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Abstract Sepsis-induced acute lung injury (ALI), characterized by severe hypoxemia and pulmonary leakage, remains a leading cause of mortality in intensive care units. The exacerbation of ALI during sepsis is largely attributed to uncontrolled inflammatory responses and endothelial dysfunction. Emerging evidence suggests an important role of Z-DNA binding protein 1 (ZBP1) as a sensor in innate immune to drive inflammatory signaling and cell death during infections. However, the role of ZBP1 in sepsis-induced ALI has yet to be defined. We utilized ZBP1 knockout mice and combined single-cell RNA sequencing with experimental validation to investigate ZBP1’s roles in the regulation of macrophages and lung endothelial cells during sepsis. We demonstrate that in sepsis, ZBP1 deficiency in macrophages reduces mitochondrial damage and inhibits glycolysis, thereby altering the metabolic status of macrophages. Consequently, this metabolic shift leads to a reduction in the differentiation of macrophages into pro-inflammatory states and decreases macrophage pyroptosis triggered by activation of the NLRP3 inflammasome. These changes significantly weaken the inflammatory signaling pathways between macrophages and endothelial cells and alleviate endothelial dysfunction and cellular damage. These findings reveal important roles for ZBP1 in mediating multiple pathological processes involved in sepsis-induced ALI by modulating the functional states of macrophages and endothelial cells, thereby highlighting its potential as a promising therapeutic target.

The species of Ramaria are coralloid-fungi with intricately branched and vividly coloured basidiomata. There are many studies on the genus Ramaria in China, but molecular phylogenetic analysis is rarely employed. In this study, we performed a multigene phylogenetic analysis to identify Ramaria species in Shanxi Province of northern China. Phylogenetic analyses based on four loci, the internal transcribed spacer region of nuclear ribosomal DNA (ITS), the nuclear large subunit ribosomal DNA (nrLSU), ATPase subunit 6 (atp6), and mitochondrial small subunit ribosomal DNA (mtSSU), revealed 13 Ramaria species from our collections. Combined with morphological examinations, 12 of them were identified as new species, plus a new report to China. The thirteen species were described and illustrated in this paper.

Abstract Klebsiella pneumoniae is among the most important Gram-negative pathogens that can cause serious nosocomial infections. The emergence and prevalence of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) pose a significant challenge to public health. In this study, we characterized thirty carbapenem-resistant K. pneumoniae (CRKP) strains from a tertiary care hospital in Sichuan province, China, by whole-genome sequencing and genome analysis. These strains were all highly resistant to carbapenem but remained susceptible to tigecycline. Of the 30 tested CRKP strains, 23 were positive for bla KPC−2 and seven for bla NDM−5. These bla KPC−2-positive strains all belonged to ST11, while bla NDM−5-positive strains belonged to five distinct STs. Phylogenetic analysis revealed a predominant intra-hospital transmission of ST11-KL64 in KPC-2-producing CRKP, and that both clonal and horizontal transmission of bla NDM−5 have occurred among NDM-5-producing CRKP strains in this hospital. Hypervirulence genes were commonly detected in the CRKP. The prevalent pLVKP-like plasmid and ICEKp seem to have contributed largely to the transmission of virulence genes in them. bla NDM−5 was located on highly similar IncX3 plasmids in the collected strains, and its truncated vision was highlighted. bla KPC−2 was primarily carried by IncFII/IncR plasmids in our collection. At least two IncFII/IncR plasmid subtypes were identified, exhibiting high similarity to many previously reported bla KPC−2-bearing plasmids from different parts of China. The findings provide an expanded knowledge of the genetic characteristics of CRKP, the transmission pattern of carbapenem-resistance genes, and also the convergence of Hv-CRKP.

