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This outlook explores how two different molecular imaging approaches might be combined to gain insight into dynamic, subcellular metabolic processes. Specifically, we discuss how matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and stimulated Raman scattering (SRS) microscopy, which have significantly pushed the boundaries of imaging metabolic and metabolomic analyses in their own right, could be combined to create comprehensive molecular images. We first briefly summarize the recent advances for each technique. We then explore how one might overcome the inherent limitations of each individual method, by envisioning orthogonal and interchangeable workflows. Additionally, we delve into the potential benefits of adopting a complementary approach that combines both MSI and SRS spectro-microscopy for informing on specific chemical structures through functional-group-specific targets. Ultimately, by integrating the strengths of both imaging modalities, researchers can achieve a more comprehensive understanding of biological and chemical systems, enabling precise metabolic investigations. This synergistic approach holds substantial promise to expand our toolkit for studying metabolites in complex environments.

Abstract Comparison is a crucial stage of site-level selection process. This study integrates the geographic information system (GIS) techniques and analyses the stability of predictions based on five machine learning models to identify key indices for site selection. The study results reveal that: (1) the relevant site selection index system was improved. The precision of predictions using the five machine learning models all reached 95%, with the deep neural networks (DNN) model achieving the highest precision at 96.4%, indicating its broader applicability for site selection. (2) A machine learning index optimisation process is proposed. Based on the results of index importance, indices are categorised as important, less important, and general. Using only the important indices yields satisfactory evaluation results. (3) A rapid assessment model was developed. In the DNN model, the results could be predicted more accurately by using approximately 25% of the data and 50% of the indices. This provides a reference for subsequent site selection for difficult-to-obtain data. This study aims to accumulate extensive data via future research to establish a model database. The database will help refine geological models for different types and stages of engineering projects and incorporate more site-specific models. The ultimate goal is to provide more convenient theoretical guidance and recommendations for subsequent site selection processes.

Abstract Background Chronic infection with Clonorchis sinensis (C.sinensis) has been associated swith the development of intrahepatic cholangiocarcinoma (ICC); however, the relationship between C.sinensis and hepatocellular carcinoma (HCC) remains uncertain. Methods This study examined 120 patients with liver cancer in the clonorchiasis endemic area of Hengzhou, Guangxi, China. The type of cancer, the differentiation grade according to Edmondson Steiner’s classification, and the pathological characteristics of HCC were determined through postoperative tissue biopsy. C.sinensis infection was detected by measuring serum specific IgG antibody, and hepatitis B virus (HBV) infection was determined by detecting serum HBsAg and HBV DNA in HCC tissues. The C.sinensis infection rates in control groups were drawn from the local general population based on previous surveys. The association between C.sinensis infection and HCC was analyzed by comparing the differences in C.sinensis infection rates between the two groups. Results Of the patients evaluated, 98 (81.7%) had HCC, 21 (17.5%) had ICC, and 1 (0.8%) had comorbidity of HCC/ICC. Among the HCC patients, 24 (24.5%) were solely infected with HBV, 71 (72.4%) were C. sinensis seropositive, and 3 (3.1%) showed no evidence of infection. C. sinensis seropositive rates in HCC patients are much higher than in general outpatient and non-liver cancer inpatients (χ 2 = 141.92, p 0.05). Among the patients with C.sinensis-related HCC, 8 (8.2%) were solely C.sinensis seropositive, while 63 (64.3%) were co-infected with HBV. Infection with C. sinensis and HBV has a significant impact on the pathological types of liver cancer (χ 2 = 22.86, p

Abstract Although immune checkpoint inhibition in particular has shown promise in cancer immunotherapy, it is not always efficient. Recent studies suggest that SMARCAL1 may play a role in tumor immune evasion, yet its pan-cancer role is unclear. We conducted a comprehensive analysis of SMARCAL1 using TCGA, GTEx, and CCLE databases, evaluating its expression, genetic alterations, epigenetic modifications, and their clinical correlations across 33 cancer types. Our findings indicate that SMARCAL1 is overexpressed in several cancers, such as Glioma, LUAD, KIRC, and LIHC, impacting prognosis. Elevated SMARCAL1 is linked to poor outcomes in Glioma, LUAD, and LIHC but correlates with better survival in KIRC. We also found significant associations between SMARCAL1 expression and DNA methylation in 13 cancers. Furthermore, SMARCAL1 expression correlates with immune infiltration, suggesting it as a potential therapeutic target in cancer immunotherapy. This study underscores the need for further research on SMARCAL1 to enhance immunotherapeutic strategies.

