frequency component (HF), and low‐frequency component (LF) (p .05), but there were significant differences in blood uric acid and homocysteine (Hcy) levels (p

As a major global health concern, coronary artery disease (CAD) demands precise, noninvasive diagnostic methods like cardiopulmonary exercise testing (CPET) for effective assessment and management, balancing the need for accurate disease severity evaluation with improved treatment decision-making. Our objective was to develop and validate a nomogram based on CPET parameters for noninvasively predicting the severity of CAD, thereby assisting clinicians in more effectively assessing patient conditions. This study analyzed 525 patients divided into training (367) and validation (183) cohorts, identifying key CAD severity indicators using least absolute shrinkage and selection operator (LASSO) regression. A predictive nomogram was developed, evaluated by average consistency index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), confirming its reliability and clinical applicability. In our study, out of 25 variables, 6 were identified as significant predictors for CAD severity. These included age (OR = 1.053, P

ABSTRACTShewanella is a prevalent bacterial genus in deep-sea environments including marine sediments, exhibiting diverse metabolic capabilities that indicate its significant contributions to the marine biogeochemical cycles. However, only a few Shewanella phages were isolated and deposited in the NCBI database. In this study, we report the isolation and characterization of a novel Shewanella phage, vB_SbaS_Y11, that infects Shewanella KR11 and was isolated from the sewage in Qingdao, China. Transmission electron microscopy revealed that vB_SbaS_Y11 has an icosahedral head and a long tail. The genome of vB_SbaS_Y11 is a linear, double-stranded DNA with a length of 62,799 bp and a G+C content of 46.9%, encoding 71 putative open reading frames. No tRNA genes or integrase-related feature genes were identified. An uncharacterized anti-CRISPR AcrVA2 gene was detected in its genome. Phylogenetic analysis based on the amino acid sequences of whole genomes and comparative genomic analyses indicate that vB_SbaS_Y11 has a novel genomic architecture and shares low similarity to Pseudomonas virus H66 and Pseudomonas phage F116. vB_SbaS_Y11 represents a potential new family-level virus cluster with eight metagenomic assembled viral genomes named Ranviridae.IMPORTANCEThe Gram-negative Shewanella bacterial genus currently includes about 80 species of mostly aquatic Gammaproteobacteria, which were isolated around the globe in a multitude of environments, such as freshwater, seawater, coastal sediments, and the deepest trenches. Here, we present a Shewanella phage vB_SbaS_Y11 that contains an uncharacterized anti-CRISPR AcrVA2 gene and belongs to a potential virus family, Ranviridae. This study will enhance the knowledge about the genome, diversity, taxonomic classification, and global distribution of Shewanella phage populations.

Xinhui tangerine peel has valuable medicinal value. The longer it is stored in an appropriate environment, the higher its flavonoid content, resulting in increased medicinal value. In order to correctly identify the age of the tangerine peel, previous studies have mostly used manual identification or physical and chemical analysis, which is a tedious and costly process. This work investigates the automatic age recognition of the tangerine peel based on deep learning and attention mechanisms. We proposed an effective ConvNeXt fusion attention module (CNFA), which consists of three parts, a ConvNeXt block for extracting low-level features’ information and aggregating hierarchical features, a channel squeeze-and-excitation (cSE) block and a spatial squeeze-and-excitation (sSE) block for generating sufficient high-level feature information from both channel and spatial dimensions. To analyze the features of tangerine peel in different ages and evaluate the performance of CNFA module, we conducted comparative experiments using the CNFA-integrated network on the Xinhui tangerine peel dataset. The proposed algorithm is compared with related models of the proposed structure and other attention mechanisms. The experimental results showed that the proposed algorithm had an accuracy of 97.17%, precision of 96.18%, recall of 96.09%, and F1 score of 96.13% for age recognition of the tangerine peel, providing a visual solution for the intelligent development of the tangerine peel industry.

ABSTRACT Viruses play crucial roles in the ecosystem by modulating the host community structure, mediating biogeochemical cycles, and compensating for the metabolism of host cells. Mariana Trench, the world’s deepest hadal habitat, harbors a variety of unique microorganisms that have adapted to its extreme conditions of low temperatures, high pressure, and nutrient scarcity. However, our knowledge about isolated hadal phage strains in the hadal trench is still limited. This study reported the discovery of a temperate phage, vB_HmeY_H4907, infecting Halomonas meridiana H4907, isolated from surface sediment from the Mariana Trench at a depth of 8,900 m. To our best knowledge, it is the deepest isolated siphovirus from the ocean. Its 40,452 bp linear dsDNA genome has 57.64% GC content and 55 open reading frames, and it is highly homologous to its host. Phylogenetic analysis and average nucleotide sequence identification reveal that vB_HmeY_H4907 is separated from the isolated phages and represents a new family, Suviridae, with eight predicted proviruses and six uncultured viral genomes. They are widely distributed in the ocean, suggesting a prevalence of this viral family in the deep sea. These findings expand our understanding of the phylogenetic diversity and genomic features of hadal lysogenic phages, provide essential information for further studies of phage-host interactions and evolution, and may reveal new insights into the lysogenic lifestyles of viruses inhabiting the hadal ocean. Importance Halomonas phage vB_HmeY_H4907 is the deepest isolated siphovirus from the ocean, and it represents a novel abundant viral family in the ocean. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral family, namely, Suviridae.