Abstract Background As a potential model organism for studies of environmental and cell biology, Paramecium duboscqui is a special euryhaline species of Paramecium that can be found in fresh, brackish, or marine water in natural salinity ranges between 0‰ and 33‰. However, the genome information as well as molecular mechanisms that account for its remarkable halotolerant traits remain extremely unknown. To characterize its genome feature, we combined PacBio and Illumina sequencing to assemble the first high-quality and near-complete macronuclear genome of P. duboscqui. Meanwhile, comparative transcriptomic profiles under different salinities gave underlying insight into the molecular mechanism of its adaptations to environmental salinity. Results The results showed that the MAC genome of P. duboscqui comprises 160 contigs, with 113 of them possessing telomere (~ 28.82 Mb haploid genome size). Through comparative genomic analyses with the other ciliate, we found that gene families encoding transmembrane transporter proteins have been expanded in P. duboscqui, showing enormous potential in salinity adaptation. Like other Paramecium, P. duboscqui utilizes TGA as its only termination codon and has reassigned TAA and TAG to encode glutamine. P. duboscqui showed different growth rates under different salinities, with an optimum growth rate in 5‰ salinity. A comparison of the transcriptomic profiles among P. duboscqui grown under different concentrations showed that genes involved in protein folding, oxygen respiration, and glutathione-dependent detoxification were upregulated in the high-salt group, whereas genes encoding DNA-binding proteins and transcription factors were upregulated in the low-salt group, suggesting distinct mechanisms for responding to low and high salinity. Weighted gene coexpression network analysis (WGCNA) linked the hub genes expressed at 30‰ salinity to cysteine-type peptidase activity, lipid transfer, sodium hydrogen exchange, and cell division, with the hub genes expressed at 0‰ salinity involved in transmembrane transport and protein localization. Conclusions This study characterizes a new euryhaline model Paramecium, provides novel insights into Paramecium evolution, and describes the molecular mechanisms that have allow P. duboscqui to adapt to different osmotic environments.

Abstract The present study aims to explore the influence of field cognitive style on the false memory of Chinese characters. Based on the related literature, this paper used Cognitive Style Figure Test (CSFT) to investigate the field cognitive style of college student and test the differences of field cognitive style in demographic variables. Using the DRM paradigm, with Chinese characters lists as experimental material. This study was to inspect whether Chinese semantic/tonetic association has any effect on false memory, and whether there is any interaction between field cognitive style and Chinese character component on it. The results showed that: (a) there were significant differences between male and female in the recognition rate of symbol types, with the recognition rate of tonetic symbol type characters being generally higher than that of semantic symbol type; (b) Chinese semantic/tonetic associations had an effect on false memory and gender has a significant difference in the recognition of critical-lures; (c) field cognitive style had no statistically significant difference in recognition rate on character component type and characters type (old characters, filler characters, and critical-lures); (d) individuals with different field cognitive styles differed significantly in the rate of misrecognition of critical-lures for semantic symbols.

Background/purpose: Oral cancer is one of the most prevalent malignant tumors in Taiwan. Due to the heterogeneity of oral cancer cells, the five-year survival rate of patients is only 50%. Post-translational modifications contribute to protein diversity and directly influence cell functions. The protein inhibitor of activated signal transducer and activator of transcription 2 (PIAS2) is known to undergo post-translational modifications, yet its impact on oral cancer remains unclear. Materials and methods: PIAS2 expression was modulated by transfecting cells with a PIAS2 expression vector or by knocking down PIAS2 using siRNA with low and high PIAS2 expression, respectively. These cells were subjected to invasion, migration, and proliferation assays to evaluate the effects of PIAS2. Changes in genotype, such as epithelial-mesenchymal transition (EMT) markers, were also examined. Additionally, the effect of cigarette smoke condensate (CSC) on PIAS2 expression in oral squamous cell carcinoma (OSCC) cells was investigated. Results: Overexpression of PIAS2 significantly increased the malignant behaviors of oral cancer cells. In YD38 and SAS cells with low PIAS2 expression, overexpression of PIAS2 enhanced proliferation, invasion, and migration. PIAS2 overexpression also affected EMT gene expression, suppressing E-cadherin and increasing fibronectin expression. Conversely, PIAS2 knockdown in OECM1 and SCC25 cells suppressed malignant behaviors and reversed EMT markers, increasing E-cadherin and decreasing fibronectin expression. Furthermore, a dose-dependent increase in PIAS2 expression was observed when OSCC cells were treated with CSC. Conclusion: PIAS2 functions as an oncogene in oral cancer, and cigarette smoking induces PIAS2 expression. Increased PIAS2 levels lead to enhanced malignancy in oral cancer.

