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Polyurethanes (PU) are one of the most used categories of plastics and have become a significant source of environmental pollutants. Degrading the refractory PU wastes using environmentally friendly strategies is in high demand. In this study, three microbial consortia from the landfill leachate were enriched using PU powder as the sole carbon source. The consortia efficiently degraded polyester PU film and accumulated high biomass within 1week. Scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle analyses showed significant physical and chemical changes to the PU film after incubating with the consortia for 48h. In addition, the degradation products adipic acid and butanediol were detected by high-performance liquid chromatography in the supernatant of the consortia. Microbial composition and extracellular enzyme analyses revealed that the consortia can secrete esterase and urease, which were potentially involved in the degradation of PU. The dominant microbes in the consortia changed when continuously passaged for 50 generations of growth on the PU films. This work demonstrates the potential use of microbial consortia in the biodegradation of PU wastes.

The existing medical imaging tools have a detection accuracy of 97% for peritoneal metastasis(PM) bigger than 0.5 cm, but only 29% for that smaller than 0.5 cm, the early detection of PM is still a difficult problem. This study is aiming at constructing a deep convolution neural network classifier based on meta-learning to predict PM.Peritoneal metastases are delineated on enhanced CT. The model is trained based on meta-learning, and features are extracted using multi-modal deep Convolutional Neural Network(CNN) with enhanced CT to classify PM. Besides, we evaluate the performance on the test dataset, and compare it with other PM prediction algorithm.The training datasets are consisted of 9574 images from 43 patients with PM and 67 patients without PM. The testing datasets are consisted of 1834 images from 21 testing patients. To increase the accuracy of the prediction, we combine the multi-modal inputs of plain scan phase, portal venous phase and arterial phase to build a meta-learning-based multi-modal PM predictor. The classifier shows an accuracy of 87.5% with Area Under Curve(AUC) of 0.877, sensitivity of 73.4%, specificity of 95.2% on the testing datasets. The performance is superior to routine PM classify based on logistic regression (AUC: 0.795), a deep learning method named ResNet3D (AUC: 0.827), and a domain generalization (DG) method named MADDG (AUC: 0.834).we proposed a novel training strategy based on meta-learning to improve the model's robustness to "unseen" samples. The experiments shows that our meta-learning-based multi-modal PM predicting classifier obtain more competitive results in synchronous PM prediction compared to existing algorithms and the model's improvements of generalization ability even with limited data.

Based on the interrelationship between the built environment and spatial–temporal distribution of population density, this paper proposes a method to predict the spatial–temporal distribution of urban population density using the depth residual network model (ResNet) of neural network. This study used the time-sharing data of mobile phone users provided by the China Mobile Communications Corporation to predict the time–space sequence of the steady-state distribution of population density. Firstly, 40 prediction databases were constructed according to the characteristics of built environment and the spatial–temporal distribution of population density. Thereafter, the depth residual model ResNet was used as the basic framework to construct the behaviour–environment agent model (BEM) for model training and prediction. Finally, the average percentage error index was used to evaluate the prediction results. The results revealed that the accuracy rate of prediction results reached 76.92% in the central urban area of the verification case. The proposed method can be applied to prevent urban public safety incidents and alleviate pandemics. Moreover, this method can be practically applied to enable the construction of a “smart city” for improving the efficient allocation of urban resources and traffic mobility.

Background Whether healthy lifestyles mediate the association of socioeconomic status (SES) with mortality in older people is largely unknown. Methods A total of 22,093 older participants (age ≥ 65 years) from 5 waves (2002–2014) of Chinese Longitudinal Healthy Longevity Survey cohort were included for analysis. Mediation analysis of lifestyles on the association of SES with all-cause mortality was conducted. Results During a mean follow-up period of 4.92 ± 4.03 years, 15,721 (71.76%) deaths occurred. Compared with high SES, medium SES increased the risk of mortality by 13.5% (HR [total effect]: 1.135, 95% CI 1.067–1.205, p p = 0.936). The total effect when participants of low SES were compared with participants of high SES was HR = 1.161 (95% CI 1.088–1.229, p p p for trend Conclusion Promotion of healthy lifestyles alone can only reduce a small proportion of socioeconomic inequity-related mortality risk in older Chinese people. Even so, healthy lifestyles are important in reducing the overall mortality risk within each SES level.

