Promising strategies in natural products treatments of psoriasis-update.

Psoriasis is a chronic, relapsing, inflammatory skin disease and has been increasing year by year. It is linked to other serious illnesses, such as psoriatic arthritis, cardiometabolic syndrome, and depression, resulting in a notable decrease in the quality of life for patients. Existing therapies merely alleviate symptoms, rather than providing a cure. An in-depth under-standing of the pathogenesis of psoriasis is helpful to discover new therapeutic targets and develop effective novel therapeutic agents, so it has important clinical significance. This article reviews the new progress in the study of pathogenesis and natural products of psoriasis in recent years. These natural products were summarized, mainly classified as terpenoids, polyphenols and alkaloids. However, the translation of experimental results to the clinic takes a long way to go.

Radiofrequency field inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells via modulating the NF-κB signaling pathway.

In this study, we investigated the inhibitory effects of radiofrequency exposure on RANKL-induced osteoclast differentiation in RAW264.7 cells, along with the underlying mechanisms. RAW264.7 cells were subjected to radiofrequency exposure at three distinct power densities: 50 µW/cm2, 150 µW/cm2, and 450 µW/cm2. The results showed that, among the three dosage levels, exposure to 150 µW/cm2 of radiofrequency radiation significantly reduced the proliferation capacity of RAW264.7 cells. RF exposure at three power densities resulted in significant increases in the level of osteoclast apoptosis and notable decreases in osteoclast differentiation. Notably, the most pronounced effects on apoptosis, differentiation in RAW 264.7 cells were observed at the 150 µW/cm2 power density. These effects were accompanied by concurrent decreases in mRNA and protein levels of osteoclast-specific genes, including RANK, NFATc1, and TRACP. Furthermore, radiofrequency exposure at power density of 150 µW/cm2 induced a significant decrease in cytoplasmic NF-κB protein levels while increasing its nuclear fraction, thereby counteracting the effects of RANKL-induced NF-κB activation. These data suggest that radiofrequency exerts inhibitory properties on RANKL-induced NF-κB transcriptional activity, subsequently indirectly suppressing the expression of downstream NF-κB target genes, such as NFATc1 and TRACP. In conclusion, our study demonstrates that radiofrequency radiation effectively inhibits osteoclast differentiation by modulating the NF-κB signaling pathway. These findings have important implications for potential therapeutic interventions in osteoporosis.

Osteoporosis is a common bone disease where bones become weak and brittle, often leading to fractures. It frequently occurs in older adults, especially postmenopausal women, due to low estrogen levels and inadequate calcium intake. This causes increased activity of bone cells called osteoclasts which break down bone tissue, resulting in severe bone loss. Currently, the primary treatment is long-term use of medications like bisphosphonates. However, these drugs can have side effects. The main adverse reactions include fever, vomiting, rash, diarrhea, dizziness, abdominal pain, musculoskeletal pain, headache, allergic-like reactions, indigestion, edema, and ocular symptoms.This study explored using radiofrequency (RF) radiation as a safe, non-invasive alternative therapy for osteoporosis. RF radiation is a type of energy used in communications like cell phones and WiFi. We tested whether exposure to 900MHz RF radiation could inhibit the formation and activity of osteoclasts to prevent excessive bone breakdown.We treated osteoclast precursor cells with RANKL, a protein that stimulates osteoclast formation. Cells were then exposed to RF radiation at various intensities. The results showed that medium-level RF radiation (150 µW/cm²) significantly suppressed RANKL-induced osteoclast differentiation and bone resorption capacity. This effect was like the osteoclast inhibition seen with estrogen treatment.Further analysis revealed that RF radiation blocks the activation of NF-κB, a key signaling molecule that promotes osteoclast formation when RANKL is present. This in turn reduced production of downstream signals like NFATc1 and TRACP which are essential for osteoclast differentiation.In summary, this study demonstrates that medium-intensity RF radiation could potentially prevent excessive osteoclastic bone resorption in osteoporosis patients by interfering with NF-κB signaling cascade. The research highlights RF radiation's promise as a novel, non-invasive osteoporosis therapy.

Few-shot meta-learning applied to whole brain activity maps improves systems neuropharmacology and drug discovery.

