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Abstract Background To develop an artificial intelligence (AI)-based model using Radiomics, deep learning (DL) features extracted from 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/Computed Tomography (PET/CT) images of tumor and cervical lymph node with clinical feature for predicting cervical lymph node metastasis (CLNM) in patients with esophageal squamous cell carcinoma (ESCC). Methods The study included 300 ESCC patients from the First Affiliated Hospital of Zhengzhou University who were divided into a training cohort and an internal testing cohort with an 8:2 ratio. Another 111 patients from Shanghai Chest Hospital were included as the external cohort. For each sample, we extracted 428 PET/CT-based Radiomics features from the gross tumor volume (GTV) and cervical lymph node (CLN) delineated layer by layer and 256 PET/CT-based DL features from the maximum cross-section of GTV and CLN images We input these features into seven different machine learning algorithms and ultimately selected logistic regression (LR) as the model classifier. Subsequently, we evaluated seven models (Clinical, Radiomics, Radiomics-Clinical, DL-Clinical, DL-Radiomics, DL-Radiomics-Clinical) using Radiomics features, DL features and clinical feature. Results The DL-Radiomics-Clinical (DRC) model demonstrated higher AUC of 0.955 and 0.916 compared to the other six models in both internal and external testing cohorts respectively. The DRC model achieved the highest accuracy among the seven models in both the internal and external test sets, with scores of 0.951 and 0.892, respectively. Conclusions Through the combination of Radiomics features and DL features from PET/CT imaging and clinical feature, we developed a predictive model exhibiting exceptional classification capabilities. This model can be considered as a non-invasive method for predication of CLNM in patients with ESCC. It might facilitate decision-making regarding to the extend of lymph node dissection, and to select candidates for postoperative adjuvant therapy.

The energy and environmental crisis pose a great challenge to human development in the 21st century. The design and development of clean and renewable energy and the solution for environmental pollution have become a hotspot in the current research. Based on the preparation of transition metal phosphates, transition metals were used as raw materials, Prussian blue-like NiFe(CN)6 as a precursor, which was in situ grown on nickel foam (NF) substrate. After low temperature phosphating treatment, a bimetallic phosphide electrocatalyst (NiFe)2P/NF was prepared on NF substrate. Using 1 mol·L−1 KOH solution as a basic electrolyte, based on the electrochemical workstation of a three-electrode system, the electrochemical catalytic oxygen evolution performance of the material was tested and evaluated. Experiments show that (NiFe)2P/NF catalyst has excellent oxygen evolution performance. In an alkaline medium, the overpotential required to obtain the catalytic current density of 10 mA·cm−2 is only 220 mV, and the Tafel slope is 67 mV·dec−1. This is largely due to: (1) (NiFe)2p/NF nanocatalysts were well dispersed on NF substrates, which increased the number of active sites exposed; (2) the hollow heterostructure of bimetallic phosphates promotes the electron interaction between (NiFe)2P and NF, increased the rate of charge transfer, and the electrical conductivity of the material is improved; and (3) theoretical calculations show that (NiFe)2P/NF hollow heterostructure can effectively reduce the dissociation barrier of water, promote the dissociation of water; furthermore, the kinetic reaction rate of electrocatalytic oxygen evolution is accelerated. Meanwhile, the catalyst still has high activity and high stability in 30 wt% concentrated alkali solution. Therefore, the construction of (NiFe)2P/NF electrocatalysts enriches the application of non-noble metal nanomaterials in the field of oxygen production from electrolytic water.

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Abstract Objectives This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. Methods Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. Result There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P

Abstract Purpose Large B‐cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. Methods The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. Results Twenty‐one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium‐sized blastoid cytology, germinal center B‐cell‐like, and CD5+ phenotype, compared with IRF4− ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4− ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. Conclusion Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy.

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the in vitro activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure–activity relationship, compound 51am was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, 51am exhibited potency against several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in the cell and cell-free systems. It also exhibited a good pharmacokinetic profile in BALB/c mice. Furthermore, the binding mode of 51am with both c-Met and VEGFR-2 provided novel insights for the discovery of selective c-Met inhibitors. Taken together, these results indicate that 51am could be an antitumor candidate meriting further development.

We study the CP-odd and CP-even observables of the B mesons decaying into a baryon and antibaryon. We estimate these observables through the P03 model and chiral selection rule. The decay branching ratio of B+→pΛ‾ is calculated to be (2.31±0.69)×10−7, which is consistent with the current experiments. The effects of the B−B‾ oscillations are considered, which largely suppress the direct CP asymmetries in the Bs0 decays. We suggest the experiments to visit Bs0→Λ(→pπ−)Λ‾(→p‾π+), where the time-averaged CP-odd observables are estimated to be large. The direct CP asymmetries of B+→pΛ‾ and B0→pp‾ are found to be (26.2±7.9)% and (−3.1±0.9)% for a positive strong phase and (−36.9±11.1)% and (4.2±1.3)% for a negative strong phase, respectively.