Summary To our knowledge, this is the first head-to-head study to evaluate QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, ESAT6-CFP10, and tuberculin skin test among adolescents. Our study highlights the value of QFT-Plus in detecting Mtb infection among high school freshmen when compared to QFT-GIT.

Abstract Radiotherapy using very-high-energy electron (VHEE) beams (50-300 MeV) has attracted considerable attention due to its advantageous dose deposition characteristics, enabling deep penetration and easy manipulation by magnetic components. One promising approach to compactly delivering these high energy electron beams in a cost-effective manner is laser wakefield acceleration (LWFA), which offers ultra-strong accelerating gradients. However, the transition from this concept to a functional machine intended for tumor treatment remains elusive. Here we present the self-developed pro- totype for LWFA-based VHEE radiotherapy, exhibiting compactness (occupying less than 5 m2) and long-term operational stability (validated over a period of one month). Subsequently, we employ this device to irradiate a tumor implanted in a mouse model. Following a dose delivery of 5.8 ± 0.2 Gy with precise tumor conformity, all irradiated mice exhibit pronounced control of tumor growth. For comparison, this tumor-control efficacy is similar to that achieved using commercial X-ray radiotherapy equipment operating at equivalent doses. These results demonstrate a compact and stable laser-driven VHEE system dedicated for preclinical studies involving small animal models and its promising prospects for future clinical translation in cancer therapy.

Abstract In this research, ultrasound-assisted enzymatic extraction of sugarcane peel polysaccharides and optimization of process conditions were used to investigate their properties and antioxidant activities. The effects of liquid-material ratio, ultrasonic temperature, ultrasonic time, and cellulase dosage on the extraction rate of SPP were investigated by one-way experiments and response surface analysis to determine the optimal process conditions. Meanwhile, structural characterization (FT-IR and NMR analyses) and antioxidant activity studies (DPPH and hydroxyl radical scavenging rates) were carried out to determine the total sugar content of SPP. The results showed that the optimal conditions for SPP extraction by the ultrasound-assisted enzymatic method were 40 mL/g liquid-material ratio, 50 °C ultrasound temperature, 40 min ultrasound time, 5% cellulase enzyme dosage, and the yield of SPP was 5.38% and the total sugar content was 75.52% under these conditions. The extracted SPP showed some scavenging ability for both DPPH and hydroxyl radicals, and the scavenging rate for both was 54.63% and 33.91%, respectively, when the mass concentration of the SPP solution was 4 mg/mL. The present study demonstrated that ultrasound-assisted enzymes can effectively extract SPP with antioxidant activity, which provides a theoretical basis for developing and utilizing sugarcane peel polysaccharides and has potential application value.

Abstract Roof-cutting and roadway retaining (RCRR) technology refers to the process of mining a coal mine face without retaining protective coal pillars. By cutting the roof, the previous section of the transportation roadway is retained as the track roadway for the next section, which has the advantages of good economic value and fast construction speed. The most important factor of RCRR effectiveness lies in the stability of the retained roadway roof, especially in areas with complex geological conditions. Due to high ground stress, ground water pressure and weak surrounding rock, the roof stabilizing and bearing mechanism is complex, restricting the promotion of RCRR. In response to above difficulties, the fiber reinforced polymer (FRP) anchoring cable is introduced for the roof stability control owing to its high strength and low costs. In this paper, the calculation formula of the bearing strength of the Fiber reinforced polymer anchoring cable in the top cutting and retaining roadway is derived. We have also discussed the effects of various strength properties of the FRP anchoring cable, including cohesion, internal friction angle, and preload, as well as layout parameters such as cable spacing, length, and diameter. The results indicate that as the strength parameters, preload, length, and diameter of FRP anchoring cable increase, so does the bearing strength of the FRP anchoring cable in the roadway. Therefore, using high-strength and high preload FRP anchoring cables with grouting reinforcement can effectively ensure the stability of the retained roadway roof. The research results can provide theoretical and practical experience for relevant engineering cases.

