VirusPredictor: XGBoost-based software to predict virus-related sequences in human data.

MOTIVATION: Discovering disease causative pathogens, particularly viruses without reference genomes, poses a technical challenge as they are often unidentifiable through sequence alignment. Machine learning prediction of patient high-throughput sequences unmappable to human and pathogen genomes may reveal sequences originating from uncharacterized viruses. Currently, there is a lack of software specifically designed for accurately predicting such viral sequences in human data. RESULTS: We developed a fast XGBoost method and software VirusPredictor leveraging an in-house viral genome database. Our two-step XGBoost models first classify each query sequence into one of three groups: infectious virus, endogenous retrovirus (ERV) or non-ERV human. The prediction accuracies increased as the sequences became longer, i.e. 0.76, 0.93, and 0.98 for 150-350 (Illumina short reads), 850-950 (Sanger sequencing data), and 2000-5000 bp sequences, respectively. Then, sequences predicted to be from infectious viruses are further classified into one of six virus taxonomic subgroups, and the accuracies increased from 0.92 to >0.98 when query sequences increased from 150-350 to >850 bp. The results suggest that Illumina short reads should be de novo assembled into contigs (e.g. ∼1000 bp or longer) before prediction whenever possible. We applied VirusPredictor to multiple real genomic and metagenomic datasets and obtained high accuracies. VirusPredictor, a user-friendly open-source Python software, is useful for predicting the origins of patients' unmappable sequences. This study is the first to classify ERVs in infectious viral sequence prediction. This is also the first study combining virus sub-group predictions. AVAILABILITY AND IMPLEMENTATION: www.dllab.org/software/VirusPredictor.html.

Accelerated discovery of high-performance Al-Si-Mg-Sc casting alloys by integrating active learning with high-throughput CALPHAD calculations.

Scandium is the best alloying element to improve the mechanical properties of industrial Al-Si-Mg casting alloys. Most literature reports devote to exploring/designing optimal Sc additions in different commercial Al-Si-Mg casting alloys with well-defined compositions. However, no attempt to optimize the contents of Si, Mg, and Sc has been made due to the great challenge of simultaneous screening in high-dimensional composition space with limited experimental data. In this paper, a novel alloy design strategy was proposed and successfully applied to accelerate the discovery of hypoeutectic Al-Si-Mg-Sc casting alloys over high-dimensional composition space. Firstly, high-throughput CALculation of PHAse Diagrams (CALPHAD) solidification simulations of ocean of hypoeutectic Al-Si-Mg-Sc casting alloys over a wide composition range were performed to establish the quantitative relation 'composition-process-microstructure'. Secondly, the relation 'microstructure-mechanical properties' of Al-Si-Mg-Sc hypoeutectic casting alloys was acquired using the active learning technique supported by key experiments designed by CALPHAD and Bayesian optimization samplings. After a benchmark in A356-xSc alloys, such a strategy was utilized to design the high-performance hypoeutectic Al-xSi-yMg alloys with optimal Sc additions that were later experimentally validated. Finally, the present strategy was successfully extended to screen the optimal contents of Si, Mg, and Sc over high-dimensional hypoeutectic Al-xSi-yMg-zSc composition space. It is anticipated that the proposed strategy integrating active learning with high-throughput CALPHAD simulations and key experiments should be generally applicable to the efficient design of high-performance multi-component materials over high-dimensional composition space.

Cordyceps militaris acidic polysaccharides improve learning and memory impairment in mice with exercise fatigue through the PI3K/NRF2/HO-1 signalling pathway.

