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Due to the pandemic, many students have been forced to study remotely. This study aims to investigate the impact of online collaboration scripts on learning outcomes in virtual reality (VR) co-creation learning activities during distance learning. The collaboration scripts were designed to foster students' remote teamwork. The participants consisted of 106 Taiwanese sixth-grade elementary students, divided equally into an experimental group and a comparison group. The experiment lasted for seven weeks, with approximately 40 minutes per week dedicated to VR co-creation activities. The experimental group followed online collaboration scripts, while the comparison group engaged in distance learning without scripts. Additionally, the researchers collected students' learning logs and analyzed behavioral sequences to enhance understanding of their learning behaviors. Epistemic network analysis was employed to analyze group interactions, focusing on Orientation, Planning, Executing, Monitoring, and Evaluation codes. Results revealed significant improvement in the experimental group's learning achievement and communication skills using online collaboration scripts in VR co-creation learning. The experimental group exhibited a stronger correlation in Planning--Executing, following the script stages, while the comparison group relied more on peer assistance. Overall, the online collaboration scripts could scaffold learning and support effective remote VR learning activities for content co-creation for elementary students.

The genus Strobilomyces, representing a diverse and widespread group of ectomycorrhizal mushroom-forming fungi, plays a crucial ecological and economical role. However, until now, a comprehensive description of its mitochondrial genome (mitogenome) has been lacking. In our current study, we have successfully assembled and analysed the mitogenomes of five Strobilomyces species. These mitogenomes span a range from 35,618 base pairs (bp) to 42,088 bp, exhibiting a higher nucleotide abundance of AT compared to GC. All five mitogenomes harbour 14 conserved protein-coding genes (PCGs), two ribosomal RNAs (rRNAs) and 24 transfer RNAs (tRNAs). Notably, the overall ratio of Ka/Ks for all PCGs was found to be less than 1.0, indicating that these genes have undergone purifying selection during evolution. Intriguingly, the mitogenomic comparison revealed two instances of gene re-arrangement, which were directly linked to the geographical distribution of the Strobilomyces species. The concatenated mitochondrial PCGs (mtPCGs) and nuclear ribosomal DNA (nrDNA) phylogenies displayed a robust congruent topology at the family level. Specifically, the Strobilomyces species clustered together and formed sister relationship with other Boletaceae species in the mtPCGs tree. In contrast, the Strobilomyces species grouped at the base of the nrDNA tree when concerning Boletaceae. This study represents the first report on the mitogenomes of the Strobilomyces genus, providing valuable insights into fungal evolution within Boletales.

Individual mobility prediction forecasts traveling activities of an individual traveler, and has wide applications in location-based services, public health, and transportation planning. Whereas, it remains challenging due to the complexity and uncertainty of human mobility. Existing methods mainly consider spatiotemporal contexts in current traveling, but overlook those in historical trips, as well as relationships between traversed road intersections. These issues hinder the model from effectively capturing complex mobility patterns. To fill this gap, we propose a novel method that incorporates current traveling features and historical activity chain to predict the coordinates of traveling destination. Specifically, (1) we construct current traveling features by extracting real-time moving states, and represent spatiotemporal correlations between traversed road intersections using word embedding; (2) we learn travel intentions as a probability vector for each historical trip, and combine it with spatiotemporal features to construct historical activity chain; (3) we construct an individual mobility prediction model using Long Short-Term Memory (LSTM) network and spatiotemporal scoring mechanism, to capture short-term and long-term dependencies in current trip and historical activity chain, respectively. Experiments on 21,890 trajectories over the whole Year 2019 of 20 representatives selected from 1916 private car travelers in Shenzhen City, reveal the effectiveness of our model. It outperforms four baselines, Random Forest (RF), Distant Neighboring Dependencies (DND), Location Semantics and Location Importance (LSI)-LSTM, as well as Intersection Transfer Preference and Current Movement Mode (ITP-CMM), by approximately 10%-15% improvement in accuracy. In addition, we further explore the impact of historical activity chain length, and destination visiting frequency on prediction, as well as the relationship between predictability and eight mobility pattern features. This study benefits potential applications such as personalized location-based service recommendations and targeted advertising, and also provides implications for understanding human mobility.

Abstract Background Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy. Methods We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*109) and low (≤ 752*109) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan–Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves. Results An optimal SII cutoff of 752*109 stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan–Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8+ T cells and Granzyme B+ CD8+ T cells in peripheral blood. Conclusion SII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.