Abstract Metabolism has been implicated in cell fate determination, particularly through epigenetic modifications. Similarly, lipid remodeling also plays a role in regulating cell fate. Here, we present comprehensive lipidomics analysis during BMP4-driven primed to naive pluripotency transition or BiPNT and demonstrate that lipid remodeling plays an essential role. We further identify Cpt1a as a rate-limiting factor in BiPNT, driving lipid remodeling and metabolic reprogramming while simultaneously increasing intracellular acetyl-CoA levels and enhancing H3K27ac at chromatin open sites. Perturbation of BiPNT by histone acetylation inhibitors suppresses lipid remodeling and pluripotency transition. Together, our study suggests that lipid remodeling promotes pluripotency transitions and further regulates cell fate decisions, implicating Cpt1a as a critical regulator between primed-naive cell fate control.

Abstract Background Low back pain has become a globally challenging health problem, and about 90% of cases are nonspecific. Due to the risks associated with opioid use and the limited effectiveness of drug treatment, acupuncture and other non-drug methods have become the first-line treatment for this disease. However, the best acupuncture method has not yet been determined. In this study, the effects of different acupuncture methods on chronic nonspecific low back pain (CNLBP) were compared by network meta-analysis, aiming at identifying the best option and providing a basis for precise treatment of CNLBP. Methods Clinical randomized controlled trials (RCTs) on acupuncture in the treatment of NSLBP were searched in eight databases including PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang Data and VIP from the inception of databases to January 21, 2024. The Cochrane risk-of-bias tool 2.0 (RoB 2.0) and Stata 15.0 (Stata Corp, College Station, Texas, USA) were used to evaluate the literature quality and meta-analysis, and the evidence quality was assessed based on GRADE guidelines. This systematic review was registered at the International Prospective Register of Systematic Reviews. Results A total of 27 articles were included, involving 2579 patients. The results of the network meta-analysis showed that the top three treatment schemes were warm needle acupuncture, intensive silver needle therapy and meridian-sinew theory-based treatment. In terms of relieving pain, the top three treatments were electrical warm needling, intensive silver needle therapy and warm needle acupuncture. In improving mobility, the top three were meridian-sinew theory-based treatment, routine acupuncture and electroacupuncture. Conclusion For CNLBP patients, warm needle acupuncture, electrical warm needling and meridian-sinew theory-based treatment are mainly recommended. If patients have significant pain, electroacupuncture is strongly suggested. On the contrary, for patients with decreased joint mobility, meridian-sinew theory-based treatment is advocated.

Abstract Background The microvascular free fibula (MFF) flap is a reliable treatment modality for mandibular reconstruction and is suitable for dental implant placement after oncologic surgery. The most common issue with the MFF flap is its limited bone height, which typically results in excessive interarch space and complicates prosthodontic therapy. Overcoming the physical limitations from tumor excision and reducing the treatment time for prosthodontic rehabilitation to improve quality of life are critical clinical challenges. Case Presentation A 64-year-old male with lower left gum and bilateral buccal cancer received a single-layer microvascular MFF flap to reconstruct a mandibular defect post-tumor excision. He underwent a bilateral modiolus Z-plasty combined with a skin flap debulking procedure to relieve oral contracture, achieving adequate mouth opening for prosthodontic rehabilitation. Scar tissue bands on the bilateral cheeks significantly affected retention and stability, hampering dental impression performance. The patient sought prosthodontic rehabilitation to enhance his chewing function and quality of life promptly. Prosthodontic rehabilitation with all-on-4 implant therapy, utilizing computer-aided design and computer-assisted manufacturing (CAD/CAM), was completed within one month. Conclusion This case utilized the all-on-4 implant system to address the insufficient fibular height for conventional dental implant placements. Dental CAD/CAM was employed to mill custom prosthetic abutments and a large titanium framework for the implant bar overdenture, compensating for the excessive interarch space between the grafted fibula and maxilla. This treatment approach successfully shortened the prosthodontic rehabilitation time and overcame anatomical limitations.

