Fabrication and characterization of oxidized starch-xanthan gum composite nanoparticles with efficient emulsifying properties.

This study involved the preparation of nanoparticles by combining oxidized starch (OS) with xanthan gum (XG), and emulsions were prepared from this nanoparticle. The physical and chemical characteristics, as well as the emulsification properties of oxidized starch-xanthan gum composite nanoparticles (OGNP), were analyzed. The findings revealed that the OGNP retained spherical shape after the addition of XG, although their diameter increased from approximately 50-150 to 200-400 nm. Zeta potential decreased with XG content. Moreover, emulsions prepared from OGNP exhibited outstanding thermal stability, also showing enhanced storage stability. In addition, emulsions had different rheological properties at different pH values. The apparent viscosity and shear stress of emulsions under alkaline conditions were lower than that of neutral conditions. NaCl increased the apparent viscosity of OGNP-stabilized emulsions while reducing their thermal stability. The nanoparticles prepared in this study have efficient emulsification properties and can extend the application of OS.

Associations between multiple urinary metals and metabolic syndrome: Exploring the mediating role of liver function in Chinese community-dwelling elderly.

BACKGROUND: Multiple metals exposure has been revealed to be related to metabolic syndrome (MetS). However, the associations and interactions between multiple metals exposure and MetS are remains controversial, and the potential mechanism of the above-mentioned is still unclear. METHODS: The associations between urinary metals and the MetS were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Bayesian kernel machine regression (BKMR) model and quantile-based g-computation (qgcomp) were applied to explore the mixed exposure and interaction effect of metals. Mediation analysis was used to explore the role of liver function. RESULTS: In the single metal model, multiple metals were significantly associated with MetS. RCS analysis further verified the associations between 8 metals and MetS. BKMR model and qgcomp showed that zinc (Zn), iron (Fe), and tellurium (Te) were the main factors affecting the overall effect. In addition, mediation analysis indicated that serum alanine aminotransferase (ALT) mediated 21.54% and 13.29% in the associations of vanadium (V) and Zn with the risk of MetS, respectively. CONCLUSIONS: Elevated urinary concentration of Zn, V, Te, copper (Cu), molybdenum (Mo), and thallium (Tl) were related to the increased risk of MetS. Conversely, Fe and selenium (Se) may be protective factors for MetS in mixed exposure. Liver function may play a key role in the association of V and Zn exposure with MetS.

Single-cell analysis reveals hypoxia-induced immunosuppressive microenvironment in intrahepatic cholangiocarcinoma.

The role of hypoxia in the tumor microenvironment of intrahepatic cholangiocarcinoma (iCCA) remains unclear. Here, we generated a comprehensive atlas of the entire tumor microenvironment and delineated the multifaceted cell-cell interactions to decipher hypoxia-induced pro-tumor immune suppression. We discovered hypoxia is significantly associated with iCCA progression via the activation of HIF1A expression. Moreover, hypoxia-dependent PPARγ-mediated fatty acid oxidation in APOE+ TAMs promoted M2 macrophage polarization by activating the HIF1A-PPARG-CD36 axis. These polarized APOE+ TAMs recruited Treg cell infiltration via the CCL3-CCR5 pair to form an immunosuppressive microenvironment. APOE+ TAMs tended to co-localize spatially with Treg cells in the malignant tissue based on spatial transcriptome data and immunofluorescence analysis results. We identified tumor-reactive CXCL13+ CD8-PreTex with specific high expression of ENTPD1 and ITGAE, which acted as precursors of CD8-Tex and had higher cytotoxicity, lower exhaustion, and more vigorous proliferation. Consequently, CXCL13+ CD8-PreTex functioned as a positive regulator of antitumor immunity by expressing the pro-inflammatory cytokines IFNG and TNF, associated with a better survival outcome. Our study reveals the mechanisms involved in hypoxia-induced immunosuppression and suggests that targeting precursor-exhausted CXCL13+CD8+ T cells might provide a pratical immunotherapeutic approach.

