64 research outputs found
Robust Weighted Sum-Rate Maximization for Transmissive RIS Transmitter Enabled RSMA Networks
Due to the low power consumption and low cost nature of transmissive
reconfigurable intelligent surface (RIS),in this paper, we propose a downlink
multi-user rate-splitting multiple access (RSMA) architecture based on the
transmissive RIS transmitter, where the channel state information (CSI) is only
accquired partially. We investigate the weighted sum-rate maximization problem
by jointly optimizing the power, RIS transmissive coefficients and common rate
allocated to each user. Due to the coupling of optimization variables, the
problem is nonconvex, and it is difficult to directly obtain the optimal
solution. Hence, a block coordinate descent (BCD) algorithm based on sample
average approximation (SAA) and weighted minimum mean square error (WMMSE) is
proposed to tackle it. Numerical results illustrate that the transmissive RIS
transmitter with ratesplitting architecture has advantages over conventional
space division multiple access (SDMA) and non-orthgonal multiple access (NOMA)
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DNMTs Play an Important Role in Maintaining the Pluripotency of Leukemia Inhibitory Factor-Dependent Embryonic Stem Cells.
Naive pluripotency can be maintained in medium with two inhibitors plus leukemia inhibitory factor (2i/LIF) supplementation, which primarily affects canonical WNT, FGF/ERK, and JAK/STAT3 signaling. However, whether one of these three supplements alone is sufficient to maintain naive self-renewal remains unclear. Here we show that LIF alone in medium is sufficient for adaptation of 2i/L-ESCs to embryonic stem cells (ESCs) in a hypermethylated state (L-ESCs). Global transcriptomic analysis shows that L-ESCs are close to 2i/L-ESCs and in a stable state between naive and primed pluripotency. Notably, our results demonstrate that DNA methyltransferases (DNMTs) play an important role in LIF-dependent mouse ESC adaptation and self-renewal. LIF-dependent ESC adaptation efficiency is significantly increased in serum treatment and reduced in Dnmt3a or Dnmt3l knockout ESCs. Importantly, unlike epiblast stem cells, L-ESCs contribute to somatic tissues and germ cells in chimeras. L-ESCs cultured under such simple conditions as in this study would provide a more conducive platform to clarify the molecular mechanism of ESCs in in vitro culture
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Activin A and BMP4 Signaling Expands Potency of Mouse Embryonic Stem Cells in Serum-Free Media.
Inhibitors of Mek1/2 and Gsk3β, known as 2i, and, together with leukemia inhibitory factor, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency (2i/L-ESCs). However, recent reports show that prolonged Mek1/2 suppression impairs developmental potential of ESCs, and is rescued by serum (S/L-ESCs). Here, we show that culturing ESCs in Activin A and BMP4, and in the absence of MEK1/2 inhibitor (ABC/L medium), establishes advanced stem cells derived from ESCs (esASCs). We demonstrate that esASCs contributed to germline lineages, full-term chimeras and generated esASC-derived mice by tetraploid complementation. We show that, in contrast to 2i/L-ESCs, esASCs display distinct molecular signatures and a stable hypermethylated epigenome, which is reversible and similar to serum-cultured ESCs. Importantly, we also derived novel ASCs (blASCs) from blastocysts in ABC/L medium. Our results provide insights into the derivation of novel ESCs with DNA hypermethylation from blastocysts in chemically defined medium
Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection
Background and objectivesDisease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms.MethodsCOVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers.ResultsThe oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway.ConclusionThe oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19
Increased site 1 affinity improves biopotency of porcine growth hormone - Evidence against diffusion dependent receptor dimerization
Based on phage display optimization studies with human growth hormone (GH), it is thought that the biopotency of GH cannot be increased. This is proposed to be a result of the affinity of the first receptor for hormone far exceeding that which is required to trap the hormone long enough to allow diffusion of the second receptor to form the ternary complex, which initiates signaling. We report here that despite similar site 1 kinetics to the hGH/hGH receptor interaction, the potency of porcine GH for its receptor can be increased up to 5-fold by substituting hGH residues involved in site 1 binding into pGH. Based on extensive mutations and BIAcore studies, we show that the higher potency and site 1 affinity of hGH for the pGHR is primarily a result of a decreased off-rate associated with residues in the extended loop between helices 1 and 2 that interact with the two key tryptophans Trp(104) and Trp(169) in the receptor binding hot spot. Our mutagenic analysis has also identified a second determinant (Lys(165)), which in addition to His(169), restricts the ability of non-primate hormones to activate hGH receptor. The increased biopotency of GH that we observe can be explained by a model for GH receptor activation where subunit alignment is critical for effective signaling
