Hypocrellin A against intrahepatic Cholangiocarcinoma via multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive and highly lethal cancer with an increasing incidence worldwide that lacks effective treatment regimens. Hypocrellin A (HA), a natural small compound isolated from S. bambusicola, has multiple biomedical activities, including antitumor activity. PURPOSE: We intended to investigate the therapeutic effects of HA on ICC and its potential mechanisms. METHODS: RBE and HuccT1 cell lines were utilized for in vitro experiments. CCK8 assay, colony formation analysis, RTCA, and immunofluorescence staining of ki67 were employed to evaluate the suppression effects of HA on proliferation. The inhibitory effects of HA on cell migration and invasion were evaluate through transwell and wound healing assays, and Hoechst 33,258 staining was performed to evaluate apoptosis. Additionally, we performed transcriptome sequencing and molecular docking for targeting identification, and immunoblotting and immunofluorescence of key molecules for validation. Two in vivo models, HuccT1 xenografts, and the primary ICC model (KRAS/P19/SB) established via hydrodynamic tail-vein injection were implemented. Multiplex immunohistochemistry (mIHC) was used to illustrate the multi-target inhibitory effects of HA. RESULTS: The IC50 values of HA against RBE and HuccT1 cells were 4.612 µM and 10.01 µM for 24 h, as determined through the CCK8 assay. Our results confirmed that HA significantly repressed the proliferation, migration, invasion, and promoted the apoptosis of ICC cells at low concentrations. Moreover, HA exerted its anti-cancer effects through multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. This inhibitory effect was rescued by Recilisib, an activator of the PI3K-AKT-mTOR pathway. Bioinformatics analysis of a multi-center RNA-Seq cohort (n = 90) demonstrated significant associations between these target pathways and the occurrence and poor prognosis of ICC. Animal studies suggested that HA strongly inhibited tumor growth in xenograft ICC models, and repressed the tumor number and size in the liver of primary ICC models by suppressing these three crucial pathways. CONCLUSION: HA, a novel natural small molecule, demonstrated promising therapeutic efficacy against ICC through its multi-target inhibitory effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in a primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for ICC.

Aptamer-controlled stimuli-responsive drug release.

Aptamers have been widely researched and applied in nanomedicine due to their programmable, activatable, and switchable properties. However, there are few reviews on aptamer-controlled stimuli-responsive drug delivery. This article highlights the mechanisms and advantages of aptamers in the construction of stimuli-responsive drug delivery systems. We summarize the assembly/reconfiguration mechanisms of aptamers in controlled release systems. The assembly and drug release strategies of drug delivery systems are illustrated. Specifically, we focus on the binding mechanisms to the target and the factors that induce/inhibit the binding to the stimuli, such as strand, pH, light, and temperature. The applications of aptamer-based stimuli-responsive drug release are elaborated. The challenges are discussed, and the future directions are proposed.

DNA Nanostructures: Advancing Cancer Immunotherapy.

Cancer immunotherapy is a groundbreaking medical revolution and a paradigm shift from traditional cancer treatments, harnessing the power of the immune system to target and destroy cancer cells. In recent years, DNA nanostructures have emerged as prominent players in cancer immunotherapy, exhibiting immense potential due to their controllable structure, surface addressability, and biocompatibility. This review provides an overview of the various applications of DNA nanostructures, including scaffolded DNA, DNA hydrogels, tetrahedral DNA nanostructures, DNA origami, spherical nucleic acids, and other DNA-based nanostructures in cancer immunotherapy. These applications explore their roles in vaccine development, immune checkpoint blockade therapies, adoptive cellular therapies, and immune-combination therapies. Through rational design and optimization, DNA nanostructures significantly bolster the immunogenicity of the tumor microenvironment by facilitating antigen presentation, T-cell activation, tumor infiltration, and precise immune-mediated tumor killing. The integration of DNA nanostructures with cancer therapies ushers in a new era of cancer immunotherapy, offering renewed hope and strength in the battle against this formidable foe of human health.

Sialidase-Chimeric Bioengineered Bacteria for Tumor-Sialoglycan-Triggered Solid Tumor Therapy.

