Aggregation-induced emission: Application in diagnosis and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.

Aloin alleviates corneal injury in alkali burn via inhibiting neutrophil extracellular traps and promoting Nrf2.

OBJECTIVE: Ocular chemical burns are a leading cause of blindness. The cornea is injured by alkali-induced oxidative disturbances and an inflammatory response. The aim of this study was to evaluate the protective effects of aloin, an antioxidant, and anti-inflammatory compound, on corneal alkali burn. MATERIALS AND METHODS: Mice eyes were injured by NaOH and subsequently treated with aloin eye drop and intraperitoneal injection. Pathological characteristics of the eyes were examined, and corneal samples were collected for further analysis. RESULTS: Aloin diminished neutrophil infiltration and the production of proinflammatory cytokines. Aloin also attenuated apoptosis in human corneal epithelial cells (HCEs) by reducing oxidative stress through the activation of the Nrf2 pathway. Additionally, aloin suppressed the formation of neutrophil extracellular traps (NETs) and inhibited their deposition on the cornea. Moreover, aloin mitigated alkali-induced apoptosis in HCEs caused by NETs. CONCLUSIONS: These findings suggest that aloin has potential as an antioxidant and anti-inflammatory compound for treating corneal alkali burn by inhibiting NETs formation and promoting Nrf2.

Baicalein Targets MAPK9 to Induce Apoptosis of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a significant global health concern. However, there are limited effective treatments available for it. The use of natural products in the management and treatment of HCC is gaining more attention. Baicalein is a flavonoid compound that has been reported to have antitumor activities in HCC. However, the direct binding targets of baicalein are still unknown. Therefore, we used the DNA-programmed affinity labeling method to identify the target of baicalein and validated its function in HCC cells. We set blank and competitive DNA probes as negative controls. The results showed that baicalein had 136 binding targets, of which 13 targets were differently expressed in HCC tissues. The enriched cellular process of these targets was apoptosis, which involved MAPK9. We tested the binding affinity of baicalein with MAPK9 as 89.7 nM (Kd) by surface plasmon resonance and analyzed the binding sites by virtual docking. Notably, the binding of baicalein with MAPK9 increased the protein levels of MAPK9 itself and the related downstream apoptosis signaling, triggering the apoptosis of HCC cells. However, the inhibitor of MAPK9, SP600125, blocked the baicalein-induced apoptosis, and the amounts of MAPK9 and downstream molecules were also decreased, indicating that baicalein acted through MAPK9 to induce apoptosis of HCC cells. In conclusion, we used the DNA-programmed affinity labeling method to identify the direct-binding target MAPK9 of baicalein and validated its function in baicalein-induced apoptosis of HCC cells, which would be helpful to understand and use baicalein in HCC therapy.

Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.

Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

The Risk of Deep Vein Thrombosis and Optimal Timing of Breast Cancer Surgery After COVID-19 Infection.

PURPOSE: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic." METHODS: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression. RESULTS: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy. CONCLUSION: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

Fractionation, spatial distribution, ecological and health risk assessment of cobalt and nickel in surface sediment of a bay along the southeast coast of China.

The fractionation and distribution of two potentially toxic elements (Co and Ni) were investigated in surface sediments to explore the pollution in Xiamen Bay, a special zone experiencing rapid economic growth and enormous environmental pressure. Relatively high concentrations were observed in nearshore areas with frequent human activities. The dominant fractions for Co and Ni were found to be residual, followed by exchangeable phase. Spatial differences in mobility and bioavailability inferred from chemical fractionations were more pronounced for Ni. Multiple evaluation methods including geo-accumulation index, risk assessment code, modified potential ecological risk index, etc., consistently indicated that pollution levels and ecological risks in the entire bay were generally classified as medium-low. However, non-carcinogenic risks of Co for children and carcinogenic risks of Ni for adults exceeded safety thresholds. Terrestrial weathering processes and industrial activities primarily contributed to the presence of these elements, while their distributions were mainly influenced by organic matter.

Characterization of MKK family genes and their responses to temperature stress and Vibrio parahaemolyticus infection in noble scallop Chlamys nobilis.