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 μg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P

Abstract The movement towards electrification is entailing deep changes in power systems. On the demand side, the adoption of electric heating (EH) has grown rapidly in recent years. To eliminate the voltage fluctuations caused by the random switching‐on/‐off behaviors of EHs in some application scenes with special‐power‐line in low voltage distribution networks (LVDNs), a swarm‐intelligence‐based coordinated control approach of EHs for voltage stabilization with zero communication burden while guaranteeing the users’ thermal comforts is researched. A novel bird‐perch‐on‐branch (BPB) ‐based swarm intelligence theory is proposed, which reveals the mapping relation between local observations and global states. On this theoretical basis, a multi‐agent reinforcement learning (MARL) framework is developed for the coordinated dispatch of EHs, where the deep‐Q‐network (DQN) algorithm is adopted to learn and generate the optimal control policy for each EH. The implementation of the proposed MADQN‐BPB approach is described based on the principle of centralized‐training and decentralized‐execution. Comparative control performances of MADQN‐BPB with a commercially available approach, and the global optimal solution are evaluated. Simulation results verify the capability of MADQN‐BPB in voltage stabilization with zero communication burden. Its control performance is close to that of the global optimal solution, and is scalable to the variations of environment.

Abstract Background Aedes albopictus is a major arbovirus vector with small stagnant water containers being its oviposition sites. Mosquitoes search for these sites based on their olfactory cues (odor and moisture emanating from the water at the oviposition site), visual cues (size and color of the site), and gustatory cues (ion and nutrient concentration in that water). The gustatory mechanism through which mosquitoes search for oviposition sites remains unknown. Methods To investigate the role of taste receptors in Ae. albopictus oviposition site selection, we developed a laboratory model. This model assessed mosquito behavior in locating and detecting oviposition sites, using a location index to quantify site preference and detection time to measure response to water presence. We compared oviposition site-searching efficiency between mosquitoes with blocked and unblocked appendages, targeting the taste organs. Transcriptome sequencing was conducted to identify differentially expressed genes between water-exposed and unexposed mosquitoes. CRISPR/Cas9 technology was then employed to generate a mutant strain with a targeted gene knockout. Results There was no significant difference between the blocked and unblocked groups in the location index. In contrast, the detection time of the unblocked group differed significantly from all other groups, including those with blocked foreleg tarsus, midleg tarsus, hindleg tarsus, all tibia, and all tarsus. Transcriptome sequencing analyses of water-exposed and unexposed mosquitoes revealed that the taste-related gene gustatory receptor 11(gr11) was differentially expressed. This gene was knocked out with CRISPR/Cas9 technology to generate a pure mutant strain with 2- and 4-bp deletions, which exhibited a significantly longer detection time than the wild-type strain. Conclusions This study reveals the role of Ae. albopictus gr11 in water detection at oviposition sites, thereby providing a theoretical basis and scientific guidelines for managing the breeding sites of these mosquitoes. Graphical Abstract

Abstract Background The transposons of the hAT superfamily are the most widespread transposons ever known. SLEEPER genes encode domesticated transposases from the hAT superfamily, which may have lost their transposable functions during long-term evolution and transformed into host proteins that regulate plant growth and development. Results This study identified 162 members of the SLEEPER gene family from Brassica napus. These members are widely distributed on 19 chromosomes, mainly in the Cn subgenome, and have promoters with various cis-acting elements related to hormone regulation, abiotic stress, and growth and development regulation. Most of the genes in this family contain similar conserved domains and motifs, and the closer the genes are distributed on evolutionary branches, the more similar their structures are. Transcriptome sequencing performed on tissues at different growth stages from B. napus line 3529 indicated that these genes had different expression patterns, and nearly half of the genes were not detectably expressed in all samples. Conclusions This study investigated the gene structure, expression patterns, evolutionary features, and gene localization of the SLEEPER family members to confirm the significance of these genes in the growth of B. napus, providing a reference for the study of transposon domestication and outstanding genetic resources for the genetic improvement of B. napus.