Myocardial ischemia-reperfusion injury (MI/RI), a complication of myocardial injury, is associated with high rates of mortality and disability. We aimed to explore the effect of nicorandil™ against MI/RI and investigated the underlying molecular mechanisms. In this in vitro study, hypoxia/reoxygenation (H/R) processing of H9c2 cells significantly suppressed the expressions of IL33 and ST2, reduced cell viability, increased production of reactive oxygen species, downregulated protein expression of Bcl-2, upregulated protein expressions of Bax, cleaved caspase3, and cleaved PARP, increased intracellular calcium overload, and induced cell apoptosis. Nicorandil processing reduced H/R-induced H9c2 cell damage. Nicorandil processing ameliorated the H/R-induced inhibition of the IL33 and ST2 expression in H9c2 cells. 5-Hydroxydecanoate blocked the effects of nicorandil on H9c2 cell viability, ROS production, and apoptosis and inhibited both IL33 and ST2. Similarly, the protective effect of nicorandil was restrained after inhibition of the IL33/ST2 pathway. Our findings suggest that the protective effect of nicorandil against H/R-induced H9c2 cell apoptosis was mediated through IL33/ST2 signaling pathway.

Background Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. Results In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. Conclusions Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Graphic abstract

Background Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. Methods Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. Results LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. Conclusions LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.

It may seem trivial to stress that our background knowledge is essential for literary interpretation, but what about practical wisdom, the inarticulable background knowledge? Can we articulate all the things that we know and are able to do in literary interpretation? Are we fully aware of all the assumptions behind our literary arguments? Instead of generally reflecting the status of hermeneutics at a macro-level, this essay argues that one way for hermeneutics to remain meaningful today is not to be tried as a theoretical whole, but as a source of sporadic inspiring arguments. To show that, at a micro-level, we can evaluate the strength of these arguments case by case without generalizing, we analyze from a cognitive perspective Gadamer���s argument that practical wisdom is crucial for literary interpretation. Using cognitive science to provide insights for literary study does not make the latter subservient to the former. Rather, cognitive poetics is a two-way street where each field complements the other by providing hypotheses and functioning as a testing ground. By demonstrating that we know more than we can tell in literary interpretation and that the three features Aristotle and Gadamer attribute to practical wisdom (contingent, inarticulable, and only learnable through experience) are at least tentatively empirically justified, this essay argues that hermeneutics has offered a noteworthy example for the two-way street of cognitive poetics., Es ist trivial, dass unser Hintergrundwissen f��r die Literaturinterpretation wesentlich ist, aber was ist mit der praktischen Weisheit, dem unartikulierbaren Hintergrundwissen? K��nnen wir alles artikulieren, was wir bei der Literaturinterpretation wissen und k��nnen? K��nnen wir uns immer aller Annahmen, die hinter unseren literarischen Argumenten stehen, voll bewusst sein? Anstatt allgemein den Status von Hermeneutik auf einer Makroebene zu reflektieren, argumentiert dieser Aufsatz, dass eine M��glichkeit f��r Hermeneutik heute sinnvoll zu bleiben darin besteht, nicht als ein theoretisches Ganzes gepr��ft zu werden, sondern als eine Quelle von sporadisch inspirierenden Argumenten. Um zu zeigen, dass wir auf einer Mikroebene die St��rke dieser Argumente von Fall zu Fall bewerten k��nnen, ohne zu verallgemeinern, analysieren wir aus einer kognitiven Perspektive Gadamers Argument, dass praktische Weisheit f��r die literarische Interpretation entscheidend ist. Die Einbeziehung der Kognitionswissenschaft in die Literaturwissenschaft bedeutet nicht, dass letztere der ersteren untergeordnet wird. Vielmehr ist die kognitive Poetik eine Zweibahnstra��e, in der jede die andere erg��nzt, indem sie Hypothesen liefert und als Testfeld fungiert. Dieser Aufsatz argumentiert, dass die Hermeneutik ein bemerkenswertes Beispiel f��r die Zweibahnstra��e der kognitiven Poetik geboten hat, indem er zeigt, dass wir in der Literaturinterpretation mehr wissen, als wir sagen k��nnen, und dass die drei Eigenschaften, die Aristoteles und Gadamer der praktischen Weisheit zuschreiben (kontingent, unartikulierbar und nur durch Erfahrung erlernbar), zumindest versuchsweise empirisch gerechtfertigt sind.

