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Abstract Disposal of unlawful interference incidents is essential for is crucial for the advancement of aviation security. Effective emergency disposal requires a comprehensive approach that includes the perspectives of airlines, airports, and passengers. In this context, each component of the disposal process can fail randomly. The objective of this research is to optimize emergency disposal decisions to enhance the efficiency of civil aviation operations, reduce accidents, and lower costs. Given the dynamic complexity of unlawful interference incidents, a dynamic fault tree consisting of 26 nodes was constructed to analyze the emergency disposal process. To explore the relationships and priorities of each event, the Dynamic Fault Tree is converted into a dynamic Bayesian network. Based on historical statistical data, simulation analysis is conducted in three aspects: posterior probability, sensitivity, and importance. Simulation results reveal that the top three critical nodes in cabin unlawful interference incidents are “structural damage to the cabin,” “inadequate training by airlines,” and “untimely airport police takeover of disruptive passengers.” Further analysis shows that (1) most of the critical nodes are associated with airlines. (2) The decision-making rationale and pathways of the critical nodes can be clearly observed and prioritized. (3) Besides airlines, other entities such as airports can implement targeted emergency disposal measures. Through quantitative analysis and simulation, this study provides decision-making guidance for participating groups on dynamic emergency disposal, thereby enhancing civil aviation security.

Abstract Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.

Abstract Background Studies on the prevalence of suicidal ideation (SI) and its associated factors among the elderly in China show considerable variability. This meta-analysis aims to clarify the epidemiological features of SI in this population. Methods We systematically searched English and Chinese databases for relevant literature up to September 15, 2022. The extracted data facilitated the calculation of prevalence and odds ratios (ORs) for factors associated with SI among China’s elderly. Results We analyzed 31 cross-sectional studies, comprising a total of 79,861 participants from over 20 provinces and municipalities. The pooled prevalence of SI was found to be 11.47% [95% confidence interval (CI): 7.82–15.71%]. Significant variations in prevalence were influenced by residence, physical health (including chronic diseases and daily living capabilities), mental health (depressive symptoms and life satisfaction), economic status, and time-specific assessment tools. Notably, the prevalence from 2011–2020 (15.59%, 95% CI: 9.08–23.44%) was almost double that of 2001–2010 (7.85%, 95% CI: 5.08–11.16%). The SI prevalence in the eastern region (8.06%, 95% CI 5.59–10.94%) was significantly lower than in the central and western regions (16.97%, 95% CI 12.04–22.53%). Fourteen factors exhibited a significant pooled OR greater than 1 (p

Abstract Characterizing the evolution of mechanical properties of hot dry rock (HDR) after supercritical CO2 (CO2(sc)) injection is crucial for assessing the heat extraction rate and reservoir security of CO2 based enhanced geothermal systems. This study designed the experiments of triaxial seepage and mechanical properties considering no CO2(sc) injection, CO2(sc) injection, and alternating injection of water-CO2(sc) (AIWC) in granite at 150–300 ℃. The experiments can reveal the mechanical properties of HDR in single-phase CO2 zone, CO2-water two-phase zone and dissolved CO2 liquid phase zone in HDR reservoir. The results indicate that the failure mode of the rock samples primarily exhibits sudden instability after no CO2(sc) injection and AIWC, whereas it predominantly manifests progressive instability after CO2(sc) injection. Compared with 25 ℃, the uniaxial compressive strength (UCS) after no CO2(sc) injection at 150–300 ℃ decreased by 13.86%–32.92%. After CO2(sc) injection, the UCS decreased by 40.79%–59.60%. After AIWC, the UCS decreased by 27.74–40.48%. This shows that the strength of rock mass in the single-phase CO2 zone is lower than that in the other two zones, and this weakening phenomenon increases with the increase of temperature difference. At the same temperature, the elasticity modulus after AIWC was greater than that after no CO2(sc) injection and CO2(sc) injection. With no CO2(sc) injection, when the temperature was increased to 200 ℃ and 300 ℃, intergranular cracks and transgranular appeared respectively. After AIWC, mineral crystals such as calcite were precipitated on the surfaces of the connected large cracks, accompanied by kaolinite clay minerals. This increases the frictional contact of the mineral particles and enhances the stability of the HDR reservoir.

Abstract Subarachnoid hemorrhage (SAH) significantly compromises the blood-brain barrier (BBB) and impairs patient recovery. This study elucidates the critical role of astrocytic Neogenin-1 (NEO1) in BBB integrity post-SAH and examines the regulatory effects of hepcidin on endothelial cell (EC) function amid NEO1-mediated disruptions in iron homeostasis. Proteomic analyses of cerebrospinal fluid (CSF) from SAH patients revealed a substantial decrease in NEO1 expression, identifying it as a key factor in BBB integrity. 111 CSF proteins were significantly reduced in early SAH stages (days 1–3), with NEO1 among the most significantly altered. This dysregulation was linked to poorer patient outcomes, as indicated by a negative correlation between NEO1 levels and Modified Rankin Scale scores six months post-SAH (R = −0.4743, P