Stock prices prediction is a highly challenging task over many years, owing to the market’s high volatility. With the development of deep learning, various studies has focused on modeling temporal patterns for stock price prediction. Most existing approaches rely on a shared neural architecture that captures temporal patterns from individual stock series and then combines these temporal representations to form stock correlations. To overcome the above-mentioned problems, a novel market-embedding with Mamba (MEM) architecture, is proposed. Specifically, MEM consists of the following architectures, coarse-grained feature aggregation, fine-grained feature aggregation, temporal feature aggregation, which can extract the discriminative patterns for stock price prediction. The various experimental results show that the proposed method MEM surpasses previous approaches on two publicly available datasets, i.e., CSI300 and CSI800.

Background: Recent years have witnessed an explosive surge in dental research related to artificial intelligence (AI). These applications have optimised dental workflows, demonstrating significant clinical importance. Understanding the current landscape and trends of this topic is crucial for both clinicians and researchers to utilise and advance this technology. However, a comprehensive scientometric study regarding this field had yet to be performed. Methods: A literature search was conducted in the Web of Science Core Collection database to identify eligible “research articles” and “reviews.” Literature screening and exclusion were performed by 2 investigators. Thereafter, VOSviewer was utilised in co-occurrence analysis and CiteSpace in co-citation analysis. R package Bibliometrix was employed to automatically calculate scientific impacts, determining the core authors and journals. Altmetric data were described narratively and supplemented with Spearman correlation analysis. Results: A total of 1558 research publications were included. During the past 5 years, AI-related dental publications drastically increased in number, from 36 to 581. Diagnostics and Scientific Reports published the most articles, whereas Journal of Dental Research received the highest number of citations per article. China, the US, and South Korea emerged as the most prolific countries, whilst Germany received the highest number of citations per article (23.29). Charité Universitätsmedizin Berlin was the institution with the highest number of publications and citations per article (29.16). Altmetric Attention Score was correlated with News Mentions (P < .001), and significant associations were observed amongst Dimension Citations, Mendeley Readers, and Web of Science Citations (P < .001). Conclusions: The publication numbers regarding AI-related dental research have been rising rapidly and may continue their upwards trend. China, the US, South Korea, and Germany had promoted the progress of AI-related dental research. Disease diagnosis, orthodontic applications, and morphology segmentation were current hotspots. Attention mechanism, explainable AI, multimodal data fusion, and AI-generated text assistants necessitate future research and exploration.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8+ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8+ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Abstract This study investigated the potential of liquid calcium aluminate cement (LCAC) as a sustainable substitute in the cement industry. The fluid form of LCAC effectively mitigates the rapid setting issues associated with traditional powdered calcium aluminate cement (CAC) and addresses logistical challenges related to transportation. Despite these advantages, challenges such as hydration conversion and subsequent compressive strength reduction, which can lead to self-degradation, have limited the application of LCAC. In addition, despite the fundamental similarity between LCAC and CAC, the significant differences in practical characteristics, including pH and reaction mechanisms, render traditional CAC methodologies less effective for LCAC. In this research, ground granulated blast-furnace slag (GGBS) was incorporated into LCAC mortar at various proportions to evaluate its potential as an auxiliary material. The findings demonstrated that the addition of GGBS noticeably enhanced the compressive strength and density of LCAC. The findings showed an optimal GGBS addition of 15% resulted in a 42.35% increase in compressive strength and a 31.23% reduction in water absorption. Microscopic structural analyses revealed that GGBS facilitated pozzolanic reactions, leading to the formation of stable Calcium-Aluminosilicate Hydrate (C-A-S-H) and Calcium Silicate Hydrate (C-S-H) gels, which mitigated self-degradation by reducing porosity. This study confirmed that LCAC can effectively address the challenges of hydration conversion and compressive strength reduction similar to CAC. The research highlighted the dual advantages of GGBS, which not only enhances the mechanical properties of LCAC but also fosters sustainability by lowering carbon emissions during both production and long-term application.