Mitogen-activated protein kinase kinase (MKK), the key element of the Mitogen-activated protein kinase (MAPK) signaling pathway, is crucial for the immune response to adverse environments in aquatic animals. Nevertheless, there is limited information regarding the role of the MKK gene family in mollusks. In our study, genome data and transcriptome were used to identify four MKK genes (CnMKK4, CnMKK5, CnMKK6, and CnMKK7) in the noble scallop. The result of the gene structure, motif analysis, and phylogenetic tree revealed that MKK genes are relatively conserved in bivalves. Moreover, four CnMKK genes were significantly highly expressed in immune-related tissues, suggesting that CnMKKs may related to bivalve immunity. Furthermore, CnMKK6 and CgMKK4 were significantly differentially expressed (P < 0.05) under 24 h of temperature stress, and all CnMKKs were significantly differentially expressed (P < 0.05) under 24 h of Vibrio parahaemolyticus infection. These results showed that the CnMKKs may have a significant impact under biotic and abiotic stresses. In conclusion, the result of the CnMKKs provides valuable insights into comprehending the function of MKK genes in mollusks.

Mitigation of cisplatin-induced acute kidney injury through oral administration of FAAH Inhibitor PF-04457845.

Fatty acid amide hydrolase (FAAH) serves as the primary enzyme responsible for degrading the endocannabinoid anandamide (AEA). Inhibition of FAAH, either through pharmacological means or genetic manipulation, can effectively reduce inflammation in various organs, including the brain, colon, heart, and kidneys. Infusion of a FAAH inhibitor into the kidney medulla has been shown to induce diuretic and natriuretic effects. FAAH knockout mice have shown protection against both post-ischemia reperfusion injury and cisplatin-induced acute kidney injury (AKI), although through distinct mechanisms. The present study was based on the hypothesis that pharmacological inhibition of FAAH activity could mitigate cisplatin-induced AKI, exploring potential renoprotective mechanism. Male wild type C57BL/6 were administered an oral gavage of a FAAH inhibitor (PF-04457845, 5mg/kg) or vehicle (10% PEG200+5% Tween80+normal saline) at 72, 48, 24, and 2 hours before and 24 and 48 hours after a single intraperitoneal injection of cisplatin (Cis, 25 mg/kg). Mice were euthanatized 72 hours after cisplatin treatment. Compared to vehicle-treated mice, PF-04457845-treated mice showed a decrease of cisplatin-induced plasma creatinine, blood urea nitrogen levels, kidney injury biomarkers (NGAL and KIM-1) and renal tubular damage. The renal protection from oral gavage of PF-04457845 against cisplatin-induced nephrotoxicity was associated with an enhanced AEA tone and reduced levels of DNA damage response biomarkers p53 and p21. Our work demonstrates that PF-04457845 effectively alleviates cisplatin-induced nephrotoxicity in mice, underscoring the potential of orally targeting FAAH as a novel strategy to prevent cisplatin nephrotoxicity. Significance Statement Oral administration of FAAH inhibitor, can reduce cisplatin-induced DNA damage response, tubular damages, and kidney dysfunction. Inactivation of FAAH could be a potential strategy to prevent cisplatin-induced nephrotoxicity.

Magic-themed motor training for daily bimanual task performance in children with unilateral spastic cerebral palsy: A systematic review and meta-analysis.

AIM: To evaluate the effectiveness of magic-themed interventions in improving daily bimanual task performance in children with unilateral spastic cerebral palsy (CP) to and elucidate the variability in outcomes. METHOD: This systematic literature review searched databases including Embase, MEDLINE, Scopus, Cochrane Central, and CINAHL. Outcome measures selected for the meta-analysis included the Children's Hand-use Experience Questionnaire, its three subscales, and the Besta subscale C. The overall efficacy of magic-themed interventions was analysed using Hedges' g as the summary measure for these outcomes. Subgroup analysis compared the efficacy of different modes of training, and a meta-regression investigated the impact of training duration. RESULTS: Analyses of four studies involving 78 children showed magic-themed training significantly improved bimanual task performance (Hedges' g = 0.327, 95% confidence interval [CI] = 0.107-0.547, p = 0.004), especially in group settings (Hedges' g = 0.435, 95% CI = 0.176-0.693, p = 0.001), compared with non-significant gains from video interventions (Hedges' g = 0.041, 95% CI = -0.380 to 0.462, p = 0.850). Additionally, training duration positively correlated with performance gains (coefficient = 0.0076 per hour, p = 0.001). INTERPRETATION: Magic-themed training, especially through group sessions and extended durations, enhances bimanual skills in children with unilateral spastic CP.

