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Abstract Ménière’s disease (MD) is a complex inner ear disorder characterized by a range of symptoms, with its pathogenesis linked to immune-related mechanisms. Our previous research demonstrated that IL-1β maturation and release can trigger cell pyroptosis, exacerbating the severity of the endolymphatic hydrops in a mouse model; however, the specific mechanism through which IL-1β influences MD symptoms remains unclear. This study conducted on patients with MD examined changes in protein signatures in the vestibular end organs (VO) and endolymphatic sac (ES) using mass spectrometry. Gene ontology and protein pathway analyses showed that differentially expressed proteins in the ES are closely related to adhesion, whereas those in the VO are related to synapse processes. Additionally, the study found elevated expression of Glutaminase (GLS) in the VO of MD patients compared to controls. Further investigations revealed that IL-1β increased glutamate levels by upregulating GLS expression in HEI-OC1 cells. Treatment with a GLS inhibitor or an IL-1β receptor antagonist alleviated auditory-vestibular dysfunction and reduced glutamate levels in mice with endolymphatic hydrops. These findings collectively suggest that imbalanced neurotransmitter release and immune responses contribute to the pathology of MD, potentially explaining the hearing loss and vertigo associated with the disease and offering new avenues for therapeutic interventions.

Abstract An increasing number of studies have shown that lead is an important cardiovascular risk factor, but the impact of cardiovascular related gene polymorphisms on lead induced cardiovascular diseases is still unclear. To assess the interaction of lead exposure and related key cardiovascular regulating gene polymorphisms on blood pressure traits, three single-nucleotide polymorphisms including NOTCH1 rs3124591, Cerebral cavernous malformations 3 (CCM3) rs3804610 and Vascular endothelial growth factor receptor type 2 (VEGFR2) rs2305948 were selected and genotyped using improved multiplex ligase detection reaction method in 568 lead exposure workers in South China. General characteristics, blood lead and biochemical parameters including glucose, lipid profile and creatinine were also collected according to standard protocols. Regression analysis was used to evaluate the association of blood pressure with lead exposure, polymorphisms and their interaction. This study displayed that CCM3 rs3804610 had a positive interaction with lead and VEGFR2 rs2305948 had a negative interaction with lead. Specifcally, compared with the wild-type population, the blood lead of the genotype population carrying the risk allele increased by 1 µg/dL, systolic blood pressure increased by 0.53 mmHg (p

Intestinal stem cells (ISCs) initiate intestinal epithelial regeneration and tumorigenesis, and they experience rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence. It is crucial to reveal the mechanism underlying such plasticity for intestinal health. Recent studies have found that metabolic pathways control stem cell fate in homeostasis, but the role of metabolism in the regeneration of ISCs after damage has not been clarified. Here, we find that in a human colorectal cancer dataset, miR-29a and b (miR-29a/b) are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy. We also show that these two microRNAs are required for intestinal stemness maintenance in mice, and their expression is induced in regenerated ISCs after irradiation injury, resulting in skewed ISC fate from differentiation towards self-renewal. This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation (FAO) and depression of oxidative phosphorylation, which in turn controls the balance between self-renewal and differentiation of ISCs. Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery. Finally, we filter the potential targets of miR-29a/b and identify Hnf4g, a transcription factor, that drives this metabolic reprogramming through regulating FAO-related enzymes. Our work discovers an important metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.

Abstract Background Sequencing-based genetic testing is widely used in biomedical research, including pathogenic microorganism detection with metagenomic next-generation sequencing (mNGS). The application of sequencing results to clinical diagnosis and treatment relies on various interpretation knowledge bases. Currently, the existing knowledge bases are primarily built through manual knowledge extraction. This method requires professionals to read extensive literature and extract relevant knowledge from it, which is time-consuming and costly. Furthermore, manual extraction unavoidably introduces subjective biases. In this study, we aimed to automatically extract knowledge for interpreting mNGS results. Method We propose a novel approach to automatically extract pathogenic microorganism knowledge based on the question-answer (QA) model. First, we construct a MicrobeDB dataset since there is no available pathogenic microorganism QA dataset for training the model. The created dataset contains 3,161 samples from 618 published papers covering 224 pathogenic microorganisms. Then, we fine-tune the selected baseline model based on MicrobeDB. Finally, we utilize ChatGPT to enhance the diversity of training data, and employ data expansion to increase training data volume. Results Our method achieves an Exact Match (EM) and F1 score of 88.39% and 93.18%, respectively, on the MicrobeDB test set. We also conduct ablation studies on the proposed data augmentation method. In addition, we perform comparative experiments with the ChatPDF tool based on the ChatGPT API to demonstrate the effectiveness of the proposed method. Conclusions Our method is effective and valuable for extracting pathogenic microorganism knowledge.