Abstract Temporal lobe epilepsy (TLE) leads to extensive degradation of the quality of life of patients. Glycyrrhizic acid (GA) has been reported to exert neuroprotective effects on status epilepticus. Herein, the current study set out to explore the functional mechanism of GA in TLE young rats. Firstly, TLE young rat models were established using the lithium chloride and pilocarpine regimen and then subjected to treatment with different doses of GA, miR‐194‐5p‐antagomir, or/and sh‐prostaglandin‐endoperoxide synthase 2 (PTGS2) to observe changes in iron content, glutathione and malondialdehyde levels, and GPX4 (glutathione peroxidase 4) and PTGS2 protein levels in the hippocampus. Neuronal injury and apoptosis were assessed through HE, Nissl, and TUNEL staining. Additionally, the expression patterns of miR‐194‐5p were detected. The binding site of miR‐194‐5p and PTGS2 was verified with a dual‐luciferase assay. Briefly, different doses of GA (20, 40, and 60 mg/kg) reduced the epileptic score, frequency, and duration in TLE young rats, along with reductions in iron content, lipid peroxidation, neuronal injury, and apoptosis in the hippocampus. Silencing of miR‐194‐5p partly annulled the action of GA on inhibiting ferroptosis and attenuating neuronal injury in TLE young rats. Additionally, PTGS2 was validated as a target of miR‐194‐5p. GA inhibited ferroptosis and ameliorated neuronal injury in TLE young rats via the miR‐194‐5p/PTGS2 axis. Overall, our findings indicated that GA exerts protective effects on TLE young rats against neuronal injury by inhibiting ferroptosis through the miR‐194‐5p/PTGS2 axis.

Purpose: This paper aims to investigate the impact of the channel numbers on the performance of B1+ mapping, by using the Bloch-Siegert shift (BSS) method. B1+ mapping plays a crucial role in various brain imaging protocols. Theory and Methods: We simulated the radiofrequency field of the human head model in six groups of multi-channel receive coil with a range of different channel numbers. MR signals were synthesized according to the standard BSS sequence, with quantified Gaussian added. Next, we combined the signals of each channel to reconstruct the B1+ map by weighted averaging and maximum likelihood estimation strategies and evaluate the bias by relative standard deviation of each coil. Results: The simulation results revealed that the accuracy of B1+ maps improved with the increasing of channel numbers, meanwhile the per channel efficiency of B1+maps accuracy gradually decrease. Both trends slowed down when the channel numbers reached 12 or above. Conclusion: Our finding suggests that increasing the channel numbers can improve the accuracy of B1+map. However, a diminishing efficiency of per channel accuracy improvement was overserved, indicating that the relationship between quality of B1+ map and the channel numbers is nonlinear. Based on these findings, our study provides a reference for determining channel numbers to achieve a balance of coil selection and manufacturing cost. It also provides a theoretical basis for evaluating other B1+ mapping techniques.

Dinutuximab (ch14.18) was the first approved monoclonal antibody against the tumor‐associated antigen disialoganglioside GD2. Despite its success in treating neuroblastoma (NB), it triggers a significant amount of neuropathic pain in patients, possibly through complement‐dependent cytotoxicity (CDC). We hypothesized that modifying ch14.18 using antibody engineering techniques, such as humanization, affinity maturation, and Fc engineering, may enable the development of next‐generation GD2‐specific antibodies with reduced neuropathic pain and enhanced antitumor activity. In this study we developed the H3‐16 IgG1m4 antibody from ch14.18 IgG1. H3‐16 IgG1m4 exhibited enhanced binding activity to GD2 molecules and GD2‐positive cell lines as revealed by ELISA, and its cross‐binding activity to other gangliosides was not altered. The CDC activity of H3‐16 IgG1m4 was decreased, and the antibody‐dependent cellular cytotoxicity (ADCC) activity was enhanced. The pain response after H3‐16 IgG1m4 antibody administration was also reduced, as demonstrated using the von Frey test in Sprague–Dawley (SD) rats. In summary, H3‐16 IgG1m4 may have potential as a monoclonal antibody with reduced side effects.

BackgroundCancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression and are known to mediate endocrine and chemotherapy resistance through paracrine signaling. Additionally, they directly influence the expression and growth dependence of ER in Luminal breast cancer (LBC). This study aims to investigate stromal CAF-related factors and develop a CAF-related classifier to predict the prognosis and therapeutic outcomes in LBC.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to obtain mRNA expression and clinical information from 694 and 101 LBC samples, respectively. CAF infiltrations were determined by estimating the proportion of immune and cancer cells (EPIC) method, while stromal scores were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify stromal CAF-related genes. A CAF risk signature was developed through univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. The Spearman test was used to evaluate the correlation between CAF risk score, CAF markers, and CAF infiltrations estimated through EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. The TIDE algorithm was further utilized to assess the response to immunotherapy. Additionally, Gene set enrichment analysis (GSEA) was applied to elucidate the molecular mechanisms underlying the findings.ResultsWe constructed a 5-gene prognostic model consisting of RIN2, THBS1, IL1R1, RAB31, and COL11A1 for CAF. Using the median CAF risk score as the cutoff, we classified LBC patients into high- and low-CAF-risk groups and found that those in the high-risk group had a significantly worse prognosis. Spearman correlation analyses demonstrated a strong positive correlation between the CAF risk score and stromal and CAF infiltrations, with the five model genes showing positive correlations with CAF markers. In addition, the TIDE analysis revealed that high-CAF-risk patients were less likely to respond to immunotherapy. Gene set enrichment analysis (GSEA) identified significant enrichment of ECM receptor interaction, regulation of actin cytoskeleton, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathway gene sets in the high-CAF-risk group patients.ConclusionThe five-gene prognostic CAF signature presented in this study was not only reliable for predicting prognosis in LBC patients, but it was also effective in estimating clinical immunotherapy response. These findings have significant clinical implications, as the signature may guide tailored anti-CAF therapy in combination with immunotherapy for LBC patients.

Objective To analyze differential expression of long non-coding RNA (lncRNA) after miR-150 over-expression by human renal tubular epithelial cell line HK-2 and explore the role of miR-150 in renal tubular injury through regulating the expression of lncRNA. Methods HK-2 cells with miR-150 mimic and scramble were sequenced by Illumina NovaSeq 6000 sequencer. The differentially expressed lncRNA expression profile, GO analysis and KEGG analysis were performed to verify miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway. Results Compared with the scramble group, 362 differential expression lncRNAs were detected in miR-150 mimic group, of which, 252 lncRNAs were down-regulated and 110 lncRNAs were up-regulated both more than 1.5-fold. The results showed that the miR-150 regulated lncRNA and function in biological process, cell components and molecular mechanisms through enrichment analysis of KEGG pathway, miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway was found and then verified by Western blot. Conclusions LncRNAs regulated by miR-150 may play some roles in pathogenesis and molecular mechanisms in human renal tubular injury.