Genome-wide identification of gap junction gene family and their expression profiles under low temperature stress in noble scallop Chlamys nobilis.

Gap junctions, formed by gap junction proteins (GJ), play crucial roles in cell signaling and immune responses. The structure and function of the GJ from vertebrates (called connexins) have been extensively studied. However, little is known about the proteins forming gap junctions in invertebrates (called innexins). In this study, 14 GJ genes of Chlamys nobilis were identified. GJ proteins are mainly distributed on the plasma membrane, and all proteins are hydrophilic Phylogenetic tree analysis showed that the GJ proteins in C. nobilis were distantly related to those in vertebrates but closely related to those in invertebrates. Conserved motifs analysis of these GJ proteins in C. nobilis identified to have 10 conserved motifs, similar to gap junction proteins in other bivalves. Moreover, expression profiles of CnGJ genes under chronic and acute low temperature stress were also investigated. Results showed that chronic low temperature stress had a significant effect on the expression levels of CnGJ genes, and the expression profiles of CnGJ genes showed significantly variation under acute low temperature stress. All these results indicated that CnGJ genes play important roles in environmental adaptation in scallops. The present study initially elucidated the function of gap junction genes in noble scallop C. nobilis, which provides new insights into the GJ genes in mollusks and will help us better understand their roles in environmental stress in scallops.

Effects of genetically proxied statins on diabetic nephropathy and retinopathy: a Mendelian randomization study.

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = - 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative.

Status and role of the ubiquitin-proteasome system in renal fibrosis.

The ubiquitin-proteasome system (UPS) is a basic regulatory mechanism in cells that is essential for maintaining cell homeostasis, stimulating signal transduction, and determining cell fate. These biological processes require coordinated signaling cascades across members of the UPS to achieve substrate ubiquitination and deubiquitination. The role of the UPS in fibrotic diseases has attracted widespread attention, and the aberrant expression of UPS members affects the fibrosis process. In this review, we provide an overview of the UPS and its relevance for fibrotic diseases. Moreover, for the first time, we explore in detail how the UPS promotes or inhibits renal fibrosis by regulating biological processes such as signaling pathways, inflammation, oxidative stress, and the cell cycle, emphasizing the status and role of the UPS in renal fibrosis. Further research on this system may reveal new strategies for preventing renal fibrosis.

Occurrence, accumulation, ecological risk, and source identification of potentially toxic elements in multimedia in a subtropical bay, Southeast China.

Potentially toxic elements (PTEs) in seawater and sediments may be amplified along the aquatic food chain, posing a health threat to humans. This study comprehensively analyzed the concentrations, distribution, potential sources, and health risk of 7 PTEs in multimedia (seawater, sediment and organism) in typical subtropical bays in southern China. The results indicated that Zn was the most abundant element in seawater, and the average concentration of Cd in sediment was 3.93 times higher than the background value. Except for As, the seasonal differences in surface seawater were not significant. The content of Zn in fishes, crustacea, and shellfish was the highest, while the contents of Hg and Cd were relatively low. Bioaccumulation factor indicated that Zn was a strongly bioaccumulated element in seawater, while Cd was more highly enriched by aquatic organisms in sediment. According to principal component analysis (PCA), and positive matrix factorization (PMF), the main sources of PTEs in Quanzhou Bay were of natural derivation, industrial sewage discharge, and agricultural inputs, each contributing 40.4 %, 24.2 %, and 35.4 %, respectively. This study provides fundamental and significant information for the prevention of PTEs contamination in subtropical bays, the promotion of ecological safety, and the assessment of human health risk from PTEs in seafood.

