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Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3−/− (Shn3 −/− ) mice with augmented osteoblast activity, we show Shn3 −/− mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3 −/− mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.

Abstract Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies.

Abstract The ultrafine cellular structure promotes the extraordinary mechanical performance of metals manufactured by laser powder‐bed‐fusion (L‐PBF). An in‐depth understanding of the mechanisms governing the thermal stability of such structures is crucial for designing reliable L‐PBF components for high‐temperature applications. Here, characterizations and 3D discrete dislocation dynamics simulations are performed to comprehensively understand the evolution of cellular structures in 316L stainless steel during annealing. The dominance of screw‐type dislocation dipoles in the dislocation cells is reported. However, the majority of dislocations in sub‐grain boundaries (SGBs) are geometrically necessary dislocations (GNDs) with varying types. The disparity in dislocation types can be attributed to the variation in local stacking fault energy (SFE) arising from chemical heterogeneity. The presence of screw‐type dislocations facilitates the unpinning of dislocations from dislocation cells/SGBs, resulting in a high dislocation mobility. In contrast, the migration of SGBs with dominating edge‐type GNDs requires collaborative motion of dislocations, leading to a sluggish migration rate and an enhanced thermal stability. This work emphasizes the significant role of dislocation type in the thermal stability of cellular structures. Furthermore, it sheds light on how to locally tune dislocation structures with desired dislocation types by adjusting local chemistry‐dependent SFE and heat treatment.

An accurate depiction of the deformation and fracture mechanisms of metal matrix composites is the key to their rational structure and property design. In the present work, the Advanced Guerson Tvergaard Needleman (AGTN) constitutive model is firstly combined with an algorithm to reconstruct realistic 3D microstructures within the finite-element framework. We employ this model to probe the elastoplastic response and fracture behaviors of aluminum matrix composites with different volume fractions of reinforcing particles (7, 14, and 21 %) and under various loading conditions (tension, compression and shear). Real microstructures are referred to reconstruct the three-dimensional model of the composites. The AGTN constitutive model is integrated with the micromechanical damage model, which is capable of independently describing the constitutive behavior of various components, including the elastoplastic damage of the metal matrix, particle-enhanced elastic-brittle failure, and the interfacial traction separation. By using the conventional SiCp/Al composite system as a model material, we examine the stress state of the matrix and fracture mechanisms under different loading conditions by using triaxiality, Lode angle and statistical analysis. In general, the damage of SiCp/Al composites can be attributed to interfacial debonding and particle fracture, whereas the latter dominates when the volume fraction of SiCp is high. Furthermore, the critical volume fraction for the transition of damage mechanisms is found to be largely dependent on the loading conditions. Our work provides a comprehensive understanding of particle-reinforced aluminum matrix composite under in-service conditions.

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract)

One of the major challenges in the aquaculture of marine organisms is the susceptibility to pathogens. Immune cells defend bacterial invasion by recognizing pathogen-associated molecular patterns (PAMPs) such as Lipopolysaccharides (LPS) in Gram-negative bacteria. The white body are key organs for immune response and hematopoiesis, and play an important role in understanding the antimicrobial biological response in gold-ringed octopus (Amphioctopus fangsiao). In the present research, transcriptome sequencing and bioinformatics analysis were conducted on A. fangsiao white body tissue after 6 h and 24 h of LPS stimulation. The results showed 2,029 and 73 differentially expressed genes (DEGs) at the 6- and 24-hour time points, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were beneficial in determining immune-related terms and signaling pathways. Subsequently, a protein-protein interaction (PPI) network was constructed and 20 hub genes, such as AKT3, MAPK14, and PIK3CA, were identified. These genes are involved in a variety of signaling pathways, including the Hippo signaling pathway, chemokine signaling pathway, and leukocyte trans endothelial migration. Using qRT-PCR, the accuracy of the 20 hub genes was verified. The present study provides a substantial theoretical foundation for the research on A. fangsiao white body immunity, enhancing the current understanding of cephalopods' innate immunity.

Sepia esculenta is a tasty and nutritious cephalopod. But the trend toward global warming is accelerating with massive emissions of greenhouse gases. An increase in seawater temperature and a decrease in pH are a great challenge for artificial breeding and culture of S. esculenta. In this study, we investigated the contingency mechanism of S. esculenta larvae under both high temperature and low pH conditions by transcriptome analysis. A total of 1235 DEGs were identified. functional enrichment analysis results suggest that high temperature and low pH conditions led to malignant proliferation in exceptional cells of S. esculenta larvae. A comprehensive analysis of the KEGG signaling pathway and protein-protein interaction network (PPI) identified sixteen key genes under both high temperature and low pH conditions. The three genes with the highest quantities of interactions or involved in more KEGG signaling pathways were identified as hub genes affecting normal physiological processes in S. esculenta. In this study, the effects of global warming and ocean acidification on the metabolism and immunity of S. esculenta larvae were preliminarily investigated to provide necessary help for S. esculenta captive breeding in the face of global climate change.

Pathogenic infections significantly limit the culture of marine organisms, such as cephalopods. However, there is a lack of immune information regarding cephalopods to address pathogen problems. Polyriboinosinic polyribocytidylic acid (Poly I:C), a synthetic virus-like molecule, can be recognized by the immune cells as pathogen-associated molecular patterns (PAMPs), and this process is often used to simulate the invasion of viruses. The white body is an immune and hematopoietic organ, and its RNA-seq information obtained from Amphioctopus fangsiao stimulated by Poly I:C is essential for understanding the antiviral immune response in this species. In this research, we performed transcriptome sequencing and bioinformatics analysis of A. fangsiao white body tissue within 24 h stimulated by Poly I:C. A large number of differentially expressed genes (DEGs) were detected in this study, including 2,613 and 8 DEGs at 6 h and 24 h, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used for searching immune-related terms and genes. A protein–protein interaction (PPI) network was constructed to identify the relationship between immune genes. Finally, the 20 hub genes including RAC1, MAPK14, PIK3CA and other seventeen hub genes were identified based on the network and pathway analyses, and we validated the accuracy of 20 hub genes using qRT-PCR. These hub genes mainly participated in PI3K-Akt signaling pathway, Chemokine signaling pathway and other signaling pathways, in addition to the ubiquitin family. These research results provided a valuable theoretical basis for researching A. fangsiao white body immunity and significantly improved our cognition about innate immunity of cephalopods.