Gradient triply periodic minimal surface (TPMS) structures are renowned for lightweight design and enhanced performance, but their complex and nonlinear configurations pose challenges in achieving targeted design goals. A new design methodology for the nonlinear gradient structure was proposed in this study, with the aim of achieving efficient and accurate modeling of complex and gradient sheet-based TPMS structures under specific performance objectives. This method utilized automated finite element (FE) simulations to obtain structure topology element densities under various boundary conditions. An artificial neural network (ANN) was then employed to efficiently predict the correspondence between these boundary conditions and topology element densities. A mapping was established between topology element densities and TPMS structural parameters, and the gradient structure was accurately constructed by using the voxel modeling technique. Taking a typical cantilever beam TPMS structure as an example of nonlinear gradient design, the results indicate that the error between the ANN-predicted and FE-simulated structure topology element densities is only 2.73 %, with prediction time being only 0.15 % of the simulation time. The thin regions of the gradient structure align with those geometrically removed in regular topology optimization scheme, achieving up to 65.45 % weight reduction, a 28.72 % improvement over the regular scheme, along with uniform structural stress transition and maximum stress reduction. TC4 alloy nonlinear gradient TPMS structures, printed by metal selective laser melting (SLM) technique, confirm the practical application value of this design method.

Abstract Background Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms. Results mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb). Conclusions In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects. Graphical abstract

Abstract Background Preoperative oral carbohydrate intake can improve the postoperative recovery of fasting patients in many kinds of surgeries; however, the effect of carbohydrates on patients undergoing daytime oral surgery is still unclear. This study was designed to evaluate the effect of preoperative oral carbohydrate intake on the quality of recovery of patients undergoing daytime oral surgery using the quality of recovery-15 (QoR-15) questionnaire. Methods Ninety-two patients scheduled for daytime oral surgery were randomly allocated to the midnight fasting group (F group, n = 45) or the carbohydrate-Outfast loading group (O group, n = 47). Participants in the F group fasted from midnight the day before surgery. Patients in the O group also fasted but received the Outfast drink (4 ml/kg) 2–3 h before the induction of anesthesia. QoR-15 questionnaire, patient well-being, and satisfaction were assessed before anesthesia induction and 24 h after surgery. Perioperative blood glucose, postoperative exhaust time, and adverse events were also recorded. Results The QoR-15 scores were significantly higher in the O group than in the F group preoperatively and postoperatively. Seven parameters representing patient well-being evaluated on a numeric rating scale (NRS, 0–10) were lower in the O group than in the F group postoperatively, except for the hunger and sleep quality scores. Patient satisfaction scores on a 5-point scale were higher in the O group than in the F group preoperatively and postoperatively. Meanwhile, the postoperative exhaust time was significantly shorter in the O group compared to the F group, while there were no significant differences in blood glucose concentrations between two groups. Conclusions Preoperative oral carbohydrate intake could improve postoperative recovery quality, well-being, and satisfaction of patients undergoing daytime oral surgery 24 h after surgery, and may serve as a treatment option for patients undergoing daytime oral surgery. Trial registration This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100053753) on 28/11/2021.

