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Abstract LC3-associated phagocytosis (LAP) is critical in host defense against invading pathogens, but the molecular mechanism for LAP activation is still unclear. Here, we find programmed cell death 6 (PDCD6) as a negative regulator of LAP. PDCD6 deficiency in mice and macrophages induces enhanced bactericidal activity and LAP formation. In parallel, lactate dehydrogenase A (LDHA) activity and lactate production is induced in macrophages challenged with bacteria, Zymosan or Pam3CSK4, while genetic ablation or pharmacological inhibition of LDHA reduces lactate levels and impairs bactericidal activity in vivo and in vitro. Mechanistically, PDCD6 interacts with LDHA to downregulate lactate metabolism, leading to reduced RUBCN lactylation at lysine33 (K33). By contrast, PDCD6-deficiency increases RUBCN lactylation, thereby promotes RUBCN interaction with VPS34, LAP formation, and protective responses. Our results thus suggest a PDCD6-LDHA-lactate-RUBCN axis of innate immunity regulation that may both contribute to protection from infectious diseases and serve as targets for therapeutic development.

Abstract Failure Modes, Effects, and Criticality Analysis (FMECA) is a commonly used method for analyzing system reliability. It is frequently applied in identifying weak points in the reliability of CNC machine tools. However, traditional FMECA has issues such as vague descriptions of risk factors, equal treatment of risk factors, and unclear directions for improving weak points. In response to the issue of vague descriptions of risk factors, this paper further expands severity (S) into machine hazard (M) and personal hazard (P), and subdivides detectability (D) into functional structural complexity (D 1) and detection cost (D 2). In addressing the issue of treating risk factors equally, this paper integrates Distance Analysis Method (DAM) and Grey Relational Analysis (GRA) to propose Distance-Grey Relational Analysis (D-GRA). Subsequently, based on the D-GRA method, the weights of each risk factor were determined by comprehensively considering expert system scores and actual economic loss indicators. In response to the issue of unclear improvement directions for weak points, this paper introduces the BCC model. It treats common failure modes of CNC machine tools as decision-making units within the BCC model, refines risk factors as input indicators, and evaluates the efficiency values of each decision-making unit based on various actual losses as output indicators. Through efficiency value analysis, it proposes improvement directions for weak points. Then, based on the weights of risk factors and the efficiency values of failure modes, a modified calculation method for the new Risk Priority Number (RPN) is proposed to amend the traditional RPN, This paper takes the electric spindle system of a certain machining center as an example, applies the proposed method to rank common failure modes with the new RPN, and compares it with other RPN calculation methods to verify the rationality of the proposed approach. Finally, it presents improvement directions for reliability enhancement.

Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

As the proportion of renewable energy infiltrating the power grid increases, suppressing its randomness and volatility, reducing its impact on the safe operation of the power grid, and improving the level of new energy consumption are increasingly important. For these purposes, energy storage stations (ESS) are receiving increasing attention. This article discusses the structure, working principle, and control methods of grid-following and grid-forming energy-storage converters, which are currently commonly used. A simulation analysis was conducted to investigate their dynamic response characteristics. The advantages and disadvantages of two types of energy storage power stations are discussed, and a configuration strategy for hybrid ESS is proposed. This paper presents research on and a simulation analysis of grid- forming and grid-following hybrid energy storage systems considering two types of energy storage according to different capacity scenarios. Finally, a comparative analysis between the systems is presented. A simulation model was established using PSD-BPA (Power System Department-Bonneville Power Administration) to analyze the impact of the capacity ratio of grid-following and grid-forming ESS on their dynamic response characteristics in a hybrid ESS. In addition, a development direction for future ESSs is indicated.

Abstract Treatment of Mycobacterium abscessus (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti‐Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH). ECH showed activity against Mab at a minimum inhibitory concentration (MIC) of 2 µg/ml. A ΔembC strain in which the embC gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078–0.0156 µg/ml). The MICs of ECH‐resistant strains screened with reference to ΔembC ranged from 0.25 to 1 µg/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ΔembC individually (MIC: 0.25–0.5 µg/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25–0.5 µg/ml). The permeability of these Mab strains with edited genes and overexpression was reduced, as evidenced by an ethidium bromide accumulation assay, but it remained significantly higher than that of the parent Mab. In summary, our study demonstrates that ECH exerts potent anti‐Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.

In Laser Powder Bed Fusion (L-PBF), surface roughness is pivotal for controlling the mechanical and functional performances, as well as the geometrical accuracy of the final product. This study extensively investigated the interactions of hatch and contour processing parameters, along with contour offset distance, on vertical surface roughness for 316L stainless steel in L-PBF. Melt pool morphology and surface arithmetic average roughness (Sa) were quantified using confocal microscopy, while scanning electron microscopy was employed to interpret the detailed microstructure of surface features. Under low volumetric energy density (VED) hatch conditions (e.g., 66.7 J/mm3), varying the contour offset distance has a negatable effect on the surface roughness when the contour VED is lower than 121.6 J/mm3, remaining relatively smooth surfaces dominated by bare melt tracks with sparely attached partially melted particles. Increasing the hatch or contour VED (e.g., 166.7 J/mm3), dross formation, identified by the microstructural differences and explained by the melt pool instability and migration, is inevitable, which dictates the surface roughness with higher Sa values. The larger contour offset distance further promotes the dross occurrence with irregularity and increases Sa. Employing a low contour VED with an appropriate offset distance and adopting the contour-first scan strategy was demonstrated as an effective solution to reduce the dross formation. Through the analysis of melt pool behavior, surface topography, and microstructure, this study elucidates the mechanisms governing dominant surface characteristics under the combined influence of hatch and contour parameters. It lays the foundation for precise control of surface roughness without altering hatching parameters, enabling the tailored manipulation of performance in additively manufactured structures.

Abstract Direct methane conversion to high-value chemicals under mild conditions is attractive yet challenging due to the inertness of methane and the high reactivity of valuable products. This work presents an efficient and selective strategy to achieve direct methane conversion through the oxidative coupling of methane over a visible-responsive Au-loaded CeO2 by photon-phonon co-driven catalysis. A record-high ethane yield of 755 μmol h−1 (15,100 μmol g−1 h−1) and selectivity of 93% are achieved under optimised reaction conditions, corresponding to an apparent quantum efficiency of 12% at 365 nm. Moreover, the high activity of the photocatalyst can be maintained for at least 120 h without noticeable decay. The pre-treatment of the catalyst at relatively high temperatures introduces oxygen vacancies, which improves oxygen adsorption and activation. Furthermore, Au, serving as a hole acceptor, facilitates charge separation, inhibits overoxidation and promotes the C-C coupling reaction. All these enhance photon efficiency and product yield.