Abstract Patients are turning to OHCs to deal with the stresses and complications of infertility. As a stigmatized disease, infertile patients may value informational support and emotional support differently, which is ignored in existing studies. Based on social support theory, this study aims to reveal the role of informational support and emotional support of doctors in infertile patient decision-making. We select Haodf.com as our data source and we collected information for all new patients of 2,989 doctors. we use Jieba word segmentation tool and TF-IDF algorithm to segment word and find keywords. Then random forest algorithm is used to classify 750 training texts and 250 test texts. We measure all the treatment experience of these new patients between September and December 2022 and then take the average value (TreatExpi). The sentiment analysis application program interface from Baidu AI-NLP is used to measure emotion state of patients and then the average value is included (EmoStai). In order to eliminate the influence of other factors, control variables including the number of patients online (#Patienti), the recommendation (Recommendationi), hospital level (Hleveli), doctor medical title (Mtitlei) and service price (Serpi). First, the effects of social support expressed from doctor and social support disclosed from peers show heterogeneity on patient decision-making. Second, the influences of informational support and emotional support also show difference. Third, the above relationships change with the characteristics of patients. Detecting different types and different sources of social support activities via text mining contributes to between understanding patient decision behavior in OHCs. This study contributes social support theory and OHC studies, and helps the management and design OHCs.

Abstract The construction of a predictive model that accurately reflects the spontaneous combustion temperature of coal in goaf is fundamental to monitoring and early warning systems for thermodynamic disasters, including coal spontaneous combustion and gas explosions. In this paper, on the basis of programming temperature experiment and industrial analysis, 381 data sets of 9 coal types are established, and feature selection was executed through the utilization of the Pearson correlation coefficient, ultimately identifying O2, CO, CO2, C2H4, C3H8, C3H8/CH4, C2H4/CH4, C2H4/C3H8, CO2/CO, and CO/O2 as input indicators for the prediction model. The chosen indicator data were divided into training and testing sets in a 4:1 ratio, the Particle Swarm Optimization (PSO) methodology was applied to optimize the parameters of the XGBoost regressor, and a universal PSO-XGBoost prediction model is proposed. A tenfold cross-validation method was employed to assess performance of PSO-XGBoost, PSO-RF, PSO-SVR, XGBoost, RF, and SVR models separately, the results underscored the superior predictive accuracy, robustness, fault tolerance, and universality of the PSO-XGBoost model.

Abstract Adoptive transfer of genetically or nanoparticle-engineered macrophages represents a promising cell therapy modality for treatment of solid tumor. However, the therapeutic efficacy is suboptimal without achieving a complete tumor regression, and the underlying mechanism remains elusive. Here, we discover a subpopulation of cancer cells with upregulated CD133 and programmed death-ligand 1 in mouse melanoma, resistant to the phagocytosis by the transferred macrophages. Compared to the CD133-PD-L1- cancer cells, the CD133+PD-L1+ cancer cells express higher transforming growth factor-β signaling molecules to foster a resistant tumor niche, that restricts the trafficking of the transferred macrophages by stiffened extracellular matrix, and inhibits their cell-killing capability by immunosuppressive factors. The CD133+PD-L1+ cancer cells exhibit tumorigenic potential. The CD133+PD-L1+ cells are further identified in the clinically metastatic melanoma. Hyperthermia reverses the resistance of CD133+PD-L1+ cancer cells through upregulating the ‘eat me’ signal calreticulin, significantly improving the efficacy of adoptive macrophage therapy. Our findings demonstrate the mechanism of resistance to adoptive macrophage therapy, and provide a de novo strategy to counteract the resistance.

Abstract In the domain of spectroscopy, miniaturization efforts often face significant challenges, particularly in achieving high spectral resolution and precise construction. Here, we introduce a computational spectrometer powered by a nonlinear photonic memristor with a WSe2 homojunction. This approach overcomes traditional limitations, such as constrained Fermi level tunability, persistent dark current, and limited photoresponse dimensionality through dynamic energy band modulation driven by palladium (Pd) ion migration. The critical role of Pd ion migration is thoroughly supported by first-principles calculations, numerical simulations, and experimental verification, demonstrating its effectiveness in enhancing device performance. Additionally, we integrate this dynamic modulation with a specialized nonlinear neural network tailored to address the memristor’s inherent nonlinear photoresponse. This combination enables our spectrometer to achieve an exceptional peak wavelength accuracy of 0.18 nm and a spectral resolution of 2 nm within the 630–640 nm range. This development marks a significant advancement in the creation of compact, high-efficiency spectroscopic instruments and offers a versatile platform for applications across diverse material systems.

