The performance of a post-induction fentanyl-test in predicting postoperative respiratory adverse events in children after adenotonsillectomy.

STUDY OBJECTIVES: Postoperative respiratory adverse events (PRAE) occurred more frequently in children having adenotonsillectomy than the general surgical population, and can require escalation of care. This study aims to assess the usefulness of post-induction fentanyl-test to predict PRAE in children with obstructive sleep apnea (OSA) after adenotonsillectomy. METHODS: Two hundred and forty patients with OSA undergoing adenotonsillectomy were included in this study. The oxygen saturation during sleep was monitored the night before adenotonsillectomy. Fentanyl-test was conducted under spontaneous breath after anesthesia induction with sevoflurane. Fentanyl-induced reduction in respiratory rate (FRR) was defined as the percentage of reduction in respiratory rate after 1 mcg/kg fentanyl administration. PRAE in the post-anesthesia care unit (PACU) included both respiratory complications and medical interventions. Receiver operating characteristic (ROC) analysis was used to assess the usefulness of fentanyl-test in predicting PRAE. RESULTS: Of the 240 children undergoing elective adenotonsillectomy, 38 children (16%) experienced PRAE in PACU. The areas under ROC curve for FRR and Nadir SpO2 were 0.756 and 0.692, respectively. FRR greater than 53% best predicted PRAE in PACU, with a sensitivity of 68% and a specificity of 72%. Patients with FRR > 53% exhibited a significantly longer duration of desaturation requiring supplementary oxygen than those with FRR ≦ 53% (p < 0.001). CONCLUSIONS: We suggest that post-induction fentanyl-test is a feasible evaluation for children undergoing adenotonsillectomy to predict early PRAE, especially for those who have not undergone polysomnography. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Effects of Individualized Opioid Analgesia Versus Conventional Opioid Analgesia After Adenotonsillectomy in Children; URL: https://clinicaltrials.gov/study/NCT04527393; Identifier: NCT04527393.

Clinical and Diagnostic Features of West Nile Virus Neuroinvasive Disease in New York City.

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting.

Theoretical study of the synergic relationships between the design parameters in energy-saving building design.

With the rapid development of the economy, people have increasingly higher requirements for the comfort of living spaces, and the result is the sharp increase in building energy consumption. Several design parameters influence living space comfort and building energy efficiency. Since the same design standard can include different design parameter combinations, synergic relationships may exist between these criteria for one case. Identifying these synergic relationships requires an inverse problem approach. This paper established a model by combining an improved genetic algorithm (IGA) and numerical calculation to determine the synergic design parameter relationships (e.g. the thermophysical building material properties and energy-saving factors). For [Formula: see text], the shading coefficient significantly influenced the linear function between the thermal conductivity and insulation thickness. In this case, the insulation thickness was exponentially related to the shading coefficient, while the thermal conductivity of the insulation material significantly impacted the synergic relationship. For [Formula: see text], the insulation thickness was a segmented function of the shading coefficient. The results verified that the proposed model was efficient and reliable for identifying the synergic relationships between energy-saving parameters. In engineering applications, designers can select the optimal design parameter combination based on the relationship curve between the parameters in this paper according to the local market conditions and specific design requirements.

Identification of End-Binding 1 Protein as Novel α-4 Giardin-Binding Partners in Giardia lamblia Trophozoites.

BACKGROUND: Giardia lamblia (syn. G. intestinalis, G. duodenalis) is a primitive opportunistic protozoon, and one of the earliest differentiated eukaryotes. Despite its primitive nature, G. lamblia has a sophisticated cytoskeleton system, which is closely related to its proliferation and pathogenicity. Meanwhile, α giardin is a G. lamblia-specific cytoskeleton protein, which belongs to the annexin superfamily. Interestingly, G. lamblia has 21 annexin-like α giardins, i.e., more than higher eukaryotes. The functional differences among α giardin members are not fully understood. METHODS: We took α-4 giardin, a member of α giardin family, as a research object. A morpholino-mediated knockdown experiment was performed to identify the effect of α-4 giardin on G. lamblia trophozoites biological traits. A yeast two-hybrid cDNA library of G. lamblia strain C2 trophozoites was screened for interaction partners of α-4 giardin. Co-immunoprecipitation and fluorescent colocalization confirmed the relationship between G. lamblia EB1 (gEB1) and α-4 giardin. RESULTS: α-4 Giardin could inhibit the proliferation and adhesion of G. lamblia trophozoites. In addition, it interacted with G. lamblia EB1 (gEB1). CONCLUSIONS: α-4 Giardin was involved in proliferation and adhesion in G. lamblia trophozoites, and EB1, a crucial roles in mitosis, was an interacting partner of α-4 giardin.