Abstract Background As a novel regional analgesic technique, ultrasound-guided pericapsular nerve group (PENG) block has some potential advantages, and we designed a randomized clinical trial (RCT) to investigate whether the ultrasound-guided PENG block combined with general anesthesia can better reduce stress response, maintain intraoperative hemodynamic stability, and reduce postoperative analgesia in elderly hip arthroplasty compared with ultrasound-guided suprainguinal fascia iliaca block (SIFIB) combined with general anesthesia. Methods Seventy-four subjects were enrolled over an 8-month period (20 April 2023 to 31 December 2023). All patients were divided into the test group (group P) and the control group (group S) using the envelope as the randomization method. The test group was treated with preoperative ultrasound-guided PENG block analgesia combined with general anesthesia and the control group was treated with preoperative ultrasound-guided SIFIB analgesia combined with general anesthesia. The primary outcome selected was the patient Visual Analogue Scale (VAS) score at 12 h postoperatively. Results After generalized estimating equations (GEE) analysis, there was a statistically significant difference in the main effect of postoperative VAS score in group P compared with group S (P = 0.009), the time effect of VAS score in each group was significantly different (P

Abstract Oligodendrocyte precursor cells (OPCs) migrate extensively using blood vessels as physical scaffolds in the developing central nervous system. Although the association of OPCs with the vasculature is critical for migration, the regulatory mechanisms important for OPCs proliferative and oligodendrocyte development are unknown. Here, a correlation is demonstrated between the developing vasculature and OPCs response during brain development. Deletion of endothelial stimulator of interferon genes (STING) disrupts angiogenesis by inhibiting farnesyl‐diphosphate farnesyltransferase 1 (FDFT1) and thereby reducing cholesterol synthesis. Furthermore, the perturbation of metabolic homeostasis in endothelial cells increases interleukin 17D production which mediates the signal transduction from endothelial cells to OPCs, which inhibits oligodendrocyte development and myelination and causes behavioral abnormalities in adult mice. Overall, these findings indicate how the endothelial STING maintains metabolic homeostasis and contributes to oligodendrocyte precursor cells response in the developing neocortex.

Nearshore water-level prediction has a substantial impact on the daily lives of coastal residents, fishing operations, and disaster prevention and mitigation. Compared to the limitations and high costs of traditional empirical forecasts and numerical models for nearshore water-level prediction, data-driven artificial intelligence methods can more efficiently predict water levels. Attention mechanisms have recently shown great potential in natural language processing and video prediction. Convolutional long short-term memory(ConvLSTM) combines the advantages of convolutional neural networks (CNN) and long short-term Memory (LSTM), enabling more effective data feature extraction. Therefore, this study proposes a ConvLSTM nearshore water level prediction model that incorporates an attention mechanism. The ConvLSTM model extracts multiscale information from historical water levels, and the attention mechanism enhances the importance of key features, thereby improving the prediction accuracy and timeliness. The model structure was determined through experiments and relevant previous studies using five years of water level data from the Zhuhai Tide Station and the surrounding wind speed and rainfall data for training and evaluation. The results indicate that this model outperforms the four other baseline models of PCCs, RMSE, and MAE, effectively predicting future water levels at nearshore stations up to 48 h in advance. Compared to the ConvLSTM model, the model with the attention mechanism showed an average improvement of approximately 10% on the test set, with a greater error reduction in short-term forecasts than that in long-term forecasts. During Typhoon Higos, the model reduced the MAE of the best-performing baseline model by approximately 3.2 and 2.4 cm for the 6- and 24-hour forecasts, respectively, decreasing forecast errors by approximately 18% and 11%, effectively enhancing the ability of the model to forecast storm surges. This method provides a new approach for forecasting nearshore tides and storm surges.

ABSTRACT The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus.IMPORTANCEThis study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.

Nonylphenol (NP), an endocrine disruptor, has been demonstrated to be a harmful environmental contaminant and toxic to organisms. In this study, to address concerns regarding the immunotoxicity of NP, we treated clam Ruditapes philippinarum hemocytes with NP in vitro and explored the underlying mechanisms of NP-induced extracellular traps (ETs). NP could induce the formation of hemocytes ETs in a dose-dependent manner. Transcriptomics analysis revealed changes of signaling pathway involved in immunity and energy metabolism in hemocytes after NP stimulation. In this process, both reactive oxygen species (ROS) and myeloperoxidase (MPO) were up-regulated. Moreover, mitogen-activated protein kinase (MAPK) signaling pathway was proved to be activated in the formation of NP-induced ETs, manifested as enhanced phosphorylation of extracellular signal-regulated kinase (ERK) but not p38 or c-Jun N-terminal kinase (JNK). In the presence of U0126, an ERK phosphorylation inhibitor, the NP-induced expression of NADPH oxidase enzyme (NOX) was significantly decreased, which further alleviated the ROS production and ultimately limited the release of ETs. NP exposure increased glucose uptake, along with enhanced activities of glycolysis-related enzymes such as hexokinase (HK) and pyruvate kinase (PK). After inhibiting glycolysis by the inhibitor 2-DG, the formation of NP-induced ETs was significantly suppressed. ERK could regulate mTOR signaling and the PI3K/AKT pathway, potentially directing ETs formation by orchestrating the glycolysis through the activation of key transcription factors c-Myc and HIF-1α. Collectively, the results preliminary confirm that the ERK-NOX-ROS axis and glycolysis are involved in NP-induced ETs formation, contributing to the cellular immunotoxicity in clam.

IntroductionEarly diagnosis of oral squamous cell carcinoma can greatly improve treatment success rate and patient survival. Although Optical Coherence Tomography (OCT) based Angiography (OCTA) is a promising in vivo technique in oral imaging, there is a need for objective assessment of oral microvasculature.MethodsThis study aimed to demonstrate a comprehensive methodology of quantitative assessing OCTA intraoral scanning results to provide measurable, reproducible data and to avoid subjective visual interpretations. Data were collected from 37 healthy subjects in total across four intraoral sites—buccal mucosa (n = 32), labial mucosa (n = 24), floor of the mouth (n = 13), and hard palate (n = 8)—using a non-invasive swept-source OCT system. Four quantitative metrics—vessel area density, vessel skeleton density, vessel diameter index, and a newly proposed weighted Tortuosity Index—were used to assess OCTA images in oral applications.ResultsThe quadruple quantitative assessment’s repeatability was evaluated to be reliable. Analysis of a benign ulcer case revealed differences in these metrics compared to healthy cases.Discussion/ConclusionIn conclusion, we demonstrated a comprehensive method to quantify microvasculature in the oral cavity, showing considerable promise for early diagnosis and clinical management of oral diseases.

