SET facilitates immune escape of microsatellite stability colorectal cancer by inhibiting c-Myc degradation.

Microsatellite stability (MSS) colorectal cancer (CRC) exhibits a low mutation load and poor immunogenicity, contributing to immune escape of tumor cells and less benefit from immune checkpoint blockade (ICB) treatment. The mechanisms underlying immunotherapeutic resistance in MSS CRC remain to be elucidated. Here, we identified that nuclear proto-oncogene SET is significantly higher expressed in MSS CRC compared to microsatellite instability (MSI) CRC and facilitates immune escape of MSS CRC. Mechanistically, SET represses the expression of C-C motif chemokine ligand 5 (CCL5) and upregulates mismatch repair (MMR) proteins expression in a c-Myc-dependent manner, which inhibits infiltration and migration of CD8+ T cells to tumor tissues and results in low immunogenicity in MSS CRC. In addition, we found that SET impairs ubiquitination and proteasomal degradation of c-Myc by disrupting the interaction between E3 ligase FBXW7 and c-Myc. Moreover, SET inhibition enhances the response to immunotherapy in MSS CRC in vivo. Overall, this study reveals the critical roles and posttranslational regulatory mechanism of SET in immune escape and highlights the SET/c-Myc axis as a potential target for immunotherapy of MSS CRC that have implications for targeting a unique aspect of this disease.

Pretreatment to terahertz absorption curves by narrow undulation constraint and Its quick implementation suggested by convex hull.

In this work, a method of pretreating THz absorption curve is proposed, which leads to minimal range in absorption, reserving necessary undulation of curve for identification by convolutional neural network. The kernel thought of proposed method is about confining the undulation of curve with a pair of narrow parallel lines and solving their optimal position by consecutively rotation of normalized curve at two fixed points. A fast algorithm is further proposed based on features of convex hull, whose procedure is described in detail. The algorithm involves definition of some important point sets, calculating and comparing slopes and determining best choice out of 4 potential rotations. The rationality of searching critical point is illustrated in a geometric way. Additionally, the adaption of the method is discussed and real examples are given to show the capacity of method to extract nonlinear information of a curve. The study suggests that methods regarding computer graphics also contributes to feature extraction with respect to THz curve and pattern recognition.

To Estimate Performance of Artificial Neural Network Model Based on Terahertz Spectrum: Gelatin Identification as an Example.

It is a necessity to determine significant food or traditional Chinese medicine (TCM) with low cost, which is more likely to achieve high accurate identification by THz-TDS. In this study, feedforward neural networks based on terahertz spectra are employed to predict the animal origin of gelatins, whose adaption to the mission is examined by parallel models built by random sample partition and initialization. It is found that the generalization performance of feedforward ANNs in original data is not satisfactory although prediction on trained samples can be accurate. A multivariate scattering correction is conducted to enhance prediction accuracy, and 20 additional models verify the effectiveness of such dispose. A special partition of total dataset is conducted based on statistics of parallel models, whose influence on ANN performance is investigated with another 20 models. The performance of the models is unsatisfactory because of notable differences in training and test sets according to principal component analysis. By comparing the distribution of the first two principal components before and after multivariate scattering correction, we found that the reciprocal of the minimum number of line segments required for error-free classification in 2-D feature space can be viewed as an index to describe linear separability of data. The rise of proposed linear separability would have a lower requirement for harsh parameter tuning of ANN models and tolerate random initialization. The difference in principal components of samples between a training set and a data set determines whether partition is acceptable or whether a model would have generality. A rapid way to estimate the performance of an ANN before sufficient tuning on a classification mission is to compare differences between groups and differences within groups. Given that a representative peak missing curve is discussed in this article, an analysis based on gelatin THz spectra may be helpful for studies on some other feature-less species.

Association of infant antibiotic exposure and risk of childhood asthma: A meta-analysis.

