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Abstract Sub-10 µm microplastics (MPs) in aquatic environments pose significant ecological and health risks due to their mobility and potential to carry harmful microcontaminants. Our effluent analysis from a Hong Kong Sewage Treatment Works shows that traditional treatment often fails to effectively remove these MPs. These small-sized MPs are commonly neglected due to challenges in accurate quantification, analysis, and removal. This study introduces a nanobubble-assisted flotation process that enhances the removal efficiency of both regular and irregular small-sized MPs from wastewater. The proposed process outperforms the traditional flotation process by fostering a more effective interaction between bubbles and MPs, increasing removal rates of MPs from 1 µm to 10 µm by up to 12% and providing a total efficiency boost of up to 17% for various particle sizes. Improvements are attributed to enhanced collision and adhesion probabilities, hydrophobic interactions, as well as better floc flotation. Supported by empirical evidence, mathematical models, and Molecular Dynamics simulations, this research elucidates the nanoscale mechanisms at play. The findings confirm the nanobubble-assisted flotation technique as an innovative and practical approach to removing sub-10 µm MPs in water treatment processes.

Abstract This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P

Abstract Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases.

Abstract CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with “one to more” aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

Background: Following recent research advancements, an increasing level of evidence had been published to indicate that celastrol exerted a therapeutic effect on a range of nervous system diseases. This study therefore aimed to investigate the potential involvement of celastrol on ferroptosis and the blood-brain barrier disruption in intracerebral haemorrhage. Methods: We established a rat intracerebral haemorrhage and adrenal pheochromocytoma cell (PC12) OxyHb models using an ACSL4 overexpression vector. Ferroptosis-related indices were assessed using corresponding assay kits, and immunofluorescence and flow cytometry were used to measure reactive oxygen species (ROS) levels. Additionally, quantitative PCR (qPCR) and western blot analyses were conducted to evaluate the expression of key proteins and elucidate the role of celastrol in intracerebral haemorrhage (ICH). Results: Celastrol significantly improved neurological function scores, blood-brain barrier integrity, and brain water content in rats with ICH. Moreover, subsequent analysis of ferroptosis-related markers, such as Fe2+, ROS, MDA, and SOD, suggested that celastrol exerted a protective effect against the oxidative damage induced by ferroptosis in ICH rats and cells. Furthermore, Western blotting indicated that celastrol attenuated ferroptosis by modulating the expression levels of key proteins, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and anti-transferrin receptor 1 (TFR1) both in vitro and in vivo. ACSL4 overexpression attenuated the neuroprotective effects of celastrol on ICH in vitro. Molecular docking analysis revealed that celastrol interacted with ACSL4 via the GLU107, GLN109, ASN111, and LYS357 binding sites. Conclusions: Celastrol exerted antioxidant properties and aids in neurological recovery after stroke by suppressing ACSL4 expression during ferroptosis. As such, this drug represented a promising pharmaceutical candidate for the treatment of ICH.