PurposeThis study aimed to evaluate the feasibility of a combination of abdominal lymph node (LN) metastasis and the number of LNs in esophageal squamous cell carcinoma (ESCC) patients to optimize its clinical nodal staging.MethodsA retrospective study, including a total of 707 ESCC patients treated with definitive radiotherapy, was conducted at two participating institutes. Different combinations of LN variables, including abdominal LN metastasis (R1: no-abdominal LN metastasis; R2: abdominal LN metastasis), were further analyzed to propose a potential revised nodal (rN) staging.ResultsThe multivariate analyses showed that the number of metastatic LN and abdominal LN metastasis were independent prognostic factors for the overall survival (OS). The results showed no significant differences in the OS between the N2 patients with abdominal LN metastasis and N3 patients. The OS of the stage III patients with abdominal LN metastasis was not significantly different from those with stage IVa. The N3R1 and N1-2R2 had similar hazard ratios (HRs). The N1R1 subset was defined as rN1, the N2R1 subset was defined as rN2, and the N3R1-2 and N1-2R2 subsets were defined as rN3. The HRs of OS of the rN2 and rN3 groups increased subsequently. The rN stage could identify the differences in the OS times of each subgroup based on the 8th AJCC cN staging or the 11th JES N staging.ConclusionsThe rN staging, including the number of metastatic LNs and abdominal LN metastasis, might serve as a potential prognostic predictor for non-surgical patients with ESCC.

To achieve stabilisation control of an underactuated bridge crane system, a new robust control strategy for the sliding mode is proposed in this paper. It can realise finite-time-convergent stabilisation control under the conditions of model uncertainty, parameter perturbation and external interference. In contrast to the existing methods, our method does not need prior information of the dynamic characteristics of the bridge crane system, and can make the system converge to the equilibrium state at the preset time. Specifically, the nonlinear model of the bridge crane system is linearised with partial feedback, and adaptive signals are introduced. Then, according to the form of the transformed system, a fast terminal sliding mode surface is constructed, and an adaptive terminal sliding mode controller is designed. According to strict analysis, the proposed control law ensures that the system converges to the equilibrium point in finite time and provides the convergence time. Finally, the effectiveness and robustness of the proposed control method are verified by comparing the simulation and experimental results with existing methods.

Stutzerimonas stutzeri is an opportunistic pathogen widely distributed in the environment and displays diverse metabolic capabilities. In this study, a novel lytic S. stutzeri phage, named vB_PstM_ZRG1, was isolated from the seawater in the East China Sea (29°09’N, 123°39’E). vB_PstM_ZRG1 was stable at temperatures ranging from -20°C to 65°C and across a wide range of pH values from 3 to 10. The genome of vB_PstM_ZRG1 was determined to be a double-stranded DNA with a genome size of 52,767 bp, containing 78 putative open reading frames (ORFs). Three auxiliary metabolic genes encoded by phage vB_PstM_ZRG1 were predicted, including Toll/interleukin-1 receptor (TIR) domain, proline-alanine-alanine-arginine (PAAR) protein and SGNH (Ser-Gly-Asn-His) family hydrolase, especially TIR domain is not common in isolated phages. Phylogenic and network analysis showed that vB_PstM_ZRG1 has low similarity to other phage genomes in the GenBank and IMG/VR database, and might represent a novel viral genus, named Elithevirus. Additionally, the distribution map results indicated that vB_PstM_ZRG1 could infect both extreme colds- and warm-type hosts in the marine environment. In summary, our finding provided basic information for further research on the relationship between S. stutzeri and their phages, and expanded our understanding of genomic characteristics, phylogenetic diversity and distribution of Elithevirus.

Abstract Non-traumatic osteonecrosis of the femoral head (ONFH) relies on multiple pathogenic factors, including intravascular coagulation, osteoporosis and lipid metabolism disorders. Despite extensively explored from various aspects, genetic mechanism underlying non-traumatic ONFH has not been fully elucidated. We randomly collected blood and necrotic tissue samples from 32 patients with non-traumatic ONFH as well as blood samples from 30 healthy individuals for whole exome sequencing (WES). Germline mutation and somatic mutation were analyzed to identify new potential pathogenic genes responsible for non-traumatic ONFH. Three genes might correlate with non-traumatic ONFH: VWF, MPRIP (germline mutations) and FGA (somatic mutations). Germline or somatic mutations in VWF, MPRIP and FGA correlate with intravascular coagulation, thrombosis, and consequently, ischemic necrosis of the femoral head.

Developmental coordination disorder (DCD) is a motor learning disability with a prevalence of 5%-6% in school-aged children, which may seriously affect the physical and mental health of affected children. Behavior analysis of children helps explore the mechanism of DCD and develop better diagnosis protocols. In this study, we investigate the behavioral pattern of children with DCD in the gross movement using a visual-motor tracking system. First, visual components of interest are detected and extracted using a series of intelligent algorithms. Then, the kinematic features are defined and calculated to describe the children behavior, including eye movement, body movement, and interacting object trajectory. Finally, statistical analysis is conducted both between groups with different motor coordination abilities and between groups with different task outcomes. The experimental results show that groups of children with different coordination abilities differ significantly both in the duration of eye gaze focusing on the target and in the degree of concentration during aiming, which can serve as behavioral markers to distinguish children with DCD. This finding also provides precise guidance for the interventions for children with DCD. In addition to increasing the amount of time spent on concentrating, we should focus on improving children’s attention levels.