Abstract Effective detection is critical for terahertz applications, yet it remains hindered by the unclear mechanisms that necessitate a deeper understanding of photosensitive materials with exotic physical phenomena. Here, we investigate the terahertz detection capabilities of the two-dimensional antiferromagnetic semimetal NbFeTe2. Our study reveals that the interaction between antiferromagnetic magnetic moments and electron spin induces disordered carriers to hop between localized states, resulting in a nonlinear increase in responsivity as temperature decreases. We integrate asymmetric electrodes to generate a sufficient Seebeck potential, enabling carriers to overcome the barrier of localized states and achieve reordering at room temperature. Additionally, the self-powered performance of the NbFeTe₂/graphene heterojunction is optimized by the built-in electric field, achieving peak responsivity of 220 V W-1 and noise equivalent power of

Abstract This study retrospectively collected clinical data from 480 patients with connective tissue diseases (CTDs) at Nanjing First Hospital between August 2019 and December 2023 to develop and validate a multi-classification machine learning (ML) model for assessing depression risk. Addressing the limitations of traditional assessment tools, six ML models were constructed using univariate analysis and the LASSO algorithm, with the categorical boosting (Catboost) model emerging as the best performer, demonstrating strong predictive ability across different depression severity levels (none_F1 = 0.879, mild_F1 = 0.627, moderate and severe_F1 = 0.588). Additionally, the study provided an interpretation of the best-performing model using SHAP and developed a user-friendly R Shiny application ( https://macnomogram.shinyapps.io/Catboost/ ) to facilitate clinical use. The findings suggest that the Catboost model represents a significant advancement in assessing depression risk among CTD patients, highlighting the potential of ML in enhancing mental health management for this patient population.

International students have the potential to contribute significantly to host countries through cultural enrichment, economic growth, and human capital development. However, their successful integration into the host society is crucial to realise these benefits. By applying the framework of the two-way integration process from acculturation theory, this study examines the employment integration of international students in Finland, a non-native English-speaking country. Our semi-structured, qualitative in-depth interviews identify several key challenges encountered by international students, including limited information about the labour market, unfamiliarity with recruitment practices, a lack of industry connections, communication gaps from recruiting companies, and host country language barriers. We provide recommendations to organisations and recruiters on how to embrace diversity in their recruitment processes, as well as suggestions to universities on how to better support international students' transition into the workforce of the host country.

The evolution behavior of free radicals in coal after the low-temperature oxidation process has been widely studied in order to explore the mechanism of coal spontaneous combustion. However, due to the influence of oxidation, the free radicals measured at room temperature are mostly non-reactive free radicals in coal, and their evolution rules cannot directly reflect the oxidation process of coal. How to measure highly active free radicals in coal at room temperature becomes the focus of research. Therefore, three coal samples with different spontaneous combustion tendencies were used, by combining macro and micro means, to analyze the gas products and free radical parameters of coal samples during low temperature oxidation and low temperature pyrolysis, in order to establish the correlation between carbon free radicals in coal and spontaneous combustion reactivity. Firstly, the spontaneous combustion tendency, oxidation and pyrolysis gas products of coal samples were analyzed, and then the free radical parameters of coal samples were tested by electron paramagnetic spectroscopy. The free radical profiles were fitted by peaks to compare the free radical parameters and the changes of various free radical concentrations during the process. It is found that, on a macro level, CO and CO2 are produced in the process of low temperature oxidation and low temperature pyrolysis, but their gas production volume fraction are different. After pyrolysis, a large number of gaseous oxidation products such as CO and CO2 are immediately produced during the normal temperature oxidation of coal samples. Indicating that coal pyrolysis yielded highly active substances, which can quickly oxidize with air at room temperature. Microscopically, The free radicals in the process of low-temperature oxidation of coal samples were affected by the chain reaction, the correlation between free radical parameters and spontaneous combustion characteristics is weak, However, The increase of alkyl free radicals and total free radicals produced by thermal decomposition can accurately reflect the spontaneous combustion characteristics of coal. Finally, alkyl radicals in coal were verified as highly active carbon solid radicals by oxidative free radical test at room temperature after pyrolysis, and its content was positively correlated with the spontaneous combustion characteristics of coal. The detection of highly active and carbon-containing solid free radicals at room-temperature was realized. The analysis method of coal spontaneous combustion characteristics based on the increase of highly active and carbon-containing solid free radicals concentration was proposed. The research provides significant importance for the discussion of the spontaneous combustion mechanism and development of highly efficient materials for coal spontaneous combustion supression.

