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Abstract The Artificial Intelligence of Things (AIoT) ecosystem faces significant challenges related to limited client energy budgets and resource heterogeneity, particularly when employing the Federated Learning (FL) framework. This paper presents a novel energy-efficient client selection algorithm for FL, designed to address these challenges by integrating Wireless Power Transfer (WPT), where WPT involves in the client selection optimization, based on real-time energy availability and resource heterogeneity. We formulate the client selection problem as a multi-dimensional knapsack problem (MKP) and solve it using dynamic programming to maximize energy efficiency while maintaining fast convergence. Experimental results show that incorporating WPT leads to a reduction in unit energy consumption by over 24.54%; while, the proposed algorithm achieves a reduction of over 15.31% compared to random selection. The proposed approach improves energy utilization, demonstrates strong resilience to client heterogeneity, and adapts efficiently to varying energy supply conditions.

Abstract Limb-girdle muscular dystrophy R8 (LGMD R8) is a hereditary muscle disease caused by biallelic defects in E3 ubiquitinated ligase gene (TRIM32). LGMD R8 is featured by high genetic heterogeneity and phenotypic diversity, most pathogenic variants are missense variants located in the NHL domain, but the genotype-phenotype correlation remains unclear. We hypothesized that various missense variants in NHL domain might have different degrees of impact on the structure and function of the protein, thus resulting in disease variability. Firstly, by analyzing present patients’ clinical data, we screen out 4 variants: R394H, D487N, V591M and P619S. Patients homozygous for the aforementioned variants exhibited significant phenotypic variability, including variations in age of onset and age of any walking aid (AWA). Then, bioinformatics analysis, cellular functional experiment and biophysical assay were used to measure the effect of above variants in TRIM32 protein oligomerization and ubiquitination to target substrates. And they revealed distinct differences in the intrinsic E3 ligase activity among various mutant TRIM32 proteins, which corresponded to differences in their oligomerization status. In conclusion, our results showed a correlation between clinical severity, protein function and oligomerization state in patients homozygous for missense variants in NHL domain. It is the first time to reveal a connection between TRIM32 variant with LGMD R8 phenotype and this finding provided valuable reference in predicting disease severity and more precise guidance to affected family on genetic counseling.

Abstract Inorganic phosphates hold significant potential as ideal natural building blocks, forming a fundamental basis for organic and biochemical synthesis. However, their limited solubility, inherent chemical stability, and low reactivity pose substantial challenges to converting phosphates into organophosphates under mild conditions. This study introduces an efficient method for the direct conversion of phosphates into P(V)-X reagents, [TBA][PO2X2] (X = Cl, F), via a redox-neutral halogenation process. This method utilizes cyanuric chloride (or cyanuric fluoride) as the halogenation reagent, in combination with 1-formylpyrrolidine and tetrabutylammonium chloride (TBAC), under ambient conditions. The approach enables effective halogenation conversion for various P(V) sources, including orthophosphates, pyrophosphoric acid, Na3P3O9 and P2O5. Furthermore, we demonstrate the synthetic utility of the P(V)-Cl reagent in the phosphorylation of diverse O-, S-, N- and C-nucleophiles. Key advantages of this conversion process include the use of inexpensive and readily available chemicals, the avoidance of high-energy redox reactions, and the generation of a reactive yet stable P(V)-X reagent.

Abstract Background Social frailty, a multidimensional construct encompassing various social behaviors, resources, and needs, significantly impacts cognitive health in older adults. Despite existing studies linking specific social factors to cognitive function, the association between social frailty and long-term cognitive trajectories remains underexplored. This study aims to evaluate the longitudinal association between social frailty and trajectory of cognitive function in dementia-free older adults. Methods This prospective cohort study used data from the National Health and Aging Trends Study (NHATS). Social frailty was assessed using the Makizako Social Frailty Index. According to the presence of social components, individuals were categorized into social frailty (≥ 2), pre-social frailty (1), and robust (0), respectively. Cognitive function was annually evaluated through memory, orientation, and executive function tests from 2011 to 2018. Mixed-effects linear models were employed to assess the associations between social frailty and changes in global and domain-specific cognitive function, adjusting for relevant covariates. Results In this study, 4956 dementia-free older adults (mean age 76.57 [7.41]) with complete at least 2 times of cognitive tests were included. Compared with the robust, social frailty was associated with significantly faster decline in global cognitive function (β = -0.041, 95% CI [-0.047, -0.036] z score per year) and domain-specific cognitive function (βmemory = -0.045, 95% CI [-0.055, -0.036] z score per year; βorientation = -0.027, 95% CI [-0.034, -0.020] z score per year; βexecutive = -0.042, 95% CI [-0.053, -0.032] z score per year) over the follow-up. Additionally, pre social frailty was associated with significantly faster decline in global cognitive function (β = -0.016, 95% CI [-0.021, -0.012] z score per year), memory function (β= -0.045, 95% CI [-0.055, -0.036] z score per year), and orientation function (β= -0.027, 95% CI [-0.034, -0.020] z score per year) over the follow-up. Conclusions Social frailty is associated with faster decline in cognition in older adults, underscoring the necessity for enhanced social support and engagement to mitigate cognitive deterioration in vulnerable populations.

Abstract Chemotherapy drug 5-Fluorouracil (5-FU) is a major treatment for many cancers; however, its efficacy is limited by chemoresistance. Here, we investigate the resistance mechanisms to 5-FU and reversal strategies in lung and breast cancer cells. Using multiple 5-FU-resistant lung cancer and breast cancer cell models, we reveal differential cellular and molecular features of 5-FU resistance between different cancer types. We further unravel the implications of immune-related processes, NOTCH and WNT signaling with 5-FU resistance. In lung cancer, the activation of WNT/β-catenin signaling promotes the resistance and blocking this signaling re-sensitizes resistant cells to 5-FU treatment. Our study not only reveals differential features and mechanisms underlying 5-FU resistance across different cancers, but also suggests potential strategies against such resistance.