Abstract Marine phosphatization events cause episodic carbonate fluorapatite (CFA) precipitation on seamounts, and are commonly linked to growth hiatuses in ferromanganese (Fe-Mn) crusts. However, the complete record of these events and their paleoenvironmental significance remains poorly understood, in large part due to poor age constraints. Here, we apply U-Pb dating to CFA in Fe-Mn crusts from Western Pacific seamounts. These data exhibit good alignment with Sr isotope ages, revealing six potential phosphatization events. This established CFA chronology tightens the timespan of phosphatization events and refines the age framework of Fe-Mn crusts. We subsequently utilize a multiproxy approach to demonstrate that the phosphatization events occurred coeval with the expansion of oceanic oxygen minimum zones. The Western Pacific Fe-Mn crusts thus document major perturbations in global oceanic phosphorus cycling, which appear to have been driven by climate-induced increases in primary productivity linked to changes in global ocean circulation.

Abstract Cell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.

Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Due to the large computational overhead, underutilization of features, and high bandwidth consumption in traditional SDN environments for DDoS attack detection and mitigation methods, this paper proposes a two-stage detection and mitigation method for DDoS attacks in SDN based on multi-dimensional characteristics. Firstly, an analysis of the traffic statistics from the SDN switch ports is performed, which aids in conducting a coarse-grained detection of DDoS attacks within the network. Subsequently, a Multi-Dimensional Deep Convolutional Classifier (MDDCC) is constructed using wavelet decomposition and convolutional neural networks to extract multi-dimensional characteristics from the traffic data passing through suspicious switches. Based on these extracted multi-dimensional characteristics, a simple classifier can be employed to accurately detect attack samples. Finally, by integrating graph theory with restrictive strategies, the source of attacks in SDN networks can be effectively traced and isolated. The experimental results indicate that the proposed method, which utilizes a minimal amount of statistical information, can quickly and accurately detect attacks within the SDN network. It demonstrates superior accuracy and generalization capabilities compared to traditional detection methods, especially when tested on both simulated and public datasets. Furthermore, by isolating the affected nodes, the method effectively mitigates the impact of the attacks, ensuring the normal transmission of legitimate traffic during network attacks. This approach not only enhances the detection capabilities but also provides a robust mechanism for containing the spread of cyber threats, thereby safeguarding the integrity and performance of the network.

Abstract Background Non‐small‐cell lung cancer (NSCLC) is a common malignancy with high morbidity and mortality. Circular RNAs are widely involved in NSCLC progression. However, the mechanism of circSLC25A16 in NSCLC has not been reported. Methods The expressions of circSLC25A16, microRNA‐335‐5p (miR‐335‐5p), and CDGSH iron–sulfur domain‐containing protein 2 (CISD2) were monitored by quantitative real‐time fluorescence polymerase chain reaction. Western blot was also carried out to measure the protein levels of CISD2, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA). For functional analysis, cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine, flow cytometry, transwell, and wound healing assays were utilized to examine cell proliferation, apoptosis, and migration. Glucose uptake and lactate production were detected using commercial kits. The relationship between miR‐335‐5p and circSLC25A16 or CISD2 was verified by dual‐luciferase reporter and RNA immunoprecipitation assays. Furthermore, tumor xenograft was established to explore the function of circSLC25A16 in vivo. Results CircSLC25A16 and CISD2 were overexpressed in NSCLC, but miR‐335‐5p was downregulated. CircSLC25A16 acted as a miR‐335‐5p sponge, and silencing of circSLC25A16 arrested cell proliferation, migration, and glycolysis, and promoted apoptosis, but these impacts were resumed by miR‐335‐5p inhibition. CISD2 was a miR‐335‐5p target, and overexpression of CISD2 abolished the suppressive function of miR‐335‐5p mimic on the malignant behavior of NSCLC cells. CircSLC25A16 could adsorb miR‐335‐5p to mediate CISD2 expression. Additionally, silencing circSLC25A16 restrained the growth of NSCLC tumor xenograft in vivo. Conclusion CircSLC25A16 facilitated NSCLC progression via the miR‐335‐5p/CISD2 axis, implying that circSLC25A16 may serve as a novel biomarker for NSCLC treatment.

Abstract Objective To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. Method In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi’s analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). Result Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients’ quality of life. Conclusion The nurses in the department of oncology have a low level of knowledge about the “good death”, and the correct understanding and view of the “good death” is the premise of the realization of " good death”. The ability of nursing staff to improve the “good death”, attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of “good death”.

