IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor.

CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+ T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+ T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.

Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A Multivariate analysis on evoked components of Chinese semantic congruity: an OP-MEG study with EEG.

The application of wearable magnetoencephalography using optically-pumped magnetometers has drawn extensive attention in the field of neuroscience. Electroencephalogram system can cover the whole head and reflect the overall activity of a large number of neurons. The efficacy of optically-pumped magnetometer in detecting event-related components can be validated through electroencephalogram results. Multivariate pattern analysis is capable of tracking the evolution of neurocognitive processes over time. In this paper, we adopted a classical Chinese semantic congruity paradigm and separately collected electroencephalogram and optically-pumped magnetometer signals. Then, we verified the consistency of optically-pumped magnetometer and electroencephalogram in detecting N400 using mutual information index. Multivariate pattern analysis revealed the difference in decoding performance of these two modalities, which can be further validated by dynamic/stable coding analysis on the temporal generalization matrix. The results from searchlight analysis provided a neural basis for this dissimilarity at the magnetoencephalography source level and the electroencephalogram sensor level. This study opens a new avenue for investigating the brain's coding patterns using wearable magnetoencephalography and reveals the differences in sensitivity between the two modalities in reflecting neuron representation patterns.

Development towards high-resolution kHz-speed rotation-free volumetric imaging.

X-ray multi-projection imaging (XMPI) has the potential to provide rotation-free 3D movies of optically opaque samples. The absence of rotation enables superior imaging speed and preserves fragile sample dynamics by avoiding the centrifugal forces introduced by conventional rotary tomography. Here, we present our XMPI observations at the ID19 beamline (ESRF, France) of 3D dynamics in melted aluminum with 1000 frames per second and 8 µm resolution per projection using the full dynamical range of our detectors. Since XMPI is a method under development, we also provide different tests for the instrumentation of up to 3000 frames per second. As the high-brilliance of 4th generation light-sources becomes more available, XMPI is a promising technique for current and future X-ray imaging instruments.

Sensory neuron transcriptomes reveal complex neuron-specific function and regulation of mec-2/Stomatin splicing.

The function and identity of a cell is shaped by transcription factors controlling transcriptional networks, and further shaped by RNA binding proteins controlling post-transcriptional networks. To overcome limitations inherent to analysis of sparse single-cell post-transcriptional data, we leverage the invariant Caenorhabditis elegans cell lineage, isolating thousands of identical neuron types from thousands of isogenic individuals. The resulting deep transcriptomes facilitate splicing network analysis due to increased sequencing depth and uniformity. We focus on mechanosensory touch-neuron splicing regulated by MEC-8/RBPMS. We identify a small MEC-8-regulated network, where MEC-8 establishes touch-neuron isoforms differing from default isoforms found in other cells. MEC-8 establishes the canonical long mec-2/Stomatin isoform in touch neurons, but surprisingly the non-canonical short isoform predominates in other neurons, including olfactory neurons, and mec-2 is required for olfaction. Forced endogenous isoform-specific expression reveals that the short isoform functions in olfaction but not mechanosensation. The long isoform is functional in both processes. Remarkably, restoring the long isoform completely rescues mec-8 mutant mechanosensation, indicating a single MEC-8 touch-neuron target is phenotypically relevant. Within the long isoform we identify a cassette exon further diversifying mec-2 into long/extra-long isoforms. Neither is sufficient for mechanosensation. Both are simultaneously required, likely functioning as heteromers to mediate mechanosensation.