Abstract With the development of smart technology and aging societies, the living and housing environments for older people are undergoing transformation. Designers must understand the changing capabilities, lifestyles, preferences, and inspirations of older people for their future homes, in which the kitchen is seen as the heart. To gain a deeper understanding of the requirements of older people in promoting healthier lifestyles and inclusive daily practices, the authors identified five key factors of kitchen design through a literature review, developing an initial model. Subsequently, a focus group was conducted in the UK to explore the perspectives and expectations of older people, where metaphors for future kitchens were collected, and further insights were used to refine the model. The refined model for a future-inclusive kitchen encompasses six dimensions: Environment/space, Technology/interaction, Emotion/affect, Health and safety, Human factors and well-being, and Sustainability. Through using metaphors, this study offers a multidimensional lens to investigate the future user experience of inclusive kitchens. The significance of this study lies in the originality of combining a literature review, and user study with design metaphors. A future-proof inclusive kitchen design model is proposed to provide guidance for future design directions of age-friendly environments.

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Abstract Background Childbirth pain is a physiological phenomenon during the delivery process, the intense pain of childbirth could bring harmful effects to pregnant women and their babies. Assessment of childbirth pain is the first step in childbirth pain intervention. Some pain assessment scales have shortcomings such as interfering in the birthing process and affecting pain perception during delivery, while the Rating Scale of Pain Expression during Childbirth (ESVADOPA) could be used as an auxiliary scale to compensate for these shortcomings. The purpose of this study was to introduce the ESVADOPA and adapt it among Chinese pregnant women to check on the psychometric properties of the translated version of ESVADOPA. Methods A new translation model based on Brislin’s classical back translation model was used to translate and cross-cultural adapt the ESVADOPA. During June 2021 and June 2022, pregnant women at Shandong Provincial Hospital Affiliated to Shandong First Medical University were invited. In the stage of translation and cross-culturally adaptation, 18 midwives and 30 pregnant women were invited to participate in the first round of pre-experiment. And in the second round of pre-experiment, 15 midwives and 20 pregnant women were invited to participate. The Chinese version of ESVADOPA was tested on a group of pregnant women (N = 487). Construct validity was evaluated by exploratory factor analysis, confirmatory factor analysis and criterion-related validity. Reliability was assessed by Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability and Guttman split-half reliability. Results The item statistical analysis and construct validity resulted in six items and one factor that explained 61.064% of the total variance. Confirmatory factor analysis showed that the data fit the one-factor structure. Criterion-related validity indicated that the scale is significantly and positively correlated with the Numeric Rating Scale (NRS). Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability, and Guttman split-half reliability of the Chinese version of ESVADOPA were 0.868, 0.896, 0.845, 0.842, respectively. Conclusion The Chinese version of the ESVADOPA with good reliability and validity data could be used to assess the pain rating of pregnant women during childbirth without interfering in the birthing process.

Abstract Background Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. Methods This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. Results The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. Conclusions The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the phylogenetic relationships of certain species remain unclear. In this study, we sequenced and obtained complete mitochondrial DNA (mtDNA) from Actitis hypoleucos and partial mtDNA from Numenius arquata, Limosa limosa, and Limnodromus semipalmatus. The complete mtDNA contained 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 tRNA genes, and a control region. Scolopacidae contained three types of start codons and five types of stop codons (including one incomplete stop codon, T--). In 13 protein-coding genes, average uncorrected pairwise distances (Aupd) revealed that ATP8 was the least conserved while COX3 had the lowest evolutionary rate. The ratio of Ka/Ks suggested that all PCGs were under purifying selection. Using two methods (maximum likelihood and Bayesian inference) to analyze the phylogenetic relationships of the family Scolopacidae, it was found that the genera Xenus and Actitis were clustered into another sister group, while the genus Phalaropus is more closely related to the genus Tringa. The genera Limnodromus, Gallinago, and Scolopax form a monophyletic group. This study improves our understanding of the evolutionary patterns and phylogenetic relationships of the family Scolopacidae.

Abstract Gas outbursts pose a significant threat in the mining of deep low‐permeability coal seams. As mining depth increases, there is a rise in coal and gas dynamic disasters, rendering the gas outburst prevention technology from shallow mining areas unsuitable for deep coal seam exploitation. Addressing the challenges posed by deep, highly gassy coal seams, this study introduces a gas outburst prevention technology integrating destressing in the close distance underlying roadway with gas drainage. The article investigates the relevant technical parameters and assesses the feasibility of this approach. First, it establishes destressing model for the underlying roadway to derive an analytical solution for stress distribution in the coal seam. Second, appropriate technical parameters are designed considering the seepage characteristics of gas in the coal seam. Finally, the gas drainage technical scheme is implemented at Qujiang coal mine to verify its on‐site effectiveness. Field test results indicate an increase in gas permeability within the coal seam following destressing in the underlying roadway, accompanied by significant improvements in the efficiency of gas drainage and the advancement speed of the coal roadway. Specifically, the driving speed of the coal roadway has escalated from 40 m/month to 150 m/month. These outcomes demonstrate the potential of this technology as a promising approach for preventing gas outbursts in the challenging context of deep, low‐permeability coal seams, facilitating swift coal roadway excavation.