Background and Aim: Physical activity is an important means to promote the comprehensive and healthy development of children's bodies and minds. The national health strategy and population policy adjustment, the development of kindergartens, and the deterioration of children's physical health have all worked together to bring unprecedented opportunities for the development of children's sports in China. The purpose of this paper is to study the background information of the contents of the curriculum of preschool physical education ability of year 4 students and develop the curriculum to improve the preschool physical education ability of year 4 students. Materials and Methods: The researcher has studied the literature on the development of physical education teachers' physical education ability curriculum to cultivate year 4 students' physical education ability from the aspects of the curriculum development process, components, implementation, and evaluation, and has studied the quality of students' teachers from textbooks, academic documents, and related research. The researcher also used a simple random sampling method to have 4 teachers as a sample. The population is 8 expert teachers in physical education. The research instruments of this study are an interview questionnaire on preschool's physical education ability and lesson plans. Results: Research findings: 1) The 6 components of the course include principles, objectives, content, instructional strategies using situational teaching methods, materials, and evaluation. 2) Preschool physical education ability which includes: 2.1) General ability, 2.2) Special ability, and 2.3) Application ability. After that, the researcher designed and completed the training course components of preschool physical education, and then evaluated the quality by five experts. The IOC value was between 3.80-4.00, and the interrater reliability value was between 0.77-0.79> 0.5. The course components were modified according to the experts' suggestions. Conclusion: The components of the course which include 6 components could improve the preschool physical education ability of year 4 students effectively.

Chronic osteomyelitis caused by implant infections is a common complication following orthopedic surgery. Preventing bacterial infection and simultaneously improving bone regeneration are the key for osteomyelitis. Current treatments include systemic antibiotics and multiple surgical interventions, but the strategies available for treatment are limited. In this study, a multifunctional engineered Bacillus subtilis (B. sub) hydrogel with sulfasalazine (SSZ) is developed to treat methicillin-resistant Staphylococcus aureus (MRSA) infection and anti-inflammatory and promote bone regeneration. B. sub in alginate hydrogels protects B. sub from being cleared by the host immune system while allowing the release of its bioactive substances, including antibacterial peptides and anti-inflammatory agents such as SSZ. The results show that the engineered probiotic hydrogels exhibit excellent antibacterial efficacy against MRSA (97 %) and prevent the development of bacterial resistance. The antibacterial effect is primarily mediated through the secretion of bioactive peptides by B. sub, which not only inhibit MRSA growth but also reduce the likelihood of resistance development. Meanwhile, the probiotic hydrogel has a greater ability to induce M2 polarization of macrophages and promote angiogenesis, resulting in enhanced osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) and thus enhancing bone regeneration. This engineered probiotic hydrogel offers a promising strategy by simultaneously combating bacterial infection and enhancing osteogenic differentiation for chronic osteomyelitis.

Abstract Background Life’s Simple 7 (LS7), developed by the American Heart Association, addresses seven key health behaviors and relationship factors. Although LS7 has been studied in relation to various chronic diseases, its association with arthritis remains unclear. This study seeks to investigate the association between LS7 and arthritis, with particular emphasis on the mediating role of body fat percentage (BFP). Methods Data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES), including 16,332 adult participants, were analyzed. The connection between LS7 and arthritis was evaluated using multivariable logistic regression, smooth curve fitting, and subgroup analysis. Mediation analysis assessed the role of BFP in this relationship. Additionally, ROC curve analysis was used to assess the predictive performance of the model, and the Boruta algorithm identified the influential factors associated with arthritis. Results After adjusting for relevant covariables, each standard deviation increase in LS7 was linked to a 13% lower likelihood of arthritis [OR = 0.87, 95% CI: 0.84, 0.89]. Participants in the highest LS7 tertile (T3) exhibited a 50% reduced likelihood of developing arthritis compared to those in the lowest tertile (T1) [OR = 0.50, 95% CI: 0.43, 0.60]. Mediation analysis confirmed that BFP significantly mediated the LS7-arthritis relationship. Furthermore, the Boruta algorithm identified LS7 and BFP as key variables associated with arthritis. Conclusion Elevated LS7 scores were associated with a lower likelihood of arthritis, with BFP serving as a mediating factor. Improving LS7 scores and managing body fat may help prevent arthritis. Due to the study’s cross-sectional design, causality cannot be confirmed. Future research should use longitudinal studies to verify these findings and target high-risk groups.