Application effect of diversified health-promoting models on rehabilitation exercises for cervical spondylotic myelopathy.

BACKGROUND: With improving living standards, the incidence of cervical spondylotic myelopathy (CSM) has become increasingly high. OBJECTIVE: The study aims to explore the effect of diversified health-promoting models on rehabilitation exercises in patients with CSM after an operation. METHOD: This was a randomized controlled trial, wherein 107 patients with CSM treated by neurosurgery were selected as the subjects. Of those, 52 patients in the control group adopted the conventional health-promoting model, while the remaining 55 patients in the intervention group adopted diversified health-promoting models. The effect of rehabilitation exercises in the two groups was evaluated according to the self-efficacy rehabilitation outcome scale, grip strength measurement of the affected limb, and Barthel index. RESULTS: At Day 3 post-operation and before discharge, the self-efficacy management of rehabilitation exercises in the intervention group was better than that of the control group (P< 0.05). The grip strength measurement of the affected limb, Japanese Orthopedic Association score of the cervical vertebra, and Barthel index of the two groups at Day 3 post-operation were lower than before the intervention and were not statistically significant (P> 0.05). However, these three items before discharge were improved when compared with those of before intervention and were statistically significant (P< 0.05). CONCLUSION: Postoperative rehabilitation exercises guided by the diversified health-promoting models for patients with CSM can improve the patients' self-efficacy management ability in rehabilitation exercises, help improve grip strength, and promote the recovery of cervical vertebra function, thereby improving the patients' quality of life.

Orientin Reduces the Effects of Repeated Procedural Neonatal Pain in Adulthood: Network Pharmacology Analysis, Molecular Docking Analysis, and Experimental Validation.

Background: Premature infants often undergo painful procedures and consequently experience repeated procedural neonatal pain. This can elicit hyperalgesia and cognitive impairment in adulthood. Treatments for neonatal pain are limited. Orientin is a flavonoid C-glycoside that has repeatedly been shown to have pharmacological effects in the past decades. The aim of this study was to systematically explore the effect of orientin on repeated procedural neonatal pain using network pharmacology, molecular docking analysis, and experimental validation. Methods: Several compound-protein databases and disease-protein databases were employed to identify proteins that were both predicted targets of orientin and involved in neonatal pain. A protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential mechanism of action. Molecular docking analysis was employed to calculate the binding energy and visualize the interactions between orientin and potential target proteins. Finally, a mouse model of repeated procedural neonatal pain was established and orientin was administered for 6 days. The mechanical and thermal pain thresholds were assessed in neonates and adult mice. A Morris water maze was employed to investigate cognitive impairment in adult mice. Results: A total of 286 proteins that were both predicted targets of orientin and involved in neonatal pain were identified. The hub proteins were SRC, HSP90AA1, MAPK1, RHOA, EGFR, AKT1, PTPN11, ESR1, RXRA, and HRAS. GO analysis indicated that the primary biological process (BP), molecular function (MF), and cellular component (CC) were protein phosphorylation, protein kinase activity, and vesicle lumen, respectively. KEGG analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway may be the key to the mechanism of action. Molecular docking analysis showed the high binding affinities of orientin for MAPK1, MAPK8, and MAPK14. In mice, orientin inhibited the hyperalgesia in the pain threshold tests in neonates and adult mice and cognitive impairment in adult mice. Immunofluorescence showed that phosphorylated MAPK1 (p-ERK) protein levels in the hippocampus and spinal dorsal horn were downregulated by orientin. Conclusion: The findings suggested that orientin alleviates neonatal pain, and the MAPK signaling pathway is involved.