Abstract We compute four-point functions with two maximal giant gravitons and two chiral primary operators at three-loop order in planar N $$ \mathcal{N} $$ = 4 Super-Yang-Mills theory. The Lagrangian insertion method, together with symmetries of the theory fix the integrand up to a few constants. Under the additional assumption of planarity, all these constants can be determined by lower loop data. The obtained result can be regarded as the planar diagram contribution to the full four-point function and is written in terms of the known three-loop conformal integrals. From the four-point function, we extract the OPE coefficients of two giant gravitons and one non-BPS twist-2 operator with arbitrary spin at three-loops, given in terms of harmonic sums. We observe an intriguingly simple relation between the giant graviton OPE coefficients and the OPE coefficients of three single-trace operators.

On April 29, 2020, China entered a normalization stage of prevention and control. By December 2021, more than 40 outbreaks had occurred in China, which reflected the shortcomings of the pandemic prevention and control measures in China at that time. As the capital city of China, Beijing faces more pressure in epidemic prevention and control. We used the COVID-19 cluster containment evaluation indicators to determine the effects of prevention and control measures on four COVID-19 outbreaks in Beijing. After considering the specificity and operability of evaluation indicators and the availability of evaluation data, the evaluation system in our study consisted of six dimensions: epidemic prevention and control effect, discovery and detection ability, precision prevention and control capability, public protection effect, medical treatment and nosocomial infection prevention and control ability, and information release and public opinion response ability. The composite scores of the prevention and control effects of the Xinfadi, Shunyi, Daxing, and Ejina Banner–associated COVID-19 outbreaks in Beijing were 62, 82, 87, and 76, respectively. In the six dimensions, the epidemic prevention and control effect, discovery and detection ability, precision prevention and control capability, and public protection effect scores for the Xinfadi outbreak were lower than those for the Shunyi, Daxing and Ejina Banner–associated outbreaks. The medical treatment and nosocomial infection prevention and control ability scores for the outbreak associated with Ejina Banner were lower than those for the Xinfadi, Shunyi, and Daxing outbreaks. In managing cluster outbreaks, Beijing was able to detect index cases early enough to reduce the scale and duration of the outbreak and consistently release official information to reduce public panic, standardize the management of centralized quarantine sites to prevent cross-infection, adhere to the “dynamic COVID‐zero” strategy to accurately prevent and control outbreaks, reduce the societal influence of the pandemic, and coordinate the epidemic prevention and control and socio-economic development.

Abstract Background The flower colour of H. syriacus ‘Qiansiban’ transitions from fuchsia to pink–purple and finally to pale purple, thereby enhancing the ornamental value of the cultivars. However, the molecular mechanism underlying this change in flower colour in H. syriacus has not been elucidated. In this study, the transcriptomic data of H. syriacus ‘Qiansiban’ at five developmental stages were analysed to investigate the impact of flavonoid components on flower colour variation. Additionally, five cDNA libraries were constructed from H. syriacus ‘Qiansiban’ during critical blooming stages, and the transcriptomes were sequenced to investigate the molecular mechanisms underlying changes in flower colouration. Results High-performance liquid chromatography‒mass spectrometry detected five anthocyanins in H. syriacus ‘Qiansiban’, with malvaccin-3-O-glucoside being the predominant compound in the flowers of H. syriacus at different stages, followed by petunigenin-3-O-glucoside. The levels of these five anthocyanins exhibited gradual declines throughout the flowering process. In terms of the composition and profile of flavonoids and flavonols, a total of seven flavonoids were identified: quercetin-3-glucoside, luteolin-7-O-glucoside, Santianol-7-O-glucoside, kaempferol-O-hexosyl-C-hexarbonoside, apigenin-C-diglucoside, luteolin-3,7-diglucoside, and apigenin-7-O-rutinoside. A total of 2,702 DEGs were identified based on the selected reference genome. Based on the enrichment analysis of differentially expressed genes, we identified 9 structural genes (PAL, CHS, FLS, DRF, ANS, CHI, F3H, F3’5’H, and UFGT) and 7 transcription factors (3 MYB, 4 bHLH) associated with flavonoid biosynthesis. The qRT‒PCR results were in good agreement with the high-throughput sequencing data. Conclusion This study will establish a fundamental basis for elucidating the mechanisms underlying alterations in the flower pigmentation of H. syriacus.

Abstract. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers, MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged by MALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically, MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

Abstract Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Abstract Background Over the past three decades, China has experienced significant changes in urban-rural, gender, and age-specific suicide mortality patterns. This study aimed to investigate the long-term trends in suicide mortality in China from 1987 to 2020. Methods Suicide mortality data were obtained from China’s National Health Commission. Joinpoint regression analysis was used to examine changes in trends and age-period-cohort modeling to estimate age, period, and cohort effects on suicide mortality from 1987 to 2020. Net drift, local drift, longitudinal age curves, and period relative risks were also calculated. Results Crude and age-standardized suicide mortality in China showed continuing downward trends from 1987 to 2020, with a more pronounced decrease in rural areas (net drift = -7.07%, p