Abstract Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages. Here, we found that L-malate exerts anti-inflammatory effect via BiP-IRF2BP2 signaling, which is a sensor of cytosolic pH in macrophages. First, L-malate, a TCA intermediate upregulated in pro-inflammatory macrophages, was identified as a potent anti-inflammatory metabolite through initial screening. Subsequent screening with DARTS and MS led to the isolation of L-malate-BiP binding. Further screening through protein‒protein interaction microarrays identified a L-malate-restrained coupling of BiP with IRF2BP2, a known anti-inflammatory protein. Interestingly, pH reduction, which promotes carboxyl protonation of L-malate, facilitates L-malate and carboxylate analogues such as succinate to bind BiP, and disrupt BiP-IRF2BP2 interaction in a carboxyl-dependent manner. Both L-malate and acidification inhibit BiP-IRF2BP2 interaction, and protect IRF2BP2 from BiP-driven degradation in macrophages. Furthermore, both in vitro and in vivo, BiP-IRF2BP2 signal is required for effects of both L-malate and pH on inflammatory responses. These findings reveal a previously unrecognized, proton/carboxylate dual sensing pathway wherein pH and L-malate regulate inflammatory responses, indicating the role of certain carboxylate metabolites as adaptors in the proton biosensing by interactions between macromolecules.

Abstract For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white‐coat hypertension (WCH), masked hypertension (MH), white‐coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome‐based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24‐h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de‐escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24‐h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively.

Abstract This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small cell lung cancer (NSCLC). Early-stage NSCLC patitents who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary endpoint were the patterns of disease progression, which were divided into local recurrence, regional failure, and distant metastasis. Kaplan-Meier method survival analysis was used to calculate overall survival (OS), progression-free survival (PFS). Cox model was used for univariate analysis and multivariate analysis. A total of 215 patients with 224 lesions were enrolled. After the median follow-up time of 50.8 months (1.0-117.9 months), 76 (35.3%) patients progressed, with regional progression occurring in 4 cases (1.8%), local and local-regional progression in 17 cases (7.9%), various distant metastases developing in 55 cases (25.6%). The OS rates at 1, 3, and 5 years were 97.1%, 80.9%, and 63.8%, respectively, with a median OS of 92.2 months (95%CI, 61.5-122.9 months). The PFS rates at 1, 3, and 5 years were 87.5%, 65.9%, and 50.8%, respectively, with a median PFS of 62.2 months (95% CI, 45.0-59.4 months). There was no significant difference in OS (P = 0.832) and PFS (P = 0.672) between the two groups with or without pathology. Multivariate analysis showed that BED and patient age were independent prognostic factors affecting early-stage lung cancer survival (all P

Abstract Understanding the intricate interplay between nanoparticle-mediated cyanobacterial interactions is pivotal in elucidating their impact on the transcriptome and lipidome. In the present study, total fatty acid methyl esters (FAMEs) in the wild-type (B481-WT) and transformant (B481-SD) Fremyella diplosiphon strains treated with nanoscale zero-valent iron nanoparticles (nZVIs) were characterized, and transcriptome changes analyzed. Comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry revealed a 20–25% higher percentage of FAMEs in nZVI-treated F. diplosiphon strain B481-SD compared to B481-WT. Accumulation of alkanes was significantly higher (> 1.4 times) in both strains treated with 25.6 mg L−1 nZVIs compared to the untreated control. In addition, we observed significantly higher levels of monounsaturated FAMEs (11%) in B481-WT in 3.2 (11.34%) and 25.6 mg L−1 (11.22%) nZVI-treated cells when compared to the untreated control (7%). Analysis of the F. diplosiphon transcriptome treated with 3.2 mg L−1 revealed a total of 1811 and 1651 genes that were differentially expressed in B481-SD and B481-WT respectively. While the expression of iron uptake and ion channel genes was downregulated, genes coding for photosynthesis, pigment, and antioxidant enzymes were significantly (p

