25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages.

Macrophages are critical to turn noninflamed "cold tumors" into inflamed "hot tumors". Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25Hhi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8+ T cell surveillance and anti-tumor response.

Synthesis and Reduction Processes of Silver Nanowires in a Silver(I) Sulfamate-Poly (Vinylpyrrolidone) Hydrothermal System.

Silver (Ag) nanowires, as an important one-dimensional (1D) nanomaterial, have garnered wide attention, owing to their applications in electronics, optoelectronics, sensors, and other fields. In this study, an alternative hydrothermal route was developed to synthesize Ag nanowires via modified reduction of Ag+. Silver sulfamate plays an important role in the formation of Ag nanowires via controlled release of free Ag+. Results of controlled experiments and characterizations such as UV-vis spectroscopy, FTIR, XPS, and 1H NMR revealed that sulfamic acid does not function as a reductant, supporting by the generation of free Ag+ instead of Ag nanostructures in hydrothermally treated silver sulfamate solution. The initial reduction of Ag+ was induced by the combination of poly (vinylpyrrolidone) (PVP) end group and degradation products. This phenomenon was supported by abundant free Ag+ in the mixed preheated silver sulfamatic and preheated PVP aqueous solutions, indicating a second and distinct Ag+ autocatalytic reduction. Thus, the roles of different reagents and Ag+ reduction must be studied for nanomaterial syntheses.

Quantitative evaluation of the proximal contact area gap change characterization under intercuspal occlusion by intraoral 3D scanning: Food impaction with tight proximal contact.

OBJECTIVE: This study aimed to present three indicators that represent the proximal contact area gap change under intercuspal occlusion and to see if and how these indicators influence food impaction with tight proximal contact. MATERIALS AND METHODS: Ninety volunteers were recruited for bite force measurement and intraoral scanning. Three-dimensional surface data and buccal bite data were obtained for 60 impacted and 60 non-impacted teeth. The scanning data were imported into the Geomagic Studio 2013 to measure three indicators, which included the gap change maximum (Δdm, µm), the buccolingual position of Δdm (P), and the gap expanded buccolingual range (S, mm). The difference between two groups of three indicators and their relationship with food impaction with tight proximal contact were analyzed by the t test, the Pearson chi-squared test, the nonparametric Mann-Whitney U test, and the binary logistic regression analysis (a = 0.05). RESULTS: All indicators (Δdm, P, and S) were statistically different (p < 0.001, p = 0.002, and p < 0.001) in the impacted and non-impacted groups. Food impaction with tight proximal contact was affected by Δdm and S (p < 0.001, p = 0.039), but not by P (p = 0.409). CONCLUSION: The excessive increase of the gap change maximum and the gap expanded buccolingual range under bite force promoted the occurrence of food impaction with tight proximal contact. CLINICAL SIGNIFICANCE: The use of intraoral scanning to measure the characteristics of the proximal contact area gap change under bite force may help to deepen our understanding of the pathogenesis of food impaction with tight proximal contact. Importantly it can provide a reference basis for individualizing and quantifying occlusal adjustment treatment.

Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects.

Neural tube defects (NTDs) are severe malformations of the central nervous system that arise from failure of neural tube closure. HECTD1 is an E3 ubiquitin ligase required for cranial neural tube closure in mouse models. NTDs in the Hectd1 mutant mouse model are due to the failure of cranial mesenchyme morphogenesis during neural fold elevation. Our earlier research has linked increased extracellular heat shock protein 90 (eHSP90) secretion to aberrant cranial mesenchyme morphogenesis in the Hectd1 model. Furthermore, overexpression of HECTD1 suppresses stress-induced eHSP90 secretion in cell lines. In this study, we report the identification of five rare HECTD1 missense sequence variants in NTD cases. The variants were found through targeted next-generation sequencing in a Chinese cohort of 352 NTD cases and 224 ethnically matched controls. We present data showing that HECTD1 is a highly conserved gene, extremely intolerant to loss-of-function mutations and missense changes. To evaluate the functional consequences of NTD-associated missense variants, functional assays in HEK293T cells were performed to examine protein expression and the ability of HECTD1 sequence variants to suppress eHSP90 secretion. One NTD-associated variant (A1084T) had significantly reduced expression in HEK293T cells. All five NTD-associated variants (p.M392V, p.T801I, p.I906V, p.A1084T, and p.P1835L) reduced regulation of eHSP90 secretion by HECTD1, while a putative benign variant (p.P2474L) did not. These findings are the first association of HECTD1 sequence variation with NTDs in humans.