Background: Prolonged length of stay (LOS) of sepsis can drain a hospital's material and human resources. This study investigated the correlations between T helper type 17 (Th17) and regulatory T (Treg) balance with LOS in sepsis. Methods: A prospective clinical observational study was designed in Changhai Hospital affiliated to Naval Medical University in Shanghai, China, from January to October 2020. The patients diagnosed with sepsis and who met the inclusion and exclusion criteria were recruited and whether the levels of cytokines, procalcitonin, subtypes, and biomarkers of T cells in the peripheral blood were detected. We analyzed the correlation between these and LOS. Results: Sixty septic patients were classified into two groups according to whether their intensive care unit (ICU) stay exceeded 14 days. The patients with LOS ≥14 days were older ([72.6±7.5] years vs. [63.3±10.4] years, P=0.015) and had higher Sequential Organ Failure Assessment (SOFA) (median [interquartile range]: 6.5 [5.0–11.0] vs. 4.0 [3.0–6.0], P=0.001) and higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (16.0 [13.0–21.0] vs. 8.5 [7.0–14.0], P=0.001). There was no difference in other demographic characteristics and cytokines, interleukin-6, tumor necrosis factor-α, and interleukin-10 between the two groups. The Th17/Treg ratio of sepsis with LOS

Abstract Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis—an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression. Methods Via the analysis of whole-exome sequencing results of tumor samples from 90 ovarian cancer patients, we compared the mutational landscape of ovarian cancer patients with that of TCGA patients to identify similarities and differences. The sequencing data were subjected to bioinformatics analysis to explore tumor driver genes and their functional roles. Furthermore, we conducted basic medical experiments to validate the results obtained from the bioinformatics analysis. Results Whole-exome sequencing revealed the mutational profile of HGSOC, including BRCA1, BRCA2 and TP53 mutations. AP3S1 emerged as the most weighted tumor driver gene. Further analysis of AP3S1 mutations and expression demonstrated their associations with patient survival and the tumor immune response. AP3S1 knockdown experiments in ovarian cancer cells demonstrated its regulatory role in tumor cell migration and invasion through the TGF-β/SMAD pathway. Conclusion This comprehensive analysis of somatic mutations in HGSOC provides insight into potential therapeutic targets and molecular pathways for targeted interventions. AP3S1 was identified as being a key player in tumor immunity and prognosis, thus providing new perspectives for personalized treatment strategies. The findings of this study contribute to the understanding of HGSOC pathogenesis and provide a foundation for improved outcomes in patients with this aggressive disease.

BackgroundFor medical diagnosis, clinicians typically begin with a patient’s chief concerns, followed by questions about symptoms and medical history, physical examinations, and requests for necessary auxiliary examinations to gather comprehensive medical information. This complex medical investigation process has yet to be modeled by existing artificial intelligence (AI) methodologies. ObjectiveThe aim of this study was to develop an AI-driven medical inquiry assistant for clinical diagnosis that provides inquiry recommendations by simulating clinicians’ medical investigating logic via reinforcement learning. MethodsWe compiled multicenter, deidentified outpatient electronic health records from 76 hospitals in Shenzhen, China, spanning the period from July to November 2021. These records consisted of both unstructured textual information and structured laboratory test results. We first performed feature extraction and standardization using natural language processing techniques and then used a reinforcement learning actor-critic framework to explore the rational and effective inquiry logic. To align the inquiry process with actual clinical practice, we segmented the inquiry into 4 stages: inquiring about symptoms and medical history, conducting physical examinations, requesting auxiliary examinations, and terminating the inquiry with a diagnosis. External validation was conducted to validate the inquiry logic of the AI model. ResultsThis study focused on 2 retrospective inquiry-and-diagnosis tasks in the emergency and pediatrics departments. The emergency departments provided records of 339,020 consultations including mainly children (median age 5.2, IQR 2.6-26.1 years) with various types of upper respiratory tract infections (250,638/339,020, 73.93%). The pediatrics department provided records of 561,659 consultations, mainly of children (median age 3.8, IQR 2.0-5.7 years) with various types of upper respiratory tract infections (498,408/561,659, 88.73%). When conducting its own inquiries in both scenarios, the AI model demonstrated high diagnostic performance, with areas under the receiver operating characteristic curve of 0.955 (95% CI 0.953-0.956) and 0.943 (95% CI 0.941-0.944), respectively. When the AI model was used in a simulated collaboration with physicians, it notably reduced the average number of physicians’ inquiries to 46% (6.037/13.26; 95% CI 6.009-6.064) and 43% (6.245/14.364; 95% CI 6.225-6.269) while achieving areas under the receiver operating characteristic curve of 0.972 (95% CI 0.970-0.973) and 0.968 (95% CI 0.967-0.969) in the scenarios. External validation revealed a normalized Kendall τ distance of 0.323 (95% CI 0.301-0.346), indicating the inquiry consistency of the AI model with physicians. ConclusionsThis retrospective analysis of predominantly respiratory pediatric presentations in emergency and pediatrics departments demonstrated that an AI-driven diagnostic assistant had high diagnostic performance both in stand-alone use and in simulated collaboration with clinicians. Its investigation process was found to be consistent with the clinicians’ medical investigation logic. These findings highlight the diagnostic assistant’s promise in assisting the decision-making processes of health care professionals.