Comparison of Accuracy and Operation Time in Robotic, Dynamic, and Static-Assisted Endodontic Microsurgery: An In Vitro Study.

INTRODUCTION: This study aimed to compare the accuracy and operation time (OT) of robotic-assisted endodontic microsurgery (RA-EMS), dynamic navigation-guided (DN-guided) EMS, and static navigation-guided (SN-guided) EMS. METHODS: Seventy-two teeth from three sets of standardized jaw models (TrueTooth, DELendo, Santa Barbara, CA) randomly assigned into three groups underwent osteotomy and root-end resection. Preoperative plans and postoperative cone-beam computed tomography images were imported into an accuracy analysis system and aligned based on the anatomical structures to assess accuracy. The OT was recorded from the moment the foot pedal was pressed down until the bur reached the target depth. Statistical analyses were conducted using Kruskal-Wallis and Scheirer-Ray-Hare tests, with significance set at p < 0.05. RESULTS: RA-EMS exhibited significantly higher accuracy than DN- and SN-guided EMS in terms of platform, angular, and resection angular deviations (p < 0.05). Additionally, RA-EMS exhibited significantly higher accuracy than DN-guided EMS in resection length deviation (p < 0.05). Significant differences were also observed in OTs between the three approaches, with SN-guided EMS showing the shortest OT, followed by RA-EMS and DN-guided EMS. Differences in jaw types within the DN-guided EMS group were observed in terms of angular deviation (p < 0.05). CONCLUSIONS: All three treatment approaches demonstrated acceptable clinical accuracy and OT. RA-EMS exhibited superior accuracy, suggesting its potential application prospects in endodontics. Further high-quality clinical studies are warranted.

Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells.

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.

Dual network structure of the AV node.

Biological systems, particularly the brain, are frequently analyzed as networks, conveying mechanistic insights into their function and pathophysiology. This is the first study of a functional network of cardiac tissue. We use calcium imaging to obtain two functional networks in a subsidiary but essential pacemaker of the heart, the atrioventricular node (AVN). The AVN is a small cellular structure with dual functions: a) to delay the pacemaker signal passing from the sinoatrial node (SAN) to the ventricles, and b) to serve as a back-up pacemaker should the primary SAN pacemaker fail. Failure of the AVN can lead to syncope and death. We found that the shortest path lengths and clustering coefficients of the AVN are remarkably similar to those of the brain. The network is ``small-world," thus optimized for energy use vs transmission efficiency. We further study the network properties of AVN tissue with knock-out of the sodium-calcium exchange transporter. In this case, the average shortest path-lengths remained nearly unchanged showing network resilience, while the clustering coefficient was somewhat reduced, similar to schizophrenia in brain networks. When we removed the global action potential using principal component analysis (PCA) in wild-type model, the network lost its ``small-world" characteristics with less information-passing efficiency due to longer shortest path lengths but more robust signal propagation resulting from higher clustering. These two wild-type networks (with and without global action potential) may correspond to fast and slow conduction pathways. Laslty, a one-parameter non-linear preferential attachment model is a good fit to all three AVN networks.

The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

BACKGROUND: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). RESULTS: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. CONCLUSIONS: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.

A Study of Biomedical Relation Extraction Using GPT Models.

Relation Extraction (RE) is a natural language processing (NLP) task for extracting semantic relations between biomedical entities. Recent developments in pre-trained large language models (LLM) motivated NLP researchers to use them for various NLP tasks. We investigated GPT-3.5-turbo and GPT-4 on extracting the relations from three standard datasets, EU-ADR, Gene Associations Database (GAD), and ChemProt. Unlike the existing approaches using datasets with masked entities, we used three versions for each dataset for our experiment: a version with masked entities, a second version with the original entities (unmasked), and a third version with abbreviations replaced with the original terms. We developed the prompts for various versions and used the chat completion model from GPT API. Our approach achieved a F1-score of 0.498 to 0.809 for GPT-3.5-turbo, and a highest F1-score of 0.84 for GPT-4. For certain experiments, the performance of GPT, BioBERT, and PubMedBERT are almost the same.

