Formononetin attenuates hepatic injury in diabetic mice by regulating macrophage polarization through the PTP1B/STAT6 axis.

BACKGROUND: Formononetin (FNT) is an isoflavone known for its anti-inflammatory properties and has been shown to reduce insulin resistance in Type 2 Diabetes Mellitus (T2DM). However, its effects and the underlying mechanisms in diabetic liver injury remain largely unexplored. METHODS: We established a T2DM-induced liver injury mouse model by feeding high-fat diet, followed by injecting streptozotocin. The mice were then treated with FNT and the liver function in these mice was assessed. Macrophage markers in FNT-treated T2DM mice or human THP-1 cells were evaluated using flow cytometry, RT-qPCR, and Western blotting. The expression of PTP1B and STAT6 in mouse liver tissues and THP-1 cells was analyzed. Molecular docking predicted the interaction between PTP1B and STAT6, which was validated via co-immunoprecipitation (Co-IP) and phos-tag analysis. Microscale thermophoresis (MST) assessed the binding affinity of FNT to PTP1B. RESULTS: FNT treatment significantly ameliorated blood glucose levels, hepatocyte apoptosis, inflammatory response, and liver dysfunction in T2DM mice. Moreover, FNT facilitated M2 macrophage polarization in both T2DM mice and high glucose (HG)-induced THP-1-derived macrophages. The PTP1B/STAT6 axis, deregulated in T2DM mice, was normalized by FNT treatment, which counteracted the T2DM-induced upregulation of PTP1B and downregulation of phosphorylated STAT6. Molecular docking and subsequent analyses revealed that PTP1B binds to and dephosphorylates STAT6 at the S325A site. In contrast, FNT strongly binds to PTP1B and influences its expression at the K116A site, promoting M2 polarization of THP-1 cells via downregulation of PTP1B. CONCLUSION: Formononetin mitigates diabetic hepatic injury by fostering M2 macrophage polarization via the PTP1B/STAT6 axis.

Effects of Lactobacillus plantarum on Broiler Health: Integrated Microbial and Metabolomics Analysis.

Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.

Self-power, multiwavelength photodetector based on a Sn-doped Ge quantum dots/hexagonal silicon nanowire heterostructure.

Tin-doped germanium quantum dots (Sn-doped Ge QDs)-decorated hexagonal silicon nanowires (h-Si NWs) were adopted to overcome the low infrared response of silicon and the excess dark current of germanium. High-quality Sn-doped Ge QDs with a narrow bandgap can be achieved through Ge-Sn co-sputtering on silicon nanowires by reducing the contact area between heterojunction materials and Sn-induced germanium crystallization. The absorption limit of the heterostructure is extended to 2.2 µm, and it is sensitive to 375-1550 nm light at 0 V, which has optimality at 1342 nm, with a photo-to-dark current ratio of over 815, a responsivity of 0.154 A/W, and a response time of 0.93 ms. The superior performance of the Sn-doped Ge QDs/h-Si NW photodetector in multiwavelength is attractive for multi-scenario applications.

Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.

Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Mediating effects of insomnia and resilience on COVID-19-related post-traumatic stress disorder and quality of life in adolescents.

The coronavirus disease-2019 (COVID-19) pandemic has impaired the quality of life (QoL) for many due to its extensive impacts. However, few studies have addressed the specific impact of COVID-19 on the mental health of adolescents, particularly post-traumatic stress disorder (PTSD). This study considered the impact of COVID-19-related PTSD on the QoL of adolescents in China, the mediating effects of insomnia, and the moderating effects of resilience. Participants included 50,666 adolescents aged 12-18 years selected using a comprehensive sampling method. We performed data collection from January 8th to January 18th, 2023, using the Children's Revised Impact of Event Scale, Pittsburgh Sleep Quality Index, Ten-item Connor-Davidson Resilience Scale, and Screening for and Promotion of Health-related QoL in Children and Adolescents Questionnaire for data collection. Male adolescents exhibited significantly lower levels of PTSD and insomnia compared to females and scored significantly higher in psychological resilience and overall QoL. Insomnia played a mediating role between PTSD and QoL. Psychological resilience moderated the impact of COVID-19-related stress on adolescents' QoL through its influence on insomnia. PTSD resulting from the COVID-19 pandemic affects the QoL of adolescents through the presence of insomnia. Psychological resilience plays a moderating role in this process. Cultivating psychological resilience in adolescents can effectively enhance their ability to cope with the impacts of sudden public events.

Development of a synthetic library of humanized nanobodies for targeted IL-6 inhibition.