A new species of Orchidaceae, Phalaenopsis zhanhuoensis, from Xichou County, Yunnan, China, is described and illustrated. The novelty is close to P. taenialis, P. wilsonii, and P. stobartiana, but differs from them by having a distinct, fleshy anterior callus with a deeply lobed apex at the base of the labellum and lateral lobes of labellum reflexed and facing outward.

Abstract Blind watermark extraction in discrete cosine transform (DCT) domain has a wide application prospect as well as a challenging subject. The imperceptibility of watermark signal makes watermark extraction a weak signal reception issue in essence. For DCT coefficients of host image generally disobey Gaussian distribution, at which the performance of linear correlated reception is no longer optimal. Aiming at this, a novel blind watermark extraction scheme combining the uncorrelated reception with adaptive bistable stochastic resonance (ABSR) technique is proposed. First, by block DCT transformation for host image, an additive watermark embedding algorithm is introduced, in which the watermarked image can be converted to one dimensional time domain weak signal (binary watermark image) reception under additive Laplacian noise (selected DCT coefficients). On this basis, through the key technology research on quantitatively cooperative resonance relationship under Laplacian noise, the ABSR system can be implemented by bistable system parameters self‐adaptive adjustment, in which the ABSR system output signal will be enhanced rather than be weakened by random noise. Finally, the ABSR‐based watermark extraction scheme is investigated, and both the visual effect, bit error ratio performance and robustness of proposed scheme are testified to be superior to that of traditional uncorrelated extraction.

Abstract Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP‐derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC‐markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP‐outer subset. Cell lineage tracing further evidence that a small number of Ctsk‐expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2‐cre‐mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.

Nanoplastics (NPs, < 1 μm) have attracted widespread attention due to their potential threats to organisms, ecosystem, and public health. However, there is limited research on the effects of NPs on cephalopods. Sepia esculenta (Mollusks, Cephalopoda, Sepioidea), an economically major species of Sepiidea family in the world, is well received by consumers for its delicious quality and rich nutrition. In the present study, S. esculenta larvae were treated with polystyrene nanoplastics (PS-NPs) at 50 μg/mL for 4 h, and then physiological biomarkers (SOD, GSTs and MDA) and RNA-Seq in the whole body were performed. Research results suggested that PS-NPs exposure had induced oxidative stress of S. esculenta larvae. In addition, several key genes and signaling pathways related to oxidative stress were obtained based on DEGs, GO and KEGG enrichment analyses, as well as PPI construction analysis of transcriptome data. This study enriches the research on the effects of NPs exposure on different organisms and provides insights and references for revealing the mechanisms of oxidative stress caused at the molecular level.

Spermatogenesis is the production of spermatozoa by the testes, a process that is associated with reproduction in males. Amphioctopus fangsiao is an economically important species from the northern coast of China, and little research has been done on spermatogenesis in this species. In this study, we performed transcriptome analysis of testis and other somatic tissues. The maturing stage of testis development was selected, in which the emergence of spermatozoa was observed. A total of 15,773 differentially expressed genes were identified, including 8,922 upregulated genes and 6,851 downregulated genes. GO and KEGG enrichment analyses were performed to explore the functions of genes related to spermatogenesis, and the interactions between genes were examined by constructing protein interaction networks. Pathways and genes related to spermatogenesis were identified, including the oxytocin signaling pathway, the calcium signaling pathway, the FOXO signaling pathway, the DNAH family, and other key genes. The expression levels of 25 key genes were verified by qRT-PCR. The results for spermatogenesis-related genes will provide insights into the processes of spermatogenesis and testis development in A. fangsiao.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and in vivo, revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies.

Introduction: Gastric cancer is one of the common malignancies worldwide, and drug resistance is a major factor contributing to the difficulty of treatment in gastric cancer. Zuojinwan (ZJW) has been found to exhibit a certain inhibitory effect on tumor cells. However, the molecular mechanisms of ZJW reversing drug resistance in gastric cancer are still unclear. Method: Human gastric cancer cisplatin-resistant cells SGC-7901/DDP and BGC-823/DDP were divided into control groups, DDP groups (10 μg/mL), 2-DG (5 mM) groups, and ZJW (50 μg/mL) combined with DDP (10 μg/mL) groups. After 48 h of culture, cell proliferation inhibition rate, glucose uptake rate, ATP, and lactate production were detected. Following lentiviral transfection to overexpress GLUT1 and HDAC1, western blot analysis was employed to examine the expression of HDAC1, P53, Ace-p53, and glucose metabolism-related proteins such as GLUT1, LDHA, HK II in the cells. Results: The combination of ZJW and DDP significantly inhibits the proliferation and glycolysis of cisplatin resistant gastric cancer cells. Compared with the DDP group, the combination of ZJW and DDP exhibited a higher inhibition rate (P

The large-scale deployment and rapid development of the new generation mobile communication system underpin the widespread application of a massive and diverse range of Internet of things (IoT) devices.However, the distributed application of IoT devices results to significant disparities in private data and substantial heterogeneity in local processing models, which severely limits the aggregation capability of global intelligent model.Therefore, to tackle the challenges of data heterogeneity, model heterogeneity, and insufficient labeling faced by intelligent modulation recognition in cognitive IoT, an algorithm was proposed for heterogeneous federated bidirectional semi-supervised modulation recognition, which incorporated bidirectional knowledge distillation.In the proposed algorithm, a public pseudo dataset was generated by variational autoencoder in the cloud for supporting uplink global knowledge distillation, and adaptively sharing to the local devices for downlink heterogeneous knowledge distillation, while integrating a semi-supervised algorithm within the distillation process.The simulation results indicate that the proposed algorithm outperforms current federated learning algorithms in terms of effectiveness and applicability in the field of communication signal processing.

Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their molecular response to acute Cd exposure remain unclear. In this study, the Pacific oyster Crassostrea gigas was used as a biological model, exposed to acute Cd stress for 96 h. Transcriptomic analyses of their gills were performed, and metabolomic analyses further validated these results. In our study, a total of 111 differentially expressed metabolites (DEMs) and 2108 differentially expressed genes (DEGs) were identified under acute Cd exposure. Further analyses revealed alterations in key genes and metabolic pathways associated with heavy metal stress response. Cd exposure triggered physiological and metabolic responses in oysters, including enhanced oxidative stress and disturbances in energy metabolism, and these changes revealed the biological response of oysters to acute Cd stress. Moreover, oysters could effectively enhance the tolerance and detoxification ability to acute Cd exposure through activating ABC transporters, enhancing glutathione metabolism and sulfur relay system in gill cells, and regulating energy metabolism. This study reveals the molecular mechanism of acute Cd stress in oysters and explores the molecular mechanism of high tolerance to Cd in oysters by using combined metabolomics and transcriptome analysis.

Near-infrared spectroscopy (NIR) has become an essential tool for non-destructive analysis in various fields, including aquaculture. This study presents a pioneering application of portable NIR spectrometers to analyze glycogen content in the gonadal tissues of the Pacific oyster (Crassostrea gigas), marking the first instance of developing quantitative models for glycogen in tetraploid C. gigas. The research also provides a comparative analysis with models for diploid and triploid oysters, underscoring the innovative use of portable NIR technology in aquaculture. Two portable NIR spectrometers were employed: the Micro NIR 1700 (908–1676 nm) and the Micro PHAZIR RX (1624–2460 nm). Near-infrared spectra were acquired from the gonadal tissues of diploid, triploid, and tetraploid C. gigas. Quantitative models for glycogen content were developed and validated using cross-validation methods. Additionally, qualitative models for different ploidies and genders were established. For the Micro NIR 1700, the cross-validation correlation coefficients (Rcv) and cross-validation relative predictive errors (RPDcv) for glycogen were 0.949 and 3.191 for diploids, 0.915 and 2.498 for triploids, and 0.902 and 2.310 for tetraploids. The Micro PHAZIR RX achieved Rcv and RPDcv values of 0.781 and 2.240 for diploids, 0.839 and 2.504 for triploids, and 0.717 and 1.851 for tetraploids. The Micro NIR 1700 demonstrated superior quantitative performance, with RPD values exceeding 2, indicating its effectiveness in predicting glycogen content across different ploidy levels. Qualitative models showed a performance index of 91.6 for diploid and 95 for tetraploid genders using the Micro NIR 1700, while the Micro PHAZIR RX achieved correct identification rates of 99.79% and 100% for diploid and tetraploid genders, respectively. However, differentiation of ploidies was less successful with both instruments. This study’s originality lies in establishing the first quantitative models for glycogen content in tetraploid C. gigas using portable NIR spectrometers, highlighting the significant advancements in non-destructive glycogen analysis. The applicability of these findings is substantial for oyster breeding programs focused on enhancing meat quality traits. These models provide a valuable phenotyping tool for selecting oysters with optimal glycogen content, demonstrating the practical utility of portable NIR technology in aquaculture.

Over the years, oysters have faced recurring mass mortality issues during the summer breeding season, with Vibrio infection emerging as a significant contributing factor. Tubules of gill filaments were confirmed to be in the hematopoietic position in Crassostrea gigas, which produce hemocytes with immune defense capabilities. Additionally, the epithelial cells of oyster gills produce immune effectors to defend against pathogens. In light of this, we performed a transcriptome analysis of gill tissues obtained from C. gigas infected with Vibrio alginolyticus for 12 h and 48 h. Through this analysis, we identified 1024 differentially expressed genes (DEGs) at 12 h post-injection and 1079 DEGs at 48 h post-injection. Enrichment analysis of these DEGs revealed a significant association with immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To further investigate the immune response, we constructed a protein–protein interaction (PPI) network using the DEGs enriched in immune-associated KEGG pathways. This network provided insights into the interactions and relationships among these genes, shedding light on the underlying mechanisms of the innate immune defense mechanism in oyster gills. To ensure the accuracy of our findings, we validated 16 key genes using quantitative RT-PCR. Overall, this study represents the first exploration of the innate immune defense mechanism in oyster gills using a PPI network approach. The findings provide valuable insights for future research on oyster pathogen control and the development of oysters with enhanced antimicrobial resistance.

Tetraploid oysters are artificially produced oysters that do not exist in nature. The successful breeding of 100% triploid oysters resolved the difficulties of traditional drug-induced triploids, such as the presence of drug residues and a low triploid induction rate. However, little is known concerning the biochemical composition and nutrient contents of such tetraploids. Therefore, we investigated compositional differences among diploid, triploid, and tetraploid Crassostrea gigas as well as between males and females of diploids and tetraploids. The findings indicated that glycogen, EPA, ∑PUFA, and omega-3 contents were significantly higher in triploid oysters than in diploids or tetraploids; tetraploid oysters had a significantly higher protein content, C14:0, essential amino acid, and flavor-presenting amino acid contents than diploids or triploids. For both diploid and tetraploids, females had significantly higher levels of glutamate, methionine, and phenylalanine than males but lower levels of glycine and alanine. In addition, female oysters had significantly more EPA, DHA, omega-3, and total fatty acids, a result that may be due to the fact that gonadal development in male oysters requires more energy to sustain growth, consumes greater amounts of nutrients, and accumulates more proteins. With these results, important information is provided on the production of C. gigas, as well as on the basis and backing for the genetic breeding of oysters.

Abstract Background Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear. Results In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure. Conclusions S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.

Abstract Innovative modes of response can greatly push forward chemical sensing processes and subsequently improve sensing performance. Classical chemical sensing modes seldom involve the transition of a delicate molecular assembly during the response. Here, we display a sensing mode for polyamine detection based on an order–order transition of iron–sulfur complexes upon their assembly. Strong validation proves that the unique order–order transition of the assemblies is the driving force of the response, in which the polyamine captures the metal ion of the iron–sulfur complex, leading it to decompose into a metal–polyamine product, accompanied by an order–order transition of the assemblies. This mechanism makes the detection process more intuitive and selective, and remarkably improves the detection efficiency, achieving excellent polyamines specificity, second-level response, convenient visual detection, and good recyclability of the sensing system. Furthermore, this paper also provides opportunities for the further application of the iron–sulfur platform in environment-related fields.