Abstract Background The airway should be thoroughly and accurately evaluated before anesthesia induction and endotracheal intubation. Awake direct laryngoscopy (ADL) can provide rapid, accurate, and intuitive airway assessment, especially for suspected difficult airways, and sometimes eliminates the need for fiberoptic intubation in some suspicious difficult airway cases. However, an optimal regimen has not been determined. Methods In this double-blind, controlled study, prior to ADL, 60 patients scheduled for general anesthesia were randomly allocated to receive 0.75 μg/kg of dexmedetomidine (Dex group, n = 20), 0.15 mg/kg of nalbuphine (Nal group, n = 20), or a placebo (control group, n = 20) intravenously over 10 min. At the same time, all study subjects received nebulized lidocaine for 15 min. The primary outcome was patient tolerance as assessed by a 5-point ADL comfort score, while secondary outcomes included satisfaction, coughing, pain, nausea and vital signs. Results Patients undergoing ADL in the Nal group had higher tolerance scores than those in the control and Dex groups [4 (3,4) vs. 3 (2,2.75), P

Abstract Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer’s disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD+-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPRmt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD+ metabolic profiles and improves MSR through the ATF4-dependent UPRmt pathway in AD-related cross-species models. At the organismal level, NAD+ repletion with NMN supplementation ameliorates mitochondrial proteotoxicity, decreases hippocampal synaptic disruption, decreases neuronal loss, and brain atrophy in mice model of AD. Remarkably, omics features of the hippocampus with NMN show that NMN leads to transcriptional changes of genes and proteins involved in MSR characteristics, principally within the astrocyte unit rather than microglia and oligodendrocytes. In brief, our work provides evidence that MSR has an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in AD mice aggravates the hallmarks of the disease; conversely, bolstering mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan.

Abstract Nutritional intervention can greatly benefit people who suffer from side effects of medical treatments by improving intestinal post‐damage recovery. The recovery process is dependent on the regeneration of intestinal epithelial cells, which is driven by Lgr5+ intestinal stem cells (ISCs). Lactoferrin (LF) is a natural milk‐abundant protein with several gut health‐related functions such as antibacterial and immunoregulation activities, thus protecting intestine from damage. However, it is unclear whether LF also plays a role in the repair of the injured intestine, despite limited clues on its ability to modulate intestinal epithelial cell growth in vitro. Here, we show that LF accelerates intestinal epithelial recovery after both dextran sulfate sodium challenge on mice and TNF‐α treatment on intestinal organoids. Furthermore, we find LF gives rise to ISC‐mediated epithelial regeneration by directly activating the Lgr5+ stem cells. Finally, we identify Lrp5/Wnt signaling as the key pathway for LF‐enhancing ISC stemness and function. Overall, our study reveals the potential of LF as a nutrient that can be applied to promote intestinal healing.

Abstract In the area of online teacher training, asynchronous collaboration faces several challenges such as limited learner engagement and low interaction quality, thereby hindering its overall effectiveness. Drawing on social comparison theory, providing social comparison feedback to teacher-learners in online asynchronous collaborative learning offers benefits, but also has drawbacks. While social comparison has been explored in diverse fields, its role in education remains unclear. In this study, we selected 95 primary and secondary school teachers participating in an online training course. Using randomized controlled trial design, we provided the experimental group with social comparison feedback, while the control group received only self-referential feedback. We used epistemic network analysis, lag sequential analysis, and social network analysis to identify the impact of social comparison feedback on group-regulated focus, group-interactive behaviors, and social network structures. The results showed that social comparison feedback significantly enhanced teachers’ online asynchronous collaborative learning.

Abstract Adaptive governance has emerged as a prominent theoretical and methodological approach in environmental governance, recognized for its capacity to address evolving conditions and future uncertainties. Despite the extensive literature on adaptive governance since its inception in 2003, a comprehensive review of the literature spanning two decades remains to be conducted. This study addresses that gap by selecting 3274 articles from the Web of Science Core Collection and performing a global scientometric visualization analysis. Our analysis identifies the most productive institutions, authors, journals, publication trends, and research frontiers in adaptive governance research. The findings reveal that there has been a significant acceleration in global research on adaptive governance over the past two decades. Furthermore, the majority of contributions to the field of adaptive governance research have been made by scholars based in the United States, Australia, England, Canada, and the Netherlands. Additionally, existing studies in adaptive governance field focus mainly on subject categories of environmental studies, environmental sciences, and ecology. Finally, the concept of adaptive governance, environmental governance, social-ecological systems, climate change adaptation and social learning were identified as hot topics and emerging trends. This study provides researchers and practitioners with an extensive understanding of the salient research themes, trends, and patterns in global adaptive governance research in an intuitive manner.