Genome-wide analysis of the cytochrome P450 gene family in Pacific oyster Crassostrea gigas and their expression profiles during gonad development.

The cytochrome P450 (CYP) gene superfamily plays a significant role in various physiological processes, producing different compounds such as hormones, fatty acids, and biomolecules. However, little information is known their roles during gonad development in Pacific oyster (Crassostrea gigas). In this study, total of 116 CgCYP (Crassostrea gigas cytochrome P450) genes were identified and their expression pattern was analyzed for the first time. The relative molecular weights of these CgCYP genes ranged from 63.52 to 113.41 kDa, and the length of encoded amino acids ranged from 103 to 993. And total 26 cis-acting elements of these CgCYP genes were identified. GO and KEGG enrichment analysis showed some CgCYP genes are essential for the metabolism of male and female sex hormones. Additionally, expression anslysis showed 69 CgCYP genes were over-expressed in early gonad development and triploid infertile individuals. More importantly, expression levels of CgCYP1, CgCYP15, CgCYP34, CgCYP46, CgCYP69, CgCYP87, CgCYP88, and CgCYP103, were found to be significantly higher in female gonad, suggesting their important roles in female gonad development. The results of this study will provide a better understanding of the CgCYP genes in the gonad development of Pacific oyster.

Improved YOLO-FastestV2 wheat spike detection model based on a multi-stage attention mechanism with a LightFPN detection head.

The number of wheat spikes has an important influence on wheat yield, and the rapid and accurate detection of wheat spike numbers is of great significance for wheat yield estimation and food security. Computer vision and machine learning have been widely studied as potential alternatives to human detection. However, models with high accuracy are computationally intensive and time consuming, and lightweight models tend to have lower precision. To address these concerns, YOLO-FastestV2 was selected as the base model for the comprehensive study and analysis of wheat sheaf detection. In this study, we constructed a wheat target detection dataset comprising 11,451 images and 496,974 bounding boxes. The dataset for this study was constructed based on the Global Wheat Detection Dataset and the Wheat Sheaf Detection Dataset, which was published by PP Flying Paddle. We selected three attention mechanisms, Large Separable Kernel Attention (LSKA), Efficient Channel Attention (ECA), and Efficient Multi-Scale Attention (EMA), to enhance the feature extraction capability of the backbone network and improve the accuracy of the underlying model. First, the attention mechanism was added after the base and output phases of the backbone network. Second, the attention mechanism that further improved the model accuracy after the base and output phases was selected to construct the model with a two-phase added attention mechanism. On the other hand, we constructed SimLightFPN to improve the model accuracy by introducing SimConv to improve the LightFPN module. The results of the study showed that the YOLO-FastestV2-SimLightFPN-ECA-EMA hybrid model, which incorporates the ECA attention mechanism in the base stage and introduces the EMA attention mechanism and the combination of SimLightFPN modules in the output stage, has the best overall performance. The accuracy of the model was P=83.91%, R=78.35%, AP= 81.52%, and F1 = 81.03%, and it ranked first in the GPI (0.84) in the overall evaluation. The research examines the deployment of wheat ear detection and counting models on devices with constrained resources, delivering novel solutions for the evolution of agricultural automation and precision agriculture.

Structure and pharmacokinetics/pharmacodynamics of the anticoagulant tetradecasaccharide oHG-14 as an intrinsic tenase inhibitor.