The integration of AI-based chatbots in language education has garnered significant attention, yet the interplay between chatbots and positive psychology remains underexplored. Filling this gap through a critical analysis of existing theories, measurement scales, and empirical evidence, this paper evaluates the potential benefits and drawbacks of incorporating AI chatbots in language learning environments and how AI chatbots may positively or negatively impact emotional dimensions of language acquisition. The findings unravel that the primary advantages of the AI chatbots are personalized instruction with rapid feedback, a decrease in anxiety levels and a surge in motivation, greater learner independence and self-directed learning, and the fostering of metacognitive abilities. Conversely, the identified obstacles encompass restricted emotional awareness, a deficiency in genuine human interaction, ethical dilemmas and privacy issues, as well as the potential reinforcement of biases and stereotypes. By highlighting the importance of learner emotions in the language learning process, this conceptual analysis review underscores the need for a nuanced understanding of how AI chatbots can support or hinder emotional engagement and motivation. The paper discusses the impacting factors of AI-based chatbots in language education, and strategies for addressing challenges and optimizing chatbot-learner interactions, such as incorporating affective computing techniques and designing culturally-sensitive chatbots. Finally, the article outlines future research directions, emphasizing the need for validated emotion scales in chatbot assisted language learning contexts, longitudinal studies, mixed-methods research, comparative analyses, and investigations into the role of chatbots in fostering emotional intelligence and intercultural competence.

China is the world’s largest CO2 emitter and coal consumer, and its coal dominated energy structure is difficult to be changed in the short term. In the context of carbon peaking and carbon neutrality, the capture and storage or conversion of carbon dioxide into renewable fuels and chemicals can reduce dependence on fossil fuels and at the same time reduce CO2 emissions, providing key technical support for the green transition of coal-fired power plants and energy chemicals. Electrocatalysis and microbial conversion are important ways to produce renewable fuels and chemicals from carbon dioxide. The reaction rate of electrocatalytic reduction of CO2 is high, but the products are mostly limited to C1 and C2 products. Microbial CO2 fixation has the advantages of high selectivity and variety of products. However, the low electron transfer and energy supply lead to a long reaction period in the microbial CO2 fixation. Integration of electrocatalysis and microbial conversion can play their advantages to efficiently produce the value-added multi-carbon products. In this paper, firstly, the reaction principles, typical products of electrocatalysis and microbial CO2 fixation under a single technical route were introduced respectively. The catalyst and reactor of electrocatalytic CO2 reduction were discussed, and the microbial species and biological metabolic pathways of microbial fixation of CO2 were summarized. Secondly, two methods of the integration of electrocatalysis and microbial conversion was reviewed, and the system structure, working principle, electrode materials and value-added products were analyzed. Finally, the technology readiness level of different coupling methods was compared, and the future prospects were highlighted from four aspects: the catalysts for electrocatalytic CO2 reduction, the engineered microbial strains, the design and integration of coupling systems and the linkage between academic research and industry.

In this paper, taking the mining of deep-buried water-covered coal seam in 4105 working face of Wenjiapo Coal Mine as an example, similar material simulation and numerical simulation methods are used to study the law of overburden failure and fracture zone development, and to explore the impact of deep-buried coal seam mining on the safety of Hongyan River. The research shows that when the working face continues to advance, the goaf area increases, and the overlying rock is bent and deformed under the action of gravity to form a separation layer. When the gravity exceeds the rock deformation limit, the overlying rock will be destroyed and deformed, and some separation layers will collapse and disappear. New separation layers are developed in the upper part of the caving body, and cracks are formed on both sides. The caving zone height of 4105 working face is stable at 164 m. With the continuous advancement of the working face, the height of the water-conducting fracture zone gradually increased and eventually stabilized at 244 m. The ground fissures extend 32 m downward from the surface. There is a 414 m rock layer above the water-conducting fracture zone as a protective layer, which is not connected to the surface and not communicated with the ground fissure. Therefore, Hongyan River will not leak, and the mining of coal seams will not affect Hongyan River.

Abstract Background White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. Case presentation We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. Conclusions This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.

Abstract Comprehending the complex interplay among urban mobility, human behavior, and the COVID-19 pandemic could deliver vital perspectives to steer forthcoming public health endeavors. In late 2022, China lifted its "Zero-COVID" policy and rapidly abandoned nearly all interventions. It provides a unique opportunity to observe spontaneous mobility changes without government restriction throughout such a pandemic with high infection. Based on 148 million travel data from the public bus, subway, and taxi systems in Shenzhen, China, our analysis reveals discernible spatial discrepancies within mobility patterns. This phenomenon can be ascribed to the heterogeneous responses of mobility behavior tailored to specific purposes and travel modes in reaction to the pandemic. Considering both the physiological effects of virus infection and subjective willingness to travel, a dynamic model is proposed and capable of fitting fine-grained urban mobility. The analysis and model can interpret mobility data and underlying population behavior to inform policymakers when evaluating public health strategies against future large-scale infectious diseases.

Abstract Electrochemical carbon dioxide/carbon monoxide reduction reaction offers a promising route to synthesize fuels and value-added chemicals, unfortunately their activities and selectivities remain unsatisfactory. Here, we present a general surface molecular tuning strategy by modifying Cu2O with a molecular pyridine-derivative. The surface modified Cu2O nanocubes by 4-mercaptopyridine display a high Faradaic efficiency of greater than 60% in electrochemical carbon monoxide reduction reaction to acetate with a current density as large as 380 mA/cm2 in a liquid electrolyte flow cell. In-situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy reveals stronger *CO signal with bridge configuration and stronger *OCCHO signal over modified Cu2O nanocubes by 4-mercaptopyridine than unmodified Cu2O nanocubes during electrochemical CO reduction. Density function theory calculations disclose that local molecular tuning can effectively regulate the electronic structure of copper catalyst, enhancing *CO and *CHO intermediates adsorption by the stabilization effect through hydrogen bonding, which can greatly promote asymmetric *CO-*CHO coupling in electrochemical carbon monoxide reduction reaction.