Abstract In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority 3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Previous research that explores the effect of ethnicity in the perception of speaker accentedness and personality traits often finds that Asian appearance contributes to a more accented and less competent impression. Importantly, most of the work done to date employed only Caucasian first language-speaking listeners; moreover, ethnicity and gender were not considered together. This study describes a series of evaluations of nine Korean (Asian) and nine German (Caucasian) second language English speakers by 41 Chinese listeners. The participants were asked to rate each speaker on an accentedness and 12 personality scales under two conditions: audio-only and audiovisual. The accentedness result indicates that with the availability of visual information, Korean speakers were rated significantly more accented than German speakers and male speakers were rated less accented than females. As for personality evaluation, the result suggests that power and competence traits share a similar trend, with Korean and female speakers being rated lower when listeners can see them, but solidarity traits show a slightly different trend. In general, Chinese listeners' bias in relation to speaker ethnicity and gender in both accentedness and personality evaluation was highlighted by the use of visual information, and a relationship between linguistic and social information was demonstrated.

Based on the purpose of improving the communication power of the computational intelligence short videos of China Communist Youth League, this paper takes six typical computational intelligence short video IDs and their popular computational intelligence short videos of the Communist Youth League at the provincial level as the research object investigates the characteristics along with the influencing factors of communication power from four aspects: expression form, content presentation, title text, and local characteristics through content analysis of Communist Youth League computational intelligence short videos. China communist youth league is the organization of young people between the ages of 14-28 which is run by chinese communist party with the purpose of training upcoming party members as well as officials. These six specific IDs of Communist youth league are selected as these accounts have consistently excellent performance in the ranking of government affairs TikTok accounts, and they have certain typicality and research significance. The novelty of this paper is an empirical analysis of Computational Intelligence short video communication. The methodologies that are included in this research are Release frequency that describes video update frequency, word frequency analysis that describes the keywords to follow in the short videos and statistical analysis of coding strategies. These Analysis were carried out through content and case study which was done using python 3.0's pandas, snownlp and other functional packages. The criterias which are used to evaluate the videos are views, likes, content, video format, form of expression, title form, local specialities show the engagement of the viewers in content as well as it helps in reaching the audience. Through the research, it is found that the computational intelligence short videos' communication power of the provincial Communist Youth League is related to video duration, expression form, video content, title text, local characteristics, and audience psychological behavior, but has no obvious positive correlation with title form. The advantage of computational intelligence short videos of the provincial Communist Youth League is that the party media has clear positioning, rich content, and innovative forms, but at the same time, there are some problems, such as unclear "youth" features, lack of local characteristics and audience interaction. This paper refines the characteristics of excellent computational intelligence in short videos of the Communist Youth League and puts forward countermeasures and suggestions for the shortcomings.

This study examines how COVID-induced and general attitudes toward Asians have changed over the course of the pandemic using nationally representative survey experiments in 2020 and 2022. First, we measured COVID-induced anti-Asian attitudes as the effect of a treatment reminding respondents of the pandemic on whether respondents would be willing to live or work with someone who is East or South Asian. The results suggest that the COVID-19 treatment worsened attitudes toward East and South Asians in the social domain and toward East Asians in the economic domain in 2020, but not in 2022. Second, we measured change in general attitudes toward Asians by comparing the control group responses in 2020 and 2022. The results demonstrate that, over the same period, general attitudes toward Asians have not improved despite growing attention toward anti-Asian biases. This finding underscores the persistence of general negative attitudes toward Asians beyond the immediate context of the pandemic and the ongoing imperative to actively address deeply ingrained biases against Asians.

