Bayesian phylogeographic inference of wheat yellow mosaic virus in China and Japan suggests that the virus migration history coincided with historical events.

Wheat yellow mosaic virus (WYMV) is one of the most serious viral pathogens causing reductions in wheat yield in East Asia. We investigated the phylodynamics of WYMV by analysing the CP, VPg and P1 genes to understand the origin and dispersal of the virus. A Bayesian phylogenetic analysis revealed that the most recent common WYMV ancestor occurred in approximately 1742 (95% credibility interval, 1439-1916) CE (Common Era), and the evolutionary rates of the VPg, CP and P1 genes were 6.669 × 10-4 (95% credibility interval: 4.575 × 10-4-8.927 × 10-4), 2.468 × 10-4 (95% credibility interval: 1.667 × 10-4-3.338 × 10-4) and 5.765 × 10-5 (95% credibility interval: 3.285 × 10-6-1.252 × 10-4), respectively. Our phylogeographic analysis indicated that the WYMV population may have originated in Henan Province, China, first spreading to Japan in the mid-19th century and stopping after the Japanese surrender in World War II. The second wave spread to Japan from Shandong Province, China, in approximately 1977, a few years after the establishment of diplomatic relations between China and Japan. Before the founding of the People's Republic of China, Henan Province was the emigration centre of WYMV in East Asia, and after the late 20th century, Jiangsu and Shandong Provinces were also the virus emigration centres in East Asia. In addition, there were two migration pathways from Japan to Jiangsu and Shandong Provinces, China, in approximately 1918 and approximately 1999 respectively. Our results suggest that the wide spread of WYMV in East Asia is strongly related to human factors.

Reassessment of pioglitazone and bladder cancer based on FAERS database.

BACKGROUND: The association between pioglitazone (PLZ) and bladder cancer (BC) remains controversial in several randomized control trials, meta-analyses of multiple prospective studies, and large-scale observational studies. RESEARCH DESIGN AND METHODS: Adverse event (AE) data from 1 January 2004 to 31 March 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis were applied to quantify the signals of PLZ related BC. RESULTS: In total, 17,627,524 AE reports were recorded in the FAERS database, of which 1366 were PLZ-related BCs. More male than female patients were reported. The median age of patients was 70 years old. The peak in the annual report occurred in 2011. A total of 602 AEs reported time to onset (TTO) and the median TTO was 1023 days. In this study, BC and BC recurrence were strong signal, whereas BC stage 0 (with cancer in situ), stage ii and iii were weak signals. CONCLUSIONS: This study comprehensively demostrated the PLZ-induced risk of BC in patients with diabetes mellitus using the FAERS database. The results demonstrated that the patients treated with PLZ were more likely to develop BC. The male and aging attributed more cases to BC-related reports of PLZ treated patients.

High Expression of Cancer-Derived Sialylated Immunoglobulin G: A Novel Biomarker for Poor Prognosis in Laryngeal Squamous Cell Carcinoma.

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer, with around 60% of patients being diagnosed at an advanced stage. Recently, cancer-derived sialylated immunoglobulin G (SIA-IgG) has been suggested to play a role in the progression of various epithelial tumors, but its significance in LSCC remains unknown. This study aimed to investigate the clinical significance of SIA-IgG as a novel biomarker in relation to the initiation, progression, and prognostication of LSCC. METHODS: Immunohistochemistry (IHC) was utilized to assess SIA-IgG expression in tumor samples from 75 LSCC patients, aiming to investigate its correlation with clinical prognosis. In vitro functional experiments were conducted to explore the impact of SIA-IgG expression on the proliferative and migratory abilities of laryngocarcinoma cells. RESULTS: High expression of SIA-IgG was associated with pT stage, pN stage, TNM stage, and recurrence during follow-up and was correlated with poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox analysis demonstrated that SIA-IgG served as an independent risk factor for OS and DFS. Knocking down SIA-IgG significantly weakened laryngocarcinoma cells' proliferation, clonogenesis, and migration abilities. CONCLUSIONS: The frequent expression of SIA-IgG in LSCC is significantly associated with poor prognosis. High levels of SIA-IgG can enhance proliferation and migration in laryngocarcinoma cells. These findings suggest that SIA-IgG has potential as a novel biomarker for LSCC.