Chinese tongue sole (Cynoglossus semilaevis) is a traditional, nutrient rich and economically valuable fish that is important for mariculture in China. It has small visceral masses, few spines, with tender and tasty flesh. Studies on the sexing mechanism of fish were carried out since the revelation of sexual reversal and hermaphroditism in the eel. Sex is the most common biological phenomenon and there are significant differences in morphology, reproductive strategies, and behavior between females and males of many organisms. Sole is a typical representative of the heterogeneous growth of males and females: adult females are approximately 2–4 times larger than males. This has constrained the sustainable development of the sole culture industry. Why do females grow faster than males? Do sex differentiation-related genes play a role in sex determination and size heteromorphism in sole? Answering these questions has important implications and applications in the genetic improvement and development of sole farming.Rimoc1 encodes a protein in the inner mitochondrial membrane that is involved in regulating the activity of complex Ⅰ of the mitochondrial respiratory chain that affects mitochondrial respiratory function. Rimoc1 interacts with the NDUFAF1 subunit of complex Ⅰ in the inner mitochondrial membrane and enhances its affinity for NADH. This increases the catalytic activity of complex Ⅰ and increases the rate of electron transfer in the mitochondrial respiratory chain. In addition, RIMOC1 interacts with proteins in other mitochondrial respiratory chain complexes (such as complex Ⅲ and complex Ⅳ) and may play a role in regulating the overall stability and function of the mitochondrial respiratory chain.This study aimed to investigate the expression differences of the rimoc1 gene in male and female Chinese tongue sole and determine its potential relationship with sex and growth. Rimoc1 expression was highest in the ovaries and muscles of females; it was not expressed in male tissues. Interestingly, its expression was relatively stable in the ovaries, but increased at 1.5- and 3-years post-hatching. Knocking out rimoc1 through siRNA interference in cell lines significantly reduced the expression levels of growth-related gene igf1, and sex differentiation-related genes sox9b and foxl2, while sox9a expression increased. Promoter activity analysis further demonstrated that the rimoc1 promoter strongly responded to transcription factors C/EBPdelta, Sox2, and c-Jun. This suggested their potential role in regulating rimoc1. Sex determination in semislipped sole occurs at approximately 50 days, while gonadal differentiation begins at 60 days. However, differentiation at the cellular level is relatively delayed, with ovarian cell differentiation usually occurring at 90–120 days with the emergence of an ovarian cavity followed by continued oocyte differentiation and sexual maturity at approximately 2 years of age. Thus, high rimoc1 expression at 90 days is consistent with the differentiation of naturally growing ovarian cells in semi-smooth tongue sole.Analysis of promoter activity showed that rimoc1 was transcriptionally active at 981 bp upstream and had strong initiation activity. The activity was enhanced following cotransfection with three transcription factors (C/EBPalpha, Sox2, and C-Jun), although only the C/EBPalpha group was significantly different. This suggested that these three transcription factors exert an enhancing effect on rimoc1 transcription. It is known that C/EBPalpha plays a major role in keratinocyte and adipocyte differentiation. However, its regulation of rimoc1 in hemipterous sole requires further investigation.There are few reports on the function of rimoc1 in sexual differentiation. Therefore, we performed the first functional investigation of rimoc1 by siRNA-mediated RNA interference in an ovarian cell line. Quantitative polymerase chain reaction showed that the expression levels of igf1, sox9a, sox9b, and foxl2 changed at different degrees after rimoc1 gene interference compared to the control group; sox9a expression was up-regulated, while the expression of igf1, sox9b, and foxl2 was down-regulated. Fish igf1 is closely related to reproductive function and gonadal development. Tilapia igf1 expression was detected from the early stages of oogenesis till oocyte maturation. At the same time, Igf1 is involved in regulating growth hormones and growth. Sexual growth dimorphism begins to appear in one-year old half-sauropod sole. The quantification of different developmental stages shows that rimoc1 expression starts to increase at 180 days until its peak expression at 1.5 years of age. It is worthwhile investigating whether rimoc1 has a potential regulatory function in growth.Sox9 is a key transcription factor that plays an important role in regulating the proliferation and differentiation of various cell types. It has a critical role in embryonic development, with expression occurring throughout this period. Its level is maintained in adult tissues and plays an important role in the repair of postnatal damage in endodermal and ectodermal organs. It has a role in sex differentiation, with sox9a and cyp19a together forming a regulatory pathway for sexual differentiation. We hypothesize that rimoc1 is involved in ovarian development and oogenesis by regulating the steroid hormone pathway. Sox9b is highly expressed in the gonads of early semi-smooth sole, and rimoc1 knockdown results in its reduced expression. This suggests that Rimoc1 and Sox9b act together to regulate Foxl2 and play a role in sex determination and differentiation, ovarian development and maintenance, embryonic development, and immune regulation in the animal. The foxl2 gene positively regulates ovarian differentiation in mice, and its sustained expression inhibits abnormal differentiation of ovarian cells to testicular cells during growth and development, thereby maintaining the female sex. Meanwhile foxl2 deletion can lead to poor ovarian development, and even female sterility. Rimoc1 knockdown results in its reduced expression, suggesting that rimoc1 may be closely associated with ovarian development in hemipelagic sole. Therefore, a deeper understanding of the function and regulatory mechanisms of rimoc1 may be the key to resolving sexual growth dimorphism.Our results suggest that rimoc1 plays a crucial role in sex differentiation and growth of Chinese tongue sole. These findings provide a foundation for further investigations into the sexual growth dimorphism of this species.