Magnesium and its alloys show strong mechanical anisotropy due to their hexagonal close-packed structure. This paper processed ambient extrusion and subsequent annealing on AZ31 magnesium alloy bars to investigate the effect of working hardening and texture weakening on yield anisotropy of magnesium alloy. After ambient extrusion, yield strength on different loading direction are improved due to working hardening. ED-yield strength has the highest increment because work hardening has a higher effect on prismatic slip. Then, yield anisotropy becomes stronger with the increase of extrusion train. During annealing, static recrystallization occurs firstly in {101‾1} twinning zones and producing recrystallized grains with random orientation. With the growth of recrystallized grains, basal fiber texture is weakened gradually. Such weak basal texture can promote the activation of basal slip when loading along ED, so ED-yield strength shows a high decrement. On this way, the yield anisotropy in AZ31 magnesium alloy bars is weakened through ambient extrusion and subsequent annealing.

Abstract Quantum clock synchronization (QCS) can measure out the high-precision clock difference among distant users, which breaks through the standard quantum limit by employing the properties of quantum entanglement. Currently, the wavelength division multiplexed QCS network has been demonstrated with a spontaneous parametric down-conversion entangled photon source. In this paper, we propose a more efficient QCS network scheme with the wavelength multicasting entangled photon source, which can decrease at least 25% of wavelength channel consumption under the identical network scale. Afterwards, a four node QCS network is demonstrated, where the wavelength multicasting entangled photon source is utilized with dual-pumped four-wave mixing silicon chip. The experimental results show that the measured time deviation is 3.4 ps with an average time of 640 s via the multiple fiber links of more than 10 km.

Abstract Transition metal carbide shows excellent performance in selective hydrogenation of acetylene, however, the carburization of Pd-based intermetallic compounds remains infeasible. Here we report the successful synthesis of an unprecedented Pd3ZnCx intermetallic carbide, via co-infiltration of zinc and carbon in one-step carburization by syngas. Utilizing state-of-the-art in situ characterizations and theoretical calculation, we unveil the dynamic evolution of Pd3ZnCx during carburization, forming a Pd3Zn like cubic phase carbide structure. A unique transitional state (Pdt) with low content of Zn/C co-infiltration is clearly identified facilitating phase transition and sustain incorporation of carbon and zinc at elevated temperatures. The Pd3ZnCx carbide shows by far the best catalytic performance in the selective hydrogenation of acetylene with a high selectivity (>90%) even at a high H2/C2H2 ratio. Our results therefore provide a co-infiltration strategy and dynamic insights for the one-step synthesis of Pd based intermetallic carbides, towards high-performance intermetallic compound for selective hydrogenation of acetylene.

Abstract Background Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. Methods Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. Results Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. Conclusion These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.

Abstract Background The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified ( 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders. Results During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54–1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52–1.84), CVD mortality (HR: 1.55, 95% CI: 1.34–1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33–1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04–1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04–1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12–1.44). For participants

Abstract Background Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. Methods This research involved 895 mother–child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath’s epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. Results The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), − 13.22 (− 23.21 to − 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), − 14.13 (− 21.59 to − 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than − 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than − 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than − 1.35, followed by a plateau between − 1.35 and − 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than − 0.67. Conclusions In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Abstract Background Cardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD. Methods A total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission. Results During the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte–lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01–1.05) and MLRs (95% CI, OR: 1.01–1.09) were significantly associated with CVD in patients with BD, respectively. Conclusions Monocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD.

Abstract We investigated the potential of the transmission line model as a digital twin of aneurysmal aorta by comparatively analyzing how a uniform lossless tube-load model were fitted to the carotid and femoral artery tonometry waveforms pertaining to (i) 79 abdominal aortic aneurysm (AAA) patients vs their matched controls (CON) and (ii) 35 AAA patients before vs after endovascular aneurysm repair (EVAR). The uniform lossless tube-load model fitted the tonometry waveforms pertaining to AAA as well as CON and EVAR. In addition, the parameters in the tube-load model exhibited physiologically explainable changes: when normalized, both pulse transit time and reflection coefficient increased with AAA and decreased after EVAR, which can be explained by the increase in arterial compliance and the decrease in arterial inertance due to the aortic expansion associated with AAA. In sum, the tube-load model may have the potential as a digital twin to enable personalized AAA monitoring.