Abstract Endometrial cancer is the most prevalent form of gynecologic malignancy, with a significant surge in incidence among youngsters. Although the advent of the immunotherapy era has profoundly improved patient outcomes, not all patients benefit from immunotherapy; some patients experience hyperprogression while on immunotherapy. Hence, there is a pressing need to further delineate the distinct immune response profiles in patients with endometrial cancer to enhance prognosis prediction and facilitate the prediction of immunotherapeutic responses. The ssGSEA method was used to evaluate the activities of the immune response pathways in patients with endometrial cancer. Unsupervised clustering was employed to identify the different immune response patterns. WGCNA was employed to identify the genes that highly correlated with the immune response patterns observed. Ninety-five machine learning combinations were utilized to identify the optimal prognosis model and the novel biomarker, SLC38A3. Experiments such as cell invasion, migration, scratch, and in vivo tumorigenicity were performed to determine the function of SLC28A3. Molecular docking techniques were employed to determine the targeted action of periodate-oxidized adenosine on SLC38A3. Patients exhibited both immune response-suppressing C1 phenotypes and immune response-activating C2 phenotypes, with significant differences in prognosis between these two phenotypes. WGCNA identified 418 genes that highly correlated with the immune response phenotypes, of which 69 genes were associated with prognosis. The immune response-related score (IRRS) established by multiple machine learning frameworks demonstrated stability in predicting patient prognosis and immune status. High expression of SLC38A3 contributes to cellular malignant traits, and periodate-oxidized adenosine bound stably to SLC38A3. IRRS accurately predicts disease prognosis and immune status in patients with endometrial cancer. SLC38A3 serves as a prognostic marker for these patients and can be stably targeted by periodate-oxidized adenosine.

Abstract Background This study aims to determine the impact of a childbirth educational intervention, based on empowerment theory, on childbirth experience and empowerment in women with fetal occiput posterior and occiput transverse malpositions. Methods A randomized controlled trial was conducted from February 2022 to December 2022 involving pregnant women with fetal occiput posterior and occiput transverse malpositions. Eligible women were randomly assigned to either the control or study group. The control group received routine care during childbirth, while the study group received routine care and a childbirth-empowering educational intervention delivered by midwives. Primary outcomes assessed were childbirth experience and patient perceptions of patient-empowering nurse behaviors in pregnant women. Secondary outcomes included pregnancy outcomes, delivery support and control, maternal coping behavior during delivery, maternal participation in delivery decisions, and perception of empowerment. Results A total of 137 pregnant women were enrolled, with 69 and 68 in the control and study groups, respectively. The study group showed significantly higher levels of childbirth experience and reported better patient perceptions of patient-empowering nurse behaviors than the control group. Additionally, the study group demonstrated higher levels of delivery support and control, maternal coping behavior, and specific aspects of perceived participation and patient perception of empowerment compared to the control group. There were no statistically significant differences in pregnancy outcomes between the two groups. Conclusion The childbirth empowering educational intervention effectively improved the childbirth experience and empowerment of women with fetal occiput posterior and occiput transverse malpositions. However, further studies are required to investigate its impact on pregnancy outcomes. Trial registration The study protocol was approved by the hospital ethics committee (approval number:2020140A01) and registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2300070915; date of first registration: 26/04/2023).

Background: Tumor-derived exosomes are involved in tumor progression and immune invasion and might function as promising noninvasive approaches for clinical management. However, there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma (ccRCC). Methods: The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC patients were correspondingly deregulated in ccRCC tissues. We adopted a two-step strategy, including Lasso and bootstrapping, to construct a novel risk stratification system termed the TDERS (Tumor-Derived Exosome-Related Risk Score). During the testing and validation phases, we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS. In addition, enrichment analysis, immune infiltration signatures, mutation landscape and therapy sensitivity between the high and low TDERS groups were compared. Finally, the impact of TDERS on the tumor microenvironment (TME) was also analysed in our single-cell datasets. Results: TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC. TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor (ICI) response across all ccRCC cohorts and other pathological types, since the average area under the curve (AUC) to predict 5-year overall survival (OS) was larger than 0.8 across the four cohorts. Patients in the TDERS high group were resistant to ICIs, while mercaptopurine might function as a promising agent for those patients. Patients with a high TDERS were characterized by coagulation and hypoxia, which induced hampered tumor antigen presentation and relative resistance to ICIs. In addition, single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited. Finally, PLOD2, which is highly expressed in fibro- and epi‑tissue, could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC in vitro. Conclusion: As a novel, non-invasive, and repeatable monitoring tool, the TDERS could work as a robust risk stratification system for patients with ccRCC and precisely inform treatment decisions about ICI therapy.

Abstract β-1,4-N-acetylgalactosaminyltransferase I (B4GALNT1) is a key glycosyltransferase for gangliosides. Its aberrant expression has been observed in various cancers, and its potential roles in tumor immunity were suggested recently. However, how B4GALNT1 regulate tumor progression and tumor immunity remains largely unknown. In this study, we aimed to investigate the roles of B4GALNT1 in hepatocellular carcinoma (HCC), particularly in reshaping the tumor immune microenvironment, and evaluate the potential beneficial effects of targeting B4GALNT1 in immunotherapy. Our data verified the aberrant upregulation of B4GALNT1 in HCC tumor tissues and tumor cells, which could be utilized as an independent prognostic factor and improve the predicting performance of traditional tumor node metastasis (TNM) system. We also demonstrated that B4GALNT1 increased the phosphorylation of Hes Family BHLH Transcription Factor 4 (HES4) via p38 mitogen-activated protein kinase (p38)/ c-Jun N-terminal kinase (JNK) signaling in tumor cells, thus increasing the transcriptional activity of HES4, which upregulated the synthesis and secretion of secreted phosphoprotein 1 (SPP1), modulated the composition of tumor-associated macrophages (TAMs) and T helper type 2 (Th2) cells, and eventually reshaped the immunosuppressive microenvironment. In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.

Abstract Image acquisition and transmission in wireless sensor networks (WSN) are core issues for some resource-deficient multimedia sensing applications. Reducing sampling rates and data transmission lowers sensor node costs and energy, addressing communication bottlenecks. Block compressed sampling (BCS) can meet the above requirements. For BCS, the sparsity or smoothness of the block signal is a crucial parameter, which determines the setting range of the sampling rate. For the sampling side of the sensor node, we cannot directly obtain the complete digital signal. Therefore, it becomes difficult to perform adaptive rate compressed sampling. In this paper, a novel adaptive sampling rate allocation scheme based on region division is proposed. First, we use a simple auxiliary vector to determine the complex and smooth regions of the current image. For the smooth region, we use a mean vector to divide each block into a residual block and a mean value block. Then the proposed prior probability sparsity estimation model is used to estimate the sparsity order of each residual block, while each mean value block requires only one measurement to restore losslessly. For the complex region, we first set a higher baseline sampling rate for it, and then adaptively allocate the remaining supplementary sampling rate based on the statistical characteristics of each block itself. Experiment results show that the proposed scheme can allocate an appropriate sampling rate to each block, reduce the total sampling rate, and significantly improve the signal reconstruction quality simultaneously.