Abstract One of the focal points in the field of intelligent transportation is the intelligent control of traffic signals (TS), aimed at enhancing the efficiency of urban road networks through specific algorithms. Deep Reinforcement Learning (DRL) algorithms have become mainstream, yet they suffer from inefficient training sample selection, leading to slow convergence. Additionally, enhancing model robustness is crucial for adapting to diverse traffic conditions. Hence, this paper proposes an enhanced method for traffic signal control (TSC) based on DRL. This approach utilizes dueling network and double q-learning to alleviate the overestimation issue of DRL. Additionally, it introduces a priority sampling mechanism to enhance the utilization efficiency of samples in memory. Moreover, noise parameters are integrated into the neural network model during training to bolster its robustness. By representing high-dimensional real-time traffic information as matrices, and employing a phase-cycled action space to guide the decision-making of intelligent agents. Additionally, utilizing a reward function that closely mirrors real-world scenarios to guide model training. Experimental results demonstrate faster convergence and optimal performance in metrics such as queue length and waiting time. Testing experiments further validate the method's robustness across different traffic flow scenarios.

Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-β as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD.

Abstract The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2−x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 μmolCH4 gcat −1 s−1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

Abstract Purpose This study evaluates biochar from crop residues as a solution to soil degradation in continuous monoculture within greenhouse agriculture, focusing on its impact on soil microbial communities and cucumber plant growth. Methods We analyzed biochar derived from tomato straw (TSB), sweet pepper straw (SPSB), and eggplant straw (ESB), assessing their nutrient content, cation exchange capacity, and adsorption rates. This study examined the effects of three concentrations (2.5%, 5%, and 7.5% w/w) of the more promising SPSB on soil properties and cucumber growth. Results SPSB showed significantly higher levels of nitrogen, phosphorus, and potassium, along with superior adsorption capacity compared to TSB and ESB. The 5% w/w SPSB concentration notably improved cucumber growth, increasing plant height by 13.01%, stem thickness by 20.79%, leaf area by 50.26%, and dry weight by 58.56% relative to the control. High-throughput sequencing revealed this concentration significantly altered soil microbial community structure, enhancing bacterial and fungal diversity. It increased beneficial bacterial groups (Firmicutes, Actinobacteria, Bacillus) and modified fungal communities, with a decrease in Ascomycota and Aspergillus and shifts in Penicillium abundance. Functional genomic analysis indicated enrichment in bacterial metabolic pathways and fungal replication and expression genes. Conclusion SPSB, especially at a 5% w/w concentration, emerges as an effective soil amendment in greenhouses affected by continuous monoculture. This approach represents a sustainable method to enhance soil health and crop productivity.

Business Development (BD) activities have become prevalent in practice, and prior research has demonstrated their potential to enhance and complement the core competencies of enterprises. However, the limited and fragmented existing literature on Business Development highlights the need for a comprehensive integration effort to reassess the theoretical foundation and overall concept. This article comprehensively reviews 125 papers on Business Development, investigates enterprises’ responses to business environment changes (which encompass environmental adaptation and resource leverage, environmental management and resource allocation, environmental creation and resource alignment, and environmental exploration and resource development), and clarifies the evolutionary trajectory of the Business Development literature research stream. Furthermore, we advance a comprehensive conceptual framework and theoretical model to identify a network of constructs and their connections with crucial dimensions of Business Development. The findings of this study significantly contribute to understanding Business Development and provide valuable insights for future research and practice.

