Dendrobium officinale Kimura et Migo polysaccharide ameliorated DNFB-induced atopic dermatitis in mice associated with suppressing MAPK/NF-κB/STAT3 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura et Migo as a valuable Chinese medicine has been used in China for more than 2000 years. Its main active components, polysaccharide (DOP), has been reported to have various pharmacological effects, including anti-inflammatory, antioxidant and alleviating AD effects. However, the precise mechanism underlying its therapeutic effect in AD remains largely unclear. AIM OF THE STUDY: The present study sought to assess the efficacy of DOP and elucidate its intricate mechanisms in ameliorating DNFB-induced AD. MATERIALS AND METHODS: Mice were sensitized with DNFB and treated with DOP application for 14 days. Treatment effects were assessed using dermatitis scores, ear thickness and scratching frequency. Epidermal thickness, mast cells and CD4+ T cells infiltration were detected by using H&E, toluidine blue staining and immunofluorescence staining respectively. Serum histamine (HIS), immunoglobulin E (IgE), thymic stromal lymphopoietin (TSLP), skin SOD, MDA, GHS, CAT, inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-4, IL-5, IL-13) and chemokine (MIP-α, MDC, MCP-1) levels were quantify by ELISA and immunohistochemistry. Additionally, qPCR and Western blot analyses were performed to assess genes and proteins expression associated with MAPK/NF-κB/STAT3 signaling pathway. RESULTS: The results indicated that DOP effectively mitigated AD-like skin lesions in mice through multiple pathways. It reduced epidermal thickness, ear thickness and scratching frequency in AD mice. Additionally, DOP mitigated inflammatory responses by decreasing the levels of inflammatory factors, as well as reducing serum levels of IgE, HIS, and TSLP. Moreover, DOP inhibited infiltration of mast cells and CD4+ T cells, suppressed the expression of skin chemokines such as MDC, MCP-1, and MIP-α, and enhanced filaggrin content in AD mice. Furthermore, DOP significantly boosted antioxidant capacity, as well as significantly reduced the expression of JAK1, STAT3, NF-κB p65, IκBα, ERK1/2, and p38 proteins and phosphorylated proteins such as p-JAK1, p-STAT3, p-NF-κB p65, p-IκBα, p-ERK1/2, and p-p38. CONCLUSIONS: These findings suggested that DOP has significant anti-AD activity, primarily through reducing inflammatory responses, improving antioxidant capacity, repairing the skin barrier, and down-regulating key genes and proteins in MAPK/NF-κB/STAT3 signaling pathway, and that this study may provide valuable insights into the development of innovative therapies for the treatment of AD.

IL-33 released during challenge phase regulates allergic asthma in an age-dependent way.

Epithelial-derived cytokines, especially type 2 alarmins (TSLP, IL-25, and IL-33), have emerged as critical mediators of type 2 inflammation. IL-33 attracts more interest for its strong association with allergic asthma, especially in childhood asthma. However, the age-dependent role of IL-33 to the development of allergic asthma remains elusive. Here, using OVA-induced allergic asthma model in neonatal and adult mice, we report that IL-33 is the most important alarmin in neonatal lung both at steady state or inflammation. The deficiency of IL-33/ST2 abrogated the development of allergic asthma only in neonates, whereas in adults the effect was limited. Interestingly, the deficiency of IL-33/ST2 equally dampened the ILC2 responses in both neonatal and adult models. However, the effect of IL-33/ST2 deficiency on Th2 responses is age-dependent, which is only blocked in neonates. Furthermore, IL-33/ST2 signaling is dispensable for OVA sensitization. Following OVA challenge in adults, the deficiency of IL-33/ST2 results in compensational more TSLP, which in turn recruits and activates lung DCs and boosts Th2 responses. The enriched γδ T17 cells in IL-33/ST2 deficient neonatal lung suppress the expression of type 2 alarmins, CCL20 and GM-CSF via IL-17A, thus might confer the inhibition of allergic asthma. Finally, on the basis of IL-33 deficiency, the additive protective effects of TSLP blocking is much more pronounced than IL-25 blocking in adults. Our studies demonstrate that the role of IL-33 for ILC2 and Th2 responses varies among ages in OVA models and indicate that the factor of age should be considered for intervention of asthma.

A Novel Therapeutic Calcium Peroxide Loaded Injectable Bio-adhesive Hydrogel Against Periodontitis.

