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Abstract For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Abstract Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T 2 -weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. Conclusions Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma. Graphic Abstract

Abstract Platycarya strobilacea belongs to the walnut family (Juglandaceae), is commonly known as species endemic to East Asia, and is an ecologically important, wind pollinated, woody deciduous tree. To facilitate this ancient tree for the ecological value and conservation of this ancient tree, we report a new high-quality genome assembly of P. strobilacea. The genome size was 677.30 Mb, with a scaffold N50 size of 45,791,698 bp, and 98.43% of the assembly was anchored to 15 chromosomes. We annotated 32,246 protein-coding genes in the genome, of which 96.30% were functionally annotated in six databases. This new high-quality assembly of P. strobilacea provide valuable resource for the phylogenetic and evolutionary analysis of the walnut family and angiosperm.

Abstract The objective of this study was to evaluate and compare the effectiveness of three different types of bariatric surgeries, namely, sleeve gastrectomy (SG), one-anastomotic gastric bypass (OAGB), and single anastomosis sleeve ileal (SASI) bypass, in the treatment of metabolic syndrome (MS). The optimal approach for managing MS remains uncertain, and thus this study aimed to provide a recent analysis of the efficacy of these surgical procedures. This retrospective study evaluated data of individuals who underwent SG, OAGB, and SASI bypass. The primary outcome measures included weight, body mass index (BMI), glucolipid metabolic index, and the occurrence of treatment-related complications within 6 to 12 months post-surgery. A total of 324 patients were included in this study. Of these, 264 patients underwent SG, 30 underwent OAGB, and 30 underwent SASI bypass. A significant decrease in weight was observed at the 6-month and 12-month marks following all three surgical procedures. Of these, patients who underwent SASI bypass exhibited the greatest reduction in weight and BMI post-surgery. Furthermore, the SASI bypass was associated with a significantly higher percentage of total weight loss (%TWL) and excess body mass index loss (%EBMIL) compared to SG and OAGB. Patients who underwent OAGB and SASI bypass demonstrated notable improvements in type 2 diabetes mellitus (T2DM). Patients who underwent SASI bypass and OAGB experienced greater postoperative comfort and reported fewer complaints of discomfort compared to the other procedure. Based on the retrospective analysis of the data, SASI bypass was associated with greater reductions in weight and BMI, higher percentages of %TWL and %EBMIL, and better improvement in T2DM compared to SG and OAGB. Therefore, both SASI bypass and OAGB were found to be more effective than SG in the treatment of MS.

Summary: 4-Octyl itaconate (4-OI), a derivative of itaconate, inhibits inflammation by alkylating its target proteins. Here, we present a click-chemistry-based protocol for detecting 4-OI-alkylated proteins in mouse primary bone-marrow-derived macrophages (BMDMs) by using an itaconate-alkyne (ITalk) probe. We describe steps for culturing and treating BMDMs and details on using click chemistry in the cell lysate. We also detail procedures for detecting alkylated proteins by western blot.For complete details on the use and execution of this protocol, please refer to Su et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Mangroves are vital coastal ecosystems that provide crucial links between land and sea. Tree height is a key indicator for assessing mangroves’ health status. Currently, there are still numerous challenges in estimating mangrove tree height. In this study, multiple deep learning and shallow machine learning regression models were developed to accurately estimate mangrove tree height using multi-dimensional Light Detection and Ranging (LiDAR) point clouds and their derivatives. We constructed a novel CNN_RepMLP model for mangrove tree height mapping. We also further verified the applicability of different types of regression models in estimating mangrove tree heights, and explored the influence of different LiDAR-derived features on the inversion accuracy for tree heights. The results indicated the following: (1) The CNN_RepMLP displayed satisfactory performance in the inversion of mangrove tree heights, and exhibited better robustness and generalization ability than the convolutional neural network (CNN) model. (2) Among the different LiDAR-derived feature combinations, combining height variables with intensity variables can not only mitigate the negative impact of height variables on inversion models, but also enhance the mangrove tree height inversion accuracy. (3) The ensemble learning framework with ExtraTrees as the meta-model can make better use of the differences and complementarities between different single base models, and exhibited better accuracy in estimating the height of mangrove trees compared with other ensemble learning models. (4) Multiple machine learning models based on multi-dimensional UAV-LiDAR point-cloud-derived features are suitable for the inversion of mangrove tree height. The CNN_RepMLP model outperformed the CNN and stacking ensemble learning models and had more detailed differentiation in terms of mangrove tree height. Its prediction results can more realistically reflect the spatial differentiation characteristics of mangrove tree height.