Purpose This study aimed to compare the effects of ground and treadmill running on energy metabolism and muscle contractile properties, providing a basis for the general public to choose running venues. Methods Ten male college students (age, 20.10 ± 1.53 years; height, 176.20 ± 5.49 cm; weight, 72.14 ± 8.25 kg; body fat percent, 12.41% ± 4.65%) were recruited in this study. Energy expenditure (EE) was measured using the accelerometer (GT9X) combined with specific estimation equations. Average heart rate (HR) was measured using a heart rate band (Polar). Muscle contractile properties were assessed by measuring muscle displacement (Dm) and contraction velocity (Vc) using tensiomyography (TMG-S1). Blood glucose (Glu) and lactate (Lac) were measured by portable devices (eB-G and Lactate Scout). The running speed was 9 km/h and the duration was 25 min. Two-way ANOVA (protocol × time) was used to analyze the effect of running protocols on energy metabolism and muscle contractile properties. Results EE of treadmill running was significantly higher than EE of ground running (protocol main effect, P < 0.001), and HR of treadmill running was significantly higher than that of ground running in the first testing time (protocol simple effect, P = 0.026; protocol × time interaction P = 0.043). The decrease in Dm of the rectus femoris after treadmill running was significantly higher than that of ground running (protocol main effect, P = 0.009). The interaction of different running protocols and testing times on Lac was significant (P = 0.025), but all results of the simple effects analysis were not statistically significant (P > 0.05). Conclusion Our study found a difference in energy expenditure between treadmill and ground running at 9 km/h with duration of 25 min. In addition, treadmills are more likely to cause a decrease in muscle displacement distance of the rectus femoris measured after exercise than ground running. Future studies are needed to further investigate whether the differences are induced by internal metabolism or the environmental conditions of running.

In anaerobic digestion (AD) system, the C/N ratio can affect utilization efficiency of organic matter and microbial community structure, thereby influencing methane production. This study investigated that the C/N ratio in AD of sewage sludge (SS) suitably enhanced by adding food waste (FW) to improve methane production efficiency. The effects of different C/N ratios (9, 11, 13, and 15) on dry thermophilic anaerobic co-digestion of SS and FW and the microbial community structure were researched. The cumulative methane production at C/N ratio of 11 reached 165.68 ± 11.88 mL/g VSadded which increased by 1.23 times compared with the mono-digestion of SS; and the cumulative methane production increased by 8.15 – 63.55% at C/N ratios of 9, 13, and 15. The methanogenic pathway changed from acetoclastic methanogenesis process to hydrogenotrophic methanogenesis process with the increasing of C/N ratio. Redundancy analysis explained that the C/N ratio had obvious effects on the variation of the microbial phylum and genus, which contributed 21.63% and 29.27%, respectively. The C/N ratio of 11 enriched the dominant bacterial phyla (Firmicutes and Thermotogae) and increased the methanogens diversity at genus level. This research found an approach that could improve methane production in the lower C/N range.