ObjectiveTo evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved.MethodsMTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups.ResultsDADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p

Background: Intracranial metastasis of gastrointestinal stromal tumors (GISTs) is uncommon and the optimal management for these patients remains undefined. The introduction of selective tyrosine kinase inhibitors (TKI) has drastically improved survival in patients with GISTs. However, its efficacy in patients with intracranial metastasis of GISTs is uncertain due to poor penetration of the blood brain barrier. The role of surgery and radiotherapy in these patients has also not been established. No large-scale studies exist, and the literature is limited to case reports. We report a case treated at our institution, conducted a literature review of existing case reports, and discussed the optimal management of patients with intracranial metastasis of GISTs. Methods: A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies with intracranial metastasis of GISTs were included, with data extracted and analyzed in totality. Results: 26 cases were included in the review. The median time to diagnosis of intracranial metastasis in patients with previously known GISTs was 66 months. Solitary metastasis was seen in 16 cases (59.3 %). 18 patients (69.72 %) underwent surgical resection; 14 had additive therapy with 9 receiving TKI. The mean duration of follow up was 11 months. Clinical response was seen in 3 patients in the non-surgical group, all 3 were treated with TKI alone. Conclusion: The effectiveness of TKI in intracranial GISTs metastasis is seen both as first-line therapy for asymptomatic lesions and as an additive treatment post-surgery. Surgery retains a key role in establishing histological and molecular diagnosis and for symptomatic relief of mass effect.

Summary: Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1–3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2–8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2–22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0–12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Summary: Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

Abstract Single‐atom alloys (SAAs) have gained increasing prominence in the field of selective hydrogenation reactions due to their uniform distribution of active sites and the unique host‐guest metal interactions. Herein, 15 SAAs are constructed to comprehensively elucidate the relationship between host‐guest metal interaction and catalytic performance in the selective hydrogenation of 4‐nitrostyrene (4‐NS) by density functional theory (DFT) calculations. The results demonstrate that the SAAs with strong host‐guest metal interactions exhibit a preference for N─O bond cleavage, and the reaction energy barrier of the hydrogenation process is primarily influenced by the host metal. Among them, Ir1Ni SAA stands out as the prime catalyst candidate, showcasing exceptional activity and selectivity. Furthermore, the Ir1Ni SAA is subsequently prepared through precise synthesis techniques and evaluated in the selective hydrogenation of 4‐NS to 4‐aminostyrene (4‐AS). As anticipated, the Ir1Ni SAA demonstrates extraordinary catalytic performance (yield > 96%). In situ FT‐IR experiments and DFT calculations further confirmed that the unique host‐guest metal interaction at the Ir‐Ni interface site of Ir1Ni SAA endows it with excellent 4‐NS selective hydrogenation ability. This work provides valuable insights into enhancing the performance of SAAs catalysts in selective hydrogenation reactions by modulating the host‐guest metal interactions.

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Comparative nutritional analysis of Porphyra yezoensis strains “Jianghai No. 1” and “Sutong No.1” revealed significant differences in crude protein, crude fat, crude fiber, crude ash, and total sugar. Both strains contained 16 amino acids, with alanine as the highest and histidine the lowest content. Methionine was determined to be the first limiting amino acid for both strains in both amino acid score and chemical score assessment. They also featured 24 fatty acids, differing notably in four saturated fatty acids and five unsaturated fatty acids. All 12 mineral elements were present, notably differing in sodium, magnesium, potassium, calcium, iron, and zinc. The “Jianghai No. 1” strain stands out with its nutrient-rich profile, featuring high protein content, low fat, and abundant minerals, which could potentially command higher market prices and generate greater economic benefits due to its superior nutritional, and set a strong foundation for its future large-scale promotion and cultivation.