Background: The stromal vascular fraction (SVF), a cluster of stem and progenitor cells isolated from adipose tissue, holds significant promise for application in regenerative medicine. However, the existing methods for SVF isolation are time-consuming and expensive. Thus, in this study, we explored a new method of SVF extraction—ultrasound-assisted SVF isolation (USASI)—and compared the viability and characteristics of SVF isolated using different methods. Methods: SVF extraction methods using different combinations of ultrasound power, ultrasound time, collagenase dosage, and collagenase digestion time were compared with those of the control group (collagenase digestion method). The cell yield and vitality of the SVF were evaluated via cell counting and trypan blue staining. The cell components and immunophenotypes of freshly isolated SVF were analyzed using flow cytometry. The proliferative capacity and differentiation potential of the SVF were also identified. Results: Ultrasonication at 95 ​W-20 kHz for 30 ​s followed by digestion with 0.15% collagenase for 30 ​min was identified as the most suitable parameter for the USASI method in isolating SVF, as recommended based on the evaluation of various tested conditions. The USASI method significantly reduced the collagenase dosage and shortened the digestion time. Compared to the collagenase digestion method, the USASI method had a higher cell yield and cell viability, with no adverse effects on cell components, proliferative capacity, or multipotential differentiation capacity. Conclusion: With reduced processing time, lower collagenase dosage, and increased cell yield without impairing the viability and characteristics of SVF, USASI holds the potential to emerge as a time-saving and cost-effective method for future clinical applications.

Background Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation.Methods This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making.Findings The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The ‘Good responder’ exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 μm, p

Host-microbe interactions are virtually bidirectional, but how the host affects their microbiome is poorly understood. Here, we report that the host is a critical modulator to regulate the lifestyle switch and pathogenicity heterogeneity of the opportunistic pathogens Serratia marcescens utilizing the Drosophila and bacterium model system. First, we find that Drosophila larvae efficiently outcompete S. marcescens and typically drive a bacterial switch from pathogenicity to commensalism toward the fly. Furthermore, Drosophila larvae reshape the transcriptomic and metabolic profiles of S. marcescens characterized by a lifestyle switch. More importantly, the host alters pathogenicity and heterogeneity of S. marcescens in the single-cell resolution. Finally, we find that larvae-derived AMPs are required to recapitulate the response of S. marcescens to larvae. Altogether, our findings provide an insight into the pivotal roles of the host in harnessing the life history and heterogeneity of symbiotic bacterial cells, advancing knowledge of the reciprocal relationships between the host and pathogen.

Mining the nutritional function of Nannochloropsis gaditana is crucial for its development and utilization. This study evaluated the protective effect of purified Nannochloropsis gaditana polysaccharides (NPS) on alcohol-induced dyslipidemia. The study used a liquid alcohol diet and an NPS intervention of 200 mg/kg.bw and 400 mg/kg.bw for 5 weeks. Compared with the model group (MC), the NPS group had a lower triglyceride (TG) and total cholesterol (TC). The relative abundance of probiotics Akkermansia, Bifidobacterium and Ligilactobacillus were significantly higher in NPS groups than those in the model group. Compared with the MC, NPS group had higher serum phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio and lower ceramide. Moreover, the expression of lipidolysis-related genes such as PGC1α and CPT-1A in the NPS group were significantly higher compared to MC. In summary, NPS attenuated ethanol-induced dyslipidemia probably by regualating gut bateria and serum metabolites, which could serve as a potential prebiotic.

The combination of typhoon-induced storm surges and astronomical tides can result in extreme seawater levels and disastrous effects on coastal socioeconomic systems. The construction of an appropriate wind field has consistently been a challenge in storm tide forecasting and disaster warning. In this study, we optimized a nonlinear regression formula based on the C15 model to determine the maximum wind radius. The simulation based on the improvement showed good accuracy for storm tides during super typhoon Mangkhut (WP262018), Saola (WP092023), and severe typhoon Hato (WP152017). The correlation coefficients were in the 0.94–0.98 range, and the peak bias was less than 5cm. The trough errors were significantly reduced compared to other wind fields. Owing to the importance and lack of the maximum wind radius (Rmax), we attempted to predict Rmax using an LSTM (Long Short-Term Memory) neural network for forecasting storm tides during strong typhoons. Constrained LSTM showed good performance in hours 6–48, and effectively enhanced the forecasting capability of storm tides during strong typhoons. The workflows and methods used herein have broad applications in improving the forecasting accuracy of strong typhoon-induced storm tides.

Summary: Memory B cells (MBCs) are essential for humoral immunological memory and can emerge during both the pre-germinal center (GC) and GC phases. However, the transcription regulators governing MBC development remain poorly understood. Here, we report that the transcription regulator Notch2 is highly expressed in MBCs and their precursors at the pre-GC stage and required for MBC development without influencing the fate of GC and plasma cells. Mechanistically, Notch2 signaling promotes the expression of complement receptor CD21 and augments B cell receptor (BCR) signaling. Reciprocally, BCR activation up-regulates Notch2 surface expression in activated B cells via a translation-dependent mechanism. Intriguingly, Notch2 is dispensable for GC-derived MBC formation. In summary, our findings establish Notch2 as a pivotal transcription regulator orchestrating MBC development through the reciprocal enforcement of BCR signaling during the pre-GC phase and suggest that the generation of GC-independent and -dependent MBCs is governed by distinct transcriptional mechanisms.

Summary: Cathelicidins, a major class of antimicrobial peptides (AMPs), hold considerable potential for antimicrobial drug development. In the present study, we identified a novel cathelicidin AMP (TC-33) derived from the Chinese tree shrew. Despite TC-33 demonstrating weak antimicrobial activity, the novel peptide TC-14, developed based on its active region, exhibited a 432-fold increase in antimicrobial activity over the parent peptide. Structural analysis revealed that TC-14 adopted an amphipathic α-helical conformation. The bactericidal mechanism of TC-14 involved targeting and disrupting the bacterial membrane, leading to rapid membrane permeabilization and rupture. Furthermore, TC-14 exhibited a high-safety profile, as evidenced by the absence of cytotoxic and hemolytic activities, as well as high biocompatibility and safety in vivo. Of note, its potent antimicrobial activity provided significant protection in a murine model of skin infection. Overall, this study presents TC-14 as a promising drug candidate for antimicrobial drug development.

