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HIV rebounds after cessation of antiretroviral therapy, representing a barrier to cure. To better understand the virus reservoir, analysis pipelines have been developed that categorize proviral sequences as intact or defective, and further determine the precise nature of the sequence defects that may be present. We investigated the effects that different analysis pipelines had on the characterization of HIV?1 proviral sequences. We used single genome amplification to generate near full?length (NFL) HIV?1 proviral DNA sequences, defined as amplicons greater than 8000 base pairs in length, isolated from peripheral blood mononuclear cells (PBMC) of treated suppressed participants with HIV?1. Amplicons underwent direct next?generation single genome sequencing and were analysed using four HIV?1 proviral characterization pipelines. Sequences were characterized as intact or defective; defective sequences were assessed for the number and types of defects present. To confirm and extend our findings, 691 proviruses from the Proviral Sequence Database (PSD) were analysed and the ProSeq?IT tool of the PSD was used to characterize both the participant and PSD proviruses. Virus sequences derived from thirteen ART?treated virologically suppressed participants with HIV were studied. A total of 693 HIV?1 proviral sequences were generated, 282 of which were NFL. An average of 53 sequences per participant was analysed. We found that proviruses often harbour multiple sequence defect types (mean 2.7, 95% confidence interval [CI] 2.5, 3.0); the elimination order used by each pipeline affected the percentage of proviruses allotted into each defect category. These differences varied between participants, depending on the number of defect categories present in a given provirus sequence. Pipeline?specific differences in characterizing the HIV?1 5? untranslated region (5? UTR) led to an overestimation of the number of intact NFL proviral sequences, a finding corroborated in the independent PSD analysis. A comparison of the four published pipelines to ProSeq?IT found that ProSeq IT was more likely to characterize proviruses as intact. The choice of pipeline used for HIV?1 provirus landscape analysis may bias the classification of defective sequences. To improve the comparison of provirus characterizations across research groups, the development of a consensus elimination pipeline should be prioritized.

Introduction HIV rebounds after cessation of antiretroviral therapy, representing a barrier to cure. To better understand the virus reservoir, analysis pipelines have been developed that categorize proviral sequences as intact or defective, and further determine the precise nature of the sequence defects that may be present. We investigated the effects that different analysis pipelines had on the characterization of HIV‐1 proviral sequences. Methods We used single genome amplification to generate near full‐length (NFL) HIV‐1 proviral DNA sequences, defined as amplicons greater than 8000 base pairs in length, isolated from peripheral blood mononuclear cells (PBMC) of treated suppressed participants with HIV‐1. Amplicons underwent direct next‐generation single genome sequencing and were analysed using four HIV‐1 proviral characterization pipelines. Sequences were characterized as intact or defective; defective sequences were assessed for the number and types of defects present. To confirm and extend our findings, 691 proviruses from the Proviral Sequence Database (PSD) were analysed and the ProSeq‐IT tool of the PSD was used to characterize both the participant and PSD proviruses. Results and discussion Virus sequences derived from thirteen ART‐treated virologically suppressed participants with HIV were studied. A total of 693 HIV‐1 proviral sequences were generated, 282 of which were NFL. An average of 53 sequences per participant was analysed. We found that proviruses often harbour multiple sequence defect types (mean 2.7, 95% confidence interval [CI] 2.5, 3.0); the elimination order used by each pipeline affected the percentage of proviruses allotted into each defect category. These differences varied between participants, depending on the number of defect categories present in a given provirus sequence. Pipeline‐specific differences in characterizing the HIV‐1 5′ untranslated region (5′ UTR) led to an overestimation of the number of intact NFL proviral sequences, a finding corroborated in the independent PSD analysis. A comparison of the four published pipelines to ProSeq‐IT found that ProSeq IT was more likely to characterize proviruses as intact. Conclusions The choice of pipeline used for HIV‐1 provirus landscape analysis may bias the classification of defective sequences. To improve the comparison of provirus characterizations across research groups, the development of a consensus elimination pipeline should be prioritized.

NF-κB is an evolutionarily conserved eukaryotic transcription factor that plays a role in many important developmental and immune-related processes by activating target gene expression. The goal of these experiments was to define the sequences required for a sea anemone NF-κB's intrinsic transactivation activity by using mutant proteins with serial deletions of the N- and C-terminal sequences. Deletion mutants were constructed that were missing the C-terminal 15, 32 or 47 amino acids (aa) or the N-terminal 17, 27 or 47 aa of the 440 aa NF-κB protein from the starlet sea anemone, Nematostella vectensis (Nv), a simple model organism in the phylum Cnidaria. These Nv-NF-κB mutants were expressed as GAL4 fusion proteins in yeast, and their transactivation activities were assessed by LacZ reporter gene assays. The deletion of 47 aa from either the N terminus or the C terminus of NF-κB completely inactivates the transactivation function of Nv-NF-κB. In addition, we identified proline-258 in the center of the protein as a key residue for the transactivation function of Nv-NF-κB. Taken together, these results demonstrate that non-conserved N- and C-terminal residues are both required for the transcriptional activating function of the sea anemone NF-κB protein, suggesting that it has a novel functional domain structure among known NF-κB proteins.

