MOCNN: A Multiscale Deep Convolutional Neural Network for ERP-Based Brain-Computer Interfaces.

Event-related potentials (ERPs) reflect neurophysiological changes of the brain in response to external events and their associated underlying complex spatiotemporal feature information is governed by ongoing oscillatory activity within the brain. Deep learning methods have been increasingly adopted for ERP-based brain-computer interfaces (BCIs) due to their excellent feature representation abilities, which allow for deep analysis of oscillatory activity within the brain. Features with higher spatiotemporal frequencies usually represent detailed and localized information, while features with lower spatiotemporal frequencies usually represent global structures. Mining EEG features from multiple spatiotemporal frequencies is conducive to obtaining more discriminative information. A multiscale feature fusion octave convolution neural network (MOCNN) is proposed in this article. MOCNN divides the ERP signals into high-, medium-and low-frequency components corresponding to different resolutions and processes them in different branches. By adding mid-and low-frequency components, the feature information used by MOCNN can be enriched, and the required amount of calculations can be reduced. After successive feature mapping using temporal and spatial convolutions, MOCNN realizes interactive learning among different components through the exchange of feature information among branches. Classification is accomplished by feeding the fused deep spatiotemporal features from various components into a fully connected layer. The results, obtained on two public datasets and a self-collected ERP dataset, show that MOCNN can achieve state-of-the-art ERP classification performance. In this study, the generalized concept of octave convolution is introduced into the field of ERP-BCI research, which allows effective spatiotemporal features to be extracted from multiscale networks through branch width optimization and information interaction at various scales.

The mechanosensory channel PIEZO1 functions upstream of angiopoietin/TIE/FOXO1 signaling in lymphatic development.

Lymphedema is a debilitating disease with no effective cure and affects an estimated 250 million individuals worldwide. Prior studies have identified mutations in piezo-type mechanosensitive ion channel component 1 (PIEZO1), angiopoietin 2 (ANGPT2), and tyrosine kinase with Ig-like and EGF-like domains 1 (TIE1) in patients with primary lymphedema. Here, we identified crosstalk between these molecules and showed that activation of the mechanosensory channel PIEZO1 in lymphatic endothelial cells (LECs) caused rapid exocytosis of the TIE ligand ANGPT2, ectodomain shedding of TIE1 by disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), and increased TIE/PI3K/AKT signaling, followed by nuclear export of the transcription factor FOXO1. These data establish a functional network between lymphedema-associated genes and provide what we believe to be the first molecular mechanism bridging channel function with vascular signaling and intracellular events culminating in transcriptional regulation of genes expressed in LECs. Our study provides insights into the regulation of lymphatic function and molecular pathways involved in human disease.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Functions of N6-methyladenosine (m6A) RNA modifications in acute myeloid leukemia.

N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA. m6A participates in RNA splicing, nuclear export, translation, and degradation through regulation by methyltransferases, methylation readers, and demethylases, affecting mRNA stability and translation efficiency. Through the dynamic and reversible regulatory network composed of " Writers-Erasers-Readers", m6A modification plays a unique role in the process of hematopoiesis. Acute myeloid leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of hematopoietic stem cells/progenitor cells. Many studies have shown that m6A-related proteins are abnormally expressed in AML and play an important role in the occurrence and development of AML, acting as carcinogenic or anticancer factors. Here, we describe the mechanisms of action of reversing m6A modification in hematopoiesis and AML occurrence and progression to provide a basis for further research on the role of m6A methylation and its regulatory factors in normal hematopoiesis and AML, to ultimately estimate its potential clinical value.

Influence of the Pd Oxidation State in PdNi Thin Films on Surface Acoustic Wave Hydrogen Sensing Performance.