Excessive exercise leads to body fatigue and destroys the balance of the oxidation/oxidation resistance system in the body, thus damaging the central nervous system and reducing learning and memory ability. Nrf2 is an important transcription factor that regulates the cell oxidative stress response. Therefore, the research and development of natural antioxidants with the effect of regulating Nrf2-related signalling pathways to improve central fatigue caused by body fatigue has application value. Methods and results: Cordyceps militaris polysaccharides were extracted, isolated and purified via DEAE-cellulose 52 and Sepharose CL-6B columns to obtain two saccharides, Cordyceps militaris acidic polysaccharides (CMPB) and CMPB-b. The results of behavioural tests showed that compared with the model group, the learning and memory abilities of the CMPB-H group (800 mg/kg) mice were remarkably improved in the dark avoidance and Morris water maze tasks (p < 0.01), and the levels of fatigue metabolites and oxidative stress in the body were obviously decreased (p < 0.01). The expression level of BDNF, PI3K, Nrf2 and HO-1 proteins in the hippocampus were significantly increased (p < 0.01). In vitro experiments, compared with the PC12 oxidative stress model group, CMPB-b high-dose group (100 µg/mL) had remarkably improved oxidative stress. CMPB-b also obviously promoted the phosphorylation of PI3K and AKT proteins (p < 0.01) and the nuclear translocation of Nrf2 (p < 0.01), and significantly increased the expression of HO-1 (p < 0.01). Conclusion: CMPB can alleviate the fatigue state of high-intensity swimming mice and improve the learning and memory impairment of exercise-fatigue mice by regulating the Nrf2-related signalling pathway. Its antioxidant active component CMPB-b exerts in vitro antioxidative neurological damage by the same mechanism. Our systematic studies provide strong supporting evidence for the future use of Cordyceps militaris acidic polysaccharides in health products to improve resistance to fatigue.

Is Tranexamic Acid Beneficial in Open Spine Surgery? and its Effects Vary by Dosage, Age, Sites, and Locations: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of tranexamic acid (TXA) in controlling blood loss during spine surgery remains unclear. With the publication of new randomized controlled trials (RCTs), we conducted a meta-analysis to determine the safety and efficacy of TXA in spine surgery. METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for relevant studies through 2022. Only RCTs were eligible for this study. The extracted data were analyzed using RevMan 5.3 software for meta-analysis. RESULTS: Twenty RCTs including 1497 patients undergoing spine surgery were included in this systematic evaluation. Compared with the control group, TXA significantly reduced total blood loss (mean difference [MD] = - 218.96, 95% confidence interval [CI] = - 309.77 to - 128.14, P < 0.00001), perioperative blood loss (MD = - 90.54, 95% CI = - 139.33 to - 41.75, P = 0.0003), postoperative drainage (MD = - 102.60, 95% CI = - 139.51 to - 65.70, P < 0.00001)，reduced hospital stay (MD = - 1.42, 95% CI = - 2.71 to - 0.14, P = 0.03), reduced total blood transfusion volume (MD = - 551.06, 95% CI = - 755.90 to - 346.22, P < 0.00001), and international normalized ratio (MD = -0.03, 95% CI = -0.04 to -0.02, P < 0.00001). CONCLUSIONS: Based on the meta-analysis of 20 RCTs, we demonstrated that TXA reduces blood loss in open spine surgery, decreases transfusion rates, and shortens hospital stays. The TXA administration during the perioperative period does not increase the incidence of postoperative complications.

Characterization of the complete chloroplast genome of the perennial plant Tradescantia ohiensis Raf. (Commelinales: Commelinaceae).

Tradescantia ohiensis Raf. (Ohio spiderwort/blue-jacket) is a perennial herb native to North America that has become widely established in China. The chloroplast (cp) genome of T. ohiensis was assembled using Illumina sequencing reads. It is 164,140 bp in length with an A + T-biased nucleotide composition, and comprises a large single-copy (LSC) region (91,248 bp), a small single-copy (SSC) region (18,426 bp), and a pair of inverted repeat (IR) regions (27,233 bp). The cp genome harbors a total of 112 gene species with 19 of them being completely or partially duplicated and 18 of them possessing one or two introns. Phylogenetic analysis suggests that T. ohiensis is most closely related to the congeneric T. virginiana.

Activation of CXCL6/CXCR1/2 Axis Promotes the Growth and Metastasis of Osteosarcoma Cells in vitro and in vivo.