The effects and mechanisms of heat stress on mammalian oocyte and embryo development.

The sum of nonspecific physiological responses exhibited by mammals in response to the disruption of thermal balance caused by high-temperature environments is referred to as heat stress (HS). HS affects the normal development of mammalian oocyte and embryos and leads to significant economic losses. Therefore, it is of great importance to gain a deep understanding of the mechanisms underlying the effects of HS on oocyte and embryonic development and to explore strategies for mitigating or preventing its detrimental impacts in the livestock industry. This article provides an overview of the negative effects of HS on mammalian oocyte growth, granulosa cell maturation and function, and embryonic development. It summarizes the mechanisms by which HS affects embryonic development, including generation of reactive oxygen species (ROS), endocrine disruption, the heat shock system, mitochondrial autophagy, and molecular-level alterations. Furthermore, it discusses various measures to ameliorate the effects of HS, such as antioxidant use, enhancement of mitochondrial function, gene editing, cultivating varieties possessing heat-resistant genes, and optimizing the animals'rearing environment. This article serves as a valuable reference for better understanding the relationship between HS and mammalian embryonic development as well as for improving the development of mammalian embryos and economic benefits under HS conditions in livestock production.

A Comparative Analysis of the Immunoglobulin Repertoire in Leukemia Cells and B Cells in Chinese Acute Myeloid Leukemia by High-Throughput Sequencing.

It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia (AML) could also express Ig and that AML-Ig played a role in leukemogenesis and AML progression. The difference between Ig from myeloblasts and B cells has not been explored. Studying the characteristics of the Ig repertoire in myeloblasts and B cells will be helpful to understand the function and significance of AML-Ig. We performed 5' RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire in myeloblasts and B cells from Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same patient, AML-Ig showed different biased V(D)J usages and mutation patterns. In addition, the CDR3 length distribution of AML-Ig was significantly different from those of B-Ig. More importantly, mutations of AML-IgH, especially Igµ, Igα, and Igδ, were different from that of B-IgH in each AML patient, and the mutations frequently occurred at the sites of post-translational modification. AML-Ig has distinct characteristics of variable regions and mutations, which may have implications for disease monitoring and personalized therapy.

Novel CAR-T Cells Specifically Targeting SIA-CIgG Demonstrate Effective Antitumor Efficacy in Bladder Cancer.

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising cancer treatment method. However, its application in bladder cancer (BC) remains limited, partially because of the absence of appropriate target molecules. Sialylated cancer-derived IgG (SIA-CIgG) is highly expressed in BC and is closely associated with malignant biological behavior. However, its potential as a target for CAR-T cell therapy to treat BC is yet to be established. Here, it is found that SIA-CIgG is highly expressed in most BC samples but displayed limited expression in normal tissues. CAR-T cells specifically targeting SIA-CIgG can effectively lyse BC cells and the cytotoxicity depends on SIA-CIgG expression. Furthermore, SIA-CIgG CAR-T cells demonstrate milder tumor cell lysis and enhanced persistence compared with human epidermal growth factor receptor 2 (HER2) CAR-T cells, which have undergone extensive clinical trials. After repeated tumor antigen challenges, SIA-CIgG CAR-T cells display substantial alterations in both the transcriptome and chromatin accessibility. When combining SIA-CIgG CAR-T cell therapy with FDA-approved drugs to treat BC, the histone deacetylase inhibitor (HDACi), vorinostat, is found to enhance the ablility of CAR-T cells for tumor cell lysis. Therefore, the combination of SIA-CIgG CAR-T cells and vorinostat is promising for BC treatment.

Comprehensive analysis of MAPK genes in the prognosis, immune characteristics, and drug treatment of renal clear cell carcinoma using bioinformatic analysis and Mendelian randomization.

