The protective effect and immunomodulatory ability of orally administrated Lacticaseibacillus rhamnosus GG against Mycoplasma pneumoniae infection in BALB/c mice.

Mycoplasma pneumoniae represents one of the significant etiologies of community-acquired pneumonia in pediatric patients. However, clinical treatment of M. pneumoniae infection in children has encountered challenges due to the escalating resistance to quinolones. Numerous studies have highlighted the potential of probiotic lactobacillus administration in boosting immune responses to bacterial and viral respiratory infections. In this study, the protective efficacy of pre-oral administration of Lacticaseibacillus rhamnosus GG (LGG), Limosilactobacillus reuteri F275, Lactiplantibacillus plantarum NCIMB 8826, L. plantarum S1 or L. plantarum S2 was evaluated in the BALB/c mice model; it was observed that among these five strains of lactobacillus, the supplementation of LGG exhibited the most significant protective effect against M. pneumoniae infection. Moreover, when administered orally, both live LGG and heat-inactivated LGG have demonstrated efficacy in reducing the burden of M. pneumoniae in the lungs and alleviating pulmonary inflammation. Oral supplementation with LGG resulted in the inhibition of neutrophil recruitment into the lungs and increased recruitment of alveolar macrophages in M. pneumoniae-infected mice. Additionally, LGG supplementation led to increased production of IL-10 and secretory IgA (sIgA), while suppressing the levels of IL-1ß, IL-6, IL-17A, and TNF-α in the lungs of mice infected with M. pneumoniae. The data suggests that supplementation with LGG can modulate immune responses, decrease pathogen load, and alleviate inflammatory injury in the lungs of M. pneumoniae-infected mice.

Association of SARS-CoV-2 infection during late pregnancy with maternal and neonatal outcomes.

BACKGROUND: Limited data on the impact of the coronavirus disease 2019 (COVID-19) during pregnancy on newborn outcomes are available. This study aimed to characterize and compare the clinical outcomes of newborns from women with and without the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during late pregnancy. METHOD: This was a retrospective cohort study of women who were either infected or not infected with the SARS-CoV-2 virus during late pregnancy. The neonatal complications associated with COVID-19-positive pregnant women were investigated and analyzed. RESULTS: Among 2063 pregnant women over 28 weeks of gestation, 1.2%, 3.3%, and 18.7% of patients with multiple pregnancies, abnormal fetal positions, and lack of maternal or neonatal follow-up data, respectively, were excluded. Patients who were COVID-19-negative (60.6%) and -positive (16.2%) remained for further analysis. SARS-CoV-2 infection was significantly associated with higher SARS-CoV-2 infection rates in newborns (0% vs. 1.49%, P < 0.01) and longer duration of hospital stay (6.39 ± 2.2 vs. 4.92 ± 1.6, P < 0.01). However, comparing neonatal complications, including Apgar score, preterm birth, low birth weight, cesarean section rate, newborn hearing, neonatal congenital heart defects, and height and weight compliance rate of 6-month-old children, between non-infected and infected participants did not reach statistical significance. CONCLUSION: SARS-CoV-2 infection in late pregnancy has no significant impact on neonatal outcomes. After six months of follow-up of the neonates, we observed that SARS-CoV-2 infection in the third trimester of pregnancy did not affect their growth and development. Hopefully, these findings will guide management strategies and clinical practice.

Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling.

PURPOSE: Heparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer. METHODS: We identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2high and HSPG2low) were established to assess anticancer effects. RESULTS: Our results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer. CONCLUSION: This study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment.

Effect of aberrant fructose metabolism following SARS-CoV-2 infection on colorectal cancer patients' poor prognosis.