PdNi alloy thin films demonstrate exceptional hydrogen sensing performance and exhibit significant potential for application in surface acoustic wave (SAW) hydrogen sensors. However, the long-term stability of SAW H2 sensors utilizing PdNi films as catalysts experiences a substantial decrease during operation. In this paper, X-ray photoelectron spectroscopy (XPS) is employed to investigate the failure mechanisms of PdNi thin films under operational conditions. The XPS analysis reveals that the formation of PdO species on PdNi thin films plays a crucial role in the failure of hydrogen sensing. Additionally, density functional theory (DFT) calculations indicate that hydrogen atoms encounter a diffusion energy barrier during the penetration process from the PdNiOx surface to the subsurface region. The identification of PdNi film failure mechanisms through XPS and DFT offers valuable insights into the development of gas sensors with enhanced long-term stability. Guided by these mechanisms, we propose a method to restore the hydrogen sensing response time and magnitude to a certain extent by reducing the partially oxidized surface of the PdNi alloy under a hydrogen atmosphere at 70 °C, thereby restoring Pd to its metallic state with zero valence.

Structure Engineering of Acridine Donor to Optimize Color Purity of Blue Thermally Activated Delayed Fluorescence Emitters.

9,9-Dimethyl-9,10-dihydroacridine (DMAC) is one of the most widely used electron donor for constructing high-performance thermally activated delayed fluorescence (TADF) emitters. However, DMAC-based emitters often suffer from the imperfect color purity, particularly in blue emitters, due to its strong electron-donating capability. To modulate donor strength, 2,7-F-Ph-DMAC and 2,7-CF3-Ph-DMAC were designed by introducing the electron-withdrawing 2-fluorophenyl and 2-(trifluoromethyl)phenyl at the 2,7-positions of DMAC. These donors were used, in combination with 2,4,6-triphenyl-1,3,5-triazine (TRZ) acceptor, to develop novel TADF emitters 2,7-F-Ph-DMAC-TRZ and 2,7-CF3-Ph-DMAC-TRZ. Compared to the F- or CF3-free reference emitter, both two emitters showed hypsochromic effect in fluorescence and comparable photoluminescence quantum yields without sacrificing the reverse intersystem crossing rate constants. In particular, 2,7-CF3-Ph-DMAC-TRZ based OLED exhibited a blue shift by up to 39 nm and significantly improved Commission International de l'Éclairage (CIE) coordinates from (0.36, 0.55) to (0.22, 0.41), while the external quantum efficiency kept stable at about 22.5%. This donor engineering strategy should be valid for improving the color purity of large amount of acridine based TADF emitters. It can be predicted that pure blue TADF emitters should be feasible if these F- or CF3-modifed acridine donors are combined with other weaker electron acceptors.

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study.

BACKGROUND: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). METHODS: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. FINDINGS: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the seasonal group and 3188 (95·4%) of 3340 in the catch-up group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. INTERPRETATION: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. FUNDING: Sanofi and AstraZeneca. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Safety and immunogenicity of the SARS-CoV-2 LYB001 RBD-based VLP vaccine (CHO cell) phase 1 in Chinese adults: a randomized, double-blind, positive-parallel-controlled study.

BACKGROUND: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured. RESULTS: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group. CONCLUSIONS: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05552573).

Revolutionizing aquatic eco-environmental monitoring: Utilizing the RPA-Cas-FQ detection platform for zooplankton.

The integration of recombinase polymerase amplification (RPA) with CRISPR/Cas technology has revolutionized molecular diagnostics and pathogen detection due to its unparalleled sensitivity and trans-cleavage ability. However, its potential in the ecological and environmental monitoring scenarios for aquatic ecosystems remains largely unexplored, particularly in accurate qualitative/quantitative detection, and its actual performance in handling complex real environmental samples. Using zooplankton as a model, we have successfully optimized the RPA-CRISPR/Cas12a fluorescence detection platform (RPA-Cas-FQ), providing several crucial "technical tips". Our findings indicate the sensitivity of CRISPR/Cas12a alone is 5 × 109 copies/reaction, which can be dramatically increased to 5 copies/reaction when combined with RPA. The optimized RPA-Cas-FQ enables reliable qualitative and semi-quantitative detection within 50 min, and exhibits a good linear relationship between fluorescence intensity and DNA concentration (R2 = 0.956-0.974***). Additionally, we developed a rapid and straightforward identification procedure for single zooplankton by incorporating heat-lysis and DNA-barcode techniques. We evaluated the platform's effectiveness using real environmental DNA (eDNA) samples from the Three Gorges Reservoir, confirming its practicality. The eDNA-RPA-Cas-FQ demonstrated strong consistency (Kappa = 0.43***) with eDNA-Metabarcoding in detecting species presence/absence in the reservoir. Furthermore, the two semi-quantitative eDNA technologies showed a strong positive correlation (R2 = 0.58-0.87***). This platform also has the potential to monitor environmental pollutants by selecting appropriate indicator species. The novel insights and methodologies presented in this study represent a significant advancement in meeting the complex needs of aquatic ecosystem protection and monitoring.

