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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.

Abstract Diseases of the female reproductive system, especially malignant tumors, pose a serious threat to women’s health worldwide. One of the key factors limiting research progress in this area is the lack of representative models. Organoid technology, especially tumor organoids, has been increasingly applied in the study of female reproductive system tumors due to their high heterogeneity, close resemblance to the physiological state, easy acquisition and cultivation advantages. They play a significant role in understanding the origin and causes of tumors, drug screening, and personalized treatment and more. This article reviews the organoid models for the female reproductive system, focusing on the cancer research advancements. It discusses the methods for constructing tumor organoids of the female reproductive tract and summarizes the limitations of current research. The aim is to offer a reference for future development and application of these organoid models, contributing to the advancement of anti-tumor drugs and treatment strategies for female reproductive tract cancer patients.

Abstract Background The association between red blood cell distribution width (RDW) to albumin ratio (RAR) and prognosis in patients with acute respiratory failure (ARF) admitted to the Intensive Care Unit (ICU) remains unclear. This retrospective cohort study aims to investigate this association. Methods Clinical information of ARF patients was collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The primary outcome was, in-hospital mortality and secondary outcomes included 28-day mortality, 60-day mortality, length of hospital stay, and length of ICU stay. Cox regression models and subgroup analyses were conducted to explore the relationship between RAR and mortality. Results A total of 4547 patients with acute respiratory failure were enrolled, with 2277 in the low ratio group (RAR = 4.83). Kaplan-Meier survival analysis demonstrated a significant difference in survival probability between the two groups. After adjusting for confounding factors, the Cox regression analysis showed that the high RAR ratio had a higher hazard ratio (HR) for in-hospital mortality (HR 1.22, 95% CI 1.07–1.40; P = 0.003), as well as for 28-day mortality and 60-day mortality. Propensity score-matched (PSM) analysis further supported the finding that high RAR was an independent risk factor for ARF. Conclusion This study reveals that RAR is an independent risk factor for poor clinical prognosis in patients with ARF admitted to the ICU. Higher RAR levels were associated with increased in-hospital, 28-day and 60-day mortality rates.

Abstract Objective We aimed to probe the diagnostic value of transvaginal color Doppler ultrasound (TV-CDU) parameters in cesarean scar pregnancy (CSP) and CSP sub-types, and the relevant factors affecting patients’ surgical effects. Methods Seventy-five CSP patients (all requested termination of pregnancy) were selected as the observation group, and 75 normal pregnant women with a history of cesarean section were selected as the control group. All the study subjects underwent TV-CDU and their cesarean scar muscle (CSM) thickness, minimum sagittal muscle thickness and resistance index (RI) of blood flow in the anterior wall of the lower uterine segment were calculated. The diagnostic value of CSM, minimum sagittal muscle thickness, and RI for CSP and CSP sub-types was analyzed. The patients in the observation group were grouped into the effective group and the ineffective group according to whether the surgical treatment was effective or not, and the independent factors affecting CSP efficacy were analyzed. Results The observation group had lower CSM, minimum sagittal muscle thickness and RI than the control group. CSM, RI, and minimum sagittal thickness in patients with type II CSP were lower than those in patients with type I, and these indicators in patients with type III were lower than those in patients with type II. The area under the curve (AUC) of CSM, RI and minimum sagittal muscle thickness in combination for CSP diagnosis and the AUC for CSP sub-types were higher than those of each indicator alone. Gestational sac size and CSM were independent factors affecting CSP treatment. Conclusion Changes in TV-CDU parameters facilitates CSP diagnosis after cesarean section. CSM, minimum sagittal muscle thickness changes, and RI in combination possesses high value for CSP diagnosis and CSP sub-types. Gestational sac size and CSM are independent factors affecting CSP treatment.

【Objective】The deposition and decomposition of solid particles in aquaculture wastewater will lead to the deterioration of aquaculture water and affect the health of fish. The study was conducted to understand the sedimentation rule of solid particles in aquaculture wastewater of Nile tilapia (Oreochromis niloticus) and its influence on the aquaculture water body, with an aim to provide a theoretical basis for the research and development and design of aquaculture wastewater treatment system.【Method】The aquaculture wastewater of Nile tilapia pond was treated by static sedimentation. Samples of aquaculture wastewater at different depths were collected at different sedimentation times, and the particle size distribution, soluble organic components and water quality indexes of aquaculture wastewater were analyzed.【Result】Static sedimentation had no significant effect on the quality of aquaculture wastewater (P > 0.05), and only reduced the mass concentrations of total nitrogen (TN), total phosphorus (TP) and chemical oxygen demand (COD) in aquaculture wastewater surface. Suspended solids and algae in aquaculture wastewater could be separated by static sedimentation (P < 0.05). After static sedimentation for 5.0 h, the TSS, chlorophyll a mass concentration, turbidity and chromaticity of two-meter-high water decreased by 3 854 mg/L, 42 mg/L, 0.23 NTU and 309 degrees respectively, and the TSS and chlorophyll a mass concentrations in aquaculture water decreased with the extension of sedimentation time. The results of particle size distribution showed that the settleable particles larger than 100 μm could be effectively separated by static sedimentation, but the fine particles lower than 30 μm could not be separated. The sedimentation velocity of solid particles was related to its particle size distribution range and mass concentration. The sedimentation velocity of solid particles decreased with the decrease of particle size distribution range and the increase of mass concentration. The results of three-dimensional fluorescence spectrum showed that the soluble organic compounds in the wastewater of Nile tilapia were mainly fulvic acid-like, and the soluble organic components in the wastewater could not be completely changed by static sedimentation.【Conclusion】Short time static sedimentation can effectively remove settleable particles in aquaculture wastewater, and the mass concentrations of TSS and chlorophyll a decrease with the extension of sedimentation time. However, static sedimentation cannot completely change the soluble organic components in the wastewater, nor can it significantly reduce the mass concentrations of nitrogen, phosphorus and other pollutants in aquaculture wastewater.