The Internet of Things (IoT) provides a major contribution to the innovation of smart manufacturing and industrial automation. Due to IoT, network devices and intelligent machines exchange information through different types of Internet connection and processes are predominantly automated. This reduces significantly the need for more human intervention and supports high performance. Nevertheless, the utilization of IoT in industrial automation called Industrial IoT (IIoT) has several issues, including the management of applications and IIoT devices. Moreover, heterogeneous networks and tremendous devices deployed in the IIoT environment require flexible configuration and reconfiguration according to the change for ensuring dynamic performance. We argue that Software-Defined Networking (SDN) is one of the technologies that can be used to solve some of the previously mentioned issues. In this paper, we propose a survey for the implementation of SDN solutions in IIoT and discuss the pros and cons brought about by this synergy named “SDN-IIoT”. We explore the current articles on SDN-IIoT by considering different crucial domains such as flow installation techniques, fault tolerance, traffic routing optimization, resource management, energy efficiency, real-time, and network security. Furthermore, we analyze Artificial Intelligence (AI)/Machine Learning (ML) tasks to improve the performance of SDN-IIoT and the deployment of different technologies like Network Function Virtualization (NFV) and Time-Sensitive Networking (TSN) in SDN-IIoT. After observing the limitations of existing SDN-IIoT architectures, we propose an improved candidate architecture for SDN-IIoT based on a hierarchical distributed control plane. The new SDN-IIoT architecture contains AI, Industrial Backhaul Network (IBN), Dynamic Hash Table (DHT), AdaptFlow protocol, and edge/cloud storages. This paper selects the five most used SDN controllers by the literature review and identifies the features of each SDN controller. In the end, we provide open challenges and future research orientations in SDN-IIoT. We hope that this paper will be helpful for engineers, organizations, and researchers on the innovation of IIoT and SDN technologies.

Background: Few studies have studied the efficacy of using immersive virtual reality (iVR) to teach surgical skills, especially by using real-world iVR recordings rather than simulations. This study aimed to investigate whether viewing 360° iVR instructional recordings produces greater improvements in basic suturing skills of students without prior medical training, beyond traditional methods like reading written manuals or watching 2D instructional videos. Materials and methods: This was a partially blinded randomized cohort study. 44 pre-university students (aged 17) were randomized equally to either the written instruction manual, 2D instructional video, or iVR recordings. All students first watched a silent 2D demonstration video of the suturing task, before attempting to place three simple interrupted sutures on a piece of meat as a baseline. The time taken for the first attempt was recorded. Students were then given an hour to train using their allocated modality. They attempted the suturing task again, and timings were re-recorded. Four blinded surgically-trained judges independently assessed the quality of the stitches placed both pre and post-intervention. One-way analysis of variance tests (ANOVAs) and independent two-sample t-tests were used to determine the effect of training modality on improvements in suturing scores and time taken to complete suturing from pre to post-training. Results: For suturing scores, the iVR group showed significantly larger score improvements than the Written Manual group (p = 0.031, Cohen's D = 0.92), while this iVR advantage was less pronounced when compared with the 2D Video group (p = 0.16, Cohen's D = 0.65). Similarly for time taken to complete suturing, the iVR group had significantly larger time improvements than the Written Manual group (p = 0.045), although this difference was less robust compared to the 2D Instructional Video group (p = 0.34). Conclusion: This study demonstrates that iVR training using real-world 360° instructional recordings produced significantly greater training gains in suturing scores and efficiency compared to reading written text. iVR training also led to larger training gains in both outcome measures than viewing 2D instructional videos, although the differences between them did not reach statistical significance.