Interleukin-6 (IL-6) is a cytokine that can bind to IL-6 receptor and induce pleiotropic effects. It serves as a critical biomarker, involved in inflammation amplification, tumor progression, and many other disease developments. Nanobodies, featuring small structure and high affinity, are a powerful and versatile tool in medical diagnostics and therapeutics. Here, based on a scaffold optimized for humanization and stability, we developed a synthetic phage display library that rapidly generated high-affinity and humanized nanobodies, negating the need for animal immunization. Using enhanced green fluorescent protein (eGFP) as a benchmark, we demonstrated that the library produced humanized nanobodies with high function and great intracellular stability. The library was then subjected to screening against IL-6. We identified a standout nanobody, NbL3, which exhibited high affinity (22.16 nM) and stability and significantly inhibited IL-6-enhanced migration on the human breast cancer cell MCF-7 at a relatively low concentration. NbL3's strong blocking activity provides a promising therapeutic alternative for the IL-6-targeted intervention strategy, underscoring the broader potential of our synthetic library as a versatile platform for the development of humanized nanobodies against multiple antigens.

Rational design of a dual-mode fluorescent probe for portable detection of pyriproxyfen in the environment and food.

The development of a fluorescent probe for pyriproxyfen (PPF) is crucial due to its potential threat to human health. However, the chemical inertness and low solubility of PPF present significant challenges for the detection of PPF in aqueous solutions using fluorescent probes. Herein, we have originally proposed a complex based on 2-(4-(dimethylamino)phenyl)-3-hydroxy-6,7-dimethoxy-4 H-chromen-4-one (HOF) and serum albumin (SA) as a dual-mode fluorescent probe, HOF@SA. This probe utilizes an indicator displacement assay (IDA) to release the dye HOF from the probe at low PPF concentrations (< 10 µM) and embeds the free dye HOF into the micelle of PPF at high concentrations (> 10 µM). This results in dual-mode fluorescent response characteristics for PPF: a turn-off response at low concentrations and a ratiometric response at high concentrations. An investigation of sensing behavior of HOF@SA for PPF detection exhibits rapid response (< 60 s), high sensitivity (LOD ∼4.7 ppb), high selectivity, and excellent visual detection capability (from cyan to yellow). Moreover, with the aid of a portable device, this method enables to analyze PPF in environmental and food samples. These results promote the advancement of a fluorescent probe approach for PPF analysis in environment and food.

Arginine Accelerates Sulfur Fluoride Exchange and Phosphorus Fluoride Exchange Reactions between Proteins.

Sulfur fluoride exchange (SuFEx) and phosphorus fluoride exchange (PFEx) click chemistries are advancing research across multiple disciplines. By genetically incorporating latent bioreactive unnatural amino acids (Uaas), these chemistries have been integrated into proteins, enabling precise covalent linkages with biological macromolecules and paving the way for new applications. However, their suboptimal reaction rates in proteins limit effectiveness, and traditional catalytic methods for small molecules are often incompatible with biological systems or in vivo applications. We demonstrated that introducing an arginine adjacent to the latent bioreactive Uaa significantly boosts SuFEx and PFEx reaction rates between proteins. This method is effective across various Uaas, target residues, and protein environments. Notably, it also enables efficient SuFEx reactions in acidic conditions, common in certain cellular compartments and tumor microenvironments, which typically hinder SuFEx reactions. Furthermore, we developed the first covalent cell engager that substantially enhances natural killer cell activation through improved covalent interaction facilitated by arginine. These findings provide mechanistic insights and offer a biocompatible strategy to harness these robust chemistries for advancing biological research and developing new biotherapeutics.

Enhancing Standardized Practices for Oral Mucositis Prevention in Pediatric Hematopoietic Stem Cell Transplantation: A Best Practice Implementation Project.

Background: Oral mucositis (OM) poses a significant challenge in children undergoing hematopoietic stem cell transplantation (HSCT). There is a gap between clinical practice and the evidence, and nursing practices is not standardized. Objective: This study aims to evaluate the effectiveness of applying the evidence for preventing HSCT chemotherapy-induced OM in children and to elevate the nurses' compliance to the evidence. Methods: Following the clinical evidence practice application model of the Joanna Briggs Institute (JBI) evidence-Based Care Center. The process included reviewing literature, extracting evidence, identifying gaps, developing audit criteria, conducting a baseline audit, creating an action plan, implementing evidence-based interventions, and assessing outcomes. Results: After the evidence implementation, 6 out of 12 audit criteria with poor compliance are significantly improved, with statistically significant differences (P<0.05). The incidence of OM decreases, with a statistically significant difference (66.6% vs 36.7%, P=0.02). The incidence of grade I, II, III, and IV OM also decreases (30% vs 23.3%, 23.3% vs 13.4%, 10% vs 0%, and 3.3% vs 0%). Ultimately, the standardized oral care practice routine and workflows to prevent OM were established. Conclusion: Bridging the gap between evidence and clinical practice can standardize nurse behavior, decrease the incidence of OM, and lower the OM severity in children undergoing HSCT.