Abstract The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications. Here we introduce a single-cell laser emitting cytometry (SLEC) for label-free nucleolus differentiation through light-matter interactions within a Fabry–Perot resonator. The separated gain medium enhances the threshold difference by 36-fold between nucleolus and its surroundings, enabling selective laser emissions at nucleolar area while maintaining lower-order mode. The laser emission image provides insights into structural inhomogeneity, temporal fluid-like dynamics, and pathological application. Lasing spectral fingerprint depicts the quantity and size of nucleoli within a single cell, showcasing the label-free flow cytometry for nucleolus. This approach holds promise for nucleolus-guided cell screening and drug evaluation, advancing the study of diseases such as cancer and neurodegenerative disorders.

Abstract Background Tranexamic acid (TXA) is a widely employed intervention in orthopedic surgeries to minimize blood loss and the need for postoperative transfusions. This study focuses on assessing the efficacy and safety of TXA specifically in undernourished older adults undergoing hip fracture procedures. Methods A total of 216 patients were classified into two groups based on the Geriatric Nutritional Risk Index: undernourished and normal. In total, 82 patients received intravenous TXA at a dosage of 15 mg/kg before incision, with an additional 1 g administered intravenously over a 3-hour period postoperatively. Postoperative hemoglobin (Hb) drop, blood transfusion rate, and the incidence of deep venous thrombosis (DVT) were assessed in each group according to the presence or absence of TXA. Additionally, demographic factors including age, sex, body mass index, and serum albumin were investigated. Results 51.9% patients were identified as undernourished, experiencing progressive anemia (Hb: 10.9 ± 1.5 g/dL) and hypoalbuminemia (serum albumin: 31.9 ± 8 g/L). In comparison with the normal group, undernourished individuals were more likely to sustain femoral neck fractures (undernutrition vs. normal: 56.2 vs. 42.3%) and less likely to incur trochanteric fractures (undernutrition vs. normal: 43.8 vs. 57.7%) (P = 0.043). TXA administration significantly reduced the transfusion rate (P = 0.014) and Hb drop (P = 0.001) in the normal nutritional group, while its impact on the undernourished group remained less pronounced. There was no significant association between TXA administration and the rate of DVT complications, irrespective of the nutritional status. Conclusions Undernutrition not only diminishes muscle strength and gait function, leading to various types of hip fractures, but it may also hinder the efficacy of TXA in reducing blood transfusion rates and blood loss.

Owing to their unique high-temperature mechanical properties and outstanding high-temperature oxidation resistance, superalloys have become key materials in aviation, aerospace, petrochemical, metallurgy, electric power, automotive, and other industrial fields. Due to the structural complexity and high manufacturing cost of the hot sections of aeroengines, vessel engines, and gas turbines, the development and practicality of superalloy welding technology are critical to satisfying the design and maintenance requirements of hot sections. In this work, the research progress of superalloy fusion welding is described. Its advantages and application scope, such as arc welding, electron beam welding, and laser welding, are elaborated. Common types of welding cracks are introduced, and the mechanisms and influencing factors of solidification cracks, liquation cracks, strain-age cracks, and ductility-dip cracks are summarized. The primary techniques to enhance the weldability of fusion welding are also examined in terms of heat input, material composition, microstructure, and welding residual stress. The requirements for the temperature-bearing level of superalloys in industrial development are constantly increasing; thus, the types of superalloys are also being iteratively updated. They have evolved from deformed superalloys to ordinary cast polycrystalline superalloys to novel superalloy materials such as directional solidification and single-crystal superalloys. Thus, continuously conducting welding research on emerging superalloys, traditional nonweldable superalloys, and dissimilar materials that are extremely incompatible with metallurgy is necessary. Because the composition and microstructure of the base material have an important bearing on weldability, it is necessary to strengthen the composition design of emerging superalloys and conventional nonweldable superalloys in future works. Moreover, it is critical to pay attention to the improvement of welding process technology and pre- and post-weld treatment methods. In particular, research on detection and elimination measures of welding residual stress should be strengthened, which is one of the most effective approaches for lowering the weld crack-sensitivity of superalloys. This is of great importance for synergistically enhancing the welding performance of superalloys. Moreover, monitoring and simulation techniques for the welding process can be used to perform in-depth research on scientific issues such as molten pool flow and welding heat and mass transfer during the fusion welding process. This is of great scientific value for promoting the development of fusion welding technology. Based on the foundation of enhancing welding processes, future work on automation and intelligence of welding processes should also gradually deepen, which is one of the important directions to improve welding stability and reliability and promote the widespread application of superalloy fusion welding.

Abstract The residue of atrazine in field soils poses a major threat to crop growth in the rotation system, raising concerns about grain security and food safety. Current agricultural production requires more efficient and cost-effective mitigation measures in response to the emerging threat. This study reported the critical concentration (0.1 mg L−1) of atrazine injury to soybean seedlings in soil pore water and how biochar amendment could influence the distribution of atrazine in different soil environments. The results showed that biochar significantly reduced the concentration of atrazine in soil pore water, for example, 0.5% biochar in red (cinnamon, fluvo-aquic, paddy, black) soil reduced atrazine concentration from 0.31 (0.20, 0.18, 0.12, 0.03) mg L−1 to 0.004 (0.002, 0.005, 0.013, 0.011) mg L−1 in pore water (P

Abstract The biodegradable polymer poly-β-hydroxybutyrate (PHB) is a promising carbon source for biological mitigation of nitrogen pollution, a significant problem in aquaculture that physical and chemical methods have not provided a comprehensive solution. Here we investigated the impact of PHB on the zero-water-change largemouth bass culture by 30- and 40-day experiments. PHB loaded into the filter circulation pump at 4 g L− 1, optimum value determined by the first experiment, significantly reduced the levels of nitrate by 99.65%, nitrite by 95.96%, and total nitrogen by 85.22% compared to the control without PHB. PHB also significantly increased denitrifying bacteria (e.g., Proteobacteria and Fusobacteria) and expression of denitrification genes (e.g., nirK and nirS) in the microbial community, improving growth and health parameters of largemouth bass. While the impact may vary in other culture systems, PHB thus demonstrated its remarkable utility in aquaculture, highlighting ecological assessment and application to larger aquaculture operations as future considerations.