Abstract Background The injection of local anesthetics, an extremely painful procedure, leads to a reduction of patients’ acceptance. Objective To investigate the efficacy and adverse reactions of 4% tetracaine gel (TG) and lidocaine-prilocaine cream (LPC) on reducing the local anesthetic injection pain for upper eyelid blepharoplasty. Methods Sixty participants were equally divided into three groups. Each patient in two treatment groups was assigned a pair of eutectic mixture of local anesthetics (EMLA) and 4% TG, and the blank control group did not receive any topical anesthetic. The primary outcome was the pain score associated with anesthetic injection. The secondary outcomes included the local cutaneous reactions and eyelid edema in 24 h postoperatively. Results The NRS score in the control group was 6.65 ± 1.60, in the 4% TG and EMLA sides of 5.75 ± 1.62 and 6.25 ± 1.48 in group A, without statistically significant (p = 0.334, 0.067, respectively). While in group B, the injection pain scores in 4% TG and EMLA sides were 4.65 ± 1.66 and 5.5 ± 1.73 (p

Abstract Background The biomechanical environment created by suture‐button fixation Latarjet is conducive to the healing and shaping of the transplanted coracoid, but its mechanism remains unclear. The latest research has found that the absence of stem cell chemokine (CXCL12) impeded bone regeneration in Sonic Hedgehog (SHH)‐deficient animals. However, whether the biomechanical environment affects SHH and CXCL12 function has not been studied. Methods Rat fracture models were constructed to simulate stress environments under non‐load‐bearing and load‐bearing conditions. The fracture healing and shaping, as well as the expression levels of SHH and CXCL12, were assessed through gross viewing, micro‐computed tomography (micro‐CT), and histochemical staining. Results Under flexible fixation, the relative bone volume (BV/TV) of rats exposed to the load‐bearing stress environment was significantly higher than that of rats under a non‐load‐bearing stress environment (p ≤ 0.05). Adverse bone shaping was not observed in rats subjected to flexible fixation. The levels of SHH and CXCL12 in load‐bearing rats exhibited significant elevation (p ≤ 0.05). Under a load‐bearing stress environment, no significant difference was observed in the BV/TV between the flexible fixation group and the rigid fixation group (p ≥ 0.05), but there was excessive hyperplasia of the fracture callus in the rigid fixation group. The levels of SHH and CXCL12 in rats subjected to rigid fixation were significantly elevated (p ≤ 0.05). Conclusions Flexible fixation and load‐bearing stress environment may contribute to bone healing and shaping by influencing the levels of SHH and CXCL12, suggested that this mechanism may be relevant to the healing and shaping of the transplanted coracoid after suture‐button fixation Latarjet.

Abstract Background Native cartilage has low capacity for regeneration because it has very few progenitor cells. Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs) and human umbilical cord‐derived MSCs (hUC‐MSCs) have been employed as promising sources of stem cells for cartilage injury repair. Reproduction of hyaline cartilage from MSCs remains a challenging endeavor. The paracrine factors secreted by chondrocytes possess the capability to induce chondrogenesis from MSCs. Methods The conditioned medium derived from chondrocytes was utilized to induce chondrogenic differentiation of hUCB‐MSCs and hUC‐MSCs. The expression levels of collagen type I alpha 1 chain (Col1a1), collagen type II alpha 1 chain (Col2a1), and SRY‐box transcription factor 9 (SOX9) were assessed through quantitative real‐time polymerase chain reaction (qRT‐PCR), Western blot (WB), and immunofluorescence (IF) assays. To elucidate the mechanism of differentiation, the concentration of transforming growth factor‐β1 (TGF‐β1) in the conditioned medium of chondrocytes was quantified using enzyme‐linked immunosorbent assay (ELISA). Meanwhile, the viability of cells was assessed using Cell Counting Kit‐8 (CCK‐8) assays. Results The expression levels of Col2a1 and SOX9 were found to be higher in induced hUC‐MSCs compared to those in induced hUCB‐MSCs. The conditioned medium of chondrocytes contained TGF‐β1. The CCK‐8 assays revealed that the proliferation rate of hUC‐MSCs was significantly higher compared to that of hUCB‐MSCs. Conclusions The chondrogenic potential and proliferation capacity of hUC‐MSCs surpass those of hUCB‐MSCs, thereby establishing hUC‐MSCs as a superior source of seed cells for cartilage tissue engineering.