The emergence of triploid oysters has freed the oyster market from the problem of interruptions in the breeding season, allowing for year-round availability. However, according to recent statistics, the phenomenon of fertility in triploid oysters has been increasing yearly, perhaps eventually leading to the loss of the sterility characteristic. This has in turn affected the oyster farming industry. Therefore, we attempted to mine key genes through transcriptomics to find the causes of triploid fertility. During our surveys and sampling, we found that most of the fertile triploid Crassostrea gigas were females, with a much smaller percentage of males. Therefore, the main objective of this study was to analyze the differences between fertile and sterile triploid female C. gigas. We performed transcriptome analysis of fertile female triploid C. gigas and sterile female triploid C. gigas and identified 2361 up-regulated differentially expressed genes (DEGs) and 1541 down-regulated DEGs, respectively. Enrichment analysis of these DEGs revealed that most GO terms and KEGG pathways were associated with mitosis. We then created a protein–protein interaction (PPI) network using genes enriched in mitosis-associated KEGG pathways. Finally, we screened and validated 26 key genes by quantitative RT-PCR and all were found to be downregulated in expression in sterile female triploids. The main cause of sterility is the suppression of the expression of genes that control the process of germ cell proliferation, the failure of the mitotic cycle to proceed smoothly, and the inability to produce an oogonium. These results can be used to explore ways to reduce the fertility of triploid C. gigas and to promote the breeding of higher quality triploid oysters.

Reinforcements in metal composites are usually dispersed at grain boundaries. We here show that the rapid solidification during laser additive manufacturing enables the spontaneous engulfment of reinforcing particles inside aluminum grains, which helps to decouple the stress concentration induced by grain boundaries and reinforcements. The additively manufactured TiB2-Al composite possesses 30% increase in tensile strength and nearly tripled ductility as compared with composite obtained by the traditional method. Our experimental investigations indicate that the intragranular dispersion of particles not only inhibits crack nucleation but also promotes strain hardening, leading to the remarkably enhanced mechanical properties.

Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified Plasmodium falciparum tyrosyl-tRNA synthetase (PfTyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against PfTyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for PfTyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within PfTyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of Plasmodium falciparum in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by P. falciparum.

Regarding the Cramer-Rao lower bound (CRLB) as a localization accuracy metric, the sufficient conditions of the LRA in the time difference of arrival (TDoA)-based localization scenario were discussed and the influence of different factors on the LRA were analyzed.Furthermore, the node placement problem for wireless sensor network (WSN) was investigated by formulating an optimization problem with the objective as average CRLB, which was solved by a genetic algorithm based on LRA pre-judgment.Simulation validates the properties of the CRLB in a single-source scenario and verifies the sufficient condition and the spatial range of the LRA.The simulation also shows that the localization accuracy determined by the proposed algorithm is improved by 33.92% higher than the uniform angle array placement scheme, 13.74% compared to the regional vertex placement scheme, and 9.65% compared to the direct genetic algorithm.

This study aims to investigate the effect of rare earth (RE) elements on the microstructure and mechanical properties of bainite/martensite (B/M) bearing steel. For this purpose, GCr15 bearing steels with different RE contents were prepared and analyzed after experiencing B/M heat treatment. The results show that RE addition significantly delays the bainite transformation by reducing grain boundary energy and carbon diffusion rate, leading to a reduction of bainite volume fraction from 27.3% for bearing steel without RE addition to less than 14.5% for RE-treated steels, and the corresponding increase of martensite volume fraction from 39.1% to more than 50.2%. The volume fraction of retained austenite (RA) remains nearly unchanged. Meanwhile, the width of the bainite needles gets refined in RE-treated steels while martensite and RA blocks become bigger. Compared with bearing steel without RE addition, larger RA blocks in RE-treated steels unexpectedly have higher stability due to higher dislocation density and surrounding phases strength. Accompanied by the change of microstructure, the hardness in RE-Treated steels improves slightly, while the fracture toughness dramatically deteriorates which can be directly explained by two mechanical phenomena during toughness test. The one is that the RA in RE-treated steels is harder to transform into martensite and thus consumes less energy; The other one gives that cracks tend to propagate along grain boundaries or martensite interfaces with less energy consumption easily in RE-treated steels instead of breaking off bainite.

Heterogeneous cellular networks (HCNs) are envisioned as a promising architecture to provide seamless wireless coverage and increase network capacity. However, the densified multi-tier network architecture introduces excessive intra- and cross-tier interference and makes HCNs vulnerable to eavesdropping attacks. In this article, a dynamic spectrum control (DSC)-assisted transmission scheme is proposed for HCNs to strengthen network security and increase the network capacity. Specifically, the proposed DSC-assisted transmission scheme leverages the idea of block cryptography to generate sequence families, which represent the transmission decisions, by performing iterative and orthogonal sequence transformations. Based on the sequence families, multiple users can dynamically occupy different frequency slots for data transmission simultaneously. In addition, the collision probability of the data transmission is analyzed, which results in closed-form expressions of the reliable transmission probability and the secrecy probability. Then, the upper and lower bounds of network capacity are further derived with given requirements on the reliable and secure transmission probabilities. Simulation results demonstrate that the proposed DSC-assisted scheme can outperform the benchmark scheme in terms of security performance. Finally, the impacts of key factors in the proposed DSC-assisted scheme on the network capacity and security are evaluated and discussed.

High-strength nanocrystalline materials come at the expense of tensile ductility, thermal stability, and electrical conductivity. Here the authors report a nanodispersion-in-nanograins strategy where ultra-nano-carbon was used to concurrently achieve above four mutually exclusive properties.