We investigated the effect of different fat sources on growth performance and intestinal health in weaned piglets. A total of 72 21-day-old weaned piglets were divided into 3 groups the CON group with 2.5% soybean oil, TRE1 with 2.5% emulsified balanced oil powder and TRE2 with 2.5% emulsified coconut oil powder. These two experimental oil powders were emulsified with the emulsifier (lysophospholipid). The average daily feed intake in TRE1 was significantly higher than that in CON (P < 0.05). The apparent total tract digestibility (ATTD) of ash in TRE1 was significantly higher than that in CON (P < 0.05). Compared with CON, TRE1 tended to improve ATTD of dry matter (P = 0.075), serum triglyceride (P = 0.062) and serum-free fatty acids (P = 0.090). The jejunal villus width of piglets in TRE1 and TRE2 was significantly increased (P < 0.05) and the duodenal crypt depth was significantly decreased (P < 0.05). Compared with CON, TRE1 significantly increased the mRNA expression levels of jejunal Occludin, Claudin-1 and ZO-1 (P < 0.05). From the results of the present study, we concluded that dietary supplementation of 2.5% emulsified balanced oil powder has more obvious effects on enhancing the growth performance of weaned piglets by improving lipid metabolism, intestinal tissue development and barrier function.

ABSTRACTVaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.

ABSTRACTHuman metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine’s efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.

The Erlang loss formula, also known as the Erlang B formula, has been known for over a century and has been used in a wide range of applications, from telephony to hospital intensive care unit management. It provides the blocking probability of arriving customers to a loss system involving a finite number of servers without a waiting room. Because of the need to introduce priorities in many services, an extension of the Erlang B formula to the case of a loss system with preemptive priority is valuable and essential. This paper analytically establishes the consistency between the global balance (steady state) equations for a loss system with preemptive priorities and a known result obtained using traffic loss arguments for the same problem. This paper, for the first time, derives this known result directly from the global balance equations based on the relevant multidimensional Markov chain. The paper also addresses the question of whether or not the well-known insensitivity property of the Erlang loss system is also applicable to the case of a loss system with preemptive priorities, provides explanations, and demonstrates through simulations that, except for the blocking probability of the highest priority customers, the blocking probabilities of the other customers are sensitive to the service time distributions and that a larger service time variance leads to a lower blocking probability of the lower priority traffic.

Vehicle exhaust is one of the major organic sources in urban areas. Old taxis equipped with failed three-way catalysts (TWCs) have been regarded as “super emitters”. Compressed natural gas (CNG) is a regular substitution fuel for gasoline in taxis. The relative effect of fuel substitution and TWC failure has not been thoroughly investigated. In this work, vehicle exhausts from gasoline and CNG taxis with optimally functioning and malfunctioning TWCs are sampled by Tenax TA tubes and then analyzed by a comprehensive two-dimensional gas chromatography-mass spectrometer (GC×GC–MS). A total of 216 organics are quantified, including 80 volatile organic compounds (VOCs) and 132 intermediate volatility organic compounds (IVOCs). Failure of TWC introduces super emitters with 30 – 70 times emission factors (EFs), 60 – 112 times ozone formation potentials (OFPs), and 34 – 92 times secondary organic aerosols (SOAs) more than normal vehicles. Specifically, for the taxi with failed TWC, the total organic EF of CNG is 16 times that of gasoline, indicating that the failure of TWC exceeds the emission reduction achieved by CNG-gasoline substitution. A significant but unbalanced reduction of ozone and SOA is observed after TWC, whereas a notable “enrichment” in IVOCs was observed. Naphthalene is a typical IVOC component strongly associated with CNG-gasoline substitution and TWC failure, which is lacking in current VOC measurement. We especially emphasize that there is an urgent need to scrap vehicles with failed TWCs in order to significantly reduce air pollution.

Abstract Rapid and accurate diagnostic tests are fundamental for improving patient outcomes and combating infectious diseases. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas12a‐based detection system has emerged as a promising solution for on‐site nucleic acid testing. Nonetheless, the effective design of CRISPR RNA (crRNA) for Cas12a‐based detection remains challenging and time‐consuming. In this study, we propose an enhanced crRNA design system with deep learning for Cas12a‐mediated diagnostics, referred to as EasyDesign. This system employs an optimized convolutional neural network (CNN) prediction model, trained on a comprehensive data set comprising 11,496 experimentally validated Cas12a‐based detection cases, encompassing a wide spectrum of prevalent pathogens, achieving Spearman's ρ = 0.812. We further assessed the model performance in crRNA design for four pathogens not included in the training data: Monkeypox Virus, Enterovirus 71, Coxsackievirus A16, and Listeria monocytogenes. The results demonstrated superior prediction performance compared to the traditional experiment screening. Furthermore, we have developed an interactive web server (https://crispr.zhejianglab.com/) that integrates EasyDesign with recombinase polymerase amplification (RPA) primer design, enhancing user accessibility. Through this web‐based platform, we successfully designed optimal Cas12a crRNAs for six human papillomavirus (HPV) subtypes. Remarkably, all the top five predicted crRNAs for each HPV subtype exhibited robust fluorescent signals in CRISPR assays, thereby suggesting that the platform could effectively facilitate clinical sample testing. In conclusion, EasyDesign offers a rapid and reliable solution for crRNA design in Cas12a‐based detection, which could serve as a valuable tool for clinical diagnostics and research applications.