P. gingivalis alters lung microbiota and aggravates disease severity of COPD rats by up-regulating Hsp90α/MLKL.

Background: Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and Results: A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated. Conclusion: These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

Closed Reduction for the Treatment of Traumatic Thoracolumbar Spondylolisthesis.

OBJECTIVE: Thoracolumbar traumatic spondylolisthesis is a relatively rare phenomenon and has poor prognosis due to serious spinal cord or cauda equina injuries. In such cases, closed reduction is a method for restoring the vertebral sequence and may play an important role in the treatment process, although whether it is actually feasible for patients with this condition requires further investigation. The present study included 9 patients with serious thoracolumbar traumatic spondylolisthesis to determine the advantages of closed reduction over total reduction through open surgery. METHODS: Data from 9 patients (cases 1-9), diagnosed with severe thoracolumbar traumatic spondylolisthesis between June 2012 and August 2023, were retrospectively reviewed. Five patients were treated with closed reduction in an emergency department and subsequently underwent delayed internal fixation surgery at least 48 hours after the injury, and 4 with similar serious injuries underwent emergency surgery. The incidence of complications and recovery of the spinal cord or cauda equina were compared between groups. RESULTS: There were no significant differences in demographic characteristics or adverse events between the 2 groups. The reduction group had a shorter surgical duration and less blood loss than the surgery group. Although patients in the surgery group may have experienced more pain, there were no significant differences between the groups in Oswestry Disability Index or Japanese Orthopaedic Association scores. Thus, regardless of whether closed reduction was chosen, patients experienced a similar quality of life for a relatively prolonged period. CONCLUSIONS: Closed reduction may be feasible for serious thoracolumbar traumatic spondylolisthesis, although the safety of this method requires further research.

Effectiveness of web-based interventions for women with urinary incontinence: protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Urinary incontinence (UI) is one of the most common chronic diseases among women, which can endanger their physical and mental health and incur a heavy financial burden on both individuals and society. Web-based interventions (WBIs) have been applied to manage women's UI, but their effectiveness has remained inconclusive. This systematic review and meta-analysis aims to explore the effectiveness of WBIs on self-reported symptom severity, condition-specific quality of life, adherence to pelvic floor muscle training (primary outcomes) and other extensive secondary outcomes among women with UI. We also aimed to investigate whether intervention characteristics (format, interactivity and main technology) have impacts on the effectiveness of primary outcomes. METHODS AND ANALYSIS: This systematic review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. 10 electronic databases will be comprehensively searched from their inception to 1 May 2024, along with grey literature searches and manual reviews of relevant reference lists to identify eligible randomised controlled trials. The methodological quality of the included studies will be assessed by two reviewers based on the Cochrane Risk of Bias Tool. Meta-analyses will be conducted via Stata V.12.0. Leave-one-out sensitivity analyses will be performed, and publication bias will be evaluated using funnel plots and Egger's test. Subgroup analyses regarding intervention format, interactivity and main technology will be carried out. ETHICS AND DISSEMINATION: No ethics approval is needed for this review since no primary data are to be collected. The results of this review will help develop an optimal WBI for women with UI, thereby providing them with maximum benefits. The findings will be disseminated via a peer-reviewed journal or conference presentation. PROSPERO REGISTRATION NUMBER: CRD42023435047.

Large Yellow Tea Polysaccharide Alleviates HFD-Induced Intestinal Homeostasis Dysbiosis via Modulating Gut Barrier Integrity, Immune Responses, and the Gut Microbiome.

