Search

ABSTRACTOrigami metamaterials have become frontiers of research in many disciplines due to their infinite design space, simple size variation, and topologically variable properties. In this study, a novel metamaterial inspired by Miura-origami tubes with a complex quasi-zero-stiffness (QZS) structure was fabricated via laser powder bed fusion (LPBF). The unit of the QZS metamaterial consists of a two-layer quadrilateral frame and two vertical springs attached to its diagonal points. The geometric accuracy, densification level and mechanical properties of the QZS parts fabricated at various processing conditions were investigated and the optimised processing parameters were determined. The displacement response of the QZS parts was analysed by experiments in conjunction with simulation analysis. The results show that the LPBF-fabricated QZS metamaterials form four extra-wide longitudinal wave band gaps under low frequencies from 660 Hz to 2500 Hz. The proposed LPBF-fabricated QZS metamaterial shows great potential in impeding the longitudinal vibration of engineering structures.

Abstract Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability‐ in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti‐inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro‐assembly under pre‐programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS‐containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS‐containing porous layer delivers dual bio‐signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.

Abstract Biology remains the envy of flexible soft matter fabrication because it can satisfy multiple functional needs by organizing a small set of proteins and polysaccharides into hierarchical systems with controlled heterogeneity in composition and microstructure. Here, it is reported that controlled, mild electronic inputs (

BackgroundTransforming rural migrant workers’ consumption potential into a consumption booster requires ensuring their equal rights as urban residents. The adequate access to Basic Public Health Services (BPHS) help effectively tackle rural migrant workers’ health challenges and promote the well-being of this vulnerable population. Assessing the welfare effects of BPHS through a consumption perspective offers valuable insights and provides policy implications for enhancing the equity of BPHS and achieving common prosperity.MethodsUtilizing the household-level data from China Migrants Dynamic Survey 2017 (CMDS 2017), this study comprehensively evaluated the effects of BPHS on rural migrant workers’ household consumption by combining the methods of OLS, PSM, and IV.ResultsThe enhancement of BPHS promotes rural migrant workers’ household consumption even after considering endogeneity problems. Mechanism analysis indicates that BPHS imposes its positive effects on rural migrant workers through improving health literacy and increasing citizenization willingness. Furthermore, we identified heterogeneous effects across individual and household characteristics of rural migrant workers, and their flow patterns.ConclusionOur analysis indicates that BPHS plays a greater role in promoting household consumption of socially vulnerable groups, such as trans-provincial migration, rural migrant workers in old generations, and with lower-level income. Overall, these results suggest that the welfare effects of BPHS are inclusive in China.

Rats were studied in social reinforcement procedures in which lever presses opened a door separating two adjacent spaces, permitting access to social interaction with a partner rat. The number of lever presses required for social interaction was systematically increased across blocks of sessions according to fixed-ratio schedules, generating demand functions at three different social reinforcement durations: 10 s, 30 s, and 60 s. The social partner rats were cagemates in one phase, and non-cagemates in a second phase. The rate at which social interactions were produced declined with the fixed-ratio price, and was well described by an exponential model that has been successfully employed with a range of social and non-social reinforcers. None of the main parameters of the model varied systematically with social interaction duration or with the social familiarity of the partner rat. On the whole, the results provide further evidence of the reinforcing value of social interaction, and its functional parallels with non-social reinforcers.

Transition metal dichalcogenides (TMDs), as one of the most promising two-dimensional (2D) materials, have attracted considerable attention for use in photodetection applications over the past few years due to their distinct properties, such as atomic-scale thickness, tunable direct bandgaps, and decent carrier mobilities at room temperature. Compared with pure 2D TMDs, the construction of hybrids consisting of TMDs and other low-dimensional materials can further improve the performance of photodetectors including their spectral range, responsivity and detectivity, which significantly boosts interest in the development of TMDs-based photodetectors. On the other hand, solution-phase synthesis methods provide a facile strategy for the scalable production of TMD hybrids, opening an exciting avenue to develop low-cost devices. In this review, we summarize the material synthesis, characterizations, and photodetection applications of the solution processable TMDs-based hybrids, as well as provide insights into their prospects.