IntroductionSensorimotor synchronization (SMS) is the human ability to align body movement rhythms with external rhythmic stimuli. While the effects of rhythmic stimuli containing only temporal information on SMS have been extensively studied, less is known about how spatial information affects SMS performance. This study investigates the neural mechanisms underlying SMS with rhythmic stimuli that include both temporal and spatial information, providing insights into the influence of these factors across different sensory modalities.MethodsThis study compared the effects temporal information and spatial information on SMS performance across different stimuli conditions. We simultaneously recorded the electroencephalogram (EEG), the electromyogram (EMG), and behavioral data as subjects performed synchronized tapping to rhythmic stimuli. The study analyzed SMS performance under conditions including auditory, visual, and auditory-visual motion stimuli (containing both temporal and spatial information), as well as auditory, visual, and auditory-visual non-motion stimuli (containing only temporal information). Specifically, the research examined behavioral data (i.e., mean asynchrony, absolute asynchrony, and variability), neural oscillations, cortico-muscular coherence (CMC), and brain connectivity.ResultsThe results demonstrated that SMS performance was superior with rhythmic stimuli containing both temporal and spatial information compared to stimuli with only temporal information. Moreover, sensory-motor neural entrainment was stronger during SMS with rhythmic stimuli containing spatial information within the same sensory modality. SMS with both types of rhythmic stimuli was found to be dynamically modulated by neural oscillations and cortical-muscular coupling in the beta band (13-30 Hz).DiscussionThese findings provide deeper insights into the combined effects of temporal and spatial information, as well as sensory modality, on SMS performance. The study highlights the dynamic modulation of SMS by neural oscillations and CMC, particularly in the beta band, offering valuable contributions to understanding the neural basis of sensorimotor synchronization.

The pregnane X receptor (PXR)/nuclear factor-kB (NF-kB) signaling pathway plays a critical role in regulating toxin-induced inflammation and apoptosis in mammals. Whether dietary curcumin (CUR) can prevent copper (Cu)-induced liver injury via this signaling pathway remains to be established in aquatic animals. Juvenile largemouth bass (Micropterus salmoides) were exposed to dietary Cu and CUR treatments for 8 weeks. The results showed that chronic Cu exposure induced oxidative stress, causing liver function damage and liver injury. Cu exposure stimulated inflammation by regulating nf-kb and pro-inflammatory genes such as tnfα and il-1β and promoted apoptotic signals in the liver by modulating bcl2 and casp3 mRNA levels. In addition, Pearson correlation analysis verified that inflammatory and apoptotic responses were important indicators of Cu-induced liver injury. CUR attenuated stress responses by enhancing the antioxidant system. Importantly, CUR significantly stimulated PXR mRNA and protein levels in the Cu + CUR group and suppressed NF-κB activation to inhibit the inflammatory and apoptotic signaling cascade. These results suggest that CUR may be an effective activator of PXR in teleost fishes, exerting cytoprotective effects on Cu-induced liver injury via a PXR-mediated NF-κB repression mechanism. In conclusion, this study is the first to demonstrate that CUR may act as a potent PXR ligand that exerts hepatoprotective effects against Cu-induced liver injury. The findings shed light on the specific regulatory role of the PXR/NF-κB signaling pathway in liver pathogenesis and its potential as a therapeutic target in teleost fishes.

Peritoneal metastasis (PM) pathophysiology is complex and not fully understood. PM, originating from gastrointestinal (GI) cancer, is a condition that significantly worsens patient prognosis due to its complex nature and limited treatment options. The non-coding RNAs (ncRNAs) have been shown to play pivotal roles in cancer biology, influencing tumorigenesis, progression, metastasis, and therapeutic resistance. Increasing evidence has demonstrated the regulatory functions of different classes of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in PM. Identifying biomarkers for early detection of PM is a crucial step towards improving patient outcomes, and how ncRNA profiles correlate with survival rates, response to therapy, and recurrence risks have raised much attention in recent years. Additionally, exploring innovative therapeutic approaches utilizing ncRNAs, such as targeted therapy and gene silencing, may offer new horizons in treating this dire condition. Recent advances in systemic treatments and the development of novel loco-regional therapies have opened doors to multimodal treatment approaches. Radical surgeries combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have shown promising results, leading to extended patient survival. Current research is focused on the molecular characterization of PM, which is crucial for early detection and developing future therapeutic strategies. By summarizing the latest findings, this study underscores the transformative potential of ncRNAs in enhancing the diagnosis, prognosis, and treatment of PM in GI cancer, paving the way for more personalized and effective clinical strategies.

Local hypoxia in tumors poses significant challenges to the effectiveness of oxygen-dependent photodynamic therapy (PDT). Herein, a versatile mitochondrial targeting and pH-responsive nanozyme platform (noted as Mito CPs-p) is developed for solving local hypoxia in tumors and enhancing the PDT efficiency. Mito CPs-p, which consists of carbon-dot-supported atomically dispersed platinum (CPs) with further surface modifications of triphenylphosphine (PPh3) and pH-responsive porphyrin polymers. The PDT of Mito CPs-p was activated in acidic tumor microenvironment and exposed platinum for catalyzing endogenous H2O2 decomposition to produce O2 at tumor sites, due to the hydrophobic-hydrophilic transition of pH-responsive porphyrin-containing polymers in Mito CPs-p from hydrophobic to hydrophilic, which can markedly enhance PDT efficiency. Besides, the rational integration of mitochondria-targeting will improve the bioavailability of reactive oxygen species and further strengthen the PDT efficiency. In vitro results indicated that Mito CPs-p has exhibited excellent mitochondrial targeting capability and the ROS yield of Mito CPs-p was dramatically amplified. In vivo data further revealed that the Mito CPs-p displayed superb therapeutic efficacy. Hence, the Mito CPs-p provides new insights for efficient PDT in hypoxia solid tumors.