Most COVID-19 patients have a positive prognosis, but patients with additional underlying diseases are more likely to have severe illness and increased fatality rates. Numerous studies indicate that cancer patients are more prone to contract SARS-CoV-2 and develop severe COVID-19 or even dying. In the recent transcriptome investigations, it is demonstrated that the fructose metabolism is altered in patients with SARS-CoV-2 infection. However, cancer cells can use fructose as an extra source of energy for growth and metastasis. Furthermore, enhanced living conditions have resulted in a notable rise in fructose consumption in individuals' daily dietary habits. We therefore hypothesize that the poor prognosis of cancer patients caused by SARS-CoV-2 may therefore be mediated through fructose metabolism. Using CRC cases from four distinct cohorts, we built and validated a predictive model based on SARS-CoV-2 producing fructose metabolic anomalies by coupling Cox univariate regression and lasso regression feature selection algorithms to identify hallmark genes in colorectal cancer. We also developed a composite prognostic nomogram to improve clinical practice by integrating the characteristics of aberrant fructose metabolism produced by this novel coronavirus with age and tumor stage. To obtain the genes with the greatest potential prognostic values, LASSO regression analysis was performed, In the TCGA training cohort, patients were randomly separated into training and validation sets in the ratio of 4: 1, and the best risk score value for each sample was acquired by lasso regression analysis for further analysis, and the fifteen genes CLEC4A, FDFT1, CTNNB1, GPI, PMM2, PTPRD, IL7, ALDH3B1, AASS, AOC3, SEPINE1, PFKFB1, FTCD, TIMP1 and GATM were finally selected. In order to validate the model's accuracy, ROC curve analysis was performed on an external dataset, and the results indicated that the model had a high predictive power for the prognosis prediction of patients. Our study provides a theoretical foundation for the future targeted regulation of fructose metabolism in colorectal cancer patients, while simultaneously optimizing dietary guidance and therapeutic care for colorectal cancer patients in the context of the COVID-19 pandemic.

Advances of biomacromolecule-based antibacterial hydrogels and their performance evaluation for wound healing: A review.

Biomacromolecule hydrogels possess excellent mechanical properties and biocompatibility, but their inability to combat bacteria restricts their application in the biomedical field. With the increasing requirements and demands for hydrogel dressings, wound dressings with antibacterial properties of biomacromolecule hydrogels reinforced by adding antibacterial agents have attracted much attention, and related reviews are emerging. In this paper, the advances of biomacromolecule antibacterial hydrogels (including chitosan, sodium alginate, Hyaluronic acid, cellulose and gelatin) were first overviewed, and the antibacterial agents incorporated into hydrogels were classified (including metals and their derivatives, carbon-based materials, and native compounds). A series of performance evaluations of antibacterial hydrogels in the process of promoting wound healing were then reviewed, including basic properties (mechanical, rheological, injectable and self-healing, etc.), in vitro experiments (hemostasis, antibacterial, anti-inflammatory, anti-oxidation, biocompatibility) and in vivo experiments (in vivo model, histomorphology analysis, cytokines). Finally, the future development of biomacromolecule-based antibacterial hydrogels for wound healing is prospected. This work can provide a useful reference for researchers to prepare practical new wound hydrogel dressings.

Engineered food-derived hesperetin as heterojunction photosensitizer for inhibiting Staphylococcus aureus and degrading patulin, and its application in perishable strawberries.

The potential contamination, including microbial and mycotoxin infection, may escape from the naked eye, posing great threats to food products. Recently, photodynamic inactivation (PDI)-based technology particular has received particular attention because of their high safety. Herein, food-derived hesperetin (Hst) was innovatively introduced as an esculent photosensitizer, engineering with food-grade TiO2 nanoparticles (NPs) to form an organic-inorganic heterojunction structure. Triggered by visible light, the obtained TiO2/Hst NPs were endowed with efficient photoactivity, achieving higher inhibition of Staphylococcus aureus (antibacterial ratio of 98.3 %). The removal capacities of the TiO2/Hst NPs towards patulin (PAT) reached approximately 17.76 µg mg-1, approximately 2 times higher than TiO2 and Hst. The engineered TiO2/Hst NPs were used as the food surface detergent to achieve the ideal inhibition of Staphylococcus aureus and patulin performance on the surface of perishable strawberries, extending the storage life of strawberries.

Thermo-responsive cascade antimicrobial platform for precise biofilm removal and enhanced wound healing.