Abstract Herein, the use of economically and environmentally friendly bis(pinacolato)diboron (B2Pin2) is described as a non‐metallic reductant in mediating Ni‐catalyzed C(sp3)–C(sp2) reductive cross‐coupling of alkyl electrophiles with aryl/vinyl halides. This method exhibits excellent suitability for heteroaryl halides and alkyl halides/Katritzky salts. The present study is compatible with an in situ halogenation of alcohol method, allowing for selective mono‐functionalization of diols and bio‐relevant alcohols (e.g., carbohydrates). The use of B2Pin2 shows potential for easy scalability without introducing additional metal impurities into the products. It is observed for the first time in the realm of cross‐electrophile coupling chemistry that B2Pin2 can sever as a reductant to reduce NiII to Ni0. This mechanistic insight may inspire the development of new reductive bond‐forming methodologies that can otherwise be difficult to achieve with a metal reductant.

Abstract The dynamic regulation of thermal radiation in the mid‐infrared region is technologically important in diverse applications such as thermal management and camouflage. However, there is a notable lack of research on the combination of infrared radiators and memristors, which can maintain previous states or modes without extra power consumption. Here, a memristive mid‐infrared radiator, where graphene nanoribbon grating serves simultaneously as a floating gate for charge storage and a tunable infrared nanoantenna for thermal radiation is proposed. This design enables precise and fast modulation, low power consumption, and scalability. Even a small change of one attocoulomb in the stored charge can produce a 1‐µm peak shift in the absorption peak. This work provides a platform for a memristive infrared thermal radiator that can be further exploited for electrochromic glazing or on‐chip radiative cooling.

Summary: The origin and evolution of trilobated body plan of the Artiopoda, a group of epibenthic euarthropods from Cambrian Lagerstätten, remain unclear. Here we examine old and new specimens of Urokodia aequalis, one of euarthropods from the Chengjiang biota, revealing new morphological details and revising its taxonomy. Urokodia possesses an elongate body with a five-segmented head, a thorax with 13–15 tergites, and a three-segmented pygidium with well-defined axial region. The ventral morphology includes paired stalked eyes, one fleshy antenna pair, the following homogeneous head and thoracic appendages, each with an annular proximal-element, an articulated stenopodous branch and a lamellar flap, and the pygidial appendages solely consisting of lamellar flaps. Cladistic analyses resolved Urokodia as the basal-most member of the Artiopoda, offering a hypothesis of the initial origin of trilobation in the pygidium. The new data, in conjunction with the presence of the elongated body plan across major lineages of euarthropods, suggest a convergent evolution of this trait.

In the study of cavitation in room-temperature fluids, the heat transfer between gas and liquid in bubble oscillation is usually assumed to be an adiabatic process for simplification. However, this heat transfer and thermodynamic mechanism is not yet understood in cryogenic fluids, especially under small amplitude oscillation conditions excited by ultrasonic field. This article studies bubble thermodynamic model under an external ultrasonic field based on the heat transfer equation for cryogenic fluids. The temperature changes inside bubbles are calculated, and the heat transfer mechanism is briefly analyzed. The results indicate that the heat transfer mechanism of bubbles depends on the relationship between ultrasonic frequency and bubble resonance frequency. By analyzing two special cases of dual-bubble and high-pressure environment, it is believed that heat transfer can be approximated as an adiabatic process under high-pressure conditions with ultrasonic frequency far from the resonance frequency. This conclusion can provide a theoretical basis for subsequent accurate calculation of heat-transfer polytropic coefficient, or void faction measurement in cryogenic two-phase flow.

Abstract cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

Abstract Background Guillain–Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. Methods Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 − 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. Results P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. Conclusions Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.

Abstract The sterile insect technique is based on the overflooding of a target population with released sterile males inducing sterility in the wild female population. It has proven to be effective against several insect pest species of agricultural and veterinary importance and is under development for Aedes mosquitoes. Here, we show that the release of sterile males at high sterile male to wild female ratios may also impact the target female population through mating harassment. Under laboratory conditions, male to female ratios above 50 to 1 reduce the longevity of female Aedes mosquitoes by reducing their feeding success. Under controlled conditions, blood uptake of females from an artificial host or from a mouse and biting rates on humans are also reduced. Finally, in a field trial conducted in a 1.17 ha area in China, the female biting rate is reduced by 80%, concurrent to a reduction of female mosquito density of 40% due to the swarming of males around humans attempting to mate with the female mosquitoes. This suggests that the sterile insect technique does not only suppress mosquito vector populations through the induction of sterility, but may also reduce disease transmission due to increased female mortality and lower host contact.