BACKGROUND: Infant antibiotic exposure may be associated with childhood asthma development. OBJECTIVE: To examine and detail this association considering potential confounders. STUDY DESIGN: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for publications from January 2011 to March 2021. Eligible studies were independently reviewed to extract data and assess quality. Random effect model was used to pool odds ratio (OR) and corresponding 95% confidence intervals (CIs). RESULTS: A total of 52 studies were included. The association of infant antibiotic exposure and childhood asthma was statistically significant for overall analysis (OR, 1.37; 95% CI, 1.29-1.45) and for studies that addressed reverse causation (RC) and confounding by indication (CbI) (1.19; 95% CI, 1.11-1.28). Significance remained after stratification by adjustment for maternal antibiotic exposure, medical consultation, sex, smoke exposure, parental allergy, birth weight, and delivery mode. In detailed analyses, macrolides (OR, 1.56; 95% CI, 1.31-1.86), antibiotic course≥5 (OR, 1.79; 95% CI, 1.36-2.36), exposure within 1 week of birth (OR, 1.82; 95% CI, 1.34-2.47), asthma developed among 1-3 years (OR, 1.84; 95% CI, 1.63-2.08), short time lag between exposure and asthma onset (OR, 2.05; 95% CI, 1.91-2.20), persistent asthma (OR, 2.61; 95% CI, 1.49-4.59), and atopic asthma (OR, 2.14; 95% CI, 1.58-2.90) showed higher pooled estimates. CONCLUSION: Infant antibiotic exposure is associated with increased risk of childhood asthma considering confounding, and the association varied with different settings of exposure and outcomes. This highlights the need for prevention of asthma after early antibiotic exposure. Heterogeneity among studies called for caution when interpretation.

Adenocarcinoma with Mixed Subtypes in the Early and Advanced Gastric Cancer.

Objective: Adenocarcinoma with mixed subtypes (AM) is a histological classification based on the WHO classification. We aimed to compare the prognosis among AM, classic adenocarcinoma (CA), mucinous adenocarcinoma (MAC), and signet-ring cell carcinoma (SRCC) in early and advanced gastric cancer (EGC and AGC), respectively. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2001 to 2016. Univariate and multivariate Cox analyses were performed to compare prognosis between AM and histologic subtypes of CA, SRCC, and MAC in ECG and ACG. A nomogram was established to predict the cancer-specific survival (CSS) of gastric cancer (GC) patients with AM. C-index, calibration curves, and receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were applied to examine the accuracy and clinical benefits. Results: In the prognosis among these four histological subtypes in EGC patients, there are no differences. For AGC patients, AM had a significantly poorer prognosis compared with CA and MAC (P=0.003, 0.029) but similar prognosis to SRCC. A nomogram based on race, T stage, N stage, M stage, and surgical modalities was proposed to predict 1- and 3-year CSS for GC patients with AM (C-index: training cohort: 0.804, validation cohort: 0.748. 1- and 3-year CSS AUC: training cohort: 0.871 and 0.914, validation cohort: 0.810 and 0.798). 1- and 3-year CSS DCA curves showed good net benefits. Conclusions: EGC patients with AM had similar survival to those with CA, MAC, and SRCC. AM was an independent predictor of poor prognosis in AGC. A nomogram for predicting the prognosis of GC patients with AM was proposed to quantitatively assess the long-term survival.

Impact of Caregiving Burden on Quality of Life of Caregivers of COPD Patients: The Chain Mediating Role of Social Support and Negative Coping Styles.