Efficacy and safety of acupressure in nausea and vomiting during pregnancy: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of acupressure on nausea and vomiting during pregnancy. METHODS: PubMed, Embase, Springer, Web of Science, and the Cochrane Library were searched for all randomized controlled trials (RCT) of treating nausea and vomiting during pregnancy by acupressure from the inception date of database to July 31st, 2023. Study selection, data extraction, and risk of bias assessment were conducted independently by researchers. The methodological quality of included studies was evaluated by the Cochrane Collaboration's bias risk assessment tool, meta-analysis by Stata 17.0 software, and publication bias by Begg's test. RESULTS: A total of 11 RCTs involving 1378 pregnant women were included in this review, which was assessed to be moderate quality. 10 RCTs involving 1298 pregnant women were assessed for the meta-analysis. The results revealed that acupressure showed significant difference on improvement in symptom score compared with sham acupressure (pooled MD, - 1.33; 95%CI [- 2.06, - 0.61]; P < 0.001) or control group (pooled MD, - 0.73; 95%CI [- 1.08, - 0.39]; P < 0.001), and incidence of effective rate compared with sham acupressure group (pooled RR, 1.78; 95%CI [1.03, 3.07]; P = 0.039). However, no statistical significance was found between acupressure and control group (pooled RR, 4.53; 95%CI [0.67, 30.48]; P = 0.120) on effective rate. On comparing acupressure with sham acupressure, there was no beneficial effect on preventing nausea and vomiting during pregnancy (pooled RR, 0.83; 95%CI [0.50, 1.38]; P = 0.476), shortening the duration of hospital stay (pooled MD, - 0.78; 95%CI [- 1.98, 0.41]; P = 0.199) and improving patient satisfaction (pooled RR, 1.36; 95%CI [0.47, 3.91]; P = 0.570). Begg's test did not reveal any publication bias. Only one RCT reported minimal acupressure-related adverse events. CONCLUSION: Acupressure may have potential favorable or encouraging effect on treating nausea and vomiting during pregnancy, but strong supportive data are not yet available. Well-designed and large-scale RCTs should be conducted for assessing and confirming the efficacy and safety of acupressure in nausea and vomiting during pregnancy.

Identity, pathogenicity and genetic diversity of Lasiodiplodia associated with stem-end rot of avocado in China.

Stem-end rot (SER) causes brown necrotic lesions in the pulp near the base of the fruit pedicel and is one of the most devastating postharvest diseases of avocados in all avocado growing regions of the world. China's avocado industry is growing very rapidly, and the planting area is expanding, but little is known about the pathogens and genetic diversity of avocado SER. To determine the causal agents of SER, avocado fruits were sampled from the main avocado-producing areas in China during 2020 and 2021. Fungal isolates were obtained from SER symptomatic avocado fruits and identified by morphology combined with phylogenetic analysis of internal transcribed spacer (ITS), translation elongation factor 1-α (EF1-α) and ß-tubulin (TUB2) gene sequences. All 101 isolates belonged to Lasiodiplodia spp., and four Lasiodiplodia species were identified, namely L. pseudotheobromae (59.41%), L. theobromae (24.75%), L. mahajangana (7.92%), L. euphorbiaceicola (1.98%), and six others are classified as Lasiodiplodia sp. (5.94%). There were only slight morphological differences in colonies and conidia of these four species of Lasiodiplodia. The pathogenicity tests showed symptoms of SER, and the 92.08% of the isolates exhibited a high level of virulence on avocado (disease index > 70), related to the disease severity on avocado fruit. All tested isolates grew well under conditions from 23 to 33℃. There was a significant difference in mycelial growth between the four species of Lasiodiplodia after treatment with high temperature or low temperature. L. pseudotheobromae growth was the fastest at 13 to 18℃, but was the lowest at 38℃ (P < 0.05). Red pigment could be produced by all tested isolates after culturing for 7 days at 38℃. The mycelial growth rate was the fastest on PDA medium, and the slowest on OMA medium but promoted spore formation (P < 0.05). In addition, was determined the genetic diversity of Lasiodiplodia pathogenic species associated with SER collected from avocado, mango, guava and soursop fruits was determined. A total of 74 isolates were clustered into 4 main ISSR groups by unweighted pair-group method with arithmetic mean (UPGMA) analysis, and the classification of this group was related to the host. Extensive diversity was detected in the Lasiodiplodia populations. The diverse geographical origins and host species significantly influenced the population differentiation, and most of the genetic variation occurred within populations (P < 0.001). This is the first study to identify the major pathogens of avocado SER in China and to survey their occurrence, pathogenicity and include a comparative analysis of genetic diversity with Lasiodiplodia spp. causing SER on other fruit hosts. Collectively, the Lasiodiplodia species complex affecting avocado showed high pathogenicity and diversity, while L. pseudotheobromae was the most frequently isolated species in China. The results of this study provide insights into the aspects of epidemic of SER disease caused by Lasiodiplodia species, which will help in developing strategies for the management and control of stem end-rot in avocado.