In this study, we present an approach to neuropharmacological research by integrating few-shot meta-learning algorithms with brain activity mapping (BAMing) to enhance the discovery of central nervous system (CNS) therapeutics. By utilizing patterns from previously validated CNS drugs, our approach facilitates the rapid identification and prediction of potential drug candidates from limited datasets, thereby accelerating the drug discovery process. The application of few-shot meta-learning algorithms allows us to adeptly navigate the challenges of limited sample sizes prevalent in neuropharmacology. The study reveals that our meta-learning-based convolutional neural network (Meta-CNN) models demonstrate enhanced stability and improved prediction accuracy over traditional machine-learning methods. Moreover, our BAM library proves instrumental in classifying CNS drugs and aiding in pharmaceutical repurposing and repositioning. Overall, this research not only demonstrates the effectiveness in overcoming data limitations but also highlights the significant potential of combining BAM with advanced meta-learning techniques in CNS drug discovery.

Feasibility and Effectiveness of Venoarterial Extracorporeal Membrane Oxygenation Plus Intra-Aortic Balloon Pump Assisted High-Risk Percutaneous Coronary Intervention in Complex Coronary Disease.

Background: Mechanical circulatory support may facilitate high-risk percutaneous coronary intervention (PCI). This study aimed to assess the feasibility, safety and effectiveness of high-risk PCI under the support of venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with intra-aortic balloon pump (IABP). Methods: We enrolled patients who received VA-ECMO plus IABP-assisted PCI procedures at our center from April 2012 to June 2018. Major adverse cardiac events (MACEs) included all-cause death, myocardial infarction, and target vessel revascularization. Results: A total of 10 patients were included, with a mean age of 71 years, EuroSCORE II of 19.9%, and SYNTAX score of 39.8. Procedural success was achieved in nine (90%) patients. The mean duration of ECMO support was 1.5 hours, and 2.6 stents were implanted per patient. Major complications included contrast-induced nephropathy needing hemodialysis in one (10%) patient, significant hemoglobin drop requiring blood transfusion in two (20%) patients, pulmonary infection in one (10%) patient, and local surgical incision infection in one (10%) patient. The accumulative mortality rates for the nine patients with procedural success were 0, 22.2%, and 44.4% at 1, 3, and 5 years follow-up, respectively. However, cardiac death occurred in only one (11.1%) patient. In addition, two patients received repeat PCI or coronary artery bypass grafting within two years following the index procedure. The overall incidence rates of MACEs were 11.1%, 44.4%, and 66.7% at 1, 3, and 5 years follow-up, respectively. Conclusions: VA-ECMO plus IABP-assisted high-risk PCI was feasible in patients with complex coronary disease, with a high procedural success rate and acceptable mid-term clinical outcomes.

Research progress of edible mushroom polysaccharide-metal trace element complexes.

Metal trace elements are crucial for human health, and the complexes of edible mushroom polysaccharides with metal trace elements are currently a research hotspot in the field of food science. This article reviews the preparation methods, structural characterization, and physiological activities of edible mushroom polysaccharide-metal trace element complexes, including iron, selenium, and zinc. Research has shown that iron complexes obtained through Co-thermal synthesis of the FeCl3 method exhibit excellent antioxidant and anti-anemia functions; selenium complexes prepared via selenium-enriched cultivation significantly enhance immunological and anti-cancer properties; zinc complexes improve lipid-lowering, liver protection, and antioxidant capabilities. However, there is an imbalance in research among different metal elements, particularly with a high density of studies on selenium complexes. These studies provide a foundation for the future development of edible mushroom polysaccharide-metal trace element complexes.

Plasmonic nanoparticle sensors: current progress, challenges, and future prospects.

Plasmonic nanoparticles (NPs) have played a significant role in the evolution of modern nanoscience and nanotechnology in terms of colloidal synthesis, general understanding of nanocrystal growth mechanisms, and their impact in a wide range of applications. They exhibit strong visible colors due to localized surface plasmon resonance (LSPR) that depends on their size, shape, composition, and the surrounding dielectric environment. Under resonant excitation, the LSPR of plasmonic NPs leads to a strong field enhancement near their surfaces and thus enhances various light-matter interactions. These unique optical properties of plasmonic NPs have been used to design chemical and biological sensors. Over the last few decades, colloidal plasmonic NPs have been greatly exploited in sensing applications through LSPR shifts (colorimetry), surface-enhanced Raman scattering, surface-enhanced fluorescence, and chiroptical activity. Although colloidal plasmonic NPs have emerged at the forefront of nanobiosensors, there are still several important challenges to be addressed for the realization of plasmonic NP-based sensor kits for routine use in daily life. In this comprehensive review, researchers of different disciplines (colloidal and analytical chemistry, biology, physics, and medicine) have joined together to summarize the past, present, and future of plasmonic NP-based sensors in terms of different sensing platforms, understanding of the sensing mechanisms, different chemical and biological analytes, and the expected future technologies. This review is expected to guide the researchers currently working in this field and inspire future generations of scientists to join this compelling research field and its branches.