Purpose: Caregivers of COPD patients experience various caregiving burden, which is related to their quality of life. We aimed to explicitly explore whether social support and negative coping styles play the chain mediating roles in the relationship between the caregiving burden of caregivers of COPD patients and their health-related quality of life. Methods: We conducted a multicenter cross-sectional survey in four hospitals using a convenience sample. Participants who met the inclusion criteria completed five relevant scales, including a sociodemographic scale. One-way ANOVA and Pearson's method were used to analyze the data accordingly, and chain mediated effect values were estimated by bootstrap method to determine whether the model holds. Results: Among the 201 caregivers who participated in this study, the mean age was 55.94 years, most of them were female (61.2%), the mean caregiving burden score was 52.39 ± 14.65, and the quality of life score was 37.97 ± 3.55. Among them, age, gender, education, relationship with the patient, and the number of chronic diseases were the main factors affecting the quality of life score of the caregivers. According to Pearson results, there was a negative correlation between quality of life and caregiving burden, and negative coping styles. The model result showed that caregiving burden could directly and negatively predict quality of life, and also predict quality of life through the chain mediation of social support and negative coping styles. Conclusion: In China, caregivers of patients with COPD experience severe levels of caregiving burden and low quality of life. The combination of adequate perceived social support and lower negative coping can be effective in alleviating caregiving burden and improving their quality of life. Therefore, healthcare professionals should provide targeted guidance to caregivers with the help of social support and interventions that regulate negative coping styles.

Impact of the COVID-19 pandemic on asthma control among children: a qualitative study from caregivers' perspectives and experiences.

OBJECTIVES: To understand the impact of the COVID-19 epidemic on asthma control in children based on caregivers' perspectives and experiences. DESIGN: This was a qualitative study deploying face-to-face, semistructured interviews. Thematic analysis was carried out to analyse the data. SETTING: Paediatric respiratory clinics in three tertiary hospitals. PARTICIPANTS: 16 caregivers providing unpaid asthma-related care and assistance to children under 14 years who had been diagnosed with asthma for more than 1 year and were not only treated with short-acting ß2-agonists. RESULTS: Six main themes were identified: (1) improved asthma control; (2) decreased willingness to seek medical care driven by fear; (3) increased adherence due to enhanced awareness of asthma control; (4) coping strategies for changes caused by COVID-19; (5) a new opportunity and (6) managing new challenges in asthma control. CONCLUSIONS: The COVID-19 outbreak and the measures in response to it have had significant impacts on asthma control among children. Children with asthma are advised to continue good asthma management, take their prescribed asthma medications as normal, wash their hands regularly and wear face masks. Regularly supported self-management and remote consultations should be provided during the COVID-19 pandemic. In addition, supporting people financially, providing continued medical support and alleviating any fear and anxiety should be considered. We anticipate that our findings will inform health promotion interventions.

High Serum Uric Acid Was a Risk Factor for Incident Asthma: An Open Cohort Study.

BACKGROUND: Several cross-sectional studies have suggested an association between SUA and asthma. However, few studies have investigated this relationship longitudinally. Although SUA is an independent risk factor for chronic kidney disease and cardiovascular diseases, its contribution to incident asthma remains uncertain. OBJECTIVE: To determine whether a high SUA was a risk factor for adult incident asthma. METHODS: By using health care data from the Shandong multicenter health check-up, 76,369 participants, aged 20 to 79 years, were identified who had an SUA determination with a mean follow-up period of 3.73±2.21 years. Multivariate modeling employed Cox proportional hazards models to verify the association between SUA and incident asthma by adjusting age, BMI, smoking habits, drinking habits, and asthma-like diseases. RESULTS: A total of 51,389 individuals were included in the analysis. Cut-off values of SUA able to discriminate asthma status were identified by means of maximally selected rank statistics in the whole participants (≥376.80umol/L), women (≥314.45umol/L), and men (≥376.80umol/L). Multivariate Cox regression analyses adjusted for covariates (age, body mass index (BMI), smoking habit, drinking habit, and asthma-like disease) identified an independent association between SUA and incident asthma in the whole participants (hazard ratio (HR) 2.92, 95% confidence intervals (CI), 1.76-4.48, P=0.00) and men (HR 3.02, 95% CI 1.70-5.39, P=0.00), but not in women. CONCLUSION: The results of the current study confirmed that high SUA was an independent risk factor for incident asthma after adjustment of potential covariates and suggested that a cut-off value related to incident asthma could be identified only in men.