Long-term high-fat diet (HFD) will induce dysbiosis and a disturbance of intestinal homeostasis. Large yellow tea polysaccharide (LYP) has been shown to improve obesity-associated metabolic disease via modulation of the M2 polarization. However, the contribution of LYP to intestinal barrier impairment and improvement mechanisms in obesity caused by an HFD are still not clear. In this study, we evaluated the impacts of LYP on the mucosal barrier function and microbiota composition in HFD-feeding mice. Results exhibited that dietary LYP supplement could ameliorate the physical barrier function via maintaining intestinal mucosal integrity and elevating tight-junction protein production, strengthen the chemical barrier function via up-regulating the levels of glucagon-like peptide-1 and increasing mucin-producing goblet cell numbers, and enhance the intestinal immune barrier function though suppressing immune cell subsets and cytokines toward pro-inflammatory phenotypes. Moreover, LYP reshaped the constitution and metabolism of intestinal flora by enriching probiotics that produce short-chain fatty acids. Overall, LYP might be used as a critical regulator of intestinal homeostasis to improve host health by promoting gut barrier integrity, modulating intestinal immune response, and inhibiting bowel inflammation.

Sonographic characteristics of diffuse sclerosing variant of papillary thyroid carcinoma with histopathological correlation: a preliminary study.

BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is a rare but high invasive subtype of papillary thyroid carcinoma, which mandates an aggressive clinical strategy. Few studies have focused on the sonographic characteristics of DSVPTC and the role of ultrasound in diagnosis and treatment of this variant remains unknown. This study aimed to identify and understand DSVPTC more accurately under ultrasound in correlation with pathology. METHODS: The ultrasound characteristics and histopathologic sections of 10 lesions in 10 DSVPTC patients who underwent thyroid surgery at our center between 2014 and 2020 were reviewed and compared with 184 lesions in 168 classic variant of papillary thyroid carcinoma (cPTC) patients. RESULTS: 6 DSVPTC cases (60%) showed the "snowstorm" pattern on sonogram and 4 cases (40%) presented hypoechoic solid nodules only. Vague borders (100.0% vs. 18.5%, P = 0.019) and abundant microcalcifications (66.7% vs. 10.9%, P = 0.037) were more common in DSVPTC nodules than in cPTC nodules, corresponding to the infiltrating boundaries and numerous psammoma bodies under the microscope respectively. Most of the DSVPTC cases had a heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) on sonograms. All DSVPTC cases had histopathological metastatic cervical lymph nodes. CONCLUSION: The sonographic "snowstorm" pattern indicated DSVPTC with whole-lobe occupation. Hypoechoic solid nodules with vague borders and abundant microcalcifications on sonogram suggested DSVPTC lesion with an ongoing invasion. Regardless of which of the two sonograms was shown, the corresponding DSVPTC lesions were aggressive and required the same attention from the surgeons.

Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype.

JOURNAL/nrgr/04.03/01300535-202419110-00029/figure1/v/2024-03-08T184507Z/r/image-tiff Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE-/- mice. However, little is known about the role of lnc_000048 in classically activated macrophage (M1) polarization. In this study, we established THP-1-derived testing state macrophages (M0), M1 macrophages, and alternately activated macrophages (M2). Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages. Flow cytometry was used to detect phenotypic proteins (CD11b, CD38, CD80). We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048. Flow cytometry, western blot, and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response, while over-expression of lnc_000048 led to the opposite effect. Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization. Moreover, catRAPID prediction, RNA-pull down, and mass spectrometry were used to identify and screen the protein kinase RNA-activated (PKR), then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR. Immunofluorescence (IF)-RNA fluorescence in situ hybridization (FISH) double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage. We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation, leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression. Taken together, these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

Improvement in the quality and productivity of Codonopsis pilosula seedlings by dazomet soil fumigation.