The combination of multi-temporal images and deep learning is an efficient way to obtain accurate crop distributions and so has drawn increasing attention. However, few studies have compared deep learning models with different architectures, so it remains unclear how a deep learning model should be selected for multi-temporal crop classification, and the best possible accuracy is. To address this issue, the present work compares and analyzes a crop classification application based on deep learning models and different time-series data to exploit the possibility of improving crop classification accuracy. Using Multi-temporal Sentinel-2 images as source data, time-series classification datasets are constructed based on vegetation indexes (VIs) and spectral stacking, respectively, following which we compare and evaluate the crop classification application based on time-series datasets and five deep learning architectures: (1) one-dimensional convolutional neural networks (1D-CNNs), (2) long short-term memory (LSTM), (3) two-dimensional-CNNs (2D-CNNs), (4) three-dimensional-CNNs (3D-CNNs), and (5) two-dimensional convolutional LSTM (ConvLSTM2D). The results show that the accuracy of both 1D-CNN (92.5%) and LSTM (93.25%) is higher than that of random forest (~ 91%) when using a single temporal feature as input. The 2D-CNN model integrates temporal and spatial information and is slightly more accurate (94.76%), but fails to fully utilize its multi-spectral features. The accuracy of 1D-CNN and LSTM models integrated with temporal and multi-spectral features is 96.94% and 96.84%, respectively. However, neither model can extract spatial information. The accuracy of 3D-CNN and ConvLSTM2D models is 97.43% and 97.25%, respectively. The experimental results show limited accuracy for crop classification based on single temporal features, whereas the combination of temporal features with multi-spectral or spatial information significantly improves classification accuracy. The 3D-CNN and ConvLSTM2D models are thus the best deep learning architectures for multi-temporal crop classification. However, the ConvLSTM architecture combining recurrent neural networks and CNNs should be further developed for multi-temporal image crop classification.

Although third-party certification has been widely regarded as an important means of controlling greenwash, an issue that hampers environmental sustainability and pollution control outcomes, third-party certification has limited effects on greenwash in Chinese green bond market. How to make third-party certification effectively prevent greenwash has become an urgent problem to solve under current context that third-party certification for green bond is not compulsory in China. We attempt to address this problem for the first time by applying two simple game models and two signalling game models through three stages. The equilibrium results show that (1) information transmission is crucial in preventing greenwash; (2) providing the incentive for issuers to undergo third-party certification is the key for third-party certification to effectively prevent greenwash in Chinese green bond market; (3) when there is the incentive for issuers to undergo third-party certification, third-party certification can function as an effective signal that separates non-greenwashing issuers from greenwashing ones, which is conducive to alleviating information asymmetry, thereby preventing greenwash effectively in green bond market. Also, the theoretical range of the incentive is determined, implying that the incentive should be within the theoretical range to play its role. This study further provides policy implications of establishing an incentive mechanism that the government should provide tax deductions and exemptions, offer financial subsidies, and grant priority approval privileges for the green bond issuers who actively adopt third-party certification. Graphical abstract

Pre-mRNA splicing is a fundamental process that plays a considerable role in generating protein diversity. Pre-mRNA splicing is also the key to the pathology of numerous diseases, especially cancers. In this review, we discuss how aberrant splicing isoforms precisely regulate three basic functional aspects in cancer: proliferation, metastasis and apoptosis. Importantly, clinical function of aberrant splicing isoforms is also discussed, in particular concerning drug resistance and radiosensitivity. Furthermore, this review discusses emerging strategies how to modulate pathologic aberrant splicing isoforms, which are attractive, novel therapeutic agents in cancer. Last we outline current and future directions of isoforms diagnostic methodologies reported so far in cancer. Thus, it is highlighting significance of aberrant splicing isoforms as markers for cancer and as targets for cancer therapy.

The paper studies the dynamic characteristics of a multi-layer foil thrust bearing (MLFTB). A modified efficient dynamic characteristic model is established, and the revised Reynolds equation coupled with the thick plate element and the boundary slip model is adopted. During the solving process, the small perturbation method is implemented. The elasto-hydrodynamic effect under geometric and operational parameters is investigated. It reflects that the dynamic characteristics can be visibly influenced by the slip effect when under tiny clearance with low bearing speed, and ought to be considered. Specifically, the maximum deviation of the axial and direct-rotational stiffness coefficients could be up to −4.93% and −5.02%, respectively. The direct-rotational stiffness is increased with the perturbation frequency; however, a turning point may exist in the cross-rotational stiffness. Additionally, both the rotational stiffness and rotational damping can be expanded at a smaller original clearance. It aims to provide prediction methods with high effectiveness and efficiency, and enrich theoretical guidance for the important MLFTB.