Abstract Laser powder bed fusion (LPBF) is an additive manufacturing technology with high practical value. In order to improve the quality of the fabricated parts, process monitoring has become a crucial solution, offering the potential to ensure manufacturing stability and repeatability. However, a cardinal challenge involves discerning a precise correlation between process characteristics and potential defects. This paper elucidates the integration of an off-axis vision monitoring mechanism via a high-speed camera focused on capturing the single-track melting phenomenon. An innovative image processing method was devised to segment the plume and spatters, while Kalman filter was employed for multi-object tracking of the spatters. The features of both the plume and spatters were extracted, and their relationship with molten states was investigated. Finally, the PSO-XGBoost algorithm was utilized to identify five molten states, achieving an accuracy of 92.16%. The novelty of this approach resides in its unique combination of plume characteristics, spatter features, and computationally efficient machine learning models, which collectively address the challenge of limited field of view prevalent in real production scenarios, thereby enhancing process monitoring efficacy. Relative to existing methodologies, the proposed PSO-XGBoost approach offers heightened accuracy, convenience, and appropriateness for the monitoring of the LPBF process. This work provides an effective and novel approach to monitor the LPBF process and evaluate the part fabrication quality for complex and changeable working conditions.

Abstract Background Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. Results In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137 –/– ) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137 –/– miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137 –/– miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. Conclusions Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137 –/– miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.

Serine/arginine-rich splicing factor 3 (SRSF3), the smallest member of the SR protein family, serves multiple roles in RNA processing, including splicing, translation, and stability. Recent studies have shown that SRSF3 is implicated in several inflammatory diseases. However, its impact on macrophage inflammation remains unclear. Herein, we determined the expression of SRSF3 in inflammatory macrophages and found that the level of SRSF3 was increased in macrophages within atherosclerotic plaques, as well as in RAW-264.7 macrophages stimulated by lipopolysaccharides. Moreover, the downregulation of SRSF3 suppressed the levels of inflammatory cytokines by deactivating the nuclear factor κB (NFκB) pathway. Furthermore, the alternative splicing of myeloid differentiation protein 2 (MD2), a co-receptor of toll-like receptor 4 (TLR4), is regulated by SRSF3. The depletion of SRSF3 increased the level of the shorter MD2B splicing variants, which contributed to inflammatory inhibition in macrophages. In conclusion, our findings imply that SRSF3 regulates lipopolysaccharide-stimulated inflammation, in part by controlling the alternative splicing of MD2 mRNA in macrophages.

Abstract Rapid tool wear conditions during the manufacturing process are crucial for the enhancement of product quality. As an extension of our recent works, in this research, a generic in-situ tool wear condition monitoring during the end milling process based on dynamic mode and abnormal evaluation is proposed. With the engagement of dynamic mode decomposition, the real-time response of the sensing physical quantity during the end milling process can be predicted. Besides, by constructing the graph structure of the time series and calculating the difference between the predicted signal and the real-time signal, the anomaly can be acquired. Meanwhile, the tool wear state during the end milling process can be successfully evaluated. The proposed method is validated in milling tool wear experiments and received positive results (the mean relative error is recorded as 0.0507). The research, therefore, paves a new way to realize the in-situ tool wear condition monitoring.

Abstract Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases.