Mitogen-activated protein kinase (MAPK) signalling is vitally important in tumour development and progression. This study is the first to comprehensively analyse the role of MAPK-family genes in the progression, prognosis, immune-cell infiltration, methylation, and potential therapeutic value drug candidates in ccRCC. We identified a novel prognostic panel of six MAPK-signature genes (MAP3K12, MAP3K1, MAP3K5, MAPK1, MAPK8, MAPK9), and introduced a robust MAPK-signature risk model for predicting ccRCC prognosis. Model construction, evaluation, and external validation using datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database demonstrated its stability, as well as high sensitivity and specificity. Enrichment analysis suggested the participation of immune-mediated mechanism in MAPK dysregulation in ccRCC. Immune-infiltration analysis confirmed the relationship and revealed that the MAPK-signature risk model might stratify immunotherapy response in ccRCC, which was verified in drug sensitivity analysis and validated in external ccRCC immunotherapy dataset (GSE67501). Potential therapeutic drug predictions for key MAPKs using DSigDB, Network Analyst, CTD, and DGIdb were subsequently verified by molecular docking with AutoDock Vina and PyMol. Mendelian randomization further demonstrated the possibilities of the MAPK-signature genes as targets for therapeutic drugs in ccRCC. Methylation analysis using UALCAN and MethSurv revealed the participation of epigenetic modifications in dysregulation and survival difference of MAPK pathway in ccRCC. Among the key MAPKs, MAP3K12 exhibited the highest significance, indicating its independent prognostic value as single gene in ccRCC. Knockout and overexpression validation experiments in vitro and in vivo found that MAP3K12 acted as a promoter of tumour progression in RCC, suggesting a pivotal role for MAP3K12 in the proliferation, migration, and invasion of RCC cells. Our findings proposed the potential of MAPK-signature genes as biomarkers for prognosis and therapy response, as well as targets for therapeutic drugs in ccRCC.

Genetic Characteristics of Non B Cell-Derived Immunoglobulin Genes.

It is widely acknowledged that immunoglobulins (Igs) are produced solely by B-lineage cells. The Ig gene is created by the rearrangement of a group of gene segments [variable (V), diversity (D), and joining (J) segments rearrangement, or V(D)J recombination], which results in the vast diversity of B cell-derived Ig responsible for recognising various antigens. Ig subsequently undergoes somatic hypermutation (SHM) and class switch recombination (CSR) after exposure to antigens, thus converting the low-affinity IgM to IgG, IgA, or IgE antibodies. IgM and IgD are primarily expressed in naïve B cells that have not been exposed to antigens, they do not undergo somatic hypermutation; hence, their variable region sequences remain the same as those in the germline. In contrast, IgG, IgA, and IgE are expressed in antigen-stimulated memory B cells or plasma cells, and thus, they often possess high-frequency mutations in their variable region sequences. Since the discovery that Ig can be produced by non-B cells, Qiu's group has investigated and compared the genetic characteristics of B cell-derived Ig and non-B cell-derived Ig. These findings demonstrated that non-B cell-derived Ig shares certain similarities with B cell-derived Ig in that the sequence of its constant region is identical to that of B cell-derived Ig, and its variable region is also strictly dependent on the rearrangement of V, D, and J gene segments. Moreover, akin to B cell-derived Ig, the V regions of IgM and IgD are rarely mutated, while IgG, IgA, and IgE produced by cancer cells are frequently mutated. However, the non-B cell-derived Ig V region sequence displays unique characteristics. (1) Unlike the vast diversity of B cell-derived Igs, non-B cell-derived Igs exhibit restricted diversity; cells from the same lineage always select the same V(D)J recombination patterns; (2) Both mRNA and proteins of RAG1/RAG2 recombinase have been detected in Ig positive cancer cell lines and normal tissues. But Ig recombination could also be found in RAG1-/- and RAG2-/- mice, suggesting that they are not necessary for the rearrangement of non-B cell-derived Igs. These features of non-B cell-derived Igs suggest a potentially undiscovered mechanism of V(D)J recombination, ligation, and SHM in non-B cells, which necessitates further investigation with advanced technology in molecular biology.

