Extracellular pH sensing by plant cell-surface peptide-receptor complexes.

The extracellular pH is a vital regulator of various biological processes in plants. However, how plants perceive extracellular pH remains obscure. Here, we report that plant cell-surface peptide-receptor complexes can function as extracellular pH sensors. We found that pattern-triggered immunity (PTI) dramatically alkalinizes the acidic extracellular pH in root apical meristem (RAM) region, which is essential for root meristem growth factor 1 (RGF1)-mediated RAM growth. The extracellular alkalinization progressively inhibits the acidic-dependent interaction between RGF1 and its receptors (RGFRs) through the pH sensor sulfotyrosine. Conversely, extracellular alkalinization promotes the alkaline-dependent binding of plant elicitor peptides (Peps) to its receptors (PEPRs) through the pH sensor Glu/Asp, thereby promoting immunity. A domain swap between RGFR and PEPR switches the pH dependency of RAM growth. Thus, our results reveal a mechanism of extracellular pH sensing by plant peptide-receptor complexes and provide insights into the extracellular pH-mediated regulation of growth and immunity in the RAM.

TIR domains of plant immune receptors are 2',3'-cAMP/cGMP synthetases mediating cell death.

2',3'-cAMP is a positional isomer of the well-established second messenger 3',5'-cAMP, but little is known about the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have the NADase function necessary but insufficient to activate plant immune responses. Here, we show that plant TIR proteins, besides being NADases, act as 2',3'-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data show that a TIR domain adopts distinct oligomers with mutually exclusive NADase and synthetase activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death in Nicotiana benthamiana (Nb), supporting an important role for these cNMPs in TIR signaling. Furthermore, the Arabidopsis negative regulator of TIR-NLR signaling, NUDT7, displays 2',3'-cAMP/cGMP but not 3',5'-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of TIRs in Nb. Our study identifies a family of 2',3'-cAMP/cGMP synthetases and establishes a critical role for them in plant immune responses.

Substrate-induced condensation activates plant TIR domain proteins.

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR-NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.

Expansion of Anticomplement Therapy Indications from Rare Genetic Disorders to Common Kidney Diseases.

Complement constitutes a major part of the innate immune system. The study of complement in human health has historically focused on infection risks associated with complement protein deficiencies; however, recent interest in the field has focused on overactivation of complement as a cause of immune injury and the development of anticomplement therapies to treat human diseases. The kidneys are particularly sensitive to complement injury, and anticomplement therapies for several kidney diseases have been investigated. Overactivation of complement can result from loss-of-function mutations in complement regulators; gain-of-function mutations in key complement proteins such as C3 and factor B; or autoantibody production, infection, or tissue stresses, such as ischemia and reperfusion, that perturb the balance of complement activation and regulation. Here, we provide a high-level review of the status of anticomplement therapies, with an emphasis on the transition from rare diseases to more common kidney diseases.

To assemble or not to assemble: metagenomic profiling of microbially mediated biogeochemical pathways in complex communities.

High-throughput profiling of microbial functional traits involved in various biogeochemical cycling pathways using shotgun metagenomic sequencing has been routinely applied in microbial ecology and environmental science. Multiple bioinformatics data processing approaches are available, including assembly-based (single-sample assembly and multi-sample assembly) and read-based (merged reads and raw data). However, it remains not clear how these different approaches may differ in data analyses and affect result interpretation. In this study, using two typical shotgun metagenome datasets recovered from geographically distant coastal sediments, the performance of different data processing approaches was comparatively investigated from both technical and biological/ecological perspectives. Microbially mediated biogeochemical cycling pathways, including nitrogen cycling, sulfur cycling and B12 biosynthesis, were analyzed. As a result, multi-sample assembly provided the most amount of usable information for targeted functional traits, at a high cost of computational resources and running time. Single-sample assembly and read-based analysis were comparable in obtaining usable information, but the former was much more time- and resource-consuming. Critically, different approaches introduced much stronger variations in microbial profiles than biological differences. However, community-level differences between the two sampling sites could be consistently observed despite the approaches being used. In choosing an appropriate approach, researchers shall balance the trade-offs between multiple factors, including the scientific question, the amount of usable information, computational resources and time cost. This study is expected to provide valuable technical insights and guidelines for the various approaches used for metagenomic data analysis.

MASP3 Deficiency in Mice Reduces but Does Not Abrogate Alternative Pathway Complement Activity Due to Intrinsic Profactor D Activity.