Pre-mRNA processing factor 19 (PRP19) is elevated in hepatocellular carcinoma (HCC); however, little is known about its function in DNA damage repair in HCC. In this study, analysis of The Cancer Genome Atlas data and our tumor models after ionizing radiation (IR) treatment indicated that increased expression of PRP19 was positively correlated with DNA damage repair. Gain of PRP19 expression induced by plasmids resulted in decreases in apoptosis and double-strand breaks (DSBs), and an increase in cell survival after IR. Loss of PRP19 expression induced by small interfering RNAs resulted in the accumulation of apoptosis and DSBs, and a decrease in cell survival. Mechanistically, the effect of PRP19 on DNA damage repair was mediated by the modulation of cyclin D1 expression in HCC. PRP19 controlled the translation of cyclin D1 by modulating eukaryotic initiation factor 4E. PRP19 affected the DNA damage repair ability of cyclin D1 by interacting with the WD40 domain. The combination of PRP19 and cyclin D1 was more valuable than each single marker for predicting the prognosis of patients. Taken together, the present results demonstrate that PRP19 promotes DNA damage repair by modulating cyclin D1 expression and function, thereby contributing to the radioresistance in HCC.

We study the Ξc−Ξc′ mixing effects in the semileptonic decays the doubly charm baryons of Ξcc. We focus on the ratio of R(θc)≡B(Ξcc→Ξc′e+νe)/B(Ξcc→Ξce+νe) and find that (R(θ0),R(−θ0))=(0.46±0.01,7.33±0.23) with θ0=0.137π, which are in sharp contrast to R(0)=2.15±0.11 without the mixing. The ratio is enhanced (suppressed) by a factor of four for a negative (positive) θc. In addition, the polarization asymmetries of Ξc(′) are found to be α(−θ0)=0.32(−0.76) and α(θ0)=−0.82(−0.38). As R and α are highly sensitive to θc and unaffected by the W-exchange contributions, they provide excellent opportunities to determine θc in the ongoing experiments.

We study the ratio of R=2Γ(Ξc0→Ξ−e+νe)/3Γ(Λc+→Λe+νe), which is found to be R=1(0.8) from the exact (broken) SU(3) flavor symmetry, in sharp contrast to the average value of Rav=0.59±0.10 from the ALICE collaboration and lattice QCD results. We propose to use the mixing of Ξc−Ξc′ to resolve the puzzle. From the mass spectra, we find that the mixing angle is |θc|=0.137(5)π, which suppresses Ξc→Ξe+νe about 20% model-independently, resulting in R≈0.6 with the SU(3) flavor breaking effect. We explicitly demonstrate that R=0.70±0.09 from the bag model, which is also consistent with Rav. To test the mixing mechanism, we recommend the experiments to measure the decays of Ξc→Ξ′(1530)e+νe, whose branching fractions are determined to be (4.4∼8.7)×10−3 and (1.3∼2.6)% for Ξc0 and Ξc+, respectively, but vanish without the mixing. In addition, nonvanishing values of B(Ξc+→Ξ′0(1530)π+) and B(Ξc+→Σ′+(1385)K‾0) will also be evidences of the mixing based on the Körner-Pati-Woo theorem, which are calculated as (3.8∼7.5)×10−3 and (6.6∼13)×10−4, respectively. We emphasize that θc is sizable and should be given serious considerations in future studies on the heavy baryon systems.

Diabetes mellitus is an independent risk factor for ischemic stroke. Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes. Stellate ganglion block can effectively regulate the inflammatory response. Therefore, it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects. In this study, we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks. The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats. Subsequently, we performed left stellate ganglion block with 1% lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion. Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content. It also improved the recovery of neurological function, increased 28-day survival rate, inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats. However, injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block, whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect. We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke. These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway. We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.

IntroductionThe effect of liver margin on colorectal cancer liver metastases (CRLM) after hepatectomy has been controversial. In this study, we conducted a postoperative follow-up study of 205 patients with CRLM to clarify whether a positive margin is significant and to define the risk factors affecting CRLM survival.MethodsThe data of 205 patients with CRLM who underwent surgical treatment at the Third Hospital of Peking University in the Department of General Surgery from January 2009 to December 2020 were retrospectively analyzed. The general data, surgical data and postoperative follow-up of the patients were statistically analyzed.ResultsThere were 130 cases (63.4%) of R0 resection and 75 cases (36.6%) of R1 resection. There were 136 males and 69 females, age 61 ± 11 years, and body mass index (BMI 24.5 ± 3.3 kg/m2). The overall survival rates at 1, 3, and 5 years for the entire cohort were 93.4%, 68.4%, and 45.5% in the R0 resection group vs. 93.2%, 53.7%, and 42% in the R1 resection group, respectively, which were not statistically significant (P = 0.520). The 1-, 3-, and 5-year disease-free survival rates of 63.2%, 33.3%, and 29.7% were significantly better in the R0 resection group than in the R1 resection group of 47.9%, 22.7%, and 17.7% (P = 0.016), respectively. After multivariable analysis, carbohydrate antigen 19-9 (CA19-9) > 39 U/ml (HR = 2.29, 95% CI: 1.39–3.79, P = 0.001), primary tumor perineural invasion (HR = 1.78, 95% CI: 1.01–3.13, P = 0.047), and BMI > 24 kg/m2 (HR = 1.75, 95% CI: 1.05–2.93, P = 0.033) were independently associated with poorer overall patient survival. The number of liver metastases >2 (HR = 1.65, 95% CI: 1.10–2.47, P = 0.016), the maximum diameter of metastases ≥50 mm (HR = 1.67, 95% CI: 1.06–2.64, P = 0.026), and vascular invasion of the primary tumor (HR = 1.65, 95% CI: 1.03–2.64, P = 0.038) were also independently associated with poorer disease-free survival.ConclusionIn patients undergoing hepatectomy for CRLM, the negative effect of the R1 margin should be downplayed, and although the disease-free survival of the R1 margin is shorter than that of the R0 margin, it has no impact on overall survival. To improve overall survival, extra attention should be given to the factors of preoperative BMI, preoperative CA19-9, and the presence of perineural invasion of the primary tumor.