To realize the energy and resource utilization from organic solid waste, a two-phase microbial desalination cell (TPMDC) was constructed using dewatered sludge and kitchen waste as the anode substrate. The performance of electricity generation and composting efficacy was investigated, along with a comprehensive assessment of the potential health risks associated with the land use of the resulting mixed compost products. Experimental outcomes revealed a maximum open-circuit voltage of 0.893 ± 0.005 V and a maximum volumetric power density of 0.797 ± 0.009 W/m³. After 90 days of composting enhanced by microbial electrochemistry, a significant organic matter removal rate of 31.13 ± 0.44 % was obtained, and the anode substrate electric conductivity was reduced by 30.02 ± 0.04 % based on the anode desalination. Simultaneously, there was an increase in the content of available nitrogen, phosphorus, and potassium, as well as an improvement in the seed germination index. The forms of heavy metals shifted from bioavailable to stable residual states. The non-carcinogenic hazard index (HI) values for heavy metals and polycyclic aromatic hydrocarbons (PAHs) during the land use of compost products were less than 1, and the total carcinogenic risk (TCR) values for heavy metals and PAHs were below the acceptable threshold of 10−4. The occupational population risk of infection from five pathogens was higher than that of the general public, with all risk values ranging from 8.67 × 10−8 to 1, where the highest risk was attributed to occupational exposure to Legionella. These outcomes demonstrated that the mixture of dewatered sludge and kitchen waste was an appropriate anode substrate to enhance TPMDC stability for electricity generation, and its compost products have promising land use suitability and acceptable land use risk, which will provide important guidance for the safe treatment and disposal of organic solid waste.

IntroductionGrazing management is essential to maintain the stability of grassland ecosystems.MethodsTo determine the optimal rest-grazing period of alpine meadow, five rest-grazing periods were set based on soil thawing and plant re-greening in this study. The niche, interspecific relationships, and stability of plant communities at different rest-grazing periods were investigated.ResultsRest-grazing during soil thawing resulted in a small niche width and niche overlap of plants, overall positive interspecific associations, and a high stability of plant communities. Delayed rest-grazing time to plant re-greening resulted in a large niche width and niche overlap of plants, overall negative interspecific associations, and a low stability of plant communities.DiscussionRest-grazing in alpine meadows should begin as soon as possible to promote healthy and sustainable utilization of grasslands.

BackgroundThis study aims to prioritize genes potentially involved in multifactorial or causal relationships with gout.MethodsUsing the Summary Data-based Mendelian Randomization (SMR) approach, this research analyzed expression quantitative trait loci (eQTL) data from blood and renal tissues and genome-wide association study (GWAS) data related to gout. It sought to identify genetic loci potentially involved in gout. Heterogeneity testing was conducted with the HEIDI test, and results were adjusted for the False Discovery Rate (FDR). Blood cis-eQTL data were sourced from the eQTLGen Consortium’s summary-level data, and renal tissue data came from the V8 release of the GTEx eQTL summary data. Gout GWAS data was sourced from the FinnGen Documentation of the R10 release.ResultSMR analysis identified 14 gene probes in the eQTLGen blood summary-level data significantly associated with gout. The top five ranked genes are: ENSG00000169231 (labeled THBS3, PSMR = 4.16 × 10−13), ENSG00000231064 (labeled THBS3-AS1, PSMR = 1.88 × 10−8), ENSG00000163463 (labeled KRTCAP2, PSMR = 3.88 × 10−6), ENSG00000172977 (labeled KAT5, PSMR = 1.70 × 10−5), and ENSG00000161395 (labeled PGAP3, PSMR = 3.24 × 10−5). Notably, increased expression of KRTCAP2 and PGAP3 is associated with an increased risk of gout, whereas increased expression of THBS3, THBS3-AS1, and KAT5 is associated with a reduced gout risk. No significant gene associations with gout were observed in renal tissue, likely due to the limited sample size of kidney tissue.ConclusionOur findings have highlighted several genes potentially involved in the pathogenesis of gout. These results offer valuable insights into the mechanisms of gout and identify potential therapeutic targets for its treatment.