In grain crops such as maize (Zea mays), leaf angle (LA) is a key agronomic trait affecting light interception and thus planting density and yield. Nitrogen (N) affects LA in plants, but we lack a good understanding of how N regulates LA. Here, we report that N deficiency enhanced lignin deposition in the ligular region of maize seedlings. In situ hybridization showed that the bZIP transcription factor gene ZmbZIP27 is mainly expressed in the phloem of maize vascular bundles. Under N-sufficient conditions, transgenic maize overexpressing ZmbZIP27 showed significantly smaller LA compared with wild type (WT). By contrast, zmbzip27ems mutant showed larger LA under both N-deficient and N-sufficient conditions compared with WT. Overexpression of ZmbZIP27 enhanced lignin deposition in the ligular region of maize in the field. We further demonstrated that ZmbZIP27 could directly bind the promoters of the microRNA genes ZmMIR528a and ZmMIR528b and negatively regulate the expression levels of ZmmiR528. ZmmiR528 knockdown transgenic maize displayed erect architecture in the field by increasing lignin content in the ligular region of maize. Taken together, these results indicate that ZmbZIP27 regulates N-mediated LA size by regulating the expression of ZmmiR528 and modulating lignin deposition in maize.

The game-based learning approach to developing students' computational thinking (CT) current has received attention from researchers. However, the compatibility between games and instruction is often insufficient to accommodate the entertaining and educational nature of the curriculum entirely, and the benefits of game-based learning could be compromised. Therefore, this study proposed a role-playing-based micro-game strategy for developing students' CT in a Python programming course, and designed a quasi-experiment to verify the effectiveness of the role-playing-based micro-game strategy. A total of 133 eighth-grade students from schools in eastern China were randomly divided into experimental and control groups. The experimental group used a role-playing-based micro-game strategy, and the control group used a traditional instructional strategy. The results showed that the experimental group scored significantly higher than the control group on the CT test, especially in the dimensions of computational concepts and computational practices. The learning engagement of the experimental group was significantly higher than that of the control group, and the learning motivation of the experimental group was significantly improved before and after the experiment. In addition, qualitative analysis of the interview data indicated that micro-game strategy on role-playing could promote classroom learning and meet the needs of the course knowledge system.

This prospective longitudinal study assessed the effects of the course management system, EDU3, on the effectiveness of the dissemination of holistic health care and evidence-based medicine (EBM) courses. Between January 2014 and December 2021, delinked data (n = 354,229) from EDU3 were analyzed. In addition to analyzing the main educational team or seed teachers responsible for opening the courses, yearly changing trends in the number and teaching styles of courses, main participants, and the diversity of teaching activities were evaluated. EDU3 precisely announced the courses opened by non-doctor major departments, including departments of medical education, nursing, and medical research, for non-doctor medical personnel. Meanwhile, the system smoothly announced doctor major departments which opened courses for doctors. A 2 times/4.5 times parallel increase in holistic health care/EBM courses from institution to department and the yearly increasing trends in the number of these courses indicated the success of this system. This study revealed that centralized training of seed teachers motivated them to open diverse department-oriented teaching activities for holistic health care and EBM. The parallel increasing trends of the number of courses opened by the institution and departments indicated the effective dissemination of holistic health care and EBM from institution to department.

Abstract A new aggregation‐induced emission (AIE) luminogen is obtained by dimerizing acridin‐9(10H)‐one (Ac), an aggregation‐caused quenching (ACQ) effect monomer via an N─N bond and forming 9H,9′H‐[10,10′‐biacridine]‐9,9′‐dione (DiAc) with D2d symmetry. The quenching of DiAc in solution is ascribed to the enhanced basicity promoting hydrogen bonding and then a hydrogen abstraction (HA) reaction and/or an unallowed transition in frontier orbitals with the same symmetry facilitating intersystem crossing. It is found that emissive Ac is one product of the non‐emissive DiAc solution in the HA reaction activated by UV irradiation. By exploiting the AIE properties and the HA reaction of DiAc, photolithographic patterning is demonstrated with a paper wetted with DiAc solution.

