The trRosetta (transform-restrained Rosetta) server is a web-based platform for fast and accurate protein structure prediction, powered by deep learning and Rosetta. With the input of a protein's ...amino acid sequence, a deep neural network is first used to predict the inter-residue geometries, including distance and orientations. The predicted geometries are then transformed as restraints to guide the structure prediction on the basis of direct energy minimization, which is implemented under the framework of Rosetta. The trRosetta server distinguishes itself from other similar structure prediction servers in terms of rapid and accurate de novo structure prediction. As an illustration, trRosetta was applied to two Pfam families with unknown structures, for which the predicted de novo models were estimated to have high accuracy. Nevertheless, to take advantage of homology modeling, homologous templates are used as additional inputs to the network automatically. In general, it takes ~1 h to predict the final structure for a typical protein with ~300 amino acids, using a maximum of 10 CPU cores in parallel in our cluster system. To enable large-scale structure modeling, a downloadable package of trRosetta with open-source codes is available as well. A detailed guidance for using the package is also available in this protocol. The server and the package are available at https://yanglab.nankai.edu.cn/trRosetta/ and https://yanglab.nankai.edu.cn/trRosetta/download/ , respectively.
With the advent of Software Defined Network (SDN) and Network Functions Virtualization (NFV), network operators can offer Service Function Chain (SFC) flexibly to accommodate the diverse network ...function (NF) requirements of their users. However, deploying SFCs efficiently on the underlying network in response to dynamic SFC requests poses significant challenges and complexities. This paper proposes a dynamic SFC deployment and readjustment method based on deep Q network (DQN) and M Shortest Path Algorithm (MQDR) to address this problem. We develop a model of the dynamic deployment and readjustment of the SFC problem on the basis of the NFV/SFC network to maximize the request acceptance rate. We transform the problem into a Markov Decision Process (MDP) and further apply Reinforcement Learning (RL) to achieve this goal. In our proposed method (MQDR), we employ two agents that dynamically deploy and readjust SFCs collaboratively to enhance the service request acceptance rate. We reduce the action space for dynamic deployment by applying the M Shortest Path Algorithm (MSPA) and decrease the action space for readjustment from two dimensions to one. By reducing the action space, we decrease the training difficulty and improve the actual training effect of our proposed algorithm. The simulation experiments show that MDQR improves the request acceptance rate by approximately 25% compared with the original DQN algorithm and 9.3% compared with the Load Balancing Shortest Path (LBSP) algorithm.
Abstract
RNA 3D structure prediction is a long-standing challenge. Inspired by the recent breakthrough in protein structure prediction, we developed trRosettaRNA, an automated deep learning-based ...approach to RNA 3D structure prediction. The trRosettaRNA pipeline comprises two major steps: 1D and 2D geometries prediction by a transformer network; and 3D structure folding by energy minimization. Benchmark tests suggest that trRosettaRNA outperforms traditional automated methods. In the blind tests of the 15
th
Critical Assessment of Structure Prediction (CASP15) and the RNA-Puzzles experiments, the automated trRosettaRNA predictions for the natural RNAs are competitive with the top human predictions. trRosettaRNA also outperforms other deep learning-based methods in CASP15 when measured by the Z-score of the Root-Mean-Square Deviation. Nevertheless, it remains challenging to predict accurate structures for synthetic RNAs with an automated approach. We hope this work could be a good start toward solving the hard problem of RNA structure prediction with deep learning.
Purely-organic clusterization-triggered emission (CTE) has displayed promising abilities in bioimaging, chemical sensing, and multicolor luminescence. However, it remains absent in the field of ...circularly polarized luminescence (CPL) due to the difficulties in well-aligning the nonconventional luminogens. We report a case of CPL generated with CTE using the solid phase molecular self-assembly (SPMSA) of poly-L-lysine (PLL) and oleate ion (OL), that is, the macroscopic CPL supramolecular film self-assembled by the electrostatic complex of PLL/OL under mechanical pressure. Well-defined interface charge distribution, given by lamellar mesophases of OL ions, forces the PLL chains to fold regularly as a requirement of optimal electrostatic interactions. Further facilitated by hydrogen bonding, the through-space conjugation (TSC) of orderly aligned electron-rich O and N atoms leads to CTE-based CPL, which is capable of transferring energy to an acceptor via a Förster resonance energy transfer (FRET) process, making it possible to develop environmentally friendly and economic CPL from sustainable and renewable materials.