Abstract Background Arthritis primarily affects older people and is a prominent cause of their activity impairment. This study aimed to examine the mediating role of depressive symptoms in the relationship between social participation and activity impairment, as well as to determine whether sex moderated the mediating effect. Methods A total of 2247 older patients with arthritis were included from the China Health and Retirement Longitudinal Study between 2015 and 2018. We first examined a simple mediation model where depressive symptoms were a mediator between social participation and activity impairment. Furthermore, sex was systematically integrated into the model as a moderator. The mediation model and moderated mediation model were analyzed using PROCESS macro. Results Mediation analysis revealed that the association between social participation and activity impairment was partially mediated by depressive symptoms (B = -0.10, 95% CI = [-0.14, -0.06]) with intermediary effect of 28.6%. Moderated mediation analysis indicated that mediation model was moderated by sex. The indirect effect of social participation on activity impairment among female patients (B = -0.15, 95% CI = [-0.21, -0.09]) was stronger than male patients (B = -0.04, 95% CI = [-0.09, -0.01]). Conclusion Social participation was the key protective factor associated with depressive symptoms and activity impairment among arthritis patients. Encouraging arthritis patients to social participation and improving the depressive symptoms might avoid activity impairment, especially for female patients.

Abstract Service continuity (SC) plays an important role in service industry. In this paper, a daily home parcel pick‐up scheduling and routing problem is studied with SC consideration. In this context, a fixed group of couriers is assigned to provide services exclusively within a specific region. Each day, customers within this region either have pre‐scheduled services in advance or stochastically make service requests during the couriers' shifts. Pre‐scheduled service request can be serviced by any courier serving the region, while stochastic service request can only be serviced by the courier most familiar with the corresponding customer. Consequently, the study problem is divided into two distinct sub‐problems: (i) the allocation of pre‐scheduled requests to couriers before their tours start and (ii) routing each courier independently to service both its allocated customers and its potential stochastic customers. The sub‐problem (ii) is formulated as a Markov decision process and an existing dynamic programming method is applied to solve it exactly. For the sub‐problem (i), Greedy Randomized Adaptive Search Procedure‐based meta‐heuristics is proposed. Finally, these meta‐heuristics are evaluated through computational experiments, yielding valuable application insights.

Abstract Pancreatitis is a crucial risk factor for pancreatic ductal adenocarcinoma (PDAC), and our previous study had proved high-temperature requirement protein A1 (HTRA1) exacerbates pancreatitis insult; however, the function and mechanism of HTRA1 in pancreatitis-initiated PDAC is still unclear. In the present paper, we clarified the expression of HTRA1 in PDAC using bioinformatics and immunohistochemistry of tissue chip, and found that HTRA1 is significantly upregulated in PDAC. Moreover, the proliferation, migration, invasion and adhesion of PANC-1 and SW1990 cells were promoted by overexpression of HTRA1, but inhibited by knockdown of HTRA1. Meanwhile, we found that HTRA1 arrested PANC-1 and SW1990 cells at G2/M phase. Mechanistically, HTRA1 interacted with CDK1 protein, and CDK1 inhibitor reversed the malignant phenotype of PANC-1 and pancreatitis-initiated PDAC activated by HTRA1 overexpression. Finally, we discovered a small molecule drug that can inhibit HTRA1, carfilzomib, which has been proven to inhibit the biological functions of tumor cells in vitro and intercept the progression of pancreatitis-initiated PDAC in vivo. In conclusion, the activation of HTRA1-CDK1 pathway promotes the malignant phenotype of tumor cells by blocking the cell cycle at the G2/M phase, thereby accelerating pancreatitis-initiated PDAC. Carfilzomib is an innovative candidate drug that can inhibit pancreatitis-initiated PDAC through targeted inhibition of HTRA1.

The electrochemical oxidation of biomass molecules coupling with hydrogen production is a promising strategy to obtain both green energy and value-added chemicals; however, this strategy is limited by the competing oxygen evolution reactions and high energy consumption. Herein, we report a hierarchical CoNi layered double hydroxides (LDHs) electrocatalyst with abundant Ni vacancies for the efficient anodic oxidation of 5-hydroxymethylfurfural (HMF) and cathodic hydrogen evolution. The unique hierarchical nanosheet structure and Ni vacancies provide outstanding activity and selectivity toward several biomass molecules because of the finely regulated electronic structure and highly-exposed active sites. In particular, a high faradaic efficiency (FE) at a high current density (99% at 100 mA cm−2) is achieved for HMF oxidation, and a two-electrode electrolyzer is assembled based on the Ni vacancies-enriched LDH, which realized a continuous synthesis of highly-pure 2,5-furandicarboxylic acid products with high yields (95%) and FE (90%).

Objective This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps.Methods We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis.Results This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21–3.19, p

Walnut kernel (WK) is a globally popular health food known for its potent antioxidant properties. WK shows a promising prospect in protecting against liver damage induced by salt processed psoraleae fructus (SPF). This study explored the impact of WK in mitigating liver damage induced by SPF in an ovariectomized (OVX) rat model. Serum metabolomics was employed to explore potential detoxification mechanisms. The levels of Farnesoid X receptor (FXR), Bile salt export pump (BSEP), and Cholesterol 7α-hydroxylase (CYP7A1) proteins were determined through western blot analysis. The results demonstrated that WK exhibits a noteworthy protective effect against liver damage induced by SPF. The WK normalized the metabolic disorder and reversed sixteen liver injury biomarkers and five metabolic pathways induced by SPF. These results demonstrated that WK exhibits a protective effect against SPF-induced liver damage in OVX rats by regulating bile acid metabolism.