Prior research has found that one rat will release a second rat from a restraint in the presence of food, thereby allowing that second rat access to food. Such behavior, clearly beneficial to the second rat and costly to the first, has been interpreted as altruistic. Because clear demonstrations of altruism in rats are rare, such findings deserve a careful look. The present study aimed to replicate this finding, but with more systematic methods to examine whether, and under what conditions, a rat might share food with its cagemate partner. Rats were given repeated choices between high-valued food (sucrose pellets) and 30-s social access to a familiar rat, with the (a) food size (number of food pellets per response), and (b) food motivation (extra-session access to food) varied across conditions. Rats responded consistently for both food and social interaction, but at different levels and with different sensitivity to the food-access manipulations. Food production and consumption was high when food motivation was also high (food restriction) but substantially lower when food motivation was low (unlimited food access). Social release occurred at moderate levels, unaffected by the food-based manipulations. When food was abundant and food motivation low, the rats chose food and social options about equally often, but sharing (food left unconsumed prior to social release) occurred at low levels across sessions and conditions. Even under conditions of low food motivation, sharing occurred on only 1% of the sharing opportunities. The results are therefore inconsistent with claims in the literature that rats are altruistically motivated to share food with other rats.

Laser additive manufacturing (LAM) of complex-shaped metallic components offers great potential for fabricating customized endovascular stents. In this study, anti-tetrachiral auxetic stents with negative Poisson ratios (NPR) were designed and fabricated via LAM. Poisson’s ratios of models with different diameters of circular node (DCN) were calculated using finite element analysis (FEA). The experimental method was conducted with the LAM-fabricated anti-tetrachiral stents to validate their NPR effect and the simulation results. The results show that, with the increase in DCN from 0.6 to 1.5 mm, the Poisson ratios of anti-tetrachiral stents varied from −1.03 to −1.12, which is in line with the simulation results. The interrelationship between structural parameters of anti-tetrachiral stents, their mechanical properties and biocompatibility was demonstrated. The anti-tetrachiral stents with a DCN of 0.9 mm showed the highest absolute value of negative Poisson’s ratio, combined with good cytocompatibility. The cytocompatibility tests indicate the envisaged cell viability and adhesion of the vascular endothelial cell on the LAM-fabricated anti-tetrachiral auxetic stents. The manufactured stents exhibit great superiority in the application of endovascular stent implantation due to their high flexibility for easy maneuverability during deployment and enough strength for arterial support.

Abstract Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 109 to 5 × 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 109 and 1 × 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 1010vp). Therefore, the maximum tolerated dose was determined to be 1 × 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.

Abstract The sparse Bayesian learning (SBL) algorithm has demonstrated its advantage in the direction of arrival (DOA) estimation. However, it requires a lot of computational cost to iteratively estimate the SBL hyperparameters from measurement data. This paper focuses on fast estimating the array shape and DOAs using SBL for a short towed line array (TLA) during manoeuvring. A parabolic model is utilised to describe the bent TLA whose bow as a hyperparameter is estimated in the SBL iterative process. Then, the basis vector pruning strategy is considered in the iteration to reduce computational cost by neglecting the impossible directions of signal presence. The converged speed of the joint estimation algorithm is further improved by approximately calculating the posterior probability density with the message passing approach. The effectiveness of the optimising joint estimation algorithm is verified using the experimental results from South China Sea.

Abstract Pass-by noise generated by high-speed trains is an important influencing factor on the surrounding environment and is getting more and more attention with the increase of speed. In the past, the aerodynamic pass-by noise prediction was usually conducted with the wind tunnel mode, ignoring the Doppler effect. In this paper, an equivalent source method considering the Doppler effect is proposed to study the aerodynamic pass-by noise. A cylinder case is considered first to verify the effectiveness of the method. Then a DSA 380 pantograph of a Chinese high-speed train is considered. The pantograph is divided into three parts, and each part is equivalent to a monopole or dipole sound source. Results show that the upper part of the pantograph is closer to a dipole source, while the middle and lower parts are closer to a monopole source. When the measurement point is directly above the pantogragh, the contribution of the upper part is the largest, while for both sides measurement points of the pantograph, the contribution of the upper part is the smallest.