Radiotherapy to cancer patients is inevitably accompanied by normal tissue injury, and the bone is one of the most commonly damaged tissues. Damage to bone marrow mesenchymal stem cells (BM-MSCs) ...induced by radiation is thought to be a major cause of radiation-induced bone loss. Exosomes exhibit great therapeutic potential in the treatment of osteoporosis, but whether exosomes are involved in radiation-induced bone loss has not been thoroughly elucidated to date. The main purpose of this study is to investigate the role of exosomes derived from BM-MSCs in restoring recipient BM-MSC function and alleviating radiation-induced bone loss.
BM-MSC-derived exosomes were intravenously injected to rats immediately after irradiation. After 28 days, the left tibiae were harvested for micro-CT and histomorphometric analysis. The effects of exosomes on antioxidant capacity, DNA damage repair, proliferation, and cell senescence of recipient BM-MSCs were determined. Osteogenic and adipogenic differentiation assays were used to detect the effects of exosomes on the differentiation potential of recipient BM-MSCs, and related genes were measured by qRT-PCR and Western blot analysis. β-Catenin expression was detected at histological and cytological levels.
BM-MSC-derived exosomes can attenuate radiation-induced bone loss in a rat model that is similar to mesenchymal stem cell transplantation. Exosome-treated BM-MSCs exhibit reduced oxidative stress, accelerated DNA damage repair, and reduced proliferation inhibition and cell senescence-associate protein expression compared with BM-MSCs that exclusively received irradiation. Following irradiation, exosomes promote β-catenin expression in BM-MSCs and restore the balance between adipogenic and osteogenic differentiation.
Our findings indicate that BM-MSC-derived exosomes take effects by restoring the function of recipient BM-MSCs. Therefore, exosomes may represent a promising cell-free therapeutic approach for the treatment of radiation-induced bone loss.
Minimizing platinum (Pt) loading while reserving high reaction efficiency in the catalyst layer (CL) has been confirmed as one of the key issues in improving the performance and application of proton ...exchange membrane fuel cells (PEMFCs). To enhance the reaction efficiency of Pt catalyst in CL, the interfacial interactions in the three-phase interface, i.e., carbon, Pt, and ionomer should be first clarified. In this study, a molecular model containing carbon, Pt, and ionomer compositions is built and the radial distribution functions (RDFs), diffusion coefficient, water cluster morphology, and thermal conductivity are investigated after the equilibrium molecular dynamics (MD) and nonequilibrium MD simulations. The results indicate that increasing water content improves water aggregation and cluster interconnection, both of which benefit the transport of oxygen and proton in the CL. The growing amount of ionomer promotes proton transport but generates additional resistance to oxygen. Both the increase of water and ionomer improve the thermal conductivity of the C. The above-mentioned findings are expected to help design catalyst layers with optimized Pt content and enhanced reaction efficiency, and further improve the performance of PEMFCs.
This study aimed to investigate the causal associations between several liver traits (liver iron content, percent liver fat, alanine transaminase levels, and liver volume) and colorectal cancer (CRC) ...risk using a Mendelian randomization (MR) approach to improve our understanding of the disease and its management.
Genetic variants were used as instrumental variables, extracted from genome-wide association studies (GWAS) datasets of liver traits and CRC. The Two-Sample MR package in R was used to conduct inverse variance weighted (IVW), MR Egger, Maximum likelihood, Weighted median, and Inverse variance weighted (multiplicative random effects) MR approaches to generate overall estimates of the effect. MR analysis was conducted with Benjamini-Hochberg method-corrected P values to account for multiple testing (P < 0.013). MR-PRESSO was used to identify and remove outlier genetic variants in Mendelian randomization (MR) analysis. The MR Steiger test was used to assess the validity of the assumption that exposure causes outcomes. Leave-one-out validation, pleiotropy, and heterogeneity testing were also conducted to ensure the reliability of the results. Multivariable MR was utilized for validation of our findings using the IVW method while also adjusting for potential confounding or pleiotropy bias.
The MR analysis suggested a causal effect between liver volume and a reduced risk of CRC (OR 0.60; 95% CI, 0.44-0.82; P = 0.0010) but did not provide evidence for causal effects of liver iron content, percent liver fat, or liver alanine transaminase levels. The MR-PRESSO method did not identify any outliers, and the MR Steiger test confirmed that the causal direction of the analysis results was correct in the Mendelian randomization analysis. MR results were consistent with heterogeneity and pleiotropy analyses, and leave-one-out analysis demonstrated the overall values obtained were consistent with estimates obtained when all available SNPs were included in the analysis. Multivariable MR was utilized for validation of our findings using the IVW method while also adjusting for potential confounding or pleiotropy bias.