Cancer-Derived Immunoglobulin G and Pancreatic Cancer.

Immunoglobulin (Ig) is traditionally believed to be produced solely by B cells. Nonetheless, mounting evidence has demonstrated that various types of Igs are extensively expressed in many cell types. Among them, IgG is found to be highly expressed in cancer cells and is thus labeled as cancer-derived IgG. Cancer-derived IgG shares identical fundamental structures with B cell-derived IgG, but displays several unique characteristics, including restricted variable region sequences and unique glycosylation modifications for those expressed by epithelial cancers. Cancer-derived IgG plays multiple crucial roles in carcinogenesis, including facilitating cancer invasion and metastasis, enhancing cancer stemness, contributing to chemoresistance, and remodeling the tumour microenvironment. Recent studies have discovered that cancer-derived sialylated IgG (SIA-IgG) is extensively expressed in pancreatic cancer cells and is predominantly located in the cytoplasm and on the cell membrane. Cancer-derived IgG expressed by pancreatic cancer presents a restrictive variable region sequence and contains a unique sialylation site of the Fab region. Functionally, cancer-derived IgG participates in pancreatic cancer progression via different mechanisms, such as promoting proliferation, facilitating migration and invasion, resisting apoptosis, inducing inflammation, and modulating the tumour microenvironment. SIA-IgG has shown potential as a clinical biomarker. The expression of SIA-IgG is associated with poor tumour differentiation, metastasis, and chemoresistance in pancreatic cancer. High expression of SIA-IgG can serve as an independent prognostic factor for pancreatic cancer. Additionally, SIA-IgG expression elevated with malignant progression for the precursor lesions of pancreatic cancer. These findings present a prospect of applying cancer-derived IgG as a novel diagnostic and therapeutic target in the management of pancreatic cancer, and aiding in overcoming the challenge in the treatment of this stubborn malignancy.

Non B Cell-Derived Immunoglobulin, A Brighter Horizon for the Future.

The canonical theory of immunology stating that "Immunoglobulin (Ig) is produced by B lymphocytes and exerts antibody activity" has been established since the 1970s. However, the discovery of non B cell-derived Igs (non B-Igs), which can exert multiple biological activities in addition to their antibody activities, necessitates a reevaluation of the classic concept of Ig. This has been documented with a number of characteristics related to their structure, modification, genetic regulation as well as the functions associated with clinical conditions, particularly multiple cancers. The discovery of non B-Ig provides us with a new perspective to better understand not only basic immunology, but also various Ig-related clinical manifestations including autoimmune diseases, chronic inflammation, and anaphylaxis. Notably, non B-Ig can directly promote the occurrence of malignant tumours.

Functions and Clinical Relevance of Liver-Derived Immunoglobulins.

Liver is the largest internal organ of the body with vital functions. In addition to its endocrine and exocrine activities, liver also plays a pivotal role in the immune system, including haematopoietic functions. Liver parenchymal cells, which are epithelial cells, have been found to possess innate immune functions by expressing pattern-recognition receptors (PRRs), producing complement components, and secreting cytokines. Intriguingly, in recent years, it has been discovered that liver epithelial cells also produce immunoglobulins (Igs), which have long been thought to be produced exclusively by B cells. Notably, even liver epithelial cells from B lymphocyte-deficient mice, including SCID mice and µMT mice, could also produce Igs. Compelling evidence has revealed both the physiological and pathological functions of liver-derived Igs. For instance, liver epithelial cells-derived IgM can serve as a source of natural and specific antibodies that contribute to innate immune responses, while liver-produced IgG can act as a growth factor to promote cell proliferation and survival in normal hepatocytes and hepatocarcinoma. Similar to that in B cells, the toll-like receptor 9 (TLR9)-MyD88 signaling pathway is also actively involved in promoting liver epithelial cells to secrete IgM. Liver-derived Igs could potentially serve as biomarkers, prognostic indicators, and therapeutic targets in the clinical setting, particularly for liver cancers and liver injury. Nevertheless, despite significant advances, much remains unknown about the mechanisms governing Ig transcription in liver cells, as well as the detailed functions of liver-derived Igs and their involvement in diseases and adaptive immunity. Further studies are still needed to reveal these underlying, undefined issues related to the role of liver-derived Igs in both immunity and diseases.

