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Abstract β-Hydroxybutyrate (β-OHB), the primary ketone body, is a bioactive metabolite that acts as both an energy substrate and a signaling molecule. Recent studies found that β-OHB inhibits the production of pro-inflammatory cytokines in macrophages, but its underlying molecular mechanisms have not yet been fully elucidated. Lysine β-hydroxybutyrylation (Kbhb), a post-translational modification mediated by β-OHB, plays a key role in regulating the expression and activity of modified proteins. However, whether macrophages undergo protein Kbhb and whether Kbhb modification regulates macrophage polarization remains largely unknown. In this study, treatment with β-OHB and ketone ester significantly decreased the lipopolysaccharide (LPS)-induced enhancement of the M1 phenotype of mouse bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and peritoneal macrophages (PMs) in vitro and in vivo. Moreover, β-OHB treatment induced global protein Kbhb, which is associated with the regulation of macrophage M1 polarization. Proteome-wide Kbhb analysis in β-OHB-treated BMDMs revealed 3469 Kbhb modification sites within 1549 proteins, among which interleukin-12-responding proteins were significantly upregulated. Our results indicated that β-OHB regulated M1 macrophage polarization by inducing Kbhb modification of the signal transducer and activator of transcription 1 (STAT1) K679 site, which inhibited its LPS-induced phosphorylation and transcription. Altogether, our study demonstrated the presence of a widespread Kbhb landscape in the β-OHB-treated macrophages and provided novel insights into the anti-inflammatory effects of β-OHB.

Diarrhea poses a significant threat to the health and well-being of weaned piglets, leading to substantial morbidity and mortality and economic loss in the pig industry. However, the structural characteristics of the gut microbiota and the key genera associated with early diarrhea in piglets within large-scale production systems are poorly understood. This study aimed to investigate the differences in the microbial community structure and the specific genera alteration between the healthy piglets and diarrhea piglets, and to identify the biomarkers of gut microbiota associated with diarrhea in piglets. A total of 250 fecal samples, including 130 healthy piglets (Duroc × Landrace × Large Yorkshire) in the Control group and 120 from diarrhea piglets in Diarrhea group, were collected from three large-scale farms as discovery cohorts and were used for 16S rRNA gene sequencing. Additionally, 150 fecal samples from another large-scale pig farm were collected for the validation trail. The Chao1 and ACE indices were obviously lower (P

Abstract With the rapid development of wearable technology, smart contact lenses (SCL) are gradually gaining attention as a breakthrough innovation. The emergence of these products suggests that smart glasses, which incorporate electronic components and visual aids, are expected to become the mainstream of human-computer interaction in the future. However, realizing this vision requires not only advanced electronics but also highly sophisticated manufacturing processes. Therefore, this paper provides an in-depth discussion on the process of manufacturing smart contact lenses using in-mold electronic decoration technology and focuses on the multi-objective problem of optimizing injection parameters such as melt temperature and holding pressure to achieve on micro-molecular displacements as well as residual stresses. First, the background and technical requirements of smart contact lenses are described in detail, emphasizing the prospect of SCL for a wide range of applications in augmented reality, healthcare, and smart assistance. Subsequently, the key role of IME technology in SCL manufacturing is discussed. Focusing on the optimization of melting temperature, holding pressure and holding time, the effects of these three key parameters on eyewear were systematically analyzed with the goal of improving the overall performance and biocompatibility of SCL. The multi-objective optimization of melting temperature and holding pressure was achieved by NSGA-III. Radial basis function interpolation was used as an auxiliary method to provide finer optimization results for NSGA-III. During the multi-objective optimization process, efforts were made to achieve uniform flow of melt temperature and optimal adjustment of holding pressure to maximize the transparency, stability and comfort of SCL. The final results obtained achieved an optimization rate of 95.60% and 93.47% for nodal displacement and residual stress, respectively, compared with the initially recommended process parameters.

Abstract Background At the end of 2021, an epidemic of reproductive abnormalities in cows occurred in Jilin Province, China, posing an urgent need for a rapid diagnosis. Results To identify the cause of the disease, a total of 172 samples were collected from 21 dead calves and 45 aborting or pregnant cows in 10 farms across the province. Routine PCR or RT-PCR detection did not find any common abortion-related agents. We then employed the viromics-based precision diagnosis method to analyze these samples, and the read-based annotation showed signals of an Akabane disease virus (AKAV) in some libraries. To further identify the virus, nested RT-PCR detection revealed that 52.3% (11/21) of dead calves and 26.6% (12/45) of cows were positive for the virus. Phylogenetic analysis of the partial fragments showed that the S segment of the virus was 100% identical to the Chinese strain TJ2016, but its M and L segments shared 94.3% and 96.5% identities with an Israeli strain. Conclusions The viromic and molecular results suggested that these animals were infected with a reassortant AKAV. Coupled with the clinical signs, the virus should be responsible for the epizootic, highlighting that molecular and serological surveys of the virus in cows during early pregnancy, as well as ecological investigation in its arthropod vectors, are necessary.

Objectives: This study aimed to explore the preferences and influencing factors of self-management behaviors in patients with recurrent gout and provide a theoretical basis for developing targeted strategies to improve self-management preferences. Methods: A total of 10 patients with recurrent gout were recruited from the gout specialist outpatient clinic at a tertiary hospital in Shenyang, Liaoning Province, China. Semi-structured interviews were conducted with these patients, and the Kawakita Jiro (KJ) method was used to analyze the interview data. Results: After four rounds of screening by five researchers, 35 codes were selected from an initial 132. After three rounds of discussion and induction, the KJ method identified seven domains of self-management behavior preferences in patients with recurrent gout: 1) extensive knowledge of gout, yet difficulty in distinguishing between accurate and inaccurate information; 2) a passive attitude of “no pain, no management”; 3) the challenge of changing entrenched daily habits; 4) the optimistic but unrealistic belief of “self-delusion”; 5) a tendency to seek medical attention late due to hopelessness of cure and familiarity with recurrences; 6) preference for analgesics for gout recurrences while neglecting long-term urate-lowering therapy (ULT); and 7) gout-related stigma. Conclusion: The results of this study showed that the self-management behavior of patients with recurrent gout could be improved, especially in the aspects of medical seeking behavior, medication compliance, daily management and emotional management. At the same time, we found that gout stigma, difficulty in distinguishing true and false knowledge of gout and negative attitude of “ignoring pain” were significantly associated with self-management behavior.

