Atherosclerosis is a complex disease, influenced by both genetic and non-genetic factors. The most important epigenetic mechanism in the pathogenesis of atherosclerosis is DNA methylation, which ...involves modification of the gene without changes in the gene sequence. Nutrients involved in one-carbon metabolism interact to regulate DNA methylation, especially folic acid and B vitamins. Deficiencies in folic acid and other nutrients, such as vitamins B6 and B12, can increase homocysteine levels, induce endothelial dysfunction, and accelerate atherosclerotic pathological processes. Supplemented nutrients can improve DNA methylation status, reduce levels of inflammatory factors, and delay the process of atherosclerosis. In this review, the influence of intestinal flora on folate metabolism and epigenetics is also considered.
Motivation: In recent years, development of a single-method fold-recognition server lags behind consensus and multiple template techniques. However, a good consensus prediction relies on the accuracy ...of individual methods. This article reports our efforts to further improve a single-method fold recognition technique called SPARKS by changing the alignment scoring function and incorporating the SPINE-X techniques that make improved prediction of secondary structure, backbone torsion angle and solvent accessible surface area.
Results: The new method called SPARKS-X was tested with the SALIGN benchmark for alignment accuracy, Lindahl and SCOP benchmarks for fold recognition, and CASP 9 blind test for structure prediction. The method is compared to several state-of-the-art techniques such as HHPRED and BoostThreader. Results show that SPARKS-X is one of the best single-method fold recognition techniques. We further note that incorporating multiple templates and refinement in model building will likely further improve SPARKS-X.
Availability: The method is available as a SPARKS-X server at http://sparks.informatics.iupui.edu/
Contact:
yqzhou@iupui.edu
High-flow nasal cannula oxygen (HFNC) is a relatively new therapy used in adults with respiratory failure. Whether it is superior to conventional oxygen therapy (COT) or to noninvasive mechanical ...ventilation (NIV) remains unclear. The aim of the present study was to investigate whether HFNC was superior to either COT or NIV in adult acute respiratory failure patients.
A review of the literature was conducted from the electronic databases from inception up to 20 October 2016. Only randomized clinical trials comparing HFNC with COT or HFNC with NIV were included. The intubation rate was the primary outcome; secondary outcomes included the mechanical ventilation rate, the rate of escalation of respiratory support and mortality.
Eleven studies that enrolled 3459 patients (HFNC, n = 1681) were included. There were eight studies comparing HFNC with COT, two comparing HFNC with NIV, and one comparing all three. HFNC was associated with a significant reduction in intubation rate (OR 0.52, 95% CI 0.34 to 0.79, P = 0.002), mechanical ventilation rate (OR 0.56, 95% CI 0.33 to 0.97, P = 0.04) and the rate of escalation of respiratory support (OR 0.45, 95% CI 0.31 to 0.67, P < 0.0001) when compared to COT. There was no difference in mortality between HFNC and COT utilization (OR 1.01, 95% CI 0.67 to 1.53, P = 0.96). When HFNC was compared to NIV, there was no difference in the intubation rate (OR 0.96; 95% CI 0.66 to 1.39, P = 0.84), the rate of escalation of respiratory support (OR 1.00, 95% CI 0.77 to 1.28, P = 0.97) or mortality (OR 0.85, 95% CI 0.43 to 1.68, P = 0.65).
Compared to COT, HFNC reduced the rate of intubation, mechanical ventilation and the escalation of respiratory support. When compared to NIV, HFNC showed no better outcomes. Large-scale randomized controlled trials are necessary to prove our findings.
PROSPERO International prospective register of systematic reviews on May 25, 2016 registration no. CRD42016039581 .
Protein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately ...predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information. In this study, we have developed a new structure-aware method
GraphSol
to predict protein solubility by attentive graph convolutional network (GCN), where the protein topology attribute graph was constructed through predicted contact maps only from the sequence.
GraphSol
was shown to substantially outperform other sequence-based methods. The model was proven to be stable by consistent
R
2
of 0.48 in both the cross-validation and independent test of the
eSOL
dataset. To our best knowledge, this is the first study to utilize the GCN for sequence-based protein solubility predictions. More importantly, this architecture could be easily extended to other protein prediction tasks requiring a raw protein sequence.