Abstract Liver kinase B1 (LKB1) is a serine/threonine kinase controlling cell homeostasis. Among post-translational modification, Sumoylation is vital for LKB1 activating adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), the key regulator in energy metabolism. Of note, AMPK-regulated fatty acid metabolism is highly involved in maintaining normal renal function. However, the regulative mechanisms of LKB1 Sumoylation remain elusive. In this study, we demonstrated that β-catenin, a notorious signal in renal fibrosis, inhibited the Sumoylation of LKB1, thereby disrupting fatty acid oxidation in renal tubular cells and triggering renal fibrosis. Mechanically, we found that Sumo3 was the key mediator for LKB1 Sumoylation in renal tubular cells, which was transcriptionally inhibited by β-catenin/Transcription factor 4 (TCF4) signaling. Overexpression of Sumo3, not Sumo1 or Sumo2, restored β-catenin-disrupted fatty acid metabolism, and retarded lipid accumulation and fibrogenesis in the kidney. In vivo, conditional knockout of β-catenin in tubular cells effectively preserved fatty acid oxidation and blocked lipid accumulation by maintaining LKB1 Sumoylation and AMPK activation. Furthermore, ectopic expression of Sumo3 strongly inhibited Wnt1-aggravated lipid accumulation and fibrogenesis in unilateral ischemia-reperfusion mice. In patients with chronic kidney disease, we found a loss of Sumo3 expression, and it was highly related to LKB1 repression. This contributes to fatty acid metabolism disruption and lipid accumulation, resulting in renal fibrosis. Overall, our study revealed a new mechanism in fatty acid metabolism dysfunction and provided a new therapeutic target pathway for regulating Sumo modification in renal fibrosis.

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Abstract Background Many studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs). Methods The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC. Results Fifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99–1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79–1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03–1.04, P

A novel coated urea (MVCU) was prepared, and its application effect was verified by field trials of oilseed rape in three main cultivation areas. Meanwhile, the nutrient release and coating layer changes of MVCU in static water at 25 °C and different soils were systematically evaluated. MVCU showed a long nutrient release time under static water (77 days) and soil incubation (140 days) conditions due to the slow degradation of the coating layer in MVCU, and its nitrogen release coincided well with oilseed rape nitrogen demand. The above results were further confirmed by FT-IR spectra and SEM analysis. Compared with conventional urea (U), the field trials of MVCU in the three main cultivation areas showed high nitrogen utilization efficiency and yield advantages in oilseed rape. The field trials results indicated that the MVCU significantly enhanced the aboveground dry matter (28.7%), the seed nitrogen concentration (9.5%) and aboveground nitrogen accumulation (42.5%) of oilseed rape at the mature stage as compared to that of the U. The oilseed rape yield enhanced by 932.8 kg/hm2, the average growth rate was 65.1%, and nitrogen utilization efficiency increased by 21.2%. In short, MVCU has the advantages of excellent slow-release performance and strong applicability, and its yield-increasing effect on oilseed rape could reach or even be better than that of traditional fertilization.

Abstract Effective visualization of infectious disease risks is crucial for the development of efficient prevention and control strategies. However, the efficacy of mainstream models is hindered by a scarcity of reliable data in target areas, a situation that is particularly acute when dealing with emerging or re‐emerging infectious diseases. Additionally, these models typically fail to integrate local disease‐related risk factors in line with the ‘One Health’ concept, resulting in inaccurate predictions. Consequently, accurately assessing infectious disease risks without reliable data is challenging. This study introduces SpatMCDA, an innovative R package designed to assess infectious disease risk areas through spatial multi‐criteria decision analysis (MCDA). SpatMCDA is structured around six core modelling steps: standardizing risk factors, determining factor weights, constructing risk maps, performing One‐at‐a‐Time sensitivity analysis, calculating the Mean of Absolute Change Rates and conducting an uncertainty analysis. By examining the case of West Nile virus (WNV) in China, this study illustrates how SpatMCDA can be useful in identifying disease transmission risks in the absence of reliable outbreak data. The assessment identified areas at risk for WNV in northwestern, eastern and southern China. By integrating spatial and epidemiological data, SpatMCDA enhances infectious diseases risk assessment in situations where data are limited. Its efficiency in using available data for accurate risk mapping and adaptability in weighting various risk factors enables tailored analyses. This tool enhances public health strategies, contributing to global health security.