ABSTRACT Psychrobacter is an important bacterial genus that is widespread in Antarctic and marine environments. However, to date, only two complete Psychrobacter phage sequences have been deposited in the NCBI database. Here, the novel Psychrobacter phage vB_PmaS_Y8A, infecting Psychrobacter HM08A, was isolated from sewage in the Qingdao area, China. The morphology of vB_PmaS_Y8A was characterized by transmission electron microscopy, revealing an icosahedral head and long tail. The genomic sequence of vB_PmaS_Y8A is linear, double-stranded DNA with a length of 40,226 bp and 44.1% G+C content, and encodes 69 putative open reading frames. Two auxiliary metabolic genes (AMGs) were identified, encoding phosphoadenosine phosphosulfate reductase and MarR protein. The first AMG uses thioredoxin as an electron donor for the reduction of phosphoadenosine phosphosulfate to phosphoadenosine phosphate. MarR regulates multiple antibiotic resistance mechanisms in Escherichia coli and is rarely found in viruses. No tRNA genes were identified and no lysogeny-related feature genes were detected. However, many similar open reading frames (ORFs) were found in the host genome, which may indicate that Y8A also has a lysogenic stage. Phylogenetic analysis based on the amino acid sequences of whole genomes and comparative genomic analysis indicate that vB_PmaS_Y8A contains a novel genomic architecture similar only to that of Psychrobacter phage pOW20-A, although at a low similarity. vB_PmaS_Y8A represents a new family-level virus cluster with 22 metagenomic assembled viral genomes, here named Minviridae. IMPORTANCE Although Psychrobacter is a well-known and important bacterial genus that is widespread in Antarctic and marine environments, genetic characterization of its phages is still rare. This study describes a novel Psychrobacter phage containing an uncharacterized antibiotic resistance gene and representing a new virus family, Minviridae. The characterization provided here will bolster current understanding of genomes, diversity, evolution, and phage-host interactions in Psychrobacter populations.

Objective Rheumatoid arthritis is an autoimmune disease characterized by synovial inflammation-driven cartilage and bone destruction, a process mainly mediated by osteoclasts. In recent years M2-like macrophages have been found to play an important role in the pathological process of RA by mediating pro-inflammatory effects, but their roles in the bone destruction of autoimmune arthritis have not been reported. Methods and Results In this study we identified that an abundant cell population of CD45 + CD11b + Gr-1 - F4/80 + CD206 + cells, which were normally classified as M2-like macrophages, was present in synovium of collagen-induced arthritis (CIA) mice, and these cells had the potential to differentiate into osteoclasts. These M2-like macrophages sorted from CIA synovium highly expressed RANK and could be activated by RANKL and M-CSF to acquire osteoclast markers and bone resorption function both in vitro and in vivo. Furthermore, in vitro differentiated M2 macrophages from both CIA mouse bone marrow and RA patient peripheral blood mononuclear cells were also able to differentiate into osteoclasts, confirming the general osteoclastogenesis capability of M2 subtype macrophages. Conclusion All these results suggest that synovial F4/80 + CD206 + M2-like macrophages in RA may be novel osteoclast precursors and contribute significantly to bone erosive changes seen in RA. Our studies provided new directions and targets for the diagnosis and treatment of rheumatoid arthritis.

IntroductionVibrio is an important bacterial genus containing many pathogenic species. Although more and more Vibrio phages were isolated, the genome, ecology and evolution of Vibrio phages and their roles in bacteriophage therapy, have not been fully revealed.MethodsNovel Vibrio phage vB_ValR_NF infecting Vibrio alginolyticus was isolated from the coastal waters of Qingdao during the Ulva prolifera blooms, Characterization and genomic feature of phage vB_ValR_NF has been analysed using phage isolation, sequencing and metagenome method.Results and DiscussionPhage vB_ValR_NF has a siphoviral morphology (icosahedral head 114±1 nm in diameter; a tail length of 231±1 nm), a short latent period (30 minutes) and a large burst size (113 virions per cell), and the thermal/pH stability study showed that phage vB_ValR_NF was highly tolerant to a range of pHs (4-12) and temperatures (-20 - 45 °C), respectively. Host range analysis suggests that phage vB_ValR_NF not only has a high inhibitory ability against the host strain V. alginolyticus, but also can infect 7 other Vibrio strains. In addition, the phage vB_ValR_NF has a double-stranded 44, 507 bp DNA genome, with 43.10 % GC content and 75 open reading frames. Three auxiliary metabolic genes associated with aldehyde dehydrogenase, serine/threonine protein phosphatase and calcineurin-like phosphoesterase were predicted, might help the host V. alginolyticus occupy the survival advantage, thus improving the survival chance of phage vB_ValR_NF under harsh conditions. This point can be supported by the higher abundance of phage vB_ValR_NF during the U. prolifera blooms than in other marine environments. Further phylogenetic and genomic analysis shows that the viral group represented by Vibrio phage vB_ValR_NF is different from other well-defined reference viruses, and can be classified into a new family, named Ruirongviridae. In general, as a new marine phage infecting V. alginolyticus, phage vB_ValR_NF provides basic information for further molecular research on phage–host interactions and evolution, and may unravel a novel insight into changes in the community structure of organisms during the U. prolifera blooms. At the same time, its high tolerance to extreme conditions and excellent bactericidal ability will become important reference factors when evaluating the potential of phage vB_ValR_NF in bacteriophage therapy in the future.