Abstract In the nearshore area, ocean current display intricate complexities due to interactions among tide, river, and coastline, which makes accurate current modeling challenging. Continuous in situ observation with high spatial and temporal resolution helps to better understand the dynamics of these currents. In this study, we used a 10‐km long submarine fiber‐optic cable with distributed acoustic sensing technology to record seismic signals associated with ocean waves. The current velocity and water depth were obtained from the velocity dispersion using frequency‐wave number analysis matched against theoretical ocean wave propagation equations. The results show remarkable agreement with observation of a nearby current meter, confirming the dominance of tidal currents as well as a small‐scale residual current. The temporal variation of water depth is consistent with observation by a nearby tidal gauge. This study demonstrates the potential of using submarine fiber‐optic cable for long‐term, high‐resolution, near real‐time nearshore current monitoring.

Abstract Binocular stereo vision relies on imaging disparity between two hemispherical retinas, which is essential to acquire image information in three dimensional environment. Therefore, retinomorphic electronics with structural and functional similarities to biological eyes are always highly desired to develop stereo vision perception system. In this work, a hemispherical optoelectronic memristor array based on Ag‐TiO2 nanoclusters/sodium alginate film is developed to realize binocular stereo vision. All‐optical modulation induced by plasmonic thermal effect and optical excitation in Ag‐TiO2 nanoclusters is exploited to realize in‐pixel image sensing and storage. Wide field of view (FOV) and spatial angle detection are experimentally demonstrated owing to the device arrangement and incident‐angle‐dependent characteristics in hemispherical geometry. Furthermore, depth perception and motion detection based on binocular disparity have been realized by constructing two retinomorphic memristive arrays. The results demonstrated in this work provide a promising strategy to develop all‐optically controlled memristor and promote the future development of binocular vision system with in‐sensor architecture.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.

ObjectiveThis study aimed to develop and assess a novel reverse dot blot assay for the simultaneous detection of 10 types of α-thalassemia alleles in the Chinese population, including six common variants of–SEA, -α3.7, -α4.2, αCS, αQS, and αWS, and four rare variants of αααanti−4.2, αααanti−3.7, --FIL deletion and--THAI deletion.MethodsThe novel thalassemia gene assay utilized a two-tier multiplex polymerase chain reaction amplification system and one round of hybridization. Genomic DNA samples were sourced from three hospitals in southern China. Each clinically validated DNA sample was re-evaluated using the new multiplex polymerase chain reaction/reverse dot blot assay Ⅲ (M-PCR/RDB Ⅲ).ResultsThe study analyzed a total of 1,148 unrelated participants, consisting of 810 thalassemia patients and 338 healthy control subjects. Valid hybridization results were obtained for 1,147 samples, with one case (thalassemia carrier) being excluded from the study due to the poor quality of DNA. All 1,147 samples, including those with α heterozygous thalassemia, α homozygous thalassemia, α compound heterozygous thalassemia, and control subjects were accurately genotyped, showing 100% concordance with the reference assays.ConclusionThe novel M-PCR/RDB Ⅲ assay proved to be simple, rapid, and precise, indicating its potential for genetic screening and clinical diagnosis of both common and rare α-thalassemia variants in Chinese populations.

Abstract Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms—Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)—customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience.

Abstract Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer’s disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ42, we developed an Aβ42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ42 misfolding, accelerating Aβ42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.

Abstract Broad bean (Vicia faba L.) has received attention from the food and animal feed industries as a sustainable, inexpensive, and versatile plant‐based protein source. However, long‐term consumption of broad bean, especially unprocessed ones, can lead to hepatic lipid accumulation. To investigate how broad bean affected hepatic lipid metabolism and its underlying mechanisms, we conducted a multi‐omics analysis of crisp grass carp (Ctenopharyngodon idellus C. et V) model with hepatic steatosis after feeding with single broad bean for 120 days. The glycolysis inhibition, increased de novo lipogenesis, abnormalities in lipid metabolism, and activation of oxidative stress were the key processes involved in broad bean‐induced hepatic lipid accumulation. Disturbances in intestinal flora caused by damage to the intestinal barrier and increased lipopolysaccharide caused by broad bean promoted hepatic lipid accumulation. Reduction of antinutritional factors and balanced diet offer potential strategies to mitigate the liver damage caused by broad bean consumption. Overall, our findings provided a theoretical basis for the wide application of broad bean as animal feeds.

Abstract N 1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.

Abstract Aim To explore the predictive value of lactate-to-albumin ratio (LAR) on 28-day mortality in patients with exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to the Intensive Care Unit (ICU). Methods According to ICD-9 and ICD-10 diagnosis codes, patients diagnosed with AECOPD in the Medical Information Mart for Intensive Care IV (v.2.2) database were selected. The primary endpoint was 28-day mortality after ICU admission. We used receiver operating characteristic (ROC) curve, Kaplan–Meier (K–M) survival curve, logistic regression analyses and subgroup analysis to assess predictive power of LAR. Results 606 patients were included in this study. The 28-day mortality was 29.7%. The area under the ROC curves (AUC) for LAR were 0.641 [95% confidence interval (CI) 0.592–0.689], which was comparable with OASIS (AUC: 0.662; 95% CI 0.616–0.709; p = 0.471) and SOFA (AUC: 0.660; 95% CI 0.612–0.708; p = 0.500). The cutoff value of LAR was 0.645 by ROC curve. The high-LAR group showed a bad prognosis in K–M analysis (p