Summary: Bombinin-BO1 (BO1), a bombinin peptide derived from the skin secretion of Bombina orientalis, exhibits broad-spectrum antimicrobial activity. To date, the anticancer effect of BO1 remains unclear. This study confirmed cytotoxicity of BO1 on hepatocellular carcinoma cells by inducing S-phase cycle block and apoptosis. In addition, BO1 was found to be localized in cytoplasm through endocytosis. The combined results of pull down, mass spectrometry, and co-immunoprecipitation suggested that BO1 induced misfolding of CDK1 and degradation by competitively binding HSP90A with Cdc37. It was verified that overexpression of HSP90A in BO1-treated cells significantly inhibited degradation of CDK1. In vivo, BO1 inhibited tumor without being toxic to individuals. This study reveals the anti-tumor mechanism of BO1 in inducing cell-cycle arrest and apoptosis by interfering with HSP90A-Cdc37-CDK1 system. This is the first study to analyze the mechanism of BO1 regulation of tumor cells, providing theoretical basis for BO1 treatment of hepatocellular carcinoma.

Deep brain stimulation (DBS) is an effective therapy for Meige syndrome (MS). However, the DBS efficacy varies across MS patients and the factors contributing to the variable responses remain enigmatic. We aim to explain the difference in DBS efficacy from a network perspective. We collected preoperative T1-weighted MRI images of 76 MS patients who received DBS in our center. According to the symptomatic improvement rates, all MS patients were divided into two groups: the high improvement group (HIG) and the low improvement group (LIG). We constructed group-level structural covariance networks in each group and compared the graph-based topological properties and interregional connections between groups. Subsequent functional annotation and correlation analyses were also conducted. The results indicated that HIG showed a higher clustering coefficient, longer characteristic path length, lower small-world index, and lower global efficiency compared with LIG. Different nodal betweennesses and degrees between groups were mainly identified in the precuneus, sensorimotor cortex, and subcortical nuclei, among which the gray matter volume of the left precentral gyrus and left thalamus were positively correlated with the symptomatic improvement rates. Moreover, HIG had enhanced interregional connections within the somatomotor network and between the somatomotor network and default-mode network relative to LIG. We concluded that the high and low DBS responders have notable differences in large-scale network architectures. Our study sheds light on the structural network underpinnings of varying DBS responses in MS patients.

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

BackgroundCombining machine learning (ML) with gait analysis is widely applicable for diagnosing abnormal gait patterns.ObjectiveTo analyze gait adaptability characteristics in stroke patients, develop ML models to identify individuals with GAD, and select optimal diagnostic models and key classification features.MethodsThis study was investigated with 30 stroke patients (mean age 42.69 years, 60% male) and 50 healthy adults (mean age 41.34 years, 58% male). Gait adaptability was assessed using a CMill treadmill on gait adaptation tasks: target stepping, slalom walking, obstacle avoidance, and speed adaptation. The preliminary analysis of variables in both groups was conducted using t-tests and Pearson correlation. Features were extracted from demographics, gait kinematics, and gait adaptability datasets. ML models based on Support Vector Machine, Decision Tree, Multi-layer Perceptron, K-Nearest Neighbors, and AdaCost algorithm were trained to classify individuals with and without GAD. Model performance was evaluated using accuracy (ACC), sensitivity (SEN), F1-score and the area under the receiver operating characteristic (ROC) curve (AUC).ResultsThe stroke group showed a significantly decreased gait speed (p = 0.000) and step length (SL) (p = 0.000), while the asymmetry of SL (p = 0.000) and ST (p = 0.000) was higher compared to the healthy group. The gait adaptation tasks significantly decreased in slalom walking (p = 0.000), obstacle avoidance (p = 0.000), and speed adaptation (p = 0.000). Gait speed (p = 0.000) and obstacle avoidance (p = 0.000) were significantly correlated with global F-A score in stroke patients. The AdaCost demonstrated better classification performance with an ACC of 0.85, SEN of 0.80, F1-score of 0.77, and ROC-AUC of 0.75. Obstacle avoidance and gait speed were identified as critical features in this model.ConclusionStroke patients walk slower with shorter SL and more asymmetry of SL and ST. Their gait adaptability was decreased, particularly in obstacle avoidance and speed adaptation. The faster gait speed and better obstacle avoidance were correlated with better functional mobility. The AdaCost identifies individuals with GAD and facilitates clinical decision-making. This advances the future development of user-friendly interfaces and computer-aided diagnosis systems.