Expression and Clinical Significance of Non B Cell-Derived Immunoglobulins in the Urinary System and Male Reproductive System.

The urinary system comprises kidneys, ureters, bladder, and urethra with its primary function being excretion, referring to the physiological process of transporting substances that are harmful or surplus out of the body. The male reproductive system consists of gonads (testis), vas deferens, and accessory glands such as the prostate. According to classical immunology theory, the tissues and organs mentioned above are not thought to produce immunoglobulins (Igs), and any Ig present in the relevant tissues under physiological and pathological conditions is believed to be derived from B cells. For instance, most renal diseases are associated with uncontrolled inflammation caused by pathogenic Ig deposited in the kidney. Generally, these pathological Igs are presumed to be produced by B cells. Recent studies have demonstrated that renal parenchymal cells can produce and secrete Igs, including IgA and IgG. Glomerular mesangial cells can express and secrete IgA, which is associated with cell survival and adhesion. Likewise, human podocytes demonstrate the ability to produce and secrete IgG, which is related to cell survival and adhesion. Furthermore, renal tubular epithelial cells also express IgG, potentially involved in the epithelial-mesenchymal transition (EMT). More significantly, renal cell carcinoma, bladder cancer, and prostate cancer have been revealed to express high levels of IgG, which promotes tumour progression. Given the widespread Ig expression in the urinary and male reproductive systems, continued efforts to elucidate the roles of Igs in renal physiological and pathological processes are necessary.

Comparison of Non B-Ig and B-Ig.

Immunoglobulin (Ig) has been widely acknowledged to be produced solely by B-lineage cells. However, growing evidence has demonstrated the expression of Ig in an array of cancer cells, as well as normal cells including epithelial cells, epidermal cells, mesangial cells, monocytes, and neutrophils. Ig has even been found to be expressed in non-B cells at immune-privileged sites such as neurons and spermatogenic cells. Despite these non-B cell-derived Igs (non-B-Igs) sharing the same symmetric structures with conventional Igs (B-Igs), further studies have revealed unique characteristics of non-B-Ig, such as restricted variable region and aberrant glycosylation. Moreover, non-B-Ig exhibits properties of promoting malignant behaviours of cancer cells, therefore it could be utilised in the clinic as a potential therapeutic biomarker or target. The elucidation of the generation and regulation of non-B-Ig will certainly broaden our understanding of immunology.

Functions and Clinical Significance of Myocardial Cell-Derived Immunoglobulins.

Immunoglobulins (Igs) have been widely accepted to be exclusively expressed by B cells. Nonetheless, this theory is challenged by mounting evidence which suggests that Igs can also be generated by non B cells (non B-Ig), including cardiomyocytes (CM). Non B-Ig exhibits unique physical and chemical characteristics, unique variable region sequences and functions, which diverge from those of B-Ig. For instance, non B-Ig demonstrates hydrophobicity, limited diversity in the variable region, and extracellular matrix protein activity. Likewise, cardiomyocytes can express different classes of Igs, including IgM, IgG, and free Igκ light chains (cardiomyocyte derived-Igs, CM-Igs). In particular, CM-Igs can be secreted into the extracellular space in various cardiovascular diseases, such as myocardial ischaemia and myocardial fibrosis where they might be involved in complement activation and direct damage to cardiomyocytes. Nevertheless, the precise pathological activity of CM-Igs remains unclear. Recently, Zhu et al. focused on studying the sequence characteristics and functions of CM-Igκ; they discovered that the CM-Igκ exhibits a unique VJ recombination pattern, high hydrophobicity, and is principally located on the intercalated discs and cross striations of the cardiomyocytes. Interestingly, loss of Igκ in cardiomyocytes results in structural disorders in intercalated discs and dysfunction in myocardial contraction and conduction. Mechanically, Igκ promotes the stabilisation of plectin, a cytoskeleton cross-linker protein that connects desmin to desomsome, to maintain the normal structure of the intercalated disc. This finding indicates that CM-Igκ plays an integral role in maintaining cytoskeleton structure. Consequently, it is imperative to reveal the physiological functions and mechanisms of pathological injury associated with CM-Igs.