Abstract Background Functional role of filum terminale (FT) was not well studied though it contains structure basis for nerve impulse conduction. We aimed to explore the possible functions of the FT from the perspective of triggered electromyography (EMG) during surgery. Methods We retrospectively reviewed intraoperative neurophysiological monitoring data from pediatric patients who underwent intradural surgeries at the lumbar level in Shanghai Children’s. Hospital from January 2018 to March 2023. Altogether 168 cases with complete intraoperative neurophysiological recordings of the FT were selected for further analysis. Triggered EMG recordings of the filum originated from two main types of surgeries: selective dorsal rhizotomy (SDR) and fatty filum transection. Results 96 cases underwent SDR and 72 cases underwent fatty filum transection. Electrical stimulation of the FT with fatty infiltration did not elicit electromyographic activity in the monitored muscles with the maximum stimulus intensity of 4.0 mA, while the average threshold for FT with normal appearance was 0.68 mA, and 89 out of 91 FT could elicit electromyographic responses in monitored channels. The threshold ratio of filum to motor nerve roots at the same surgical segment was significantly higher in patients with fatty filum, and a cut-off point of 21.03 yielded an area under curve of 0.943, with 100% sensitivity and 85.71% specificity. Conclusion Filum with normal appearance can elicit electromyographic activity in the lower limbs/anal sphincter similar to the performance of the cauda equina nerve roots. The threshold of fatty filum is different from that of normal appearing FT. Triggered EMG plays an important role in untethering surgeries.

Abstract Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.

Abstract Objective To explore the clinical features, diagnosis, treatment and prognosis of Langerhans cell histiocytosis (LCH) of the skull in children. Methods This study retrospectively summarized the clinical manifestations, treatment methods and follow-up status of children with skull LCH who were admitted to the Department of Neurosurgery of Shanghai Children’s Hospital from January 2014 to June 2021. Results A total of 23 patients confirmed by histology as LCH received hospitalization treatment, including 14 males and 9 females, aged (5.76 ± 3.86) years old. The clinical manifestations were mostly incidentally discovered head masses that gradually enlarged (19 cases, 82.61%). Only 2 cases are affected by multiple systems, while the rest are affected by single systems. 9 patients were involved in multiple skull lesions, and 14 patients had local skull lesions. All patients underwent surgical intervention, with 17 patients undergoing total resection and 6 patients undergoing biopsy. 21 patients received chemotherapy after surgery. The median follow-up was 2.46 years (range 0.33–6.83 years). 21 patients had their symptoms and signs under control or even resolved, and 2 patients experienced recurrence during follow-up. The overall control rate reached 91.30%. Conclusion Personalized treatment plans according to different clinical types. Regular outpatient follow-up is crucial to monitor disease recurrence and late effects.

Abstract In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

The combination of mobile edge computing (MEC) and radio frequency-based wireless power transfer (WPT) presents a promising technique for providing sustainable energy supply and computing services at the network edge. This study considers a wireless-powered mobile edge computing system that includes a hybrid access point (HAP) equipped with a computing unit and multiple Internet of Things (IoT) devices. In particular, we propose a novel multi-user cooperation scheme to improve computation performance, where collaborative clusters are dynamically formed. Each collaborative cluster comprises a source device (SD) and an auxiliary device (AD), where the SD can partition the computation task into various segments for local processing, offloading to the HAP, and remote execution by the AD with the assistance of the HAP. Specifically, we aims to maximize the weighted sum computation rate (WSCR) of all the IoT devices in the network. This involves jointly optimizing collaboration, time and data allocation among multiple IoT devices and the HAP, while considering the energy causality property and the minimum data processing requirement of each device. Initially, an optimization algorithm based on the interior-point method is designed for time and data allocation. Subsequently, a priority-based iterative algorithm is developed to search for a near-optimal solution to the multi-user collaboration scheme. Finally, a deep learning-based approach is devised to further accelerate the algorithm’s operation, building upon the initial two algorithms. Simulation results show that the performance of the proposed algorithms is comparable to that of the exhaustive search method, and the deep learning-based algorithm significantly reduces the execution time of the algorithm.