Members of the genus Tetrasphaera are putative polyphosphate accumulating organisms (PAOs) that have been found in greater abundance than Accumulibacter in many full-scale enhanced biological phosphorus removal (EBPR) wastewater treatment plants worldwide. Nevertheless, previous studies on the effect of environmental conditions, such as pH, on the performance of EBPR have focused mainly on the response of Accumulibacter to pH changes. This study examines the impact of pH on a Tetrasphaera PAO enriched culture, over a pH range from 6.0 to 8.0 under both anaerobic and aerobic conditions, to assess its impact on the stoichiometry and kinetics of Tetrasphaera metabolism. It was discovered that the rates of phosphorus (P) uptake and P release increased with an increase of pH within the tested range, while PHA production, glycogen consumption and substrate uptake rate were less sensitive to pH changes. The results suggest that Tetrasphaera PAOs display kinetic advantages at high pH levels, which is consistent with what has been observed previously for Accumulibacter PAOs. The results of this study show that pH has a substantial impact on the P release and uptake kinetics of PAOs, where the P release rate was >3 times higher and the P uptake rate was >2 times higher at pH 8.0 vs pH 6.0, respectively. Process operational strategies promoting both Tetrasphaera and Accumulibacter activity at high pH do not conflict with each other, but lead to a potentially synergistic impact that can benefit EBPR performance.

Objectives To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. Methods Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. Results Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. Conclusions Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

Vibrio is a kind of common gram-negative bacteria, which is widely distributed in marine and estuarine environments. In the study, a novel marine phage vB_VhaP_PG11, infecting Vibrio hangzhouensis, was isolated from the offshore waters of Qingdao, China. vB_VhaP_PG11 is a double-stranded DNA phage. The whole genome proteomic tree shows that vB_VhaP_PG11 phage is related to two Vibrio phages, Vibrio phage 1.238.A._10N.261.52.F10 and Vibrio phage 1.245.O._10N.261.54.C7, but with low homology. Their amino acids identity with vB_VhaP_PG11 is 42.77 and 41.49% respectively. The prediction results of genome-blast distance phylogeny (GBDP) and the analysis gene-sharing network indicate that vB_VhaP_PG11 belongs to a new genus in Schitoviridae, named Qingschitovirus. The study of Vibrio phage vB_VhaP_PG11 provides basic information contributing to a better understanding of interactions between Vibrio phages and their hosts and helps analyze unknown viral sequences in the metagenomic database.

Pseudomonas is a ubiquitous and ambiguous opportunistic pathogen, and plays an important ecological role in the ocean. Here, a new species, Pseudomonas phage vB_PsaP_M1, is described, which was isolated from the surface coastal waters of Qingdao, China. vB_PsaP_M1 contains a linear, double-stranded 89,387-bp genome with a GC content of 41.04% and encoding 184 putative open reading frames (ORFs). There were 50 conservative domains were predicted with BLASTp, including two auxiliary metabolic genes (Phosphate-inducible gene phoH and signal peptide peptidase A, sppA). Phylogenetic analysis of whole genome amino acid sequence and comparative genomic analysis showed that vB_PsaP_M1 has a distant evolutionary relationship with previously isolated viruses and can be grouped into a family-level novel viral cluster (VC_61) with eleven uncultured, assembled viral genomes, named as Psaeviridae. Psaeviridae contains two ORFs (ORFs 117 and 127), which were not detected in the genomes of other viral families, confirming the proposal for a new family. Combined with its ability to infect Pseudomonas and its representation of an unstudied viral family, vB_PsaP_M1 may be an important and novel model system for the study of interactions between viruses and host cells in marine ecosystems.

BackgroundThis study aims to analyze the prognostic significance of the metastatic lymph node (mLN) size in non-small cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT) to provide some information for the optimization of clinical nodal (cN) staging.MethodsA retrospective study with 325 NSCLC patients was conducted between January 2011 and December 2018 at two participating institutes. We evaluated the potential relationship between the mLN size and the survival to propose a potential revised nodal (rN) staging.ResultsKaplan–Meier analyses showed significant differences in the overall survival (OS) based on the cN staging and the size of mLNs (N0, ≤2 cm, and >2 cm). We found that the nodal size correlated statistically with the response to CRT. The HRs of OS for patients with bulky mLNs increase significantly compared with patients in the non-bulky mLNs group in the cN2-3 group. Interestingly, the HRs of patients with bulky cN2 disease and non-bulky cN3 disease were similar to each other. We classified the patients into five subsets: N0, rN1(cN1), rN2(non-bulky cN2), rN3a(bulky cN2, and non-bulky cN3), and rN3b(bulky cN3). In our study, the rN stage showed better prognostic discrimination than the 8th IASLC cN staging and was an independent prognostic factor for survival.ConclusionsIn addition to the anatomic location, the size of mLNs correlated statistically with the response to CRT and should be incorporated into the cN staging system to predict survival more accurately.

Abstract We conducted a multicentre cross-sectional survey of COVID-19 patients to evaluate the acute psychological impact on the patients with coronavirus disease 2019 (COVID-19) during isolation treatment based on online questionnaires from 2 February to 5 March 2020. A total of 460 COVID-19 patients from 13 medical centers in Hubei province were investigated for their mental health status using online questionnaires (including Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Patient Health Questionnaire-15, and Insomnia Severity Index scales). Among all 460 COVID-19 patients, 187 (40.65%) of them were healthcare workers (HCWs). 297 (64.57%) of them were females. The most common psychological problems were somatization symptoms (66.09%, n = 304), followed by depression (53.48%, n = 246), anxiety (46.30%, n = 213), problems of insomnia (42.01%, n = 171), and then self-mutilating or suicidal thoughts (23.26%, n = 107). Of all the patients, 15.65% (n = 72) had severe somatization symptoms, and 2.83% (n = 13) had severe (almost every day) self-mutilating or suicidal thoughts. The most common psychological problems for HCWs were somatization symptoms (67.84%, n = 125), followed by depression (51.87%, n = 97), anxiety (44.92%, n = 84), problems of insomnia (36.18%, n = 55), and then self-mutilating or suicidal thoughts (20.86%, n = 39). Patients with lower education levels were found to be associated with higher incidence of self-mutilating or suicidal thoughts (odds ratio [OR], 2.68, 95% confidence interval [95% CI], 1.66–4.33 [P