Background: Bacterial infection, tissue hypoxia and inflammatory response can hinder infected wound repair. This study aimed to develop a multifunctional specific therapeutic photo-activated release nanosystem [HMPB@MB@AuNPs@PMB@HA (HMAPH)] by loading photosensitizer methylene blue (MB) into hollow mesoporous Prussian blue nanostructures and modifying the surface with gold particles, polymyxin B (PMB) and hydrophilic hyaluronic acid. Methods: The HMAPH was characterized using transmission electron microscopy, UV-vis, Fourier-transform infrared spectroscopy, X-ray diffraction and X-ray photon spectroscopy. The photothermal performance, iron ion release and free radical generation of the HMAPH were measured under different conditions to investigate its thermo-responsive cascade reaction. The antibacterial ability of HMAPH was investigated using live/dead fluorescence tests. The morphology and membrane integrity of Pseudomonas aeruginosa (P. aeruginosa) were investigated using transmission electron microscopy. The anti-biofilm activity of HMAPH was evaluated using crystal violet and SYBR Green I staining. Finally, we established a mouse model of a skin wound infected by P. aeruginosa to confirm the in vivo effectiveness of HMAPH. We used immunofluorescent staining, hematoxylin-eosin staining, Masson staining and enzyme-linked immunosorbent assay to examine whether HMAPH promoted wound healing and reduced inflammatory damage. Results: In this study, hyaluronic acid was decomposed under the action of hyaluronidase. Also, the exposed nanomaterials specifically bound to the outer membrane of P. aeruginosa through PMB to increase the membrane sensitivity to photodynamic treatment. Under dual-light irradiation, a large amount of iron ions released by HMAPH underwent a Fenton reaction with H2O2 in bacteria to generate hydroxyl radicals (•OH), enabling direct killing of cells by hyperthermia. Additionally, the photodynamic activity of MB released by photo-induced activation led to the generation of reactive oxygen species, achieving synergistic and effective inhibition of P. aeruginosa. HMAPH also inhibited biofilm formation and downregulated the expression of virulence factors. In vivo experiments revealed that HMAPH accelerated the healing of P. aeruginosa-infected wounds by promoting angiogenesis and skin regeneration, inhibiting the inflammatory response and promoting M1 to M2 polarization. Conclusions: Our study proposed a strategy against bacteria and biofilms through a synergistic photothermal-photodynamic-Fenton reaction, opening up new prospects for combating biofilm-associated infections.

Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage.

Cervical lymphatic vessels (cLVs) have been shown to drain solutes and cerebrospinal fluid (CSF) from the brain. However, their hydrodynamical properties have never been evaluated in vivo. Here, we developed two-photon optical imaging with particle tracking in vivo of CSF tracers (2P-OPTIC) in superficial and deep cLVs of mice, characterizing their flow and showing that the major driver is intrinsic pumping by contraction of the lymphatic vessel wall. Moreover, contraction frequency and flow velocity were reduced in aged mice, which coincided with a reduction in smooth muscle actin expression. Slowed flow in aged mice was rescued using topical application of prostaglandin F2α, a prostanoid that increases smooth muscle contractility, which restored lymphatic function in aged mice and enhanced central nervous system clearance. We show that cLVs are important regulators of CSF drainage and that restoring their function is an effective therapy for improving clearance in aging.

Three New Steroids from the Roots of Marsdenia tenacissima.

Three undescribed pregnane steroids, 12ß-O-4-hydroxybenzoyl tenacigenin D (1), 12ß-O-4-hydroxybenzoyl tenacigenin A (2), and 11α-nicotinoyl-17ß-marsdenin (3), along with two known analogues (4 and 5), were isolated from the roots of Marsdenia tenacissima. Their structures were elucidated using one- and two-dimensional NMR, high-resolution electron ionization-mass spectrometry, single-crystal X-ray diffraction data, and experimental and density-functional-theory-calculated electronic circular dichroism measurements. All isolated compounds were evaluated for their cytotoxic activities against human lung cancer cells (A549), ovarian carcinoma cells (SKOV-3), gastric cancer cells (MGC 803) and breast cancer cells (MCF-7). Notably, 3 exhibited significant cytotoxic activity against both A549 (median inhibitory concentration (IC50)=16.79 µM) and SKOV-3 (IC50=12.30 µM) cells while exhibiting moderate cytotoxicity on MGC803 and MCF-7 cells.