We study CP violation in b-baryon decays of Ξb−→Ξ−D with D=D0,D¯0 and Di(i=1,2). We find that these baryonic decay processes provide an ideal opportunity to measure the weak phase due to the absence of the relative strong phase. Explicitly, we relate ρ¯ and η¯ the CKM elements with the decay rate ratios of Ri=Γ(Ξb−→Ξ−Di)/Γ(Ξb−→Ξ−D0) without the charge conjugate states. As a complementary, we also examine the decay distributions of Λb→Λ(→pπ−)D. There are in total 32 decay observables, which can be parameterized by 9 real parameters, allowing the experiments to extract the angle γ≡arg⁡(−VudVub⁎/VcdVcb⁎) in the CKM unitarity triangle. In addition, the feasibilities of the experimental measurements are discussed. We find that ρ¯ and η¯ can be extracted at LHCb Run3 from Ξb−→Ξ−D, and a full analysis of Λb→Λ(→pπ−)D is available at LHCb Run4.

AIM: To study the effect of miR-26b on lens epithelial cells induced by transforming growth factor beta (TGF-β) 2 and the underlying signaling pathways. METHODS: Human lens epithelial cell line B-3 (HLE-B3) was incubated with TGF-β2 (5 ng/mL) and then transfected with miR-26b mimics. The expression of miR-26b was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), while 5'-bromodeoxyuridine (BrdU) and wound-healing assays were used to measure the growth and migration of HLE-B3 cells, respectively. The expression of epithelial-mesenchymal transition (EMT) markers and the activity of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway were measured by Western blotting assay and immunofluorescence staining. Electron microscopy was also used to observe cellular morphology. RESULTS: The expression levels of miR-26b were significantly reduced in human posterior capsular opacification-attached lens tissue and TGF-β2-stimulated HLE-B3 cells. In the presence of TGF-β2, the growth, migration, and EMT of HLE-B3 cells were distinctly enhanced; these effects were attenuated by the administration of miR-26b mimics. Furthermore, the overexpression of miR-26b significantly reduced upregulation of the PI3K/Akt pathway when stimulated by TGF-β2 in HLE-B3 cells. Moreover, the addition of an activator (740 Y-P) led to the upregulation of the PI3K/Akt pathway and abolished the protective effect of miR-26b on the HLE-B3 cells that was mediated by TGF-β2. CONCLUSION: The miR-26b suppresses TGF-β2-induced growth, migration, and EMT in HLE-B3 cells by regulating the PI3K/Akt signaling pathway.

With the rapid development of tourism and the Internet industry, tourism activities have increasingly become a fashion behavior of people. The role of intelligent tourism resources in tourism activities has gradually become prominent. In order to meet the needs of all kinds of users, the tourism management system services are developing in the direction of diversification and individualization, and recommending the tourism resource products that best meet the needs of users to users has become a top priority. This article aims to improve the practical value of the system through the intelligent functions of the tourism management system based on information security in the intelligent recommendation of tourism resources. The tourism management system can display the received information about tourists. Through the experimental research of the accompanying information security algorithm and the analysis of the recommendation of the tourism system, the intelligent functions of the tourism management system based on information security can be captured in the intelligent recommendation of tourism resources. Develop the tourism management system to solve efficiency problems and realize tourism management information. Experimental results show that based on information security, 80% of tourists have become a popular choice for smart recommendation countries, which will bring more convenience to tourists during the game.

Abstract Background To investigate the renal dysfunction in patients with hyperuricemia by employing a multiparametric MRI protocol, consisting of quantitative water molecule diffusion, microstructure, microscopic perfusion, and oxygenation measurements in kidneys. Materials and methods A total of 48 patients with hyperuricemia (HU) and 22 age-matched healthy control subjects (HC) were enrolled in the study. For each participant, three different functional magnetic resonance imaging (fMRI) sequences were acquired and analyzed, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and blood-oxygen-level-dependent MRI (BOLD). Thereafter, an independent two-sample t-test was applied to discover the significant differences of MRI indices between the hyperuricemia (HU) and HC groups, and the specific potential biomarkers between two subgroups of HU group (asymptomatic hyperuricemia group (AH) and gouty arthritis group (GA)). Further, multivariate logistic regression analyses were performed to classify the AH from the GA group using the MRI indices with significant between-group differences. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated to assess the performance of each MR index for differentiation between the AH and GA groups. Results Ten parametric values of the HU group were significantly lower than those of the HC group among the 14 fMRI parameters (P

Abstract Background Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. Methods TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. Results We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. Conclusions Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan–Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8+ T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

Aiming at the problem of how edge computing and Content Delivery Network (CDN) edge nodes implementing the resource coordination, the technology and method of CDN cache software adapting to virtual machines and containers are proposed. By comparing and analyzing the performance test data of CDN in three deployment modes of physical machine, container and virtual machine, the performance loss caused by CDN virtualization is evaluated. The performance loss of the container mode is small, and its performance is comparable to the physical machine. The performance loss of the virtual machine mode is large, and its performance is equivalent to about 75%of the physical machine. According to the nominal value of performance, the virtualized CDN edge node can release most of the central processing unit, memory and disk resources, and achieve resource sharing with edge computing.