Abstract In the last decade, laboratory-scale single-junction perovskite solar cells have achieved a remarkable power conversion efficiency exceeding 26.1%. However, the transition to industrial-scale production has unveiled a significant efficiency gap. The central challenge lies in the difficulty of achieving uniform, high-quality perovskite films on a large scale. To tackle this issue, various innovative strategies for manipulating crystallization have emerged in recent years. Based on an in-depth fundamental understanding of the nucleation and growth mechanisms in large-area perovskite films prepared through blade/slot-die coating methods, this review offers a critical examination of crystallization manipulation strategies for large-area perovskite solar modules. Lastly, we explore future avenues aimed at enhancing the efficiency and stability of large-area PSMs, thereby steering the field toward commercially viable applications.

Abstract Quadrotor technology has become increasingly important in the field of photovoltaic (PV) solar farm monitoring, but short battery life is one of the primary factors limiting its further application. To address above issue, this study proposes a linear temporal logic (LTL)-based path planning algorithm that considers the need for charging together with multiple visits to PV equipments, a single visit to communication equipment, and the avoidance of restricted regions, which enables the long-term monitoring of PV solar farms. Particularly, the location of a charging station can be determined optimally and efficiently by a heuristic algorithm based on the nonlinear programming and branch and bound (NLP-BB) algorithm. The simulation results indicate that the proposed method effectively solves the long-term monitoring path planning problem that is coupled with the optimal deployment of the charging station.

Objective To investigate the effect of stereotactic minimally invasive surgery on immune level and activities of daily living in elderly patients with glioma. Methods Ninety elderly patients with glioma admitted to the First Affiliated Hospital of Harbin Medical University from March 2020 to February 2022 were selected as the study subjects and divided into two groups according to the random number table, 45 cases for each group. The control group was treated with conventional craniotomy and the observation group was treated with stereotactic minimally invasive surgery. The clinical efficacy, activities of daily living (ADL) score, National Institutes of Health Stroke Scale (NIHSS) score, peripheral blood immune parameters T helper (Th) 1, Th2 and Th17 levels were compared between the two groups. Results The overall response rate in the observation group was higher than that in the control group. The recurrence rate at 1 year after surgery was lower than that in the control group. After treatment, the ADL score in the observation group was higher than that in the control group, the NIHSS score was lower than that in the control group, the Th1 level was higher than that in the control group, and the Th2 and Th17 levels were lower than those in the control group. The differences were statistically significant (P

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

Abstract Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The ‘CMRxRecon’ dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Rats were studied in social reinforcement procedures in which lever presses opened a door separating two adjacent spaces, permitting access to social interaction with a partner rat. The number of lever presses required for social interaction was systematically increased across blocks of sessions according to fixed-ratio schedules, generating demand functions at three different social reinforcement durations: 10 s, 30 s, and 60 s. The social partner rats were cagemates in one phase, and non-cagemates in a second phase. The rate at which social interactions were produced declined with the fixed-ratio price, and was well described by an exponential model that has been successfully employed with a range of social and non-social reinforcers. None of the main parameters of the model varied systematically with social interaction duration or with the social familiarity of the partner rat. On the whole, the results provide further evidence of the reinforcing value of social interaction, and its functional parallels with nonsocial reinforcers. [ABSTRACT FROM AUTHOR]

Abstract The precise and effective activation of the immune response is crucial in promising therapy curing cancer. Photoimmunotherapy (PIT) is an emerging strategy for precise regulation and highly spatiotemporal selectivity. However, this approach faces a significant challenge due to the off‐target effect and the immunosuppressive microenvironment. To address this challenge, a nanoscale full‐active pharmaceutical ingredient (API) photo‐immune stimulator was developed. This formulation overcomes the limitations of PIT by strengthening the ability to penetrate tumors deeply and inducing precise and potent mitochondria‐targeted dual‐mode photodynamic therapy and photothermal therapy. Along with inhibiting overexpressed Hsp90, this nanosensitizer in turn improves the immunosuppressive microenvironment. Ultimately, this mitochondria‐targeted PIT demonstrated potent antitumor efficacy, achieving a remarkable inhibition rate of ≥95% for both established primary tumors and distant abscopal tumors. In conclusion, this novel self‐delivery full‐API nanosystem enhances the efficacy of phototherapy and reprograms the immunosuppressive microenvironment, thereby holding great promise in the development of precise and effective immunotherapy.

