In pigs, three circovirus species within the genus Circovirus have been identified so far, including the non‐pathogenic Porcine circovirus 1 (PCV1), the pathogenic Porcine circovirus 2 (PCV2) and the ...recently identified Porcine circovirus 3 (PCV3). In April 2019, a new circovirus with a distinct relationship to other circoviruses was identified in several pigs with severe clinical disease in Hunan province, China. The size of the viral genome, tentatively designated as porcine circovirus type 4 (PCV4), is 1,770 nucleotides (nt). PCV4 shows the highest genomic identity to mink circovirus (66.9%) and has identities of 43.2%–51.5% to the other PCV genomes. Two major genes, a replicase (Rep) gene spanning 891 nt and a capsid (Cap) gene spanning 687 nt, were predicted. Furthermore, a TaqMan® real‐time polymerase chain reaction (PCR) targeting the replicase gene was developed to investigate the prevalence of PCV4 in 187 clinical samples from Hunan province, China. The results revealed an overall PCV4 prevalence of 12.8%, with the highest positive rates in nasal swabs (28.5%, 6/21) followed by serum samples (13.4%, 11/82). The clinical significance and pathogenesis of this virus needs further investigation.
The oldest porcine circovirus type 2 (PCV2) sequence dates back to 1962 and is among several hundreds of publicly available PCV2 sequences. Despite this resource, few studies have investigated the ...global genetic diversity of PCV2. To evaluate the phylogenetic relationship of PCV2 strains, 1680 PCV2 open reading frame 2 (ORF2) sequences were compared and analysed by methods of neighbour-joining, maximum-likelihood, Bayesian inference and network analysis. Four distinct clades were consistently identified and included PCV2a, PCV2b, PCV2c and PCV2d; the p-distance between PCV2d and PCV2b was 0.055±0.008, larger than the PCV2 genotype-definition cut-off of 0.035, supporting PCV2d as an independent genotype. Among the 1680 sequences, 278-285 (16.5-17 %) were classified as PCV2a, 1007-1058 (59.9-63 %) as PCV2b, three (0.2 %) as PCV2c and 322-323 (19.2 %) as PCV2d, with the remaining 12-78 sequences (0.7-4.6 %) classified as intermediate clades or strains by the various methods. Classification of strains to genotypes differed based on the number of sequences used for the analysis, indicating that sample size is important when determining classification and assessing PCV2 trends and shifts. PCV2d was initially identified in 1999 in samples collected in Switzerland, now appears to be widespread in China and has been present in North America since 2012. During 2012-2013, 37 % of all investigated PCV2 sequences from US pigs were classified as PCV2d and overall data analysis suggests an ongoing genotype shift from PCV2b towards PCV2d. The present analyses indicate that PCV2d emerged approximately 20 years ago.
Abnormal findings include (1) hyperdynamic cardiac function, presented as the increase of cardiac output (CO) and ejection faction (EF) of the left ventricular (LV), with/without the decrease of ...peripheral vascular resistance, which is often seen in the early stage following the systemic inflammatory response; (2) acute stress-induced (takotsubo) cardiomyopathy, characterized as LV segmental contraction abnormalities and apical ballooning 1; (3) right ventricular (RV) enlargement and acute pulmonary hypertension, which are mainly caused by “internal factors” (including alveolar and pulmonary capillary damage caused by inflammation, hypoxia, and hypercapnia, leading to the increase of RV afterload) and “external factors” (including fluid overload, which causes the increase of RV preload, and unsuitable mechanical ventilation parameter setting, which affects the cardiac function by cardiopulmonary interaction); further, LV function will be affected because the right and left hearts are in the same pericardium; and (4) diffuse myocardial inhibition in the late stage, which is often caused by severe hypoxia, and long term of anoxia and inflammation. Critical ultrasonography is of great significance in fast identifying the types of shock and guide hemodynamic management. Since the focused cardiac ultrasound (FOCUS) was proposed in 2010 2, many different types of FOCUS exams for rapid evaluation of emergency or ICU patients have been introduced, including the focus-assessed transthoracic echocardiography (FATE) advanced FATE protocol 3, fluid administration limited by lung sonography (FALLS) protocol 4, and critical care chest ultrasonic examination (CCUE) protocol 5. In COVID-19 patients, the most common types of shock are septic shock and cardiogenic shock; however, we still need to exclude obstructive shock (massive pericardial effusion, right heart collapse, heart swing, RV enlargement and “D sign,” tricuspid valve regurgitation, pulmonary artery or deep vein thrombosis, etc.) and hypovolemic shock (decrease of CO, “papillary muscle kissing sign,” IVC collapse and high respiratory variability, etc.) first.
Background
Diffusion weighted imaging (DWI) at multiple b‐values has been used to predict the pathological complete response (pCR) to neoadjuvant chemoradiotherapy for locally advanced rectal cancer. ...Non‐Gaussian models fit the signal decay of diffusion by several physical values from different approaches of approximation.
Purpose
To develop a deep learning method to analyze DWI data scanned at multiple b‐values independent on Gaussian or non‐Gaussian models and to apply to a rectal cancer neoadjuvant chemoradiotherapy model.
Study Type
Retrospective.
Population
A total of 472 participants (age: 56.6 ± 10.5 years; 298 males and 174 females) with locally advanced adenocarcinoma were enrolled and chronologically divided into a training group (n = 200; 42 pCR/158 non‐pCR), a validation group (n = 72; 11 pCR/61 non‐pCR) and a test group (n = 200; 44 pCR/156 non‐pCR).
Field Strength/Sequence
A 3.0 T MRI scanner. DWI with a single‐shot spin echo‐planar imaging pulse sequence at 12 b‐values (0, 20, 50, 100, 200, 400, 600, 800, 1000, 1200, 1400, and 1600 sec/mm2).