Abstract Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Abstract Photovoltaic power generation is a promising method for generating electricity with a wide range of applications and development potential. It primarily utilizes solar energy and offers sustainable development, green environmental benefits, and abundant solar energy resources. However, there are many external factors that can affect the output characteristics of Photovoltaic cells and the effectiveness of the grid-connected control system. This study describes the introduction of Modular Multilevel Converter (MMC) technology into photovoltaic power generation systems to improve power generation efficiency. It proposes optimizing and improving the technology by adjusting the temperature and magnitude of lighting and combining traditional algorithms to propose a composite control algorithm. The photovoltaic power generation system employs the modular multi-level converter technology to enhance power generation efficiency alongside optimization and improvement. The temperature and size of light are regulated alongside the traditional algorithm to introduce the composite control algorithm. The improved composite algorithm surpasses the traditional one after experimental comparison of the results. The testing of a model photovoltaic power grid-connected system shows that the combination of modular multi-level converter technology and a photovoltaic grid-connected system, incorporating composite proportional integral control and quasi-proportional resonant control algorithms, yields improved results and feasibility. With rationality and effective control. The simulation results show that at 0.5 s, the light intensity suddenly increases from 750 to 1000 W/m2, and the direct-current voltage suddenly increases for a short time, but then decreases rapidly and finally returns to a stable level close to the rated voltage. From this, it can be seen that when the light intensity continues to change, the voltage value on the direct-current bus side of this MMC grid-tied photovoltaic system can still be maintained close to the rated value, ensuring the operational stability of the entire system. Sensibly and effectively controlled. The implementation of MMC technology in photovoltaic power generation systems enhances power generation efficiency, whilst simultaneously supporting the advancement of photovoltaic power generation and contributing towards environmental protection in the long term.

In this paper, we consider maximum hands-off control problem governed by a nonlinear dynamical system, where the maximum hands-off control constraint is characterized by an $ L^{0} $ norm. For this problem, we first approximate the $ L^{0} $ norm constraint by a $ L^{1} $ norm constraint. Then, the control parameterization together with sequential adaptive switching time optimization technique is proposed to approximate the optimal control problem by a sequence of finite-dimensional optimization problems. Furthermore, a smoothing technique is exploited to approximate the non-smooth maximum operator and an error analysis is investigated for this approximation. The gradients of the cost functional with respect to the decision variables in the approximate problem are derived. On the basis of these results, we develop a gradient-based optimization algorithm to solve the resulting optimization problem. Finally, an example is solved to demonstrate the effectiveness of the proposed algorithm.

Abstract Background Pyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI. Methods and results The expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis. Conclusion Our results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI. Graphical Abstract We found that the expression of ACSS2 was significantly increased in RTECs in septic AKI. ACSS2-deficient mice displayed resistance to renal damage in this model. ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the KLF5/NF-κB pathway in RTECs. Pharmacological inhibition of KLF5 suppressed NLRP3 activation and caspase-1 cleavage by downregulating of NF-κB. Our results suggest that ACSS2 is a pro-pathogenic mediator of cell pyroptosis of RTECs and renal inflammation in sepsis-induced AKI.

Traditional imaging methods have limitations in the diagnosis of peripheral lung lesions. The aim of this study is to evaluate the diagnostic value of the distance measurement method based on ultrasound image-based inverted electrostrain (rEBUS) combined with thoracoscopic lung biopsy (TBLB) for peripheral lung lesions. A group of patients with peripheral lung lesions were recruited for the study, and rEBUS examination was performed simultaneously during TBLB. Using rEBUS ultrasound images combined with electrostrain information, evaluate the morphological characteristics of peripheral lung lesions and the elastic properties of internal tissues. By comparing with pathological examination results, both rEBUS-D-TBLB and rEBUS-GS-TBLB have a higher positive diagnostic rate for PPL under bronchoscopy. However, rEBUS-D-TBLB is more effective in diagnosing benign PPL with ≥ 3 cm PPL than rEBUS-GS-TBLB. The rEBUS-TBLB combined ranging method has shown high accuracy and sensitivity in diagnosing peripheral lung lesions. Ultrasound images provide clear morphological features of the tumor, while the electrical strain information of rEBUS provides elastic information of the internal tissue of the tumor, further improving the accuracy of diagnosis.

At present, RC utility tunnels are widely used in urban utility tunnels. As a typical confined space, the complex load effect generated by the internal gas explosion of the gas tank of utility tunnel may lead to local damage or overall destruction of the structure of RC utility tunnel. Therefore, it is an important topic to improve the anti-explosion capability of the utility tunnel and ensure the normal operation of the utility tunnel after gas explosion. UHPC structure is considered to have excellent anti-explosion performance, so a ribbed thin-walled UHPC utility tunnel structure was proposed, which improved the overall stiffness and anti-explosion performance of the UHPC utility tunnel through the ribbed section. In view of the shortcomings of fluid-solid coupling method in gas simulation, Computational Fluid Dynamics (CFD) was used to calculate the overpressure distribution after gas explosion in UHPC utility tunnel. The accuracy of UHPC constitutive model and prestress simulation method was verified by testing results from the gas explosion on unbonded prestressed UHPC slab. The gas explosion damage mechanism of ribbed thin-walled UHPC utility tunnel, UHPC-NC combined utility tunnel and RC utility tunnel were comparatively analyzed. And the pre-fabricated stiffener height, UHPC slab thickness and UHPC strength were investigated on the anti-explosion performance of ribbed thin-walled UHPC utility tunnel against gas explosion. It is found that the UHPC strength needs to be enhanced dramatically to improve the blast resistance. The anti-explosion capability of utility tunnel can be effectively increased by increasing the rib height or increasing the thickness of the UHPC utility tunnel structure, and the damage pattern of the utility tunnel can also be changed from flexure-shear failure to bending failure. The results of the study can provide a reference for the damage analysis and anti-explosion design of ribbed thin-walled UHPC utility tunnels.