High sugar content in peanut seeds is one of the major breeding objectives for peanut flavor improvement. In order to explore the genetic control of sugar accumulation in peanut kernels, we constructed a recombinant inbred line population of 256 F2:6-7 lines derived from the Luhua11 × 06B16 cross. A high-resolution genetic map was constructed with 3692 bin markers through whole genome re-sequencing. The total map distance was 981.65 cM and the average bin marker distance was 0.27cM. A major stable QTL region (qSCB09/qSSCB09) was identified on linkage group (LG) B09 associated with both sucrose content (SC) and soluble sugar content (SSC) explaining 21.51-33.58% phenotypic variations. This major QTL region was consistently detected in three environments and mapped within a physical interval of 1.56 Mb on chromosome B09, and six candidate genes were identified. These results provide valuable information for further map-based cloning of favorable allele for sugar content in peanut.

Hippo pathway coordinate developmental processes through regulating cell growth, proliferation and programmed death. However, mollusks achieved little focus so far on the role of this significant pathway during larval development. In this study, three core genes, hippo, warts and yorkie, were identified in Haliotis discus hannai. They mainly expressed at trochophore and veliger stages. Positive signals of yorkie occurred near the edge of shell field at the trochophore stage (12 and 15 hpf), then tended to overlap with hippo and warts (18 hpf). In veliger larva after torsion (at 30 hpf), their expression appeared in several non-overlapping areas. These findings suggested their important roles in post-embryonic development. Silencing of yorkie led to 90 % cumulative mortality at 60 h posttreatment, with a 33 %-highest abnormality rate, meanwhile significantly upregulated the relative expression of hippo and warts at 6 h and 12 h posttreatment (P

ObjectiveTo investigate whether changes occur in the dynamic functional connectivity (dFC) of motor cerebellum with cerebral cortex in juvenile myoclonic epilepsy (JME).MethodsWe adopted resting-state electroencephalography—functional magnetic resonance imaging (EEG-fMRI) and a sliding-window approach to explore the dFC of motor cerebellum with cortex in 36 JME patients compared with 30 and age-matched health controls (HCs). The motor cerebellum was divided into five lobules (I–V, VI, VIIb, VIIIa, and VIIIb). Additionally, correlation analyses were conducted between the variability of dFC and clinical variables in the Juvenile Myoclonic Epilepsy (JME) group, such as disease duration, age at disease onset, and frequency score of myoclonic seizures.ResultsCompared to HCs, the JME group presented increased dFC between the motor cerebellum with SMN and DMN. Specifically, connectivity between lobule VIIb and left precentral gyrus and right inferior parietal lobule (IPL); between lobule VIIIa and right inferior frontal gyrus (IFG) and left IPL; and between lobule VIIIb and left middle frontal gyrus (MFG), bilateral superior parietal gyrus (SPG), and left precuneus. In addition, within the JME group, the strength of dFC between lobule VIIIb and left precuneus was negatively (r = −0.424, p = 0.025, Bonferroni correction) related with the frequency score of myoclonic seizures.ConclusionIn patients with JME, there is a functional dysregulation between the motor cerebellum with DMN and SMN, and the variability of dynamic functional connectivity may be closely associated with the occurrence of motor symptoms in JME.

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

Liquid biopsy is gradually being applied in the clinical diagnosis and treatment of lung cancer. At present, with the development of metabolomics, more and more metabolic biomarkers are considered as potential sensitive markers reflecting the occurrence and development of tumors. This article summarizes the changes in the main metabolic pathways of lung cancer, including glucose metabolism, amino acid metabolism, lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and purine metabolism. Meanwhile, this article reviews the role of metabolic biomarkers in the early diagnosis of lung cancer, predicting disease progression, and evaluating the efficacy of chemotherapy and immunotherapy, aiming to provide effective biomarkers for tumor diagnosis and treatment.

Bivalves are affected by various stressors, such as global warming and microplastics, in the marine environment. Microplastics are one of the most concerning pollutants worldwide, and high seawater temperatures caused by global warming influence the survival of marine organisms. However, little is known about the combined effects of elevated temperature and microplastics (MPs) on marine organisms, and most studies conducted in recent years have investigated the two factors, respectively. Thus, it is necessary to investigate the combined effects of elevated temperature and MP exposure on marine life. The Pacific oyster Crassostrea gigas is a widely distributed marine mollusk, and has very important economic value. The aim of the current study was to explore the toxic effects of elevated temperature and microplastic co-exposure on the hemocyte function, immune-related gene expression, and energy metabolism of C. gigas. In the current study, oysters were exposed to three levels of microplastics (no microplastics, 6 μm microplastics: SPS-MPs, and 50~60 μm microplastics: LPS-MPs) and two temperature levels (20 ℃ and 25 ℃) for 21 days, and the phagocytosis rate and reactive oxygen species (ROS) content of hemocytes, glycogen content in digestive glands, and immune-related gene expression in digestive glands and gills were examined on the 21st day. 2', 7'-Dichlorodihydrofluorescein diacetate and fluorescent microspheres were used to measure the ROS content and phagocytosis ratein hemocytes of C. gigas by flow cytometry, respectively. The glycogen content was measured using detection kits. Total RNA was isolated by TRIzol reagent, and the concentration was measured by Nanodrop. M-MLV Reverse Transcriptase was used for cDNA synthesis. The expressions of immune-related genes [inhibitor of NF-κB (IκB), p53, and heat shock protein 90 (HSP90)] were examined by quantitative real-time PCR in the digestive glands and gills of oysters from each treatment group. Two-way ANOVA was used to analyze the interactive effects of elevated temperature and microplastics on tested parameters of oysters using SPSS software. The results showed that exposure to SPS-MPs could elevate ROS content and reduce phagocytosis in hemocytes, but no significant interaction was found between elevated temperature and microplastic effects on ROS content and phagocytosis rate in hemocytes (P > 0.05). The 25 ℃+LPS-MPs exposure significantly decreased phagocytosis in hemocytes compared with single LPS-MPs and elevated temperature exposures (P < 0.05). Single SPS-MPs exposure significantly decreased phagocytosis in hemocytes compared with single LPS-MPs exposure (P < 0.05). In digestive glands, there was a significant interaction between elevated temperature and microplastics in glycogen content (P < 0.05), and the combined exposure could increase the glycogen content compared with other treatments. In digestive glands, the 25 ℃+LPS-MPs exposure significantly increased glycogen content compared with single elevated temperature and single LPS-MPs exposure (P < 0.05). In digestive glands and gills, there was a significant interaction between elevated temperature and microplastics in the expressions of HSP90, IκB, and p53 genes (P < 0.05). The 25 ℃+SPS-MPs exposure significantly upregulated the expression of HSP90, IκB, and p53 genes in the digestive glands of oysters compared with single SPS-MPs and single elevated temperature exposures (P < 0.05). The 25 ℃+SPS-MPs exposure significantly downregulated the expression of the HSP90 gene in the gills of oysters compared with single SPS-MPs exposure (P < 0.05). Single elevated temperature and single microplastics exposure significantly upregulated the expression of the IκB gene compared with the control in gills (P < 0.05). The combined exposure of elevated temperature and microplastics showed a significant antagonistic effect on the expression of the p53 gene in gills. Microplastics exposure downregulated p53 gene expression compared with the control at 20 ℃, while it upregulated p53 gene expression compared with single elevated temperature at 25 ℃. These results indicated that the p53 gene plays an important role in regulating the immune response in both digestive glands and gills. The interaction between elevated temperature and microplastics on the mRNA expression of HSP90 and IκB genes in digestive glands of C. gigas was size-dependent: A synergistic effect was found between SPS-MPs and elevated temperature, and an antagonistic effect was found between LPS-MPs and elevated temperature. A significant antagonistic effect was found between elevated temperature and microplastics on the mRNA expression of the IκB gene in gills, and the regulation pattern was different from that in the digestive glands, indicating that the regulation effect of the IκB gene was tissue-specific. In conclusion, the combined exposure of elevated temperature and microplastics can increase the glycogen content in the digestive glands of C. gigas, induce an immune response in digestive glands and gills, and trigger the oxidative stress response in hemocytes. Microplastics can cause stronger oxidative stress in hemocytes than elevated temperature. Moreover, a significant interactive effect was found between elevated temperature and microplastics on glycogen content in digestive glands and the expression of immune-related genes (HSP90, p53, and IκB) in digestive glands and gills. The results of this study provide valuable information for evaluating the toxic effects of microplastics on marine organisms under a global warming background.