Identification and Functional Characterization of Alternative Transcripts of LncRNA HNF1A-AS1 and Their Impacts on Cell Growth, Differentiation, Liver Diseases, and in Response to Drug Induction.

The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction.

Multistatic Integrated Sensing and Communication System Based on Macro-Micro Cooperation.

A novel multistatic integrated sensing and communication (ISAC) system based on macro-micro cooperation for the sixth-generation (6G) mobile network is proposed. Instead of using macrosites at both the transmitter and receiver sides, microsites are considered as receivers in cooperative sensing. This system is important since microsites can be deployed more flexibly to reduce their distances to the sensing objects, providing better coverage for sensing service. In this work, we first analyze the deployment problem of microsites, which can be deployed along the radius and azimuth angle to cover macrosite cells. The coverage area of each microsite is derived in terms of its position in the cell. Then, we describe an efficient estimating approach for obtaining the position and velocity of sensing objects in the macrosite cell. By choosing multiple microsites around the targeted sensing area, joint data processing with an efficient optimization method is also provided. Simulation results show that the multistatic ISAC system employing macro-micro cooperation can improve the position and velocity estimation accuracy of objects compared to systems employing macrosite cooperation alone, demonstrating the effectiveness and potential for implementing the proposed system in the 6G mobile network.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

A brief overview of passive microvalves in microfluidics: Mechanism, manufacturing, and applications.

Microvalves play a crucial role in manipulating fluid states within a microfluidic system and are finding widespread applications in fields such as biology, medicine, and environmental preservation. Leveraging the characteristics and features of microvalves enables the realization of various complicated microfluidic functions. Continuous advancement in the manufacturing process contributes to more flexible control modes for passive microvalves. As a consequence, these valves are progressively shrinking in size while simultaneously improving in precision and stability. Although active microvalves have the benefits of low leakage, rapid response time, and wide adaptability range, the energy supply system limits the size and even their applicability in integration and miniaturization. In comparison, passive microvalves have the advantage of relying solely on the fluid flow or fluid driving pressure to control the open/close of fluid flow over active microvalves, in spite of having slightly reduced control accuracy. Their self-sustaining feature is highly consistent with the need for assembly and miniaturization in the point-of-care testing technology. Hence, these valves have attracted significant interest for research and application purposes. This review focuses on the recent literature on passive microvalves and details existing passive microvalves from three different aspects: operating principle, processing method, and applications. This work aims to increase the visibility of passive microvalves among researchers and enhance their comprehension by classifying them according to the aforementioned three aspects, facilitating the practical applications and further developments of passive microvalves. Additionally, this paper is expected to serve as a comprehensive and systematic reference for interdisciplinary researchers that intend to design related microfluidic systems.

Genome-wide characterization and expression analysis of the HD-Zip II gene family in response to drought and GA3 stresses in Nicotiana tabacum.