The author presents the design and development of vibration performance detection and analysis system for commercial vehicles based on the theory of mechanical vibration performance testing and analysis theory, vibration signal acquisition and time domain analysis theory and Fourier transform principle.. The system performs the functions of data acquisition, signal analysis, spectrogram display, data storage, control output and time domain and frequency domain. Further, this system is used to test the vibration of commercial vehicles on the road to verify the integrity and reliability of the system function. The results of the experiments show that all functions of the system achieved the system design goals, and moreover, it shows that the system has strong practicability and high economy.

The periods of flower bud differentiation and fruit growth for Camellia oleifera overlap greatly affect the allocation of photoassimilates to flower buds and fruit, resulting in obvious alternate bearing. To export the cause and mitigate alternate bearing of Camellia oleifera, the allocation of photoassimilates to buds and fruit supplied by leaves at different node positions was studied by the addition of labeled 13CO2 during the slow fruit growth stage. The fate of 13C photoassimilated carbon was followed during four periods: slow fruit growth (4 hours and 10 days after 13C labeling); rapid growth (63 days after 13C labeling); oil conversion (129 days after 13C labeling); and maturation (159 days after 13C labeling). Photosynthetic parameters and leaf areas of the leaves shared a common pattern (fifth > third > first), and the order of photosynthetic parameters of different fruit growth stages was as follows: oil conversion > maturation > rapid growth > slow growth. The most intense competition between flower bud differentiation and fruit growth occurred during the oil conversion stage. Dry matter accumulation in different sinks occurred as follow: fruit > flower bud > leaf bud. Photoassimilates from the labeled first leaf were mainly translocated to the first flower bud, and the upper buds were always differentiated into flower buds. The photoassimilates from the labeled third leaf were distributed disproportionately to the third flower bud and fruit. They distributed more to the third flower bud, and the middle buds formed either flower or leaf buds. However, the photoassimilates from the labeled fifth leaf were primarily allocated to the fruit that bore on the first node of last year’s bearing shoot, and basal buds did not form flower buds. Based on our results, the basal leaves should be retained for a high yield in the current year, and the top leaves should be retained for a high yield in the following year. Our results have important implications for understanding the management of flower and fruit in C. oleifera. The thinning of fruit during the on-crop year can promote flower bud formation and increase the yield of C. oleifera crops in the following year. During the off-year, more fruit should be retained to maintain the fruit yield. The thinning of middle-upper buds could promote more photoassimilates allocate to the fruit.

Metallic clusters have received tremendous interest due to the unusual structure and bonding along with potential as the motif for novel nanomaterials. Herein, the global minimum structures of neutral and anionic Mgn0/− and CaMgn0/− (n = 2–15) clusters have been searched by utilizing the CALYPSO program with subsequent DFT calculations. For each cluster size, a large number of stable structures were converged, and then, the most stable ones were identified in light of the PES spectra and total energies. The results show that the most stable structures transform from planar to three-dimensional geometry at n = 3 and the hollow framework at n = 8, then to filled cage-like structure at n = 13. For all CaMgn0/− clusters, the Ca atom prefers to occupy the external capped site. The simulated PES, IR, and Raman spectra could provide additional ways to identify the structure of these clusters in the following experiments. In the range of studied size, a tower-like CaMg9 cluster is uncovered and proved to be a magic number cluster with superior stability. Analysis of charge transfer, molecular orbitals, multi-center bonds, and ELF reveals that the CaMg9 has 20 valence electrons of closed-shell 1S21P61D102S2 and more strong Ca-Mg bonds caused by spd hybridization.

Marine-derived microorganisms possess the unique metabolic pathways to produce structurally novel secondary metabolites with potent biological activities. In this study, bioactivity-guided isolation of the marine deep-sea-derived fungus Aspergillus flavipes DS720 led to the characterization of four indole alkaloids (compounds 1–4) and four polyketides (compounds 5–8), such as two new indoles, flavonoids A (1) and B (2) with a C-6 reversed prenylation, and a new azaphilone, flaviazaphilone A (5). Their chemical structures were unambiguously established by an extensive interpretation of spectroscopic data, such as 1D/2D NMR and HRESIMS data. The absolute configurations of the new compound 5 were solved by comparing the experimental and calculated Electronic Circular Dichroism (ECD) spectra. Since sufficient amount of flavonoids A (1) was obtained, 1 was subjected to a large-scale cytotoxic activity screening against 20 different human tumor cell lines. The results revealed that 1 showed broad-spectrum cytotoxicities against HeLa, 5637, CAL-62, PATU8988T, A-375, and A-673 cell lines, with the inhibition rates of more than 90%. This study indicated that the newly discovered indole alkaloid 1 may possess certain potential for the development of lead compounds in the future.