Abstract Background Protein aggregates can be found in peripheral organs, such as the heart, kidney, and pancreas, but little is known about the impact of peripherally misfolded proteins on neuroinflammation and brain functional recovery following ischemic stroke. Methods Here, we studied the ischemia/reperfusion (I/R) induced brain injury in mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryABR120G), by examining neuroinflammation and brain functional recovery following I/R in comparison to their non-transgenic (Ntg) littermates. To understand how peripherally misfolded proteins influence brain functionality, exosomes were isolated from CryABR120G and Ntg mouse blood and were used to treat wild-type (WT) mice and primary cortical neuron-glia mix cultures. Additionally, isolated protein aggregates from the brain following I/R were isolated and subjected to mass-spectrometric analysis to assess whether the aggregates contained the mutant protein, CryABR120G. To determine whether the CryABR120G misfolding can self-propagate, a misfolded protein seeding assay was performed in cell cultures. Results Our results showed that CryABR120G mice exhibited dramatically increased infarct volume, delayed brain functional recovery, and enhanced neuroinflammation and protein aggregation in the brain following I/R when compared to the Ntg mice. Intriguingly, mass-spectrometric analysis of the protein aggregates isolated from CryABR120G mouse brains confirmed presence of the mutant CryABR120G protein in the brain. Importantly, intravenous administration of WT mice with the exosomes isolated from CryABR120G mouse blood exacerbated I/R-induced cerebral injury in WT mice. Moreover, incubation of the CryABR120G mouse exosomes with primary neuronal cultures induced pronounced protein aggregation. Transduction of CryABR120G aggregate seeds into cell cultures caused normal CryAB proteins to undergo dramatic aggregation and form large aggregates, suggesting self-propagation of CryABR120G misfolding in cells. Conclusions These results suggest that peripherally misfolded proteins in the heart remotely enhance neuroinflammation and exacerbate brain injury following I/R likely through exosomes, which may represent an underappreciated mechanism underlying heart-brain crosstalk.

The detection of wood defects plays an important role in the processing and production of wood, the deep learning methods have achieved outstanding results in this field in recent years. There are still two unresolved problems, one is that the category of defects is unbalanced and difficult to obtain, and the other is the effective modeling of defects with different sizes and irregular shapes. Here an alternative detection method is proposed. For the problem of imbalance in defect categories, a generative data augmentation method, cycle generative adversarial network (GAN), is used to generate new defective images, while seven online data augmentation schemes are used to solve the problem of difficult access to defective data. The layered deformable mask region-based convolutional neural network (Mask R-CNN) is constructed to address the challenges of modeling irregular defects and contextual information extraction. By creating layered connections between residual modules, a larger receptive field is achieved at each layer of the network, while deformable convolution is used to better fit the shape of the defects. Finally, the upgraded model is trained and used to locate and segment defects simultaneously. Ablation experiments show that the enhanced model performs better than the original model in terms of localization and segmentation. Meanwhile, it is excellent relative to baseline object detection algorithms, instance segmentation algorithms, and other methods for detecting wood defects.

Background and AimAcute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents.MethodsWe performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments.ResultsThe survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments.ConclusionG-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration NumberClinicalTrials.gov, identifier (NCT02331745).

Fired brick is a universal building material, produced by thousand-year-old technology, which throughout history has seldom served any other purpose. Here, the authors show that bricks can store energy after chemical treatment to convert their iron oxide content into conducting polymer nanofibers.

The quick and intelligent requests and answers in artificial intelligence (AI) are inseparable from intelligent data. Knowledge graph makes data more intelligent by establishing association among data, which provides convenience for intelligent search, reasoning and analysis of data. Resource Description Framework (RDF) is an effective data representation model of knowledge graph. This paper takes RDF as the research object and proposes an incremental partition method of intelligent data (IPID) to realize the distributed storage of large-scale AI data. First, IPID gives a mixed object function integrating edge cut and load balancing. Second, IPID devises the initial and incremental partitioning algorithms of RDF. The initial partition divides the original RDF graph into kernel vertices, boundary vertices and free vertices. The boundary and freedom nodes select the kernel vertex with the maximum gain of object function to form a sub-partition. And the incremental partition is in charge of the selection of sub-partition of new and deleted data by the object function. Meanwhile, the incremental partition algorithm would also execute a dynamic adjustment strategy at a certain time interval according to the balance and tightness of sub-partition to satisfy the partitioning object. Finally, IPID is tested on the knowledge graph datasets. The experimental results show that the object function guarantees the quality of knowledge graph partition in edge cut and load balancing, and effectively realizes the incremental partition.

Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels. Despite having advancement in the use of thrombolytic and clot removal medicine, significant numbers of stroke patients are still left out without option for treatment. In this review, we summarize recent research work on the activation of δ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury. Moreover, as activation of δ-opioid receptor by a non-peptidic δ-opioid receptor agonist also modulates the expression, maturation and processing of amyloid precursor protein and β-secretase activity, the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.