Osteosarcoma (OS) is a malignant primary bone tumor with high metastatic rate. C-X-C motif chemokine ligand 6 (CXCL6) and its receptor C-X-C motif chemokine receptor 1/2 (CXCR1/2) have been found to participate in the process of carcinogenesis. In this study, we evaluated the role of CXCL6/CXCR1/2 axis in proliferation and metastasis of OS cells. According to our results, the mRNA and protein expressions of CXCL6, CXCR1, and CXCR2 in multiple OS cell lines were determined. Treatment with exogenous CXCL6 for more than 72 h significantly promoted the proliferation of OS cells. Blocking the effect of endogenous CXCL6 restrained the migration, invasion and epithelial-mesenchymal transition (EMT) as evidenced by increased E-cadherin level, decreased N-cadherin and Snail levels in OS cells. On the contrary, exogenous CXCL6 administration enhanced the migration and invasive abilities of OS cells. Moreover, silencing of CXCR1/2 suppressed migration, invasion and EMT of OS cells with or without treatment with exogenous CXCL6. In addition, exogenous CXCL6 promoted the activation of PI3K/AKT and ß-catenin signaling pathways, which could be repressed by CXCR2 knockdown. Inactivation of PI3K/AKT or ß-catenin pathway by specific inhibitors effectively suppressed CXCL6-induced migration, invasion and EMT of OS cells. Finally, overexpression of CXCL6 significantly contributed to tumor growth, pulmonary metastasis and activation of PI3K/AKT and ß-catenin pathways in nude mice in vivo, which were repressed by treatment with CXCR2 antagonist. Our results suggest that CXCL6/CXCR1/2 axis promotes the proliferation and metastasis of OS cells.

Recognition of the toxicity of aristolochic acid.

WHAT IS KNOWN AND OBJECTIVE: Aristolochic acid (AA) is an abundant compound in Aristolochia plants and various natural herbs. In the 1990s, a slimming formula used in Belgium that contains Aristolochia fangchi was reported to cause kidney damage and bladder cancer, and aristolochic acid nephropathy (AAN) is now well recognized worldwide. In October 2017, researchers reported an AA signature that is closely associated with hepatocellular carcinoma (HCC) worldwide. COMMENT: There are differing opinions on the toxicity of AA, and different countries have taken different measures to address the issue. There is a lack of clarity on the causal role of AA in hepatocarcinogenesis and on the potential underlying mechanisms for the reported nephrotoxicity and carcinogenicity. The toxicity of AA differs depending on gender and age, and other risk factors that could explain the variability in the toxicity of AA remain to be identified. WHAT IS NEW AND CONCLUSION: Whether preparations containing AA, such as many Chinese medicines, should be used remains controversial, and this issue warrants further investigation before definite conclusions can be drawn.

A selenium polysaccharide from Platycodon grandiflorum rescues PC12 cell death caused by H2O2 via inhibiting oxidative stress.

In this paper, a selenium polysaccharide (PGP1) was isolated from the radix of Platycodon grandiflorum. We investigated the protective capacity of PGP1 against the hydrogen peroxide (H2O2)-induced oxidative damage in cultured rat pheochromocytoma (PC12) cells. Cells were pretreated with various doses of PGP1 (50, 100 and 200µg/mL) for 24h before exposure to 0.5mM H2O2 for 12h. Cell viability, LDH release, apoptotic rates, malondialdehyde (MDA) content, antioxidant enzyme superoxide dismutase (SOD) activity and intracellular accumulation of reactive oxygen species (ROS) were determined. The results showed pretreatment of PC12 cells with PGP1 prior to H2O2 exposure inhibited the decrease of cell viability, decreased the apoptotic rates, prevented membrane damage (LDH release) and attenuated intracellular ROS formation in PC12 cells injured by H2O2. Meanwhile, PGP1 increased SOD activity, while it decreased the level of MDA and the production of lipid peroxidation, in PC12 cells after H2O2 exposure. These findings suggested that PGP1 may be considered as a potential useful antioxidant agent in reducing neuronal oxidative damage via inhibiting oxidative stress.