The intrinsic tenase complex (iXase) is an attractive antithrombotic target to treat or prevent pathological thrombosis with negligible bleeding risk. Fucosylated glycosaminoglycan (FG) is a promising anticoagulant by inhibiting iXase. A depolymerized FG (dHG-5) as an anticoagulant has been approved for clinical trials. Given that dHG-5 is a multi-component drug candidate consisting of a homologous series of oligosaccharides, it is difficult to predict a clear pharmacokinetics. Here, as a major oligosaccharide component, the tetradecasaccharide (oHG-14) was purified from dHG-5 and its structure was defined as L-Fuc3S4S-α(1,3)-L-Δ4,5GlcA-α(1,3)-{D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ß(1,3)-}3-D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ol. oHG-14 showed potent iXase inhibitory activity in vitro and antithrombotic effect in vivo comparable to dHG-5. After single subcutaneous administration of oHG-14 at 8, 14.4 and 32.4 mg/kg to rats, the absolute bioavailability was 71.6 %-80.9 % determined by the validated bioanalytical methods. The maximum concentration (Cmax) was 3.73, 8.07, and 11.95 µg/mL, respectively, and the time reaching Cmax (Tmax) was about 1 h. oHG-14 was mainly excreted by kidney as the parent compound with the elimination kinetics of first-order linear model. Anticoagulant activity of oHG-14 was positively correlated with its concentration in rat plasma. The pharmacokinetics/pharmacodynamics (PK/PD) of oHG-14 is similar to that of dHG-5. This study could provide supportive data for the clinical trial of dHG-5 and further development of pure oligosaccharide as an antithrombotic drug candidate.

Free Radical Scavenging Effect and Immunomodulatory Activity of Total Saponins Extract of Ginseng Fibrous Roots.

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1ß in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.

Expression of microbial lipase in filamentous fungus Aspergillus niger: a review.

Lipase has high economic importance and is widely used in biodiesel, food, detergents, cosmetics, and pharmaceutical industries. The rapid development of synthetic biology and system biology has not only paved the way for comprehensively understanding the efficient operation mechanism of Aspergillus niger cell factories but also introduced a new technological system for creating and optimizing high-efficiency A. niger cell factories. In this review, all relevant data on microbial lipase enzyme sources and general properties are gathered and updated. The relationship between A. niger strain morphology and protein production is discussed. The safety of A. niger strain is investigated to ensure product safety. The biotechnologies and factors influencing lipase expression in A. niger are summarized. This review focuses on various strategies to improve lipase expression in A. niger. The summary of these methods and the application of the gene editing technology CRISPR/Cas9 system can further improve the efficiency of constructing the engineered lipase-producing A. niger.

Identification of Mycoplasma pneumoniae proteins interacting with NOD2 and their role in macrophage inflammatory response.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is a cell wall-deficient microorganism known to cause chronic respiratory infections in both children and adults. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor primarily responsible for identifying muramyl dipeptide (MDP) found in bacterial cell walls. Previous experiments have demonstrated that Mycoplasma ovipneumoniae induces macrophage autophagy through NOD2. In this study, we conducted RNA-seq analysis on macrophages infected with M. pneumoniae and observed an up-regulation in the expression of genes associated with the NOD2 signaling pathway. Mechanistic investigations further revealed the involvement of the NOD2 signaling pathway in the inflammatory response of macrophages activated by M. pneumoniae. We utilized GST pull-down technology in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to pinpoint the M. pneumoniae proteins that interact with NOD2. Additionally, co-immunoprecipitation (Co-IP) and immunofluorescence co-localization techniques were used to confirm the interaction between DUF16 protein and NOD2. We found that DUF16 protein can enter macrophages and induce macrophage inflammatory response through the NOD2/RIP2/NF-κB pathway. Notably, the region spanning amino acids 13-90 was identified as a critical region necessary for DUF16-induced inflammation. This research not only broadens our comprehension of the recognition process of the intracellular receptor NOD2, but also deepens our understanding of the development of M. pneumoniae infection.

Surface-Enhanced Raman Spectroscopy: Current Understanding, Challenges, and Opportunities.

While surface-enhanced Raman spectroscopy (SERS) has experienced substantial advancements since its discovery in the 1970s, it is an opportunity to celebrate achievements, consider ongoing endeavors, and anticipate the future trajectory of SERS. In this perspective, we encapsulate the latest breakthroughs in comprehending the electromagnetic enhancement mechanisms of SERS, and revisit CT mechanisms of semiconductors. We then summarize the strategies to improve sensitivity, selectivity, and reliability. After addressing experimental advancements, we comprehensively survey the progress on spectrum-structure correlation of SERS showcasing their important role in promoting SERS development. Finally, we anticipate forthcoming directions and opportunities, especially in deepening our insights into chemical or biological processes and establishing a clear spectrum-structure correlation.