As the most common form of dementia and a progressive neurodegenerative disorder, Alzheimer’s disease (AD) affects over 10% world population with age 65 and older. The disease is neuropathologically associated with progressive loss of neurons and synapses in specific brain regions, deposition of amyloid plaques and neurofibrillary tangles, neuroinflammation, blood–brain barrier (BBB) breakdown, mitochondrial dysfunction, and oxidative stress. Despite the intensive effort, there is still no cure for the disorder. Stem cell-derived exosomes hold great promise in treating various diseases, including AD, as they contain a variety of anti-apoptotic, anti-inflammatory, and antioxidant components. Moreover, stem cell-derived exosomes also promote neurogenesis and angiogenesis and can repair damaged BBB. In this review, we will first outline the major neuropathological features associated with AD; subsequently, a discussion of stem cells, stem cell-secreted exosomes, and the major exosome isolation methods will follow. We will then summarize the recent data involving the use of mesenchymal stem cell- or neural stem cell-derived exosomes in treating AD. Finally, we will briefly discuss the challenges, perspectives, and clinical trials using stem cell-derived exosomes for AD therapy.

With the rapid development of artificial intelligence technology, the exploration and application in the field of intelligent education has become a research hotspot of increasing concern. In the actual classroom scenarios, students’ classroom behavior is an important factor that directly affects their learning performance. Specifically, students with poor self-management abilities, particularly specific developmental disorders, may face educational and academic difficulties owing to physical or psychological factors. Therefore, the intelligent perception and identification of school-aged children’s classroom behaviors are extremely valuable and significant. The traditional method for identifying students’ classroom behavior relies on statistical surveys conducted by teachers, which incurs problems such as being time-consuming, labor-intensive, privacy-violating, and an inaccurate manual intervention. To address the above-mentioned issues, we constructed a motion sensor-based intelligent system to realize the perception and identification of classroom behavior in the current study. For the acquired sensor signal, we proposed a Voting-Based Dynamic Time Warping algorithm (VB-DTW) in which a voting mechanism is used to compare the similarities between adjacent clips and extract valid action segments. Subsequent experiments have verified that effective signal segments can help improve the accuracy of behavior identification. Furthermore, upon combining with the classroom motion data acquisition system, through the powerful feature extraction ability of the deep learning algorithms, the effectiveness and feasibility are verified from the perspectives of the dimensional signal characteristics and time series separately so as to realize the accurate, non-invasive and intelligent children’s behavior detection. To verify the feasibility of the proposed method, a self-constructed dataset (SCB-13) was collected. Thirteen participants were invited to perform 14 common class behaviors, wearing motion sensors whose data were recorded by a program. In SCB-13, the proposed method achieved 100% identification accuracy. Based on the proposed algorithms, it is possible to provide immediate feedback on students’ classroom performance and help them improve their learning performance while providing an essential reference basis and data support for constructing an intelligent digital education platform.

Infectious pneumonia is one of the most common complications after bone marrow transplantation (BMT), which is considered to be associated with poor reconstitution and functional maturation of alveolar macrophages (AMs) post-transplantation. Here, we present evidence showing that lack of IL-13-secreting group 2 innate lymphoid cells (ILC2s) in the lungs may underlay poor AM reconstitution in a mouse model of haploidentical BMT (haplo-BMT). Recombinant murine IL-13 was able to potentiate monocyte-derived AM differentiation in vitro. When intranasally administered, a cocktail of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and CCL2 not only promoted donor monocyte-derived AM reconstitution in haplo-BMT-recipient mice but also enhanced the innate immunity of the recipient animals against pulmonary bacterial infection. These results provide a useful clue for a clinical strategy to prevent pulmonary bacterial infection at the early stage of recipients post-BMT.

To achieve non-destructive testing for small size weld beads of metal workpieces, we developed a new testing method of closed magnetic circuit reluctance measurement. According to the shape and volume of the small size weld defects of the metal workpiece, a reluctance detection model was established in the detection environment of alternating magnetic field. The relationship between different weld defects and closed magnetic circuit reluctance was quantitatively analyzed to achieve the identification of weld defects. A particle swarm optimization algorithm (PSO) was applied to optimize the cost-sensitive support vector machine (CS-SVM), which effectively reduced the coupling errors caused by the limitation of the workpiece coupling size. This new method was used to verify the weld bead detection of representative carbide saw blades. Compared with the basic support vector machine, the improved cost-sensitive support vector machine has better performance in the classification of unbalanced samples. The experimental results showed this new method can detect the weld bead of carbide saw blade with the correct rate to 98.2%. It reduced the interference of coupling error effectively. The improved cost-sensitive support vector machine not only improved the detection accuracy, but also avoided the possibility that the defective weld workpiece samples are misclassified into qualified workpieces. This study provides a guarantee for safe production and has great significance in engineering applications. The new method provides an effective solution for the application of reluctance testing technology in small size weld bead detection.