BackgroundCholecystitis with incarcerated gallstones (CIG) is a type of acute abdomen in the field of hepatobiliary surgery. Whether gallbladder-preserving surgery (GPS) can be performed to treat it, however, depends on the improvement of gallbladder contractile function. The present study aimed to investigate the changes in gallbladder contractile function and its influencing factors after minimally invasive GPS for CIG.MethodsA total of 95 patients with CIG treated in the Aerospace Center Hospital between May 2017 and May 2019 were enrolled as the study subjects. All patients received minimally invasive GPS. The patients' operation-related conditions (including stone removal success rate, duration of surgery, intraoperative blood loss, etc.), changes in gallbladder contractile function, and influencing factors of GPS were analyzed.ResultsAmong the 95 patients included in the study, the success rate of stone removal was 100%, the duration of surgery was 76.0 ± 26.5 min, and the intraoperative blood loss was 10.17 ± 4.43 ml. The rate of good gallbladder contractile function at one and two years after surgery was significantly higher than before surgery (P

ObjectiveDelayed enhancement cardiac CT is a reliable tool for the diagnosis of left atrial appendage thrombus but limited for scanning heterogeneity. We aimed to explore the improvement of the 1 and 3-min delay phase at the diagnostic level to detect left atrial appendage thrombus, in order to set up a reasonable CT scanning scheme.Materials and MethodsA total of 6,524 patients were continuously retrieved from January 2015 to September 2020 retrospectively. The patients had undergone Transesophageal echocardiography (TEE) and cardiac CT with complete period include the arterial enhancement phase, 1 and 3-min delay phase, TEE were used as the reference standard. The final study included 329 patients. Three experienced radiologists independently assessed each phase of the cardiac CT images for thrombus diagnosis. We explored the improvement of the diagnostic ability of different delayed contrast-enhanced phases for left atrial appendage thrombus detection. Multiple logistic regression analysis were used for further high-risk stratification to avoid an additional 1-min delayed scan.ResultsIn total, 29 thrombosis were detected at TEE. For all cardiac CT phases, sensitivity and negative predictive were 100%. The specificity were 0.54, 0.93, and 1.00, respectively; The positive predictive values (PPV) were 0.17, 0.57, and 1.00, respectively; Area under curve (AUC) were 0.75, 0.95, and 0.98, respectively. High risk factors that cannot be clearly diagnosed with 1-min delay phase included reduced cardiac function, increased CHA2DS2-VAScscore and left atrial enlargement. Compared with the arterial enhanced phase, increased radiation doses in the 1 and 3-min delay phases were 1.7 ± 1.3 msv and 1.5 ± 0.8 msv (mean ± standard deviation).ConclusionUsing TEE as the reference standard, early contrast-enhanced CT scanning with 1 and 3-min delay is necessary for the diagnosis of left appendage thrombus, which could significantly improve the diagnostic efficiency. Patients with high-risk stratification are suitable for direct 3-min delayed scanning.

We consider the thermodynamics of the Einstein-power-Yang–Mills AdS black holes in the context of the gauge-gravity duality. Under this framework, Newton’s gravitational constant and the cosmological constant are varied in the system. We rewrite the thermodynamic first law in a more extended form containing both the pressure and the central charge of the dual conformal field theory, i.e., the restricted phase transition formula. A novel phenomena arises: the dual quantity of pressure is the effective volume, not the geometric one. That leads to a new behavior of the Van de Waals-like phase transition for this system with the fixed central charge: the supercritical phase transition. From the Ehrenfest’s scheme perspective, we check out the second-order phase transition of the EPYM AdS black hole. Furthermore the effect of the non-linear Yang–Mills parameter on these thermodynamic properties is also investigated.

Aging is becoming a severe social phenomenon globally, and the improvements in health care and increased health awareness among the elderly have led to a dramatic increase in the number of surgical procedures. Because of the degenerative changes in the brain structure and function in the elderly, the incidence of perioperative neurocognitive disorders (PND) is much higher in elderly patients than in young people following anesthesia/surgery. PND is attracting more and more attention, though the exact mechanisms remain unknown. A growing body of evidence has shown that the gut microbiota is likely involved. Recent studies have indicated that the gut microbiota may affect postoperative cognitive function via the gut-brain axis. Nonetheless, understanding of the mechanistic associations between the gut microbiota and the brain during PND progression remains very limited. In this review, we begin by providing an overview of the latest progress concerning the gut-brain axis and PND, and then we summarize the influence of perioperative factors on the gut microbiota. Next, we review the literature on the relationship between gut microbiota and PND and discuss how gut microbiota affects cognitive function during the perioperative period. Finally, we explore effective early interventions for PND to provide new ideas for related clinical research.

Background: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. Methods: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. Findings: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. Interpretation: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC. Keywords: microRNA-134, PLXNA1, MAPK signalling pathway, Esophageal squamous cell carcinoma, Proliferation, Apoptosis, Lymph node metastasis

Recent studies have demonstrated the benefits of metformin on patients with lymphomas. B-cell receptor (BCR)-PI3K-AKT pathway-dependent cholesterol synthesis may represent a positive feedback mechanism responsible for the pathogenesis of BCR-dependent diffuse large B-cell lymphomas (DLBCLs). Thus, restriction of lipid synthesis would affect the integrity of lipid-forming membranes and block the BCR signaling pathway. Our in vitro findings suggested that the blocking effect of metformin on BCR signaling pathway is possibly exerted via blocking the biosynthesis of cholesterol. A retrospective case-control study was subsequently conducted on type II diabetic patients with DLBCL who were on metformin. Metformin was identified to be associated with improved response rate and PFS in diabetic patients and appeared to be an effective therapeutic drug against DLBCL.

Objective This study aimed to evaluate the joint monitoring of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in vertebral canal decompression surgery for acute spinal cord injury. Methods Twenty-four patients, who were admitted to the hospital for the surgical treatment of spinal cord injury with SEP and MEP monitoring, were assigned to the intraoperative monitoring group (group I). In addition, 24 patients who were admitted to the hospital for the surgical treatment of spinal cord injury without SEP or MEP monitoring were assigned to the control group (group C). Results In group I, there were significant changes before and after decompression surgery in the P40 latency and amplitude, and in the latency of MEP in the abductor hallucis brevis (AHB), in patients with improved spinal nerve function following surgery. In contrast, there were no significant differences in the P40 latency or amplitude, or the latency of MEP in the AHB, in patients who showed no improvement after surgery. Conclusion In vertebral canal decompression surgery for acute spinal cord injury, the application of joint MEP and SEP monitoring can timely reflect changes in spinal cord function.