Expression and Function of Mammary Epithelial Cell-Derived Immunoglobulins.

Over the past 20 years, increasing evidence has demonstrated that immunoglobulins (Igs) can be widely generated from non B cells, including normal and malignant mammary epithelial cells. In normal breast tissue, the expression of IgG and IgA has been identified in epithelial cells of mammary glands during pregnancy and lactation, which can be secreted into milk, and might participate in neonatal immunity. On the other hand, non B-IgG is highly expressed in breast cancer cells, correlating with the poor prognosis of patients with breast cancer. Importantly, a specific group of IgG, bearing a unique N-linked glycan on the Asn162 site and aberrant sialylation modification at the end of the novel glycan (referred to as sialylated IgG (SIA-IgG)), has been found in breast cancer stem/progenitor-like cells. SIA-IgG can significantly promote the capacity of migration, invasiveness, and metastasis, as well as enhance self-renewal and tumorigenicity in vitro and in vivo. These findings suggest that breast epithelial cells can produce Igs with different biological activities under physiological and pathological conditions. During lactation, these Igs could be the main source of milk Igs to protect newborns from pathogenic infections, while under pathological conditions, they display oncogenic activity and promote the occurrence and progression of breast cancer.

Characteristics and Clinical Implications of Immunoglobulins Derived from Non B Cells in the Skin.

Skin is the most prominent tissue and organ, as well as the first line of defence, of the body. Because it is situated on the body's surface, it is constantly exposed to microbial, chemical, and physical factors such as mechanical stimulation. Therefore, skin has evolved substantial immune defences, regenerative ability, and anti-injury capacity. Epidermal cells produce antibacterial peptides that play a role in immune defence under physiological conditions. Additionally, IgG or IgA in the skin also participates in local anti-infective immunity. However, based on the classical theory of immunology, Ig can only be produced by B cells which should be derived from local B cells. This year, thanks to the discovery of Ig derived from non B cells (non B-Ig), Ig has also been found to be expressed in epidermal cells and contributes to immune defence. Epidermal cell-derived IgG and IgA have been demonstrated to have potential antibody activity by binding to pathogens. However, these epidermal cell-derived Igs show different microbial binding characteristics. For instance, IgG binds to Staphylococcus aureus and IgA binds to Staphylococcus epidermidis. Epidermal cells producing IgG and IgA may serve as an effective defense mechanism alongside B cells, providing a novel insight into skin immunity.

Multi-Modal Melt-Processing of Birefringent Cellulosic Materials for Eco-Friendly Anti-Counterfeiting.

Ubiquitous anti-counterfeiting materials with a rapidly rising annual consumption (over 1010 m2) can pose a serious environmental burden. Biobased cellulosic materials with birefringence offer attractive sustainable alternatives, but their scalable solvent-free processing remain challenging. Here, a dynamic chemical modification strategy is proposed for multi-modal melt-processing of birefringent cellulosic materials for eco-friendly anti-counterfeiting. Relying on the thermal-activated dynamic covalent-locking of the spatial topological structure of preferred oriented cellulose, the strategy balances the contradiction between the strong confinement of long-range ordered structures and the molecular motility required for entropically-driven reconstruction. Equipped with customizable processing forms including mold-pressing, spinning, direct-ink-writing, and blade-coating, the materials exhibit a wide color gamut, self-healing efficiency (94.5%), recyclability, and biodegradability. Moreover, the diversified flexible elements facilitate scalable fabrication and compatibility with universal processing techniques, thereby enabling versatile and programmable anti-counterfeiting. The strategy is expected to provide references for multi-modal melt-processing of cellulose and promote sustainable innovation in the anti-counterfeiting industry.