The use of ligand conjugation onto nanoparticle surfaces as an active targeting strategy has gained significant attention in the pursuit of improving tumor‐specific delivery and retention. However, the chemical conjugation of targeting moieties often induces alterations in the physicochemical properties of nanoparticles, including size, conformation, charge‐to‐mass ratio, and hydrophilicity/lipophilicity, resulting in unexpected biodistribution and pharmacokinetic profiles. Here, the enhanced active targeting efficiency achieved by integrating cyclic arginine–glycine–aspartic acid (cRGD) peptides onto ultrasmall nanocarrier H‐dot while preserving its essential physicochemical and pharmacokinetic attributes is investigated. The resulting cRGD/H‐dots demonstrate improved cellular uptake via integrin αvβ3 receptors, accompanied by negligible cytotoxicity. Notably, the active targeting efficacy of cRGD/H‐dots compared to unmodified H‐dots (1.2%ID/g, two‐fold increase) is quantitatively evaluated, validated through fluorescence imaging and histological analysis. The findings highlight that cRGD/H‐dots offer enhanced tumor targetability and prolonged tumoral retention while maintaining active renal clearance of unbound molecules.

By employing the classic system poly(3-hexylthiophene-2,5-diyl): [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM), organic bulk heterojunction films were applied on an indium tin oxide substrate using a one-step spin-coating method, without requiring any complex manufacturing processes, to obtain self-powered photodetectors (PDs) with a simple preparation process. The fullerene material was introduced to create a bulk heterojunction film with proper phase separation and greatly enrich the donor/acceptor dissociation interface, thus improving the high exciton binding energy and short exciton diffusion distance. The built-in electric field formed by the Schottky junction at the interface between the active layer and electrode can enhance the separation of excitons and the transport of charge carriers, realizing optical detection without external energy sources. Moreover, femtosecond transient absorption was employed to investigate the exciton dynamics in organic films and analyze the working mechanism of self-powered detection performance. The long-lived behavior of carriers and the formation of charge transfer states were further verified, which contributed to the enhanced performance of the device. As a result, the self-powered PD-based Schottky bulk heterojunction presents a high light on/off ratio of over 104 (0 V) and fast response speed with rise and decay times of 33 and 36 µs, respectively, under a 532 nm light illumination. These results provide theoretical and experimental verification of this technique for the development of self-powered PDs in the field of organic materials.

BackgroundCarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels.Methods1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage.ResultsThe overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage.ConclusionNomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

The RNA N6-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood. In this study, we demonstrated that METTL3 was overexpressed and associated with poor survival in most PCa patients. METTL3 inhibitor STM2457 reduced m6A levels of PCa cells, thus inhibiting their proliferation, colony formation, migration, invasion, and stemness in vitro. Furthermore, STM2457 suppressed PCa progression in both the CDX and PDX models in vivo. MeRIP-seq analysis coupled with biological validation revealed that STM2457 influenced multiple biological processes in PCa cells, mainly through the IGFBP3/AKT pathway. We also proved that STM2457 induced DNA damage and showed synergistic anti-PCa effects with the PARP inhibitor olaparib both in vitro and in vivo. All in all, this work provides a novel therapeutic strategy for targeting RNA m6A modifications for the treatment of PCa and provides a meaningful reference for further clinical trials.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20–0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Carbon ion beam irradiation (CIBI) is a highly efficient mutagenesis for generating mutations that can be used to expand germplasm resources and create superior new germplasm. The study investigated the effects of different doses of CIBI (50 Gy, 100 Gy, 150 Gy, 200 Gy and 300 Gy) on seed germination and seedling survival, seedling morphological and physiological traits of an elite centipedegrass cultivar Ganbei. The results showed that irradiation greater than 50 Gy cause inhibition of seed germination, and the semi-lethal dose (LD50) is around 90 Gy for CIBI treated seeds of Ganbei. A carbon ion beam-mutagenized centipedegrass population was generated from Ganbei, with irradiation dosages from 50 Gy to 200 Gy. More than ten types of phenotypic variations and novel mutants with heritable tendencies mainly including putative mutants of stolon number, length and diameter, of internode length, of leaf length and width, of leaf chlorophyll content, of stolon growth rate, of aboveground tissue dry weight, of sward height were identified. While the total sugar content of the plants from irradiated seeds showed no obvious change in all treatments as compared to the control, the crude protein content displayed significant reduction at a high-dose treatment of 200 Gy. Genetic polymorphism was detected in mutagenized centipedegrass population using SSR-PCR analysis, suggesting that CIBI caused alteration of larger fragments of the DNA sequence. As a result, a preliminary batch of mutants was screened in this study. In summary, carbon ion beam mutagenesis is an effective way for developing centipedegrass germplasm with wider variation, and treating seeds with CIBI at a dosage of ~100 Gy could be effective in centipedegrass mutation breeding.