Abstract Using stable isotope analysis, we assessed the relative contributions of the main protein contributors fishmeal, soya and sunflower meal to mature abalone muscle and gonad tissue over 1 year. Prerequisites for the use of stable isotope mixing models were established in this species. The δ13C and δ15N discrimination factors and turnover rates were influenced by diet composition, and there were tissue‐specific and sex‐specific differences. Abalone were fed the two combination diets (fishmeal–soya and fishmeal–sunflower meal) grew at similar rates. However, feed was most efficiently utilised in abalone fed a combination of fishmeal and soya. The relative contribution of fishmeal, soya and sunflower meal to female and male abalone tissue growth fluctuated throughout the 1‐year study. Overall, fishmeal contributed over 50% of the gonad (54%–82%) and muscle (54%–84%) tissue growth in females. Similarly, fishmeal contributed over 50% of gonad tissue growth of male abalone, ranging from 59% to 87%, while the contribution to meat tissue growth in males ranged from 44% to 94%. These findings support the importance of laboratory studies when using stable isotope analysis and mixing models for nutrient allocation in aquaculture.

Abstract Background Normalized decision support system for lumbar disc herniation (LDH) will improve reproducibility compared with subjective clinical diagnosis and treatment. Magnetic resonance imaging (MRI) plays an essential role in the evaluation of LDH. This study aimed to develop an MRI‐based decision support system for LDH, which evaluates lumbar discs in a reproducible, consistent, and reliable manner. Methods The research team proposed a system based on machine learning that was trained and tested by a large, manually labeled data set comprising 217 patients' MRI scans (3255 lumbar discs). The system analyzes the radiological features of identified discs to diagnose herniation and classifies discs by Pfirrmann grade and MSU classification. Based on the assessment, the system provides clinical advice. Results Eventually, the accuracy of the diagnosis process reached 95.83%. An 83.5% agreement was observed between the system's prediction and the ground‐truth in the Pfirrmann grade. In the case of MSU classification, 95.0% precision was achieved. With the assistance of this system, the accuracy, interpretation efficiency and interrater agreement among surgeons were improved substantially. Conclusion This system showed considerable accuracy and efficiency, and therefore could serve as an objective reference for the diagnosis and treatment procedure in clinical practice.

ObjectiveJianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth.Methods300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF.ResultsJPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration.ConclusionThese findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration.

Abstract With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all‐in‐one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch‐type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid‐state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3–4.5 V), the pouch‐type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self‐generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch‐type cells are attributed to the robust and stable anion‐induced electrode‐electrolyte interphases and local solid‐state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high‐performance batteries.

BackgroundA new aging biomarker epigenetic clock has been developed. There exists a close link between aging and gut microbiota, which may be mediated by inflammatory cytokines. However, the relationship between the epigenetic clock, gut microbiota, and the mediating substances is unclear.MethodsTwo large genome-wide association meta-analyses were analyzed by two-sample Mendelian randomization. The results between gut microbiota and epigenetic clock were investigated using the four methods (Inverse variance weighted, MR-Egger, weighted median, MR-PRESSO). Genetic correlation was measured by Linked disequilibrium score regression (LDSC). The correctness of the study direction was checked by the Steiger test. Cochran’s Q statistic and MR-Egger intercept were used as sensitivity analyses of the study. The two-step method was used to examine the mediating role of inflammatory cytokines. We use the Benjamini-Hochberg correction method to correct the P value.ResultsAfter FDR correction, multiple bacterial genera were significantly or suggestively associated with four epigenetic clocks (GrimAge, HannumAge, IEAA, PhenoAge). And we detected several inflammatory factors acting as mediators of gut microbiota and epigenetic clocks.ConclusionThis study provides genetic evidence for a positive and negative link between gut microbiota and aging risk. We hope that by elucidating the genetic relationship and potential mechanisms between aging and gut microbiota, we will provide new avenues for continuing aging-related research and treatment.

Cognitive impairment (CI) has been reported in 29–70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1–4, WM1–8, WM2–6, WM2–7, WM2–8, WM4–8, WM5–8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.

Introduction The invasion of important structures in locally advanced thyroid cancer (LATC) hinders radical resection, increases the risk of recurrence and even prevents surgery. Creating the opportunity for radical operation in patients with LATC is critical for improving their prognosis. Multitarget tyrosine kinase inhibitors were used as neoadjuvant therapy in several studies. Donafenib produced survival benefits over placebo in Chinese patients with radioiodine-refractory differentiated thyroid cancer in a recent study, but its efficacy in the neoadjuvant setting remains unknown. This study thus aims to assess the efficacy and safety of donafenib as neoadjuvant therapy in LATC.Methods and analysis DONATHYCA is a prospective, exploratory, single-arm phase II study evaluating the efficacy and safety of donafenib as neoadjuvant therapy in patients with LATC. 13 patients will be enrolled. The primary endpoint is the objective response rate as per Response Evaluation Criteria in Solid Tumours V.1.1. The secondary objectives include progression-free survival, the duration of response, the disease control rate, the R0/R1 resection rate, quality of life and toxicity during treatment according to Common Terminology Criteria for Adverse Events V.4.0. Patients will receive donafenib 300 mg two times a day continuously in a 21-day treatment cycle for six cycles.Ethics and dissemination This study was approved by the Ethics Committee of Fujian Cancer Hospital (K2023-144-02) on 27 July 2023 and registered in the China Clinical Trial Registry on 20 September 2023. The results of the study will be presented at academic conferences and published in scientific publications.Trial registration number ChiCTR2300075973