Exploring Genetic Drug Targets in Acne Vulgaris: A Comprehensive Proteome-Wide Mendelian Randomization Study.

BACKGROUND: Acne vulgaris presents a substantial clinical challenge due to its complex pathophysiology and significant impact on quality of life. Identification of novel therapeutic targets for acne using genetic tools can guide the development of more effective treatments. METHODS: Utilizing a dataset comprising 35 559 Icelandic individuals, we performed proteomic analyses to quantify 4709 circulating proteins. We integrated these data with acne-specific genome-wide association studies (GWAS) encompassing 34 422 acne patients and 364 991 controls. Mendelian randomization (MR) analyses employed the TwoSampleMR tool and Summary-data-based Mendelian Randomization (SMR) to estimate the causal effects of identified proteins on acne risk. Colocalization analyses assessed the likelihood of shared genetic etiology between protein levels and acne using the "coloc" R package. RESULTS: Our proteome-wide MR analysis initially identified 128 proteins potentially associated with acne risk. Following multiple testing corrections using the Benjamini-Hochberg method, fatty acid synthase (FASN) and tissue inhibitor of metalloproteinases 4 (TIMP4) remained significantly associated with acne risk. FASN exhibited a protective effect against acne (OR = 0.768, 95% CI: 0.676-0.872, p = 4.685E-05), while TIMP4 was associated with an increased risk (OR = 1.169, 95% CI: 1.103-1.241, p = 1.956E-07). Colocalization analysis supported a shared genetic basis for these protein-acne associations, with posterior probabilities indicating strong evidence of shared causal variants. CONCLUSION: Our findings highlight the utility of integrative genomic approaches in identifying potential therapeutic targets for acne. FASN and TIMP4, in particular, demonstrate strong potential as targets for therapeutic intervention, pending further validation through clinical research. These results offer a foundation for targeted acne treatment development, aligning with personalized medicine principles.

Synthesis and characterization of the trans- and cis-isomers of N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine and their attempted detection in human urine.

1,3-Butadiene (BD) is a carcinogenic air pollutant. N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (MHBMA3 or 4HBeMA), an urinary BD metabolite with unspecified configuration, is considered the most sensitive BD biomarker and has been used in routine biomonitoring since 2012. However, two issues remain unaddressed: why its concentrations are unusually high relative to other urinary BD biomarkers and why some authors reported no detection of the biomarker whereas other authors readily quantitated it. To address the issues, we synthesized and structurally characterized the authentic trans- and cis-isomers of MHBMA3 (designated NE and NZ, respectively), developed an isotope-dilution LC-MS/MS method for their quantification, and examined 67 urine samples from barbecue restaurant personnel (n = 47) and hotel administrative staff (n = 20). The restaurant personnel were exposed to barbecue fumes, which contain relatively high concentrations of BD. The results showed that NE and NZ had highly similar NMR spectra, and were difficult to be well separated chromatographically. The NMR data showed that the MHBMA3 isomer investigated in most previous studies was NE. We did not detect NE and NZ in any samples; however, an interfering peak with varying heights was observed in most samples. Notably, under the chromatographic conditions used in the literature, the peak exhibited indistinguishable retention time from that of NE. Thus, it is highly likely that the interfering peak has been mis-identified as NE in previous studies, providing a reasonable explanation for the high MHBMA3 concentration in urine. The contradiction in the presence of MHBMA3 in urine was also caused by the mis-identification, because the researchers who reported the absence of MHBMA3 were actually detecting NZ. Thus, we clarified the confusion on MHBMA3 in previous studies through correctly identifying the two MHBMA3 isomers. The presence of NE and NZ in human urine warrants further investigations.

Anticancer potential of active alkaloids and synthetic analogs derived from marine invertebrates.

