Membrane-bound trehalase enhances cadmium tolerance by regulating cell apoptosis in Neocaridina denticulata sinensis.

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.

Comparative transcriptomic analysis primarily explores the molecular mechanism of compound eye formation in Neocaridina denticulata sinensis.

Compound eyes formation in decapod crustaceans occurs after the nauplius stage. However, the key genes and regulatory mechanisms of compound eye development during crustacean embryonic development have not yet been clarified. In this study, RNA-seq was used to investigate the gene expression profiles of Neocaridina denticulata sinensis from nauplius to zoea stage. Based on RNA-seq data analysis, the phototransduction and insect hormone biosynthesis pathways were enriched, and molting-related neuropeptides were highly expressed. There was strong cell proliferation in the embryo prior to compound eye development. The formation of the visual system and the hormonal regulation of hatching were the dominant biological events during compound eye development. The functional analysis of DEGs across all four developmental stages showed that cuticle formation, muscle growth and the establishment of immune system occurred from nauplius to zoea stage. Key genes related to eye development were discovered, including those involved in the determination and differentiation of the eye field, eye-color formation, and visual signal transduction. In conclusion, the results increase the understanding of the molecular mechanism of eye formation in crustacean embryonic stage.

In Situ Structural Densification of Hydrogel Network and Its Interface with Electrodes for High-Performance Multimodal Artificial Skin.

The multisensory responsiveness of hydrogels positions them as promising candidates for artificial skin, whereas the mismatch of modulus between soft hydrogels and hard electrodes as well as the poor adhesion and conductance at the interface greatly impairs the stability of electronics devices. Herein, we propose an in situ postprocessing approach utilizing electrochemical reactions between metals (Zn, etc.) and hydrogels to synergistically achieve strong adhesion of the hydrogel-electrode interface, low interfacial impedance, and local strain isolation due to the structural densification of the hydrogel network. The mechanism is that Zn electrochemically oxidizes to Zn2+ and injects into the hydrogel, gradually forming a mechanically interlocked structure, Zn2+-polymer dual-helix structural nodes, and a high-modulus ZnO from the surface to the interior. Compared to untreated samples, the treated sample displays 8.7 times increased interfacial adhesion energy between the hydrogel and electrode (87 J/m2), 95% decreased interfacial impedance (218.8 Ω), and a high-strain isolation efficiency (εtotal/εisolation > 400). Akin to human skin, the prepared sensor demonstrates multimodal sensing capabilities, encompassing highly sensitive strain perception and simultaneous perception of temperature, humidity, and oxygen content unaffected by strain interference. This easy on-chip preparation of hydrogel-based multimodal sensor array shows great potential for health and environment monitoring as artificial skin.

Different machine learning methods based on maxillary sinus in sex estimation for northwestern Chinese Han population.

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

Integration of bioinformatics and machine learning approaches for the validation of pyrimidine metabolism-related genes and their implications in immunotherapy for osteoporosis.

BACKGROUND: Osteoporosis (OP), the "silent epidemic" of our century, poses a significant challenge to public health, predominantly affecting postmenopausal women and the elderly. It evolves from mild symptoms to pronounced severity, stabilizing eventually. Unique among OP's characteristics is the altered metabolic profile of affected cells, particularly in pyrimidine metabolism (PyM), a crucial pathway for nucleotide turnover and pyrimidine decomposition. While metabolic adaptation is acknowledged as a therapeutic target in various diseases, the specific role of PyM genes (PyMGs) in OP's molecular response remains to be clarified. METHODS: In pursuit of elucidating and authenticating PyMGs relevant to OP, we embarked on a comprehensive bioinformatics exploration. This entailed the integration of Weighted Gene Co-expression Network Analysis (WGCNA) with a curated list of 37 candidate PyMGs, followed by the examination of their biological functions and pathways via Gene Set Variation Analysis (GSVA). The Least Absolute Shrinkage and Selection Operator (LASSO) technique was harnessed to identify crucial hub genes. We evaluated the diagnostic prowess of five PyMGs in OP detection and explored their correlation with OP's clinical traits, further validating their expression profiles through independent datasets (GSE2208, GSE7158, GSE56815, and GSE35956). RESULTS: Our analytical rigor unveiled five PyMGs-IGKC, TMEM187, RPS11, IGLL3P, and GOLGA8N-with significant ties to OP. A deeper dive into their biological functions highlighted their roles in estrogen response modulation, cytosolic calcium ion concentration regulation, and GABAergic synaptic transmission. Remarkably, these PyMGs emerged as potent diagnostic biomarkers for OP, distinguishing affected individuals with substantial accuracy. CONCLUSIONS: This investigation brings to light five PyMGs intricately associated with OP, heralding new avenues for biomarker discovery and providing insights into its pathophysiological underpinnings. These findings not only deepen our comprehension of OP's complexity but also herald the advent of more refined diagnostic and therapeutic modalities.