ObjectiveThis study investigates the reinforcing effects and monoamine oxidase-A (MAO-A) inhibitory properties of heated tobacco products (HTPs), comparing them to nicotine alone. It also examines brand-specific differences in MAO-A inhibition to provide a deeper understanding of the role of non-nicotine constituents in HTP use.MethodsA rat self-administration model was used to evaluate the reinforcement patterns of HTP-T (tobacco flavor), HTP-M (menthol flavor), and nicotine under fixed-ratio schedules. In vitro assays were performed to measure the MAO-A inhibitory effects of nicotine, HTP-T, and HTP-M. Additionally, chemical composition analyses of HTP-T and HTP-M aerosols were conducted and compared to identify potential MAO inhibitors. Finally, in vitro assessments of MAO-A inhibition were performed across various HTP brands to determine whether significant differences in MAO-A inhibition exist among different HTP products.ResultsHTP-T showed self-administration patterns comparable to nicotine, while HTP-M demonstrated significantly higher reinforcement. In vitro analyses revealed that both HTP-T and HTP-M exhibited MAO-A inhibition at high nicotine-equivalent concentrations (>10−2–10−1 mM), with HTP-M showing stronger inhibition. In contrast, Nicotine alone showed no MAO-A inhibition. Brand-specific differences in MAO-A inhibitory effects were also observed, potentially driven by variations in aerosol composition.ConclusionsHTP-M's enhanced reinforcement could be attributed to its higher MAO-A inhibition and menthol's synergistic effects on nicotine. Brand-specific variations in MAO inhibition highlight the impact of non-nicotine constituents on HTP use. While this study provides valuable insights into HTPs, its reliance on animal models and in vitro assays highlights the necessity for human studies conducted under real-world conditions.

Abstract Unlike animals, plants are unable to move and lack specialized immune cells and circulating antibodies. As a result, they are always threatened by a large number of microbial pathogens and harmful pests that can significantly reduce crop yield worldwide. Therefore, the development of new strategies to control them is essential to mitigate the increasing risk of crops lost to plant diseases. Recent developments in genetic engineering, including efficient gene manipulation and transformation methods, gene editing and synthetic biology, coupled with the understanding of microbial pathogenicity and plant immunity, both at molecular and genomic levels, have enhanced the capabilities to develop disease resistance in plants. This review comprehensively explains the fundamental mechanisms underlying the tug‐of‐war between pathogens and hosts, and provides a detailed overview of different strategies for developing disease resistance in plants. Additionally, it provides a summary of the potential genes that can be employed in resistance breeding for key crops to combat a wide range of potential pathogens and pests, including fungi, oomycetes, bacteria, viruses, nematodes, and insects. Furthermore, this review addresses the limitations associated with these strategies and their possible solutions. Finally, it discusses the future perspectives for producing plants with durable and broad‐spectrum disease resistance.

Stroke patients are susceptible to malnutrition as a result of dysphagia, neurological impairments, and altered levels of consciousness. The nutritional status of individuals post-stroke is a critical determinant influencing the efficacy of rehabilitation outcomes. Therefore, there is great interest in the possible role of nutrients in promoting recovery after stroke. This article examines the enhancement of rehabilitation outcomes through the improvement of nutritional status. A comprehensive literature search was conducted using the PubMed, Cochrane, Web of Science, and Embase databases. Articles relevant to this topic, published from the inception of each database until November 2024, were identified. The selection was restricted to randomized controlled clinical trials, irrespective of language or publication date. The search specifically targeted studies involving stroke patients, encompassing both hemorrhagic and ischemic types, and interventions that combined nutritional supplementation with rehabilitation therapy. Studies with a focus on stroke prevention were excluded. Full-text articles that met the inclusion criteria were retrieved from the aforementioned sources. In instances where both a full report and a conference abstract were available for the same study, only the full report was considered. A total of 751 studies were considered for inclusion in this scoping review. Following a rigorous screening process, 13 studies were selected for detailed analysis. All selected studies were randomized controlled clinical trials. The findings indicate that supplementation with nutrients such as proteins, vitamins, essential amino acids, and antioxidants can enhance activities of daily living, improve balance function, and reduce neurological deficits in post-stroke patients. This review aims to synthesize current evidence regarding the effects of various nutrients and dietary regimens on limb rehabilitation in post-stroke patients, with the goal of providing new insights to facilitate the accelerated recovery of this population.