Abstract Objective of the study Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related mortality globally. Metastasis, responsible for treatment failures, underscores the urgency to comprehend molecular drivers of invasion and migration. Central to the invasive and migratory processes underlying metastasis is the protein Talin1. However, the role and underlying mechanisms governing Talin1's involvement in HCC have remained elusive. Methods A total of 100 HCC specimens were collected from patients who underwent hepatectomy in our center. The expression level of talin1 was measured to evaluate the correlationship of talin1 and the development of HCC. In vitro and in vivo experiments were conducted to verify the characteristic of talin1 in HCC. RNA-seq and bioinformatics analysis were performed to identify the downstream signal pathway of talin1 and their impact on HCC development. Results Here, we reported elevated levels of Talin1 mRNA and protein in HCC tissues. Meanwhile, downregulation of Talin1 significantly reduced the HCC cell proliferation and metastasis in vitro and in vivo. Furthermore, elevating NRG-1, a downstream target of Talin1, enhanced metastasis of HCC cells. More importantly, attenuation of Talin1 inhibited HCC progression through decreasing the stabilization of NRG1 mRNA, consequently regulating the expression of NRG1 and its involvement in mediating the PI3K/AKT pathway. Conclusion Taken together, Talin1 regulates cellular proliferation, metastasis, and invasiveness by modulating NRG1/PI3K/AKT axis, suggesting that Talin1 emerges as a promising candidate for treating HCC.

Abstract Optical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.

Abstract Reservoir engineering is a powerful technique to autonomously stabilize a quantum state. Traditional schemes involving multi-body states typically function for discrete entangled states. In this work, we enhance the stabilization capability to a continuous manifold of states with programmable stabilized state selection using multiple continuous tuning parameters. We experimentally achieve 84.6% and 82.5% stabilization fidelity for the odd and even-parity Bell states as two special points in the manifold. We also perform fast dissipative switching between these opposite parity states within 1.8 μs and 0.9 μs by sequentially applying different stabilization drives. Our result is a precursor for new reservoir engineering-based error correction schemes.

Abstract Doped van der Waals heterostructures host layer-hybridized trions, i.e. charged excitons with layer-delocalized constituents holding promise for highly controllable optoelectronics. Combining a microscopic theory with photoluminescence (PL) experiments, we demonstrate the electrical tunability of the trion energy landscape in naturally stacked WSe2 bilayers. We show that an out-of-plane electric field modifies the energetic ordering of the lowest lying trion states, which consist of layer-hybridized $$\Lambda$$ Λ -point electrons and layer-localized K-point holes. At small fields, intralayer-like trions yield distinct PL signatures in opposite doping regimes characterized by weak Stark shifts in both cases. Above a doping-asymmetric critical field, interlayer-like species are energetically favored and produce PL peaks with a pronounced Stark red-shift and a counter-intuitively large intensity arising from efficient phonon-assisted recombination. Our work presents an important step forward in the microscopic understanding of layer-hybridized trions in van der Waals heterostructures and paves the way towards optoelectronic applications based on electrically controllable atomically-thin semiconductors.

This paper centers on stochastic Hopfield neural networks with variable coefficients and infinite delay. First, we propose an integral inequality that improves and extends some existing works. Second, by employing some inequalities and stochastic analysis techniques, some sufficient conditions for ensuring Pth moment generalized exponential stability are established. Our results do not necessitate the construction of a complex Lyapunov function or rely on the assumption of bounded variable coefficients, and our results expand some existing works. At last, to illustrate the efficacy of our result, we present several simulation examples.

Abstract Background Premature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy. Methods The study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36). Discussion The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice. Trial registration Clinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Objective: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). Methods: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. Conclusions: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Abstract This study presents a high-accuracy, all-fiber mode division multiplexing (MDM) reconstructive spectrometer (RS). The MDM was achieved by utilizing a custom-designed 3 × 1 mode-selective photonics lantern to launch distinct spatial modes into the multimode fiber (MMF). This facilitated the information transmission by increasing light scattering processes, thereby encoding the optical spectra more comprehensively into speckle patterns. Spectral resolution of 2 pm and the recovery of 2000 spectral channels were accomplished. Compared to methods employing single-mode excitation and two-mode excitation, the three-mode excitation method reduced the recovered error by 88% and 50% respectively. A resolution enhancement approach based on alternating mode modulation was proposed, reaching the MMF limit for the 3 dB bandwidth of the spectral correlation function. The proof-of-concept study can be further extended to encompass diverse programmable mode excitations. It is not only succinct and highly efficient but also well-suited for a variety of high-accuracy, high-resolution spectral measurement scenarios. Graphical Abstract

Abstract Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients’ therapy response and prognosis.