Abstract Phase-separating peptides (PSPs) self-assembling into coacervate microdroplets (CMs) are a promising class of intracellular delivery vehicles that can release macromolecular modalities deployed in a wide range of therapeutic treatments. However, the molecular grammar governing intracellular uptake and release kinetics of CMs remains elusive. Here, we systematically manipulate the sequence of PSPs to unravel the relationships between their molecular structure, the physical properties of the resulting CMs, and their delivery efficacy. We show that a few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. We also demonstrate that the optimized PSPs CMs display excellent transfection efficiency in hard-to-transfect cells such as primary fibroblasts and immune cells. Our findings provide molecular guidelines to precisely program the material properties of PSP CMs and achieve tunable cellular uptake and release kinetics depending on the cargo modality, with broad implications for therapeutic applications such as protein, gene, and immune cell therapies.

This study intends to explore the extraction process, physical and chemical properties, antioxidant and hypoglycemic activities of polysaccharides from wild bitter melon (WBM). Using the peel of fresh WBM fruit as raw material, based on the single factor experimental results, the liquid-to-material ratio, ultrasonic time and ultrasonic power in the ultrasound-assisted extraction (UAE) process were optimized by Box-Behnken response surface. Two polysaccharide components of WBP50 and WBP75 were obtained through UAE of the optimal conditions and gradient alcohol precipitation, and their physical and chemical properties, in vitro antioxidant and hypoglycemic abilities were evaluated. The results showed that: under the conditions of liquid-to-material ratio of 16 mL/g, ultrasonic time of 16 min, and ultrasonic power of 312 W, the actual yield of crude WBM polysaccharide (WBP) was 8.33%±0.13%. The total sugar, protein, total phenols, total flavonoids, and uronic acid contents of WBP50 and WBP75 were 76.73%/73.38%, 4.78%/0.35%, 0.36%/0.25%, 2.06%/0.86% and 72.85%/49.58%, respectively. The average molecular weights were 27.59 kDa and 23.20 kDa, respectively. WBPs were mainly composed of galacturonic acid, galactose, rhamnose, arabinose, and glucose. The DPPH, ABTS+ and hydroxyl radicals scavenging abilities of WBP50 and WBP75 were 11.28/11.40 μg Trolox/mg, 40.87/44.42 μg Trolox/mg, and 52.47/99.89 U/mg, respectively. Regarding hypoglycemic ability, both WBPs had certain α-amylase inhibitory ability and strong α-glucosidase inhibitory ability. The α-glucosidase inhibition rate of WBP50 and WBP75 reached 93.34%±1.11% and 79.04%±0.76% at a concentration of 750 μg/mL. The UAE of WBP has the advantages of time saving, convenience, high efficiency and low energy consumption, and the extracted WBPs have natural antioxidant and hypoglycemic functional activities. This study lays the foundation for future structural analysis and functional mechanism research of WBPs and provides theoretical references for developing hypoglycemic products and high-value utilization of WBPs.

Abstract Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.

Abstract Unravelling abrupt alterations in the gut microbiota of wild species associated with nutritional stress is imperative but challenging for wildlife conservation. This study assessed the nutritional status of wild red deer during winter on the basis of changes in faecal nitrogen (FN) and urea nitrogen/creatinine (UN: C) levels and identified gut microbes associated with nutritional status via nutritional control experiments and metagenomic sequencing. The FN of wild red deer in winter 2022 was significantly lower than that in winter 2021 (p

Abstract Background The current review aims to explore the evidence regarding the effectiveness of mandibular advancement orthodontic appliances with maxillary expansion device in treating pediatric Obstructive Sleep Apnea (OSA). Materials and methods A systematic literature search was conducted across PubMed, Cochrane Central, Web of Science, Embase, Scopus databases, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and Wanfang. The research involved children and adolescents (under 16 years old) who received mandibular advancement and maxillary expansion functional orthopedic appliances for OSA treatment. We performed narrative reviews and subsequently amalgamated the findings from the studies. Results Six articles were included for review. Although a small number of studies were included, the research suggested the potential advantages of mandibular advancement for children with OSA. Following treatment, there was a decrease in AHI/RDI, an improvement in sleep quality, and the increase in oxygen saturation. Conclusions The limited quantity and quality of existing studies necessitate caution when drawing conclusions about the effectiveness of mandibular advancement and maxillary expansion for OSA. In the future, larger and well-designed randomized controlled trials (RCTs) are needed to provide more robust evidence. Patients should be carefully selected, and their orthodontic indications should be thoroughly evaluated before inclusion in such trials.We encourage researchers to design studies that monitor patients over several years to provide a comprehensive understanding of the long-term effectiveness. Trial registration This study was registered in PROSPERO(CRD42023480407) on November 20, 2023.

Abstract Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention. One emerging machine learning paradigm that addresses this concern is federated learning (FL). FL enables multiple entities to collaboratively build machine learning models while preserving data privacy and security. In this study, we present a multicenter BCa magnetic resonance imaging (MRI) dataset. The dataset comprises 275 three-dimensional bladder T2-weighted MRI scans collected from four medical centers, and each scan includes diagnostic pathological labels for muscle invasion and pixel-level annotations of tumor contours. Four FL methods are used to assess the baseline of the dataset for both the task of diagnosing muscle-invasive bladder cancer and automatic bladder tumor lesion segmentation.