BackgroundGallstones represent a prevalent health issue globally, resulting in significant annual healthcare costs. While tobacco exposure is recognized for its association with numerous diseases, its correlation with gallstones remains contentious. Serum cotinine, a metabolite of nicotine, serves as a widely utilized indicator for assessing tobacco exposure. Crucially, no research has yet examined the association between serum cotinine levels and the gallstones.MethodsThis study is designed as a cross-sectional analysis, utilizing data from the NHANES public database. The relationship between serum cotinine levels and gallstones was analyzed using multinomial logistic regression models and smooth curve fitting. Subgroup analyses and interaction tests were performed to examine the potential contributions of different populations and covariates to the findings.ResultsA total of 5,856 participants were included in this study. After adjusting for relevant covariates, the multiple logistic regression model results indicated that for each unit increase in serum cotinine concentration above 0.29 ng/mL, there was a 29% increase in the prevalence of gallstones. Furthermore, smooth curve fitting analysis revealed a positive correlation between these variables. These findings underscore the impact of tobacco exposure on gallstone prevalence.ConclusionThis study demonstrates a positive correlation between tobacco exposure, as measured by serum cotinine levels, and the prevalence of gallstones, thus adding to the body of existing research on this relationship.

The study focuses on the critically endangered Dabry’s sturgeon (Acipenser dabryanus), a species on the brink of extinction in the wild. This research investigates the role of the Forkhead box protein L2 (foxl2) in the gonadal development and differentiation of this species. The foxl2 gene, known for its role in various physiological processes, including sexual maturation, is hypothesized to play a significant role in the sex differentiation of Dabry’s sturgeon. This study cloned the full-length cds sequence of the foxl2 gene and analyzed its expression across various tissues, focusing on its response to estradiol treatment. Our findings indicate that foxl2 is predominantly expressed in ovaries and shows a dose-dependent response to estradiol, suggesting its potential role in ovarian differentiation. This research underscores the importance of foxl2 in understanding reproductive biology and offers a foundation for future conservation strategies.

Abstract Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.

ABSTRACT: The present study aimed to investigate the effects of dietary fermented blueberry pomace (FBP) supplementation on production performance, egg quality and nutritional value, plasma biochemical parameters, follicle number, reproductive hormones, lipid metabolism, and antioxidant capacity of laying hens during the late laying period. A total of 320 (345-d-old) Yukou Jingfen No. 8 laying hens were randomly divided into 4 groups, with eight replicates per group and 10 hens per replicate. The birds were fed a basal diet (control group) and a basal diet supplemented with 0.25, 0.5, and 1.0% FBP. The trial lasted 56 d. The results showed that FBP (0.25−1.0%) supplementation increased the egg albumen height and Haugh unit compared with the control group on d 14, while 0.5 to 1.0% FBP increased the eggshell thickness compared with the 0.25% FBP group on d 28 of the trial (P < 0.05). The methionine content in egg white was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP group. The CAT activity in the ovary was increased (P < 0.05) in the FBP groups compared with the control group, while plasma GSH-PX activity was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP and 0.5% FBP groups. Dietary FBP supplementation up-regulated (P < 0.05) gene expressions related to lipid metabolism in the liver (ACC, FAS, SCD1, and SREBP1) and yolk precursor synthesis (ESR2 and VTG II). Moreover, CYP11A1 expression in the ovary was up-regulated (P < 0.05) in the FBP groups compared with the control group, as well as in the 0.25% FBP group compared with the 1.0% FBP group. In summary, dietary FBP supplementation improved egg quality and nutritional value, ovarian antioxidant capacity, and yolk precursor synthesis, while 1.0% FBP had better effects than 0.25 and 0.5% doses.