OBJECTIVES: Periodontitis is a prevalent oral disease that can significantly impact patients' life quality and systemic health. However, non-surgical subgingival scaling is largely compromised due to poor patient compliance, leading to a high recurrence rate of periodontitis. Therefore, this research aims to explore new approaches to enhance the effectiveness of existing local drug administration therapies. MATERIALS AND METHODS: Gelatin-oxidized dextran hydrogel loaded with calcium peroxide and penicillin (CP-P hydrogel) was synthesized and characterized using Universal mechanical testing machine, Fourier transform infrared spectroscopy, swelling test, and dissolved oxygen meter. Furthermore, the cytotoxicity, osteogenic ability, antibacterial behavior, and alveolar bone regenerating capability of CP-P hydrogel were conducted both in vitro and in vivo. RESULTS: The CP-P hydrogel demonstrated excellent mechanical properties, minimal swelling, and ideal biocompatibility. It created more favorable environments in the periodontal pocket by reversing anaerobic environment, eliminating drug-resistant bacteria and enhancing the therapeutic potency of drugs. By continuously releasing drugs in the periodontal pocket, the CP-P hydrogel effectively inhibited bacteria and reduce local inflammation response. In addition to bacteriostatic effects, the CP-P hydrogel also promoted the expression of osteogenic genes and enhanced osteogenic differentiation of PDLSCs in vitro. CONCLUSIONS: CP-P hydrogel can be developed as a new therapeutic platform to enhance the effectiveness of local drug administration strategy against periodontitis.

Point-of-care Testing HbA1c screening for type 2 diabetes in urban and rural areas of China: a cost-effectiveness analysis.

Background: Point-of-care Testing (POCT) glycosylated hemoglobin (HbA1c) is a convenient, cheap, effective and accessible screening method for type 2 diabetes in rural areas and community settings that is widely used in the European region and Japan, but not yet widespread in China. The study is the first to evaluate the cost-effectiveness of POCT HbA1c, fasting capillary glucose (FCG), and venous blood HbA1c to screen for type 2 diabetes in urban and rural areas of China, and to identify the best socio-economically beneficial screening strategy. Methods: Based on urban and rural areas in China, economic models for type 2 diabetes screening were constructed from a social perspective. The subjects of this study were adults aged 18-80 years with undiagnosed type 2 diabetes. Three screening strategies were established for venous blood HbA1c, FCG and POCT HbA1c, and cost-effectiveness analysis was performed by Markov models. One-way sensitivity analysis and probabilistic sensitivity analysis were performed on all parameters of the model to verify the stability of the results. Results: Compared with FCG, POCT HbA1c was cost-effective with an incremental cost-utility ratio (ICUR) of $500.06/quality-adjusted life year (QALY) in urban areas and an ICUR of $185.10/QALY in rural areas, within the willingness-to-pay threshold (WTP = $37,653). POCT HbA1c was cost-effective with lower cost and higher utility compared with venous blood HbA1c in both urban and rural areas. In the comparison of venous blood HbA1c and FCG, venous blood HbA1c was cost-effective (ICUR = $20,833/QALY) in urban areas but not in rural areas (ICUR = $41,858/QALY). Sensitivity analyses showed that the results of the study were stable and credible. Conclusions: POCT HbA1c was cost-effective for type 2 diabetes screening in both urban and rural areas of China, which could be considered for future clinical practice in China. Factors such as geographic location, local financial situation and resident compliance needed to be considered when making the choice of venous blood HbA1c or FCG.

The ß-d-manno-heptoses are immune agonists across kingdoms.

Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-ß-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the ß-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.

Finite immune imprinting on neutralizing antibody responses to Omicron subvariants by repeated vaccinations.

OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

IGF2BP3 participates in the pathogenesis of recurrent spontaneous abortion by regulating ferroptosis.

The aberrant invasive capability of trophoblast cells is widely acknowledged as a primary mechanism underlying RSA. Recently, IGF2BP3 has been implicated in various cancers due to its influence on cellular invasion and migration. However, whether IGF2BP3 involve in the occurrence of RSA and the specific functions it assumes in the development of RSA remain elusive. In our study, we firstly collected villous tissues from RSA and those with normal pregnancies individuals to performed Protein sequencing and then detected the expression of IGF2BP3 through Western blot, qRT-PCR and immunohistochemistry. Secondly, we analyzed the single-cell data (GSE214607) to assess the expression of IGF2BP3 in invasive EVT trophoblasts. Thirdly, we utilized lentivirus technology to establish HTR-8/SVneo cell lines with stable IGF2BP3 knockdown and RNA-seq analysis was employed to investigate the GO functional pathway enrichment of IGF2BP3. Meanwhile, the effect of IGF2BP3 knockdown on trophoblast cells apoptosis, migration, and ferroptosis was evaluated through functional experiments. Additionally, LPS-induced abortion animal model was constructed to evaluate IGF2BP3 expression in placental tissues. A significant downregulation of IGF2BP3 was observed in the villous tissues of RSA patient, a finding corroborated by subsequent single cell sequencing results. Furthermore, it suggested that IGF2BP3 may be involved in the migration and apoptotic processes of trophoblast cells. Mechanistic research indicated that IGF2BP3 knockdown could compromise GPX4 mRNA stability, leading to the promotion of ferroptosis. Finally, our investigation observed the down-regulation of IGF2BP3 expression in placental villous tissues of an LPS-induced abortion animal model. Our findings revealed that IGF2BP3 was downregulated in the villous tissues of RSA patients. Mechanically, down-regulation of IGF2BP3 may induce RSA by promoting GPX4-mediated ferroptosis and inhibiting trophoblast invasion and migration. Our study may provide new targets and research directions for the pathogenesis of RSA.

Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

Efficacy, acceptability and tolerability of second-generation antipsychotics for behavioural and psychological symptoms of dementia: a systematic review and network meta-analysis.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown. METHODS: The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms. RESULTS: Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=-1.77, 95% CI -2.80 to -0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs. CONCLUSION: Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.

A Robust Induced Fit Docking Approach with the Combination of the Hybrid All-Atom/United-Atom/Coarse-Grained Model and Simulated Annealing.

Molecular docking remains an indispensable tool in computational biology and structure-based drug discovery. However, the correct prediction of binding poses remains a major challenge for molecular docking, especially for target proteins where a substrate binding induces significant reorganization of the active site. Here, we introduce an Induced Fit Docking (IFD) approach named AA/UA/CG-SA-IFD, which combines a hybrid All-Atom/United-Atom/Coarse-Grained model with Simulated Annealing. In this approach, the core region is represented by the All-Atom(AA) model, while the protein environment beyond the core region and the solvent are treated with either the United-Atom (UA) or the Coarse-Grained (CG) model. By combining the Elastic Network Model (ENM) for the CG region, the hybrid model ensures a reasonable description of ligand binding and the environmental effects of the protein, facilitating highly efficient and reliable sampling of ligand binding through Simulated Annealing (SA) at a high temperature. Upon validation with two testing sets, the AA/UA/CG-SA-IFD approach demonstrates remarkable accuracy and efficiency in induced fit docking, even for challenging cases where the docked poses significantly deviate from crystal structures.

The research status and future direction of polyetheretherketone in dental implant -A comprehensive review.

Currently, dental implants primarily rely on the use of titanium and titanium alloys. However, the extensive utilization of these materials in clinical practice has unveiled various problems including stress shielding, corrosion, allergic reactions, cytotoxicity, and image artifacts. As a result, polyetheretherketone (PEEK) has emerged as a notable alternative due to its favorable mechanical properties, corrosion resistance, wear resistance, biocompatibility, radiation penetrability and MRI compatibility. Meanwhile, the advancement and extensive application of 3D printing technology has expanded the range of medical applications for PEEK, including artificial spines, skulls, ribs, shinbones, hip joints, and temporomandibular joints. In this review, we aim to assess the advantages and disadvantages of PEEK as a dental implant material, summarize the measures taken to address its shortcomings and their effects, and provide insight into the future potential of PEEK in dental implant applications, with the goal of offering guidance and reference for future research endeavors.

Spin states of metal centers in electrocatalysis.

Understanding the electronic structure of active sites is crucial in efficient catalyst design. The spin state, spin configurations of d-electrons, has been frequently discussed recently. However, its systematic depiction in electrocatalysis is lacking. In this tutorial review, a comprehensive interpretation of the spin state of metal centers in electrocatalysts and its role in electrocatalysis is provided. This review starts with the basics of spin states, including molecular field theory, crystal field theory, and ligand field theory. It further introduces the differences in low spin, intermediate spin, and high spin, and intrinsic factors affecting the spin state. Popular characterization techniques and modeling approaches that can reveal the spin state, such as X-ray absorption microscopy, electron spin resonance spectroscopy, Mössbauer spectroscopy, and density functional theory (DFT) calculations, are introduced as well with examples from the literature. The examples include the most recent progress in tuning the spin state of metal centers for various reactions, e.g., the oxygen evolution reaction, oxygen reduction reaction, hydrogen evolution reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, nitrate reduction reaction, and urea oxidation reaction. Challenges and potential implications for future research related to the spin state are discussed at the end.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

Equol: a metabolite of gut microbiota with potential antitumor effects.