Abstract The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as “osteogenesis-angiogenesis coupling”, which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 (ZBTB16) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair. Graphical Abstract

Skin aging is an increasingly prominent topic in the context of healthy aging. During the aging process, the skin’s barrier function diminishes, its water content decreases, wrinkles begin to form, and changes occur in the gut microbiota composition. However, the relationship between gut microbiota and skin aging remains unclear. In this study, we explored skin rejuvenation in aged mice through fecal microbiota transplantation (FMT) using feces from young mice. The results demonstrated enhanced water retention, thickened stratum corneum, increased collagen content, and improved epithelial cell differentiation in aged mice following FMT. Notably, FMT particularly increased the abundance of Lactobacillus and Lactococcus in aged mice, which were nearly undetectable in untreated aged mice. Non-targeted and targeted metabolomics analyses indicated that FMT significantly elevated levels of tryptophan (Trp) and its microbiota metabolites (e.g., indole-3-lactic acid (ILA)) in the feces and serum of aged mice. Both Trp and ILA appeared to rejuvenate aged skin by activating the aryl hydrocarbon receptor (AhR) to promote epidermal cell differentiation. In conclusion, FMT from young mice rejuvenated aged skin via Trp-metabolizing bacteria (Lactobacillus and Lactococcus) and Trp-derived metabolites, suggesting that interventions targeting Trp metabolites may effectively improve skin aging.

Abstract To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diagnosed ALS patients and 32 control subjects without neurological disorders underwent routine MRI (magnetic resonance imaging) and DTI scans. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) at axial levels of internal capsules and cerebral peduncles along the corticospinal tract (CST) were measured. The study compared the differences of DTI parameters between ALS patients and controls using the Mann-Whitney U test. Diagnostic efficacy of each DTI metric was evaluated using the receiver operating characteristic (ROC) curve. NFs (NFL and pNFH levels in serum and CSF) were measured by enzyme-linked immunosorbent assay. Correlation analyses were conducted between DTI parameters and NFs. Capsule-MD and Peduncle-MD in ALS patients were higher than those in controls; whereas Capsule-FA and Peduncle-FA in ALS patients were lower than those in controls (all, p

Abstract The tectonic of the Middle and Late Ordovician in the western margin of the north China Platform is complex, and the accumulation models of organic matter of the Wulalike Formation formed during this period are still unclear. Total organic carbon (TOC) content, mineral composition, organic carbon isotope composition, as well as the major and trace elements in the shale samples were all measured in this study. The Wulalike Formation was formed during a tectonic transition from a passive continental margin to an active continental margin. Hydrocarbon-forming organisms are mainly algae. Primary productivity, terrigenous input, and sedimentation rates influence input, dilution, and degradation of organic matter. The degree of degradation, redox, and basin restriction control the preservation of organic matter. The TOC of the Wulalike Formation is determined by the input and preservation degree of organic matter at different sedimentary periods. The organic matter accumulation model in the Wulalike Formation is controlled by regional structures, dominated by sedimentation rate and preservation conditions.

Abstract The role of circulating metabolome in cognitive impairment is inconclusive, and whether the associations are in the severity-dependent manner remains unclear. We aimed to identify plasma metabolites associated with cognitive impairment and evaluate the added predictive capacity of metabolite biomarkers on incident cognitive impairment beyond traditional risk factors. In the Rugao Longevity and Ageing Study (RuLAS), plasma metabolome was profiled by nuclear magnetic resonance spectroscopy. Participants were classified into the cognitively normal, moderately impaired, and severely impaired groups according to their performance in two objective cognitive tests. A two-step strategy of cross-sectional discovery followed by prospective validation was applied. In the discovery stage, we included 1643 participants (age: 78.9 ± 4.5 years) and conducted multinomial logistic regression. In the validation stage, we matched 68 incident cases of cognitive impairment (moderately-to-severely impaired) during the 2-year follow-up with 204 cognitively normal controls by age and sex at a 1:3 ratio, and conducted conditional logistic regression. We identified 28 out of 78 metabolites cross-sectionally related to severely impaired cognition, among which IDL particle number, ApoB in IDL, leucine, and valine were prospectively associated with 28%, 28%, 29%, and 33% lower risk of developing cognitive impairment, respectively. Incorporating 13 metabolite biomarkers selected through Lasso regression into the traditional risk factors-based prediction model substantially improved the ability to predict incident cognitive impairment (AUROC: 0.839 vs. 0.703, P

Abstract This study first investigated how FNDC5 affected the development of oral cancer and revealed the role of FNDC5 in the migration and invasion of oral cancer. The present work evaluated differential FNDC5 expression within oral cancer samples versus matched non-carcinoma samples based on GEO database analysis and immunohistochemistry. We then generated oral cancer cell lines with FNDC5 overexpression and knockdown to determine the role of altered FNDC5 expression in the migration and invasion of oral cancer. PI3K inhibitor was used for investigating the possible mechanism underlying FNDC5 during EMT of oral cancer. Finally, these in-vitro results were validated using the lung metastatic nude mouse model. According to our results, FNDC5 level markedly decreased within oral cancer compared with adjacent samples and FNDC5 overexpression inhibited migration, invasion as well as EMT of oral cancer, while FNDC5 knockdown promoted oral cancer cell EMT. In addition, PI3K inhibitors blocked the induction of oral cancer cells EMT by FNDC5 knockdown. In vivo experiments further demonstrated the above results. This work is the first to illustrate the impact of FNDC5 on inhibiting migration and invasion of oral cancer, and our results suggest that FNDC5 affects EMT of oral cancer via the inhibition of PI3K/Akt/Snail pathway.

Abstract Objective Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve “seamless” management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. Methods This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. Results A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1–3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP, heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p

Abstract The presence of chlorophenols in water poses a significant threat to human health and the environment. In response to this issue, a study was undertaken to evaluate the catalytic capabilities of chlorinated Heme towards common chlorophenols present in water, such as 2,4-dichlorophenol, 2,4,6-trichlorophenol, and pentachlorophenol. The study employed the B3LYP method, a sophisticated computational technique within density functional theory, to investigate the molecular interactions and transformations involved. It scrutinized structural parameters, Wiberg Bond Indices, which offer insights into the strength and nature of chemical bonds, along with spectroscopic data including infrared vibrational spectra, ultraviolet-visible absorption spectra, and molecular fluorescence spectra. Furthermore, the research analyzed molecular binding energies and orbital energy levels before and after the formation of complexes between Heme and the targeted chlorophenols. The findings indicate that Heme displays a notable activation characteristic towards these chlorophenols. This suggests that Heme could act as an effective catalyst in the degradation of chlorophenols in water, presenting a novel approach to water purification. The theoretical insights derived from this study are invaluable, potentially guiding the development of more efficient catalytic systems for treating chlorophenol-contaminated water, thereby reducing the environmental and health risks associated with these hazardous compounds.