Abstract This study examined the effect of various clarification treatments on the physicochemical properties, volatile compounds, and sensory attributes of kiwi wines produced from five different kiwifruit (Actinidia deliciosa) varieties. The degree of clarification had a minimal impact on physicochemical parameters, including the content of residual sugar, ethanol, volatile acid, titratable acidity (except for the kiwifruit variety ‘Qinmei’), and the pH value. However, wines made from unclarified juices (muddy juice and pulp) displayed a higher glycerol content than those made from clarified juices. The cluster heat map and principal component analyses (PCA) demonstrated that kiwi wines produced from clarified kiwi juices possessed a higher ester content, whereas muddy juice and pulp wines contained elevated levels of higher alcohols. Quantitative descriptive analysis (QDA) indicated that clarified juice wines outperformed muddy juice and pulp wines in terms of purity, typicality, harmony, intensity, and freshness, with negligible differences in terms of palate acidity. Moreover, the clarified juice wines featured more characteristic kiwi wine aromas (kiwifruit, passionfruit, and pineapple) compared with that of the muddy juice and pulp wines, which exhibited an increased grassy flavour. Although the 100-NTU kiwifruit juice-fermented wine did not show an advantage in the cluster heat map and PCA, it presented better freshness, typicality, and intensity in the QDA, as well as a more passionfruit aroma. Based on the orthogonal partial least-squares discriminant analysis, A. deliciosa ‘Xuxiang’ was deemed to be the most suitable variety for vinification. This study provides crucial insights for enhancing the production of high-quality kiwi wine.

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

Accurate, rapid and sensitive detection of specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in human samples is crucial for preventing and assessing pandemics, especially in the case of recent COVID-19 outbreaks. However, simultaneous and efficient detection of IgG and IgM in a single system remains challenging. Herein, we developed a multicolor nanosystem capable of quantitatively analyzing anti-SARS-CoV-2 IgG and IgM with high sensitivity within 20 ​min. The detection system consists of core-shell upconversion nanoparticles (csUCNPs), secondary antibodies labeled with fluorescent dyes (sab), and magnetic nanocrystals (PMF). By leveraging the Förster resonance energy transfer (FRET) effect, the photoluminescence (PL) intensity of blue and green regions is restored for IgG and IgM detection, respectively. Inspiringly, owing to the introducing of PMF, the limits of detection (LODs) of IgG and IgM tested are improved to 89 ​fmol ​L−1 and 19.4 ​fmol ​L−1, representing about 416-folds and 487-folds improvement over only-dye dependent system, respectively. Mechanistic investigations reveal that the high collective effect and surface energy transfer efficiency from csUCNPs to PMF contribute to the enhanced detection sensitivity. The assay enables us to quantify clinical vaccinated samples with high specificity and precision, suggesting our multicolor platform can be a promising alternative for clinical point-of-care serological assay.

IntroductionAlcanivorax, a typical alkane-degrading bacterium, has demonstrated the ability to utilize inorganic electron donor in some reports. However, a comprehensive analysis of its potentiality to utilize inorganic electron donor is still lacking.MethodsIn this study, genomic and phylogenetic analyzes were used to explore the potential oxidative capacity of inorganic compounds in Alcanivorax. And its functions were verified through physiological experiments.ResultsThe sulfur oxidation-related genes sqr and tsdA are prevalent and have various evolutionary origins. Potential genes for CO oxidation were present in 39 strains, whereas genes associated with iron, hydrogen, and ammonia oxidation were either rare or absent. The physiological functions of Sqr and TsdA were confirmed in six representative strains under heterotrophic conditions. Adding thiosulfate enhanced Alcanivorax growth. However, Alcanivorax bacteria perform sulfide detoxification through Sqr rather than by gaining energy via sulfide oxidation Although no strain was confirmed to be chemoautotrophs, we discovered that the two clades, A. xenomutans and A. profundimaris, can grow under conditions with very low organic matter.DiscussionThe ability to utilize inorganic compounds as a supplementary energy source and adapt to carbon oligotrophic growth may contribute to the prevalence of Alcanivorax in marine ecosystems.