Abstract In this paper, a nodal detection method for the detection and optimization of barrel helix offsets is proposed. The barrel used in this experiment is a 6-helix barrel. Moreover, the special properties of the film of Polyetheretherketone (PEEK) material are used to cover the surface of the barrel helix with a virtual in-mold decoration (IMD) film, and the unique nature of the film die offset in the IMD is utilized to detect the position of the barrel helix. The area with a large die index is the area with a large helix offset in the barrel, and the IMD die index is introduced to quantify the data. The IMD die index is used to determine the helix offset of the damaged barrel. The novelty of this work is that each node can use the die index to efficiently detect the position of the barrel helix deviation, carry out subsequent optimization and repair work through the optimization of the injection molding parameters and the design optimization of the barrel and verify the experiment by comparing the results. Through the steady-state simulation research mode, different permutations and combinations of the two process parameters are simulated to study their effects. Quantitative reference indicators include but are not limited to dependent variables such as the fluid flow velocity, shear rate, temperature distribution and phase transition, and the shear heating process of the injection screw is taken into account in the mold flow analysis to ensure that the die index value is more accurate. It can be seen from the analysis results that the temperature of the barrel changes after the groove depth and groove width are changed, and the effect ratio of the groove depth is lower than that of the groove width in the same degree of size change.

Abstract Background Preoperative oral carbohydrate intake can improve the postoperative recovery of fasting patients in many kinds of surgeries; however, the effect of carbohydrates on patients undergoing daytime oral surgery is still unclear. This study was designed to evaluate the effect of preoperative oral carbohydrate intake on the quality of recovery of patients undergoing daytime oral surgery using the quality of recovery-15 (QoR-15) questionnaire. Methods Ninety-two patients scheduled for daytime oral surgery were randomly allocated to the midnight fasting group (F group, n = 45) or the carbohydrate-Outfast loading group (O group, n = 47). Participants in the F group fasted from midnight the day before surgery. Patients in the O group also fasted but received the Outfast drink (4 ml/kg) 2–3 h before the induction of anesthesia. QoR-15 questionnaire, patient well-being, and satisfaction were assessed before anesthesia induction and 24 h after surgery. Perioperative blood glucose, postoperative exhaust time, and adverse events were also recorded. Results The QoR-15 scores were significantly higher in the O group than in the F group preoperatively and postoperatively. Seven parameters representing patient well-being evaluated on a numeric rating scale (NRS, 0–10) were lower in the O group than in the F group postoperatively, except for the hunger and sleep quality scores. Patient satisfaction scores on a 5-point scale were higher in the O group than in the F group preoperatively and postoperatively. Meanwhile, the postoperative exhaust time was significantly shorter in the O group compared to the F group, while there were no significant differences in blood glucose concentrations between two groups. Conclusions Preoperative oral carbohydrate intake could improve postoperative recovery quality, well-being, and satisfaction of patients undergoing daytime oral surgery 24 h after surgery, and may serve as a treatment option for patients undergoing daytime oral surgery. Trial registration This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100053753) on 28/11/2021.

Abstract Peat moss (Sphagnum) is a non-vascular higher plant with unique xylem-like hyaline (H) cells that are accompanied by photosynthetic chlorophyllous cells. These cellular structures play crucial roles in water storage and carbon sequestration. However, it is largely unknown how peat moss develops the H cells. This study systematically explored the Sphagnum Developmental Cell Atlas and Lineage and classified leaf cell development into two lineages with six stages (S0-S5) based on changes in key cellular traits, including the formation of spiral secondary cell walls (S4) and the presence of water pores (S5). Cell lineage-specific subcellular remodeling was transcriptionally regulated during leaf development, and vacuole-mediated clearance of organelles and cell death led to mature dead H cells. Interestingly, expression of land plant conserved Vascular-related NAC Domain (VND) genes correlated with H cell formation. Overall, these results suggest that the origination of xylem-like H cells is related to VND, likely through the neofunctionalization of vacuole-mediated cell death to attempt xylem formation in peat moss, suggesting potential uncoupling of xylem and phloem cell origins. This study positions peat moss as a potential model organism for studying integrative evolutionary cell biology.

Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.

Timely and stable sealing of uncontrolled high-pressure hemorrhage in emergency situations outside surgical units remains a major clinical challenge, contributing to the high mortality rate associated with trauma. The currently widely used hemostatic bioadhesives are ineffective for hemorrhage from major arteries and the heart due to the absence of biologically compatible flexible structures capable of simultaneously ensuring conformal tough adhesion and biomechanical support. Here, inspired by the principle of chromatin assembly, we present a tissue-conformable tough matrix for robust sealing of severe bleeding. This hierarchical matrix is fabricated through a phase separation process, which involves the in-situ formation of nanoporous aggregates within a microporous double-network (DN) matrix. The dispersed aggregates disrupt the rigid physical crosslinking of the original DN matrix and function as a dissipative component, enabling the aggregate-based DN (aggDN) matrix to efficiently dissipate energy during stress and achieve improved conformal attachment to soft tissues. Subsequently, pre-activated bridging polymers facilitate rapid interfacial bonding between the matrix and tissue surfaces. They synergistically withstand considerable hydraulic pressure of approximately 700 mmHg and demonstrate exceptional tissue adhesion and sealing in rat cardiac and canine aortic hemorrhages, outperforming the commercially available bioadhesives. Our findings present a promising biomimetic strategy for engineering biomechanically compatible and tough adhesive hydrogels, facilitating prompt and effective treatment of hemorrhagic wounds.