Extant research on salespersons’ regulatory foci has mainly focused on behaviors that are congruent with salespersons’ regulatory orientations (dominant pathway) to the neglect of alternate, yet essential salesperson behaviors that may render less “fit” (supplemental pathway). Moreover, the literature is also silent on managerial actions that can motivate salespeople to perform even when the environment is not conducive to perceived fit. Using a triadic dataset from salespeople, their managers, and archival performance records, the authors find that a competitive psychological climate can strengthen the regulatory fit of promotion focus and adaptive selling, which can be further reinforced (inadvertently disrupted) if managers deploy outcome (behavioral) control. By contrast, prevention focus shows an opposite pattern, in which behavioral control strengthens, whereas outcome control weakens, the perceived fit of prevention focus and service behaviors in a highly competitive climate. Importantly, our findings elucidate the complementary (as opposed to contradictory) nature of the dual process model of dominant and supplemental pathways, by illustrating their positive synergistic effect on salesperson performance. Together, these findings clarify the underlying dual mechanisms of regulatory foci and their respective boundary conditions, thereby shedding light on ambiguities in extant literature and providing actionable managerial guidance.

Aberrant RHO guanine nucleotide exchange factor (RhoGEF) activation is chief mechanism driving abnormal activation of their GTPase targets in transformation and tumorigenesis. Consequently, a small-molecule inhibitor of RhoGEF can make an anti-cancer drug. We used cellular, mouse, and humanized models of RAC-dependent BCR-ABL1-driven and Ph-like acute lymphoblastic leukemia to identify VAV3, a tyrosine phosphorylation–dependent RacGEF, as the target of the small molecule IODVA1. We show that through binding to VAV3, IODVA1 inhibits RAC activation and signaling and increases pro-apoptotic activity in BCR-ABL1-transformed cells. Consistent with this mechanism of action, cellular and animal models of BCR-ABL1-induced leukemia in Vav3-null background do not respond to IODVA1. By durably decreasing in vivo RAC signaling, IODVA1 eradicates leukemic propagating activity of TKI-resistant BCR-ABL1(T315I) B-ALL cells after treatment withdrawal. Importantly, IODVA1 suppresses the leukemic burden in the treatment refractory pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models better than standard-of-care dasatinib or ponatinib and provides a more durable response after treatment withdrawal. Pediatric leukemia samples with diverse genetic lesions show high sensitivity to IODVA1 ex vivo and this sensitivity is VAV3 dependent. IODVA1 thus spearheads a novel class of drugs that inhibits a RacGEF and holds promise as an anti-tumor therapy.

The fate of antibiotic resistance genes (ARGs) in full-scale anaerobic digestion (AD) of food waste (FW) and in the soil applied with biogas slurry has not been fully understood. In this study, 12 targeted ARGs and intI1 in FW, intermediate product, and biogas slurry from three full-scale AD were analyzed. The results showed that subcritical water pretreatment was an effective method for ARG attenuation, by which the absolute abundance of total targeted ARGs was removed by 99.69%. The predominant ARGs (ermB, tetM, and tetW) in FW were removed more than 99% after subcritical water pretreatment. The result of field experiments with biogas slurry as fertilizer showed that the absolute abundance of several ARGs (sul2, tetM, blaOXA-1, blaTEM) and intI1 accumulated significantly compared to the control group (CK) during three consecutive growth stages of the rice. The detected abundance of ARGs in paddy field soil increased from 190.50 (CK) to 8.87 × 104 copies/g (wet weight) (soil) during tillering stage, and increased from 4102.65 (CK) to 4.38 × 104 copies/g (wet weight) (soil) during heading time. Biogas slurry improved the soil nutrients (TN, AN, TP, and AP); meanwhile, the concentrations of total salt and Cl− increased. Network analysis indicated that 28 genera were the possible hosts of ARGs; variation partitioning analysis (VPA) indicated that microbial communities (contribution 59.30%) were the main factors that affected the fate of ARGs and intI1.