New wheat straw fermentation feed: recombinant Schizosaccharomyces pombe efficient degradation of lignocellulose and increase feed protein.

Wheat straw contains a high amount of lignin, hindering the action of cellulase and hemicellulase enzymes, leading to difficulties in nutrient absorption by animals from straw feed. However, currently, the biological treatment of straw relies primarily on fungal degradation and cannot be directly utilized for the preparation of livestock feed. This study focuses on enzymatic co-fermentation of wheat straw to produce high-protein, low-cellulose biological feed, integrating lignin degradation with feed manufacturing, thereby simplifying the feed production process. After the optimization using Box-Behnken Design for the feed formulation, with a glucose oxidase addition of 2.46%, laccase addition of 3.4%, and malonic acid addition of 0.6%, the wheat straw feed prepared in this experiment exhibited a true protein content of 9.35%. This represented a fourfold increase compared to the non-fermented state, and the lignocellulose degradation rate of wheat straw reached 45.42%. These results not only highlight the substantial enhancement in protein content but also underscore the significant advancement in lignocellulose breakdown. This formulation significantly enhanced the palatability and nutritional value of the straw feed, contributing to the industrial development of straw feed.

A gene based combination test using GWAS summary data.

BACKGROUND: Gene-based association tests provide a useful alternative and complement to the usual single marker association tests, especially in genome-wide association studies (GWAS). The way of weighting for variants in a gene plays an important role in boosting the power of a gene-based association test. Appropriate weights can boost statistical power, especially when detecting genetic variants with weak effects on a trait. One major limitation of existing gene-based association tests lies in using weights that are predetermined biologically or empirically. This limitation often attenuates the power of a test. On another hand, effect sizes or directions of causal genetic variants in real data are usually unknown, driving a need for a flexible yet robust methodology of gene based association tests. Furthermore, access to individual-level data is often limited, while thousands of GWAS summary data are publicly and freely available. RESULTS: To resolve these limitations, we propose a combination test named as OWC which is based on summary statistics from GWAS data. Several traditional methods including burden test, weighted sum of squared score test [SSU], weighted sum statistic [WSS], SNP-set Kernel Association Test [SKAT], and the score test are special cases of OWC. To evaluate the performance of OWC, we perform extensive simulation studies. Results of simulation studies demonstrate that OWC outperforms several existing popular methods. We further show that OWC outperforms comparison methods in real-world data analyses using schizophrenia GWAS summary data and a fasting glucose GWAS meta-analysis data. The proposed method is implemented in an R package available at https://github.com/Xuexia-Wang/OWC-R-package CONCLUSIONS: We propose a novel gene-based association test that incorporates four different weighting schemes (two constant weights and two weights proportional to normal statistic Z) and includes several popular methods as its special cases. Results of the simulation studies and real data analyses illustrate that the proposed test, OWC, outperforms comparable methods in most scenarios. These results demonstrate that OWC is a useful tool that adapts to the underlying biological model for a disease by weighting appropriately genetic variants and combination of well-known gene-based tests.

Genome-Wide Identification, Evolution and Expression Profile Analysis of NAC Transcription Factor in Simmondsia chinensis.

NAC transcription factors (TFs) are one of the largest plant-specific gene families and play important roles in plant growth, development, and the biotic and abiotic stress response. Although the sequencing of Jojoba (Simmondsia chinensis) has been completed, the genome-wide identification and analysis of its NAC TFs has not been reported. In this study, a total of 57 genes were identified in Jojoba, which were divided into eight groups based on phylogenetic analysis. The genes clustered in the same groups have a similar gene structure and motif distribution. Based on the analysis of cis-elements in NAC TFs, nine cis-acting elements were identified in the promoter region that involved in light response, hormonal response, and stress response. Synteny analysis showed a greater collinearity between Jojoba and V. vinifera than Arabidopsis thaliana. The 24 genes in the Jojoba NAC TFs are derived from fragment replication, which may be the main source of NAC amplification. Gene expression analysis identified seven genes that were highly expressed in seeds. The differential expression analysis of NAC TFs in cotyledon and embryonic axis tissues showed that the expression of 10 genes was up-regulated and 1 gene was down-regulated. This study provides more information on the classification, gene structure, conserved motif, and evolution of NAC TFs in Jojoba, facilitating further exploration of their specific functional analysis in Jojoba seed development.