Abstract Background Controversy exists regarding the origin of femoral torsion, and specific treatment rules regarding the optimal position of femoral osteotomy in patients with recurrent patellar subluxation and excessive femoral torsion are scarce. Purpose To establish a novel classification system for such patients, and to compare clinical and radiological outcomes after distal derotational femoral osteotomy (DDFO) between femoral torsion at proximal (neck and shaft) and distal levels. Methods Between January 2014 and June 2019, patients who underwent DDFO were retrospectively reviewed. The segmental torsion analysis was performed to establish a novel classification system, and classify included patients into two groups: 35 patients in proximal torsion group and 38 patients in distal torsion group. These patients were followed-up for at least 3 years. Clinical evaluations included functional outcomes, physical examinations, quality of life, activity level, satisfaction, and complications. Radiological outcomes included patellofemoral osteoarthritis, congruence, and alignment. Results Type I was defined as the proximal torsion. Type II was defined as the distal torsion. Proximal torsion group had lower postoperative femoral torsion (12.6 ± 2.6° vs. 14.8 ± 3.6°; P = .004) and higher surgical correction angle (21.6 ± 5.0° vs. 19.1 ± 3.0°; P = .009). All clinical and radiological outcomes improved significantly in both groups, but proximal torsion group had significantly higher quality of life (EQ-5D-5L: 0.96 ± 0.06 vs. 0.91 ± 0.07; P = .003. EQ-VAS: 92.0 ± 6.0 vs. 88.7 ± 5.8; P = .021) and Tegner activity score (5.2 ± 1.5 vs. 4.5 ± 1.4; P = .040), and fewer patellofemoral osteoarthritis (8.6% vs. 26.3%; P = .048). Two patients in the distal torsion group had subjective patellar instability. The percentage of patients with anterior knee pain was higher in the distal torsion group. Conclusion A novel classification system for patients with recurrent patellar subluxation and excessive femoral torsion based on segmental femoral torsion analysis was established. DDFO was more appropriate for patients with proximal torsion, yielding higher surgical correction angle, and better clinical and radiological outcomes. Study design Cohort study; Level of evidence, 3.

Abstract Solid fuel combustion exposure is a leading global health risk factor, yet evidence on its effects, especially on vulnerable children, is sparse. This large-scale, multi-center prospective study aimed to address this gap by involving 9997 schoolchildren across China between 2013 and 2015. Here we show that lung function levels exhibited a marginally significant decline among children exposed to solid fuel usage. Specifically, FVC and FEV1 decreased by 21.2 mL (95% CI: −15.7, 58.1) and 24.1 mL (−8.4, 56.6), respectively. Additionally, PEF, FEF25 and FEF75 decreased by 25.7 mL/s (−46.5, 98.0), 32.7 mL/s (−42.7, 108.2), and 35.4 mL/s (−5.9, 76.7), respectively. Persistent exposure to solid fuel usage in children led to greater lung damage. Children with allergy history were more susceptible to solid fuel exposure. Our study highlights the adverse impact of solid fuel usage on children and the need to promote clean fuel usage for this vulnerable population.

Abstract Traditional routing algorithms have several limitations that become increasingly significant in the context of Software-Defined Networking (SDN). Firstly, these algorithms often have limited support for Quality of Service (QoS) requirements, making them less suitable for handling diverse traffic types efficiently. Moreover, current SDN controllers leverage a default shortest-path routing approach, which does not allow for more dynamic and flexible traffic management based on real-time network policies. To address these issues, this paper introduces a Dynamic Fuzzy Routing algorithm based on Deep Reinforcement Learning (DRL) for SDN that provides guaranteed latency and bandwidth (DFRDRL). DFRDRL provides intelligent and efficient routing that adapts to dynamic traffic by considering path-state criteria and using DRL. Fuzzy logic mainly performs online routing between an ingress-egress pair. To adapt to dynamic traffic changes, DFRDRL can predict the traffic matrix in real time. Meanwhile, DFRDRL reduces the routing reliance on network topology by weighting the network based on critical nodes. Additionally, when the network experiences congestion based on the traffic matrix, a deferral mechanism is applied to prioritize requests with lower resource demands. This mechanism helps ensure efficient resource allocation by temporarily postponing or queuing higher-demand requests, thereby optimizing overall network performance during periods of congestion. The simulation results show that the performance of DFRDRL is better than the equivalent algorithms in terms of latency and throughput. Also, DFRDRL is about 2.5% more efficient than the best existing algorithm in terms of admission rate of routing requests.

To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called “DEL Zipper”, can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection. By performing the selection against both G-quadruplex, we have identified novel hits that interact with RNA targets and the results are validated through binding. This study demonstrates that the “DEL Zipper” method is a robust screening assay that has potential for discovering small molecule ligands for diverse RNA targets.

Porphyromonas gingivalis (P. gingivalis) is a gram-negative bacterium and the main causative agent of periodontitis, a disease closely associated with the development of periodontal disease. The progression of periodontitis, a chronic infectious disease, is intricately linked to the inflammatory immune response. Inflammatory cytokines act on periodontal tissues via immunomodulation, resulting in the destruction of the periodontal tissue. Recent studies have established connections between periodontitis and various systemic diseases, including cardiovascular diseases, tumors, and neurodegenerative diseases. Neurodegenerative diseases are neurological disorders caused by immune system dysfunction, including Alzheimer’s and Parkinson’s diseases. One of the main characteristics of neurodegenerative diseases is an impaired inflammatory response, which mediates neuroinflammation through microglial activation. Some studies have shown an association between periodontitis and neurodegenerative diseases, with P. gingivalis as the primary culprit. P. gingivalis can cross the blood-brain barrier (BBB) or mediate neuroinflammation and injury through a variety of pathways, including the gut-brain axis, thereby affecting neuronal growth and survival and participating in the onset and progression of neurodegenerative diseases. However, comprehensive and systematic summaries of studies on the infectious origin of neurodegenerative diseases are lacking. This article reviews and summarizes the relationship between P. gingivalis and neurodegenerative diseases and its possible regulatory mechanisms. This review offers new perspectives into the understanding of neurodegenerative disease development and highlights innovative approaches for investigating and developing tailored medications for treating neurodegenerative conditions, particularly from the viewpoint of their association with P. gingivalis.

The discovery of exotic muonic atoms, including antimatter hydrogen muonic atoms and kaon muonic atoms, constitutes a milestone in our ability to make and study new forms of matter. Relativistic heavy-ion collisions provide the only likely condition for production and detection of these exotic atoms. Taking Coulomb correlations into account from the time of the fireball freeze-out, which refers to the cessation of hadronic interactions in the high-temperature, high-density region formed after the collision, until the formation of a stable atom has dramatic consequences on the expected yields of these atoms. When the coalescence model with the assumption of quantum wave function localization is applied to the formation of muonic atoms, we find that the atom yields are about two orders of magnitude higher than previously predicted.