Electric vehicles and battery energy storage are effective technical paths to achieve carbon neutrality, and lithium-ion batteries (LiBs) are very critical energy storage devices, which is of great significance to the goal. However, the battery’s characteristics of instant degradation seriously affect its long life and high safety applications. The aging mechanisms of LiBs are complex and multifaceted, strongly influenced by numerous interacting factors. Currently, the degree of capacity fading is commonly used to describe the aging of the battery, and the ratio of the maximum available capacity to the rated capacity of the battery is defined as the state of health (SOH). However, the aging or health of the battery should be multifaceted. To realize the multi-dimensional comprehensive evaluation of battery health status, a novel SOH estimation method driven by multidimensional aging characteristics is proposed through the improved single-particle model. The parameter identification and sensitivity analysis of the model were carried out during the whole cycle of life in a wide temperature environment. Nine aging characteristic parameters were obtained to describe the SOH. Combined with aging mechanisms, the current health status was evaluated from four aspects: capacity level, lithium-ion diffusion, electrochemical reaction, and power capacity. The proposed method can more comprehensively evaluate the aging characteristics of batteries, and the SOH estimation error is within 2%.

Abstract Background Stress cardiomyopathy (SCM) is an acute heart failure syndrome characterized by transient, usually reversible left ventricular systolic dysfunction with normal or enhanced basal compensatory wall motion abnormalities involving the left ventricular anterior septum and apex, resulting in a “ballooning” appearance. However, it has rarely been reported in patients undergoing spinal surgery. Case presentation We report a case of severe stress cardiomyopathy in a scoliosis patient with pectus excavatum who underwent spinal corrective surgery. During the wake-up period, circulatory collapse occurred. After multidisciplinary consultation, the patient was diagnosed with stress cardiomyopathy. At last, she had a good prognosis after a series of treatments including ECMO. Conclusion Stress cardiomyopathy is a reversible but uncommon condition. It can cause death if it is not diagnosed in time. Consequently, this report should improve the awareness of orthopedists and anesthesiologists for timely identification and management. For patients with potential risk factors, timely preoperative intervention should be performed to reduce the occurrence of stress cardiomyopathy.

Yanyuan County is located on the southeastern edge of the Qinghai-Tibet Plateau, with strong regional tectonic activities. Under the internal and external dynamics actions, landslide disasters are extremely developed in the country, which has caused huge casualties and economic losses. It is necessary to carry out landslide susceptibility assessment and then control the regional landslide disasters scientifically. Based on the 1∶50000 geological disaster survey in Yanyuan County, this study selected 13 landslide susceptibility evaluation factors, including elevation, slope, slope direction, terrain curvature, distance from fault, stratigraphic lithology, distance from water body, average annual rainfall, topographic wetness index, stream power index, normalized difference vegetation index, distance from road, and land use type. Based on 27596 grid points of landslide disaster data, combining the traditional Frequency Ratio (FR) model with the advantages of quantitative analysis and data quantification and the emerging Deep Neural Network (DNN) model with the powerful nonlinear learning and fitting ability, The FR-DNN coupling model was constructed to evaluate landslide susceptibility. The study area is divided into five levels: extremely high susceptibility area, high susceptibility area, medium susceptibility area, low susceptibility area, and extremely low susceptibility area, with an area percentage of 11.90%, 18.38%, 18.34%, 9.13%, and 42.25%, respectively. The accuracy was verified by the AUC value of the ROC curve. The AUC values of the FR model and the FR-DNN coupling model are 0.754 and 0.859, respectively. The prediction accuracy of the FR-DNN coupling model is improved by 10.5% compared with that of the FR model, indicating that the FR-DNN coupling model has better prediction ability and is more suitable for landslide susceptibility evaluation in the study area.

The escalating challenges in water treatment, exacerbated by climate change, have catalyzed the emergence of innovative solutions. Novel adsorption separation and membrane filtration methodologies, achieved through molecular structure manipulation, are gaining traction in the environmental and energy sectors. Separation technologies, integral to both the chemical industry and everyday life, encompass concentration and purification processes. Macrocycles, recognized as porous materials, have been prevalent in water treatment due to their inherent benefits: stability, adaptability, and facile modification. These structures typically exhibit high selectivity and reversibility for specific ions or molecules, enhancing their efficacy in water purification processes. The progression of purification methods utilizing macrocyclic frameworks holds promise for improved adsorption separations, membrane filtrations, resource utilization, and broader water treatment applications. This review encapsulates the latest breakthroughs in macrocyclic host-guest chemistry, with a focus on adsorptive and membrane separations. The aim is to spotlight strategies for optimizing macrocycle designs and their subsequent implementation in environmental and energy endeavors, including desalination, elemental extraction, seawater energy harnessing, and sustainable extraction. Hopefully, this review can guide the design and functionality of macrocycles, offering a significantly promising pathway for pollutant removal and resource utilization.

Abstract Injection molding is a common plastic processing technique that allows melted plastic to be injected into a mold through pressure to form differently shaped plastic parts. In injection molding, in-mold electronics (IME) can include various circuit components, such as sensors, amplifiers, and filters. These components can be injected into the mold to form a whole within the melted plastic and can therefore be very easily integrated into the molded part. The brain–computer interface (BCI) is a direct connection pathway between a human or animal brain and an external device. Through BCIs, individuals can use their own brain signals to control these components, enabling more natural and intuitive interactions. In addition, brain–computer interfaces can also be used to assist in medical treatments, such as controlling prosthetic limbs or helping paralyzed patients regain mobility. Brain–computer interfaces can be realized in two ways: invasively and noninvasively, and in this paper, we adopt a noninvasive approach. First, a helmet model is designed according to head shape, and second, a printed circuit film is made to receive EEG signals and an IME injection mold for the helmet plastic parts. In the electronic film, conductive ink is printed to connect each component. However, improper parameterization during the injection molding process can lead to node displacements and residual stress changes in the molded part, which can damage the circuits in the electronic film and affect its performance. Therefore, in this paper, the use of the BCI molding process to ensure that the node displacement reaches the optimal value is studied. Second, the multistrategy differential evolutionary algorithm is used to optimize the injection molding parameters in the process of brain–computer interface formation. The relationship between the injection molding parameters and the actual target value is investigated through Latin hypercubic sampling, and the optimized parameters are compared with the target parameters to obtain the optimal parameter combination. Under the optimal parameters, the node displacement can be optimized from 0.585 to 0.027 mm, and the optimization rate can reach 95.38%. Ultimately, by detecting whether the voltage difference between the output inputs is within the permissible range, the reliability of the brain–computer interface after node displacement optimization can be evaluated.