ACE2 Shedding and the Role in COVID-19 Wang, Jieqiong; Zhao, Huiying; An, Youzhong
Frontiers in cellular and infection microbiology,
01/2022, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe ...acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.
Background. Bloodstream infection is amongst the leading causes of mortality for critical postoperative patients. However, data, especially from developing countries, are scary. Clinical ...decision-making tools for predicting postoperative bloodstream infection-related mortality are important but still lacking. Objective. To analyze the distribution of pathogens and develop a nomogram for predicting mortality in patients with postoperative bloodstream infection in the surgical intensive care unit. Methods. The clinical data, infection and pathogen-related data, and prognosis of patients with PBSI in the SICU from January 2017 to January 2022 were retrospectively collected. The distribution of pathogens and clinical characteristics of patients with PBSI were analyzed. The patients were assigned to a died group and a survived group according to their survival status. Independent predictors for mortality were identified by univariate and multivariate analyses. A nomogram for predicting PBSI-related death was developed based on these independent predictors. Calibration and decision-curve analysis were established to evaluate the nomogram. We collected postoperative patients admitted to our center from February 2022 to June 2023 as external validation sets to verify the nomogram. We also add the Brier score to further validate the model. Results. In the training set, 7128 patients admitted to the SICU after different types of surgery were collected. A total of 198 patients and 308 pathogens were finally enrolled. The mean age of patients with PBSI was 64.38 ± 16.22 (range 18–90) years, and 56.1% were male. Forty-five patients (22.7%) died in the hospital. Five independent predictors including BMI, APACHE II score, estimated glomerular filtration rate (eGFR), urine volume in the first 24 hours after surgery, and peak temperature before positive blood cultures were selected to establish the nomogram. The area under the receiver operating characteristic curve for the prediction model was 0.922. Calibration curve and decision curve analysis showed good performance of the nomogram. Seventy patients with PBSI were collected as an external validation set, and thirteen patients died in this set. The external validation set was used to validate the nomogram, and the results showed that the AUC was 0.930 which was higher than that in the training set indicating that the nomogram had a good discrimination. The brier score was 0.087 for training set and 0.050 for validation set. Conclusions. PBSI was one of the key issues that clinicians were concerned and could be assessed with a good predictive model using simple clinical factors.
Abstract Recent advances in NIR triggering upconversion-based photodynamic therapy have led to substantial improvements in upconversion-based nanophotosensitizers. How to obtain the high efficiency ...of singlet oxygen generation under low 980 nm radiation dosage still remains a challenge. A highly efficient nanophotosensitizer, denoted as UCNPs-ZnPc, was constructed for photodynamic therapy, which is based on near infrared (NIR) light upconversion nanoparticle (UCNP) and Zn(II)-phthalocyanine (ZnPc) photosensitizer (PS). The high1 O2 production efficiency came from the enhancement of the 660 nm upconversion emission of NaYF4 :Yb3+ , Er3+ UCNP with 25% Yb3+ doping, covalent assemblage of UCNP and ZnPc which significantly shortened the distance and enhanced the energy transfer between the two. The high1 O2 production led to a secure and efficient PDT treatment, as evidenced by the in vivo test where UCNPs-ZnPc of 50 mg per kg body weight was locally injected into the liver tumor in mice, a low 980 nm radiation dose of 351 J/cm2 (0.39 W/cm2 ) and short irradiation duration of 15 min were sufficient to perform image-guided PDT and caused the liver tumor inhibitory ratio of approximately 80.1%. Histological analysis revealed no pathological changes and inflammatory response in heart, lung, kidney, liver or spleen.
Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma ...(ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC.
Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3β) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3β, and the detection rates of plasma circGSK3β for ESCC were investigated.
We demonstrated that upregulated expression of circGSK3β was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3β promoted ESCC cell migration and invasion via direct interaction with GSK3β and inhibiting GSK3β activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3β expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively.
CircGSK3β exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3β have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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