Nanoplastics (NPs), as a new type of pollutant with a size small than 1 μm, are ubiquitous and harmful to organisms. There has been an increasing amount of research concerning the effects of NPs on organisms over recent years, especially on aquatic animals. However, there is a limited study on the impact of NPs on mollusk cephalopods. In this research, Sepia esculenta, belonging to Cephalopoda, Coleoidea, Sepioidea, was selected to explore the effects caused by NPs exposure. The S. esculenta larvae were exposed to polystyrene NPs (PS-NPs) with diameter 50 nm (100 mg/L) for 4 h. The detection of oxidative stress biomarkers displayed an obvious increase in SOD (superoxide dismutase) activity and MDA (malondialdehyde) level. Then, RNA-Seq was performed to explore the oxidative stress response at mRNA level. The transcriptome analysis demonstrated that the expression of 2,570 genes was affected by PS-NPs. Besides, the signaling pathways of ribosome, ribosome biogenesis in eukaryotes, proteasome, and MAPK were enriched. This study not only provides novel references for understanding the mechanisms of oxidative stress response induced by NPs, but also reminds us to follow with interest the influence of acute exposure to NPs.

Study region: Second Songhua River basin (SSRB), Northeast China. Study focus: Accurately assessing future flood risks is the premise and foundation of flood control and water resources management. At present, studies are still lacking in assessing future watershed flood risks that consider climate change and social development in Northeast China and the relative flood risk assessment framework. This study proposed an integrated flood assessment framework containing the AHP, entropy weight, and GCM downscaling methods, which was implemented in the SSRB, a typical watershed in Northeast China, to estimate future basin flood risks under climate change and social development. New hydrological insights for the region: The flood risk in the SSRB will increase significantly in the mid-term (2051–2075) and long-term (2076–2100) future. The areas under the four scenarios with greater than high-risk levels will expand by 28.9 %, 105.6 %, 165.6 %, and 156.7 %, respectively, compared to the historical scenario. The newly added areas mainly located in the lower reaches. Precipitation changes are the primary reason for the future flood risks. The increased GDP under a higher forcing degree will also significantly increase the flood risk in the long-term future in the lower reaches. Based on these above findings, extreme precipitation forecasting and flood management in downstream areas in the basin need to be enhanced. Energy-saving and emission-reduction measures should be simultaneously implemented.

The primary influencer of aquaculture quality in Amphioctopus fangsiao is pathogen infection. Both lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (Poly I:C) are recognized by the pattern recognition receptor (PRR) within immune cells, a system that frequently serves to emulate pathogen invasion. Hemolymph, which functions as a transport mechanism for immune cells, offers vital transcriptome information when A. fangsiao is exposed to pathogens, thereby contributing to our comprehension of the species’ immune biological mechanisms. In this study, we conducted analyses of transcript profiles under the influence of LPS and Poly I:C within a 24 h period. Concurrently, we developed a Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules and genes. Further, we carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to investigate the primary modular functions. Co-expression network analyses unveiled a series of immune response processes following pathogen stress, identifying several key modules and hub genes, including PKMYT1 and NAMPT. The invaluable genetic resources provided by our results aid our understanding of the immune response in A. fangsiao hemolymph and will further our exploration of the molecular mechanisms of pathogen infection in mollusks.

Sepia esculenta is a cephalopod widely distributed in the Western Pacific Ocean, and there has been growing research interest due to its high economic and nutritional value. The limited anti-stress capacity of larvae renders challenges for their adaptation to high ambient temperatures. Exposure to high temperatures produces intense stress responses, thereby affecting survival, metabolism, immunity, and other life activities. Notably, the molecular mechanisms by which larval cuttlefish cope with high temperatures are not well understood. As such, in the present study, transcriptome sequencing of S. esculenta larvae was performed and 1,927 differentially expressed genes (DEGs) were identified. DEGs were subjected to functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The top 20 terms of biological processes in GO and 20 high-temperature stress-related pathways in KEGG functional enrichment analysis were identified. A protein-protein interaction network was constructed to investigate the interaction between temperature stress-related genes. A total of 30 key genes with a high degree of participation in KEGG signaling pathways or protein-protein interactions were identified and subsequently validated using quantitative RT-PCR. Through a comprehensive analysis of the protein-protein interaction network and KEGG signaling pathway, the functions of three hub genes (HSP90AA1, PSMD6, and PSMA5), which belong to the heat shock protein family and proteasome, were explored. The present results can facilitate further understanding of the mechanism of high temperature resistance in invertebrates and provide a reference for the S. esculenta industry in the context of global warming.

Sea cucumber Apostichopus japonicus, an important marine benthic animal, is particularly sensitive to environmental temperature stress, which affected the growth, metabolism, and reproduction even survival. In this study, we used whole genome bisulfite sequencing (WGBS) to perform a comprehensive comparative analysis of the DNA methylation profiles of A. japonicus at three temperatures: normal (20 °C), aestivation (26 °C), and lethal (32 °C). The results showed that the total methylation level was highest in group T26 and lowest in group T32. Most of the DNA methylation occurred on the C bases of the CG type, and the degree of DNA methylation on the CG-type C bases was 13.32–14.99%, reflecting a moderate level of DNA methylation. Comparison of differentially methylated regions (DMRs) in the CG sequence context, we identified 17,174 DMRs in group T26_vs_T20 and 16,216 DMRs in group T32_vs_T26. There were more hypermethylated regions than hypomethylated regions, and this difference was more obvious in group T32_vs_T26. DMRs analysis of the promoter regions and the gene body regions identified more DMR-related genes in the gene body region than in the promoter region in both comparison groups (T26_vs_T20 and T32_vs_T26). GO and KEGG analysis showed that pathways such as protein processing in the endoplasmic reticulum, ubiquitin mediated proteolysis, and endocytosis, etc., were highly enriched in the DMR-related genes in the comparison groups. Some of these pathways that were significantly enriched in the hypermethylated genes in group T26_vs_T20 but were enriched in the hypomethylated genes in group T32_vs_T26. Enrichment analysis of genes both differentially methylated and differentially expressed showed that downregulated genes in group T32_vs_T26 that were also hypomethylated in the gene body region were significantly enriched in the metabolic and the antioxidant-related glutathione metabolism pathway. Our results suggested that DNA methylation develop a lot of variation in the regulation of the response of A. japonicus to two levels of heat stress: at aestivation temperature and at lethal temperature, and there are many differences between the two. The results of this study provide important insights into the epigenetic mechanisms underlying the response of A. japonicus to the pressure of environmental temperature.