Abstract Strengthening rural household resilience (RHR) and bolstering their ability to withstand the impacts of risk are essential for advancing the modernization of rural areas in developing countries reliant on small-scale agrarian economies. Using the microdata from the China Labor-force Dynamics Survey (CLDS), this study systematically measures and explores the rural household resilience index (RHRI) of China. The results indicate that: (1) Chinese RHRI exhibits a fluctuating upward trend over time and presents a pattern of clustered spatial distribution; (2) While the details of index evolution vary among the four major regions and eight agricultural zones, an improvement in resilience levels has been achieved; (3) High absorptive capacity and low stability characterize the current state of Chinese rural households, factors such as rural markets, economic organizations, rural gentry assistance, and collective operating income are the most important indicators influencing the RHRI; (4) The resilience level of Chinese rural households shows significant spatial correlation and variations, primarily driven by regional disparities. The main contribution of this study is to enrich and refine the construction, measurement, and interpretation of the resilience system for Chinese rural households. It also offers insights for the development and response strategies of rural household in other regions of the world.

Abstract Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3+ cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions. ScRNA expression profiles and ex vivo blocking studies further identify TNF signaling as a pathway responsible for macrophage-derived CXCL10 and CTL activation. Based on the trajectory analysis, ICI-activated T cells from whole blood are proposed to serve as the initial cells involved in inflammation, that lead to monocytes differentiating into macrophages and increasing their susceptibility to migrate to the lesion sites. Compared with systemic corticosteroids treatment, ICI-induced SJS/TEN patients treated with biologic TNF blockade showed a significantly rapid recovery and no recurrence of SCAR with continuous ICI therapy. Our findings identify that macrophage-eliciting CTL contribute to the pathogenesis of ICI-induced epidermal necrolysis and provide potential therapeutic targets for the management and prevention of SCAR induced by ICI therapy.

Abstract Implantable catheters are susceptible to severe complications due to non-specific protein adhesion on their surfaces. Polyethylene glycol (PEG) coatings, the gold standard for resistance to non-specific protein adhesion, present a challenge in achieving high-density grafting, which significantly restricts their use as anti-biofouling coatings. Herein, we exploited the strong interaction between polyphenols (PCs) and polycations (K6-PEG) to graft PEG onto the surface of PC-Cu (A network of metal polyphenols composed of proanthocyanidins and metal copper ions, with expectation for the coating with excellent resistance to non-specific protein adhesion (PC-Cu@K6-PEG). The introduction of K6-PEG resulted in enhanced stability and modulus of PC-Cu, as well as a reduction in the surface adhesion energy and contact angle of PC-Cu. In contrast to previously reported PEG coatings, PC-Cu@K6-PEG exhibited a markedly elevated grafting density of PEG (4.06 chains/nm²), which was more than double the highest value previously reported (1.9 chains/nm²), due to the diffusing ability of K6-PEG throughout the PC-Cu networks. PC-Cu@K6-PEG displays robust resistance to a variety of proteins, microbials, and platelet attachment, thereby preventing thrombosis. The coating ability of PC-Cu onto diverse substrates, combined with the simple, straightforward and environmentally benign process of fabricating PC-Cu@K6-PEG, suggests that this strategy has significant potential for use in anti-biofouling surfaces.