Abstract Background Asthma is currently one of the most common of respiratory diseases, severely affecting the lives of patients. With the in‐depth study of the role of the nervous system and sex hormones on the development of asthma, it has been found that the nervous system and sex hormones are related to each other in the pathway of asthma. Objective To investigate the effects of sex hormones and the nervous system on the development of asthma. Methods In this review, we searched for a large number of relevant literature to elucidate the unique mechanisms of sex hormones and the nervous system on asthma development, and summarized several common targets in the pathways of sex hormones and the nervous system on asthma. Conclusion We summarize several common important targets in the pathways of action of sex hormones and the nervous system in asthma, provide new directions and ideas for asthma treatment, and discuss current therapeutic limitations and future possibilities. Finally, the article predicts future applications of several important targets in asthma therapy.

On Taiwan’s offshore islands of Kinmen, the water supply infrastructure has experienced various challenges stemming from the physical and social conditions of islands. These conditions are related to islands’ distinct characteristics, such as smallness, boundedness, and remoteness, collectively referred to as islandness. This paper combines perspectives from infrastructure and island studies to examine how islandness-related effects have contributed to infrastructure failures. Drawing from interviews and document analysis, it explores the issues faced by the reservoirs and the desalination plant in Kinmen, including small storage and poor water quality, lack of energy and technical capacities, high production and maintenance costs, and poor seawater quality. Then, based on the above case study and a document analysis of water supply technical reports on Taiwan’s offshore islands, some shared islandness-related conditions are identified and categorized in relation to smallness, remoteness and peripherality, and ocean materiality. While offering generalizability, it is crucial to note that these conditions are not seen as determined but rather as relational and contingent upon other factors. Through such examination, the paper contributes to the discussion surrounding islandness and infrastructure breakdowns, shedding lights on the relational effects of islandness on water supply infrastructure.

Summary: Background: Although numerous prognostic scores have been developed for patients with cirrhosis after Transjugular intrahepatic portosystemic shunt (TIPS) placement over years, an accurate machine learning (ML)-based model remains unavailable. The aim of this study was to develop and validate a ML-based prognostic model to predict survival in patients with cirrhosis after TIPS placement. Methods: In this retrospective study in China, patients diagnosed with cirrhosis after TIPS placement from 2014 to 2020 in our cohort were included to develop a ML-based model. Patients from the other two tertiary hospitals between 2016 and 2022 were as external validation cohort. The random forest (RF) model was built using 7 selected features via the least absolute shrinkage and selection operator (LASSO) regression, and subsequent 10-fold cross-validation was performed. Findings: A total of 400 patients in our cohort were included (median age and interquartile range, 59 (50, 66); 240 men). Two hundred and eighty patients made up the training set and 120 were in the testing set, and 346 patients were included in the external validation cohort. Seven attributes were selected: Na, ammonia (Amm), total bilirubin (Tb), albumin (Alb), age, creatinine (Cr), and ascites. These parameters were included in a new score named the RF model. The accuracy, precision, recall, and F1 Score of the RF model were 0.84 (95% CI: 0.76, 0.91), 0.84 (95% CI: 0.77, 0.91), 0.99 (95% CI: 0.95, 1.00), 0.91 (95% CI: 0.81, 0.10) in the testing set, and 0.88 (95% CI: 0.84, 0.91), 0.89 (95% CI: 0.85, 0.92), 0.99 (95% CI: 0.97, 1.00), 0.93 (95% CI: 0.85, 0.97) in the validation cohort, respectively. The calibration curve showed a slope of 0.875 in the testing set and a slope of 0.778 in the external validation cohort, suggesting well calibration performance. The RF model outperformed other scoring systems, such as the (Child-Turcotte-Pugh score) CTP, (model for end-stage liver disease) MELD, (sodium MELD) MELD-Na, (Freiburg index of post-TIPS survival) FIPS and (Albumin-Bilirubin) ALBI, showing the highest (area under the curve) AUC of 0.82 (95% CI: 0.72, 0.91) and 0.7 (95% CI: 0.60, 0.79) in predicting 1-year survival across the testing set and external validation cohort. Interpretation: This study developed a RF model that better predicted 1-year survival for patients with cirrhosis after TIPS placement than the other scores. Funding: National Natural Science Foundation of China (grant numbers 81900552 and 82370628).