Sperm storage is an important reproductive strategy in Amphioctopus fangsiao. Sperm can be stored in the oviducal glands up to eight months before fertilization. However, studies on the underlying storage mechanisms remain limited. In this study, the morphological structures of the oviductal glands and the changes adapted for sperm storage and fertilization were investigated by Hematoxylin eosin (HE) staining, transmission electron microscopy (TEM), and Alcian blue periodic acid Schiff (AB-PAS) staining. Results revealed that the nucleo-cytoplasmic ratio of the peripheral gland cells decreased and the eosinophilic secretory granules (glycoproteins) appeared in the cytoplasm and lumen during sperm storage. The cytoplasm of the central gland appeared vacuolated and AB pH 2.5 (+) secretions (acid mucins) were dispersed in the cells. These secretions may pass through the central cavity into the oviducts and be involved in zygote packaging. The spermathecae are composed of columnar epithelial ciliated cells with secretory functions. PAS (+) glycoproteins were found in the lumen, providing a microenvironment conducive to sperm survival. Cilia in the oviducts, central cavity, and spermathecae may help with sperm delivery, storage, and release, and egg transport. This study enhances our understanding of the biological reproduction process in A. fangsiao.

Millimeter-wave radar has demonstrated its high efficiency in complex environments in recent years, which outperforms LiDAR and computer vision in human activity recognition in the presence of smoke, fog, and dust. In previous studies, researchers mostly analyzed either 2D (3D) point cloud or range–Doppler information from radar echo to extract activity features. In this paper, we propose a multi-model deep learning approach to fuse the features of both point clouds and range–Doppler for classifying six activities, i.e., boxing, jumping, squatting, walking, circling, and high-knee lifting, based on a millimeter-wave radar. We adopt a CNN–LSTM model to extract the time-serial features from point clouds and a CNN model to obtain the features from range–Doppler. Then we fuse the two features and input the fused feature into the full connected layer for classification. We built a dataset based on a 3D millimeter-wave radar from 17 volunteers. The evaluation result based on the dataset shows that this method has higher accuracy than utilizing the two kinds of information separately and achieves a recognition accuracy of 97.26%, which is about 1% higher than other networks with only one kind of data as input.

Micro-tools comprising difficult-to-machine materials have seen widespread application in micro-manufacturing to satisfy the demands of micro-part processing and micro-device development. Taking micro-shafts as an example, the related developmental technology, based on wire electric discharge grinding (WEDG) as the core method, is one of the key technologies used to prepare high-precision micro-shafts. To enable efficient and high-precision machining of micro-shafts with target diameters, instead of performing multiple repeated on-machine measurements and reprocessing, a geometric constraint strategy is proposed based on the previously introduced twin-mirroring-wire tangential feed electrical discharge grinding (TMTF-WEDG). This strategy encompasses the tool setting method, tangential feed distance compensation, and an equation that establishes the relationship between tangential distance and diameter variation. These components are derived from a key points analysis of the geometric constraints. The micro-shafts with diameters of 50 µm and consistencies of ±1.5 µm are repeatedly processed. A series of micro-shafts with diameters ranging from 30 µm to 120 µm achieve geometric constraints with a diameter accuracy of ±2 µm, accompanied by the complete continuous automation of the entire process. Accordingly, it can be concluded that the geometric constraint strategy is flexible and stable and can be controlled with high precision in the TMTF-WEDG process.

Sepia esculenta is an economically important mollusk distributed in the coastal waters of China. Juveniles are more susceptible to stimulation by the external environment than mature individuals. The ocean salinity fluctuates due to environmental changes. However, there is a lack of research on the salinity adaptations of S. esculenta. Therefore, in this study, we investigated the differential expression of genes in S. esculenta larvae after stimulation by low salinity. RNA samples were sequenced and 1039 differentially expressed genes (DEGs) were identified. Then, enrichment analysis was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Finally, a protein–protein interaction network (PPI) was constructed, and the functions of key genes in S. esculenta larvae after low-salinity stimulation were explored. We suggest that low salinity leads to an excess proliferation of cells in S. esculenta larvae that, in turn, affects normal physiological activities. The results of this study can aid in the artificial incubation of S. esculenta and reduce the mortality of larvae.

BackgroundLong working hours (LWH) and shift work are harmful to the physical and mental health of occupational groups.ObjectiveTo understand the status quo of LWH and shift work of migrant workers in Shanghai, and to analyze the influence of the above two factors on sleep of the population.MethodsFrom July to September 2018, a cross-sectional survey using questionnaires was conducted among 3215 in-service employees at seven workplaces with more than 300 employees in six selected districts of Shanghai using multi-stage random sampling method. A total of 2976 valid questionnaires were collected, with a valid response rate of 92.6%. The questionnaires included general demographic characteristics, personal health behavior, work-related factors, weekly working hours, shift work, and sleep. Univariate analysis and logistic regression analysis were used to investigate the relationships of LWH and shift work with sleep, and an interaction item was included to evaluate potential interaction between LWH and shift work.ResultThe average age of the subjects was (30.98±9.49) years old, the male to female ratio was 1∶1.20, and 2382 workers were reported without local residency (80.0%). Among the migrant workers, the average weekly working hours was (57.23±13.14) h, the proportions of LWH (weekly working hours>40 h), extra LWH (weekly working hours>55 h), and shift work were 80.6% (1919/2382), 60.3% (1436/2382), and 25.4% (600/2366), respectively, all above were significantly higher than those of local workers. The prevalence rates of insomnia and lack of sleep among the migrant workers were 46.3% (1091/2356) and 25.4% (597/2354), respectively. The results of logistic regression model showed that after adjusting demographic characteristics such as gender, age, education level, and monthly income, as well as occupation and personal health behavior, compared with working hours ≤40 h per week, working 55-60 h per week was a risk factor for insomnia of migrant workers (OR=1.33, 95%CI: 1.02-1.72), while working >60 h per week was a risk factor for both insomnia (OR=1.37, 95%CI: 1.05-1.78) and insufficient sleep (OR=1.73, 95%CI: 1.28-2.35) of migrant workers. Shift work was only associated with insomnia (OR=1.37, 95%CI: 1.11-1.69). Meanwhile, working hours>60 h per week and shift work had an interaction effect on insomnia of migrant workers (OR=2.35, 95%CI: 1.20-4.60).ConclusionLWH and shift work are prominent among migrant workers, and there is an interaction between LWH and shift work with insomnia.