Abstract To reduce the uncertainty estimation of clouds and improve the forecast of surface shortwave radiation (SSR) over the Tibetan Plateau, a new cloud assimilation system is proposed which is the first attempt to directly apply the four-dimensional local ensemble transform Kalman filter method to assimilate the cloud optical thickness (COT). The high-resolution spatial and temporal data assimilated from the next-generation geostationary satellite Himawari-8, with the high-assimilation frequency, realized an accurate estimation of the clouds and radiation forecasting. The COT and SSR were significantly improved after the assimilation by independent verification. The correlation coefficient (CORR) of the SSR was increased by 11.3%, and the root-mean-square error (RMSE) and mean bias error (MBE) were decreased by 28.5% and 58.9%, respectively. The 2-h cycle assimilation forecast results show that the overestimation of SSR has been effectively reduced using the assimilation system. These findings demonstrate the high potential of this assimilation technique in forecasting of SSR in numerical weather prediction. The ultimate goal that to improve the model forecast through the assimilation of cloud properties requires further studies to achieve.

ABSTRACTWith increasing demand for scratch-resistant flexible electronics, the development of transparent coatings with good scratch resistance and self-healing properties has emerged as a key research topic. In this study, a high-strength self-healing poly(urethane – urea) (PUU)-based nanocomposite coating was prepared by introducing functionalized nanodiamond (ND) into a PUU matrix via solution blending. The PUU matrix had hard-segment repeating units and was constructed using isophorone diamine and isophorone isocyanate. The ND particles were modified using a silane coupling agent, 3-aminopropyltriethoxysilane, to obtain well-dispersed KH-ND nanoparticles. KH-ND promoted microphase separation in the PU matrix, inducing the formation of dense and homogeneous hard domains that dissipated stress, prevented further crack development, and improved the mechanical properties and scratch resistance of the coating. In addition, the coating exhibited excellent self-healing properties. Fourier-transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were used to characterize the self-healing and hardening mechanisms of the coating. The environmentally friendly PUU/KH-ND coating is easy to prepare and has broad application prospects in transparent and anti-scratch coatings for flexible electronics, automobiles, and home appliances.

The landslide is a widespread and devastating natural disaster, posing serious threats to human life, security, and natural assets. Investigating efficient methods for accurate landslide detection with remote sensing images has important academic and practical implications. In this article, we proposed an LS-YOLO, a novel and effective model for landslide detection with remote sensing images. We first built a multiscale landslide dataset (MSLD) and introduced random seeds in the data augmentation to increase data robustness. Considering the multiscale characteristic of landslides in remote sensing images, a multiscale feature extraction module is designed based on efficient channel attention, average pooling, and spatial separable convolution. To increase the receptive field of the model, dilated convolution is employed to the decoupled head. Specifically, the context enhancement module consisting of dilation convolutions is added to the decoupled head regression task branch, and then the improved decoupled head is to replace the coupled head in YOLOv5s. Extensive experiments show that our proposed model has high performance for multiscale landslide detection and outperforms other object detection models (faster RCNN, SSD, EfficientDet-D0, YOLOv5s, YOLOv7, and YOLOX). Compared with the baseline model YOLOv5s, the AP of the LS-YOLO for detecting landslides has increased by 2.18%–97.06%.

Creating a 3D shape design from free-hand sketches is a challenging task due to the sparse and ambiguous information from sketches. In this work, we propose DualShape, a sketch-based 3D shape design interface with part generation and retrieval. DualShape first decouples the model generation into two parts: a composite part retrieval module using a sketch-based feature matching method and a sketch-based part generation module using a deep learning approach with implicit function representation. We then propose an assembly module for the obtained part models to accomplish the task of 3D shape generation from input sketches. In addition, we provide an optimization module that allows users to optimize and manually adjust the assembled model to achieve satisfying models. For the reconstruction interface, shadow guidance was utilized to assist users with the retrieved 3D models matching the input strokes as background references in real time. To verify the effectiveness of the DualShape system, we conducted the comparison experiments and the user study. The results show that DualShape is more user-friendly and is able to generate 3D models with richer details. We believe this work would provide a novel paradigm for hybrid 3D model generation in computer graphics.

In response to the demand for high-power, long-pulse-width 532 nm lasers in the medical and industrial processing fields, this paper explains how the laser cavity of a high-power Nd:YAG 532 nm laser can be extended while maintaining the laser’s q-parameter by using a 4f optical system. The results show that at a repetition rate of 10 kHz, the extended cavity achieved a maximum average power of 112 W. Compared with the short cavity, the power was not significantly reduced. The pulse width was extended from 56 ns to 85 ns, and its broadening ratio reached 46.5%. The laser maintained good beam quality during high-power operation.