An increasing number of studies have shown that the consumption of soybeans and soybeans products is beneficial to human health, and the biological activity of soy products may be attributed to the presence of Soy Isoflavones (SI) in soybeans. In the intestinal tracts of humans and animals, certain specific bacteria can metabolize soy isoflavones into equol. Equol has a similar chemical structure to endogenous estradiol in the human body, which can bind with estrogen receptors and exert weak estrogen effects. Therefore, equol plays an important role in the occurrence and development of a variety of hormone-dependent malignancies such as breast cancer and prostate cancer. Despite the numerous health benefits of equol for humans, only 30-50% of the population can metabolize soy isoflavones into equol, with individual variation in gut microbiota being the main reason. This article provides an overview of the relevant gut microbiota involved in the synthesis of equol and its anti-tumor effects in various types of cancer. It also summarizes the molecular mechanisms underlying its anti-tumor properties, aiming to provide a more reliable theoretical basis for the rational utilization of equol in the field of cancer treatment.

The microbiota in patients with interstitial cystitis/bladder pain syndrome: a systematic review.

OBJECTIVE: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines. MATERIALS AND METHODS: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts. RESULTS: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle-Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls. CONCLUSIONS: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment.

A materials terminology knowledge graph automatically constructed from text corpus.

A scalable, reusable, and broad-coverage unified material knowledge representation shows its importance and will bring great benefits to data sharing among materials communities. A knowledge graph (KG) for materials terminology, which is a formal collection of term entities and relationships, is conceptually important to achieve this goal. In this work, we propose a KG for materials terminology, named Materials Genome Engineering Database Knowledge Graph (MGED-KG), which is automatically constructed from text corpus via natural language processing. MGED-KG is the most comprehensive KG for materials terminology in both Chinese and English languages, consisting of 8,660 terms and their explanations. It encompasses 11 principal categories, such as Metals, Composites, Nanomaterials, each with two or three levels of subcategories, resulting in a total of 235 distinct category labels. For further application, a knowledge web system based on MGED-KG is developed and shows its great power in improving data sharing efficiency from the aspects of query expansion, term, and data recommendation.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

The gut microbiota derived metabolite trimethylamine N-oxide: Its important role in cancer and other diseases.

An expanding body of research indicates a correlation between the gut microbiota and various diseases. Metabolites produced by the gut microbiota act as mediators between the gut microbiota and the host, interacting with multiple systems in the human body to regulate physiological or pathological functions. However, further investigation is still required to elucidate the underlying mechanisms. One such metabolite involved in choline metabolism by gut microbes is trimethylamine (TMA), which can traverse the intestinal epithelial barrier and enter the bloodstream, ultimately reaching the liver where it undergoes oxidation catalyzed by flavin-containing monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). While some TMAO is eliminated through renal excretion, remaining amounts circulate in the bloodstream, leading to systemic inflammation, endoplasmic reticulum (ER) stress, mitochondrial stress, and disruption of normal physiological functions in humans. As a representative microbial metabolite originating from the gut, TMAO has significant potential both as a biomarker for monitoring disease occurrence and progression and for tailoring personalized treatment strategies for patients. This review provides an extensive overview of TMAO sources and its metabolism in human blood, as well as its impact on several major human diseases. Additionally, we explore the latest research areas related to TMAO along with future directions.

Evaluation of the therapeutic effect of Sacha inchi oil in atopic dermatitis mice.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition characterized by a multifaceted pathogenesis, which encompasses immune system signaling dysregulation, compromised skin barrier function, and genetic influencers. Sacha inchi (Plukenetia volubilis L.) oil (SIO) has demonstrated potent anti-inflammatory and antioxidant properties, however, the mechanism underlying the beneficial effects of SIO on AD remains unclear. This study aims to investigate the anti-AD effect of SIO and its possible molecular mechanism in mice with AD. The results demonstrated that SIO significantly reduced the degree of skin lesions and scratching, and improved the skin thickness and mast cell infiltration in AD mice. Furthermore, SIO significantly reduced the levels of immunoglobulin E, histamine and thymic stromal lymphopoietin in serum of AD mice. Additionally, it inhibited the expression of tumor necrosis factor-γ, interferon-γ, interleukin-2, interleukin-4, interleukin 1ß and other inflammatory cytokines in the lesions skin of mice. The Western blotting analysis revealed that SIO exhibited an upregulatory effect on the protein expression of filaggrin and loricrin, while concurrently exerting inhibitory effects on the protein expression and phosphorylation levels of P38, ERK, NF-κB, and IκBα within their respective signaling pathways. Consequently, it can be inferred that SIO exerts a significant anti-atopic dermatitis effect by modulating the P38, ERK, NF-κB, and IκBα signaling pathways. This study contributes to expand the research and development potential of SIO, and provides novel insights and potential therapeutic strategies for AD treatment.