As a typical tight sandstone gas reservoir in the Ordos Basin, the second member of the Shanxi Formation in the XQ gas field in the Ordos Basin has had rich gas reservoirs and good development effects in the past. On the basis of previous studies, this paper brings new understanding to the sedimentary model of this area. Nine kinds of single lithofacies and seven kinds of lithofacies combinations are determined. Braided fluvial fan deposits in distributive fluvial systems likely developed in this area. The study area is part of the middle subfacies of this sedimentary facies, and five kinds of sedimentary microfacies environments developed. Finally, establishing sedimentary model based on sedimentary characteristics. The braided fluvial fan sedimentary model based on DFS is of great significance for deepening the understanding of terrestrial sedimentary systems and providing guidance for the exploration and development of oil and gas bearing basins.

IntroductionAmidst an emerging infectious disease outbreak, the rational allocation of vaccines and medical resources is crucial for controlling the epidemic’s progression.MethodAnalysing COVID-19 data in Taiyuan City from December 2022 to January 2023, this study constructed a SV1V2V3EIQHR dynamics model to assess the impact of COVID-19 vaccination and resource allocation on epidemic trends.ResultsVaccination significantly reduces infection rates, hospitalisations, and severe cases, while also curtailing strain on medical resources by reducing congestion periods. An early and sufficient reserve of medical resources can delay the onset of medical congestion, and with increased maximum capacity of medical resources, the congestion’s end can be accelerated. Stronger resource allocation capabilities lead to earlier congestion resolution within a fixed total resource pool.DiscussionIntegrating vaccination and medical resource allocation can effectively reduce medical congestion duration and alleviate the epidemic’s strain on medical resource capacity (CCMR).

Abstract Vasculogenic mimicry (VM) describes a process by which tumor cells formed a novel microcirculation pattern in an endothelial cell‐free manner. Clinically, VM is associated with aggressive phenotype and poor patient survival. However, the current models for investigating VM include 2D monolayer cultures, Matrigel‐based cultures, and animal models, each of which has limitations. Matrigel‐based models often exhibit batch‐to‐batch variations, while in vivo tumor models currently produce insufficient amounts of VM. There is currently no suitable tumor model to discover new therapeutic targets against VM. Herein, we establish an extracellular matrix (ECM)‐based engineered tumor model in vivo and in vitro. In this study, we demonstrate that matrix proteins enhanced the VM formation in the engineered xenograft model. Furthermore, we also investigated the role of collagen/fibronectin (FN) in melanoma progression and VM formation. Compared with cells cultured on TCPS plates, the B16F10 cells cultured on collagen/FN coated plates showed increased proliferation and stemness, and significantly enhanced invasion and formation of VM networks. Molecular mechanism analysis showed that Integrin/VE‐cadherin/EphA2/PI3K/MMP‐2 signaling pathways are responsible for VM formation. Our results indicate that collagen/FN matrix plays an important role in VM formation in melanoma, suggesting that ECM protein is a potential therapeutic target for anti‐VM therapy for melanoma.

Osteoporotic femoral neck fractures (OFNFs) pose a significant orthopedic challenge in the elderly population, accounting for up to 40% of all osteoporotic fractures and leading to considerable health deterioration and increased mortality. In addressing the critical need for early identification of osteoporosis through routine screening of femoral neck bone mineral density (FNBMD), this study developed a user-friendly prediction model aimed at men aged 50 years and older, a demographic often overlooked in osteoporosis screening. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study involved outlier detection and handling, missing value imputation via the K nearest neighbor (KNN) algorithm, and data normalization and encoding. The dataset was split into training and test sets with a 7:3 ratio, followed by feature screening through the least absolute shrinkage and selection operator (LASSO) and the Boruta algorithm. Eight different machine learning algorithms were then employed to construct predictive models, with their performance evaluated through a comprehensive metric suite. The random forest regressor (RFR) emerged as the most effective model, characterized by key predictors such as age, body mass index (BMI), poverty income ratio (PIR), serum calcium, and race, achieving a coefficient of determination (R²) of 0.218 and maintaining robustness in sensitivity analyses. Notably, excluding race from the model resulted in sustained high performance, underscoring the model’s adaptability. Interpretations using Shapley additive explanations (SHAP) highlighted the influence of each feature on FNBMD. These findings indicate that our predictive model effectively aids in the early detection of osteoporosis, potentially reducing the incidence of OFNFs in this high-risk population.

Currently, solid waste accumulates significantly, including red mud (RM) and fly ash (FA). Meanwhile, traditional cement-based curing agents pose challenges due to their high energy consumption and substantial pollution during the remediation of heavy metal-contaminated soil. In light of the need for resource utilization of solid waste and demands for energy conservation and emission reduction, this study investigates the stabilization/solidification of Cu2+-contaminated loess using a novel curing agent. This agent comprises low-energy, environmentally friendly high-belite sulfoaluminate cement (HBSAC) and quicklime (CaO) mixed with RM and FA. The study evaluates the samples across various metrics, including mechanical properties, permeability, pH, conductivity, leached ion concentration, and microstructure, to systematically investigate the curing effect and mechanism of the new curing agent on contaminated soil. It conducts an assessment related to the economics and carbon emissions of the solidified body. The results show that the optimal ratio for the curing agent consists of RM and FA, CaO, and HBSAC at 20%, 5%, and 7%, respectively, with a water-to-solid ratio of 0.38 and a mass ratio of RM to FA at 13:2. This new curing agent not only possesses superior properties but also offers excellent economic benefits and reduces carbon emissions. It holds significant potential for applications in the remediation of Cu2+-contaminated soils.

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

Abstract Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water‐in‐oil‐in‐water (W/O/W) technique, was employed to fabricate Fe3O4‐based poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound‐assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM‐coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high‐fat diet fed to ApoE−/− (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet‐membrane‐coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.