Enhancing prostate cancer segmentation on multiparametric magnetic resonance imaging with background information and gland masks.

BACKGROUND: The landscape of prostate cancer (PCa) segmentation within multiparametric magnetic resonance imaging (MP-MRI) was fragmented, with a noticeable lack of consensus on incorporating background details, culminating in inconsistent segmentation outputs. Given the complex and heterogeneous nature of PCa, conventional imaging segmentation algorithms frequently fell short, prompting the need for specialized research and refinement. PURPOSE: This study sought to dissect and compare various segmentation methods, emphasizing the role of background information and gland masks in achieving superior PCa segmentation. The goal was to systematically refine segmentation networks to ascertain the most efficacious approach. METHODS: A cohort of 232 patients (ages 61-73 years old, prostate-specific antigen: 3.4-45.6 ng/mL), who had undergone MP-MRI followed by prostate biopsies, was analyzed. An advanced segmentation model, namely Attention-Unet, which combines U-Net with attention gates, was employed for training and validation. The model was further enhanced through a multiscale module and a composite loss function, culminating in the development of Matt-Unet. Performance metrics included Dice Similarity Coefficient (DSC) and accuracy (ACC). RESULTS: The Matt-Unet model, which integrated background information and gland masks, outperformed the baseline U-Net model using raw images, yielding significant gains (DSC: 0.7215 vs. 0.6592; ACC: 0.8899 vs. 0.8601, p < 0.001). CONCLUSION: A targeted and practical PCa segmentation method was designed, which could significantly improve PCa segmentation on MP-MRI by combining background information and gland masks. The Matt-Unet model showcased promising capabilities for effectively delineating PCa, enhancing the precision of MP-MRI analysis.

Kopsileuconines A-D: bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

Recent Advances in Basic Studies of Low-Intensity Pulsed Ultrasound in Periodontal Tissue Regeneration: A Systematic Review.

Approximately half of the adult population is suffering from periodontal disease, and conventional periodontal treatment strategies can only slow the progression of the disease. As a kind of tissue engineering, periodontal regeneration brings hope for the treatment of periodontal disease. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound with a frequency of 1-3 MHz and a much lower intensity (< 1W/cm2) than traditional ultrasound energy and output. LIPUS has been adopted for a variety of therapeutic purposes due to its bioeffects such as thermal, mechanical, and cavitation effects, which induce intracellular biochemical effects and lead to tissue repair and regeneration ultimately. In this systematic review, we summarize the basic research of LIPUS in the treatment of periodontal disease in periodontal disease animal models and the influence of LIPUS on the biological behavior (including promoting osteogenic differentiation of stem cells and inhibiting inflammatory response) and potential mechanism of periodontal ligament stem cells (PDLSCs), hoping to provide new ideas for the treatment of periodontal disease. We believe that LIPUS can be used as an auxiliary strategy in the treatment of periodontal disease and play an exciting and positive role in periodontal regeneration.

Corrigendum: Correlation between degeneration of cervical intervertebral disc degeneration of paravertebral muscle.

[This corrects the article DOI: 10.3389/fendo.2024.1391970.].

Preserving Molecular Tuning for Enhanced Electrocatalytic CO2-to-Ethanol Conversion.

Modifying catalyst surface with small molecular-additives presents a promising avenue for enhancing electrocatalytic performance. However, challenges arise in preserving the molecular-additives and maximizing their tuning effect, particularly at high current-densities. Herein, we develop an effective strategy to preserve the molecular-additives on electrode surface by applying a thin protective layer. Taking 4-dimethylaminopyridine (DMAP) as an example of a molecular-additive, the hydrophobic protection layer on top of the DMAP-functionalized Cu-catalyst effectively prevents its leaching during CO2 electroreduction (CO2R). Consequently, the confined DMAP molecules substantially promote the CO2-to-multicarbon conversion at low overpotentials. For instance, at a potential as low as -0.47 V vs. reversible hydrogen electrode, the DMAP-functionalized Cu exhibits over 80% selectivity towards multi-carbon products, while the pristine Cu shows only ~35% selectivity for multi-carbon products. Notably, ethanol appears as the primary product on DMAP-functionalized Cu, with selectivity approaching 50% at a high current density of 400 mA cm-2. Detailed kinetic analysis, in-situ spectroscopies, and theoretical calculations indicate that DMAP-induced electron accumulations on surface Cu-sites decrease the reaction energy for C-C coupling. Additionally, the interactions between DMAP and oxygenated intermediates facilitate the ethanol formation pathway in CO2R. Overall, this study showcases an effective strategy to guide future endeavors involving molecular tuning effects.