In recent years, the number of cancers has soared, becoming one of the leading causes of human death. At the same time, marine anticancer substances have been the focus of marine drug research. Marine alkaloids derived from marine invertebrates like sponges are an important class of secondary metabolites, which have good bioactivities of blocking the cancer cell cycle, inducing autophagy and apoptosis of cancer cells, inhibiting cancer cell invasion and proliferation. They show potential as anticancer drug candidates. Therefore, in this review, we focus on the detailed introduction of bioactive alkaloids and their synthetic analogs from marine invertebrates, such as 4-chloro fascapysin and other 41 kinds of marine alkaloids or marine alkaloid synthetic analogs. They have significant anticancer activities on breast cancer, cervical cancer, colorectal cancer, prostate cancer, lung cancer, liver cancer, and so on. It provides new candidate compounds for anticancer drug research and provides a reference basis for marine drug resources research.

Enhanced degradation of exogenetic citrinin by glycosyltransferases in the oleaginous yeast Saitozyma podzolica zwy-2-3.

The contamination by the toxin citrinin (CIT), produced by fungi, has been reported in agricultural foods and is known to be nephrotoxic to humans. In this study, we found that CIT could be effectively degraded by the oleaginous yeast Saitozyma podzolica zwy-2-3. Four genes encoding glycosyltransferases (GTs) in S. podzolica zwy-2-3 (SPGTs) were identified by evolutionary and structural analyses. The overexpression of SPGTs enhanced CIT degradation to 0.56 mg/L/h in S. podzolica zwy-2-3 by increasing ATP and glutathione (GSH) contents to oxidize CIT and scavenge reactive oxygen species (ROS). Besides, SPGTs promoted lipid synthesis by 9.3 % of S. podzolica zwy-2-3 under CIT stress. These results suggest that SPGTs in oleaginous yeast play a pivotal role in enhancing CIT degradation and lipid accumulation. These findings provide a valuable basis for the application of GTs in oleaginous yeast to alleviate CIT contamination in agricultural production, which may contribute to food safety.

Mn-Catalyzed Electrooxidative Radical Cascade Cyclization for the Synthesis of 6-Phosphorylated Quinoxalino[2,1-b]quinazolin-12-ones.

Due to their important potential medicinal value, chemists are pursuing mild and efficient methods to synthesize structurally diverse quinazolinone derivatives. In this paper, a series of isocyano-tethered N-aryl quinazolinones were designed and synthesized to conduct electrocatalytic radical cascade cyclization reactions with phosphine oxides by utilizing inexpensive MnII salt as the catalyst. The desired 6-phosphorylated quinoxalino[2,1-b]quinazolin-12-ones were obtained in moderate to good yields.

Artificial Intelligence-Related Dental Research: Bibliometric and Altmetric Analysis.

BACKGROUND: Recent years have witnessed an explosive surge in dental research related to artificial intelligence (AI). These applications have optimised dental workflows, demonstrating significant clinical importance. Understanding the current landscape and trends of this topic is crucial for both clinicians and researchers to utilise and advance this technology. However, a comprehensive scientometric study regarding this field had yet to be performed. METHODS: A literature search was conducted in the Web of Science Core Collection database to identify eligible "research articles" and "reviews." Literature screening and exclusion were performed by 2 investigators. Thereafter, VOSviewer was utilised in co-occurrence analysis and CiteSpace in co-citation analysis. R package Bibliometrix was employed to automatically calculate scientific impacts, determining the core authors and journals. Altmetric data were described narratively and supplemented with Spearman correlation analysis. RESULTS: A total of 1558 research publications were included. During the past 5 years, AI-related dental publications drastically increased in number, from 36 to 581. Diagnostics and Scientific Reports published the most articles, whereas Journal of Dental Research received the highest number of citations per article. China, the US, and South Korea emerged as the most prolific countries, whilst Germany received the highest number of citations per article (23.29). Charité Universitätsmedizin Berlin was the institution with the highest number of publications and citations per article (29.16). Altmetric Attention Score was correlated with News Mentions (P < .001), and significant associations were observed amongst Dimension Citations, Mendeley Readers, and Web of Science Citations (P < .001). CONCLUSIONS: The publication numbers regarding AI-related dental research have been rising rapidly and may continue their upwards trend. China, the US, South Korea, and Germany had promoted the progress of AI-related dental research. Disease diagnosis, orthodontic applications, and morphology segmentation were current hotspots. Attention mechanism, explainable AI, multimodal data fusion, and AI-generated text assistants necessitate future research and exploration.

Physical Reservoir Computing Using van der Waals Ferroelectrics for Acoustic Keyword Spotting.