Performance and protein conformation of thermally treated silver carp (Hypophthalmichthys molitrix) and scallop (Argopecten irradians) blended gels.

BACKGROUND: The quality of surimi-based products can be improved by combining the flesh of different aquatic organisms. The present study investigated the effects of incorporating diverse ratios of unwashed silver carp (H) and scallop (A) and using various thermal treatments on the moisture, texture, microstructure, and conformation of the blended gels and myofibrillar protein of surimi. RESULTS: A mixture ratio of A:H = 1:3 yielded the highest gel strength, which was 60.4% higher than that of scallop gel. The cooking losses of high-pressure heating and water-bath microwaving were significantly higher than those of other methods (P < 0.05). Moreover, the two-step water bath and water-bath microwaving samples exhibited a more regular spatial network structure compared to other samples. The mixed samples exhibited a microstructure with a uniform and ordered spatial network, allowing more free water to be trapped by the internal structure, resulting in more favorable gel properties. The thermal treatments comprehensively modified the tertiary and quaternary structures of proteins in unwashed mixed gel promoted protein unfurling, provided more hydrophobic interactions, enhanced protein aggregation and improved the gel performance. CONCLUSION: The findings of the present study improve our understanding of the interactions between proteins from different sources. We propose a new method for modifying surimi's gel properties, facilitating the development of mixed surimi products, as well as enhancing the efficient utilization of aquatic resources. © 2024 Society of Chemical Industry.

Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs.

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.

Cellulose nanocrystals intercalated clay biocomposite for rapid Cr(VI) removal.

The application of bentonite (Bt) as an adsorbent for heavy metals has been limited due to its hydrophobicity and insufficient surface area. Herein, we present cellulose nanocrystal (CNC) modified Bt composite (CNC@Bt) with enhanced efficiency for Cr(VI) removal. CNC@Bt exhibited an increased specific surface area and a porous structure, while maintaining the original crystal structure of Bt. This was achieved through a synergistic function of ion exchange, hydrogen bonding, electrostatic interactions, and steric hindrance. The adsorption of Cr(VI) by CNC@Bt followed the pseudo-second-order kinetic and Langmuir isotherm adsorption model. Moreover, the process was endothermic and spontaneous. At an initial Cr(VI) concentration of 20 mg/L and pH = 4.0, 10 g/L CNC@Bt achieved a removal rate of 92.7%, and the adsorption capacity was 1.85 mg/g, significantly higher than bare Bt (37.9% and 0.76 mg/g). The removal efficiency remained consistently above 80% over a wide pH range, indicating the potential practical applicability of CNC@Bt. With its fast adsorption rate, pH adaptability, and stable performance, CNC@Bt presents promising prospects for the rapid treatment of Cr-contaminated wastewater.

Bioinformatic validation and machine learning-based exploration of purine metabolism-related gene signatures in the context of immunotherapeutic strategies for nonspecific orbital inflammation.

Background: Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA. Despite its significance, the contribution of Purine Metabolism Genes (PMGs) to the pathophysiological landscape of NSOI remains a mystery, highlighting a critical gap in our understanding of the disease's molecular underpinnings. Methods: To bridge this knowledge gap, our study embarked on an exploratory journey to identify and validate PMGs implicated in NSOI, employing a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 92 known PMGs, we aimed to pinpoint those with potential roles in NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), facilitated a deep dive into the biological functions and pathways associated with these PMGs. Further refinement through Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled the identification of key hub genes and the evaluation of their diagnostic prowess for NSOI. Additionally, the relationship between these hub PMGs and relevant clinical parameters was thoroughly investigated. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the seven PMGs identified as potentially crucial to NSOI pathology. Results: Our investigation unveiled seven PMGs (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, and ALLC) as intimately connected to NSOI. Functional analyses shed light on their involvement in processes such as peroxisome targeting sequence binding, seminiferous tubule development, and ciliary transition zone organization. Importantly, the diagnostic capabilities of these PMGs demonstrated promising efficacy in distinguishing NSOI from non-affected states. Conclusions: Through rigorous bioinformatics analyses, this study unveils seven PMGs as novel biomarker candidates for NSOI, elucidating their potential roles in the disease's pathogenesis. These discoveries not only enhance our understanding of NSOI at the molecular level but also pave the way for innovative approaches to monitor and study its progression, offering a beacon of hope for individuals afflicted by this enigmatic condition.