Habitual dietary changes have the potential to induce alterations in the host’s gut microbiota. Mandarin fish (Siniperca chuatsi), an aquatic vertebrate species with distinct feeding habits, were fed with natural feeds (NF) and artificial feeds (AF) to simulate the effects of natural and processed food consumption on host gut microbiota assemblages. The results showed that the alpha diversity index was reduced in the AF diet treatment, as lower abundance and diversity of the gut microbiota were observed, which could be attributed to the colonized microorganisms of the diet itself and the incorporation of plant-derived proteins or carbohydrates. The β-diversity analysis indicated that the two dietary treatments were associated with distinct bacterial communities. The AF diet had a significantly higher abundance of Bacteroidota and a lower abundance of Actinomycetota, Acidobacteriota, and Chloroflexota compared to the NF group. In addition, Bacteroidota was the biomarker in the gut of mandarin fish from the AF treatment, while Acidobacteriota was distinguished in the NF treatments. Additionally, the increased abundance of Bacteroidota in the AF diet group contributed to the improved fermentation and nutrient assimilation, as supported by the metabolic functional prediction and transcriptome verification. Overall, the present work used the mandarin fish as a vertebrate model to uncover the effects of habitual dietary changes on the evolution of the host microbiota, which may provide potential insights for the substitution of natural foods by processed foods in mammals.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection. This new method improves packaging of yield-inhibiting transgenes by up to 10-fold, and generates rAAV batches with reduced plasmid backbone contamination that otherwise cannot be eliminated in downstream processing. When tested in mice and compared with rAAV produced by standard triple transfection, low-cis rAAV shows comparable or superior potency and results in diminished plasmid backbone DNA and RNA persistence in tissue. Mechanistically, low-cis triple transfection relies on the extensive replication of transgene cassette (i.e., inverted terminal repeat-flanked vector DNA) in HEK293 cells during production phase. This cost-effective method can be easily implemented and is widely applicable to producing rAAV of high quantity, purity, and potency.

Abstract Physiological regulation of transgene expression is a major challenge in gene therapy. Onasemnogene abeparvovec (Zolgensma®) is an approved adeno-associated virus (AAV) vector gene therapy for infants with spinal muscular atrophy (SMA), however, adverse events have been observed in both animals and patients following treatment. The construct contains a native human survival motor neuron 1 (hSMN1) transgene driven by a strong, cytomegalovirus enhancer/chicken β-actin (CMVen/CB) promoter providing high, ubiquitous tissue expression of SMN. We developed a second-generation AAV9 gene therapy expressing a codon-optimized hSMN1 transgene driven by a promoter derived from the native hSMN1 gene. This vector restored SMN expression close to physiological levels in the central nervous system and major systemic organs of a severe SMA mouse model. In a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec, the 2nd-generation vector showed better safety and improved efficacy in SMA mouse model.

Abstract Nme2Cas9 has been established as a genome editing platform with compact size, high accuracy, and broad targeting range, including single-AAV-deliverable adenine base editors. Here, we engineer Nme2Cas9 to further increase the activity and targeting scope of compact Nme2Cas9 base editors. We first use domain insertion to position the deaminase domain nearer the displaced DNA strand in the target-bound complex. These domain-inlaid Nme2Cas9 variants exhibit shifted editing windows and increased activity in comparison to the N-terminally fused Nme2-ABE. We next expand the editing scope by swapping the Nme2Cas9 PAM-interacting domain with that of SmuCas9, which we had previously defined as recognizing a single-cytidine PAM. We then use these enhancements to introduce therapeutically relevant edits in a variety of cell types. Finally, we validate domain-inlaid Nme2-ABEs for single-AAV delivery in vivo.

Abstract Fibre‐reinforced polymer (FRP)/rigid polyurethane foam (RPUF) interface is susceptible to moisture intrusion in addition to natural ageing during operation. This study investigated the influence of moisture intrusion on the FRP/RPUF interface under natural ageing using experiments and molecular dynamics (MD) simulations. Water absorption, shear strength, and leakage current tests were used to clarify the changes in the interface performance. The degradation mechanism of moisture intrusion at the interface under natural ageing was revealed by MD simulation and micro‐characterisation. The results show that the natural ageing of interfacial materials will slightly reduce the quality of the interface but will reduce the water resistance of the material and promote the process of water intrusion into the interface. In addition, water mainly invades the interface through RPUF. After water penetration, the interfacial bonding strength and insulation performance significantly decreased. Plasticisation and hydrolysis of interfacial materials are the main reasons for decreased interfacial adhesion. Hydrolysis can cause irreversible damage to the interface, increasing interface defects and water absorption. The vicious cycle of material hydrolysis is the ultimate cause of interfacial debonding. The polar molecules produced by this process and the water absorbed by the interface caused the degradation of the interface insulation performance.

Wind turbines are one of the important carriers of clean energy utilization. Accurately and rapidly detecting wind turbine objects in large-scale remote sensing images can effectively monitor the development activities and optimize energy utilization. Addressing the detection challenges posed by the complex distribution scenes and the slender, dispersed structural characteristics of wind turbines in remote sensing images, this article proposes a remote sensing image wind turbine detector, RSWDet, based on neural networks. RSWDet comprises two innovative key modules. The first is a dual-branch structured point set detection head, which, through training, adapts to the unique features of wind turbines, enabling accurate detection in large-scale complex backgrounds. The second is the Low-level Feature Enhancement module, which compensates for the loss of wind turbine feature information during sampling by leveraging rich low-level feature information. Experimental verification of RSWDet was conducted on datasets and real-world scenes. The results demonstrate that RSWDet exhibits significant advantages compared to other algorithms, achieving the highest average accuracy of 83.1%, Precision of 97.8%, and Recall of 99% on the validation set. In the actual multiscene GF2 remote sensing image test, with a threshold of 0.4, the Precision can reach 85.3%, and the Recall can reach 89.9%.