Neo-5,10-seco-clerodane diterpenoids from Schnabelia terniflora.

Three new neo-5,10-seco-clerodane diterpenoids (1-3), four previously undescribed ethoxy/methoxy acetal analogues (4-7), one new etherified labdane diterpenoid (8), and seven known diterpenoids (9-15) were isolated from the whole plant of Schnabelia terniflora. Their structures were established on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction data, calculated electronic circular dichroism (ECD), and Mo2(OAc)4-induced circular dichroism. Compounds 2 and 3 represent the first examples of neo-5,10-seco-clerodane diterpenoids containing a 1H-pyrrole-2,5-dione and a pyrrolidine-2,5-dione moiety, respectively. A plausible biosynthetic pathway for 1-3 is proposed. All diterpenoids were evaluated for their cytotoxic activity against non-small-cell lung cancer lines (A549 and H460) and gastric cancer lines (HGC27 and AGS). Among them, 2 and 14 showed moderate cytotoxicity against four cell lines.

Bridged triphenylamine-based fluorescent probe for selective and direct detection of HSA in urine.

Human serum albumin (HSA) serves as a crucial indicator for therapeutic monitoring and biomedical diagnosis. In this study, a near infrared (NIR) fluorescent probe, termed BTPA, characterized a donor-π-acceptor (D-π-A) structure based on bridged triphenylamine (TPA) was developed. BTPA exhibited outstanding sensitivity and selectivity towards HSA among various analysts, with a remarkable 50-fold fluorescence enhancement with a significant Stokes shift (∼190 nm) and a wide linear detection range of 0-20 µM of HSA. Especially, BTPA displayed selectivity for discrimination of HSA from BSA. Job's Plot analysis suggested a 1:1 stoichiometry for the formation of the BTPA-HSA complex. Displacement assays and molecular docking demonstrated that BTPA binds to subdomain IB of HSA which could effectively avoid interference from most drugs. Besides, BTPA have good biocompatibility and could detect of exogenous HSA with a relatively low fluorescence background. For practical applications, BTPA was tested for detecting HSA levels in human urine without any pretreatment, showing detection capability in the range of 0-10 µM with a fast response (<30 s), a limit of detection (LOD) of 0.12 µM and good recoveries (81.7-92.9 %), highlighting the high performance of bridged triphenylamine-based probe BTPA.

Chitosan-puerarin composite hydrogel with magnetic enhanced photothermal properties as sustained antimicrobial coatings for beef preservation.

The bactericidal properties of traditional food coatings mostly depend on the amount of fungicides present, which reduces the sustainability of food packaging. Herein, we proposed a magnetic field to precisely modulate the near-infrared (NIR) absorption activity to enhance antimicrobial coatings sustainability. Inspired by the typical grinding procedure, the assembly of CP/Fe3O4@TA nanofiber hydrogel was proposed as the coating, applying mechanical force and encouraging the collision of effective molecules of puerarin (PUE), chitosan (CS), and Fe3O4@TA NFs. This hydrogel design offers precise control over the physical and chemical properties, including appearance, viscoelasticity, and rheology. Particularly, significant changes in photothermal performance were observed as a result of magnetic regulation of NIR absorption activity. As a result, the CP/Fe3O4@TA coatings achieve effective bacteria killing performance under NIR irradiation, magnetocaloric effect, boric acid adsorption, and aggregation interference. Finally, the hydrogel coating was applied to the beef surface and serves as an effective barrier against the growth of pathogenic bacteria, thereby preserving the freshness and tenderness of the beef. The finding from this work is expected to open up a new way in active nano hydrogel coating for food preservation.

Identification and validation of ferroptosis-related prognostic gene signature in patients with cervical cancer.