Abstract Background Non-invasive diagnosis of distal tibiofibular syndesmosis instability (DTSI) was a great challenge to clinicians. We designed a new method, the Standing on single foot-Binding test, and investigated the accuracy of the test in the diagnosis of distal tibiofibular syndesmosis instability in adults with a history of ankle injury. Methods 85 participants with ankle injury were subjected to the Standing on single foot-Binding test, MRI and palpation to detect the distal tibiofibular syndesmosis instability (DTSI) and the findings were compared with ankle arthroscopic results. Both participants and arthroscopist were blind to the predicted results of the clinical tests. Sensitivity, specificity, PPV, NPV, LR+, LR − and their 95% CIs were calculated for each of the clinical tests as well as for the positive clinical diagnosis. Results The Standing on single foot-Binding test (SOSF-B test) outperformed MRI and palpation, in terms of sensitivity (87.5%/84.38%), specificity (86.79%/86.79%), PPV (80%/79.41%), NPV (92%/91.2%), LR+ (6.625/6.39), LR- (0.14/0.18) and diagnostic accuracy (87.06/85.88), among others, in the diagnosis of distal tibiofibular syndesmosis instability (DTSI). The diagnostic performance of 20° SOSF-B test was virtually identical to that of 0° SOSF-B test. According to the prevalence (28.7%) of DTSI and LR of four tests, the post-test probability could be used in clinical practice for the prediction of DTSI. Conclusion This prospective and double-blind diagnostic test showed that the SOSF-B test is clinically feasible for the diagnosis of distal tibiofibular syndesmosis instability (DTSI), and new diagnostic tools for rapid screening of distal tibiofibular syndesmosis instability (DTSI). Level of evidence II.

Abstract Reactive oxygen species (ROS), such as superoxides (O2 •−) and hydroxyl groups (OH·), are short-lived molecules containing unpaired electrons. Intracellular ROS are believed to be mainly produced by the mitochondria and NADPH oxidase (NOX) and can be associated with various physiological processes, such as proliferation, cell signaling, and oxygen homeostasis. In recent years, many studies have indicated that ROS play crucial roles in regulating ultraviolet (UV)-induced photodamage of the skin, including exogenous aging, which accounts for 80% of aging. However, to the best of our knowledge, the detailed signaling pathways, especially those related to the mechanisms underlying apoptosis in which ROS are involved have not been reviewed previously. In this review, we elaborate on the biological characteristics of ROS and its role in regulating UV-induced photodamage of the skin.

Abstract Copper-based catalysts serve as the predominant methanol steam reforming material although several fundamental issues remain ambiguous such as the identity of active center and the aspects of reaction mechanism. Herein, we prepare Cu/Cu(Al)O x catalysts with amorphous alumina-stabilized Cu2O adjoining Cu nanoparticle to provide Cu0−Cu+ sites. The optimized catalyst exhibits 99.5% CH3OH conversion with a corresponding H2 production rate of 110.8 μmol s−1 gcat −1 with stability over 300 h at 240 °C. A binary function correlation between the CH3OH reaction rate and surface concentrations of Cu0 and Cu+ is established based on kinetic studies. Intrinsic active sites in the catalyst are investigated with in situ spectroscopy characterization and theoretical calculations. Namely, we find that important oxygen-containing intermediates (CH3O* and HCOO*) adsorb at Cu0−Cu+ sites with a moderate adsorption strength, which promotes electron transfer from the catalyst to surface species and significantly reduces the reaction barrier of the C−H bond cleavage in CH3O* and HCOO* intermediates.