Complement factor D (FD) is a rate-limiting enzyme of the alternative pathway (AP). Recent studies have suggested that it is synthesized as an inactive precursor and that its conversion to enzymatically active FD is catalyzed by mannan-binding lectin-associated serine protease 3 (MASP3). However, whether MASP3 is essential for AP complement activity remains uncertain. It has been shown that Masp1/3 gene knockout did not prevent AP complement overactivation in a factor H-knockout mouse, and a human patient lacking MASP3 still retained AP complement activity. In this study, we have assessed AP complement activity in a Masp3-knockout mouse generated by CRISPR/Cas9 editing of the Masp1/3 gene. We confirmed specific Masp3 gene inactivation by showing intact MASP1 protein expression and absence of mature FD in the mutant mice. Using several assays, including LPS- and zymosan-induced C3b deposition and rabbit RBC lysis tests, we detected plasma concentration-dependent AP complement activity in Masp3 gene-inactivated mice. Thus, although not measurable in 5% plasma, significant AP complement activity was detected in 20-50% plasma of Masp3 gene-inactivated mice. Furthermore, whereas FD gene deletion provided more than 90% protection of CD55/Crry-deficient RBCs from AP complement-mediated extravascular hemolysis, Masp3 gene deletion only provided 30% protection in the same study. We also found pro-FD to possess intrinsic catalytic activity, albeit at a much lower level than mature FD. Our data suggest that MASP3 deficiency reduces but does not abrogate AP complement activity and that this is explained by intrinsic pro-FD activity, which can be physiologically relevant in vivo.

Activation of the alternative complement pathway modulates inflammation in thoracic aortic aneurysm/dissection.

Thoracic aortic aneurysm/dissection (TAAD) is a lethal vascular disease, and several pathological factors participate in aortic medial degeneration. We previously discovered that the complement C3a-C3aR axis in smooth muscle cells promotes the development of thoracic aortic dissection (TAD) through regulation of matrix metalloproteinase 2. However, discerning the specific complement pathway that is activated and elucidating how inflammation of the aortic wall is initiated remain unknown. We ascertained that the plasma levels of C3a and C5a were significantly elevated in patients with TAD and that the levels of C3a, C4a, and C5a were higher in acute TAD than in chronic TAD. We also confirmed the activation of the complement in a TAD mouse model. Subsequently, knocking out Cfb (Cfb) or C4 in mice with TAD revealed that the alternative pathway and Cfb played a significant role in the TAD process. Activation of the alternative pathway led to generation of the anaphylatoxins C3a and C5a, and knocking out their receptors reduced the recruitment of inflammatory cells to the aortic wall. Moreover, we used serum from wild-type mice or recombinant mice Cfb as an exogenous source of Cfb to treat Cfb KO mice and observed that it exacerbated the onset and rupture of TAD. Finally, we knocked out Cfb in the FBN1C1041G/+ Marfan-syndrome mice and showed that the occurrence of TAA was reduced. In summary, the alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.NEW & NOTEWORTHY The alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.

Phytophthora sojae Effector PsCRN108 Targets CAMTA2 to Suppress HSP40 Expression and ROS Burst.

Oomycete pathogens secrete numerous crinkling and necrosis proteins (CRNs) to manipulate plant immunity and promote infection. However, the functional mechanism of CRN effectors is still poorly understood. Previous research has shown that the Phytophthora sojae effector PsCRN108 binds to the promoter of HSP90s and inhibits their expression, resulting in impaired plant immunity. In this study, we found that in addition to HSP90, PsCRN108 also suppressed other Heat Shock Protein (HSP) family genes, including HSP40. Interestingly, PsCRN108 inhibited the expression of NbHSP40 through its promoter, but did not directly bind to its promoter. Instead, PsCRN108 interacted with NbCAMTA2, a negative regulator of plant immunity. NbCAMTA2 was a negative regulator of NbHSP40 expression, and PsCRN108 could promote such inhibition activity of NbCAMTA2. Our results elucidated the multiple roles of PsCRN108 in the suppression of plant immunity and revealed a new mechanism by which the CRN effector hijacked transcription factors to affect immunity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

The Phytophthora sojae effector PsFYVE1 modulates immunity-related gene expression by targeting host RZ-1A protein.

