Dodder (
spp.) is a parasitic weed damaging many plants and agricultural production. The native obligate parasite
Choisy (Japanese dodder) parasitizes
Lour.,
Burm. F.,
L.f.,
H.B.K. and
Linn, ...respectively. Five Japanese dodders growing on different plants exhibit slightly different metabolites and amounts which present different pharmacological effects. Among these plants, a significant antiviral activity against influenza A virus (IAV) was found in Japanese dodder parasitizing on
Lour. (CL). To further explore methanol extract components in Japanese dodder (CL), four undescribed aromatic glycosides, cuscutasides A-D (compounds
-
) were isolated, together with twenty-six known compounds
-
. The chemical structures of
-
were elucidated using a combination of spectroscopic techniques. The eighteen isolated compounds were evaluated for antiviral activity against IAV activity. Among them, 1-monopalmitin (
) displayed potent activity against influenza A virus (A/WSN/1933(H1N1)) with EC
2.28 ± 0.04 μM and without noteworthy cytotoxicity in MDCK cells. The interrupt step of
on the IAV life cycle was determined. These data provide invaluable information for new applications for this otherwise harmful weed.
A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease ...progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm for breath phase detection and adventitious sound detection at the recording level has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchus labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests using long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.
Parkinson's disease (PD) is a common neurodegenerative disease. The pathological hallmark of PD is a progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta in the brain, ...ultimately resulting in severe striatal dopamine deficiency and the development of primary motor symptoms (e.g., resting tremor, bradykinesia) in PD. Acupuncture has long been used in traditional Chinese medicine to treat PD for the control of tremor and pain. Accumulating evidence has shown that using electroacupuncture (EA) as a complementary therapy ameliorates motor symptoms of PD. However, the most appropriate timing for EA intervention and its effect on dopamine neuronal protection remain unclear. Thus, this study used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model (systemic-lesioned by intraperitoneal injection) and the 1-methyl-4-phenylpyridinium (MPP⁺)-lesioned rat model (unilateral-lesioned by intra-SN infusion) of PD, to explore the therapeutic effects and mechanisms of EA at the GB34 (Yanglingquan) and LR3 (Taichong) acupoints. We found that EA increased the latency to fall from the accelerating rotarod and improved striatal dopamine levels in the MPTP studies. In the MPP⁺ studies, EA inhibited apomorphine induced rotational behavior and locomotor activity, and demonstrated neuroprotective effects via the activation of survival pathways of Akt and brain-derived neurotrophic factor (BDNF) in the SN region. In conclusion, we observed that EA treatment reduces motor symptoms of PD and dopaminergic neurodegeneration in rodent models, whether EA is given as a pretreatment or after the initiation of disease symptoms. The results indicate that EA treatment may be an effective therapy for patients with PD.
Rationale
Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis and pancreatic cancer (PC) is one of the most lethal types of cancer that is symptomless in the early stage. Because ...the clinical and image findings of CP can overlap that of pancreatic cancer (PC) which leads to confusion in the diagnosis and treatment of PC, discovery/verification/validation of more accurate protein biomarkers to diagnose CP and PC is in urgent need.
Methods
The PubMed, Web of Science, and Google Scholar were searched using the keywords: ‘biomarker’, ‘marker’, ‘chronic pancreatitis’, “pancreatic cancer” or “proteomics” for highly related researches. We focused on the articles published after the year 2005 in this review.
Results
We introduce the background to CP and PC and summarize the diagnosis of CP and PC, analytically validated protein biomarkers, and proteomic approaches for discovery/verification/validation. The potential use of mass spectrometry (MS) in clinical diagnosis is also discussed.
Conclusions
Continuously improving sensitivity of MS can provide deeper proteome for new marker discovery and high reliability for protein marker verification, validation, and clinical diagnosis. The analytically validated protein markers could be considered as targeted protein biomarkers for developing a MS platform in the clinical validation process or clinical diagnosis of CP and PC.
The complexity of the proteome often limits the number of identified proteins in the nanoflow LC-MS (nanoLC-MS) analysis of samples. Therefore, peptide fractionation is essential for reducing the ...sample complexity and improving the proteome coverage. In this study, to achieve high-pH reversed-phase (RP)-well plate fractionation for high-throughput proteomics analysis, C18 particles were coated on a 96-well plate, and the sample-loading processes were optimized for high-pH fractionation. The sample capacity of the high-pH RP-well plate was estimated to be ~6 μg of protein. There were 1.85- and 1.71-fold increases in the number of protein groups and peptides identified, respectively, with high-pH RP-well plate fractionation, compared to those without fractionation. In addition, with alkaline C18 well plate fractionation, exosome markers could be detected using ~1 μg of a protein digest of exosomes by microflow LC-MS (microLC-MS). These results illustrate that high-pH RP-well plate fractionation has superior sensitivity and effectiveness in preparing trace amounts of proteins for deep proteome analysis.