Cryoprotective Effects and Quality Maintenance of Antifreeze Proteins and Peptides on Aquatic Products: A Review.

Aquatic products are gaining popularity due to their delicacy and high nutrient value. However, they are perishable, with a short shelf-life. Frozen storage is associated with adverse effects, leading to protein oxidation and degradation, thereby altering the protein's structural integrity and subsequently influencing the palatability of protein-based food products. To address these challenges, novel antifreeze peptides have gained significant attention. Antifreeze peptides are a class of small molecular weight proteins or protein hydrolysates that offer protection to organisms in frozen or sub-frozen environments. They offer distinct advantages over conventional commercial antifreeze agents and natural antifreeze proteins. This review provides an overview of the current state of research on antifreeze agents, elucidates their characteristics and mechanisms, and examines their applications in aquatic products. Furthermore, the article offers insights into the prospective development and application prospects of antifreeze peptides.

Superhydrophobic Co-MOF-based sponge for efficient oil-water separation utilizing photothermal effect.

Effectively addressing crude oil spills remains a global challenge due to its high viscosity and limited flow characteristics. In this study, we successfully prepared a modified sponge (PCP@MS) by embedding the photothermal material of Co-HHTP and coating the melamine sponge (MS) with low-surface-energy polydimethylsiloxane (PDMS). The PCP@MS exhibited outstanding hydrophobicity with WCA of 160.2° and high oil absorption capacity of 59-107 g/g. The PCP@MS showed high separation efficiency of 99.2% for various oil-water mixtures, along with notable self-cleaning properties and mechanical stability. The internal micro-nano hierarchical structure on the sponge surface significantly enhanced light absorption, synergizing with the photo-thermal conversion properties of Co-HHTP, enabled PCP@MS to achieve a surface temperature of 109.2 °C under 1.0 solar light within 300 s. With the aid of solar radiation, PCP@MS is able to heat up quickly and successfully lowering the viscosity of the surrounding crude oil, resulting in an oil recovery rate of 8.76 g/min. Density functional theory (DFT) calculation results revealed that Co-HHTP featured a zero-gap band structure, rendering advantageous electronic properties for full-wavelength light absorption. This in situ solar-heated absorbent design is poised to advance the practical application of viscous oil spill cleanup and recovery.

Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach.

BACKGROUND: This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS. METHODS: A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets. RESULTS: This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results. CONCLUSION: In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.

Effects of Edible Organic Acid Soaking on Color, Protein Physicochemical, and Digestion Characteristics of Ready-to-Eat Shrimp upon Processing and Sterilization.

Soft-packed ready-to-eat (RTE) shrimp has gradually become popular with consumers due to its portability and deliciousness. However, the browning caused by high-temperature sterilization is a non-negligible disadvantage affecting sensory quality. RTE shrimp is processed through "boiling + vacuum soft packing + high temperature and pressure sterilization". Ultraviolet-visible (UV) spectroscopy with CIELAB color measurement showed that phytic acid (PA) + lactic acid (LA), PA + citric acid (CA), and PA + LA + CA soaking before cooking alleviated browning, as well as UVabsorbance and the browning index (BI). Meanwhile, UV spectroscopy and fluorescence spectroscopy showed that organic acid soaking reduced the content of carbonyl, dityrosine, disulfide bonds, surface hydrophobicity, and protein solubility, but promoted the content of free sulfhydryl and protein aggregation. However, in vitro digestion simulations showed that organic acid soaking unexpectedly inhibited the degree of hydrolysis and protein digestibility. This study provides the basis for the application of organic acids as color protectors for RTE aquatic muscle product.

Sex estimation using maxillary sinus volume for Chinese subjects based on cone-beam computed tomography.

BACKGROUND: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT). METHODS: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth. RESULTS: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus. CONCLUSIONS: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable.

Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice.

PURPOSE: PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. METHODS: We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. RESULTS: The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7-/- female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7-/- mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. CONCLUSIONS: The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Identification of clinical prognostic factors and analysis of ferroptosis-related gene signatures in the bladder cancer immune microenvironment.