Oomycete pathogens secrete numerous effectors to manipulate plant immunity and promote infection. However, relatively few effector types have been well characterized. In this study, members of an FYVE domain-containing protein family that are highly expanded in oomycetes were systematically identified, and one secreted protein, PsFYVE1, was selected for further study. PsFYVE1 enhanced Phytophthora capsici infection in Nicotiana benthamiana and was necessary for Phytophthora sojae virulence. The FYVE domain of PsFYVE1 had PI3P-binding activity that depended on four conserved amino acid residues. Furthermore, PsFYVE1 targeted RNA-binding proteins RZ-1A/1B/1C in N. benthamiana and soybean (Glycine max), and silencing of NbRZ-1A/1B/1C genes attenuated plant immunity. NbRZ-1A was associated with the spliceosome complex that included three important components, glycine-rich RNA-binding protein 7 (NbGRP7), glycine-rich RNA-binding protein 8 (NbGRP8), and a specific component of the U1 small nuclear ribonucleoprotein complex (NbU1-70K). Notably, PsFYVE1 disrupted NbRZ-1A-NbGRP7 interaction. RNA-seq and subsequent experimental analysis demonstrated that PsFYVE1 and NbRZ-1A not only modulated pre-mRNA alternative splicing (AS) of the necrotic spotted lesions 1 (NbNSL1) gene, but also co-regulated transcription of hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (NbHCT), ethylene insensitive 2 (NbEIN2), and sucrose synthase 4 (NbSUS4) genes, which participate in plant immunity. Collectively, these findings indicate that the FYVE domain-containing protein family includes potential uncharacterized effector types and also highlight that plant pathogen effectors can regulate plant immunity-related genes at both AS and transcription levels to promote disease.

Cyclometalated gold(III)-hydride under oriented external electric fields: a new strategy to modulate its reactivity?

Selected gold complexes have been regarded as promising anti-cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off-target thiol-proteins. Recently, a novel gold(III)-hydride complex (abbreviated as 1) with visible light-induced thiol reactivity has been reported as potent photo-activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au-H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF-strategy to activate this reported gold(III)-hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field-activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.

A novel long noncoding RNA-lncRNA-AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide-induced myocardial depression.

Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.

Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy.

The antitumor strategies based on innate immunity activation have become favored by researchers in recent years. In particular, strategies targeting antiphagocytic signaling blockade to enhance phagocytosis have been widely reported. For example, the addition of prophagocytic signals such as calreticulin could make the strategy significantly more effective. In this study, an antitumor strategy that combines photodynamic therapy (PDT) with CD47 blockade has been reported. This approach promotes the maturation of dendritic cells and the presentation of tumor antigens by PDT-mediated tumor immunogenic cell death, as well as the enhancement of cytotoxic T lymphocyte infiltration in tumor areas and the phagocytic activity of phagocytes. Furthermore, the downregulation and blockage of CD47 protein could further promote phagocytic activity, strengthen the innate immune system, and ultimately elevate the antitumor efficacy and inhibit tumor metastasis.

Effect of Transcutaneous Electrical Nerve Stimulation Based on Wrist-Ankle Acupuncture Theory for Pain Relief during Non-Anesthetic Colonoscopy: A Randomized Controlled Trial.

BACKGROUND: Colonoscopy is essential for diagnosing colorectal diseases but can cause pain during the procedure. This study explores the analgesic effects of Transcutaneous Electrical Nerve Stimulation based on Wrist-Ankle Acupuncture theory (TENS-WAA) in non-anesthetic colonoscopy. METHODS: This prospective study included 120 participants undergoing non-anesthetic colonoscopies. The trial group receiving low-frequency, high-intensity TENS-WAA adjusted to the maximum tolerable current, while the control group received minimal current. Primary outcome was the retrospective pain VAS score. Secondary outcomes included time, heart rate, and credibility/expectancy questionnaire (CEQ) scores (ChiCTR2300076524). RESULTS: Participants who received TENS-WAA intervention reported significantly lower pain VAS scores than the control group (estimated median difference -1.1, 95% CI: -2 to -0.4, P=0.002). Male participants in the trial group experienced significantly lower pain scores than the control group (mean difference -1.4, 95% CI: -2.41 to -0.39, P=0.008). Additionally, the trial group also had significantly lower heart rates (P<0.001) and higher CEQ scores (P=0.001) than the control group. No adverse events were reported. CONCLUSION: TENS-WAA effectively reduces pain during non-anesthetized colonoscopy, especially in male participants, providing a promising non-invasive analgesic method.

Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.

INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.

Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.

Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

Comparative Analysis of Volatile Compounds in the Flower Buds of Three Panax Species Using Fast Gas Chromatography Electronic Nose, Headspace-Gas Chromatography-Ion Mobility Spectrometry, and Headspace Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

The flower buds of three Panax species (PGF: P. ginseng; PQF: P. quinquefolius; PNF: P. notoginseng) widely consumed as health tea are easily confused in market circulation. We aimed to develop a green, fast, and easy analysis strategy to distinguish PGF, PQF, and PNF. In this work, fast gas chromatography electronic nose (fast GC e-nose), headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were utilized to comprehensively analyze the volatile organic components (VOCs) of three flowers. Meanwhile, a principal component analysis (PCA) and heatmap were applied to distinguish the VOCs identified in PGF, PQF, and PNF. A random forest (RF) analysis was used to screen key factors affecting the discrimination. As a result, 39, 68, and 78 VOCs were identified in three flowers using fast GC e-nose, HS-GC-IMS, and HS-SPME-GC-MS. Nine VOCs were selected as potential chemical markers based on a model of RF for distinguishing these three species. Conclusively, a complete VOC analysis strategy was created to provide a methodological reference for the rapid, simple, and environmentally friendly detection and identification of food products (tea, oil, honey, etc.) and herbs with flavor characteristics and to provide a basis for further specification of their quality and base sources.

Therapeutic potential of enzymatically extracted eumelanin from squid ink in type 2 diabetes mellitus ICR mice: Multifaceted intervention against hyperglycemia, oxidative stress and depression.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that poses significant health risks due to its numerous complications. However, the effects of eumelanin on oxidative stress, hyperglycemia and depression in diabetic mice have not been extensively studied. RESULTS: Our study employed an enzymatic approach to extract eumelanin from squid ink and characterized it using spectroscopic techniques. Remarkably, eumelanin extracted with alkaline-neutral-flavor protease (ANF) displayed superior inhibitory activity against α-glucosidase and α-amylase, while enhancing glucose utilization and hepatic glycogen synthesis in human hepatocellular carcinoma cell line (HepG2) insulin resistance model. Further evaluation of ANF in a T2DM ICR mouse model demonstrated its significant potential in alleviating hyperglycemia, reducing glycosylated serum protein levels, improving glucose tolerance and modulating total cholesterol and low-density lipoprotein levels, as well as antioxidant indices at a dosage of 0.04 g kg-1 . Additionally, ANF exhibited positive effects on energy levels and reduced immobility time in antidepressant behavioral experiments. Moreover, ANF positively influenced the density and infiltration state of renal cells, while mitigating inflammatory enlargement and deformation of liver cells, without inducing any adverse effects in mice. CONCLUSION: Overall, these findings underscore the significant therapeutic potential of ANF in the treatment of T2DM and its associated complications. By augmenting lipid and glucose metabolism, mitigating oxidative stress and alleviating depression, ANF emerges as a promising candidate for multifaceted intervention. © 2023 Society of Chemical Industry.

Differences in rice component distribution across layers and their relationship with taste.

BACKGROUND: Rice taste is closely associated with endosperm composition, which varies among different rice layers. Although clarifying the relationship between this difference and nutritional taste can guide rice breeding and cultivation practices, research on this topic is limited. RESULTS: Here, typical rice varieties having excellent and poor taste characteristics were selected to analyze the distribution characteristics and differences of their components. The varieties with excellent taste exhibited lower apparent amylose content (AAC) and protein content (PC), lesser short-chain (Fa) and long-chain (Fb3 ) amylopectin (AP) and more medium-chain (Fb1+2 ) AP, higher long-to-short chain ratio (Fa:Fb3 ), and higher nitrogen (N), magnesium (Mg) and calcium (Ca) content in layer 1 (L1) than the varieties with poor taste. Layer 2 (L2) played a key role in AAC and PC regulation in the varieties with excellent taste by reducing AAC and appropriately increasing PC, consequently improving rice taste. AP structure in layer 3 (L3) substantially affected the taste of the two types of varieties. The mineral content was the highest in L1, and increased potassium (K), Ca, and Mg content improved taste in all varieties. CONCLUSION: AAC in each layer contributes to rice taste. PC and minerals primarily act on L1 and L2, whereas AP acts on L2 and L3. Therefore, the endosperm formation process should be exploited for improving rice taste. Furthermore, key resources and cultivation should be identified and regulated, respectively, to improve rice taste. © 2023 Society of Chemical Industry.