BackgroundInflammation is considered to play an important role in chronic obstructive pulmonary disease (COPD) and acute myocardial infarction (AMI), but the relationship between inflammation and poor prognosis in these patients has not yet been studied.MethodsWe enrolled AMI patients combined with COPD and divided them into three groups according to the tertiles of neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) respectively. Logistic regression analyses were used to identify risk factors for in-hospital all-cause death in these patients. Covariates were adjusted stepwise to determine the association between inflammatory markers and poor prognosis. Also, the receiver operating characteristic (ROC) curve was used to evaluate the greatest predictive indicator for all-cause death.ResultsA total of 281 AMI patients combined with COPD were enrolled, of which 31 experienced in-hospital mortality. The risk of all-cause death was significantly higher among those with higher NLR. The highest tertile of NLR was significantly associated with an increased risk of all-cause death (all P

BackgroundWhile some studies have suggested a link between gut microbiota (GM) and abortion, the causal relationship remains unclear.MethodsTo explore the causal relationship between GM and abortion, including spontaneous abortion (SA) and habitual abortion (HA), we performed a two-sample Mendelian randomization (MR) analysis. We used summary statistics data from MiBioGen and FinnGen for genome-wide association studies (GWAS), with GM data as the exposure variable and abortion data as the outcome variable.ResultsIn the absence of heterogeneity and horizontal pleiotropy, the inverse-variance weighted (IVW) method identified five genetically predicted GM genera linked to the risk of abortions. Lactococcus was negatively correlated with the risk of SA, whereas the Eubacterium fissicatena group was positively correlated with the risk of SA. Genetic predictions of Coprococcus3 and Odoribacter were linked to a reduced risk of HA, while the Eubacterium ruminantium group was associated with an increased risk of HA.ConclusionOur study suggests a genetic causal relationship between specific GM and two types of abortions, improving our understanding of the pathological relationship between GM and abortion.

IntroductionFeeding bamboo powder is a kind of fiber raw material mainly composed of insoluble dietary fiber (IDF). In this study, IDF-based rice husk meal and feeding bamboo powder were used to compare the effects of bamboo fiber on fecal microflora and the performance of lactating sows and their offspring piglets.MethodsThirty healthy crossbred gilts (Yorkshire × Landrace) at day 105 of gestation were randomly allocated into three groups: CON, TRE1 supplemented with 2% BBF1 (feeding bamboo powder), and TRE2 supplemented with 2% BBF2 (99% feeding bamboo powder +1% bamboo fiber polymer material). The reproductive performance, serum indexes, and fecal microbiota of sows and piglets were analyzed. The results showed that, compared with CON, the average feed intake of sows in TRE1 during the second week of lactation was significantly increased by 21.96% (p

Abstract Dendrite growth and other side‐reaction problems of zinc anodes in aqueous zinc‐ion batteries heavily affect their cycling lifespan and Coulombic efficiency, which can be effectively alleviated by the application of polymer‐based functional protection layer on the anode. However, the utilization rate of functional groups is difficult to improve without destroying the polymer chain. Here, a simple and well‐established strategy is proposed by controlling the orientation of functional groups (─SO3H) to assist the optimization of zinc anodes. Depending on the electrostatic effect, the surface‐enriched ─SO3H groups increase the ionic conductivity and homogenize the Zn2+ flux while inhibiting anionic permeation. This approach avoids the destruction of the polymer backbone by over‐sulfonation and amplifies the effect of functional groups. Therefore, the modified sulfonated polyether ether ketone (H‐SPEEK) coating‐optimized zinc anode is capable of longtime stable zinc plating/stripping, and moreover an enhanced cycling steadiness under high current densities is also detected in a series of Zn batteries with different cathode materials, which achieved by the inclusion of H‐SPEEK coating without causing any harmful effects on the electrolyte and cathode. This work provides an easy and efficient approach to further optimize the plating/stripping of cations on metal electrodes, and sheds lights on the scale‐up of high‐performance aqueous zinc‐ion battery technology.

Summary: X-ray detection is crucial across various sectors, but traditional techniques face challenges such as inefficient data transmission, redundant sensing, high power consumption, and complexity. The innovative idea of a retinomorphic X-ray detector shows great potential. However, its implementation has been hindered by the absence of active layers capable of both detecting X-rays and serving as memory storage. In response to this critical gap, our study integrates hybrid perovskite with hydrion-conductive organic cations to develop a groundbreaking retinomorphic X-ray detector. This novel device stands at the nexus of technological innovation, utilizing X-ray detection, memory, and preprocessing capabilities within a single hardware platform. The core mechanism underlying this innovation lies in the transport of electrons and holes within the metal halide octahedral frameworks, enabling precise X-ray detection. Concurrently, the hydrion movement through organic cations endows the device with short-term resistive memory, facilitating rapid data processing and retrieval. Notably, our retinomorphic X-ray detector boasts an array of formidable features, including reconfigurable short-term memory, a linear response curve, and an extended retention time. In practical terms, this translates into the efficient capture of motion projections with minimal redundant data, achieving a compression ratio of 18.06% and an impressive recognition accuracy of up to 98.6%. In essence, our prototype represents a paradigm shift in X-ray detection technology. With its transformative capabilities, this retinomorphic hardware is poised to revolutionize the existing X-ray detection landscape.