Abstract Objective To assess the efficacy and safety of using the adjustable flanged technique for secondary implantation of four-point scleral‑fixated posterior chamber intraocular lenses with two parallel 6−0 polyglactin sutures. Methods Two parallel 6−0 polyglactin sutures were passed separately through the two haptics on the horizontal line of the 4-haptic IOL. The four externalized sutures were then trimmed and cauterized to form flanges. The best corrected visual acuity, intraocular pressure, and complications in all patients were observed and recorded. Results The flanged technique using two parallel 6−0 polyglactin sutures was applied to 14 aphakic eyes. The average preoperative best corrected visual acuity was 1.00 ± 0.88 LogMAR (Snellen 20/200), which improved to 0.42 ± 0.38 LogMAR (Snellen 20/48) at the final follow-up (P = 0.004). None of the patients experienced vitreous hemorrhage, low intraocular pressure, or issues with exposed or broken sutures. Conclusion The simplicity of the technique, along with its ability to accommodate adjustments post-implantation, allows for optimal positioning and reduces risks like IOL tilt or dislocation. Overall, this is a promising approach to secondary IOL implantation, with potential benefits for both patient outcomes and surgical efficiency.

Abstract We study that the different-mode (waveguide-connected) power splitter [(W)PS] can provide different-mode testing points for the optical testing. With the PS or WPS providing two different-mode testing points, the measured insertion losses (ILs) of the three-channel and dual-mode waveguide crossing (WC) for both the fundamental transverse electric (TE0) and TE1 modes are less than 1.8 dB or 1.9 dB from 1540 nm to 1560 nm. At the same time, the crosstalks (CTs) are lower than −17.4 dB or −18.2 dB. The consistent test results indicate the accuracy of the (W)PS-based testing circuit. Additionally, combining the tunable tap couplers, the (W)PS can provide multiple testing points with different modes and different transmittances.

Pogostemon cablin essential oil (PEO), extracted from P. cablin, has anti-oxidant, anti-inflammatory, and anti-stress properties, as well as the ability to improve gastrointestinal digestion. This study aims to evaluate the effects of PEO on the performance, rumen epithelial morphology, and barrier function in heat-stressed beef cattle. Thirty-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0 (control), 50, 100, or 150 mg/kg in the feed concentrate (n = 9). All experimental cattle were fed under high temperature and humidity in summer for 60 days. The results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group (P = 0.032). All PEO treatments reduced the diamine oxidase activity (P = 0.004) and malondialdehyde content (P = 0.008) in serum. In addition, the content of 70 kDa heat shock protein in the 100 mg/kg group was increased, and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group (P

Abstract Background The bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women. Methods The researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women. Results There were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04–0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01–0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11–1.12), P = 0.07]. Conclusion Tai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis.

Abstract The primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape.

Abstract Background Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Abstract Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment.

Abstract Background Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. Methods This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. Results During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear

Abstract The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson’s disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Background: Senile pruritus (SP), characterized by idiopathic itch in individuals aged 60 years and older without primary skin lesions, significantly impacts sleep and quality of life. Effective alternative treatments are needed. Acupuncture has been suggested as a potential intervention to alleviate pruritus; however, its role in managing SP remains uncertain. This study aims to evaluate the efficacy and safety of acupuncture for SP. Methods: This single-center, parallel, two-arm, randomized, sham-controlled trial will enroll 200 patients diagnosed with SP in a 1:1 ratio to either the acupuncture or sham acupuncture group, receiving acupuncture or sham acupuncture three sessions weekly for six weeks. Participants, outcome assessors, and the statisticians will be blinded. The primary outcome is the change from baseline in the Average Pruritus Numerical Rating Scale (AP-NRS) score at week 6. Secondary outcomes include changes in AP-NRS (at other timepoints), Peak Pruritus Numerical Rating Scale (PP-NRS), number of scratch episodes, itchy area of body surface, overall dry skin score (ODS), the Dermatology Life Quality Index (DLQI), the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale (HADS), and Patient Global Impression of Change (PGIC). Long-term effects of acupuncture will also be explored. Adverse events and additional treatments will be monitored throughout the study period. The modified intention-to-treat (mITT) population which includes participants who complete baseline assessments and receive at least one treatment session will be analyzed. Discussion: This trial represents the first rigorously designed, single-center, randomized, sham-controlled study assessing the effects and safety of acupuncture for senile pruritus. We used valid outcome measurements which can provide valuable insights into the patient's symptoms and facilitate tracking symptoms over time and evaluate treatment effectiveness. This study may provide valuable insights into the research topic and inform future research. Ethics and dissemination: This study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-087-KY). Trial registration: Registered with ClinicalTrials.gov (NCT06506240) on July 11, 2024.