A modified static characteristic model for the multi-layer foil thrust bearing (MLFTB) is established. In this model, the finite difference method and the thick plate element are implemented, the compressible Reynolds equation is linearized by the Newton–Raphson method, and the evolution law of the static characteristics with the geometric and operational parameters is derived by iterative solution. The results indicate that the bearing capacity could be generally decreased by around 3.15% when considering the slip boundary condition, which should not be neglected. Also, when under the rigorous wedge effect, the pressure peak near the mini clearance exhibits an obvious double peak shape. The bearing capacity can be slightly enhanced by an increase in the tilt angle of the thrust disk. In comparison to data in the literature, the current model shows satisfactory precision for the multi-layer foil thrust bearing. It aims to provide effective predictive means and theoretical reference for MLFTB.

Necrotizing enterocolitis (NEC) represents a severe condition in infants, with perforation being a particularly critical pathological manifestation. However, there is an absence of guidelines regarding the refeeding of infants recovering from perforation subsequent to NEC. This study aimed to determine the optimal refeeding method for term infants recovering from perforation after NEC. The study encompassed three aspects: the timing of enteral nutrition (EN) resumption, the progression of EN, and the method of EN resumption. Ninety full-term neonates who developed perforation following NEC and underwent surgical intervention were included. These samples were divided into early enteral nutrition (EEN, < 7 days) and late enteral nutrition (LEN, ≥ 7 days) groups based on the timing of EN resumption; faster increase (FI, ≥ 20 ml/kg/d) and slower increase (SI, < 20 ml/kg/d) groups based on the progression of EN; intact protein formula (IPF), special medical formula (SMF, including EHF and AABF), and mixed feeding (MF) groups based on the method of EN resumption. EEN infants had a lower incidence of intestinal stenosis and reoperation (43.5% vs. 77.6%, p  = 0.002; 60.9% vs. 82.1%, p  = 0.038), and a shorter duration of hospital stay after surgery and parenteral nutrition (PN) than LEN infants (14 days vs. 20 days, p  < 0.001; 11 days vs. 17 days, p  < 0.001). Faster increasing feed volumes was associated with shorter duration of hospital stay and parenteral nutrition (15 days vs. 20 days, p  < 0.001; 14 days vs. 17 days, p  < 0.001), but a slower rate of weight gain (0.020 kg vs. 0.129 kg, p  < 0.01). The time to repeat NPO in SMF group is shorter than IPF an MF groups (3 days vs. 4 days and 9 days, p  = 0.025). Our study demonstrates the beneficial effects of early enteral feeding and fast advancement of feed volumes in term infants with NEC and perforation after surgery, specifically in reducing short-term complications and the duration of hospital stay following surgery and PN. Additionally, this study suggests that IPF and MF significantly contribute to stimulate intestinal adoption recovery.

Background IL-35–producing Bregs and Treg cells critically regulate chronic illnesses worldwide via mechanisms related to disrupting the gut microbiota composition. However, whether the gut microbiota regulates these IL-35 + cells remains elusive. We herein investigated the regulatory effects of the gut microbiota on IL-35 + cells by using genetically modified mouse models of obesity. Results We first found that gut Reg4 promoted resistance to high-fat diet-induced obesity. Using 16S rRNA sequencing combined with LC-MS (liquid chromatography–mass spectrometry)/MS, we demonstrated that gut Reg4 associated with bacteria such as Lactobacillus promoted the generation of IL-35 + B cells through 3-idoleacetic acid (IAA) in the presence of LPS. HuREG4 IECtg mice fed a high-fat diet exhibited marked IL-35 + cell accumulation in not only their adipose tissues but also their colons, whereas decreased IL-35 + cell accumulation was observed in the adipose and colon tissues of Reg4 knockout (KO) mice. We also found that Reg4 mediated HFD-induced obesity resistance via IL-35. Lower levels of IAA were also detected in the peripheral blood of individuals with obesity compared with nonobese subjects. Mechanistically, IAA together with LPS mediated IL-35 + B cells through PXR and TLR4. KO of PXR or TLR4 impaired the generation of IL-35 + B cells. Conclusion Together, IAA and LPS induce the generation of IL-35 + B cells through PXR and TLR4. ESFDmA-1LKhrrc6QfnM_pP Video Abstract