Establishing and maintaining protected areas is a pivotal strategy for attaining the post-2020 biodiversity target. The conservation objectives of protected areas have shifted from a narrow emphasis on biodiversity to encompass broader considerations such as ecosystem stability, community resilience to climate change, and enhancement of human well-being. Given these multifaceted objectives, it is imperative to judiciously allocate resources to effectively conserve biodiversity by identifying strategically significant areas for conservation, particularly for mountainous areas. In this study, we evaluated the representativeness of the protected area network in the Qinling Mountains concerning species diversity, ecosystem services, climate stability and ecological stability. The results indicate that some of the ecological indicators are spatially correlated with topographic gradient effects. The conservation priority areas predominantly lie in the northern foothills, the southeastern, and southwestern parts of the Qinling Mountain with areas concentrated at altitudes between 1,500–2,000 m and slopes between 40°–50° as hotspots. The conservation priority areas identified through the framework of inclusive conservation optimization account for 22.9 % of the Qinling Mountain. Existing protected areas comprise only 6.1 % of the Qinling Mountain and 13.18 % of the conservation priority areas. This will play an important role in achieving sustainable development in the region and in meeting the post-2020 biodiversity target. The framework can advance the different objectives of achieving a quadruple win and can also be extended to other regions.

Long QT syndrome type 2 (LQT2), caused by mutations in the KCNH2 gene, is an inherited ion channel disorder associated with sudden death in adolescents. In this study, we generated a patient-specific induced pluripotent stem cell (iPSC) line XXMUFAi001-A using non-integrative Sendai reprogramming technology from an individual carrying a heterozygous point mutation (c.2690 A>C) in KCNH2. XXMUFAi001-A cell line exhibited expression of pluripotency markers and demonstrated teratoma formation capability in vivo, as well as the potential to differentiate into all three germ layers. The establishment of XXMUFAi001-A is crucial for investigating the pathogenesis and drug screening of LQT2.

This study develops an innovative method for analyzing and clustering tonal trends in Chinese Yue Opera to identify different vocal styles accurately. Linear interpolation is applied to process the time series data of vocal melodies, addressing inconsistent feature dimensions. The second-order difference method extracts tonal trend features. We introduce a fuzzy C-means clustering method enhanced by quantum particle swarm optimization (QPSO) to manage data uncertainties, improving classification accuracy and convergence speed. Additionally, we employ a cross-correlation function to eliminate uncertainties from tonal transition redundancies. We designed a detection algorithm using trend data to validate our clustering method, thereby enhancing the accuracy of the analysis of tonal ranges and potential models. This method detects whether Yue Opera adheres to traditional rhythmic norms and models the regularity of musical tones and vocal patterns. Simulation results reveal that our approach achieves a 91.4% accuracy in classifying vocal styles, surpassing traditional methods and demonstrating its potential for identifying various styles. This research offers technical support for Yue Opera music education and interdisciplinary research. The findings enhance the quality of artistic creation and performance in Yue Opera, ensuring its preservation and development.

O turismo responsável exige ações igualmente responsáveis de operadores de turismo, governos, residentes e turistas. A teoria das cenas diz respeito aos esforços para a construção de belos ambientes naturais e culturais, oferecendo recursos adequados para as várias partes interessadas atuando nos quarteirões urbanos e permitindo que turistas e residentes desfrutem de qualidade de vida e de uma experiência ambiental restauradora profunda e de longo prazo. Ao mesmo tempo, o estudo também fornece aos gestores de quarteirões urbanos um recurso estratégico de desenvolvimento responsável e sustentável que considera de maneira abrangente os benefícios econômicos e sociais do desenvolvimento local. Este artigo examina uma amostra de 53 quarteirões culturais urbanos chineses, coleta comentários de turistas relacionados a esses espaços para classificá-los e organizá-los, extrai palavras-chave de materiais de avaliação de turistas e obtém tendências de demanda de mercado em diferentes dimensões da teoria das cenas. Em seguida, oferecemos sugestões de desenvolvimento para que esses quarteirões possam criar cenas que fortaleçam as áreas em termos de legitimidade, autenticidade e teatralidade da forma como delineado pela teoria das cenas.

The short-lived ionized emission lines in early spectroscopy of the nearby Type II supernova SN 2024ggi signify the presence of dense circumstellar matter (CSM) close to its progenitor star. We proposed the Atacama Large Millimeter/submillimeter Array (ALMA) observations by its Director's Discretionary Time program to catch the potential synchrotron radiation associated with the ejecta–CSM interaction. Multiepoch observations were conducted using ALMA band 6 at +8, +13, and +17 days after the discovery. The data show nondetections at the position of SN 2024ggi with a 3 σ upper limit of less than 0.15 mJy, corresponding to a luminosity of approximately 8 × 10 ^24 erg s ^−1 Hz ^−1 . In this paper, we leverage the nondetections to place constraints on the properties of CSM surrounding SN 2024ggi. We investigate both the Wind and Eruptive models for the radial distribution of CSM, assuming a constant mass-loss rate in the Wind model and a distance-variant mass-loss rate in the Eruptive model. The derived CSM distribution for the Wind model does not align with the early-time spectral features, while the ALMA observations suggest a mass-loss rate of ~5 × 10 ^−3 M _⊙ yr ^−1 for the Eruptive model. Conducting multiepoch millimeter/submillimeter observations shortly after the explosion, with a cadence of a few days, could offer a promising opportunity to capture the observable signature of the Eruptive model.

Background: Resistance to radiotherapy is a major component in the failure of nasopharyngeal carcinoma (NPC) treatment. Enhancing autophagy in nasopharyngeal carcinoma may increase its radiation sensitivity, making it critical to find autophagy-modulating targets. Methods: The level of KIF15 was determined in NPC patients. Then, radiation-resistant NPC cells were produced to explore the mechanism in NPC. KIF15 was suppressed, and cell function and autophagy-related variables were examined in radiation-resistant NPC cells. Then the autophagy pathway was blocked, and the link between KIF15 and autophagy was confirmed. Finally, an NPC murine model was established, with tumors implanted in aberrant sites, and the relationship discovered at the cell level was confirmed in vivo. All statistical significance was determined using the student's t-test and one-way ANOVA. Results: Elevated amounts of KIF15 were discovered to be significantly expressed in NPC tissues and played a role in the radioresistance of NPC, a phenomenon attributed to METTL3-mediated m6A methylation. Blocking KIF15 resulted in decreased cell proliferation, increased cell death, and the activation of autophagy, ultimately making NPC more sensitive to radiation. This also resulted in decreased tumor development and increased levels of autophagy and apoptosis in vivo KIF15 interacted with STAT3, retaining it in the cytoplasm. Overexpression of STAT3 reversed the inhibitory effects of KIF15 knockdown on NPC and also reversed the influence of sh-KIF15 on autophagy activation. Inhibition of KIF15 decreased the inhibitory effect of STAT3 on ATG7, thereby upregulating autophagy activation in radio-resistant NPC cells. Conclusion: The increased expression of KIF15 was found to be associated with the progression of NPC and play a role in the development of radioresistance in NPC. Inhibiting KIF15 was shown to impede tumor growth and improve the sensitivity of NPC to radiotherapy by triggering autophagy via the STAT3/ATG7 pathway.