The well-established cell-of-origin (COO) algorithm categorizes diffuse large B-cell lymphoma (DLBCL) into activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subgroups through gene expression profiling. We aimed to develop and validate a qPCR-based gene expression assay to determine the COO subgroups of DLBCL with formalin-fixed paraffin-embedded (FFPE) tissue. We first established a DLBCL transcriptome database of 1,016 samples retrieved from three published datasets (GSE10846, GSE22470, and GSE31312). With this database, we identified a qPCR-based 32-gene expression signature (DLBCL-COO assay) that is significantly associated with the COO subgroups. The DLBCL-COO assay was further validated in a cohort of 160 Chinese DLBCL patients. Biopsy samples from DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO subtypes based on the immunohistochemistry (IHC) algorithm (Han's algorithm), DLBCL-COO assay, and global gene expression profiling with RNA-seq. For 111 paired FFPE and fresh DLBCL samples, the concordance between the IHC, qPCR, and RNA-seq methods was 77.5% and 91.9%, respectively. The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the “gold standard” RNA-seq compared with the IHC assignment with Han's algorithm (P = 0.005). Furthermore, the overall survival of GCB patients defined by the DLBCL-COO assay was significantly superior to that of ABC patients (P = 0.023). This effect was not seen when the tumors were classified by the IHC algorithm. The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These findings demonstrated that the DLBCL-COO assay might serve as a useful tool for guiding prognostic and therapeutic options for DLBCL patients.

The main goal of spinal cord rehabilitation is to restore walking ability and improve walking quality after spinal cord injury (SCI). The spatiotemporal parameters of walking and the parameters of plantar pressure can be obtained using a plantar pressure analysis system. Previous studies have reported step asymmetry in patients with bilateral SCI. However, the asymmetry of other parameters in patients with SCI has not been reported. This was a prospective, cross-sectional study, which included 23 patients with SCI, aged 48.1 ± 14.5 years, and 28 healthy subjects, aged 47.1 ± 9.8 years. All subjects underwent bare foot walking on a plantar pressure measurement device to measure walking speed and spatiotemporal parameters. Compared with healthy subjects, SCI patients had slower walking speed, longer stride time and stance time, larger stance phase percentage, and shorter stride length. The peak pressures under the metatarsal heads and toe were lower in SCI patients than in healthy subjects. In the heel, regional impulse and the contact area percentage in SCI patients were higher than those in healthy subjects. The symmetry indexes of stance time, step length, maximum force, impulse and contact area were increased in SCI patients, indicating a decline in symmetry. The results confirm that the gait quality, including spatiotemporal variables and plantar pressure parameters, and symmetry index were lower in SCI patients compared with healthy subjects. Plantar pressure parameters and symmetry index could be sensitive quantitative parameters to improve gait quality of SCI patients. The protocols were approved by the Clinical Research Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2015PS54J) on August 13, 2015. This trial was registered in the ISRCTN Registry (ISRCTN42544587) on August 22, 2018. Protocol version: 1.0.

Abstract Background Circular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown. Methods High-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines. Results Totally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis. Conclusions In conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.

The drying curves, moisture effective diffusivity and drying activation energy of winter jujube slices were here investigated at different drying temperatures (55, 60, 65, 70, 75, and 80°C), wind speeds (6, 7, 8, 9, and 10 m/s) and pulsation rates (rotatational speed of material disk: 4, 5.5, and 7 rpm) in a single-factor experiment design. A mathematical model of pulsed air-jet impingement drying for winter jujube slices was fitted and verified. The results showed that the entire drying process could be described as falling rate drying; the moisture effective diffusivity was in the range 1.52-4.93 × 10-9 m2/s and increased with increasing drying temperature, wind speed and pulsation rate. The drying activation energy was 43.9 kJ/mol as determined using the Arrhenius equation. According to the statistical parameters of the correlation coefficient (R2), root mean square error (RMSE) and the sum of squared errors (SSE), the modified Page model was selected as best for representing the correlation between moisture ratio and drying time.

Abstract It has been found that the zero mode of a five-dimensional Elko spinor could be localized on branes by introducing a Yukawa-type coupling between the Elko spinor and the background scalar field or the Ricci scalar. However, the Yukawa-type coupling is not appropriate for all brane models. In this paper, we explore other localization mechanism for the Elko spinor by introducing the non-minimal coupling $$f(\phi )\mathfrak {L}_{Elko}$$ f(ϕ)LElko between the five-dimensional Elko spinor and the background scalar field. We give the general expressions of the Elko zero mode and the function $$f(\phi )$$ f(ϕ) . Through two thick brane models and three concrete examples, we show that the Elko zero mode can be localized on the branes by this new mechanism. This provides us more possibilities of localizing the Elko zero mode.

Vanadium-titanium magnetite is one of the important raw materials for iron making in a blast furnace. Ca3TiFe2O8, which is a mineral of vanadium-titanium sinter, was discovered to form during the process; however, its formation mechanism is not clear. In this work, an X-ray diffraction analysis, an elemental spectroscopy, and a TG-DSC were employed to investigate the formation mechanism of Ca3TiFe2O8 and the formation law at different temperatures and at CaO and TiO2 contents in the CaO-TiO2 -Fe2O3 system. The formation mechanism of Ca3TiFe2O8 is clarified:CaO reacts with Fe2O3 to form Ca2 Fe2O5, and then continues to react with the CaTiO3 to form Ca3TiFe2O8. The longer the reaction time, the greater is the amount of Ca3TiFe2O8 formed. However, the effect of temperature on the formation of Ca3TiFe2O8 is not obvious. It is found that high CaO content contributes to the formation of Ca3TiFe2O8. Further, so long as TiO2 is present, Ca3TiFe2O8 is formed under the condition of equal molar concentration Fe2O3 and CaO.