1.9-3.6 µm supercontinuum generation in a very short highly nonlinear germania fiber with a high mid-infrared power ratio.

In this Letter, a high-power supercontinuum (SC) laser source which spanned from 1.9 to 3.6 µm with an all-fiber configuration was reported. This SC laser was obtained by concatenating a thulium-doped fiber amplifier (TDFA) and a 12 cm long highly nonlinear germania fiber. A 1.9-2.7 µm SC laser from the TDFA was spectrally broadened continuously into the mid-infrared region (>3 µm) in the following germania fiber. When the repetition rate was 2 MHz, the obtained SC laser had a maximum output power of 6.12 W with an optical conversion efficiency of 15.3% with respect to the TDFA pump power. The SC laser had a spectral bandwidth of 1506 nm ranging from 1944 to 3450 nm at the -20 dB level. The SC power with wavelengths >3 µm was 2.9 W, corresponding to a high power ratio of 47.4% in the mid-infrared region. The achieved power ratio in the mid-infrared region, as well as the long wavelength cutoff, to the best of our knowledge, were the best results ever reported in germania fibers.

A polysaccharide from the leaves of Aralia elata induces apoptosis in U-2 OS cells via mitochondrial-dependent pathway.

In the present study, we isolated and characterized one purified polysaccharide (AEP-1) from the leaves of Aralia elata, and investigated its effect on human osteosarcoma (OS) U-2 OS cell line and analyzed its mechanism. MTT assays showed that AEP-1 markedly inhibited the growth of U-2 OS cells in a dose- and time-dependent fashion, suggesting a cytotoxic effect. The AEP-1 also dose-dependently induced DNA fragmentation and caused apoptotic death in U-2 OS cells. The event of apoptosis was accompanied by increased ratio of Bax/Bcl-2, depolarization of mitochondrial membrane potential (Δym) and the release of cytochrome c from mitochondria into the cytoplasm. Moreover, AEP-1 treatment triggered the activation of caspase-9 and caspase-3, as well as the cleavage of poly (ADP-ribose) polymerase (PAPR) in U-2 OS cells. All these results suggests that the induction of apoptosis by AEP-1 in U-2 OS cells occurs through the mitochondria-dependent pathway and AEP-1 may be useful in treating OS and improving cancer chemotherapy.

300 W-level, wavelength-widely-tunable, all-fiber integrated thulium-doped fiber laser.

A high-power, wavelength-tunable, all-fiber integrated thulium-doped fiber laser (TDFL) at 2 µm is presented. The TDFL has a compact configuration which only consists of a low power seed oscillator and a stage of fiber power amplifier. The seed oscillator adopts a tunable band-pass filter as the wavelength selective element, matching the gain spectrum of thulium-doped fiber. It can provide ~5 W single-mode seed laser with superb spectral characteristics, and the lasing wavelength is adjustable from 1890 to 2050 nm. The fiber power amplifier provides a total gain of ~17 dB at 2 µm which boosts the signal power to the 300 W-level. The maximum average power reaches 327.5 W at 1930 nm with the highest slope efficiency of 57.4%. This TDFL can afford >270 W lasing operation over the whole tuning range of 140 nm spanning from 1910 to 2050 nm, together with high spectral quality and power stability. This is the first demonstration, to the best of our knowledge, on an all-fiber integrated wavelength-widely-tunable TDFL at 2 µm with output power at the 300 W-level. The results are of great interest for many applications.

0.6-3.2 µm supercontinuum generation in a step-index germania-core fiber using a 4.4 kW peak-power pump laser.