E2F1-driven histone demethylase KDM6B enhances thyroid malignancy via manipulating TFEB-dependent autophagy axis.

Aberrant epigenetic modifications or events regulate autophagy to influence tumor progression, which has gained increasing attention. KDM6B is an essential histone demethylase that participates in multiple processes of tumors, but its role in thyroid carcinoma (THCA) remains to be unknown. Here, in this study, we used the MTT assay to screen and validate that KDM6B is an essential demethylase for THCA. KDM6B promotes THCA proliferation, migration, invasion in vitro and in vivo. Transcriptional factor E2F1 directly binds to the promoter region of KDM6B and regulates its mRNA levels in THCA. E2F1 partially depended on KDM6B to exert its oncogenic functions. Mechanistically, KDM6B binds to TFEB promoter region and mediates the demethylation of H3K27me3. KDM6B depended on TFEB to activate a series of lysosomal-related genes. KDM6B enhances autophagy process, as evidenced by elevated p62 and Beclin-1 proteins. KDM6B depended on TFEB-driven autophagy activity to accelerate THCA progression. Lastly, targeting autophagy with 3-MA could notably abrogate growth of KDM6Bhigh THCA, but has mild influence on KDM6Blow THCA. Together, this study identified KDM6B as an essential epigenetic regulator for THCA, functioning as an autophagy regulator. The fundamental mechanisms underlying E2F1/KDM6B/TFEB axis provided novel vulnerabilities for THCA treatment.

Network pharmacology and molecular docking prediction, combined with experimental validation to explore the potential mechanism of Qishen Yiqi pills against HF-related cognitive dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ. AIMS OF THE STUDY: The study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments. RESULTS: 384 common targets were identified by intersecting QSYQ 'compound targets' and 'cognitive dysfunction' disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus. CONCLUSION: This study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.

XinLi formula, a traditional Chinese decoction, alleviates chronic heart failure via regulating the interaction of AGTR1 and AQP1.

BACKGROUND: XinLi formula (XLF) is a traditional Chinese medicine used in clinical practice to treat chronic heart failure (CHF) in humans, with remarkable curative effect. However, the mechanism remains unknown. PURPOSE: The goal of the current investigation was to determine how XLF affected CHF in a rat model of the condition brought on by ligation of the left anterior descending coronary artery, and to investigate the underlying mechanism. STUDY DESIGN AND METHODS: Cardiac function was detected by echocardiography. The contents of myocardial enzymes, Ang II, ALD, TGF-ß1, and inflammatory factors were measured by ELISA. Myocardial injury and myocardial fibrosis were evaluated by HE and Masson staining. Myocardial edema was assessed by cardiac mass index and transmission electron microscopy. Using Western blot and immunohistochemistry to examining the protein expression of inflammasome, TGF-ß1, AGTR1, and AQP1 in the left ventricle. Furthermore, the interaction of AGTR1 and AQP1 was evaluated by co-immunoprecipitation. RESULTS: XLF attenuated myocardial enzymes and myocardial injury, and improved cardiac function in rats with CHF after myocardial infarction. It also reduced Ang II and ALD levels in CHF rats, and suppressed the expression of AGTR1 and TGF-ß1, finally alleviated myocardial fibrosis. By mechanism, XLF inhibited the expression of NLRP3 inflammasome proteins, reduced the plasma contents of IL-1ß, IL-18, IL-6 and TNF-α. Additionally, XLF inhibited the expression of AQP1 and the interaction of AGTR1 and AQP1, alleviating myocardial edema. The common structure of the main chemical constituents of XLF were glycoside compounds with glycosyl. CONCLUSION: XLF ameliorated CHF, which was evidenced by the alleviation of myocardial fibrosis by inhibiting AGTR1/NLRP3 signal, as well as the attenuation of myocardial edema by suppressing the interaction of AGTR1 and AQP1.

Effects of specialized nursing intervention based on quantitative assessment strategy on psychological state and quality of life of patients with senile dementia.