Herein, a YAG/10 at% Yb:YAG/YAG transparent ceramic planar waveguide (PWG) gain medium has been molded via inkjet printing and dry pressing molding. The composition and rheological property of ink are optimized along with the printing process to enhance the printing accuracy and quality. The PWG has dimensions of 13.5 × 8.0 × 1.8 mm3, while the thickness of the core Yb:YAG layer is ≈190 μm. The in‐line transmittance of the PWG reaches 81.7% at 1030 nm, and the average grain size is ≈2.3 μm. The diffusion characteristics of Yb ions across the interface between the cladding YAG layer and the core Yb:YAG layer are investigated by calculating the diffusion coefficient and the mean diffusion distance of 172Yb ions. The Yb:YAG PWG oscillator, which is pumped from a single end by a 940 nm laser diode, produces continuous wave laser at a wavelength of 1030 nm and exhibits the highest power (3.8 W) and highest absorbed–output slope efficiency (64.6%).

BackgroundDysphagia is a common complication after stroke, which not only brings adverse outcomes but also greatly affects the quality of life of patients. At present, there is no systematic review or meta-analysis to comprehensively evaluate the epidemiological characteristics of post-stroke dysphagia (PSD). A systematic review of the prevalence, risk factors, and prognosis of PSD is essential.MethodsThrough 31 December 2022, a comprehensive literature search was performed for observational studies related to PSD. Five databases were retrieved. Random-effects models were used to estimate the pooled prevalence, odds ratio (OR), and 95% CIs.ResultsA total of 34 studies were included, and the results showed that the overall prevalence of PSD was 46.6% (95% CI, 0.405–0.528). The prevalence of dysphagia in ischemic stroke and hemorrhagic stroke was 43.6% (95% CI 0.370–0.501) and 58.8% (95% CI 0.519–0.654), respectively. The prevalence of PSD in Africa was 49.4% (95% CI, 0.196–0.792), in Asia was 40.1% (95% CI, 0.348–0.454), in Europe was 45.8% (95% CI, 0.327–0.590), in North America was 44.3% (95% CI, 0.370–0.517), in South America was 57.5% (95% CI, 0.441–0.708), and in Oceania was 64.1% (95%CI, 0.558, 0.724). In risk factor analysis, hypertension, previous stroke, and atrial fibrillation were significantly associated with the occurrence of PSD, pooled OR = 1.179 [(95% CI, 1.002–1.386), p

Combined with the validations of the nonlinear material models, this study addresses the nonlinear dynamic response, damage mechanisms and failure modes of reinforced concrete frame structures under rockfall impacts, utilizing explicit dynamic analysis software for detailed model of structures. The findings indicate that the peak impact force is primarily influenced by the impact velocity and subsequently by the impact mass, while the impact location exerts the least influence; A linear relationship is observed between the maximum impact force and rockfall diameter, whereas a nonlinear association exists with rockfall velocity; Predominant failure modes include global and local failures, with damage and failure predominantly concentrated on the impacted columns and their surrounding components; Notably, similar damage levels were observed for corner and edge middle columns of structures under rockfall impacts; The column base, mid-column and column top primarily exhibit flexural-shear failure, flexural failure and flexural-shear failure, respectively; Given the higher rate of plastic energy absorption during mid-column impacts compared to column base and top impacts, a rockfall striking mid-column results in higher dynamic response and greater structural damage. This study can provide useful reference in design and restoration of low-rise reinforced concrete frame structures located in areas prone to frequent geological disasters.

Abstract Background Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. Purpose Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. Methods First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan–Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. Results A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. Conclusion A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.