An ultra-broadband supercontinuum was generated in a short piece of step-index germania-core fiber using a fiber laser with a peak power of 4.4 kW. The pure germania core made this fiber capable of propagating light towards the desirable mid-infrared region. The spectral broadening characteristics towards the mid-infrared region under different lengths of germania-core fiber were investigated using pump pulses of 4.4 kW and 1.1 ns at 1550 nm. The large nonlinear refractive index of germania and the small core size of germania-core fiber produced a nonlinear coefficient as high as 11.8 (W km)-1 at 1550 nm, which was beneficial for supercontinuum generation. The pump wavelength was located in the anomalous dispersion regime and close to the zero dispersion wavelength of this germania-core fiber, 1.426 µm. Eventually, an ultra-broadband supercontinuum source with a spectrum spanning from 0.6 to 3.2 µm was obtained and had a total output power of 350 mW at an optimized germania-core fiber length of 0.8 m. This work is the first demonstration, to the best of our knowledge, of a germania-core fiber-based ultra-broadband supercontinuum source that spans from the visible region to the mid-infrared region.

An adaptive integrated algorithm for noninvasive fetal ECG separation and noise reduction based on ICA-EEMD-WS.

High-resolution fetal electrocardiogram (FECG) plays an important role in assisting physicians to detect fetal changes in the womb and to make clinical decisions. However, in real situations, clear FECG is difficult to extract because it is usually overwhelmed by the dominant maternal ECG and other contaminated noise such as baseline wander, high-frequency noise. In this paper, we proposed a novel integrated adaptive algorithm based on independent component analysis (ICA), ensemble empirical mode decomposition (EEMD), and wavelet shrinkage (WS) denoising, denoted as ICA-EEMD-WS, for FECG separation and noise reduction. First, ICA algorithm was used to separate the mixed abdominal ECG signal and to obtain the noisy FECG. Second, the noise in FECG was reduced by a three-step integrated algorithm comprised of EEMD, useful subcomponents statistical inference and WS processing, and partial reconstruction for baseline wander reduction. Finally, we evaluate the proposed algorithm using simulated data sets. The results indicated that the proposed ICA-EEMD-WS outperformed the conventional algorithms in signal denoising.

Fully biobased and supertough polylactide-based thermoplastic vulcanizates fabricated by peroxide-induced dynamic vulcanization and interfacial compatibilization.

A fully biobased and supertough thermoplastic vulcanizate (TPV) consisting of polylactide (PLA) and a biobased vulcanized unsaturated aliphatic polyester elastomer (UPE) was fabricated via peroxide-induced dynamic vulcanization. Interfacial compatibilization between PLA and UPE took place during dynamic vulcanization, which was confirmed by gel measurement and NMR analysis. After vulcanization, the TPV exhibited a quasi cocontinuous morphology with vulcanized UPE compactly dispersed in PLA matrix, which was different from the pristine PLA/UPE blend, exhibiting typically phase-separated morphology with unvulcanized UPE droplets discretely dispersed in matrix. The TPV showed significantly improved tensile and impact toughness with values up to about 99.3 MJ/m(3) and 586.6 J/m, respectively, compared to those of 3.2 MJ/m(3) and 16.8 J/m for neat PLA, respectively. The toughening mechanisms under tensile and impact tests were investigated and deduced as massive shear yielding of the PLA matrix triggered by internal cavitation of VUPE. The fully biobased supertough PLA vulcanizate could serve as a promising alternative to traditional commodity plastics.

Attenuation of vaccinia Tian Tan strain by removal of viral TC7L-TK2L and TA35R genes.

Vaccinia Tian Tan (VTT) was attenuated by deletion of the TC7L-TK2L and TA35R genes to generate MVTT3. The mutant was generated by replacing the open reading frames by a gene encoding enhanced green fluorescent protein (EGFP) flanked by loxP sites. Viruses expressing EGFP were then screened for and purified by serial plaque formation. In a second step the marker EGFP gene was removed by transfecting cells with a plasmid encoding cre recombinase and selecting for viruses that had lost the EGFP phenotype. The MVTT3 mutant was shown to be avirulent and immunogenic. These results support the conclusion that TC7L-TK2L and TA35R deletion mutants can be used as safe viral vectors or as platform for vaccines.