Acoustic keyword spotting (KWS) plays a pivotal role in the voice-activated systems of artificial intelligence (AI), allowing for hands-free interactions between humans and smart devices through information retrieval of the voice commands. The cloud computing technology integrated with the artificial neural networks has been employed to execute the KWS tasks, which however suffers from propagation delay and the risk of privacy breach. Here, we report a single-node reservoir computing (RC) system based on the CuInP2S6 (CIPS)/graphene heterostructure planar device for implementing the KWS task with low computation cost. Through deliberately tuning the Schottky barrier height at the ferroelectric CIPS interfaces for the thermionic injection and transport of the electrons, the typical nonlinear current response and fading memory characteristics are achieved in the device. Additionally, the device exhibits diverse synaptic plasticity with an excellent separation capability of the temporal information. We construct a RC system through employing the ferroelectric device as the physical node to spot the acoustic keywords, i.e., the natural numbers from 1 to 9 based on simulation, in which the system demonstrates outstanding performance with high accuracy rate (>94.6%) and recall rate (>92.0%). Our work promises physical RC in single-node configuration as a prospective computing platform to process the acoustic keywords, promoting its applications in the artificial auditory system at the edge.

Cold-hot Janus electrochemical aptamer-based sensor for calibration-free determination of biomolecules.

Real-time, high-frequency measurements of pharmaceuticals, metabolites, exogenous antigens, and other biomolecules in biological samples can provide critical information for health management and clinical diagnosis. Electrochemical aptamer-based (EAB) sensor is a promising analytical technique capable of achieving these goals. However, the issues of insufficient sensitivity, frequent calibration and lack of adapted portable electrochemical device limit its practical application in immediate detection. In response we have fabricated an on-chip-integrated, cold-hot Janus EAB (J-EAB) sensor based on the thermoelectric coolers (TECs). Attributed to the Peltier effect, the enhanced/suppressed current response can be generated simultaneously on cold/hot sides of the J-EAB sensor. The ratio of the current responses on the cold and hot sides was used as the detection signal, enabling rapid on-site, calibration-free determination of small molecules (procaine) as well as macromolecules (SARS-CoV-2 spike protein) in single step, with detection limits of 1 µM and 10 nM, respectively. We have further demonstrated that the J-EAB sensor is effective in improving the ease and usability of the actual detection process, and is expected to provide a universal, low-cost, fast and easy potential analytical tool for other clinically important biomarkers, drugs or pharmaceutical small molecules.

Rapid nanomolar detection of cocaine in biofluids by electrochemical aptamer-based sensor with low-temperature effect for drugged driving screening.

Cocaine is one of the most abused illicit drugs, and its abuse damages the central nervous system and can even lead directly to death. Therefore, the development of simple, rapid and highly sensitive detection methods is crucial for the prevention and control of drug abuse, traffic accidents and crime. In this work, an electrochemical aptamer-based (EAB) sensor based on the low-temperature enhancement effect was developed for the direct determination of cocaine in bio-samples. The signal gain of the sensor at 10 °C was greatly improved compared to room temperature, owing to the improved affinity between the aptamer and the target. Additionally, the electroactive area of the gold electrode used to fabricate the EAB sensor was increased 20 times by a simple electrochemical roughening method. The porous electrode possesses more efficient electron transfer and better antifouling properties after roughening. These improvements enabled the sensor to achieve rapid detection of cocaine in complex bio-samples. The low detection limits (LOD) of cocaine in undiluted urine, 50% serum and 50% saliva were 70 nM, 30 nM and 10 nM, respectively, which are below the concentration threshold in drugged driving screening. The aptasensor was simple to construct and reusable, which offers potential for drugged driving screening in the real world.

TopMarker: Computational screening biomarkers of hepatocellular carcinoma from transcriptome and interactome based on differential network topological parameters.

Identifying diagnostic biomarkers for cancer is crucial in the field of personalized medicine. The available transcriptome and interactome provide unprecedented opportunities and challenges for biomarker screening. From a systematic perspective, network-based medicine methods provide alternative approaches to organizing the available high-throughput omics data for deciphering molecular interactions and their associations with phenotypic states. In this work, we propose a bioinformatics strategy named TopMarker for discovering diagnostic biomarkers by comparing the network topology differences in control and disease samples. Specifically, we build up gene-gene interaction networks in the two states of control and disease respectively. The network rewiring status across the two networks results in differential network topologies reflecting dynamics and changes in normal samples when compared with those in disease. Thus, we identify the potential biomarker genes with differential network topological parameters between the control and disease gene networks. For a proof-of-concept study, we introduce the computational pipeline of biomarker discovery in hepatocellular carcinoma (HCC). We prove the effectiveness of the proposed TopMarker method using these candidate biomarkers in classifying HCC samples and validate its signature capability across numerous independent datasets. We also compare the discriminant power of biomarker genes identified by TopMarker with those identified by other baseline methods. The higher classification performances and functional implications indicate the advantages of our proposed method for discovering biomarkers from differential network topology.

Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network.

Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.

Enhancement of lipid synthesis by the transcription factor Asg1 in Saitozyma podzolica zwy-2-3 under dissolved oxygen stress.

Microbial oils have been of considerable interest as food additives and biofuel resources due to high lipid contents, but lipid accumulation of oleaginous microorganisms can be induced by environmental stresses, such as dissolved oxygen (DO), which limit large-scale lipid production. Here, DO stress gave rise to the endogenous nitric oxide (NO) level to mediate S-nitrosylation of SpAsg1, regulating the lipid accumulation in Saitozyma podzolica zwy-2-3. Notably, qRT-PCR, yeast one-hybrid, dual-luciferase reporter assays, and metabolomics analysis exhibited that overexpression of SpAsg1 promoted lipid synthesis by directly regulation of glucose metabolism, enhancing glucose uptake, ATP and NADPH contents under DO stress. Meanwhile, SpAsg1 improved the antioxidant capacity to reduce the intracellular reactive oxygen species (ROS) and NO levels. Overall, we systematically investigated the regulation of SpAsg1 on lipid metabolism of S. podzolica zwy-2-3 under DO stress, which sheds light on further studies for alleviating oxygen limitation of lipid production in microbial industry.

Granzyme B secreted by T cells is involved in anti-bacterial immune response of tilapia.

Secreted by natural killer cells and cytotoxic T lymphocytes, Granzyme B is involved in regulating the adaptive immune response in vertebrates and plays a pivotal role in resisting virus invasion and removing pathogens. Although it had been extensively studied in mammals, the involvement of Granzyme B in adaptive immune response of early vertebrates remained elusive. In this study, we investigated the Granzyme B in Oreochromis niloticus (OnGrB), found that its function domain was conserved. Additionally, OnGrB was widely expressed in various tissues and could respond to T-cell activation in vitro at the transcriptional level. Furthermore, we prepared the recombinant OnGrB (rOnGrB) as an immunogen to develop a mouse anti-OnGrB monoclonal antibody (mAb). Using this anti-OnGrB mAb as a tool, we explored the expression of OnGrB in the adaptive immune response of tilapia. Our findings revealed that T cell was a significant source of OnGrB production, the expression of OnGrB at the protein level and the proportion of OnGrB + T cells increased after both T cell activation in vitro and infection with Edwardsiella piscicida in vivo. More importantly, our findings also preliminarily illuminated that p65 could regulate the transcriptional activity of OnGrB. These results indicated that OnGrB was involved in the adaptive immunity of tilapia and played a critical role in T cell function in teleost. Our study provided theoretical support and new perspectives for understanding adaptive immunity in teleost.

Novel extracellular lipase gene Lip1728 influences nutrient-dependent performance bacterial quorum sensing of Burkholderia pyrrocinia WZ10-3.

Quorum sensing (QS) is a cellular communication mechanism in which bacteria secrete and recognize signaling molecules to regulate group behavior. Lipases provide energy for bacterial cell growth but it is unknown whether they influence nutrient-dependent QS by hydrolyzing substrate. A high-yield lipase-producing strain, Burkholderia pyrrocinia WZ10-3, was previously identified in our laboratory, but the composition of its crude enzymes was not elucidated. Here, we identified a key extracellular lipase, Lip1728, in WZ10-3, which accounts for 99 % of the extracellular lipase activity. Lip1728 prefers to hydrolyze triglycerides at sn-1,3 positions, with pNP-C16 being its optimal substrate. Lip1728 exhibited activity at pH 5.0-10.0 and regardless of the presence of metal ions. It had strong resistance to sodium dodecyl sulfate and short-chain alcohols and was activated by phenylmethanesulfonylfluoride (PMSF). Lip1728 knockout significantly affected lipid metabolism and biofilm formation in the presence of olive oil. Finally, oleic acid, a hydrolysate of Lip1728, influenced the production of the signal molecule N-acyl homoserine lactone (AHL) and biofilm formation by downregulating the AHL synthetase gene pyrI. In conclusion, Lip1728, as a key extracellular lipase in B. pyrrocinia WZ10-3, exhibits superior properties that make it suitable for biodiesel production and plays a crucial role in QS.