Bio-Responsive Macromolecular Drug and Small-Molecular Drug Conjugates: Nanoparticulate Prodrugs for Tumor Microenvironment Heterogeneity Management and Therapeutic Response Enhancement.

How to break through the poor response of current drug therapy, which often resulted from tumor microenvironment heterogeneity (TMH), remains an enormous challenge in the treatment of critical diseases. In this work, a practical solution on bio-responsive dual-drug conjugates for overcoming TMH and improving antitumor treatment, which integrates the advantages of macromolecular drugs and small-molecular drugs, is proposed. Nanoparticulate prodrugs based on small-molecular drug and macromolecular drug conjugates are designed as a robust weapon for programmable multidrug delivery at tumor-specific sites: the tumor microenvironment acid condition triggers delivery of macromolecular aptamer drugs (AX102) to manage TMH (including tumor stroma matrix, interstitial fluid pressure, vasculature network, blood perfusion, and oxygen distribution), and intracellular lysosomal acid condition activates rapid release of small-molecular drugs (doxorubicin and dactolisib) to enhance curative effects. As compared with doxorubicin chemotherapy, the tumor growth inhibition rate is enhanced by 47.94% after multiple tumor heterogeneity management. This work verifies that the nanoparticulate prodrugs facilitate TMH management and therapeutic response enhancements, as well as elucidates synergetic mechanisms for drug resistance reversal and metastasis inhibition. It is hoped that the nanoparticulate prodrugs will be an excellent demonstration of the co-delivery of small-molecular drugs and macromolecular drugs.

Polymorphisms at amino acid positions 85 and 86 in succinate dehydrogenase subunit C of Colletotrichum siamense: Implications for fitness and intrinsic sensitivity to SDHI fungicides.

Among succinate dehydrogenase inhibiter (SDHI) fungicides, penthiopyrad and benzovindiflupyr particularly inhibit Colletotrichum. Studying SDH amino acid polymorphism in Colletotrichum, along with its fungicide binding sites, is key to understanding their mechanisms of action. This study explores the SDH amino acid polymorphisms in Colletotrichum siamense strains from rubber trees in China and their interaction with SDHI fungicides, specifically penthiopyrad and benzovindiflupyr. Sequencing revealed most polymorphisms were in the SDHC subunit, particularly at positions 85 and 86, which are key to penthiopyrad resistance. Among 33 isolates, 33.3 % exhibited a substitution at position 85, and 9 % at position 86. A strain with W85L and T86N substitutions in SDHC showed reduced SDH activity, ATP content, mycelial growth, and virulence, and decreased sensitivity to penthiopyrad but not benzovindiflupyr. Molecular docking with Alphafold2 modeling suggested distinct binding modes of the two fungicides to C. siamense SDH. These findings underscore the importance of SDHC polymorphisms in C. siamense's fitness and sensitivity to SDHIs, enhancing our understanding of pathogen-SDHI interactions and aiding the development of novel SDHI fungicides.

Single-cell transcriptomic analyses reveal cellular and molecular patterns of rubber tree response to early powdery mildew infection.