OBJECTIVES: To explore the effects of specialized nursing intervention based on quantitative evaluation strategy on the psychological state and quality of life of senile dementia patients. METHODS: 92 senile dementia patients were divided into the control and intervention groups (n = 46 each). Control group was given routine nursing intervention, while intervention group was given specialized nursing intervention based on the quantitative evaluation strategy. Patients' self-care ability, cognitive function, nursing compliance, psychological state, quality of life, and patient satisfaction indexes were measured. RESULTS: After nursing interventions, the self-care ability (71.73 ± 4.31 vs 63.82 ± 3.97 points) and cognitive functions such as orientation (7.96 ± 1.02 vs 6.53 ± 1.15), memory (2.16 ± 0.39 vs 1.69 ± 0.31), visual-spatial copying (3.78 ± 0.53 vs 3.02 ± 0.65), language skills (7.49 ± 1.26 vs 6.05 ± 1.28), and recall ability (2.13 ± 0.26 vs 1.75 ± 0.28) were significantly improved in the intervention group compared to the control group (P ˂ 0.05). The patient's compliance in the intervention group (95.65%) was prominently higher than the control group (80.43%) (P < 0.05). Notably, patient's psychological state (anxiety and depression) in the intervention group (47.42 ± 3.12 vs 51.39 ± 3.16, 48.52 ± 2.51 vs 52.83 ± 2.49) was better than the control group (P < 0.05). Furthermore, the quality of life was significantly improved in the intervention group (88.11 ± 1.11 vs 71.52 ± 1.24) compared to the control group (P < 0.05). Also, patients' satisfaction with nursing services in the intervention group (97.83%) was higher than the control group (78.26%) (P < 0.05). CONCLUSIONS: Specialized nursing intervention based on quantitative evaluation strategy can effectively improve patients' self-care ability, and cognitive function, reduce anxiety and depression and enhance the quality of life, which is worthy of clinical promotion and application.

PA0575 (RmcA) interacts with other c-di-GMP metabolizing proteins in Pseudomonas aeruginosa PAO1.

As a central signaling molecule, c-di-GMP (bis-(3,5)-cyclic diguanosine monophosphate) is becoming the focus for research in bacteria physiology. Pseudomonas aeruginosa PAO1 genome contains highly complicated c-di-GMP metabolizing genes and a number of these proteins have been identified and investigated. Especially, a sophisticated network of these proteins is emerging. In current study, mainly through Bacteria-2-Hybrid assay, we found PA0575 (RmcA), a GGDEF-EAL dual protein, to interact with two other dual proteins of PA4601 (MorA) and PA4959 (FimX). These observations imply the intricacy of c-di-GMP metabolizing protein interactions. Our work thus provides one piece of data to increase the understandings to c-di-GMP signaling.

Identification and verification of α-11 giardin-interacting protein / 中国血吸虫病防治杂志

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Comparison of clinical effects of corneal topography-guided FS-LASIK and TICL implantation for myopia with moderate to high astigmatism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the clinical efficacy of the myopic with moderate to high astigmatism correction between corneal topography-guided femtosecond laser in situ keratomileusis(FS-LAISK)and Toric implantable collamer lens(TICL).METHODS: A total of 60 patients(115 eyes)with moderate to high astigmatism in myopia(115 eyes)from June 2019 to June 2021 and treated in the refractive center of Heyuan Aier Eye Hospital were enrolled in the study, then were divided into Group A and Group B according to the operations they would accept. There were 32 patients(62 eyes)in the Group A treated with corneal topography-guided FS-LASIK and 28 patients(53 eyes)in the Group B treated with TICL implantation. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical diopter and residual astigmatism were recorded preoperatively and postoperatively at 3mo, surgical safety and efficacy were evaluated, and the Alpins vector analysis was used to evaluate the astigmatism.RESULTS: The postoperative at 3mo, there were no differences in the safety index(1.163±0.167 vs 1.136±0.194)and the efficacy index(1.145±0.159 vs 1.123±0.196)between the patients of the two groups(P&#x003E;0.05). However, the astigmatism vector analysis showed that there were statistically differences in the index of success index [0.125(0.091, 0.200)vs 0.200(0.167, 0.250)], the correction index [1.000(0.902, 1.066)vs 0.834(0.783, 0.869)] and the flattening index [1.000(0.922, 1.079)vs 0.835(0.795, 0.870)](P&#x003C;0.01).CONCLUSION:Corneal topography-guided FS-LASIK and TICL implantation were effective and safe in correcting myopia with moderate to high astigmatism, and corneal topography-guided FS-LASIK perform better than TICL implantation for the astigmatism correction.