Dazomet is a dry powder formulation that releases toxic gas containing methyl isothiocyanate, which controls soil-borne pests and weeds, improving crop yields when applied to moist soils. To explore the efficacy of dazomet fumigation in the cultivation of the perennial herb Codonopsis pilosula, four typical cultivars (G1, G2, W1 and TCK) in Gansu Province were selected for seedling cultivation after soil fumigation (F) by dazomet, and non-fumigated soil was used as a control (CK). The experiments took 2 years to complete. The functional diversity of the soil enzymes and microorganisms, seedling emergence and physiological characteristics, and the quality and yield of Codonopsis seedlings and Radix were assessed. The results showed that the seed emergence rate, seedling re-green rate and several antioxidant enzymatic activities improved in the treatments involving soil fumigation with dazomet, and membrane lipid peroxidation in the seedlings decreased. On average, compared with those of the respective controls, the root viability and yield of the seedlings of the tested cultivars also increased by 34.87% and 42.4%, respectively, and the incidence of root rot in the seedlings was reduced by 83.9%, compared with their respective controls. After harvest, the yield increased by 23.9%, the incidence of root rot decreased by 61.3%, increase in yield and a 61.3% reduction in incidence, and the medicinal materials were determined to be safe and residue-free. The effects of fumigation were cultivar-specific and were especially prominent in G2. Therefore, soil fumigation with dazomet could improve the quality and productivity of Codonopsis pilosula seedlings. Taken together, these findings suggest that when herbs are bred by seedling transplantation, especially cultivars of good quality but poor resistance or species with rare germplasm resources, soil fumigation provides a way to improve cultivation effectiveness and, more importantly, ensures the probability of successfully breeding the species.

Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity.

According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA-ERK1/2-ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA-treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

The prognostic values of estimating intraperitoneal pressure in the occurrence of abdominal wall complications in peritoneal dialysis patients.

BACKGROUND: Increased intraperitoneal pressure is associated with abdominal wall complications and technical failure of peritoneal dialysis (PD). Several equations have been developed to estimate intraperitoneal pressure. We aimed to assess the prognostic yield of the intraperitoneal pressure as estimated by current equations on the occurrence of abdominal wall complications in peritoneal dialysis patients. METHODS: This is a retrospective analysis of data from a prospective cohort which recruited 1207 incident PD patients. Estimated intraperitoneal pressure was calculated using four available equations (according to Sigogne, Castellanos, Scanziani and de Jesus Ventura). Abdominal wall complications were recorded during follow-up. Univariate analysis and multivariate analysis with competing risk regression were used to assess the predictive power of the estimates of intraperitoneal pressure in the occurrence of abdominal wall complications. RESULTS: During a median follow-up of 30 months, 66 (5.5%) patients (1.6/100 patient-years) developed abdominal wall complications. The median time to the occurrence of abdominal wall complications was 5.7 months. Only the estimated intraperitoneal pressure by the de Jesus Ventura equation significantly predicted abdominal wall complications by using univariate analyses. Associations between estimated intraperitoneal pressure by the de Jesus Ventura equation and the occurrence of abdominal wall complications disappeared after adjusting for significant clinical factors. CONCLUSIONS: We verified the prognostic value of estimation of intraperitoneal pressure by four available equations in predicting abdominal wall complications in our single-center PD cohort. Due to a low diagnostic yield, a novel equation for estimating the intraperitoneal pressure is urgently needed.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease in the world. Immunity is the major contributing factor in NAFLD; however, the interaction of immune cells and hepatocytes in disease progression has not been fully elucidated. As a popular species for studying NAFLD, zebrafish, whose liver is a complex immune system mediated by immune cells and non-immune cells in maintaining immune tolerance and homeostasis. Understanding the cellular composition and immune environment of zebrafish liver is of great significance for its application in NAFLD. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing (scRNA-seq). By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two subtypes of distinct resident macrophages with inflammatory and non-inflammatory functions and characterized the successive stepwise development of T cell subclusters in the liver. Importantly, we uncovered the possible regulation of macrophages and T cells on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for an in-depth study of immune cells targeting hepatocytes to regulate the immune balance in NAFLD.

Deep-learning-based renal artery stenosis diagnosis via multimodal fusion.