As a perennial woody plant, the rubber tree (Hevea brasiliensis) must adapt to various environmental challenges through gene expression in multiple cell types. It is still unclear how genes in this species are expressed at the cellular level and the precise mechanisms by which cells respond transcriptionally to environmental stimuli, especially in the case of pathogen infection. Here, we characterized the transcriptomes in Hevea leaves during early powdery mildew infection using single-cell RNA sequencing. We identified 10 cell types and constructed the first single-cell atlas of Hevea leaves. Distinct gene expression patterns of the cell clusters were observed under powdery mildew infection, which was especially significant in the epidermal cells. Most of the genes involved in host-pathogen interactions in epidermal cells exhibited a pattern of dramatically increased expression with increasing pseudotime. Interestingly, we found that the HbCNL2 gene, encoding a nucleotide-binding leucine-rich repeat protein, positively modulated the defence of rubber leaves against powdery mildew. Overexpression of the HbCNL2 gene triggered a typical cell death phenotype in tobacco leaves and a higher level of reactive oxygen species in the protoplasts of Hevea leaves. The HbCNL2 protein was located in the cytomembrane and nucleus, and its leucine-rich repeat domain interacted with the histidine kinase-like ATPase domain of the molecular chaperone HbHSP90 in the nucleus. Collectively, our results provide the first observation of the cellular and molecular responses of Hevea leaves to biotrophic pathogen infection and can guide the identification of disease-resistance genes in this important tree species.

Causal inference and observational data.

Observational studies using causal inference frameworks can provide a feasible alternative to randomized controlled trials. Advances in statistics, machine learning, and access to big data facilitate unraveling complex causal relationships from observational data across healthcare, social sciences, and other fields. However, challenges like evaluating models and bias amplification remain.

Comprehensive analysis of MAPK gene family in Populus trichocarpa and physiological characterization of PtMAPK3-1 in response to MeJA induction.

Mitogen-activated protein kinases (MAPKs) play important roles in plant growth and development, as well as hormone and stress responses by signaling to eukaryotic cells, through MAPK cascade, the presence of various cues; thereby, regulating various responses. The MAPK cascade consists mainly of three gene families, MAPK, MAPKK, and MAPKKK, which activate downstream signaling pathways through sequential phosphorylation. Although the MAPK cascade gene family has been reported in several species, there is a lack of comprehensive analysis in poplar. We identified 21 MAPK genes, 11 MAPKK genes, and 104 MAPKKK genes in Populus trichocarpa. The phylogenetic classification was supported by conservative motif, gene structure and motif analysis. Whole genome duplication has an important role in the expansion of MAPK cascade genes. Analysis of promoter cis-elements and expression profiles indicates that MAPK cascade genes have important roles in plant growth and development, abiotic and biotic stresses, and phytohormone response. Expression profiling revealed a significant upregulation of PtMAPK3-1 expression in response to drought, salt and disease stresses. Poplar transiently overexpressing PtMAPK3-1 and treated with methyl jasmonic acid (MeJA) had higher catalase and peroxidase levels than non-overexpressing poplar. This work represents the first complete inventory of the MAPK cascade in P. trichocarpa, which reveals that PtMAPK3-1 is induced by the MeJA hormone and participates in the MeJA-induced enhancement of the antioxidant enzyme system.

Optimization of Signal Space Separation for Optically Pumped Magnetometer in Magnetoencephalography.

Magnetoencephalography (MEG) is a noninvasive functional neuroimaging modality but highly susceptible to environmental interference. Signal space separation (SSS) is a method for improving the SNR to separate the MEG signals from external interference. The origin and truncation values of SSS significantly affect the SSS performance. The origin value fluctuates with respect to the helmet array, and determining the truncation values using the traversal method is time-consuming; thus, this method is inappropriate for optically pumped magnetometer (OPM) systems with flexible array designs. Herein, an automatic optimization method for the SSS parameters is proposed. Virtual sources are set inside and outside the brain to simulate the signals of interest and interference, respectively, via forward model, with the sensor array as prior information. The objective function is determined as the error between the signals from simulated sources inside the brain and the SSS reconstructed signals; thus, the optimized parameters are solved inversely by minimizing the objective function. To validate the proposed method, a simulation analysis and MEG auditory-evoked experiments were conducted. For an OPM sensor array, this method can precisely determine the optimized origin and truncation values of the SSS simultaneously, and the auditory-evoked component, for example, N100, can be accurately located in the temporal cortex. The proposed optimization procedure outperforms the traditional method with regard to the computation time and accuracy, simplifying the SSS process in signal preprocessing and enhancing the performance of SSS denoising.

Straw lignin degradation by lignin peroxidase from Irpex lacteus cooperated with enzymes and small molecules.