The unresectable or postoperative recurrence of advanced metastatic colorectal cancer (CRC) is the difficulty of its clinical management, and pharmacological therapy is the main source of benefit. Immune checkpoint inhibitors are therapeutic options but are effective in approximately 5 % of patients with deficient mismatch repair (MMR)/microsatellite instability CRC and are ineffective in patients with MMR-proficient (pMMR)/microsatellite stable (MSS) CRCs, which may be associated with the tumor microenvironment (TME). Here, we propose a new combination strategy and evaluate the efficacy of rapamycin (Rapa) combined with anti-PD-1 (αPD-1) in CT26 tumor-bearing mice, azoxymethane (AOM)/dextran sodium sulfate (DSS) inflammation-associated CRC mice, CT26-Luc tumor-bearing mice with postoperative recurrence, and CT26 liver metastasis mice. The results revealed that Rapa improved the therapeutic effect of αPD-1 and effectively inhibited colorectal carcinogenesis, postoperative recurrence, and liver metastasis. Mechanistically, Rapa improved the anticancer effect of αPD-1, associated with Rapa reprograming of the immunosuppressive TME. Rapa effectively depleted α-SMA+ cancer-associated fibroblasts and degraded collagen in the tumor tissue, increasing T lymphocyte infiltration into the tumor tissue. Rapa induced the downregulation of programed cell death 1 ligand 1 (PD-L1) protein and transcript levels in CT26 cells, which may be associated with the inhibition of the mTOR/P70S6K signaling axis. Furthermore, co-culture of tumor cells and CD8+ T lymphocytes demonstrated that Rapa-induced PD-L1 downregulation in tumor cells increased spleen-derived CD8+ T lymphocyte activation. Therefore, Rapa improves the anti-tumor effect of αPD-1 in CRCs, providing new ideas for its use to improve combinatorial strategies for anti-PD-1 immunotherapy.

As the proportion of wind and photovoltaic power plants characterized by intermittency and volatility in the electric power system is increasing continuously, it restricts the development of renewable energy at a higher proportion and a larger scale. CSP has the dual functions of peak-regulating power supply and energy storage, which can provide important support for grid access and power regulation for renewable energy power. In this study, the capacity configuration and economy of integrated wind–solar–thermal–storage power generation system were analyzed by the net profit economic model based on the adaptive weight particle swarm algorithm. A case study was conducted on a 450 MW system in Xinjiang, China. The effects of heat storage capacity, capacity ratio of wind power and photovoltaic to molten salt parabolic trough power generation on the economy of the integrated power generation system were obtained under the condition that the system output should meet the power load. The results show that when the capacity ratio is fixed and the heat storage capacity increases, the net profit of the system increases first and then decreases. When the heat storage capacity is fixed, the net profit of the system increases with the increase of the capacity ratio, but when the capacity ratio exceeds 5:1, the upward trend is gradually slowed down. When there are different heat storage capacities and capacity ratios, the lowest peak-shaving electricity prices corresponding to the net profit break-even point of the integrated system are obtained.

Red blood cell substitutes offer a solution to the problem of blood shortage and side effects of blood transfusion. Hemoglobin-based oxygen carriers (HBOCs) are one of the promising substitutes for red blood cells. Vasoactivity, which refers to the side effect of HBOCs that causes vasoconstriction and subsequent hypertension, limits the clinical application of HBOCs. In this study, an ex vivo method for the evaluation of vasoactivity induced by HBOCs was established based on isolated rat mesenteric artery vessels and the DMT120CP system. The DMT120CP system, equipped with a flowmeter, permits the control of intravascular pressure, pressure gradient, and flow conditions with high accuracy, simulating the physiological conditions for isolated vessels. The concentration of noradrenaline was optimized to 1 × 10−6∼3 × 10−6 M. PEGylated bovine hemoglobin (PEG-bHb) was synthesized and perfused into the vessel for vasoactivity evaluation, with bHb as the positive control and PSS buffer solution as the negative control. PEG-bHb showed a hydration diameter of 15.5 ± 1.4 nm and a P50 value of 6.99 mmHg. PEG-bHb exhibited a colloid osmotic pressure of 64.1 mmHg and a viscosity of 1.73 cp at 40 mg/mL. The established vasoactivity evaluation method showed significant differences in samples (bHb or PEG-bHb) with different vasoactivity properties. The vasoconstriction percentage induced by PEG-bHb samples synthesized in different batches showed coefficients of variation less than 5%, indicating good applicability and repeatability. The established evaluation method can be applied to study the vasoactivity induction and elimination strategies, promoting the clinical application of HBOCs.