BACKGROUND: Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and poses a significant burden in terms of both incidence and mortality rates on a global scale. Among all BLCA cases, non-muscle invasive bladder cancer constitutes approximately 75% of the total. In recent years, the concept of ferroptosis, an iron-dependent form of regulated cell death marked by the accumulation of lipid peroxides, has captured the attention of researchers worldwide. Nevertheless, the precise involvement of ferroptosis-related genes (FRGs) in the anti-BLCA response remains inadequately elucidated. METHODS: The integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of FRGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and FRGs, unraveling their functional relevance and potential implications in BLCA. RESULTS: FRGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including MYBPH, SOST, SPRR2A, and CRNN, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CYP4F8, PDZD3, CRTAC1, and LRTM1 were identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles. CONCLUSIONS: FRGs are associated with the onset and progression of BLCA. A FRGs signature offers a viable alternative to predict BLCA, and these FRGs show a prospective research area for BLCA targeted treatment in the future.

Glutamine metabolism-related genes and immunotherapy in nonspecific orbital inflammation were validated using bioinformatics and machine learning.

BACKGROUND: Nonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis and progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect in cancer. Metabolic reprogramming is known to influence clinical outcomes in various malignancies. However, comprehensive research on glutamine metabolism's significance in NSOI is lacking. METHODS: This study conducted a bioinformatics analysis to identify and validate potential glutamine-related molecules (GlnMgs) associated with NSOI. The discovery of GlnMgs involved the intersection of differential expression analysis with a set of 42 candidate GlnMgs. The biological functions and pathways of the identified GlnMgs were analyzed using GSEA and GSVA. Lasso regression and SVM-RFE methods identified hub genes and assessed the diagnostic efficacy of fourteen GlnMgs in NSOI. The correlation between hub GlnMgs and clinical characteristics was also examined. The expression levels of the fourteen GlnMgs were validated using datasets GSE58331 and GSE105149. RESULTS: Fourteen GlnMgs related to NSOI were identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, and GFPT2. Biological function analysis indicated their involvement in responses to extracellular stimulus, mitochondrial matrix, and lipid transport. The diagnostic performance of these GlnMgs in distinguishing NSOI showed promising results. CONCLUSIONS: This study successfully identified fourteen GlnMgs associated with NSOI, providing insights into potential novel biomarkers for NSOI and avenues for monitoring disease progression.

Coherent spore dispersion via drop-leaf interaction.

The dispersion of plant pathogens, such as rust spores, is responsible for more than 20% of global crop yield loss annually. However, the release mechanism of pathogens from flexible plant surfaces into the canopy is not well understood. In this study, we investigated the interplay between leaf elasticity and rainfall, revealing how a flexible leaf structure can generate a lateral flow stream, with embedded coherent structures that enhance transport. We first modeled the linear coupling between drop momentum, leaf vibration, and the stream flux from leaf surfaces. With Lagrangian diagnostics, we further mapped out the nested coherent structures around the fluttering profile, providing a dynamical description for local spore delivery. We hope the mechanistic details extracted here can facilitate the construction of physically informed analytical models for local crop disease management.

Ghrelin inhibits myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway.

AIMS: Endoplasmic reticulum stress(ERS) can induce inflammation mediated by NLRP3 inflammatory bodies and link inflammation with oxidative stress in myocardial tissue. Ghrelin is an endogenous growth hormone-releasing peptide that has been proven to have multiple effects, such as regulating energy metabolism and inhibiting inflammation. However, the role of ghrelin in myocardial injury in diabetic rats and the mechanism have not been reported. RESULTS: We found that ghrelin could improve endoplasmic reticulum stress and inflammatory pyroptosis in the myocardial tissue of diabetic rats and reduce ERS and NLRP3 inflammasome crosstalk in H9C2 cardiomyocytes. Interestingly, ghrelin could activate the PI3K/AKT signalling pathway, playing a role in inhibiting endoplasmic reticulum stress and reducing the expression of pyroptosis-related proteins. However, these protective effects could be largely eliminated by LY294002. CONCLUSIONS: In summary, we demonstrated that ghrelin inhibited myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway. Our results provide new insights into the mechanism of diabetic myocardial injury induced by high glucose and high palmitic acid and ghrelin-mediated anti-inflammatory protection and provide potential therapeutic targets and strategies for diabetic cardiomyopathy.

Ghrelin improves lipid metabolism but not glucose metabolism in rats with diabetic cardiomyopathy.Ghrelin improves cardiac dysfunction and structure disorder in diabetic cardiomyopathy.Ghrelin inhibits cardiomyocyte pyroptosis in diabetic cardiomyopathy by regulating myocardial endoplasmic reticulum stress and NLRP3 inflammasome activation.The protective effect mediated by ghrelin may be related to the activation of PI3K/AKT signal pathway.