Stroke induces complex pathological cascades in the affected brain area, leading to brain injury and functional disability. To fight against cerebral ischemia/reperfusion-induced neuronal death, numerous neuroprotective strategies and reagents have been studied. However, translation of these neuroprotective drugs to clinical trials has been unsuccessful. To date, the tissue plasminogen activator is still the only FDA-approved drug for treating ischemic stroke. Thus, it is obligatory to identify and validate additional therapeutic strategies for stroke. A stroke rarely occurs without any other pathophysiological condition; but instead, it often has multi-morbidity conditions, one of which is cardiac disease. Indeed, up to half of the stroke cases are associated with cardiac and large artery diseases. As an adequate blood supply is essential for the brain to maintain its normal function, any pathophysiological alterations in the heart are frequently implicated in stroke outcomes. In this review, we summarize some of the cardiovascular factors that influence stroke outcomes and propose that considering these factors in designing stroke therapies should enhance success in clinical trials. We also highlight the recent advances regarding the potential effect of protein aggregates in a peripheral organ, such as in the heart, on ischemic stroke-caused brain injury and functional recovery. Including these and other comorbidity factors in the future therapeutic strategy designs should facilitate translational success toward developing effective combinational therapies for the disorder.

The root of Codonopis bulleynana Forest ex Diels (cbFeD), a tonic food widely used in Yunnan Province of China, was found to have a wide range of pharmacological effects. The present study was designed to investigate the anti-fibrotic effect of water extracts of cbFeD in chronic liver injury mice model induced by carbon tetrachloride (CCl4) and to explore its underlying mechanisms. Phytochemical analysis revealed multiple components were present in the water extract of cbFeD and the compounds were mostly enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc. Treatment with cbFeD significantly attenuated liver injury and fibrosis in CCl4-administered mice evidenced by improved liver histology, ameliorated apoptosis of hepatocytes, and decreased transaminase levels in the serum. Decreased activities of superoxide dismutase (SOD) and catalase (CAT) were markedly reversed upon treatment with cbFeD while levels of malondialdehyde (MDA) and glutathione (GSH) were significantly restored towards normal values. cbFeD also suppressed intrahepatic inflammatory cell infiltration and Kupffer cell activation. Furthermore, our study revealed an inhibitory effect of cbFeD on hepatic stellate cells (HSCs) activation both in vitro and in vivo. In conclusion, cbFeD could exert a protective role against liver fibrosis in mice model induced by CCl4 that is comparable to the positive control silymarin and might be developed into a promising anti-fibrotic drug.

Background Tumor-associated macrophages (TAMs) resemble M2-polarized cells with potent immunosuppressive activity and play a pivotal role in tumor growth and progression. Converting TAMs to proinflammatory M1-like phenotype is thus an attractive strategy for antitumor immunotherapy.Methods A mouse IgG1 (kappa) monoclonal Ab, M-860, specific to human lactoferrin (LTF) was generated by using the traditional hybridoma cell fusion technology. TAMs were generated by culturing human and mouse CD14+ monocytes in tumor-conditioned media containing a cytokine cocktail containing recombinant interleukin-4 (IL-4), interleukin-10 (IL-10) and macrophage colony stimulating factor (M-CSF). TAMs after treatment with immunocomplex (IC) between human LTF and M860 (LTF-IC) were phenotypically and functionally characterized by flow cytometry (FACS), ELISA, Q-PCR and killing assays. The antitumor effects of LTF-IC were further analyzed using in vivo experiments employing tumor-bearing human FcγRIIa-transgenic mouse models.Results Through coligation of membrane-bound CD14 and FcγRIIa, LTF-IC rendered TAMs not only M2 to M1 conversion, evidenced by increased tumor necrosis factor α production, down-regulated M2-specific markers (CD206, arginase-1 and vascular endothelial growth factor) and upregulated M1-specific markers (CD86 and HLA-DR) expression, but also potent tumoricidal activity in vitro. LTF-IC administration conferred antitumor protective efficacy and prolonged animal survival in FcγRIIa-transgenic mice, accompanied by accumulation of M1-like macrophages as well as significantly reduced infiltration of immunosuppressive myeloid-derived suppressor cells and regulatory T cells in solid tumor tissues.Conclusions LTF-IC is a promising cancer therapeutic agent capable of converting TAMs into tumoricidal M1-like cells.

Robotic systems generally employ resource description framework (RDF) to express heterogeneous data coming from different sensors. With the access of more terminals, the RDF volume in robotic systems is becoming larger and larger, posing new significant challenges to the storage and retrieval of RDF data. This paper proposes a star-based partitioning and index algorithm for RDF data of robotic systems. First, we construct a two-hop star structure by MapReduce and HDFS, and get a coarsened weighted graph. Next, a balance partitioning algorithm is used to divide the weighted graph. After partitioning, a compressed and linked S-tree index is proposed to improve the query efficiency. Experiments are executed on benchmark and real data sets to evaluate the studied partitioning and index methods. Results show that our partitioning method has a lower replication ratio, and a better load balancing performance, so our method is efficient for star query and competitive in complex query.

Abstract Thin film thermocouples (TFTCs) can provide more precise in situ temperature measurement for aerospace propulsion systems without disturbance of gas flow and surface temperature distribution of the hot components. ITO/PtRh:PtRh TFTC with multilayer structure was deposited on alumina ceramic substrate by magnetron sputtering. After annealing, the TFTC was statically calibrated for multiple cycles with temperature up to 1000 °C. The TFTC with excellent stability and repeatability was realized for the negligible variation of EMF in different calibration cycles. It is believed that owing to oxygen diffusion barriers by the oxidation of top PtRh layer and Schottky barriers formed at the grain boundaries of ITO, the variation of the carrier concentration of ITO film is minimized. Meanwhile, the life time of TFTC is more than 30 h in harsh environment. This makes ITO/PtRh:PtRh TFTC a promising candidate for precise surface temperature measurement of hot components of aeroengines.