Background and objective The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. Methods We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. Results All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. Conclusion Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Background: Our goal was to add an auxiliary examination method for the detection of cervical cancer, and to further explore its application value in clinical staging and treatment. Methods: Shear wave elastography (SWE) technique was used to examine the cervical hardness of patients, and the maximum, mean and minimum values of elastic modulus were recorded, with differences being compared. The area under the receiver operating characreristic (ROC) curve and diagnostic efficacy of elastic modulus were compared with Medcalc software. The differences of elastic modulus values under different parameters were compared in the cervical cancer group. Results: The mean, maximum and minimum values of the cervical cancer group were all the highest, and the differences were statistically significant. The area under the ROC curves were 0.925, 0.909 and 0.873, respectively. For the mean and maximum values, the Youden indexes were 0.79 and 0.72, the positive likelihood ratios were 21.74 and 19.97, and the negative likelihood ratios were 0.18 and 0.25. The optimal cut-off point was 82.2 kilpoascal (kPa) for maximum value and was 66.5 kPa for mean value. Elastic modulus were all significantly different according to International Federation of Gynecology and Obstetrics (FIGO) stages and tumor lesion size. Also, elastic modulus of cervical cancer patients before and after radiotherapy were statistically significant. Conclusions: SWE technology has an application value in the detection of cervical cancer. The mean and maximum values have higher diagnostic accuracy. SWE technology also has potential clinical application value in the clinical staging and treatment of cervical cancer, but further studies with larger sample sizes are needed.

Single-machine due-window assignment scheduling with delivery times and variable processing times is investigated, where the variable processing time of a job means that the processing time is a function of its position in a sequence and its resource allocation. Currently, there are multiple optimization objectives for the due-window assignment problem, and there is a small amount of research on optimization problems where the window starting time, the rejected cost and the optimal scheduling are jointly required. The goal of this paper is to minimize the weighed sum of scheduling cost, resource consumption cost and outsourcing measure under the optional job outsourcing (rejection). Under two resource allocation models (i.e., linear and convex resource allocation models), the scheduling cost is the weighted sum of the number of early–tardy jobs, earliness–tardiness penalties and due-window starting time and size, where the weights are positional-dependent. The main contributions of this paper include the study and data simulation of single-machine scheduling with learning effects, delivery times and outsourcing cost. For the weighed sum of scheduling cost, resource consumption cost and outsourcing measure, we prove the polynomial solvability of the problem. Under the common and slack due-window assignments, through the theoretical analysis of the optimal solution, we reveal that four problems can be solved in O(n6) time, where n is the number of jobs.

Purpose: TNF family members (TFMs) play a crucial role in different types of cancers, with TNF Receptor Superfamily Member 19 (TNFRSF19) standing out as a particularly important member in this category. Further research is necessary to investigate the potential impact of TFMs on prognosis prediction and to elucidate the function and potential therapeutic targets linked to TNFRSF19 expression in gliomas. Methods: Three databases provided the data on gene expression and clinical information. Fourteen prognostic members were found through univariate Cox analysis and subsequently utilized to construct TFMs-based model in LASSO and multivariate Cox analyses. TFMs-based subtypes based on the expression profile were identified using an unsupervised clustering method. Machine learning algorithm identified key genes linked to prognostic model and subtype. A sequence of immune infiltrations was evaluated using the ssGSEA and ESTIMATE algorithms. Immunohistochemistry was used to examine the patterns of expression and the clinical significance of TNFRSF19. Results: Our development of a prognostic model and subtypes based on the TNF family was successful, resulting in accurate predictions of prognosis. The findings indicate that TNFRSF19 exhibited strong performance. Upregulation of TNFRSF19 was correlated with malignant phenotypes and poor prognosis, which was confirmed through immunohistochemistry. TNFRSF19 played a role in reshaping the immunosuppressive microenvironment in gliomas, and multiple drug-targeted TNFRSF19 molecules were identified. Conclusions: The TMF-based prognostic model and subtype can facilitate treatment decisions for glioma. TNFRSF19 is an outstanding representative of a predictor of prognosis and immunotherapy effect in gliomas.