Post-radiation circulating tumor DNA as a prognostic factor in locally advanced esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant and deadly tumor. Radiation therapy is one of the primary treatments for locally advanced ESCC. However, the biomarkers for prognosis of definitive radiation remain undefined. Peripheral blood circulating tumor (ct)DNA provides information of tumor genetic alterations and has been confirmed as a potential non-invasive biomarker for several types of cancer. The present study investigated the clinical implications of ctDNA detection in patients with ESCC and receiving definitive radiation therapy. Patients with locally advanced ESCC were retrospectively recruited. Plasma samples were collected before, during and following radiation therapy. Next-generation sequencing was performed to identify somatic mutations in 180 genes. A total of 69 baseline and post-radiation plasma samples were collected from 25 patients. A total of 59 non-silent single nucleotide variants were present in 33 genes. All pre-radiation and 58.3% (14/24) of post-radiation samples had at least one mutation. Patients with lymph node metastases (LNM) exhibited a higher number of pre-radiation mutations compared with those without LNM. The variables, progression-free survival (PFS) and overall survival (OS) of the patients with one baseline mutation were not significantly different compared with that in patients with more than one baseline mutation. Patients with initial ctDNA-positive post-radiation samples exhibited significantly reduced PFS (P=0.047) and OS (P=0.005) compared with that in patients with ctDNA-negative samples. The post-radiation plasma ctDNA status was an independent prognostic factor from univariate and multivariate analyses. Dynamic monitoring of ctDNA during follow-up was examined. The results indicated that ctDNA was a predictive and prognostic marker in patients with ESCC and receiving definitive radiation therapy, which may guide subsequent treatment.

Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function.

The N-myc downstream regulated gene (NDRG) family members are dysregulated in several tumors. Functionally, NDRGs play an important role in the malignant progression of cancer cells. However, little is known about the potential implications of NDRG4 in pancreatic ductal adenocarcinoma (PDAC). The aim of the current study was to elucidate the expression pattern of NDRG4 in PDAC and evaluate its potential cellular biological effects. Here, we firstly report that epigenetic-mediated silencing of NDRG4 promotes PDAC by regulating mitochondrial function. Data mining demonstrated that NDRG4 was significantly down-regulated in PDAC tissues and cells. PDAC patients with low NDRG4 expression showed poor prognosis. Epigenetic regulation by DNA methylation was closely associated with NDRG4 down-regulation. NDRG4 overexpression dramatically suppressed PDAC cell growth and metastasis. Further functional analysis demonstrated that up-regulated NDRG4 in SW1990 and Canpan1 cells resulted in attenuated mitochondrial function, including reduced ATP production, decreased mitochondrial membrane potential, and increased fragmented mitochondria. However, opposite results were obtained for HPNE cells with NDRG4 knockdown. These results indicate that hypermethylation-driven silencing of NDRG4 can promote PDAC by regulating mitochondrial function and that NDRG4 could be as a potential biomarker for PDAC patients. [BMB Reports 2020; 53(12): 658-663].

Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer.