Abstract Hepatocellular carcinoma (HCC) is a common malignancy with poor survival and requires long-term follow-up. Hence, we collected information on patients with Primary Hepatocellular Carcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a deep learning with a multilayer neural network (the NMTLR model) for predicting the survival rate of patients with Primary Hepatocellular Carcinoma. HCC patients pathologically diagnosed between January 2011 and December 2015 in the SEER (Surveillance, Epidemiology, and End Results) database of the National Cancer Institute of the United States were selected as study subjects. We utilized two deep learning-based algorithms (DeepSurv and Neural Multi-Task Logistic Regression [NMTLR]) and a machine learning-based algorithm (Random Survival Forest [RSF]) for model training. A multivariable Cox Proportional Hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into a training set and a test set in a 7:3 ratio. The training dataset underwent hyperparameter tuning through 1000 iterations of random search and fivefold cross-validation. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-year, 3-year, and 5-year survival rates was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Area Under the Curve (AUC). The primary outcomes were the 1-year, 3-year, and 5-year overall survival rates. Models were developed using DeepSurv, NMTLR, RSF, and Cox Proportional Hazards regression. Model differentiation was evaluated using the C-index, calibration with concordance plots, and risk stratification capability with the log-rank test. The study included 2197 HCC patients, randomly divided into a training cohort (70%, n = 1537) and a testing cohort (30%, n = 660). Clinical characteristics between the two cohorts showed no significant statistical difference (p > 0.05). The deep learning models outperformed both RSF and CoxPH models, with C-indices of 0.735 (NMTLR) and 0.731 (DeepSurv) in the test dataset. The NMTLR model demonstrated enhanced accuracy and well-calibrated survival estimates, achieving an Area Under the Curve (AUC) of 0.824 for 1-year survival predictions, 0.813 for 3-year, and 0.803 for 5-year survival rates. This model's superior calibration and discriminative ability enhance its utility for clinical prognostication in Primary Hepatocellular Carcinoma. We deployed the NMTLR model as a web application for clinical practice. The NMTLR model have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with primary liver cancer.

Abstract Dual‐mode readout platforms with colorimetric and electrochemiluminescence (ECL) signal enhancement are proposed for the ultrasensitive and flexible detection of the monkeypox virus (MPXV) in different scenes. A new nanotag, Ru@U6‐Ru/Pt NPs is constructed for dual‐mode platforms by integrating double‐layered ECL luminophores and the nanozyme using Zr‐MOF (UiO‐66‐NH2) as the carrier, which not only generates enhanced ECL and colorimetric signals but also provide greater stability than that of commonly used nanotags. Dual‐mode platforms are used within 15 min from the “sample in” to the “result out” steps, without nucleic acid amplification. The colorimetric mode allows the screening of MPXV with the visual limit of detection (vLOD) of 0.1 pM (6 × 108 copies µL−1) and the ECL mode supports quantitative detection of MPXV with an LOD as low as 10 aM (6 copies·µL−1), resulting in a broad sensing range of 60 to 3 × 1011 copies·µL−1 (10 orders of magnitude). Validation is conducted using 50 clinical samples, which is 100% concordant to those of quantitative polymerase chain reaction (qPCR), indicating that Ru@U6‐Ru/Pt NPs‐based dual‐mode sensing platforms showed great promise as rapid, sensitive, and accurate tools for diagnosis of the nucleic acid of MPXV and other infectious pathogens.

This study assessed the impacts of monosodium glutamate (MSG) on the growth performance, feed utilization, feed intake, and appetite regulation of Chinese mitten crab, Eriocheir sinensis. A total of 240 juvenile crabs (9.16 ± 0.21 g) were assigned to six experimental diets supplemented with MSG at 0 %, 0.20 %, 0.39 %, 0.59 %, 0.78 % and 0.98 %. The results demonstrated that 0.59 % MSG supplementation significantly enhanced the weight gain rate (WGR), specific growth rate (SGR), and feed utilization of juvenile E. sinensis by increasing feed intake (FI) (p < 0.05). Moreover, dietary moderate MSG improved the mid-intestine morphology, such as height of microvillus (HMV), width of microvillus (WMV), and thickness of muscularis (TM). The qRT-PCR analysis demonstrated that the mRNA expression levels of the appetite-stimulating neural signals agouti related protein (agrp) and ghrelin were increased significantly by dietary moderate MSG (p < 0.05). Conversely, the mRNA levels of protein kinase B (akt), target of rapamycin (tor) and 4E-binding protein (4e-bp), as well as appetite-suppressing neural signals pro-opiomelanocortin (pomc), corticotropin-releasing factor (crf) and peptide yy (pyy) were significantly down-regulated (p < 0.05). The two-slope broken-line regression analysis of SGR in relation to dietary MSG levels suggested that the optimum dietary MSG level for juvenile E. sinensis was 5.6 g/kg. Collectively, MSG may potentially stimulate or suppress the appetite regulation neural signals/hormones, thereby modulating the feeding behavior of E. sinensis.