A major complication of a joint replacement is prosthesis loosening caused by inflammatory osteolysis, leading to the revision of the operation. This is due to the abnormal activation of osteoclast differentiation and function caused by periprosthetic infection. Therefore, targeting abnormally activated osteoclasts is still effective for treating osteolytic inflammatory diseases. CDZ173 is a selective PI3K inhibitor widely used in autoimmune-related diseases and inflammatory diseases and is currently under clinical development. However, the role and mechanism of CDZ173 in osteoclast-related bone metabolism remain unclear. The possibility for treating aseptic prosthesis loosening brought on by inflammatory osteolysis illness can be assessed using an LPS-induced mouse cranial calcium osteolysis model. In this study, we report for the first time that CDZ173 has a protective effect on LPS-induced osteolysis. The data show that this protective effect is due to CDZ173 inhibiting the activation of osteoclasts in vivo. Meanwhile, our result demonstrated that CDZ173 had a significant inhibitory effect on RANKL-induced osteoclasts. Furthermore, using the hydroxyapatite resorption pit assay and podosol actin belt staining, respectively, the inhibitory impact of CDZ173 on bone resorption and osteoclast fusion of pre-OC was determined. In addition, staining with alkaline phosphatase (ALP) and alizarin red (AR) revealed that CDZ173 had no effect on osteoblast development in vitro. Lastly, CDZ173 inhibited the differentiation and function of osteoclasts by weakening the signal axis of PI3K-AKT/MAPK-NFATc1 in osteoclasts. In conclusion, our results highlight the potential pharmacological role of CDZ173 in preventing osteoclast-mediated inflammatory osteolysis and its potential clinical application.

Semicarbazide (SMC), also known as carbamoyl hydrazide, is a key intermediate for the organic synthesis of drugs, pesticides, and a panoply of other applications. It is also regarded as a landmark metabolite of nitrofurazone, a banned veterinary drug. SMC produced in different ways will eventually enter the ocean and become an emerging marine pollutant, affecting the physiological metabolism, behavioral activities, and even survival of aquatic organisms. Sea cucumbers are sediment-feeding organisms, and their risk of exposure to pollutants has attracted increasing attention. In this study, an integrated proteomic and metabolomic approach was used to investigate the responses of Apostichopus japonicus treated with SMC (3.72 g/L) for 72 h. After SMC treatment, the proteins and metabolites of A. japonicus intestine changed significantly. The results showed that 342 differentially expressed proteins were identified, of which 174 were upregulated, 168 were downregulated, and 74 differentially expressed metabolites, of which 62 were upregulated and 12 were downregulated. These differential proteins and metabolites were primarily involved in energy metabolism, lipid metabolism, signal transduction, immune regulation, autophagy, and apoptosis. On the basis of a combination of proteomic and metabolomic data, a hypothetical network of proteins, metabolites, and pathways in sea cucumbers was also described; the resulting network indicated several significant biological activities in response to SMC. This work offers a thorough analysis of the intricate mechanisms by which sea cucumbers respond to SMC stress and indicates numerous possible indicators for further research on creatures exposed to SMC. Further, our results provide scientific guidance for pollution control of Apostichopus japonicus culture to ensure healthy breeding.

Long noncoding RNAs (lncRNAs) have been reported to play a key role in regulating tumor microenvironment and immunity. Cancer-associated fibroblasts (CAFs) are abundant in many tumors. However, the functional and clinical significance of lncRNAs specifically expressed in CAFs has not been fully elucidated. In this study, we identified a list of 95 CAF-specific lncRNAs (FibLnc), including HHLA3, TP53TG1, ST7-AS1, LINC00536, ZNF503-AS1, MIR22HG, and MAPT-AS1, based on immune cell transcriptome expression profiling data. Based on the Cancer Genome Atlas and Gene Expression Omnibus datasets, we found that the FibLnc score predicted differences in overall patient survival and performed well in multiple datasets. FibLnc score was associated with the clinical stage of patients with breast cancer but did not significantly correlate with the PAM50 classification. Functional analysis showed that FibLnc was positively correlated with signaling pathways associated with malignant tumor progression. In addition, FibLnc was positively correlated with tumor mutational load and could predict immunotherapy response in patients with breast cancer receiving anti-PD-1 or anti-CTLA4 therapy. Our proposed FibLnc score was able to reflect the status of the immune environment and immunotherapeutic response in breast cancer, which could help explore potential therapeutic decisions and regulatory mechanisms of CAF-specific lncRNAs.

Background and purposeResection of radiation-induced ulcers often causes full-thickness defects of the chest wall. We retrospectively reviewed and evaluated 17 patients to explore a method of chest wall reconstruction.Materials and methodsA total of 17 breast cancer patients with radiation-induced ulcers were included. Various type of prostheses and flaps were used, results of clinic were evaluated.ResultsSixteen patients had full-thickness defects and one patient had only a soft tissue defect and underwent reconstruction with a pedicle latissimus dorsi (LD) myocutaneous flap. Among all 16 full-thickness defect cases, 15 patients underwent bony thoracic reconstruction using polymesh/3D-printed titanium plates or methyl methacrylate. For soft tissue reconstruction, 13 patients reconstruction using a free deep inferior epigastric perforator (DIEP) flap in combination with a contralateral transverse rectus abdominis myocutaneous (TRAM) flap, and 2 underwent pure free DIEP flap reconstruction. Among all the patients 15 healed with no complications, and 2 patients had delayed healing on the edges of the flaps.ConclusionsDistant pedicle or free flap can used for soft tissue defect coverage, for those severe patients with full-thickness defects and used prostheses, free deep inferior epigastric perforator flap in combination with a contralateral transverse rectus abdominis myocutaneous flap (TRAM + DIEP) would be an applicable choice.