The power metal oxide semiconductor field effect transistor is used extensively in analog circuits and digital circuits. However, it is also the highest failure rate component in the power electronics system. In order to avoid serious failures in the electrical system, it is necessary to predict the remaining useful life of the metal oxide semiconductor field effect transistor. With the aim to accurately predict the remaining useful life, this article presents an improved particle filter method, which can estimate the metal oxide semiconductor field effect transistor degradation degree by the on-resistance (Ron) changing data. This method is based on the particle filter algorithm, which is suitable for nonlinear and non-Gaussian system; at the same time, the proposed method can avoid the degeneracy phenomenon in the particle filter. First, the strong tracking Kalman filter is used as the importance function to update the particles with the latest observation in the sample process. The Metropolis–Hastings algorithm is used to introduce some new particles to guarantee the effective particle number in the resampling process. The experimental results indicate that the improved particle filter algorithm can obtain more effective remaining useful life prognostic than that of the particle filter.

Background/Aims: MicroRNAs (miRNAs) are reported to regulate cell invasion and functions by interfering with the translation of target mRNAs, but the role of miRNAs in esophageal cancer (EC) remains unclear. Methods: RT-PCR and Western blot were used to detect the expression of miRNAs and candidate genes in EC samples (n=89). miR-140 mimics and inhibitor were tansfected in human TE-1 and Eca-109 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. The markers of EMT were detected by using Western blot. Results: miR-140 expression was decreased in the EC tissues compared with the corresponding adjacent tumor tissues. Low expression of miR-140 promotes cell invasion by using transwell assay, while the effect of miR-140 high expression is reverse. Slug, a target gene of miR-140, was examined by luciferase assay and Western blot. Conclusions: miR-140 may regulate the cell invasion of EC via controlling Slug expression.

Aviation bearing assembled detection is the final barrier to quality and safety. Therefore, an accurate detection method of aviation bearing that is based on local characteristics is designed to solve the detection problem of mis-assembly and miss-assembly of balls in aviation bearing assembled. When considering the spatial limitation of aviation bearing assembled image acquisition, the dynamic distribution of balls and the interference of lubricating grease on the surface, a dynamic local ball segmentation model that is based on U-Net network with symmetrical structure is designed to achieve the accurate segmentation of the local ball region of aviation bearing. Subsequently, an incomplete circle fitting algorithm is designed based on the segmented local ball image and Hough transform principle. These two algorithms make the measurement error of aviation bearing ball size less than 100 μm. Using bearings validates the algorithm. The results show that the accuracy of dynamic local ball segmentation model that is based on U-Net network with symmetrical structure is over 99%. At the same time, on the basis of accurate segmentation in aviation bearing local ball, the designed Hough circle algorithm is used for circle detection. The experimental results show that the false detection rate of mis-assembly and miss-assembly of balls is less than 3%. Further, the goal of zero-missed detection of mis-assembly and miss-assembly of balls in aviation bearing is achieved. The accurate segmentation of aviation bearing local ball and the effective identification of mis-assembly and miss-assembly of balls are realized. This method can provide a theory for the improvement of mis-assembly and miss-assembly of balls detection in aviation bearing. Furthermore, it has high application value.

Summary DNA damage response (DDR) and the centrosome cycle are two of the most critical processes for maintaining a stable genome in animals. Sporadic evidence suggests a connection between these two processes. Here, we report our findings that six Fanconi Anemia (FA) proteins, including FancI and FancJ, localize to the centrosome. Intriguingly, we found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC). We further show that, in addition to its role in interstrand crosslinking (ICL) repair, FancJ also regulates the normal centrosome cycle as well as ICL induced centrosome amplification by activating the polo-like kinase 1 (PLK1). We have uncovered a novel function of FancJ in centrosome biogenesis and established centrosome amplification as an integral part of the ICL response.

Poly(ADP-ribose) polymerase-1 (PARP-1) is the guardian of the genome acting as a sentinel for genomic damage. However, PARP-1 is also mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. The biochemistry underlying PARP-1-mediated cell death has remained elusive, although NAD+ consumption and energy failure have been thought to be one of the possible molecular mechanisms. Recent observations link PARP-1 activation with translocation of apoptosis-inducing factor (AIF) to the nucleus and indicate that AIF is an essential downstream effector of PARP-1-mediated cell death. PARP-1 activation signals AIF release from the mitochondria, resulting in a novel, caspase-independent pathway of programmed cell death. These recent findings suggest that AIF maybe a target for development of future therapeutic treatment for many neurological disorders involving excitotoxicity.

Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington's disease (HD) patient fibroblasts into neurons by modulation of cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neuron-like cells directly converted from HD patient fibroblasts recapitulate the major aspects of neuropathological characteristics of HD and thus provide an additional model for understanding the disorder and validation of therapeutic reagents.

Singular value decomposition (SVD) is a widely used and powerful tool for signal extraction under noise. Noise attenuation relies on the selection of the effective singular value because these values are significant features of the useful signal. Traditional methods of selecting effective singular values (or selecting the useful components to rebuild the faulty signal) consist of seeking the maximum peak of the differential spectrum of singular values. However, owing to the small number of selected effective singular values, these methods lead to excessive de-noised effects. In order to get a more appropriate number of effective singular values, which preserves the components of the original signal as much as possible, this paper used a difference curvature spectrum of incremental singular entropy to determine the number of effective singular values. Then the position was found where the difference of two peaks in the spectrum declines in an infinitely large degree for the first time, and this position was regarded as the boundary of singular values between noise and a useful signal. The experimental results showed that the modified methods could accurately extract the non-stationary bearing faulty signal under real background noise.