Ridge B is one of the least studied areas in Antarctica but has been considered to be a potential location for the oldest ice on Earth. Among important parameters for calculating where very old ice may exist, geothermal heat flux (GHF) is critical but poorly understood. Here, GHF is determined by quantifying the transitions between dry and wet basal conditions using a radioglaciological method applied to airborne radio-echo sounding data. GHF is then constrained by a thermodynamic model matched to the transitions. The results show that GHF in Ridge B varies locally and ranges from 48.5 to 65.1 mW m−2, with an average value of 58.0 mW m−2, which is consistent with the current known GHF constrained by subglacial lakes and derived from Vostok ice core temperature measurements. Our work highlights the value of considering local GHF when locating the oldest ice in this potential region or other regions.

Abstract Background Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. Case presentation In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child’s thrombus has dissolved, and the myocardial ischemia has resolved. Conclusions This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

The strain rate dependence of mechanical behavior in an AlSi10Mg alloy with different states fabricated by laser powder bed fusion (LPBF) was investigated systematically via thermodynamic calculations, microstructure characterization and mechanical characteristic evaluation in the present study. The results show that there is a close relationship among the material state, microstructure and dynamic mechanical behavior. Before tensile deformation, the as-built specimen possesses a fine equiaxed grain structure and a typical cellular structure surrounded by continuously distributed particles; the annealed specimen has coarser equiaxed grain structures and particles, but no cellular structure is present. Both the as-built and annealed specimens exhibit weak strain rate sensitivity, and the strain rate sensitivity parameters are 0.01 and 0.024, respectively. Under specific strain rate conditions, the as-built specimen has a higher strength and lower elongation than the annealed specimen. After tensile deformation, there is a significant increase in the dislocation density. Independent of the material state, the dislocation density increases with increasing strain rate. Compared with the as-built specimen, the annealed specimen has a stronger strain rate sensitivity because of the greater dislocation density variation.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is one of the most common urological diseases and the most common subtype of renal cell carcinoma. Nuclear mitochondria‐related genes (MTRGs) play an essential role in cancer, but their effect on ccRCC has not been clarified. This work aimed to investigate the role of nuclear MTRGs in ccRCC. Methods We collected nuclear MTRGs from the MITOMAP database and obtained the ccRCC profile from the TCGA database. Gene expression validation came from the GEO database. The ccRCC subtypes were determined by unsupervised clustering analysis based on the nuclear MTRGs. Immune scores were computed using the EPIC algorithm. The drug sensitivity scores were calculated using GDSC resources. A nomogram explored the diagnostic value of the nuclear MTRGs. Results In total, 11 nuclear MTRGs were identified as both related to prognosis and differentially expressed in ccRCC, showing a significant positive correlation with CD274 expression. We determined two subtypes of ccRCC based on these genes and found remarkable differences in survival status, immune infiltration, mutation landscape, and drug sensitivity between the two subtypes. The high‐MTRG group had a better prognosis and a lower tumor stage than the low‐MTRG group. Immune checkpoint blockade therapy was more effective for the high‐MTRG group. A nomogram based on the nuclear MTRGs concluded that patients with a higher score had poorer survival. SUCLA2 (succinate‐CoA ligase ADP‐forming subunit beta) was identified as the hub gene linked to ccRCC. High SUCLA2 expression showed a correlation with better survival and a negative correlation with the tumor mutation burden in ccRCC. Pan‐cancer analysis revealed wide‐ranging roles for SUCLA2 across human tumors. Conclusions Nuclear MTRGs play vital roles in determining the molecular features, immune infiltration, and drug sensitivity of ccRCC. High levels of nuclear MTRGs may indicate a better prognosis for patients with ccRCC. SUCLA2 is a representative nuclear MTRG and may serve as a protective biomarker in ccRCC. Our study provides therapeutic guidance and potential biomarkers for ccRCC patients, and contributes to the advancement of precision medicine.

The objectives of this study were to investigate the diagnostic efficacy of dynamic contrast-enhanced Computed Tomography (CT) and tumor markers and their combined evaluation in renal cancer patients. A total of eighty male patients with solid renal lesions were selected from our hospital and categorized into two groups based on pathological examination findings: renal cancer group and benign lesion group. A comparison was made between the findings of dynamic contrast-enhanced CT and tumor markers and the diagnostic efficacy of either mono or combined evaluation were compared. Receiver operating characteristic curves were plotted to better analyze and compare different diagnostic techniques. The serum concentrations of carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), midkine (MK) and matrix metalloproteinase 9 (MMP-9) in renal cancer patients were significantly higher than those with benign lesions (p < 0.05). The Receiver Operating Characteristic (ROC) curve analysis demonstrated that the combination of dynamic contrast-enhanced CT and tumor markers had the highest area under the curve. This difference was statistically significant (p < 0.05). The analysis of the overall model quality results revealed that the model values for both single and combination indicators exceeded 0.5, with the combined indicators having the highest value of (0.84). The diagnostic efficacy of dynamic contrast-enhanced CT combined with tumor markers for renal cancer is significantly higher than either the dynamic contrast-enhanced CT or tumor markers alone. The combination of dynamic contrast-enhanced CT and tumor markers has a significant therapeutic benefit in diagnosing renal cancer. We envisage that, this approach can offer valuable guidance for the clinical diagnosis and treatment of renal cancer.