Optical Coherence Tomography (OCT)-based angiography (OCTA) is a high-resolution, high-speed, and non-invasive imaging method that can provide vascular mapping of subcutaneous tissue up to approximately 2 mm. In dermatology applications of OCTA, handheld probes are always designed with a piece of transparent but solid contact window placed at the end of the probe to directly contact the skin for achieving better focusing between the light source and the tissue, reducing noise caused by minor movements. The pressure between the contact window and the skin is usually uncontrollable, and high external pressure affects the quality of microvascular imaging by compressing the vessels and obstructing the underlying blood flow. Therefore, it is necessary to determine a pressure range to ensure that the vessels can be fully imaged in high-quality images. In this paper, two pressure sensors were added to the existing handheld OCT probe, and the imaging probe was fixed to a metal stand and adjusted vertically to change the pressure between the probe and the tested skin site, a gradient of roughly 4 kPa (with 1–2 kPa error) increase was applied in each experiment, and the impact of pressure to the vessel was calculated. The experiment involved a total of five subjects, three areas of which were scanned (palm, back of the hand, and forearm). The vessel density was calculated to evaluate the impact of external pressure on angiography. In addition, PSNR was calculated to ensure that the quality of different tests was at a similar level. The angiography showed the highest density (about 10%) when the pressure between the contact window on the probe and the test area was between 3 and 5 kPa. As the pressure increased, the vascular density decreased, and the rate of decrease varied in different test areas. After fitting all the data points according to the different sites, the slope of the fitted line, i.e., the rate of decrease in density per unit value of pressure, was found to be 4.05% at the palm site, 6.93% at the back of the hand, and 4.55% at the forearm site. This experiment demonstrates that the pressure between the skin and contact window is a significant parameter that cannot be ignored. It is recommended that in future OCTA data collection processes and probe designs, the impact of pressure on the experiment be considered.

The co-occurrence of distinct lung cancer types within the same lobe is an exceedingly rare phenomenon. Here, we present a unique case wherein primary invasive squamous cell carcinoma and invasive adenocarcinoma concurrently manifested in the identical lung lobe. Additionally, we provide a comprehensive overview of the diagnosis and treatment approaches for multiple primary lung cancers, along with highlighting existing challenges based on the most recent guidelines. Our case underscores the importance of sampling each lesion individually, conducting separate diagnostic procedures, and determining the histological subtype for effective treatment planning irrespective of their location or size.

Abstract Background Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients. Methods A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole‐exome sequencing was performed, followed by validation by Sanger sequencing. Results The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease. Conclusions We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.

Microorganisms, especially rare microbial species, are crucial in estuarine ecosystems for driving biogeochemical processes and preserving biodiversity. However, the understanding of the links between ecosystem multifunctionality (EMF) and the diversity of rare bacterial taxa in estuary ecosystems remains limited. Employing high-throughput sequencing and a variety of statistical methods, we assessed the diversities and assembly process of abundant and rare bacterioplankton and their contributions to EMF in a subtropical estuary. Taxonomic analysis revealed Proteobacteria as the predominant phylum among both abundant and rare bacterial taxa. Notably, rare taxa demonstrated significantly higher taxonomic diversity and a larger species pool than abundant taxa. Additionally, our findings highlighted that deterministic assembly processes predominantly shape microbial communities, with heterogeneous selection exerting a stronger influence on rare taxa. Further analysis reveals that rare bacterial beta-diversity significantly impacts to EMF, whereas alpha diversity did not. The partial least squares path modeling (PLS-PM) analysis demonstrated that the beta diversity of abundant and rare taxa, as the main biotic factor, directly affected EMF, while temperature and total organic carbon (TOC) were additional key factors to determine the relationship between beta diversity and EMF. These findings advance our understanding of the distribution features and ecological knowledge of the abundant and rare taxa in EMF in subtropical estuaries, and provide a reference for exploring the multifunctionality of different biospheres in aquatic environments.

Introduction: With amazing clinical efficacy, Yangyin Qingfei Decoction Plus (YQDP), a well-known and age-old Chinese compound made of ten Chinese botanical drugs, is utilized in clinical settings to treat a range of respiratory conditions. This study examines the impact of Yangyin Qingfei Decoction (YQDP) on lung tissue metabolic products in severe Mycoplasma pneumoniae pneumonia (SMPP) model mice and examines the mechanism of YQDP in treating MP infection using UPLC-MS/MS technology.Methods: YQDP’s chemical composition was ascertained by the use of Agilent 1260 Ⅱ high-performance liquid chromatography. By using a nasal drip of 1010 CCU/mL MP bacterial solution, an SMPP mouse model was created. The lung index, pathology and ultrastructural observation of lung tissue were utilized to assess the therapeutic effect of YQDP in SMPP mice. Lung tissue metabolites were found in the normal group, model group, and YQDP group using UPLC-MS/MS technology. Using an enzyme-linked immunosorbent test (ELISA), the amount of serum inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), was found. Additionally, the protein expression of PI3K, P-PI3K, AKT, P-AKT, NF-κB, and P-NF-κB was found using Western blot.Results: The contents of chlorogenic acid, paeoniflorin, forsythrin A, forsythrin, and paeonol in YQDP were 3.480 ± 0.051, 3.255 ± 0.040, 3.612 ± 0.017, 1.757 ± 0.031, and 1.080 ± 0.007 mg/g respectively. YQDP can considerably lower the SMPP mice’s lung index (p < 0.05). In the lung tissue of YQDP groups, there has been a decrease (p < 0.05) in the infiltration of inflammatory cells at varying concentrations in the alveoli compared with the model group. A total of 47 distinct metabolites, including choline phosphate, glutamyl lysine, L-tyrosine, 6-thioinosine, Glu Trp, 5-hydroxydecanoate, etc., were linked to the regulation of YQDP, according to metabolomics study. By controlling the metabolism of porphyrins, pyrimidines, cholines, fatty acids, sphingolipids, glycerophospholipids, ferroptosis, steroid hormone biosynthesis, and unsaturated fatty acid biosynthesis, enrichment analysis suggested that YQDP may be used to treat SMPP. YQDP can lower the amount of TNF-α and IL-6 in model group mice as well as downregulate P-PI3K, P-AKT, and P-NF-κB expression (p < 0.05).Conclusion: A specific intervention effect of YQDP is observed in SMPP model mice. Through the PI3K/Akt/NF-κB signaling pathways, YQDP may have therapeutic benefits by regulating the body’s metabolism of α-Linoleic acid, sphingolipids, glycerophospholipids, arachidonic acid, and the production of unsaturated fatty acids.