An artificial solid electrolyte interphase (SEI) with lithiophilic sites and chemical bonds anchoring lithium polysulfides (LiPSs) has been developed as a potential solution to protect the lithium (Li) metal anode of Lithium−sulfur (Li–S) batteries. This strategy aims to guide consistent Li deposition and relieve lithium corrosion. Herein, the evolution process of lithiophilic sites based on aluminum fluoride (AlF3) in an artificial SEI is disclosed in Li–S batteries with metal−based lithiophilic sites. The polyester polymer (PMMA and PPC)/AlF3 artificial SEI (MPAF−SEI) was homogeneously anchored on Li anode by in−situ polymerization. The conversion of AlF3 into Li–Al and LiF lithiophilic sites effectively reduce the Li nucleation overpotential and prevents the formation of Li dendrites. At the same time, the polymer can anchor LiPSs by chemical bonds and prevents Li corrosion. The optimized MPAF−SEI protected Li demonstrates excellent stability for over 3000 h at a capacity of 1 mAh cm−2 in Li || Li symmetric cells. The Li–S battery with low N/P (4) exhibits a capacity of 532.6 mAh g −1 over 300 cycles lifespan at 0.5 C.

Abstract Amidst the burgeoning field of cancer nanomedicine, dense extracellular matrices and anomalous vascular structures in the tumor microenvironment (TME) present substantial physical barriers to effective therapeutic delivery. These physical barriers hinder the optimal bioavailability of nanomedicine. Here, we propose a pioneering dual-modal strategy for overcoming physical barriers via soft organosilica nanocapsules (SMONs). Hyaluronidase-modified flexible spheres work by degrading the extracellular matrix and utilizing their flexible characteristics to enhance penetration into deeper layers. Compared with their stiff counterparts, the SMONs show diminished Young’s modulus, then the inherent softness of the SMONs confers distinct advantages, and significantly augmented cellular internalization within 4T1 cells, leading to an amplified in vitro photodynamic therapeutic effect. Furthermore, hyaluronidase-functionalized SMONs (SMONs-HAase) exhibit enhanced tumor penetration in 3D spheroids. Post incorporation of the photosensitizer chlorin e6, when administered intravenously, these soft organosilica nanocapsules amplify the efficacy of photodynamic therapy. In addition, RNA-seq analysis of SMONs-HAase-Ce6 shows it alters gene expression, degrading the extracellular matrix and impairing mitochondrial function. To sum up, this work elucidates the potential of a dual-modal strategy, highlighting the promise of SMONs in overcoming TME physical barriers and optimizing therapeutic outcomes. Graphical abstract

Abstract Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer. Additionally, we explore its expression in extra-pulmonary NEN (EP-NEN) using a standardized DLL3 IHC assay. DLL3 expression is enriched in SCLC, LCNEC along with combined histology lung cancers. Moreover, we find a wide range of DLL3 expression in high-grade EP-NEN. We describe heterogenous DLL3 expression not only in SCLC but also in different NEN types. This comprehensive characterization of DLL3 can help guide future clinical trial design targeting DLL3 in NEN including LCNEC and EP-NEN that are lacking standard of care treatment options.

Abstract Drought, a prevalent abiotic stressor, significantly impacts plant yield and quality. Melatonin (MT), a potent and economical growth regulator, plays a pivotal role in augmenting crop resilience against stress. This study investigated the efficacy of exogenous MT on drought-stressed celery seedlings by comprehensively analyzing phenotypic, physiological, and molecular attributes. The results revealed that exogenous MT mitigated celery seedling damage under drought stress, lowered malondialdehyde (MDA) concentrations, elevated oxidase activities, osmolyte levels, chlorophyll content, and augmented light energy conversion efficiency. Transcriptomic analysis demonstrated that MT could regulate chlorophyll synthesis genes (AgPORA1 and AgDVR2), contributing to heightened photosynthetic potential and increased drought tolerance in celery. Moreover, MT was found to modulate glycolytic pathways, upregulate pyruvate synthesis genes (AgPEP1 and AgPK3), and downregulate degradation genes (AgPDC2 and AgPDHA2), thereby promoting pyruvate accumulation and enhancing peroxidase activity and drought tolerance. The RNA-seq and qRT-PCR analyses demonstrated similar results, showing the same general expression trends. The study elucidates the physiological and molecular mechanisms underlying MT’s stress-alleviating effects in celery seedlings, offering insights into MT-based strategies in plant cultivation and breeding for arid environments.

Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P

Abstract This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E–03 in training cohort; 0.75 vs 0.69, P = 5.49E–04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.