Exploring Large Language Models for Acronym, Symbol Sense Disambiguation, and Semantic Similarity and Relatedness Assessment.

Acronyms, abbreviations, and symbols play a significant role in clinical notes. Acronym and symbol sense disambiguation are crucial natural language processing (NLP) tasks that ensure the clarity and consistency of clinical notes and downstream NLP processing. Previous studies using traditional machine learning methods have been relatively successful in tackling this issue. In our research, we conducted an evaluation of large language models (LLMs), including ChatGPT 3.5 and 4, as well as other open LLMs, and BERT-based models, across three NLP tasks: acronym and symbol sense disambiguation, semantic similarity, and relatedness. Our findings emphasize ChatGPT's remarkable ability to distinguish between senses with minimal or zero-shot training. Additionally, open source LLM Mixtrial-8x7B exhibited high accuracy for acronyms with fewer senses, and moderate accuracy for symbol sense accuracy. BERT-based models outperformed previous machine learning approaches, achieving an impressive accuracy rate of over 95%, showcasing their effectiveness in addressing the challenge of acronym and symbol sense disambiguation. Furthermore, ChatGPT exhibited a strong correlation, surpassing 70%, with human gold standards when evaluating similarity and relatedness.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Diagnostic performance of mpox virus (MPXV) real-time PCR assays: multicenter assessment and extended sensitivity analysis.

PURPOSE: To comprehensively investigate the diagnostic performance of routinely used assays in MPXV testing, the National Center of Clinical Laboratories in China conducted a nationwide external quality assessment (EQA) scheme and an evaluated nine assays used by ≥ 5 laboratories in the EQA. METHODS: MPXV virus-like particles with 2700, 900 and 300 copies/mL were distributed to 195 EQA laboratories. For extended analysis, triple-diluted samples from 9000 to 4.12 copies/mL were repeated 20 times using the assays employed by ≥ 5 laboratories. The diagnostic performance was assessed by analyzing EQA data and calculating the limits of detection (LODs). RESULTS: The performance was competent in 87.69% (171/195) of the participants and 87.94% (175/199) of the datasets. The positive percentage agreements (PPAs) were greater than 99% for samples at 2700 and 900 copies/mL, and 95.60% (761/796) for samples at 300 copies/mL. The calculated LODs for the two clades ranged from 228.44 to 924.31 copies/mL and were greater than the LODs specified by the respective kits. EasyDiagnosis had the lowest calculated LODs and showed superior performance in EQA, whereas BioGerm and Sansure, with higher calculated LODs, did not perform well in EQA. CONCLUSION: This study provides valuable information from the EQA data and evaluation of the diagnostic performance of MPXV detection assays. It also provided insights into reagent optimization and enabled prompt public health interventions for the outbreak.

Endolysins: a new antimicrobial agent against antimicrobial resistance. Strategies and opportunities in overcoming the challenges of endolysins against Gram-negative bacteria.

Antibiotic-resistant bacteria are rapidly emerging, and the increasing prevalence of multidrug-resistant (MDR) Acinetobacter baumannii poses a severe threat to humans and healthcare organizations, due to the lack of innovative antibacterial drugs. Endolysins, which are peptidoglycan hydrolases encoded by a bacteriophage, are a promising new family of antimicrobials. Endolysins have been demonstrated as an effective therapeutic agent against bacterial infections of A. baumannii and many other Gram-positive and Gram-negative bacteria. Endolysin research has progressed from basic in vitro characterization to sophisticated protein engineering methodologies, including advanced preclinical and clinical testing. Endolysin are therapeutic agent that shows antimicrobial properties against bacterial infections caused by drug-resistant Gram-negative bacteria, there are still barriers to their implementation in clinical settings, such as safety concerns with outer membrane permeabilizers (OMP) use, low efficiency against stationary phase bacteria, and stability issues. The application of protein engineering and formulation techniques to improve enzyme stability, as well as combination therapy with other types of antibacterial drugs to optimize their medicinal value, have been reviewed as well. In this review, we summarize the clinical development of endolysin and its challenges and approaches for bringing endolysin therapies to the clinic. This review also discusses the different applications of endolysins.