Background: Ferroptosis is an iron-dependent cell death, which is distinct from the other types of regulated cell death. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in cervical cancer (CC) remains unclear. This study aims to explore the ferroptosis-related prognostic genes (FRPGs) expression profiles and their prognostic values in CC. Methods: The ferroptosis-related genes (FRGs) were obtained from The Cancer Genome Atlas (TCGA) and FerrDb databases. Core FRGs were determined by the Search Tool for the Retrieval of Interacting Genes (STRING) website. FRPGs were identified using univariate and multivariate Cox regressions, and the ferroptosis-related prognostic model was constructed. FRPGs were verified in clinical specimens. The relationship between FRPGs and tumor infiltrating immune cells were assessed through the CIBERSORT algorithm and the LM22 signature matrix. Bioinformatics functions of FRPGs were explored with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: Thirty-three significantly up-regulated and 28 down-regulated FRGs were screened from databases [P<0.05; false discovery rate (FDR) <0.05; and |log2 fold change (FC)| ≥2]. Twenty-four genes were found closely interacting with each other and regarded as hub genes (degree ≥3). Solute carrier family 2 member 1 (SLC2A1), carbonic anhydrases IX (CA9), and dual oxidase 1 (DUOX1) were identified as independent prognostic signatures for overall survival (OS) in a Cox regression. Time-dependent receiver operating characteristic (ROC) curves showed the predictive ability of the ferroptosis-related prognostic model, especially for 1-year OS [area under the curve (AUC) =0.76]. Consistent with the public data, our experiments demonstrated that the mRNA levels of SLC2A1 and DUOX1, and the protein levels of SLC2A1, DUOX1, and CA9 were significantly higher in the tumor tissues. Further analysis showed that there was a significant difference in the proportion of tumor infiltrating immune cells between the low- and high-risk group based on our prognostic model. The function enrichment of FRPGs was explored by applying Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Conclusions: In this study, the features of FRPGs in CC were pictured. The results implicated that targeting ferroptosis may be a new reliable biomarker and an alternative therapy for CC.

Genetic support for the causal association between 91 circulating inflammatory proteins and atopic dermatitis: A two-sample Mendelian randomization trial.

BACKGROUND: Atopic dermatitis (AD) is a refractory disease that occurs in clinical practice. One of the most common inflammatory skin diseases, its occurrence and development are related to inflammation. Nevertheless, the precise nature of the relationship between circulating inflammatory proteins and AD remains uncertain. METHODS: A two-sample MR analysis was performed to determine the causal relationship between the expression of 91 circulating inflammatory proteins and AD by using genome-wide association study (GWAS) summary statistics data from the FinnGen consortia. The robustness of the MR results was assessed by means of sensitivity analysis. RESULTS: The causal relationship between the expression of nine specific circulating inflammatory proteins and AD was corroborated by the inverse variance weighted (IVW) method. The findings indicated that three circulating inflammatory proteins, namely, interleukin-18 receptor 1 [OR (CI) = 1.08 (1.05-1.11); p = 0.000001)], interleukin-8 [OR (CI) = 1.07 (1.00-1.14); p = 0.036244)], and tumor necrosis factor ligand superfamily member 14 [OR (CI) = 1.05 (1.00-1.10); p = 0.036842)], were positively correlated with AD. Additionally, six circulating inflammatory proteins were negatively correlated with AD: the T-cell surface glycoprotein CD5 [OR (CI) = 0.89 (0.84-0.95); p = 0.000191)], macrophage colony-stimulating factor 1 [OR (CI) = 0.93 (0.88-0.99); p = 0.031422)], fractalkine [OR (CI) = 0.91 (0.85-0.97); p = 0.003067)], interleukin-24 [OR (CI) = 0.91 (0.83-0.99); p = 0.031673)], signaling lymphocytic activation molecule [OR(CI) = 0.94 (0.89-1.00); p = 0.039818)], and urokinase-type plasminogen activator [OR(CI) = 0.95 (0.90-1.00); p = 0.037037)]. CONCLUSION: This study confirms the potential causal relationship between circulating inflammatory proteins and AD and provides guidance for the clinical diagnosis and treatment of AD.

Fragmentation Patterns of Phenolic C-Glycosides in Mass Spectrometry Analysis.