Metabolic Syndrome and Incident Asthma in Chinese Adults: An Open Cohort Study.

BACKGROUND: Although metabolic syndrome is awell-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial. OBJECTIVE: The aim of this study was to explore the associations of metabolic syndrome and its components with incident asthma in Chinese adults. METHODS: We conducted an open cohort study of participants who were asthma-free at baseline (n=42,304) in the Shandong multi-center health check-up longitudinal study from 2004 to 2015. Participants aged ≥20 years and had regular physical examination (once ayear) more than three times during follow-up. RESULTS: Ninety subjects (38 women and 52 men) developed incident asthma over 12 years of follow-up. Our study suggested that metabolic syndrome itself was not significantly associated with incident asthma in either women or men (P>0.050). Interestingly, we found that overweight and/or obesity was arisk factor for incident asthma among women but not men in the Cox proportional hazards model after adjusting covariates (adjusted incidence rate ratio (IRR)= 2.940, 95% confidence interval (CI): 1.467-5.894, P=0.002). The result was consistent with the Poisson regression model (hazard ratio (HR)= 2.241, 95% CI: 1.135-4.988, P=0.026). After stratifying according to overweight and/or obesity, we found that female subjects with overweight and obesity were associated with the occurrence of incident asthma (P<0.050). However, we did not find this result among men. CONCLUSION: Metabolic syndrome was not significantly associated with incident asthma in both women and men; however, overweight and/or obesity was shown to be asignificant risk factor for incident asthma but only in women, not in men.

The prognostic and clinicopathological value of tumor-associated macrophages in patients with colorectal cancer: a systematic review and meta-analysis.

PURPOSE: There is a growing literature on the significance of tumor-associated macrophages (TAMs) in colorectal cancer (CRC). However, the role of TAMs in predicting the prognosis of CRC remains controversial. The current study aims to determine the prognostic and clinicopathological value of different types and distribution of TAMs in CRC. METHODS: A comprehensive literature search of PubMed, Embase, and Cochrane Library databases was conducted from the inception to 1 September 2019. The correlations of TAMs with overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and clinicopathological characteristics were analyzed. RESULTS: A total of 5,575 patients from 29 studies were included in this meta-analysis. The pooled hazard ratios (HRs) indicated that high density of pan-macrophages in tumor invasive margin (IM) was associated with better OS (HR = 0.57, 95%CI = 0.38-0.85), DFS (HR = 0.32, 95%CI = 0.19-0.52), and CSS (HR = 0.56, 95%CI = 0.41-0.77). Moreover, the high density of pan-macrophages in tumor center (TC) was correlated with better DFS (HR = 0.66, 95%CI = 0.45-0.96). However, high expression of M2 macrophages in TC was associated with poor DFS (HR = 2.42, 95%CI = 1.45-4.07) and CSS (HR = 1.74, 95%CI = 1.24-2.44). High M2 macrophages density in IM was also associated with short DFS (HR = 2.81, 95%CI = 1.65-4.77). In addition, the results showed that high density of pan-macrophages in IM was associated with no tumor metastasis, while high M2 macrophages density in TC was correlated with poor tumor differentiation. CONCLUSION: High Pan-TAMs density in IM has a positive effect on the prognosis of CRC patients, while high density M2 macrophage infiltration in TC is a strong indicator of poor prognosis.

SET nuclear proto-oncogene gene expression is associated with microsatellite instability in human colorectal cancer identified by co-expression analysis.