Abstract In the era of 5 G, the rise in power density in miniaturized, flexible electronic devices has created an urgent need for thin, flexible, polymer-based electrically and thermally conductive nanocomposites to address challenges related to electromagnetic interference (EMI) and heat accumulation. However, the difficulties in establishing enduring and continuous transfer pathways for electrons and phonons using solid-rigid conductive fillers within insulative polymer matrices limit the development of such nanocomposites. Herein, we incorporate MXene-bridging-liquid metal (MBLM) solid-liquid bi-continuous electrical-thermal conductive networks within aramid nanofiber/polyvinyl alcohol (AP) matrices, resulting in the AP/MBLM nanocomposite with ultra-high electrical conductivity (3984 S/cm) and distinguished thermal conductivity of 13.17 W m−1 K−1. This nanocomposite exhibits excellent EMI shielding efficiency (SE) of 74.6 dB at a minimal thickness of 22 μm, and maintains high EMI shielding stability after enduring various harsh conditions. Meanwhile, the AP/MBLM nanocomposite also demonstrates promising heat dissipation behavior. This work expands the concept of creating thin films with high electrical and thermal conductivity.

Asymmetric ring-expansion reactions of silacyclobutanes (SCBs) with alkynes have evolved as one of the powerful protocols for the construction of silicon-stereogenic compounds. However, the achievement of highly enantioselective annulation of SCBs with terminal alkynes remains a challenge. Herein, we report a rhodium-catalyzed asymmetric annulation reaction of SCBs with terminal alkynes, which relies on the newly identified chiral sulfinamide phosphine ligand Ming-Phos. This catalytic system exhibits unique effects under mild conditions, leading to the direct synthesis of structurally diverse chiral silacycles in moderate to good yields with high enantioselectivities (up to 95% ee).

Abstract The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Interventional treatment for left ventricular free wall or apex perforation is rarely reported. This current case report describes a male patient in his 70 s with left ventricular perforation caused by pericardiocentesis that was successfully treated through interventional means. The patient was admitted to the hospital due to chest pain accompanied by asthmatic breathing difficulties that had lasted for the previous 10 h. Two years previously, the patient had a history of thymoma, during which pericardial effusion was discovered, leading to multiple hospitalizations for pericardial fluid aspiration. On the 10th day of admission, a chest computed tomography scan confirmed iatrogenic left ventricular apical perforation and haemorrhagic anaemia, after which interventional transcatheter left ventricular perforation sealing was performed. Postoperatively, the patient was conscious, with stable vital signs and no particular discomfort. The successful implementation of this interventional procedure suggests a new minimally invasive solution for treating left ventricular perforation caused by pericardiocentesis or interventional catheterization.

Objective This study developed a nomogram combining longitudinal and transverse ultrasound radiomics with clinical factors to identify human epidermal growth factor receptor 2 (HER2) status in invasive breast cancer (BC).Materials and methods We analyzed 537 invasive BC patients from two hospitals: 436 in the training cohort (Hospital A) and 101 in the test cohort (Hospital B). From longitudinal and transverse ultrasound planes, 788 radiomics features were extracted, with dimensionality reduced using least absolute shrinkage and selection operator regression. A radiomics nomogram integrating clinical predictors and radiomics scores (Rad-scores) was constructed.Results Fifteen and sixteen features from longitudinal and transverse ultrasound planes, respectively, were selected to generate Rad-scores, which differed significantly between HER2-positive and HER2-negative groups in both cohorts (p

Background Lung adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancer cases, and has the highest incidence among lung cancer subtypes. Recent studies have suggested that long non-coding RNAs (lncRNAs) play a crucial role in the initiation and progression of lung adenocarcinoma.Methods Based on integrative analysis through databases, we screened Long intergenic non-protein coding RNA 00839 (LINC00839) as one of the most highly upregulated lncRNAs in lung adenocarcinoma. In vitro and in vivo experiments demonstrated that LINC00839 promotes lung adenocarcinoma proliferation, migration, and invasion and that it is present in exosomes secreted by lung adenocarcinoma cells.Results In the cytoplasm, LINC00839 regulates the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway by acting as a molecular sponge of miR-17-5p, thereby influencing the biological behavior of lung adenocarcinoma cells. LINC00839 binds to Polypyrimidine tract binding protein 1 (PTBP1) in the nucleus to regulate the nuclear translocation of NF-κB p65 molecules and, consequently, the transcription of downstream molecules.Conclusions Our study confirmed that LINC00839 promotes the biological progression of lung adenocarcinoma by performing dual roles in the cytoplasm and nucleus to co-regulate the NF-κB signaling pathway.

Objectives The TP53 mutation, a prevalent tumor suppressor gene alteration, is linked to chemotherapy resistance, increased relapse rates and diminished overall survival (OS) in acute myeloid leukemia (AML) patients.Methods In this study, we characterize the TP53 mutation phenotypes across various AML cohorts utilizing The Cancer Genome Atlas (TCGA) data. We devised a TP53-related prognostic signature derived from differentially expressed genes between mutated and wild-type TP53 AML specimens. In-depth analyses were conducted, encompassing genetic variation, immune cell infiltration and prognostic stratification.Results A six-gene TP53-related signature was established using least absolute shrinkage and selection operator (LASSO)–Cox regression, demonstrating robust prognostic predictability. This signature exhibited strong performance in both the OHSU validation cohorts, an independent Gene Expression Omnibus (GEO) validation cohort (GSE71014) and proved by results of the in vivo experiment. Finally, we used single cell database (GSE198681) to observe the characteristics of these six genes.Discussion Our study may facilitate the development of efficacious therapeutic approaches and provide a novel idea for future research. Conclusion: The TP53-related signature and pattern hold the potential to refine prognostic stratification and underscore emerging targeted therapies.