BACKGROUND: Many phenolic C-glycosides possess nutritional benefits and pharmacological efficacies. However, the MS/MS fragmentation pattern of phenolic C-glycosides analysis is understudied. This paper aims to determine the MS/MS fragmentation patterns of phenolic C-glycosides. METHOD: Ten compounds with different sugar moieties, aglycones, and substitutes were analyzed to determine the impact of these structural features on MS/MS fragmentation using UPLC-QTOF-MS analysis. RESULTS: The results showed that water loss followed by RDA reaction and alpha cleavage in the C-C bonded sugar moieties are the major fragmentation pathways. Additionally, the sugar cleavage was not affected by the skeleton and the substitute of the aglycones. These results suggested that the fragmentation patterns of phenolic C-glycosides differ from those in the O-glycosides, where the O-C glycosidic bond is the most cleavage-liable bond in MS/MS analysis. CONCLUSIONS: These MS/MS fragmentation patterns can be used for the identification of C-glycosides from dietary components and herbal medicine as well as developing robust methods using MRM methods to quantify C-glycosides.

Race Dialogues and Potential Application in Clinical Environments: A Scoping Review.

BACKGROUND: Race dialogues, conversations about race and racism among individuals holding different racial identities, have been proposed as one component of addressing racism in medicine and improving the experience of racially minoritized patients. Drawing on work from several fields, we aimed to assess the scope of the literature on race dialogues and to describe potential benefits, best practices, and challenges of conducting such dialogues. Ultimately, our goal was to explore the potential role of race dialogues in medical education and clinical practice. METHODS: Our scoping review included articles published prior to June 2, 2022, in the biomedicine, psychology, nursing and allied health, and education literatures. Ultimately, 54 articles were included in analysis, all of which pertained to conversations about race occurring between adults possessing different racial identities. We engaged in an interactive group process to identify key takeaways from each article and synthesize cross-cutting themes. RESULTS: Emergent themes reflected the processes of preparing, leading, and following up race dialogues. Preparing required significant personal introspection, logistical organization, and intentional framing of the conversation. Leading safe and successful race dialogues necessitated trauma-informed practices, addressing microaggressions as they arose, welcoming participation and emotions, and centering the experience of individuals with minoritized identities. Longitudinal experiences and efforts to evaluate the quality of race dialogues were crucial to ensuring meaningful impact. DISCUSSION: Supporting race dialogues within medicine has the potential to promote a more inclusive and justice-oriented workforce, strengthen relationships amongst colleagues, and improve care for patients with racially minoritized identities. Potential levers for supporting race dialogues include high-quality racial justice curricula at every level of medical education and valuation of racial consciousness in admissions and hiring processes. All efforts to support race dialogues must center and uplift those with racially minoritized identities.

Cu(II)-chelated ovalbumin mimicking the active centre of superoxide dismutase: Structure, antioxidant and antibacterial properties for food preservation application.

Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.

Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies.

ABSTACT: To our knowledge, venetoclax is the first example of personalized medicine for multiple myeloma (MM), with meaningful clinical activity as a monotherapy and in combination in patients with myeloma harboring the t(11:14) translocation. However, despite the high response rates and prolonged progression-free survival, a significant proportion of patients eventually relapse. Here, we aim to study adaptive molecular responses after the acquisition of venetoclax resistance in sensitive t(11:14) MM cell models. We therefore generated single-cell venetoclax-resistant t(11:14) MM cell lines and investigated the mechanisms contributing to resistance as well as the cells' sensitivity to other treatments. Our data suggest that acquired resistance to venetoclax is characterized by reduced mitochondrial priming and changes in B-cell lymphoma-2 (BCL-2) family proteins' expression in MM cells, conferring broad resistance to standard-of-care antimyeloma drugs. However, our results show that the resistant cells are still sensitive to immunotherapeutic treatments, highlighting the need to consider appropriate sequencing of these treatments after venetoclax-based regimens.

Unveiling the Roles of Alloyed Boron in Hexavalent Chromium Removal Using Borohydride-Synthesized Nanoscale Zerovalent Iron: Electron Donor and Antipassivator.

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.

Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

OBJECTIVE: This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. METHODS: The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. RESULTS: Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. CONCLUSION: The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.