OBJECTIVES: Maximizing the utility value of enzymes was achieved by exploring the effects of small molecules on the efficiency of lignin degradation by lignin peroxidase. METHODS: Using wheat straw as raw material and taking lignin degradation rate as index, it was found that laccase, glucose oxidase, malonic acid, citric acid, ZnSO4, CaCl2 could promote the lignin degradation by the lignin peroxidase from Irpex lacteus, respectively. Moreover, glucose oxidase, malonic acid and CaCl2 had obvious synergy effects on lignin degradation by the lignin peroxidase. RESULTS: The optimal conditions of lignin degradation were obtained by response surface experiment: 4% glucose oxidase, 0.74% malonic acid and 3.29% CaCl2 were added for synergistic degradation at 37 â„ƒ with 50% of water content. After 72 h quickly enzymatic hydrolysis, the degradation rate of lignin was 45.84%. CONCLUSIONS: A new green and efficient method for lignin removal from straw was obtained, which provided a reference for the efficient utilization of straw and lignin peroxidase.

Metal-phenolic capsules with ROS scavenging reshape the oxidative microenvironment of atherosclerosis.

Arterial injury makes the tissue in a state of high oxidative stress. At the same time, abnormal lipid metabolism can further lead to bleeding and thrombosis. Therefore, the anti-inflammatory and anti-oxidant polyphenol, EGCG was organically complexed with Fe3+ to form a metal-phenolic framework carrier. And the antihyperlipidemic drug, atorvastatin (ATV) was loaded into the carrier to enhance the bioavailability, and simultaneously alleviate the oxidative stress of the inflammatory site and abnormal lipid metabolism. The results confirmed that the obtained material EGCG-Fe-ATV had good biocompatibility and biosafety effect. In addition, EGCG-Fe-ATV showed outstanding anti-inflammatory, anti-oxidant and lipid-lowering properties. These therapeutic outcomes of EGCG-Fe-ATV were achieved by reducing systemic and local oxidative stress and inflammation, alleviating inflammatory cell infiltration in plaques, and modulating lipid synthesis and transferase to alter cholesterol transport. In conclusion, the combination of metal-phenolic capsules with ATV provides a new strategy for reshaping the oxidative microenvironment of atherosclerosis.

Laser-assisted hatching improves pregnancy outcomes in frozen-thawed embryo transfer cycles of cleavage-stage embryos: a large retrospective cohort study with propensity score matching.

INTRODUCTION: Laser-assisted hatching (LAH) is a commonly used adjunct technique; however, its effectiveness has not been fully established. OBJECTIVE: We evaluated the effects of LAH on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles of cleavage-stage embryos. MATERIALS AND METHODS: This retrospective study involved 5779 FET cycles performed at the Reproductive and Genetic Center in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2016 and December 2020. After propensity score matching, 3535 FET cycles were included, out of which 1238 were subjected to LAH while the remaining 2297 cycles were non-LAH (NLAH). The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR) while secondary outcomes included implantation rate (IR), biochemical pregnancy rate (BPR), ectopic pregnancy rate (EPR), pregnancy loss rate (PLR), multiple pregnancy rate (MPL), and monozygotic twinning rate (MTR). Logistic regression analysis was conducted to adjust for possible confounders. Subgroup analysis was also performed based on the endometrial preparation regimen. RESULTS: The LAH group exhibited a higher LBR, compared to the NLAH group (34.9% vs. 31.4%, OR = 1.185, 95% CI = 1.023, 1.374, P = 0.024). Additionally, the LAH group showed a decreasing trend in PLR and EPR; however, differences were insignificant (P = 0.078, P = 0.063 respectively). Differences in IR (24.6% vs. 24.3%), BPR (41.8% vs. 40.4%), CPR (40.7% vs. 38.3%), MPR (14.1% vs. 17.3%), and MTR (1.4% vs. 1.1%) were insignificant. Subgroup analysis revealed that LAH may be more conducive for pregnancy outcomes in hormone replacement cycles. CONCLUSIONS: In summary, LAH has an increased chance of achieving live births. However, further prospective studies should be performed to confirm our findings.