Research on the Mechanism of Metaldehyde on Pomacea canaliculata.

Golden apple snail (Pomacea canaliculata), a major alien invasive organism in China, affects food production and poses a threat to human health. Metaldehyde is a highly effective, commonly used snail killer with low toxicity. Virulence determination, tissue section, iTRAQ and RNA interference were used to systematically study the toxicity of metaldehyde on P. canaliculata. The molluscicidal activity tests showed that metaldehyde exhibits strong toxicity against P. canaliculata. Physiological and biochemical data indicate that metaldehyde can cause damage to the gills, liver, pancreas, and kidneys of snails, also reduce the oxygen consumption rate and ammonia excretion rate of golden apple snails, and cause neurological diseases. The proteome of the gill region of the golden apple snail after exposure to metaldehyde was analyzed by using iTRAQ technology. A total of 360 differential proteins were identified, and four target proteins were screened, namely, alpha-protein kinase 1 (ALPK1), cubilin (CUBN), sodium- and chloride-dependent GABA transporter 2 (GAT2), and acetylcholinesterase (AChE). RNAi was used to target the four proteins. After the ALPK1 and CUBN protein genes were interfered with by metaldehyde treatment, it was found that the mortality rate of the golden apple snail significantly increased. However, interference of GAT2 and AChE protein genes by metaldehyde led to no significant change in the mortality rates of the snails. The histopathological observation of the gill showed that the rate of cilia shedding in the gill decreased after the interference of ALPK1 and CUBN protein genes.

Supramolecular metallic foams with ultrahigh specific strength and sustainable recyclability.

Porous materials with ultrahigh specific strength are highly desirable for aerospace, automotive and construction applications. However, because of the harsh processing of metal foams and intrinsic low strength of polymer foams, both are difficult to meet the demand for scalable development of structural foams. Herein, we present a supramolecular metallic foam (SMF) enabled by core-shell nanostructured liquid metals connected with high-density metal-ligand coordination and hydrogen bonding interactions, which maintain fluid to avoid stress concentration during foam processing at subzero temperatures. The resulted SMFs exhibit ultrahigh specific strength of 489.68 kN m kg-1 (about 5 times and 56 times higher than aluminum foams and polyurethane foams) and specific modulus of 281.23 kN m kg-1 to withstand the repeated loading of a car, overturning the previous understanding of the difficulty to achieve ultrahigh mechanical properties in traditional polymeric or organic foams. More importantly, end-of-life SMFs can be reprocessed into value-added products (e.g., fibers and films) by facile water reprocessing due to the high-density interfacial supramolecular bonding. We envisage this work will not only pave the way for porous structural materials design but also show the sustainable solution to plastic environmental risks.

Upregulation of GPX4 drives ferroptosis resistance in scleroderma skin fibroblasts.

The pathogenesis of systemic sclerosis (SSC) fibrosis involves the rapid proliferation of skin fibroblasts, and current anti-fibrotic treatments are limited. This study investigated the relationship between ferroptosis and SSC skin fibroblasts. We observed that erastin-induced ferroptosis was suppressed in SSC fibroblasts. RSL3, a direct inhibitor of Glutathione Peroxidase 4 (GPX4), significantly reduced the viability of the fibroblasts, and upregulation of GPX4 in the SSC fibroblasts contributed to ferroptosis resistance. Furthermore, we demonstrated that transferrin receptor 1 (TfR1) was a crucial transporter for iron deposition in the fibroblasts. Collectively, our results highlight that GPX4 inhibition could enhance the sensitivity to ferroptosis by SSC fibroblasts, which showed distinct characteristics of iron metabolism that were not observed in normal fibroblasts in this study. Taken together, these results suggest that targeting ferroptosis could be a therapeutic strategy for the treatment of SSC.