Progress of metal-loaded biochar-activated persulfate for degradation of emerging organic contaminants.

In recent years, studies on the degradation of emerging organic contaminants by sulfate radical (SO4-·) based advanced oxidation processes (SR-AOPs) have triggered increasing attention. Metal-loaded biochar (Me-BC) can effectively prevent the agglomeration and leaching of transition metals, and its good physicochemical properties and abundant active sites induce outstanding in activating persulfate (PS) for pollutant degradation, which is of great significance in the field of advanced oxidation. In this paper, we reviewed the preparation method and stability of Me-BC, the effect of metal loading on the physicochemical properties of biochar, the pathways of pollutant degradation by Me-BC-activated PS (including free radical pathways: SO4-·, hydroxyl radical (·OH), superoxide radicals (O2-·); non-free radical pathways: singlet oxygen (1O2), direct electron transfer), and discussed the activation of different active sites (including metal ions, persistent free radicals, oxygen-containing functional groups, defective structures, etc.) in the SR-AOPs system. Finally, the prospect was presented for the current research progress of Me-BC in SR-AOPs technology.

Single-atom catalysts activate persulfate to degrade emerging organic contaminants in aqueous environments.

Single-atom catalysts (SACs) exhibit outstanding catalytic activity due to their highly dispersed metal centers. Activating persulfates (PS) with SACs can generate various reactive oxygen species (ROS) to efficiently degrade emerging organic contaminants (EOCs) in aqueous environments, offering unique advantages such as high reaction rates and excellent stability. This technique has been extensively researched and holds enormous potential applications. In this paper, we comprehensively elaborated on the synthesis methods of SACs and their limitations, and factors influencing the catalytic performance of SACs, including metal center characteristics, coordination environment, and types of substrates. We also analyzed practical considerations for application. Subsequently, we discussed the mechanism of SACs activating PS for EOCs degradation, encompassing adsorption processes, radical pathways, and non-radical pathways. Finally, we provide prospects and outline our vision for future research, aiming to guide advancements in applying this technique.

Modulatory effects of necroptosis: A potential preventive approach to control diseases in fish.

Necroptosis is a caspase-independent programmed cell death process characterized by morphological similarities to necrosis and the potential to cause significant inflammatory reactions. The initiation, execution, and inhibition of necroptosis involve a complex interplay of various signaling proteins. When death receptors bind to ligands, necroptosis is triggered through the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/Mixed Lineage Kinase Domain-Like (MLKL) axis, leading to inflammatory reactions in the surrounding tissues. This process encompasses numerous physiological regulatory mechanisms and contributes to the development and progression of certain diseases. The mechanisms of necroptosis were not well conserved across terrestrial and aquatic organisms, with differences in some components and functions. Given the significant challenges that aquatic animal diseases pose to aquaculture, research interest in necroptosis has surged recently, particularly in studies focusing on fish. Understanding necroptosis in fish can lead to interventions that offer potential breakthroughs in disease inhibition and fish health improvement.

The Influence of Adding B4C and CeO2 on the Mechanical Properties of Laser Cladding Nickel-Based Coatings on the Surface of TC4 Titanium Alloy.

The development of titanium alloys is limited by issues such as low hardness, poor wear resistance, and sensitivity to adhesive wear. Using laser cladding technology to create high-hardness wear-resistant coatings on the surface of titanium alloys is an economical and efficient method that can enhance their surface hardness and wear resistance. This paper presents the preparation of two types of nickel-based composite coatings, Ni60-Ti-Cu-xB4C and Ni60-Ti-Cu-B4C-xCeO2, on the surface of TC4 titanium alloy using laser cladding. When the B4C addition was 8 wt.%, the hardness of the cladding layer was the highest, with an average microhardness of 1078 HV, which was 3.37 times that of the TC4 substrate. The friction coefficient was reduced by 24.7% compared to the TC4 substrate, and the wear volume was only 2.7% of that of the substrate material. When the CeO2 content was 3 wt.%, the hardness of the cladding layer was the highest, with an average microhardness of 1105 HV, which was 3.45 times that of the TC4 substrate. The friction coefficient was reduced by 33.7% compared to the substrate material, and the wear volume was only 1.8% of that of the substrate material.

Mecapegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study.

BACKGROUND: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. METHODS: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. RESULTS: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. CONCLUSION: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

BEROLECMI: a novel prediction method to infer circRNA-miRNA interaction from the role definition of molecular attributes and biological networks.

Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.