Ratiometric fluorescent films with high amine sensitivity and stability were developed to monitor the freshness of beef and pork. Fluorescein isothiocyanate (FITC) and red carbon quantum dots (R-CQD) were used as the amine-responsive indicator and internal reference, respectively. The electrospun films prepared by immobilizing FITC and R-CQD complex (F-R) into polyvinylidene fluoride (PVDF) under 35 %, 55 % and 75 % of relative humidity (RH) were named F-R@PVDF-1, F-R@PVDF-2 and F-R@PVDF-3, respectively. In comparison, the F-R@PVDF-2 film exhibited the highest sensitivity to trimethylamine (TMA), demonstrating a limit of detection (LOD) value of 1.59 μM, and meanwhile high stability during storage with ΔE value of 1.99 after 14 days of storage at 4 °C. The F-R@PVDF-2 film also showed a significant fluorescent red-to-brown color change during meat freshness monitoring at 4 °C. Conclusively, this study reported a new ratiometric fluorescent film that can be used to track the freshness of meats in food packaging.

IntroductionSalmonella, Escherichia coli, Lawsonella intracellularis, and Brachyspira hyodysenteriae are the primary pathogens responsible for gastrointestinal diseases in pigs, posing a significant threat to the health and productivity of pig production systems. Pathogen detection is a crucial tool for monitoring and managing these infections.MethodsWe designed primers and probes targeting the invA gene of Salmonella, the 23S rRNA gene of Escherichia coli, the aspA gene of Lawsonella intracellularis, and the nox gene of Brachyspira hyodysenteriae. We developed a quadruplex TaqMan real-time quantitative PCR assay capable of simultaneously detecting these four pathogens.ResultsThis assay demonstrated high sensitivity, with detection limits of 100 copies/μL for the recombinant plasmid standards pEASY-23S rRNA, pEASY-aspA, and pEASY-nox, and 10 copies/μL for pEASY-invA. The standard curves exhibited excellent linearity (R2 values of 0.999, 0.999, 1, and 0.998, respectively) and high amplification efficiencies (93.57%, 94.84%, 85.15%, and 81.81%, respectively). The assay showed high specificity, with no cross-reactivity detected against nucleic acids from Streptococcus suis, porcine epidemic diarrhoea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), Pasteurella multocida, Clostridium perfringens, Gracilaria parapsilosis, porcine delta coronavirus (PDCoV), porcine group A rotavirus (GARV), and porcine teschovirus (PTV). The assay also exhibited excellent repeatability, with inter- and intra-assay coefficient of variation (CV) ranging from 0.15% to 1.12%. High concentrations of nucleic acids did not interfere with the detection of low concentrations, ensuring robust performance in complex samples. Among 263 diarrhoeic samples, the assay detected Salmonella in 23.95%, Escherichia coli in 26.24%, Lawsonella intracellularis in 33.84%, and Brachyspira hyodysenteriae in 22.43%.DiscussionThis quadruplex TaqMan qPCR assay offers a rapid, sensitive, and specific tool for the simultaneous detection of Salmonella, Escherichia coli, Lawsonella intracellularis, and Brachyspira hyodysenteriae in pigs.

In power systems, potential transformers (PTs) are responsible for stepping down high voltage to low voltage. However, a short circuit between turns on the primary side of a generator outlet PT can significantly reduce the secondary phase voltage, leading to voltage imbalances and generating fundamental zero-sequence voltage. This situation is analogous to a stator winding ground fault, often resulting in incorrect protective operations. To prevent such malfunctions, this paper analyzes the causes of false tripping through simulation and proposes a fault diagnosis model based on the Circular Sparrow Search Algorithm (CSSA)-optimized Gaussian Mixture Model (GMM), referred to as the CSSA-GMM model. A fault simulation model was established using Simulink to verify the differences between turn-to-turn short circuits and stator ground faults, and their electrical characteristics were studied. The results indicate that under different fault types, parameters such as the three-phase primary current and three-phase secondary voltage exhibit varying relationships and fault variations. By optimizing the GMM parameters using CSSA and comprehensively analyzing the voltage and current characteristics, this model can effectively diagnose turn-to-turn short circuit faults at various short-turn ratios, achieving an accuracy rate of up to 98%. This approach clearly distinguishes PT turn-to-turn short circuits from generator outlet stator ground faults, providing new insights for fault recognition and supporting the intelligent development of relay protection systems.

IntroductionStreptococcus suis (SS) is one of the most important pathogens causing major economic losses in the global pig farming industry and is a serious threat to public health safety. It has multiple serotypes, with poor cross-protection between serotypes, and effective typing methods are lacking.MethodsIn this study, a quadruplex TaqMan fluorescence quantitative PCR assay that can differentiate between Streptococcus suis types 2, 7 and 9 was developed using the gdh gene, a generic gene for Streptococcus suis, and cps2J, cps7H and cps9J, genes encoding podocarp-associated genes for types 2, 7 and 9, respectively, as targets.ResultsThe method is specific enough to accurately type Streptococcus suis pigmentosus without detecting non-target pathogens (Escherichia coli, Pasteurella multocida, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and et al). The sensitivity was high, with a minimum lower detection line of 10 copies for P-SS and P-SS9, and 100 copies for P-SS2 and P-SS7. The standard curves generated showed good linearity with R2 of 0.999, 0.999, 0.997 and 0.998 respectively. The repeatability was good, with coefficients of variation between batch to batch and batch to batch tests ranging from 0.21% to 1.10%. Testing of 156 samples yielded 68 positive and 88 negative samples, of which the positive rate of SS was 5.77% (9/156), SS2 was 20.51% (32/156), SS7 was 8.33% (13/156) and SS9 was 9.6% (15/156), which was in line with the existing fluorescent quantitative PCR assay of 93.75%~100%, which was higher than the detection rate of conventional PCR.DiscussionThe quadruplex TaqMan fluorescence quantitative PCR method of Streptococcus suis generic, type 2, 7 and 9 established in this study can accurately differentiate the three serotypes of Streptococcus suis that currently have high prevalence and pathogenicity, which is of great importance for accurate clinical prevention and treatment, epidemiological investigation and vaccine development.