BACKGROUNDS AND AIMS: Microsatellite instability (MSI) is one of the promising biomarkers in human colorectal cancers (CRCs), and it is influenced by an intricate gene interaction network. Hence, we aimed to identify and validate hub genes associated with MSI CRC and to illustrate its underlying mechanisms. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to investigate potential regulatory targets and relationships between key modules and hub genes associated with MSI CRC. RESULTS: In the red module (r = 0.83), SET nuclear proto-oncogene (SET) was selected due to its high intra-modular connectivity and module membership. In the test sets, SET expression was downregulated in MSI CRCs compared to that in microsatellite stability (MSS) CRCs. SET expression level had a good performance in stratifying patients into MSI or MSS CRCs (area under the curve = 0.953). Moreover, the BRAF V600E mutation was highly associated with SET expression, and MSI/HLA- samples showed lower levels of SET mRNA expression than MSS/HLA- samples. Finally, gene set enrichment analysis (GSEA) indicated that patients in the SET low expression group were enriched in base excision repair. CONCLUSION: SET was identified and validated as a novel potential biomarker in MSI CRCs, and SET probably acts through regulating the base excision repair pathway.

Layer Caused an Anisotropic Terahertz Response of a 3D-printed Simulative Shale Core.

Energy demands have motivated the development of shale formations as significant unconventional reservoirs. The anisotropy of shales plays a significant role in both the mechanical behavior and engineering activities. Alternating layers presented in shales affect the propagation of waves, causing anisotropy at various frequencies. Simplifying the complicated interior structures of shales is conducive to characterize the anisotropic properties. Therefore, simulative shale core samples were designed and fabricated using additive manufacturing processes, and layer-caused dielectric anisotropy was investigated by terahertz (THz) time-domain spectroscopy. On the basis of effective medium theory, the change of the optical length caused by refraction of rays was discussed and modeled. It is believed that the refraction of rays at the interfaces is the source of THz propagation anisotropy in the multilayered structure, and the anisotropy degree is mainly influenced by the layer thickness as well as the refractive index.

The Detection of Water Flow in Rectangular Microchannels by Terahertz Time Domain Spectroscopy.

Flow characteristics of water were tested in a rectangular microchannel for Reynolds number (Re) between 0 and 446 by terahertz time domain spectroscopy (THz-TDS). Output THz peak trough intensities and the calculated absorbances of the flow were analyzed theoretically. The results show a rapid change for Re < 250 and a slow change as Re increases, which is caused by the early transition from laminar to transition flow beginning nearly at Re = 250. Then this finding is confirmed in the plot of the flow resistant. Our results demonstrate that the THz-TDS could be a valuable tool to monitor and character the flow performance in microscale structures.

Uniaxial Negative Thermal Expansion and Mechanical Properties of a Zinc-Formate Framework.

The thermal expansion behavior of a metal-formate framework, Zn(HCOO)2·2(H2O) (1), has been systematically studied via variable temperature single-crystal X-ray diffraction. Our results demonstrate that this formate exhibits significant negative thermal expansion (NTE, -26(2) MK-1) along its c-axis. Detailed structural analyses reveal that the large NTE response is attributed to the 'hinge-strut' like framework motion. In addition, the fundamental mechanical properties of framework 1 have been explored via nanoindentation experiments. The measured elastic modulus and hardness properties on the (00-2)/(100)/(110) facets are 35.5/35.0/27.1 and 2.04/1.83/0.47 GPa, respectively. The stiffness and hardness anisotropy can be correlated well with the underlying framework structure, like its thermoelastic behavior.

Discriminating the Mineralogical Composition in Drill Cuttings Based on Absorption Spectra in the Terahertz Range.

Understanding the geological units of a reservoir is essential to the development and management of the resource. In this paper, drill cuttings from several depths from an oilfield were studied using terahertz time domain spectroscopy (THz-TDS). Cluster analysis (CA) and principal component analysis (PCA) were employed to classify and analyze the cuttings. The cuttings were clearly classified based on CA and PCA methods, and the results were in agreement with the lithology. Moreover, calcite and dolomite have stronger absorption of a THz pulse than any other minerals, based on an analysis of the PC1 scores. Quantitative analyses of minor minerals were also realized by building a series of linear and non-linear models between contents and PC2 scores. The results prove THz technology to be a promising means for determining reservoir lithology as well as other properties, which will be a significant supplementary method in oil fields.