Abstract Background Natural proteins occupy a small portion of the protein sequence space, whereas artificial proteins can explore a wider range of possibilities within the sequence space. However, specific requirements may not be met when generating sequences blindly. Research indicates that small proteins have notable advantages, including high stability, accurate resolution prediction, and facile specificity modification. Results This study involves the construction of a neural network model named TopoProGenerator(TPGen) using a transformer decoder. The model is trained with sequences consisting of a maximum of 65 amino acids. The training process of TopoProGenerator incorporates reinforcement learning and adversarial learning, for fine-tuning. Additionally, it encompasses a stability predictive model trained with a dataset comprising over 200,000 sequences. The results demonstrate that TopoProGenerator is capable of designing stable small protein sequences with specified topology structures. Conclusion TPGen has the ability to generate protein sequences that fold into the specified topology, and the pretraining and fine-tuning methods proposed in this study can serve as a framework for designing various types of proteins.

Abstract The invasive capacity of lung adenocarcinoma (LUAD) is an important factor influencing patients’ metastatic status and survival outcomes. However, there is still a lack of suitable biomarkers to evaluate tumor invasiveness. LUAD molecular subtypes were identified by unsupervised consistent clustering of LUAD. The differences in prognosis, tumor microenvironment (TME), and mutation were assessed among different subtypes. After that, the invasion-related gene score (IRGS) was constructed by genetic differential analysis, WGCNA analysis, and LASSO analysis, then we evaluated the relationship between IRGS and invasive characteristics, TME, and prognosis. The predictive ability of the IRGS was verified by in vitro experiments. Next, the “oncoPredict” R package and CMap were used to assess the potential value of IRGS in drug therapy. The results showed that LUAD was clustered into two molecular subtypes. And the C1 subtype exhibited a worse prognosis, higher stemness enrichment activity, less immune infiltration, and higher mutation frequency. Subsequently, IRGS developed based on molecular subtypes demonstrated a strong association with malignant characteristics such as invasive features, higher stemness scores, less immune infiltration, and worse survival. In vitro experiments showed that the higher IRGS LUAD cell had a stronger invasive capacity than the lower IRGS LUAD cell. Predictive analysis based on the “oncoPredict” R package showed that the high IRGS group was more sensitive to docetaxel, erlotinib, paclitaxel, and gefitinib. Among them, in vitro experiments verified the greater killing effect of paclitaxel on high IRGS cell lines. In addition, CMap showed that purvalanol-a, angiogenesis-inhibitor, and masitinib have potential therapeutic effects in the high IRGS group. In summary we identified and analyzed the molecular subtypes associated with the invasiveness of LUAD and developed IRGS that can efficiently predict the prognosis and invasive ability of the tumor. IRGS may be able to facilitate the precision treatment of LUAD to some extent.

Abstract Background In 2022, Omicron outbreaks occurred at multiple sites in China. It is of great importance to track the incidence trends and transmission dynamics of coronavirus disease 2019 (COVID-19) to guide further interventions. Methods Given the population size, economic level and transport level similarities, two groups of outbreaks (Shanghai vs. Chengdu and Sanya vs. Beihai) were selected for analysis. We developed the SEAIQRD, ARIMA, and LSTM models to seek optimal modeling techniques for waves associated with the Omicron variant regarding data predictive performance and mechanism transmission dynamics, respectively. In addition, we quantitatively modeled the impacts of different combinations of more stringent interventions on the course of the epidemic through scenario analyses. Results The best-performing LSTM model showed better prediction accuracy than the best-performing SEAIQRD and ARIMA models in most cases studied. The SEAIQRD model had an absolute advantage in exploring the transmission dynamics of the outbreaks. Regardless of the time to inflection point or the time to R t curve below 1.0, Shanghai was later than Chengdu (day 46 vs. day 12/day 54 vs. day 14), and Sanya was later than Beihai (day 16 vs. day 12/day 20 vs. day 16). Regardless of the number of peak cases or the cumulative number of infections, Shanghai was higher than Chengdu (34,350 vs. 188/623,870 vs. 2,181), and Sanya was higher than Beihai (1,105 vs. 203/16,289 vs. 3,184). Scenario analyses suggested that upgrading control level in advance, while increasing the index decline rate and quarantine rate, were of great significance for shortening the time to peak and R t below 1.0, as well as reducing the number of peak cases and final affected population. Conclusions The LSTM model has great potential for predicting the prevalence of Omicron outbreaks, whereas the SEAIQRD model is highly effective in revealing their internal transmission mechanisms. We recommended the use of joint interventions to contain the spread of the virus.

Abstract The carbonate rock formations have obvious dual media characteristics, fracture development and good physical conditions, which are the main seepage channels and storage spaces for gas after the reconstruction of underground gas storage. The carbonate strata of the Ordovician system are important natural gas reservoirs in the eastern area of Sulige Gas Field in the Ordos Basin, and the identification and characterization of their fractures are of great significance for the modeling of fractures in the later stage and the improvement of the operation scheme of the gas storage. At present, there is little research on fractures, which restricts exploration and development. Therefore, taking the 39–61 gas storage reservoir in the eastern area of Sulige Gas Field in the Ordos Basin as the research object, this paper identifies and studies the characteristics of the fractures by core, microscopic, conventional logging curves, and imaging logging identification. The results show that the fracture length ranges from 5 to 15 cm and the width ranges from 0.1 to 3 mm. The fracture angles are mostly between 75° and 90° and the main direction is NW–SE. In conventional logging curves, porosity logging has a good response to fractures, while resistivity logging has a general response to fractures; In layers with more developed fractures, natural gamma values are mostly higher than 40API, rock volume density is less than 2.8 g/cm3, neutron porosity is greater than 12.5%, and acoustic time difference is greater than 160 μ s/m. This study is of great significance for improving the identification of carbonate fractures, enriching the relevant theories, and providing guidance for the construction of carbonate gas storage.