PURPOSE: Diagnosing Renal artery stenosis (RAS) presents challenges. This research aimed to develop a deep learning model for the computer-aided diagnosis of RAS, utilizing multimodal fusion technology based on ultrasound scanning images, spectral waveforms, and clinical information. METHODS: A total of 1485 patients received renal artery ultrasonography from Peking Union Medical College Hospital were included and their color doppler sonography (CDS) images were classified according to anatomical site and left-right orientation. The RAS diagnosis was modeled as a process involving feature extraction and multimodal fusion. Three deep learning (DL) models (ResNeSt, ResNet, and XCiT) were trained on a multimodal dataset consisted of CDS images, spectrum waveform images, and individual basic information. Predicted performance of different models were compared with senior physician and evaluated on a test dataset (N = 117 patients) with renal artery angiography results. RESULTS: Sample sizes of training and validation datasets were 3292 and 169 respectively. On test data (N = 676 samples), predicted accuracies of three DL models were more than 80% and the ResNeSt achieved the accuracy 83.49% ± 0.45%, precision 81.89% ± 3.00%, and recall 76.97% ± 3.7%. There was no significant difference between the accuracy of ResNeSt and ResNet (82.84% ± 1.52%), and the ResNeSt was higher than the XCiT (80.71% ± 2.23%, p < 0.05). Compared to the gold standard, renal artery angiography, the accuracy of ResNest model was 78.25% ± 1.62%, which was inferior to the senior physician (90.09%). Besides, compared to the multimodal fusion model, the performance of single-modal model on spectrum waveform images was relatively lower. CONCLUSION: The DL multimodal fusion model shows promising results in assisting RAS diagnosis.

Telomere-to-telomere gapless genome assembly of the Chinese sea bass (Lateolabrax maculatus).

Chinese sea bass (Lateolabrax maculatus) is a highly sought-after commercial seafood species in Asian regions due to its excellent nutritional value. With the rapid advancement of bioinformatics, higher standards for genome analysis compared to previously published reference genomes are now necessary. This study presents a gapless assembly of the Chinese sea bass genome, which has a length of 632.75 Mb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (626.61 Mb), and telomeres were detected on 34 chromosome ends. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 54.25. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study also identified repeating elements in 20.90% (132.25 Mb) of the genome and inferred 22,014 protein-coding genes. These results establish meaningful groundwork for exploring the evolution of the Chinese sea bass genome and advancing molecular breeding techniques.

Mechanism of interaction between L-theanine and maize starch in ultrasonic field based on DFT calculations: Rheological properties, multi-scale structure and in vitro digestibility.

The digestibility of starch-based foods is receiving increased attention. To date, the full understanding of how including L-theanine (THE) can modify the structural and digestive properties of starch has not been fully achieved. Here, we investigated the multi-scale structure and digestibility of maize starch (MS) regulated by THE in ultrasound field and the molecular interactions. Ultrasound disrupted the structure of starch granules and opened the molecular chains of starch, promoting increased THE binding and producing more low-order or disordered crystal structures. In this case, the aggregation of starch molecules, especially amylose, was reduced, leading to increased mobility of the systems. As a result, the apparent viscosity, G', and G" were significantly decreased, which retarded the starch regeneration. Density functional theory calculations indicated that there were mainly non-covalent interactions between THE and MS, such as hydrogen bonding and van der Waals forces. These interactions were the main factors contributing to the decrease in the short-range ordering, the helical structure, and the enthalpy change (ΔH) of MS. Interestingly, the rapidly digestible starch (RDS) content of THE modified MS (MS-THE-30) decreased by 17.89 %, while the resistant starch increased to 26.65 %. These results provide new strategies for the safe production of resistant starch.

DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response.

Detection of cytosolic nucleic acids by pattern recognition receptors, including STING and RIG-I, leads to the activation of multiple signalling pathways that culminate in the production of type I interferons (IFNs) which are vital for host survival during virus infection. In addition to protective immune modulatory functions, type I IFNs are also associated with autoimmune diseases. Hence, it is important to elucidate the mechanisms that govern their expression. In this study, we identified a critical regulatory function of the DUSP4 phosphatase in innate immune signalling. We found that DUSP4 regulates the activation of TBK1 and ERK1/2 in a signalling complex containing DUSP4, TBK1, ERK1/2 and IRF3 to regulate the production of type I IFNs. Mice deficient in DUSP4 were more resistant to infections by both RNA and DNA viruses but more susceptible to malaria parasites. Therefore, our study establishes DUSP4 as a regulator of nucleic acid sensor signalling and sheds light on an important facet of the type I IFN regulatory system.