With the rapid development of unmanned aerial vehicle technology and the continuous growth of requirements demanded in engineering applications, flapping-wing unmanned aerial vehicles are playing an increasingly important role in the national economy and livelihood because of their advantages such as good concealment, rapid maneuverability, high flexibility, and excellent economic performance. However, due to the limitations of the operating environment and their rapid maneuvering, the wings of flapping-wing unmanned aerial vehicles often have continuous high-frequency vibrations. These undesirable vibrations can affect the stability of the system and reduce its service life. In addition, flapping-wing unmanned aerial vehicles adjust their attitude rapidly and accurately during operation to accomplish assigned tasks. Therefore, this study focuses on the issues of vibration suppression and attitude control for flapping-wing unmanned aerial vehicles with rigid–flexible coupling wings. First, considering the impact of external disturbances on a flapping-wing unmanned aerial vehicle, using the Hamiltonian principle, the flapping-wing system comprising the homogeneous rigid link connected with the heterogeneous flexible link is modeled as an infinite dimensional distributed parameter system. The dynamic equations of the flapping-wing unmanned aerial vehicle are expressed as nonhomogeneous partial differential equations coupled with ordinary differential equations. Afterward, based on the original model with infinite-dimensional state space, two boundary control laws are designed to stabilize the system of the flapping-wing unmanned aerial vehicle by applying the back-stepping method. Different from the traditional modal control methods, the proposed control scheme can avoid overflow instability and control all system modals. An auxiliary input signal and disturbance adaptive law are constructed to cancel the impact of external disturbances via the robust control strategy. The developed disturbance rejection technique greatly relaxes the assumptions about external disturbances. By arranging the sensors and actuators at the body of the flapping-wing unmanned aerial vehicle and the connection point of the rigid–flexible coupling wing, the vibrations of the flexible wing are regulated into the vicinity around the original position and the attitude angle positions of the rigid and flexible wings are adjusted to the desired angular positions. It is worth noting that the proposed boundary control scheme exhibits great feasibility, cost-effectiveness, and robustness. Using the Lyapunov stability theory, it is rigorously proven that the closed-loop system is uniformly bounded stable. Finally, numerical simulations are conducted to demonstrate the effectiveness and performance of the designed control scheme.

Detecting glucose accurately and sensitively from clinical samples like tears and saliva is still difficult. We have created a sensor that can detect glucose with high sensitivity and accuracy by combining the use of glucose oxidase (GOx) to catalyze glucose, a pistol-like DNAzyme (PLDz) to transform the signal, gold nanoparticles (AuNPs) to enhance the optical properties and the exonuclease-III (Exo-III) to amplify the signal. As a result, the proposed method exhibits a low detection limit of 7.5 pM and a wide detection range covering seven orders of magnitude. The suggested dual-mode strategy provides a sensitive, precise and specific detection method for glucose. Another advantage is that the dual-mode technique significantly improves the precision and consistency of the measurements, demonstrating its immense potential for use in biomedical research and clinical diagnostics.

Abstract Documenting tangible cultural heritage using 3D modeling techniques is gradually becoming an indispensable component of archaeological practice. The 3D modeling techniques based on photogrammetry and LiDAR scanning enable high-accuracy and high-realistic reconstruction of archaeological sites, and have been proven a powerful tool for documenting archaeological excavations. However, dynamically documenting an ongoing excavation using these techniques is still considered tedious, time-consuming, expensive, and dependent on expertise. Moreover, the application of 3D modeling techniques in archaeological excavations still faces some technical challenges, such as modeling with multi-source and multi-scale data, fusing local models at different times into a whole, achieving fast modeling while GPU workstations are not available in the field, and evaluating the quality of 3D models. As a result, there are still very few archaeological teams deeply engaged in dynamic documentation with 3D modeling techniques, and traditional drawing sketches and taking photographs still dominate. In these senses, documenting the archaeological excavation at the Yunxian Man site (located in Hubei, China) is an invaluable opportunity for exploration and practice. Archaeologists determined to conduct dynamically documenting at the beginning of the 6th excavation project for the site, and established a rotation system to reconcile physical excavation with digital preservation. Through repeated practice and communication, we proposed a workflow and pursued several new methods to enhance the feasibility of dynamically documenting, and obtained 4D models of the ongoing archaeological excavations. In 2022, the Yunxian Man site unearthed the most intact fossil of hominin cranium from about one million years ago in the Eurasian continent, preserving important and scarce anatomical features of early humans in Asia. As the original taphonomic context of the fossil corroded away during physical excavations, the digital documentation consisting of 4D models serves as permanent original data source in subsequent archaeological research. Moreover, we obtained cross-scale 3D models from geographical environment to archaeological site, excavation area, and cultural remains, and all of these 3D models are in an actual, unified coordinate framework. Thus, we can contribute to multidisciplinary cross-collaborative research through data sharing. Considering that digital documentations serve a great value in archaeological research, this paper focuses on sharing the workflow and methods to facilitate digital preservation for more archaeological projects.

Abstract Background Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Mucinous adenocarcinoma (MAC) is a potential poor prognosis subgroup of rectal cancer. However, the predictive value of MAC in NCRT treatment of LARC is controversial. Methods A comprehensive literature search of PubMed, Embase, and the Cochrane Library was performed. All studies examining the effect of MAC on CRT response in LARC were included. Outcomes of MAC were compared with non-specific adenocarcinoma (AC) by using random-effects methods. Data were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The main outcomes were the rates of pathological complete response (pCR), tumor and nodal down-staging, positive resection margin rate, local recurrence, and overall mortality. Results Fifteen studies containing comparative data on outcomes in a total of 9,238 patients receiving NCRT for LARC were eligible for inclusion. MAC had a reduced rate of pCR (OR, 0.38; 95% CI, 0.18–0.78) and tumor down-staging (OR, 0.31; 95% CI, 0.22–0.44) following NCRT compared with AC. MAC did not significantly affect nodal down-staging (OR, 0.42; 95% CI, 0.16–1.12) after NCRT. Conclusion MAC of LARC was found to be a negative predictor of response to NCRT with lower rates of pCR and tumor down-staging for LARC. The nodal down-staging of MAC was relatively lower than that of AC, although the differences were not statistically significant.

Abstract. Background:. Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood. Methods:. We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results:. Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxia-telangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity. Conclusion:. In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

In order to enhance the driving ability of autonomous vehicles on structured roads and enable them to plan safe and comfortable paths, we propose an obstacle avoidance path strategy for autonomous vehicles based on genetic algorithm. The use of Frenet-Serret enhances the adaptability of the algorithm in complex environments. In order to improve the generation and optimisation of obstacle avoidance trajectory, we establish an anti-collision model. When the vehicle faces a potential collision with an obstacle, the genetic algorithm quickly iterates and selects the first nine genes to generate the rough solution and convex space of the path. Combined with convex space, the quadratic programming method will numerically optimise the generated rough solution to generate an accurate path that satisfies the constraints. In addition, in order to ensure the safety and comfort in the process of obstacle avoidance, based on the dynamic constraints of the vehicle, the speed planning is used to determine the speed curve. We simulate in various scenarios involving moving obstacles. The real-time simulation based on the HIL platform proves that the proposed path planning strategy is effective in various driving scenarios.