Reprogrammed glucose metabolism of enhanced aerobic glycolysis, also known as Warburg effect, which exerts a significant contributor to cancer progression, is regarded as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer via metabolic reprogramming are mostly unknown, including esophagal cancer (EC). Here, we showed that how the lncRNA urothelial carcinoma associated 1 (UCA1) exerts pro-oncogene in regulating EC glucose metabolism. Firstly, we found that upregulated UCA1 expression enhances the malignant phenotypes of EC, including poor outcome, larger tumor size, positive lymphatic invasion, and advanced pathological stages. UCA1 silencing could suppress EC cell proliferation and metastasis. Following, bioinformatics analyses revealed that UCA1 regulated the HK2 expression through functioning as a competing endogenous RNA (ceRNA). Mechanistically, UCA1 overexpression could elevate the activation of HK2 oncogenes via inhibition of miR-203 activity, as evidenced by the positive correlation of UCA1 with HK2 and inverse correlation with miR-203 expression. Luciferase activity assay further verified the targeting relationship between UCA1, miR-203, and HK2. Upregulated UCA1 in EC cells significantly suppressed the degradation of HK2 by miR-203. Further research showed that upregulated UCA1 effectively increased the rate of glucose uptake, lactate output, and ECAR value, all of which can be attenuate by HK2 interference and 2-DG, whereas knockdown of UCA1 had the opposite effect. In sum, our findings suggest that the UCA1/miR-203/HK2 axis contributes to EC development by reprogramming tumor glucose metabolism, providing new insight into the management of EC patients.

Bioactivity-guided isolation of anti-inflammatory components from Phyllanthus emblica.

Phyllanthus emblica (P. emblica) is a traditionally edible fruit that is good for treatment of biliary diseases, bronchitis, etc. It has obvious anti-inflammatory activity, but few studies focus on its anti-inflammatory active substance basis. The purpose of this study was to explore the material basis of anti-inflammatory activity of P. emblica, purify, and identify anti-inflammatory active monomers. Fisetin and gallic acid, which were identified after separation from ethanol extract components of P. emblica, exhibited the best anti-inflammatory effects, markedly inhibiting nitric oxide and proinflammatory cytokine levels in LPS-stimulated macrophages. In particular, fisetin with significant anti-inflammatory activity was firstly identified from P. emblica. For the first time, our research systematically revealed the material basis of the anti-inflammatory effects of P. emblica from the perspective of the composition of the bioactive substances and provided scientific research methods and ideas for researching bioactive monomers in other plant extracts.

Progress of researches on the role of neutrophil extracellular traps in the immune responses against parasites / 中国血吸虫病防治杂志

Neutrophil extracellular trap (NET) is a type of bead-like, fibrous and reticular substances that is actively released by activated inflammatory neutrophils during the stage of infections or inflammatory responses. NET, which is composed of chromatin DNA and multiple intracellular protein components, may wrap pathogens to limit their diffusions. Meanwhile, NET may kill pathogens via a wide range of antibacterial proteins, which is considered as the third antibacterial mechanism of neutrophils, in addition to phagocytosis and degranulation. Recent studies have shown the involvement of NET in the immune response against parasitic infections. This review summarizes the advances of NETs in the immune responses against parasitic infections, so as to provide insights into the elucidation of the pathogenesis and development of therapeutics of parasitic diseases.

Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration.

PI3Kδ is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, we describe the identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation. The initially identified compound (13) had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the molecule pointing to solvent was tolerated (enzyme inhibition pIC50 > 9), and by careful manipulation of the pKa and lipophilicity, we were able to discover compounds (20b, 20f) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated.

Improving prediction of burial state of residues by exploiting correlation among residues.

BACKGROUND: Residues in a protein might be buried inside or exposed to the solvent surrounding the protein. The buried residues usually form hydrophobic cores to maintain the structural integrity of proteins while the exposed residues are tightly related to protein functions. Thus, the accurate prediction of solvent accessibility of residues will greatly facilitate our understanding of both structure and functionalities of proteins. Most of the state-of-the-art prediction approaches consider the burial state of each residue independently, thus neglecting the correlations among residues. RESULTS: In this study, we present a high-order conditional random field model that considers burial states of all residues in a protein simultaneously. Our approach exploits not only the correlation among adjacent residues but also the correlation among long-range residues. Experimental results showed that by exploiting the correlation among residues, our approach outperformed the state-of-the-art approaches in prediction accuracy. In-depth case studies also showed that by using the high-order statistical model, the errors committed by the bidirectional recurrent neural network and chain conditional random field models were successfully corrected. CONCLUSIONS: Our methods enable the accurate prediction of residue burial states, which should greatly facilitate protein structure prediction and evaluation.