Background: B cells can function as antigen-presenting cells by presenting antigens captured by the B-cell receptor (BCR) on Class II Major Histocompatibility Complex (MHC II) to T cells. In addition, B-cells can also maintain immune homeostasis by expressing PD-L1 and suppressing T-cell activity. Epstein-Barr virus (EBV) infection can disrupt B-cell function and lead to B cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Here we show that EBV-positive DLBCL (EBV+ DLBCL) has decreased expression of BCR and MHC II, but over-expressed PD-L1, which may lead to immune evasion. Methods: An EBV+ DLBCL cohort (n = 30) and an EBV- DLBCL control cohort (n = 83) were established. Immunostaining of PD-L1, MHC II, MHC II Transactivator (CIITA) and pBTK was performed on automated stainer. H-score was used to denote the results of staining of PD-L1 and pBTK. Break apart and deletion of CIITA locus was studied by fluorescent in situ hybridization. Surface immunoglobulin mean fluorescent insensitivity (MFI) was detected by flow cytometry to demonstrate the level BCR. Results: EBV+ DLBCL showed significantly lower expression of CIITA and MHC II compared to EBV- DLBCL. Genetic aberrations involving CIITA were also more common in EBV+ DLBCL, with 23% break apart events and 6% deletion events, comparted to 2% break apart and 0% deletion in EBV- DLBCL. In addition to the loss of antigen presentation molecule, the antigen capture receptor, BCR, was also down-regulated in EBV+ DLBCL. Accordingly, BCR signaling was also significantly decreased in EBV+ DLBCL as denoted by the respective pBTK levels. Conclusions: EBV+ DLBCL shows over expression of the T-cell inhibitory ligand, PD-L1. Antigen capture and presentation system were disrupted, and T-cell inhibitory molecule was hijacked in EBV+ DLBCL, which may contribute to immune escape in this high risk disease. Therapies targeting these aberrations may improve the outcome of patients with EBV+ DLBCL.

Renal fibrosis is glomerulosclerosis and renal tubulointerstitial fibrosis caused by the increase of interstitial cells and intercellular substances and the accumulation of extracellular matrix, and is a common pathological manifestation of renal disease progressing to end-stage renal failure. It has proved that Astragalus polysaccharide (AP) has curative effect on renal disease; however, its therapeutic mechanism on renal fibrosis is still unclear. Metabolomics approach provides an opportunity to identify novel molecular biomarkers. The purpose of this study is to study the changes of serum metabolic profile of rats with unilateral tubal ligation and replication of renal fibrosis model and the therapeutic effect of AP on it. The blood samples of rats in the control group, renal fibrosis model group, and AP treatment group collected on the 21st day were analyzed by metabolomics method based on UPLC-Q-TOF-MS. Principal component analysis (PCA) showed that clustering was obvious and significantly separated, and paired partial least squares discriminant analysis (OPLS-DA) was used for further analysis. Combined with the network databases such as HMDB and KEGG and a large number of literatures, 32 potential biomarkers related to renal fibrosis were preliminarily screened out and further verified by MS/MS secondary debris information. After pretreatment with AP, 20 biomarkers were significantly regulated, and correlated with phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, etc. It also revealed the metabolic changes of renal fibrosis and intervention effect of AP. These data uncover a link between metabolism and the molecular mechanism with potential implications in the understanding of the intervention effect of AP. Conclusively, UPLC-Q-TOF-MS–based metabolomics can be valuable and promising strategy to understand the disease mechanism and natural drug pretreatment.

Objective: The present study aimed to evaluate the prognostic value of Acute Physiology and Chronic Health Evaluation (APACHE; II and III), Chinese Stroke Scale (CSS), National Institutes of Health Stroke Score (NIHSS), activities of daily living (ADL) (Barthel index, BI), and Glasgow Coma Scale (GCS) scores for stroke patients.Methods: A total of 352 stroke patients were evaluated using APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores within 24 h after admission. And these patients were consecutive admissions to the hospital. The endpoint was in-hospital death. The scores of these scales were compared between the survival group and death group, and the receiver operating characteristic (ROC) curves were drawn. The ability of each scoring system to predict the prognosis of patients was evaluated using the area under the ROC curve, and the areas under the curves (AUCs) of these six scales were compared.Results: The AUCs of the APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores were 0.882, 0.867, 0.832, 0.859, 0.838, and 0.819, respectively.Conclusion: APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores have good predictive values in the prognosis of stroke patients. APACHE II is superior among the other five scales.

Although lipopolysaccharides (LPS) have been used to establish animal models of memory loss akin to what is observed in Alzheimer’s disease (AD), the exact mechanisms involved have not been substantiated. In this study, we established an animal model of learning and memory impairment induced by LPS and explored the biological processes and pathways involved. Mice were continuously intraperitoneally injected with LPS for 7 days. Learning- and memory-related behavioral performance and the pathological processes involved were assessed using the Morris water maze test and immunostaining, respectively. We detected comprehensive expression of C1q, C3, microglia, and their regulatory cytokines in the hippocampus. After 7 days of LPS administration, we were able to observe LPS-induced learning and memory impairment in the mice, which was attributed to neural impairment and synapse loss in the hippocampus. We elucidated that the immune system was activated, with the classical complement pathway and microglial phagocytosis being involved in the synapse loss. This study demonstrates that an LPS-injected mouse can serve as an early memory impairment model for studies on anti-AD drugs.