Development and clinical application of radiomics in lung cancer
Abstract Since the discovery of X-rays at the end of the 19th century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics. These techniques have given rise to genomics, proteomics, metabolomics and other systems biology subspecialties, including radiogenomics. Radiogenomics is an important revolution in the traditional visually identifiable imaging technology and constitutes a new branch, radiomics. Radiomics is aimed at extracting quantitative imaging features automatically and developing models to predict lesion phenotypes in a non-invasive manner. Here, we summarize the advent and development of radiomics, the basic process and challenges in clinical practice, with a focus on applications in pulmonary nodule evaluations, including diagnostics, pathological and molecular classifications, treatment response assessments and prognostic predictions, especially in radiotherapy
Performance of radiomics models derived from different CT reconstruction parameters for lung cancer risk prediction
Abstract Background This study analysed the performance of radiomics features extracted from computed tomography (CT) images with different reconstruction parameters in differentiating malignant and benign pulmonary nodules. Methods We evaluated routine chest CT images acquired from 148 participants with pulmonary nodules, which were pathologically diagnosed during surgery in West China Hospital, including a 5 mm unenhanced lung window, a 5 mm unenhanced mediastinal window, a 5 mm contrast-enhanced mediastinal window and a 1 mm unenhanced lung window. The pulmonary nodules were segmented, and 1409 radiomics features were extracted for each window. Then, we created 15 cohorts consisting of single windows or multiple windows. Univariate correlation analysis and principal component analysis were performed to select the features, and logistic regression analysis was performed to establish models for each cohort. The area under the curve (AUC) was applied to compare model performance. Results There were 75 benign and 73 malignant pulmonary nodules, with mean diameters of 18.63 and 19.86 mm, respectively. For the single-window setting, the AUCs of the radiomics model from the 5 mm unenhanced lung window, 5 mm unenhanced mediastinal window, 5 mm contrast-enhanced mediastinal window and 1 mm unenhanced lung window were 0.771, 0.808, 0.750, and 0.771 in the training set and 0.711, 0.709, 0.684, and 0.674 in the test set, respectively. Regarding the multiple-window setting, the radiomics model based on all four windows showed an AUC of 0.825 in the training set and 0.743 in the test set. Statistically, the 15 models demonstrated comparable performances (P > 0.05). Conclusion A single chest CT window was acceptable in predicting the malignancy of pulmonary nodules, and additional windows did not statistically improve the performance of the radiomics models. In addition, slice thickness and contrast enhancement did not affect the diagnostic performance
Clinicopathological Analysis of Pulmonary Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Background and objective As a rare disease, pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT), is often misdiagnosed. The aim of this study is to summarize the clinical and pathological features of this disease and improve the awareness of doctors. Methods Seven cases (female 5, male 2) diagnosed of PMZL-MALT in West China Hospital between November 2008 and November 2010, were analyzed retrospectively, including their symptoms, radiological findings, pathological examinations, treatment and prognosis. Results The median age of the patients were 62 years old (range 34-79 years). Six patients suffered from cough and sputum. Pulmonary consolidation was the most frequent manifestation, leading a misdiagnosis of pneumonia with CT examinations. Pathological diagnosis was obtained via fiberoptic bronchoscopy in six patients and percutaneous pulmonary biopsy for the rest one. In the seven cases, immunohistochemical results showed CD20(+), CD79a(+), while CD3 epsilon(-), CD5(-), CyclinD1(-), CD10(-), Bcl-2(-) and CD30(-). Additionally, the expression of Ki-67 was below 10%. Further PCR analysis showed evidence of immunoglobulin heavy chain gene rearrangement in tissues from six subjects. Based on the disease location and patients’ wishes, compared with two cases just receiving symptomatic treatments, the other five ones took in chemotherapies. Conclusion Since there were no specific clinical features for patients of PMZL-MALT, histopathological examination was the only effective means to confirm the diagnosis
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