BackgroundChannel selection has become the pivotal issue affecting the widespread application of non-invasive brain-computer interface systems in the real world. However, constructing suitable multi-objective problem models alongside effective search strategies stands out as a critical factor that impacts the performance of multi-objective channel selection algorithms. This paper presents a two-stage sparse multi-objective evolutionary algorithm (TS-MOEA) to address channel selection problems in brain-computer interface systems.MethodsIn TS-MOEA, a two-stage framework, which consists of the early and late stages, is adopted to prevent the algorithm from stagnating. Furthermore, The two stages concentrate on different multi-objective problem models, thereby balancing convergence and population diversity in TS-MOEA. Inspired by the sparsity of the correlation matrix of channels, a sparse initialization operator, which uses a domain-knowledge-based score assignment strategy for decision variables, is introduced to generate the initial population. Moreover, a Score-based mutation operator is utilized to enhance the search efficiency of TS-MOEA.ResultsThe performance of TS-MOEA and five other state-of-the-art multi-objective algorithms has been evaluated using a 62-channel EEG-based brain-computer interface system for fatigue detection tasks, and the results demonstrated the effectiveness of TS-MOEA.ConclusionThe proposed two-stage framework can help TS-MOEA escape stagnation and facilitate a balance between diversity and convergence. Integrating the sparsity of the correlation matrix of channels and the problem-domain knowledge can effectively reduce the computational complexity of TS-MOEA while enhancing its optimization efficiency.

Summary: Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord’s significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-μm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.

Abstract Exosomes are indispensable for intercellular communications. Tumor microenvironment (TME) is the living environment of tumor cells, which is composed of various components, including immune cells. Based on TME, immunotherapy has been recently developed for eradicating cancer cells by reactivating antitumor effect of immune cells. The communications between tumor cells and TME are crucial for tumor development, metastasis, and drug resistance. Exosomes play an important role in mediating these communications and regulating the reprogramming of TME, which affects the sensitivity of immunotherapy. Therefore, it is imperative to investigate the role of exosomes in TME reprogramming and the impact of exosomes on immunotherapy. Here, we review the communication role of exosomes in regulating TME remodeling and the efficacy of immunotherapy, as well as summarize the underlying mechanisms. Furthermore, we also introduce the potential application of the artificially modified exosomes as the delivery systems of antitumor drugs. Further efforts in this field will provide new insights on the roles of exosomes in intercellular communications of TME and cancer progression, thus helping us to uncover effective strategies for cancer treatment.

ObjectiveMajor pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC.MethodsThis retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups.ResultsIn total, 91 LUSC patients who met the study’s eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001).ConclusionThe MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders.Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes.Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5-day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p < 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively).Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity.

Graves' ophthalmopathy (GO) is an extrathyroidal manifestation of Graves' disease, Orbital fibroblasts (OFs) are recognized as key players in GO pathogenesis, involved in orbital inflammation, tissue remodeling, and fibrosis. This study offers a primary exploration of cell behavior and characteristics on OFs from GO (GO-OFs), and compared to OFs from healthy control (HC-OFs). Results reveal that GO-OFs exhibit delayed migration from tissue fragments, while no significant difference in cell proliferation is observed between GO-OFs and HC-OFs. Aberrant expression pattern of surface proteins Thy-1, TSHR, and IGF-1R suggests shared autoantigens and pathways between GO and GD, contributing to inflammation and fibrosis. Investigations into cytokine responses unveil elevated secretion of hyaluronic acid (HA) and prostaglandin E2 (PGE2) in GO-OFs, emphasizing their role in tissue remodeling. These findings deepen our understanding of OFs in GO pathogenesis, offering potential therapeutic avenues.

Abstract Background The clinical significance of protein tyrosine phosphatase nonreceptor type 11 mutation (PTPN11mut) in acute myeloid leukemia (AML) is underestimated. Methods We collected the data of AML patients with mutated PTPN11 and wild‐type PTPN11 (PTPN11wt) treated at our hospital and analyzed their clinical characteristics and prognosis. Results Fifty‐nine PTPN11mut and 124 PTPN11wt AML patients were included. PTPN11mut was more common in myelomonocytic and monocytic leukemia, and was more likely to co‐mutate with KRAS, KMT2C, NRAS, U2AF1, NOTCH1, IKZF1, and USH2A mutations than PTPN11wt. The overall survival for AML patients with PTPN11mut was significantly shorter than that for those with PTPN11wt (p = 0.03). The negative impact of PTPN11mut on overall survival was pronounced in the “favorable” and “intermediate” groups of ELN2017 risk stratification, as well as in the wild‐type NPM1 group (p = 0.01, p = 0.01, and p = 0.04). Conclusion PTPN11mut is associated with distinct clinical and molecular characteristics, and adverse prognosis in AML patients.