Mass mortalities of oysters during the summer have been reported for years. Among the biological factors causing oyster death in summer, Vibrio infection is considered to be the most important factor. Vibrio alginolyticus is one of the main pathogens causing oyster diseases. V. alginolyticus can cause disease and death of fish, shrimp, shellfish, and other aquatic products. Human infection with V. alginolyticus can also cause skin infections, external ear canal infections, and other diseases. Hemocytes in the blood of Crassostrea gigas resemble vertebrate macrophages and play an important role in the immune regulation of organisms. Therefore, it is of great significance to analyze the blood transcriptome to study the anti-pathogen mechanism of the C. gigas. In our study, we performed a transcriptome profile of gene expression on C. gigas infected with V. alginolyticus at 12 and 48 hours, and identified 2,494 and 1,165 differentially expressed genes (DEGs) at two sampling time points. Then, the functions of DEGs were identified using GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analysis, revealing that there were multiple significantly enriched GO terms and KEGG signaling pathways related to immunity. And a protein-protein interaction (PPI) network was construct using DEGs enriched in significant enriched immune-related KEGG signaling pathways. At last, we screened and validated 12 key genes with multiple protein interaction numbers or involved in more KEGG signaling pathways, and verified their expression changes by quantitative RT-PCR (qRT-PCR). For the first time, we studied the immune defense mechanism of C. gigas blood based on protein-protein interaction network, which explains how C. gigas lacking specific immunity survive in a pathogen-rich environment. This research provides reference for solving the problem of high mortality of C. gigas and other mollusks in summer, and provides reference for the future production of some disease-resistant C. gigas.

Sepia esculenta is a popular economic cephalopod with high yield, delicious meat, and rich nutrition. With the rapid development of heavy industry and medical industry, a large amount of waste has been released into the ocean recklessly in recent years, inducing a significant increase in the content of heavy metals, especially cadmium (Cd) and copper (Cu), in the ocean. This phenomenon significantly affects the growth and development of S. esculenta, causing a serious blow to its artificial breeding. In this study, transcriptome analysis is used to initially explore immune response mechanisms of Cd and Cu co-exposed juvenile S. esculenta. The results show that 1,088 differentially expressed genes (DEGs) are identified. And DEGs functional enrichment analysis results suggests that co-exposure may promote inflammatory and innate immune responses in juvenile S. esculenta. Fifteen key genes that might regulate the immunity of S. esculenta are identified using protein-protein interaction (PPI) network and KEGG enrichment analyses, of which the three genes with the highest number of interactions or involve in more KEGG pathways are identified as hub genes that might significantly affect the immune response processes. Comprehensive analysis of PPI network and KEGG signaling pathway is used for the first time to explore co-exposed S. esculenta juvenile immune response processes. Our results preliminarily reveal immune response mechanisms of cephalopods exposed to heavy metals and provide a valuable resource for further understanding of mollusk immunity.

As the quality of life improves, there is an increasing demand for nutrition-rich marine organisms like fish, shellfish, and cephalopods. To address this, artificial cultivation of these organisms is being explored along with ongoing research on their growth and development. A case in point is Amphioctopus fangsiao, a highly valued cephalopod known for its tasty meat, nutrient richness, and rapid growth rate. Despite its significance, there is a dearth of studies on the A. fangsiao growth mechanism, particularly of its larvae. In this study, we collected A. fangsiao larvae at 0, 4, 12, and 24 h post-hatching and conducted transcriptome profiling. Our analysis identified 4467, 5099, and 4181 differentially expressed genes (DEGs) at respective intervals, compared to the 0 h sample. We further analyzed the expression trends of these DEGs, noting a predominant trend of continuous upregulation. Functional exploration of this trend entailed GO and KEGG functional enrichment along with protein–protein interaction network analyses. We identified GLDC, DUSP14, DPF2, GNAI1, and ZNF271 as core genes, based on their high upregulation rate, implicated in larval growth and development. Similarly, CLTC, MEF2A, PPP1CB, PPP1R12A, and TJP1, marked by high protein interaction numbers, were identified as hub genes and the gene expression levels identified via RNA-seq analysis were validated through qRT-PCR. By analyzing the functions of key and core genes, we found that the ability of A. fangsiao larvae to metabolize carbohydrates, lipids, and other energy substances during early growth may significantly improve with the growth of the larvae. At the same time, muscle related cells in A. fangsiao larvae may develop rapidly, promoting the growth and development of larvae. Our findings provide preliminary insights into the growth and developmental mechanism of A. fangsiao, setting the stage for more comprehensive understanding and broader research into cephalopod growth and development mechanisms.

As a quintessential marine teleost, Paralichthys olivaceus demonstrates vulnerability to a range of pathogens. Long-term infection with Edwardsiella tarda significantly inhibits fish growth and even induces death. Gills, blood, and kidneys, pivotal components of the immune system in teleosts, elicit vital regulatory roles in immune response processes including immune cell differentiation, diseased cell clearance, and other immunity-related mechanisms. This study entailed infecting P. olivaceus with E. tarda for 48 h and examining transcriptome data from the three components at 0, 8, and 48 h post-infection employing weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network analysis. Network analyses revealed a series of immune response processes after infection and identified multiple key modules and key, core, and hub genes including xpo1, src, tlr13, stat1, and mefv. By innovatively amalgamating WGCNA and PPI network methodologies, our investigation facilitated an in-depth examination of immune response mechanisms within three significant P. olivaceus components post-E. tarda infection. Our results provided valuable genetic resources for understanding immunity in P. olivaceus immune-related components and assisted us in further exploring the molecular mechanisms of E. tarda infection in teleosts.

In order to improve the security performance of low earth orbit (LEO) satellite downlink communication system, a cooperative UAV was employed to send jamming signals against the eavesdroppers.In particular, the downlink transmission was based on the orthogonal time frequency space (OTFS) technique to combat the severe Doppler effect caused by the high mobility of the LEO satellite.The closed form expression for the security outage probability (SOP) was derived at the legitimate receiver, where a novel moment matching approach was used for finding a summed probability distribution function (PDF) of the shadowed-Rician (SR) distributed terms.Simulation results prove that the SOP performance advantage of the downlink LEO satellite communication achieved by OTFS over OFDM scheme, and show the effectiveness of employing unmanned aerial vehicle (UAV) jammer in terms of enhancing secrecy transmission.