The study provides tentative evidence for a causal role of liver volume in CRC, while genetically predicted levels of liver iron content, percent liver fat, and liver alanine transaminase levels were not associated with CRC risk. The findings may inform the development of targeted therapeutic interventions for colorectal liver metastasis (CRLM) patients, and the study highlights the importance of MR as a powerful epidemiological tool for investigating causal associations between exposures and outcomes.
Bursaphelenchus xylophilus is a pest that interferes with the health of forests and hinders the development of the forestry industry, and its spread is influenced by changes in abiotic factors and ...human activities. The potential distribution areas of B. xylophilus in China under four shared-economic pathways were predicted using the optimized MaxEnt model (version 3.4.3), combining data from a variety of environmental variables: (1) prediction of natural environmental variables predicted under current climate models; (2) prediction of natural environmental variables + human activities under current climate models; and (3) prediction of natural environmental variables under the future climate models (2050s and 2070s). Meanwhile, whether the niche of B. xylophilus has changed over time is analyzed. The results showed that human activities, precipitation in the driest month, annual precipitation, and elevation had significant effects on the distribution of B. xylophilus. In the current conditions, human activities greatly reduced the survival area of B. xylophilus, and its suitable distribution area was mainly concentrated in the southwestern and central regions of China. Under the influence of climate change in the future, the habitat of B. xylophilus will gradually spread to the northeast. In addition, the ecological niche overlap analysis showed that B. xylophilus in future climate was greater than 0.74. This study provides important information for understanding the ecological adaptation and potential risk of B. xylophilus, which can help guide the decision making of pest control and forest protection.
Permanent magnet synchronous motors (PMSMs) with inverters are widely used in electric vehicles (EVs). However, current harmonics caused by the nonlinearity of the inverter generate torque ripples ...and give rise to torsional vibration in the vehicle driveline. This paper proposes a new compensation method to suppress the torque ripples. This method extracts the 6th-order harmonic component online from the d-axis and q-axis currents with the approximate Fourier transform, and adopts a harmonic current PI regulator to calculate compensation voltage, which is added to the voltage reference to compensate the nonlinearity of the inverter. After correcting the current distortion and improving the motor torque smoothness, the torsional vibration of the driveline caused by the motor pulsating torque is reduced. According to the simulation results, the 6th-order of motor torque ripple and the torsional vibration response is reduced about 26–28%, which confirms the validity of the proposed strategy. The proposed method does not need any additional hardware and can be implemented broadly in PMSM drives.
Peripheral neuropathic pain (NeP), induced by surgical intervention, is a well-known complication or sequela that remains a clinical challenge with few effective treatments. Ideal animal models that ...can recapitulate surgery-associated NeP remain to be established for both mechanistic studies and drug discovery.
We aimed to establish a new rat model of postsurgical NeP and describe its characteristics, as well as screen-promising therapeutic analgesics.
Experimental research in rats.
The research took place in the laboratory of Xinqiao Hospital of the Third Military Medical University.
To mimic the surgical procedure associated with peripheral nerve injury (PNI), we established a transient compression injury (TCI) in the sciatic nerve. Behavioral tests of nociception were used to confirm the effect and the time course of this pain model. Histological assessments (transmission electron microscopy evaluation and immunohistochemistry) were performed to observe the neuropathological and immunological features. RNA sequencing (RNA-seq) of injured nerves and dorsal root ganglia (DRGs) was conducted to reveal the underlying mechanism in the newly established animal model and screen promising therapeutic targets.
We established a rat model of TCI of the PN and detected nociceptive hypersensitivity of the injured (ipsilateral) nerve by behavioral tests. This animal model of NeP was further confirmed by observing time-dependent changes in mechanical allodynia and thermal hyperalgesia, as well as by examining the activation of microglia in the ipsilateral spinal dorsal horn. Pathophysiologically, TCI induced macroscopic nerve swelling and demyelination, which resulted in inflammatory responses in ipsilateral nerves. We also found inflammatory cell infiltration in the ipsilateral nerve that was sustained for several weeks, which further exacerbated local inflammation and oxidative stress. Moreover, RNA-seq revealed remarkably upregulated inflammatory reactions in PNs and the DRGs. Notably, the overexpression of inflammatory mediators and the infiltration of macrophages and microglia triggered remote immune responses in DRGs. Based on the RNA-seq results, we also confirmed that gabapentin (GBP) exerts therapeutic effects in TCI-induced NeP by regulating alpha2delta-1.
We did not compare the new rat model with the classical pain model (like chronic constriction injury or spared nerve injury) in histology or transcriptomics.
We established a new rat model of NeP and thoroughly characterized neuroinflammation in the injured nerve and DRGs. Based on the upregulated genes in DRGs in this model, we screened a promising analgesic (GBP) capable of reducing pain hypersensitivity in surgery-associated NeP.
PDF