BACKGROUND: Homeodomain-leucine ZIPper (HD-ZIP) transcription factors play crucial roles in plant growth, development, and stress responses. The HD-ZIP family is categorised into four groups (HD-ZIP I-IV). While extensive genome-wide studies have been conducted on the HD-ZIP I, III, and IV subfamily in Nicotiana tabacum (tobacco), comprehensive reports on the HD-ZIP II subfamily genes are limited. METHODS: Bioinformatics resources and tools were utilised to analyse molecular characteristics, phylogenetic homology, and protein interactions. Expression pattern analyses in various tissues and the relative expression of NtHD-ZIP II genes under drought and GA3 treatment were assessed by qRT-PCR. RESULTS: In this study, 24 HD-ZIP II members were systematically identified and categorised into seven independent clades through phylogenetic analysis involving tobacco and other plant species. We found that 19 NtHD-ZIP II genes exhibited tissue-specific expression. The transcripts of NtHD-ZIPII3, 4, 14, 23, 24 were notably induced under the drought treatments, while those of NtHD-ZIPII7, 11, 12, 20 were suppressed. Furthermore, NtHD-ZIPII15 transcripts decreased following GA3 treatment, whereas the transcripts of NtHD-ZIPII7, 8, 11, 12 were induced after GA3 treatment. Notably, an increase in trichomes was observed in tobacco leaves treated with GA3 and subjected to drought. CONCLUSIONS: The expression levels of some HD-ZIP II genes were altered, and an increase in glandular trichomes was induced under GA3 and drought treatments in tobacco. Overall, our findings provide insights into the expression patterns of NtHD-ZIP II genes and will facilitate their functional characterisation in future studies.

A tempo-spatial controllable microfluidic shear-stress generator for in-vitro mimicking of the thrombus.

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Small peptides: novel targets for modulating plant-rhizosphere microbe interactions.

The crucial role of rhizosphere microbes in plant growth and their resilience to environmental stresses underscores the intricate communication between microbes and plants. Plants are equipped with a diverse set of signaling molecules that facilitate communication across different biological kingdoms, although our comprehension of these mechanisms is still evolving. Small peptides produced by plants (SPPs) and microbes (SPMs) play a pivotal role in intracellular signaling and are essential in orchestrating various plant development stages. In this review, we posit that SPPs and SPMs serve as crucial signaling agents for the bidirectional cross-kingdom communication between plants and rhizosphere microbes. We explore several potential mechanistic pathways through which this communication occurs. Additionally, we propose that leveraging small peptides, inspired by plant-rhizosphere microbe interactions, represents an innovative approach in the field of holobiont engineering.

MSLTE: multiple self-supervised learning tasks for enhancing EEG emotion recognition.

Objective. The instability of the EEG acquisition devices may lead to information loss in the channels or frequency bands of the collected EEG. This phenomenon may be ignored in available models, which leads to the overfitting and low generalization of the model.Approach. Multiple self-supervised learning tasks are introduced in the proposed model to enhance the generalization of EEG emotion recognition and reduce the overfitting problem to some extent. Firstly, channel masking and frequency masking are introduced to simulate the information loss in certain channels and frequency bands resulting from the instability of EEG, and two self-supervised learning-based feature reconstruction tasks combining masked graph autoencoders (GAE) are constructed to enhance the generalization of the shared encoder. Secondly, to take full advantage of the complementary information contained in these two self-supervised learning tasks to ensure the reliability of feature reconstruction, a weight sharing (WS) mechanism is introduced between the two graph decoders. Thirdly, an adaptive weight multi-task loss (AWML) strategy based on homoscedastic uncertainty is adopted to combine the supervised learning loss and the two self-supervised learning losses to enhance the performance further.Main results. Experimental results on SEED, SEED-V, and DEAP datasets demonstrate that: (i) Generally, the proposed model achieves higher averaged emotion classification accuracy than various baselines included in both subject-dependent and subject-independent scenarios. (ii) Each key module contributes to the performance enhancement of the proposed model. (iii) It achieves higher training efficiency, and significantly lower model size and computational complexity than the state-of-the-art (SOTA) multi-task-based model. (iv) The performances of the proposed model are less influenced by the key parameters.Significance. The introduction of the self-supervised learning task helps to enhance the generalization of the EEG emotion recognition model and eliminate overfitting to some extent, which can be modified to be applied in other EEG-based classification tasks.

Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract.

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities.

Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.