Abstract Multi-resonance thermally activated delayed fluorophores have been actively studied for high-resolution photonic applications due to their exceptional color purity. However, these compounds encounter challenges associated with the inefficient spin-flip process, compromising device performance. Herein, we report two pure-blue emitters based on an organoboron multi-resonance core, incorporating a conformationally flexible donor, 10-phenyl-5H-phenophosphazinine 10-oxide (or sulfide). This design concept selectively modifies the orbital type of high-lying excited states to a charge transfer configuration while simultaneously providing the necessary conformational freedom to enhance the density of excited states without sacrificing color purity. We show that the different embedded phosphorus motifs (phosphine oxide/sulfide) of the donor can finely tune the electronic structure and conformational freedom, resulting in an accelerated spin-flip process through intense spin-vibronic coupling, achieving over a 20-fold increase in the reverse intersystem crossing rate compared to the parent multi-resonance emitter. Utilizing these emitters, we achieve high-performance pure-blue organic light-emitting diodes, showcasing a top-tier external quantum efficiency of 37.6% with reduced efficiency roll-offs. This proposed strategy not only challenges the conventional notion that flexible electron-donors are undesirable for constructing narrowband emitters but also offer a pathway for designing efficient narrow-spectrum blue organic light-emitting diodes.

Orthotopic implantation in vivo is the ultimate target of tissue-engineering organoids research, aiming to achieve sustaining survival after implantation. However, the limited representation of a complex microenvironment in implanted accepter hampers a comprehensive understanding of long-term maintenance of tissue-engineering organoids, especially in liver. In this research, we developed a 3D bioprinting method using gelatin methacryloyl (GelMA) hydrogel to fabricate lobule-like hepatorganoids, which faithfully mimic the structure of hepatic lobules with lower level of hypoxia (lobule vs 60°, 90°, control; 0.4880 vs 1.009, 0.6778, 0.8704; p

Summary: Addressing the joint control problem of pneumatic muscle-driven robots, this study aims to design a bionic reflex mechanism to enhance the robots’ adaptive capacity to various disturbances. Based on the biological reflex mechanism, we developed a spindle reflex and deep tendon reflex control system based on CPG (central pattern generator) to mitigate the sudden impact on the hip joint and the continuous blocking force on the knee joint, respectively. The spindle reflex controller incorporates the fast response of sliding mode control to effectively minimize the trajectory deviation of the hip joint under impact disturbances. The deep tendon reflex controller integrates RBF neural network adaptive control and the Tegotae framework to suppress excessive tension in the knee joint and augment the system’s adaptability to the blocking force disturbances. The experimental results confirm that the two reflex mechanisms significantly enhance the robustness and flexibility of the pneumatic muscle-driven robot in motion.

Hole transfer at the semiconductor-electrolyte interface is a key elementary process in (photo)electrochemical (PEC) water oxidation. However, up to now, a detailed understanding of the hole transfer and the influence of surface hole density on PEC water oxidation kinetics is lacking. In this work, we propose a model for the first time in which the surface accumulated hole density in BiVO4 and Mo-doped BiVO4 samples during water oxidation can be acquired via employing illumination-dependent Mott-Schottky measurements. Based on this model, some results are demonstrated as below: (1) Although the surface hole density increases when increasing light intensity and applied potential, the hole transfer rate remains linearly proportional to surface hole density on a log-log scale. (2) Both water oxidation on BiVO4 and Mo-doped BiVO4 follow first-order reaction kinetics at low surface hole densities, which is in good agreement with literature. (3) We find that water oxidation active sites in both BiVO4 and Mo-doped BiVO4 are very likely to be Bi5+, which are produced by photoexcited or/and electro-induced surface holes, rather than VOx species or Mo6+ due to their insufficient redox potential for water oxidation. (4) Introduction of Mo doping brings about higher OER activity of BiVO4, as it suppresses the recombination rate of surface holes and increases formation of Bi5+. This surface hole model offers a general approach for the quantification of surface hole density in the field of semiconductor photoelectrocatalysis.

Bile duct lesion, including benign (eg. occlusion, cholelithiasis, dilatation, malformation) and malignant (cholangiocarcinoma) diseases, is a frequently encountered challenge in hepatobiliary diseases, which can be repaired by interventional or surgical procedures. A viable cure for bile duct lesions is implantation with biliary stents. Despite the placement achieved by current clinical biliary stents, the creation of functional and readily transplantable biliary stents remains a formidable obstacle. Excellent biocompatibility, stable mechanics, and absorbability are just a few benefits of using bioengineered biliary stents, which can also support and repair damaged bile ducts that drain bile. Additionally, cell sources & organoids derived from the biliary system that are loaded onto scaffolds can encourage bile duct regeneration. Therefore, the implantation of bioengineered biliary stent is considered as an ideal treatment for bile duct lesion, holding a broad potential for clinical applications in future. In this review, we look back on the development of conventional biliary stents, biodegradable biliary stents, and bioengineered biliary stents, highlighting the crucial elements of bioengineered biliary stents in promoting bile duct regeneration. After providing an overview of the various types of cell sources & organoids and fabrication methods utilized for the bioengineering process, we present the in vitro and in vivo applications of bioengineered biliary ducts, along with the latest advances in this exciting field. Finally, we also emphasize the ongoing challenges and future development of bioengineered biliary stents.

BackgroundTo determine the role of N6-methyladenosine (m6A) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).MethodsConsensus clustering was performed to identify the subgroups with distinct immune or m6A modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays. For experimental validation, the regulation of METTL3/m6A axis in the expression of candidate genes by RIP-qPCR assay in A549 and H460 cell lines. Co-culture experiments with human T cells were performed to evaluate the impact of METTL3 on the enhancement of anti-tumor immunity through in vitro experiments.ResultsWe identified 282 m6A regulator genes and 955 immune-related genes, selecting seven key genes (SFTPC, CYP24A1, KRT6A, PTTG1, S100P, FAM83A, and ANLN) to develop a risk score model using Lasso regression. High-risk patients, determined by this model, exhibited poorer prognosis, increased immune infiltration, higher tumor mutational burden, more neoantigens, and elevated PD-L1 expression. These findings were validated by two independent databases and LUAD tissue microarrays. METTL3 was found to impact the mRNA expression of these genes, with METTL3 deficiency abolishing these interactions. Inhibition of METTL3 enhanced anti-tumor immunity, T cell activation, exhaustion, and infiltration in vitro.ConclusionThis risk score system shows promise for prognostic prediction and the development of personalized treatment strategies for LUAD patients.