Urban forest soil is often disturbed by rapid urbanization. Organic mulching is effective for improving soil quality and aggregate stability. This study evaluated how soil binding agents changed aggregate stability through organic mulching in urban forest soils. Three treatments were applied in Jiufeng National Forest Park, Beijing: (1) no organic mulch (control); (2) wood chips alone (5 cm thickness); and, (3) wood chips + wood compost (This mulch was divided into two layers, the upper layer of wood chips (2.5 cm), the lower layer wood compost (2.5 cm)). Soil samples were collected from the surface 10- cm soil layer and fraction into four aggregates. Glomalin-related soil protein and soil organic carbon were measured in bulk soil and the four aggregates. The results show that wood chips + wood compost increased the proportion of large and small macroaggregates, mean weight diameter and geometric mean diameter. The total and easily extractable glomalin-related soil protein were higher in the wood chips + wood compost. However, soil organic carbon was lower in the wood chips alone application compared to the controls and wood chips + wood compost. Easily extractable / total glomalin-related soil protein and glomalin-related soil protein / soil organic carbon ratios of wood chips alone and wood chips + wood compost had increased trend compared to the controls but did not reach significant levels (p > 0.05). Mean weight diameter and geometric mean diameter correlated positively with total and easily extractable glomalin-related soil protein but were not positively correlated with soil organic carbon, the ratios of easily extractable and total glomalin-related soil protein, and the ratios of glomalin-related soil protein and soil organic carbon. Redundancy analysis revealed that total glomalin-related soil protein was the most important driver for soil aggregate stability, especially the total glomalin-related soil protein of small macroaggregates. The results suggest that wood chips + wood compost enhanced soil aggregate stability through the increase of glomalin-related soil protein. Wood chips alone cannot enhance soil aggregate stability in urban forests in the short term.

The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1+ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC, resulting in depression-like behavior in SFN-treated CSDS mice. Finally, the knockout of Nrf2 and downregulation of TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice and SFN-treated CSDS mice were associated with the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway. These data indicate that alterations in the interaction between Nrf2 and TREM2 may play a role in the pathophysiology of depression-like behavior in mice.

Background Oxidative stress plays an important role in the progression of various types of tumors. However, its role in esophageal squamous cell carcinoma (ESCC) has seldom been explored. This study aimed to discover prognostic markers associated with oxidative stress in ESCC to improve the prediction of prognosis and help in the selection of effective immunotherapy for patients. Results A consensus cluster was constructed using 14 prognostic differentially expressed oxidative stress-related genes (DEOSGs) that were remarkably related to the prognosis of patients with ESCC. The infiltration levels of neutrophils, plasma cells, and activated mast cells, along with immune score, stromal score, and estimated score, were higher in cluster 1 than in cluster 2. A prognostic signature based on 10 prognostic DEOSGs was devised that could evaluate the prognosis of patients with ESCC. Calculated risk score proved to be an independent clinical prognostic factor in the training, testing, and entire sets. P53 signaling pathway was highly enriched in the high-risk group. The calculated risk score was positively related to the infiltration levels of resting mast cells, memory B cells, and activated natural killer (NK) cells and negatively associated with the infiltration levels of M1 and M2 macrophages. The relationship between clinical characteristics and risk score has not been certified. The half-maximal inhibitory concentration (IC50) values for sorafenib and gefitinib were lower for patients in the low-risk group. Conclusion Our prognostic signature based on 10 prognostic DEOSGs could predict the disease outcomes of patients with ESCC and had strong clinical value. Our study improves the understanding of oxidative stress in tumor immune microenvironment (TIME) and provides insights for developing improved and efficient immunotherapy strategies.

Microscope such as fluorescence microscope, confocal microscope and two-photon microscope plays an important role in life science, laser processing and other fields. However, most microscopes only have discrete zoom rates. In this paper, a continuous optical zoom microscope with extended depth of field and 3D reconstruction is demonstrated for the first time. It consists of a zoom objective lens, a microscope holder, an adjustable three-dimensional object stage, an Abbe condenser and an LED light source. The zoom objective lens is composed of several liquid lenses and solid lenses. By adjusting the applied voltage to the liquid lens, the proposed microscope can achieve a large continuous magnification from 10? to 60?. Moreover, an improved shape from focus (SFF) algorithm and image fusion algorithm are designed for 3D reproduction. Based on the liquid lenses, the axial focusing position can be adjusted to obtain images with different depths, and then the extended depth of field and 3D reconstruction can be realized. Our experimental results demonstrate the feasibility of the proposed microscope. The proposed microscope is expected to be applied in the fields of pathological diagnosis, biological detection, etc.