ObjectiveTo explore any correlation between serum urate (SU) level or insulin resistance (IR) and metabolic dysfunction associated steatotic liver disease (MASLD) in patients with metabolic syndrome (MS).MethodsData from all MASLD patients, diagnosed by liver biopsy, were enrolled and divided into MASLD alone group and MASLD with MS group. They were subdivided into hyperuricemia group and normal SU group to find correlation between SU/IR and MASLD in patients with MS and independent risk factors for MASLD.ResultsData from 539 MASLD patients were analyzed. Body mass index (BMI) (p = 0.000), waist circumference (WC) (p = 0.004), and low-density lipoprotein (LDL) (p = 0.000) were dramatically higher in MASLD with MS group than those with MASLD alone; MASLD with MS patients had significantly more family history of diabetes (p = 0.000) and hypertension (p = 0.000) than patients with MASLD alone. Height (p = 0.000), weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.001), and LDL (p = 0.007) were dramatically higher in hyperuricemia patients than those with normal SU. SU was inversely associated with age (p = 0.000) and high-density lipoprotein (HDL) (p = 0.003), and positively correlated with weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.000), TG (p = 0.000), and LDL (p = 0.000). Logistic Regression analysis showed that age (p = 0.031), TG (p = 0.002), LDL (p = 0.010), HbA1c (p = 0.026), and family history of hypertension (p = 0.000) may be independent risk factors for MASLD in patient with MS.ConclusionInsulin resistance (IR) in MASLD patients with MS, but not higher SU levels, has closer correlation with the occurrence of MASLD in patients with family history of hypertension and diabetes having higher BMI, LDL, HbA1c.

This study aims to explore factors that affect individual residents’ behaviors contributing to reducing carbon emissions (low-carbon behaviors), based on the empirical analysis of the choice of adoption and the extent of adoption of low-carbon practices, such as using low-carbon transportation and energy-saving, in Kunming, China. We use spatial econometric regression models to consider positive spillover of low-carbon behaviors amongst residents as people tend to obtain knowledge and learn good actions from those located nearby. The results show the existence of positive spillover effects of low-carbon behaviors across several types of low-carbon practices. We find that location effects, such as access to parks, residents’ knowledge of carbon neutrality, and science communications in the local community are the most important determinants of residents’ low-carbon behaviors. The findings may provide insights into designing supporting policies to incentivize residents’ low-carbon behaviors and contribute to the pathway toward carbon neutrality from the micro-perspective.

Microplastics are widespread pollutants in aquatic environments, posing a significant threat to the health of marine ecosystems. However, little is known about the impact of plastics on deep-sea microbial communities. In this paper, we investigated the effects of polystyrene (PS) microplastics with three particle sizes (60 nm, 600 nm and 1 µm) and three concentrations (10, 50, 150 mg/L) as well as PS films (1 × 1 cm) on the deep-sea microbial community inoculated with water of 3370 m water depth from Pacific Ocean by using reactive oxygen species (ROS) detection, growth rate, scanning electron microscope (SEM) and high-throughput sequencing. Microplastics surface rotting (600 nm and 1 µm) and further fragmentation (60 nm) were observed caused by plastic-degrading microbial erosion after 50 days’ incubation. Similarly, deformation of PS film, including formation of obvious wrinkles and deep pits and the generation of microplastics and nanoplastics were also observed. Microplastics from commercial and plastic films could stimulate the bacterial community to secrete extracellular polymeric substance (EPS), favouring biofilm formation and resistance to external stress. Compared with larger microplastics, 60 nm microplastics and plastic films significantly inhibited the growth of bacterial communities with enhanced ROS production. The abundance of Moraxellaceae dominated in all enriched samples with the addition of microplastics, while the abundance of Alcanivoracaceae also increased in the 60 nm and plastic film enrichments, in contrast to dominant bacteria of Colwelliaceae, Marinobacteraceae, Rhodobacteraceae and Alcanivoracaceae the deep seawater in situ. Correspondingly, the functional changes of the communities were observed via functional prediction by 16S rRNA gene based on their alterations in bacterial community structure. The study provides insights into the effects of microplastics and nanoplastics on deep-sea microbial communities.