Assessment
DWI signals from manually delineated tumor region were converted into a signature‐like picture by concatenating all histograms from different b‐values. Pathological results (pCR/non‐pCR) were used as the ground truth for deep learning. Gaussian and non‐Gaussian methods were used for comparison.
Statistical Tests
Analysis of variance for age; Chi‐square for gender and pCR/non‐pCR; area under the receiver operating characteristic (ROC) curve (AUC); DeLong test for AUC. P < 0.05 for significant difference.
Results
The AUC in the test group is 0.924 (95% CI: 0.866–0.983) for the signature‐like pictures converted from 35 bins, and it is 0.931 (95% CI: 0.884–0.979) for the signature‐like pictures converted from 70 bins, which is significantly (Z = 3.258, P < 0.05) larger than Dapp, the best predictor in non‐Gaussian methods with AUC = 0.773 (95% CI: 0.682–0.865).
Data Conclusion
The proposed signature‐like pictures provide more accurate pretreatment prediction of the response to neoadjuvant chemoradiotherapy than the fitted methods for locally advanced rectal cancer.
Evidence Level
3
Technical Efficacy
Stage 2
Abstract
Raman optical activity (ROA) is effective for studying the conformational structure and behavior of chiral molecules in aqueous solutions and is advantageous over X-ray crystallography and ...nuclear magnetic resonance spectroscopy in sample preparation and cost performance. However, ROA signals are inherently minuscule; 3–5 orders of magnitude weaker than spontaneous Raman scattering due to the weak chiral light–matter interaction. Localized surface plasmon resonance on metallic nanoparticles has been employed to enhance ROA signals, but suffers from detrimental spectral artifacts due to its photothermal heat generation and inability to efficiently transfer and enhance optical chirality from the far field to the near field. Here we demonstrate all-dielectric chiral-field-enhanced ROA by devising a silicon nanodisk array and exploiting its dark mode to overcome these limitations. Specifically, we use it with pairs of chemical and biological enantiomers to show >100x enhanced chiral light–molecule interaction with negligible artifacts for ROA measurements.
Porcine circovirus type 4 (PCV4) is a newly emerging virus, with both PCV4 genomic DNA and specific antibodies detected in swine herds in several provinces in China and South Korea. Although the ...virus was first identified in 2019 in Hunan, China, retrospective research suggests that serum samples collected as early as 2008 were positive for PCV4 antibody. Infections with only PCV4 or co-infections with other pathogens have been associated with several clinical manifestations, but its pathogenesis remains to be determined. The purpose of this review was the following: (1) to characterize PCV4 epidemiology by assessing evolutionary dynamics and genetic diversity of PCV4 strains circulating in swine herds; (2) to reconstruct a computerized 3D model to analyze PCV4 Cap properties; (3) and to summarize the current evidence of PCV4-associated clinical-pathological manifestations. The origin of PCV4 is apparently distinct from other PCV, based on analysis of phylogenetic trees. Of note, PCV4 shares an ancient common ancestor with mink circoviruses. Furthermore, the amino acid residue at position 27 of the PCV4 Cap is a key benchmark to distinguish PCV4a (
S) from PCV4b (
N), based on PCV4 strains currently available, and variation of this residue may alter Cap antigenicity. In addition, the capsid surface of PCV4 has characteristics of increased polar residues, compared to PCV2, which raises the possibility that PCV4 may target negatively charged host receptors to promote virus infection. Further studies are required, including virus isolation and culture, and more detailed characterization of molecular epidemiology and genetic diversity of PCV4 in swine herds.
Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein‐based cyclometalated IrIII complex, ...Ir‐Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir‐Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death. Moreover, Ir‐Rhein can overcome cisplatin resistance. Co‐incubation experiment, 3D tumor spheroids experiment and transcriptome analysis reveal that Ir‐Rhein shows promising antiproliferation performance for cisplatin‐resistant cancer cells with the regulation of platinum resistance‐related transporters. To our knowledge, this is a new strategy to overcome metallodrug resistance with a mitochondria‐relevant treatment.
A new strategy to fight metallodrug resistance through mitochondria‐relevant treatment is reported. The cyclometalated IrIII complex Ir‐Rhein could inhibit the metabolic adaptation of cancer cells by inducing severe mitochondrial damage and dysfunction. Moreover, complex Ir‐Rhein could overcome metallodrug resistance through the regulation of the platinum resistance‐related transporters.
Plants form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which facilitates the acquisition of scarce minerals from the soil. In return, the host plants provide sugars and lipids to ...its fungal partner. However, the mechanism by which the AM fungi obtain sugars from the plant has remained elusive.
In this study we investigated the role of potential SWEET family sugar exporters in AM symbiosis in Medicago truncatula.
We show that M. truncatula SWEET1b transporter is strongly upregulated in arbuscule-containing cells compared to roots and localizes to the peri-arbuscular membrane, across which nutrient exchange takes place. Heterologous expression of MtSWEET1b in a yeast hexose transport mutant showed that it mainly transports glucose. Overexpression of MtSWEET1b in M. truncatula roots promoted the growth of intraradical mycelium during AM symbiosis. Surprisingly, two independent Mtsweet1b mutants, which are predicted to produce truncated protein variants impaired in glucose transport, exhibited no significant defects in AM symbiosis. However, arbuscule-specific overexpression of MtSWEET1bY57A/G58D, which are considered to act in a dominant-negative manner, resulted in enhanced collapse of arbuscules.
Taken together, our results reveal a (redundant) role for MtSWEET1b in the transport of glucose across the peri-arbuscular membrane to maintain arbuscules for a healthy mutually beneficial symbiosis.
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