Summary: Polygenic scores (PGSs) are quantitative metrics for predicting phenotypic values, such as human height or disease status. Some PGS methods require only summary statistics of a relevant genome-wide association study (GWAS) for their score. One such method is Lassosum, which inherits the model selection advantages of Lasso to select a meaningful subset of the GWAS single-nucleotide polymorphisms as predictors from their association statistics. However, even efficient scores like Lassosum, when derived from European-based GWASs, are poor predictors of phenotype for subjects of non-European ancestry; that is, they have limited portability to other ancestries. To increase the portability of Lassosum, when GWAS information and estimates of linkage disequilibrium are available for both ancestries, we propose Joint-Lassosum (JLS). In the simulation settings we explore, JLS provides more accurate PGSs compared to other methods, especially when measured in terms of fairness. In analyses of UK Biobank data, JLS was computationally more efficient but slightly less accurate than a Bayesian comparator, SDPRX. Like all PGS methods, JLS requires selection of predictors, which are determined by data-driven tuning parameters. We describe a new approach to selecting tuning parameters and note its relevance for model selection for any PGS. We also draw connections to the literature on algorithmic fairness and discuss how JLS can help mitigate fairness-related harms that might result from the use of PGSs in clinical settings. While no PGS method is likely to be universally portable, due to the diversity of human populations and unequal information content of GWASs for different ancestries, JLS is an effective approach for enhancing portability and reducing predictive bias.

PurposeTo assess the prognostic significance of β2-microglobulin decline index (β2M DI) in multiple myeloma (MM).Methods150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing β2M DI was built up based on the data in training cohort. The validation group was used to verify the model.Resultsβ2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p

The Nostradamus attack was originally proposed as a security vulnerability for a hash function by Kelsey and Kohno at EUROCRYPT 2006. It requires the attacker to commit to a hash value y of an iterated hash function H. Subsequently, upon being provided with a message prefix P, the adversary’s task is to identify a suffix S such that H(P∥S) equals y. Kelsey and Kohno demonstrated a herding attack requiring O(√n · 22n/3) evaluations of the compression function of H, where n represents the output and state size of the hash, placing this attack between preimage attacks and collision searches in terms of complexity. At ASIACRYPT 2022, Benedikt et al. transform Kelsey and Kohno’s attack into a quantum variant, decreasing the time complexity from O(√n · 22n/3) to O( 3√n · 23n/7). At ToSC 2023, Zhang et al. proposed the first dedicated Nostradamus attack on AES-like hashing in both classical and quantum settings. In this paper, we have made revisions to the multi-target technique incorporated into the meet-in-the-middle automatic search framework. This modification leads to a decrease in time complexity during the online linking phase, effectively reducing the overall attack time complexity in both classical and quantum scenarios. Specifically, we can achieve more rounds in the classical setting and reduce the time complexity for the same round in the quantum setting.

Titanium (Ti) and its alloys are commonly used implant materials in orthopedics due to their good corrosion resistance, mechanical properties, and biocompatibility. However, the inherent biological inertness of the Ti surface leads to insufficient osseointegration and antibacterial ability, which may result in implant failure. Hydroxyapatite (HA) is currently the most widely used material in the biomedical field. It is one of the bioactive coating materials because of its chemical and structural similarity to natural bone. At present, many techniques are used to deposit HA as a coating material on Ti implants. The stability of the HA coating is the most important factor in determining the success of the implant. In addition, biofunctional ions have been introduced into HA coatings to enhance functional performance. This article aims to present the crystal structure and characteristics of HA and the principle of doping ions into HA. The preparation methods for the deposition of HA functional coatings on Ti and its alloys are introduced and discuss its advantages and limitations. In addition, the coating of doped HA on the surface of Ti and its alloys to improve their surface properties for bone integration is also reviewed.

The etiology of recurrent spontaneous abortion (RSA) is extremely complex, as there are 40–50% of patients with unexplained miscarriages, known as unexplained RSA (URSA). URSA affects approximately 1–2% of females of childbearing age and has a massive impact on the physical and mental conditions of both patients and their families. The pathogenesis of the disease remains unclear, making its treatment complicated. In recent years, considerable progress has been made in the exploration of the URSA immune balance mechanism and it has been universally acknowledged that a balanced immune response (as abnormal immunity) may be the root cause of poor pregnancy outcomes. This review discussed and summarized the effects of immune cells and blocking antibodies (BAs) on URSA based on the current state of knowledge in this area. Additionally, molecular genetics also plays an essential role in the incidence rate of URSA since the role of genetic polymorphism in the pathogenesis of URSA has been thoroughly studied. Nonetheless, the outcomes of these studies are inconsistent, particularly across populations. This paper reviewed previous studies on URSA and maternal genetic polymorphism, focusing on and synthesizing the most important findings to date, and providing diagnostic recommendation for URSA patients with clinical symptoms.

Compared with the conventional hot-dip galvanized steel, an optimized strength-ductility combination was obtained by the combination of continuous galvanizing line (CGL) compatible quenching and austempering (QAT) treatment and pre-quenching, i.e., “pre-quenching + CGL-QAT”. The effects of the pre-quenching on the microstructure and mechanical performance were analyzed by using dilatometry, SEM, AES-EBSD, TEM and XRD technique. Compared with QAT samples, pre-quenching could eliminate the blocky M-A islands and promote the formation of lath reversed austenite and bainite ferrite in “pre-quenching + CGL-QAT” samples. Meanwhile, a large fraction (22.7–25.8%) of lath RA were obtained, such that brittle intergranular fracture can be prevented. The lath bainite/ferrite structures and sufficient TRIP effect enhanced the strength-ductility combination with an UTS reaching 1000 MPa and TEL around 30%. The fracture mainly presents ductile fracture and results in a ductile fracture surface with large dimples. The excellent strength-ductility combination with a UTS above 980 MPa, a YS of 625 MPa, a TEL of 29.1% and a higher PSE around 30 GPa·% can be obtained, which exceeds the current commercial hot-dip galvanized steel grades.

Abstract Background Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined. Methods We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed. Results A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy. Conclusion 2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO. Synopsis SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.