Graphical abstract
In order to optimize the efficiency of the Fused deposition modeling (FDM) process, this study used polylactic acid (PLA) material under different parameters (the printing angle and the raster angle) ...to fabricate specimens and to explore its tensile properties. The effect of the ultraviolet (UV) curing process on PLA materials was also investigated. The results showed that the printing and raster angles have a high impact on the tensile properties of PLA materials. The UV curing process enhanced the brittleness and reduced the elongation of PLA material. Different effects were observed on tensile strength and modulus of specimens printed with different parameters after UV curing. The above results will be a great help for researchers who are working to achieve sustainability of PLA materials and FDM technology.
We examine whether initiations of bank loans with financial covenants motivate banks to monitor borrowers’ accounting practice and result in a higher quality of reported accruals and a better ...information environment for firms. We document that, relative to loans without financial covenants, loans with financial covenants lead to an improvement in accrual quality measured by the extent to which accruals can be mapped into cash flows. The effect of loan covenants on accrual quality is stronger when external monitoring by non‐bank stakeholders (i.e., institutional investors and financial analysts) is weaker. Furthermore, initiations of bank loans with financial covenants are related to subsequent improvements in analysts’ information environment. The evidence supports the view that bank monitoring improves accounting quality.
Patient engagement helps to improve health outcomes and health care quality. However, the overall relationships among patient engagement measures and health outcomes remain unclear. This study aims ...to integrate expert knowledge and survey data for the identification of measures that have extensive associations with other variables and can be prioritized to engage patients.
We used the 2014 International Health Policy Survey (IHPS), which provided information on elder adults in 11 countries with details in patient characteristics, healthcare experiences, and patient-physician communication. Patient engagement or support was measured with eight variables including patients' treatment choices, involvement, and treatment priority setting. Three types of care were identified: primary, specialist and chronic illness care. Specialists were doctors specializing in one area of health care. Chronic illness included eight chronic conditions surveyed. Expert knowledge was used to assist variable selection. We used Bayesian network models consisting of nodes that represented variables of interest and arcs that represented their relationships.
Among 25,530 participants, the mean age was 68.51 years and 57.40% were females. The distributions of age, sex, education, and patient engagement were significantly different across countries. For chronic illness care, written plans provided by professionals were linked to treatment feasibility and helpfulness. Whether professionals contacted patients was associated with the availability of professionals they could reach for chronic illness care. For specialist care, if specialists provided treatment choices, patients were more likely to be involved and discuss about what mattered to them.
The strategies to engage patients may depend on the types of care, specialist or chronic illness care. For the study on the observational IHPS data, network modeling is useful to integrate expert knowledge. We suggest considering other theory-based patient engagement in major surveys, as well as engaging patients in their healthcare by providing written plans and actively communicating with patients for chronic illnesses, and encouraging specialists to discuss and provide treatment options.
•Polymerization of OVA and OVT induced by TGase was analyzed.•OVA and OVT were poorer substrates for TGase.•Polymerization of OVA occurred following TGase with 2-ME and heat ...pretreatment.•Polymerization of OVT occurred following TGase with l-Cys pretreatment.
The effects of transglutaminase (TGase, 1.0 unit/mL) with heat (95 °C, 5 min), 2-mercaptoethanol (2-ME, 0.83 %), and l-cysteine (l-Cys, 50 mM) pretreatment on the cross-linking of ovalbumin (OVA) and ovotransferrin (OVT) were investigated. SDS-PAGE revealed that although the polymerization of OVA and OVT did not occur after 3 h of incubation at 40 °C with TGase, OVA polymerized into high molecular weight polymers following TGase with 2-ME and heat pretreatment after 3 h of incubation. The surface hydrophobicity and reactive sulfhydryl (SH) groups of OVA samples significantly increased from 4065.7 ± 136.7 and 89.3 ± 1.2 SH groups (μmol/g) to 31483.6 ± 342.7 and 119.5 ± 3.7 SH groups (μmol/g), respectively. Similar results were obtained for OVT with TGase and l-Cys pretreatment and a 3-h incubation at 40 °C. The use of TGase, a reducing agent, and/or heat pretreatment can be used for the polymerization of OVA and OVT.
Abstract
Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains ...elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing
c
GAS/
D
ncV-like
n
ucleotidyl
t
ransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2’3’-phosphodiester linkage through intermediate pppU3’−5’pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases.
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