Triflic Acid-Promoted 1,2-Amino Migration Reactions in α-Arylaminoacrylamides: Access to Substituted ß-Aminoamides.

A straightforward synthesis of substituted ß-aminoamides from α-arylamino-ß-hydroxyacrylamides, α-arylamino-ß-oxoamides, or their tautomeric mixture has been described. The (E)-enol triflate intermediates are readily generated in situ from these substrates in the presence of triflic anhydride (Tf2O) and triethylamine (Et3N) in a chemoselective manner and undergo triflic acid (TfOH)-promoted cyclization and ring-opening reactions with alcohols to deliver the desired products. The one-pot two-step synthetic protocol features the use of readily available starting materials, mild reaction conditions, high chemoselectivity, operational simplicity, and a wide range of synthetic potential of the products.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Facile synthesis of a carbon supported lithium iron phosphate nanocomposite cathode material from metal-organic framework for lithium-ion batteries.

Lithium iron phosphate (LiFePO4, LFP) has become one of the most widely used cathode materials for lithium-ion batteries. The inferior lithium-ion diffusion rate of LFP crystals always incurs poor rate capability and unsatisfactory low-temperature performances. To meet with the requirements from the ever-growing market, it is of great significance to synthesize carbon supported LFP nanocomposite (LFP/C) cathode materials using cost effective and environmentally friendly methods. In this work, an LFP/C cathode material is straightforwardly prepared from a metal-organic framework (MOF) precursor ferric gallate (Fe-GA) using its self-template effect. The Fe-GA precursor is firstly fabricated from the redox coprecipitation reaction between Fe foils and gallic acid (GA) molecules in mild aqueous phase. Then the Fe-GA is directly converted to the LFP/C sample after a following solid-state reaction. In half-cells, the LFP/C composite exhibits a reversible capacity of 109.7 mAh·g-1 after 500 cycles under the current rate of 100 mA·g-1 at 25 °C as well as good rate capabilities. In the LFP/C//graphite full-cells, the LFP/C composite can deliver a reversible capacity of 71.4 mAh·g-1 after 50 cycles in the same condition as the half-cells. The electrochemical performances of the LFP/C cathode in half-cells at lower temperature of -10 °C are also examined. Particularly, the evolution of samples has been explored and the lithium-ion storage mechanism of the LFP/C cathode has been unveiled. The sample synthesis protocol is straightforward, eco-friendly and atomic efficient, which can be considered to have good potential for scaling-up.

Benzylic Trifluoromethyl Accelerates 1,6-Elimination Toward Rapid Probe Activation.

Activity-based detection of hydrogen sulfide in live cells can expand our understanding of its reactivity and complex physiological effects. We have discovered a highly efficient method for fluorescent probe activation, which is driven by H 2 S-triggered 1,6-elimination of an α-CF 3 -benzyl to release resorufin. In detecting intracellular H 2 S, 4-azido-(α-CF 3 )-benzyl resorufin offers significantly faster signal generation and improved sensitivity compared to 4-azidobenzyl resorufin. Computed free energy profiles for the 1,6-elimination process support the hypothesis that a benzylic CF 3 group can reduce the activation energy barrier toward probe activation. This novel probe design allows for near-real-time detection of H 2 S in HeLa cells under stimulation conditions.