IntroductionTunnel composting technology for preparing Agaricus subrufescens cultivation media can achieve a higher biological efficiency (BE) and a lower contamination rate (CR). However, this technology lacks in-depth and systematic study.MethodsIn the present study, the changes in the microbiome and microbial metabolic functions were surveyed using metagenomic analysis. The physicochemical parameters, agronomic properties and nutritional qualities were also evaluated.Results and discussionResults showed that the contents of cellulose, hemicellulose and lignin dropped to 10.18, 11.58, 27.53%, respectively at the end of composting. The tunnel composting technology led to significant increases in crude protein content (32.56%) and crude fiber content (13.68%). Variations of physicochemical characteristics led to different successions of microbial communities. Bacteria manifested significantly higher abundance than fungi. Firmicutes, Actinobacteriota, Chloroffexi and Deinococcota were the predominant bacterial phyla. Ascomycota and Basidiomycota were the dominant fungal phyla in the thermophilic phase. Pseudonocardia, Truepera, and Thermopolyspora were positively correlated with the yield of A. subrufescens. In addition to TN, most of the physicochemical properties were significantly correlated with fungal communities in the thermophilic phase. The metabolisms of carbohydrate, amino acid and energy were the primary enrichment pathways. These findings deepen the understanding of microbial communities composition during the composting of A. subrufescens substrates. Moreover, this study provides a basis for improving tunnel composting technology.

Abstract Peptide coacervates self‐assembling via liquid‐liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non‐cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, we identify the key steps by which droplets enter the cell. We find that the uptake follows a non‐canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia‐like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge‐ and cholesterol‐dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors – interfering with actin and tubulin polymerization – confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non‐specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate‐based strategies for intracellular delivery of macromolecular therapeutics.

Micro/nanoplastics (MNPs) and heavy metals (HMs) coexist worldwide. Existing studies have reported different or even contradictory toxic effects of co-exposure to MNPs and HMs on plants, which may be related to various influencing factors. In this study, existing publications were searched and analyzed using CiteSpace, meta-analysis, and machine learning. CiteSpace analysis showed that this research field was still in the nascent stage, and hotspots in this field included accumulation, cadmium (Cd), growth, and combined toxicity. Meta-analysis revealed the differential association of seven influencing factors (MNP size, pollutant treatment duration, cultivation media, plant species, MNP type, HM concentration, and MNP concentration) and 8 physiological parameters receiving the most attention. Co-exposure of the two contaminants had stronger toxic effects than HM treatment alone, and phytotoxicity was generally enhanced with increasing concentrations and longer exposure durations, especially when using nanoparticles, hydroponic medium, dicotyledons producing stronger toxic effects than microplastics, soil-based medium, and monocotyledons. Dry and fresh weight analysis showed that co-exposure to MNPs and Cd resulted in significant phytotoxicity in all classifications. Concerning the MNP types, polyolefins partially attenuated plant toxicity, but both modified polystyrene (PS) and biodegradable polymers exacerbated joint phytotoxicity. Finally, machine learning was used to fit and predict plant HM concentrations, showing five classifications with an accuracy over 80 %, implying that the polynomial regression model could be used to predict HM content in plants under complex pollution conditions. Overall, this study identifies current knowledge gaps and provides guidance for future research.

The contemporary interpretation of Lao-Zhuang’s thought reveals a multidimensional dialogue between tradition and modernity, the local and the exotic, and East and West. The interaction between Lao-Zhuang’s thoughts and Western religious philosophy can be explored through the lens of mysticism. By examining the non-material nature of the Tao, the transcendence of language, and the cultivation goal of the unity of nature and humanity, we can discern the relationship between the cultivation practices in Lao-Zhuang’s thought and religious mysticism. The chaos, uncertainty, infinity and nothingness associated with the non-physical Tao present a subtle and mysterious depiction of nature. The silence of the perfect man, who sees things in terms of the Tao, along with their conversion to the Tao, steadfastness to the Tao, flexibility in treating things according to the Tao and freedom to be one with the Tao, provides an ethical realm of inner cultivation. Through the dialogue between Lao-Zhuang’s philosophy and Western religion, we can uncover the commonalities and differences between Chinese and Western cultures, as well as the significant value of Lao-Zhuang’s thought in contemporary cultural and philosophical discussions. Contribution: This article examines the relationship between cultivation practice in Lao-Zhuang’s thought and religious mysticism from the perspective of cross-cultural research. By discussing the immateriality and infinity of ‘Tao,’ as well as the relationship between Tao and name, speech and debate, it presents the mystery of Tao. Through the non-cognitive practice mode of real people, they experience ‘Tao’ and achieve the realm of ‘Harmony between nature and man,’ demonstrating the mystery of cultivation efforts.

Abstract Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell‐derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell‐derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Ningxia is one of the well-known wine producing regions in China. However, the oenological and aroma characteristics of indigenous yeasts remains hidden. The fermentative and oenological properties including stress resistance, hydrogen sulfide, foam production levels; killer phenotype, and flocculation of 89 Ningxia indigenous Saccharomyces cerevisiae isolates and ten commercial yeasts were evaluated. The fermentative and oenological properties of the tested strains varied significantly. They could resist 500 g/L glucose, 300 mg/L SO2, 14% (v/v) ethanol and pH 2.8, and produce more esters. They also produce low levels of ethanol and could conduct fermentations vigorously and at a high rate. Cabernet Sauvignon wines made with NXU 21–24 showed the high intensity of tropical fruit, dry fruit, temperate fruit, and spicy flavor. The floral flavor in NXU 21–102 fermented wine is very intense. The indigenous S. cerevisiae strains of NXU 21–102 and NXU 21–24 exhibited potential use as starter cultures in wine production.