Herbivore-avoided plant patches are one of the initial characteristics of natural grassland degradation. These vegetation patches can intensify the spatial heterogeneity of soil nutrients within these grasslands. However, the effects of non-edible plant patches patches on the spatial heterogeneity of microorganisms have not been sufficiently studied in alpine meadows of the Qinghai-Tibetan Plateau, especially patches formed by herbaceous plants. To answer this question, soil nutrients, plant assembly, and microbial communities were measured inside, around, and outside of Artemisia smithii patches. These were 0 m (within the patch), 0–1 m (one meter from the edge of the patch), 1–2 m (two meters from the edge of the patch), 2–3 m (three meters from the edge of the patch), and >30 m (non-patch grassland more than thirty meters from the edge of the patch). Our results showed that A. smithii patches accumulated more aboveground biomass (AGB) within the patches (0 m), and formed fertile islands with the soil around the patches. Additionally, A. smithii patches increased soil bacterial diversity within (0 m) and around (0–1 m) the patches by primarily enriching copiotrophic bacteria (Actinobacteria), while the diversity of fungal communities increased mainly in the 0–1 m area but not within the patches. Bacterial community diversity was driven by pH, urease, nitrate nitrogen (NO3−-N), and microbial biomass carbon (MBC). The contents of soil water (SWC), soil organic matter (SOM), urease, NO3−-N, and MBC were the main factors influencing the diversity of the fungal community. This study elucidates the vegetation, nutrients, and microbial heterogeneity and their interrelationships, which are observed in fertile islands of herbivore-avoided plant patches in alpine meadows, and provides further insights into the spatial pattern of nutrients in patchy degraded grasslands.

This study aimed to evaluate the impacts of wild and breeding juvenile rice field eel under conditions of ammonia and heat stress. The growth performance (FBW, WGR, SGR, and FCR) of 360 wild (24.22 ± 0.30 g) and 360 breeding (24.16 ± 0.27 g) strains was significantly hindered by ammonia and heat stress. The inhibitory effects were more obvious when the two stresses were combined. The growth performance and survival rates of the breeding strains outperformed that of the wild strains under identical stress conditions, this was explained by the expression of the growth-related gene (gh). They have increased the enzyme activity (CAT and GSH-Px) and expression of immune-related genes (cat, gpx3, and hsp90α) in response to oxidative stress. However, the results of certain indicator enzymes indicate the presence of oxidative damage in their tissues. The presence of an inflammatory response in the tissues was suggested by the up-regulation of genes associated with pro-inflammatory cytokines (il-1β and il-8) and the down-regulation of genes related to anti-inflammatory cytokines (il-10). Additionally, the presence of tissue damage was shown by the up-regulation of genes connected to apoptosis (cas2, cas8, and cas9) and the down-regulation of genes connected to tight junctions (zo-1). Nevertheless, it is noteworthy that breeding strains exhibited superior adaptability to ammonia and heat stress in comparison to wild strains.

Monopterus albus is one of China’s renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in M. albus aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean M. albus juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of M. albus juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 M. albus juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%–85.33%, which was significantly higher than that of the other three bait groups (p < 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) (p > 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups (p < 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO2−-N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups (p < 0.05), there was no significant difference in TAN content among the treatment groups (p > 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups (p < 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups (p > 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, Tenebrio molitor could potentially serve as one of the alternative feeds during the initial stages of M. albus juveniles stocking.

Abstract Aortic root aneurysm is a potentially life‐threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single‐nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell‐type‐specific transcriptomic and cis‐regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

Abstract Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

Abstract An organic synaptic transistor (OST) that utilizes a multiple‐annealing process and an ion gate to achieve significant reductions in operating voltage and increases in transconductance is demonstrated. The OST exhibits an ultra‐short‐term plasticity (USTP) with a maximum retention time of only 20.7 ms, which does not increase with the number and duration of spikes. This is the shortest retention time yet achieved by an ion‐gel‐regulated synaptic transistor. In addition, OST‐integrated array exhibits a tunable weight plasticity and a short weight refresh time for a stable image resetting in ample time of

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-β1, tgf-β2, and tgf-β3 (P < 0.05) and higher il-1β, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.