BACKGROUND: Colorectal neuroendocrine carcinomas (CRNECs) are highly aggressive tumours with poor prognosis and low incidence. To date, the genomic landscape and molecular pathway alterations have not been elucidated. METHODS: Tissue sections and clinical information of CRNEC (n = 35) and CR neuroendocrine tumours (CRNETs) (n = 25) were collected as an in-house cohort (2010–2020). Comprehensive genomic and expression panels (AmoyDx® Master Panel) were applied to identify the genomic and genetic alterations of CRNEC. Through the depiction of the genomic landscape and transcriptome profile, we compared the difference between CRNEC and CRNET. Reverse transcription-polymerase chain reaction and immunofluorescence staining were performed to confirm the genetic alterations. RESULTS: High tumour mutation load was observed in CRNEC compared with CRNET. CRNECs showed a “cold” immune landscape and increased endothelial cell activity compared with NETs. Importantly, PAX5 was aberrantly expressed in CRNEC and predicted a poor prognosis of CRNECs. CCL5, a factor that is considered an immunosuppressive factor in several tumour types, was strongly expressed in CRNEC patients with long-term survival and correlated with high CD8(+) T cell infiltration. CONCLUSION: Through the depiction of the genomic landscape and transcriptome profile, we demonstrated alterations in molecular pathways and potential targets for immunotherapy in CRNEC.

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P

The separation efficiency of photocarriers is an important part of photocatalytic efficiency. Construction of composite with good contact is a hot topic. In this work, Bi2WO6 is successfully connected with BiOI to form the chemical bonding interface through the same crystal unit, where a precipitation transformation phenomenon is revealed. The chemical bonding interface is conducive to transmission and separation of photocarriers to realize rapid and stable transport and separation through the interface, which is based on the photocurrent density of Bi2WO6/BiOI (BWOI) is about 6 and 40 times higher than Bi2WO6 and BiOI, and the transfer resistance of BWOI is around 5 and 10 times lower than Bi2WO6 and BiOI. Thus, the photocatalytic activity of BWOI is 2.8 and 33.35 times as much as those of Bi2WO6 and BiOI. During the photocatalysis process, photogenerated holes (h+) and superoxide radical (·O2−) are the main oxidizers, and the constructed the chemical bonding interface displays excellent photostability.

Background The WNT signal pathway has myriad family members, which are broadly involved in embryonic development and human cancer. Over-activation of WNT-β-Catenin signaling promotes cancer cell proliferation and survival. However, how diverse components of WNT signaling specifically engaged in distinct tumor types remains incompletely understood. Methods We analyzed the transcriptomic profiling of WNT ligands and receptors/co-receptors among 26 different tumor types to identify their expression pattern, and further verified these results using clinical oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LUSC) samples. At the same time, we also detected WNT7B expression in oral inflammation and carcinoma, and constructed stable WNT7B knockdown OSCC cell lines to study the effects of WNT7B on the cell migration and invasion ability. Results We found a group of tumor-specific WNT members, including a panel of squamous cell carcinomas (SCCs) specific upregulated WNT ligands and receptors, WNT5A, WNT7B, FZD7 and GPC1. We further revealed a significant correlation between these protein expression characteristics and clinical outcomes of OSCC and LUSC patients. Moreover, WNT7B was demonstrated to contribute to the development of oral chronic inflammation and OSCC, partly due to promoting the invasion ability of tumor cells. Conclusions These results demonstrate that the function of WNT ligands and receptors in specific tumors depends on the origination of tumor tissue type. Collectively, they support the use of WNT components as a highly specific target for pan-tissue-type originated tumors.