In this study, three fermentation treatments of spontaneous fermentation (SF), direct inoculation of CECA (YF), and inoculation with CECA after addition of dimethyl dicarbonate (YDF) were carried out. Multivariate statistical analysis approved that CECA inoculation significantly influenced the composition of 141 metabolites (15 volatile organic compounds (VOCs) and 126 non-VOCs), mainly consisting of 36 acids and derivatives and 25 lipids and lipid-like molecules. YF and YDF wines exhibited similar correlations with aroma types, while there were differences in the kinds and number of VOCs. Moreover, CECA-inoculated fermentation was more favorable to the formation of aftertaste-A, umami, sourness, and richness. The KEGG metabolic pathway analysis indicated that the inoculation strategy significantly affected the amino acid metabolism. The antimicrobial treatment effectively enhanced bitterness, astringency, umami and saltiness while reducing acidity. Further studies are needed to assess the effects of antimicrobial treatment on lipid metabolism.

Background: Deep convolutional neural networks have garnered considerable attention in numerous machine learning applications, particularly in visual recognition tasks such as image and video analyses. There is a growing interest in applying this technology to diverse applications in medical image analysis. Automated three-dimensional Breast Ultrasound is a vital tool for detecting breast cancer, and computer-assisted diagnosis software, developed based on deep learning, can effectively assist radiologists in diagnosis. However, the network model is prone to overfitting during training, owing to challenges such as insufficient training data. This study attempts to solve the problem caused by small datasets and improve model detection performance. Methods: We propose a breast cancer detection framework based on deep learning (a transfer learning method based on cross-organ cancer detection) and a contrastive learning method based on breast imaging reporting and data systems (BI-RADS). Results: When using cross organ transfer learning and BIRADS based contrastive learning, the average sensitivity of the model increased by a maximum of 16.05%. Conclusion: Our experiments have demonstrated that the parameters and experiences of cross-organ cancer detection can be mutually referenced, and contrastive learning method based on BI-RADS can improve the detection performance of the model.

Abstract Gridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh3-cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H…H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|g PL | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications.

Abstract In this paper, we consider a coupling mechanism between the kinetic term and the gravity, in which a coupling function F (R) is introduced into the kinetic term of the five-dimensional scalar field. Based on this scenario, we investigate the localization of scalar fields in three specific braneworld models: the Minkowski brane, the de Sitter brane, and the Anti-de Sitter brane. The brane models considered here are regular with no singularity for scalar curvature. For the Minkowshi brane case, the zero mode can always be localized on the brane, and the massive modes can be localized or quasi-localized on the brane. For the dS4 brane case, two forms of factor F (R) is considered. The zero mode can always be localized, and the massive modes could be quasi-localized on the brane. Besides, with the second coupling factor, the scalar zero mode could be localized on the both sides of the origin of extra dimension, while the massive modes could be quasi-localized on the origin. Lastly, for the AdS4 brane case, the localization of the scalar zero mode requires the consideration of a coupling potential V (Φ, φ), while the massive modes can still be localized on the brane with an infinite number.

Abstract Background To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. Methods A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. Results There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with

Abstract Background Process approach is valuable for memory assessment in Alzheimer’s disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. Methods 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A’), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. Results ROC analysis showed the value of A’, B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A’ and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. Conclusion This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.

Objective: Accurate infant brain parcellation is crucial for understanding early brain development; however, it is challenging due to the inherent low tissue contrast, high noise, and severe partial volume effects in infant magnetic resonance images (MRIs). The aim of this study was to develop an end-to-end pipeline that enabled accurate parcellation of infant brain MRIs. Methods: We proposed an end-to-end pipeline that employs a two-stage global-to-local approach for accurate parcellation of infant brain MRIs. Specifically, in the global regions of interest (ROIs) localization stage, a combination of transformer and convolution operations was employed to capture both global spatial features and fine texture features, enabling an approximate localization of the ROIs across the whole brain. In the local ROIs refinement stage, leveraging the position priors from the first stage along with the raw MRIs, the boundaries of the ROIs are refined for a more accurate parcellation. Results: We utilized the Dice ratio to evaluate the accuracy of parcellation results. Results on 263 subjects from National Database for Autism Research (NDAR), Baby Connectome Project (BCP) and Cross-site datasets demonstrated the better accuracy and robustness of our method than other competing methods. Conclusion: Our end-to-end pipeline may be capable of accurately parcellating 6-month-old infant brain MRIs.

Abstract Image-based artificial intelligence (AI) systems stand as the major modality for evaluating ophthalmic conditions. However, most of the currently available AI systems are designed for experimental research using single-central datasets. Most of them fell short of application in real-world clinical settings. In this study, we collected a dataset of 1,099 fundus images in both normal and pathologic eyes from 483 premature infants for intelligent retinopathy of prematurity (ROP) system development and validation. Dataset diversity was visualized with a spatial scatter plot. Image classification was conducted by three annotators. To the best of our knowledge, this is one of the largest fundus datasets on ROP, and we believe it is conducive to the real-world application of AI systems.

Abstract Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). Methods A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. Results Two cis-compound benign intronic variants of FBN1 (c.3464–4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein’s secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel β sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. Conclusions To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

Abstract Blood orange (BO) is a rare red-fleshed sweet orange (SWO) with a high anthocyanin content and is associated with numerous health-related benefits. Here, we reported a high-quality chromosome-scale genome assembly for Neixiu (NX) BO, reaching 336.63 Mb in length with contig and scaffold N50 values of 30.6 Mb. Furthermore, 96% of the assembled sequences were successfully anchored to 9 pseudo-chromosomes. The genome assembly also revealed the presence of 37.87% transposon elements and 7.64% tandem repeats, and the annotation of 30,395 protein-coding genes. A high level of genome synteny was observed between BO and SWO, further supporting their genetic similarity. The speciation event that gave rise to the Citrus species predated the duplication event found within them. The genome-wide variation between NX and SWO was also compared. This first high-quality BO genome will serve as a fundamental basis for future studies on functional genomics and genome evolution.