ObjectiveTo explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression.MethodsA total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function.ResultsThe sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P

[Abstract]: Objective: The objective is to construct a random forest model for predicting the occurrence of Myofascial pelvic pain syndrome (MPPS) and compare its performance with a logistic regression model to demonstrate the superiority of the random forest model. Methods: We retrospectively analyze the clinical data of female patients who underwent pelvic floor screening due to chronic pelvic pain at the Pelvic Floor Rehabilitation Center of the Third Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. A total of 543 female patients meeting the study's inclusion and exclusion criteria are randomly selected from this dataset and allocated to the MPPS group. Furthermore, 702 healthy female patients who underwent pelvic floor screening during routine physical examinations within the same timeframe are randomly selected and assigned to the non-MPPS group. Chi-square test and rank-sum test are used to select demographic variables, pelvic floor pressure assessment data variables, and modified Oxford muscle strength grading data for logistic univariate analysis. The selected variables are further subjected to multivariate logistic regression analysis, and a random forest model is also established. The predictive performance of the two models is evaluated by comparing their accuracy, sensitivity, specificity, precision, receiver operating characteristic (ROC) curve, and area under the curve (AUC) area. Results: Based on a dataset of 1245 cases, we implement the random forest algorithm for the first time in the screening of MPPS. In this investigation, the Logistic regression model forecasts the accuracy, sensitivity, specificity, and precision of MPPS at 69.96 %, 57.46 %, 79.63 %, and 68.57 % respectively, with an AUC of the ROC curve at 0.755. Conversely, the random forest prediction model exhibits accuracy, sensitivity, specificity, and precision rates of 87.11 %, 90.66 %, 90.91 %, and 83.51 % respectively, with an AUC of the ROC curve at 0.942. The random forest model showcases exceptional predictive performance during the initial screening of MPPS. Conclusion: The random forest model has exhibited exceptional predictive performance in the initial screening evaluation of MPPS disease. The development of this predictive framework holds significant importance in refining the precision of MPPS prediction within clinical environments and elevating treatment outcomes. This research carries profound global implications, given the potentially elevated misdiagnosis rates and delayed diagnosis proportions of MPPS on a worldwide scale, coupled with a potential scarcity of seasoned healthcare providers. Moving forward, continual refinement and validation of the model will be imperative to further augment the precision of MPPS risk assessment, thereby furnishing clinicians with more dependable decision-making support in clinical practice.

Background: Aim to investigate the impact of bedside assistant's work experience and learning curve on the short-term safety and efficacy in robotic-assisted laparoscopic radical hysterectomy for early-stage cervical cancer. Methods: Our research retrospectively retrieved 120 cases of early-stage cervical cancer patients who underwent robotic-assisted laparoscopic radical hysterectomy at the First Affiliated Hospital of Guangxi Medical University. According to the different work experiences of the two bedside assistants (BA), patients were divided into a research group (inexperienced BA 1) and a control group (experienced BA 2). Furthermore, the learning curves of these BAs were plotted separately and divided into two distinct phases by cumulative summation: the first learning phase and the second master phase. Result: In terms of work experience, comparing BA 1 with BA 2 who was more experienced, although the average operative time was prolonged by 29 min (P＜0.001), it did not increase the incidence of operative complication [24.4 % VS 29.1 %, P = 0.583], positive resection margin [4.9 % VS 7.6 %, P = 0.714], intraoperative organ damage [0 % VS 2.5 %, P = 0.546] and there was no significant difference in the number of lymph nodes [19 VS 15, P = 0.103]. Additionally, comparing two distinct phases of the same bedside assistant, there was no significant increasing rate in terms of operative complication, positive resection margin, intraoperative organ damage, and the number of lymph nodes (P＞0.05) neither BA 1 nor BA 2, except for a slight extension of operative time about 20 min in learning phase (P＜0.05). Conclusion: In robotic-assisted laparoscopic radical hysterectomy for early-stage cervical cancer, work inexperience and the learning phase of BA only result in a slight extension of operative time, without causing worse short-term surgical outcomes.

The addition of Sn into the raw materials is currently one of the most widely used methods to improve the purity and mechanical properties of Ti3AlC2. It follows in this work to investigate the oxidation behavior of the resulting Ti3Al0.8Sn0.2C2 at 1200 °C with the oxidation time up to 500 h. The oxidation kinetics shows that its oxidation resistance is much worse than that of common MAX phases including Ti3AlC2, Ti2AlC, and Cr2AlC. The oxide layer mainly consists of TiO2 and Al2O3, with only a small amount of SnO2 at the beginning of the oxidation stage. Cracks induced by the internal thermal stress penetrate through the entire oxide layer after only 1 h, which is an important reason for the rapid oxidation of the internal substrate layer. This work is expected to provide some inspiration and reference for Ti3Al0.8Sn0.2C2 used as the potential high-temperature structural material.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].