Adoptive cell therapies for solid tumors are usually limited by off-target antigens, incapable tissue infiltration, and cell function exhaustion. In contrast, bacterial cells possess the inherent competencies of preferential tumor targeting, deep tissue penetration, and high intratumoral bioactivity and represent promising alternatives to overcome these challenges. Here, a sialic-acid-responsive regulatory gene circuit is engineered into Escherichia coli MG1655 to express cytolysin of hemolysin E (HlyE). Furthermore, sialidases are bioorthogonally decorated onto the surface of azido-functionalized bioengineered bacteria for recognizing tumor sialoglycans and cleaving their sialosides into free sialic acids. As chemical inducers, sialic acids feedbackingly activate the bacterial gene circuit to produce HlyE and lyse tumor cells. This study mimics the tumor antigen-induced cytotoxin production and cell lysis that occurs in chimeric antigen receptor T (CAR-T) cells yet surmounts the intrinsic limitations of adoptive cell therapies. Moreover, sialidase-mediated tumor cell desialylation also reverses the immunosuppressive effect of glycoimmune checkpoints and further improves the therapeutic effect of solid tumors.

Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer.

The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with a gallium-polyphenol network (LGG@Ga-poly), bolster immunotherapy in pancreatic cancer by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets pancreatic tumors specifically, and selectively eradicates tumor-promoting Proteobacteria and microbiota-derived lipopolysaccharides through a gallium-facilitated disruption of bacterial iron respiration. This elimination of intratumor microbiota impedes the activation of tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 and interleukin-1ß expression by tumor cells, diminishing immunotolerant myeloid populations, and improving the infiltration of cytotoxic T lymphocytes in tumors. Moreover, LGG@Ga-poly hampers pancreatic tumor growth in both preventive and therapeutic contexts, and amplifies the antitumor efficacy of immune checkpoint blockade in preclinical cancer models in female mice. Overall, we offer evidence that thoughtfully designed biomaterials targeting intratumor microbiota can efficaciously augment immunotherapy for the challenging pancreatic cancer.

Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study.

Background: Mitochondrial dysfunction has been shown to play a critical role in cancer biology. However, its involvement in intrahepatic cholangiocarcinoma (iCCA) remains significantly understudied. Methods: RNA sequencing data of 30 pairs of iCCA and paracancerous tissues were collected from the First Affiliated Hospital of Wenzhou Medical University (WMU). The WMU cohort (n = 30) was integrated with public TCGA (n = 30) and GSE107943 (n = 30) datasets to establish a multi-center iCCA cohort. We merged the TCGA and GSE107943 cohorts into an exploration cohort to develop a mitochondria signature for prognosis assessment, and utilized the WMU cohort for external validation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmarker analyses were used for functional interpretation of iCCA associated mitochondria-related genes (MRGs). In addition, unsupervised clustering was performed to identify mitochondria-based iCCA subtypes with the data of three institutions. Further investigations were conducted to examine the impact of mitochondrial dysfunction on drug responses, alteration of the tumor immune microenvironment, and immune responses. Results: Two hundred and sixty-three iCCA-related MRGs were identified to be related to fatty acid metabolism, oxidative phosphorylation, and apoptosis. Through univariate and multivariate Cox, and LASSO analyses, a mitochondria signature with five optimal MRGs was established to evaluate the prognosis of iCCA patients with the AUC values ranged from 0.785 to 0.928 in the exploration cohort. The signature also exhibited satisfactory performance in the WMU cohort with AUC values of 0.817-0.871, and was identified as an independent risk predictor in both cohorts. Additionally, we found that patients with higher mitochondria score with poor prognosis presented lower infiltration levels of CD4+ T-cell, NK cells, and monocytes, and demonstrated higher sensitivity to targeted therapies, including sorafenib. Furthermore, two distant mitochondria-based subtypes were determined, and subtype 2 was associated with shorter survival time and immunosuppressive tumor microenvironment. Finally, the differential protein expression of five key MRGs was verified by Immunohistochemistry. Conclusion: We found mitochondrial dysfunction modulates aberrant metabolism, oxidative stress, immune responses, apoptosis, and drug sensitivity in iCCA. A mitochondria signature and two mitochondria-based iCCA subtypes were identified for clinical risk stratification and immunophenotyping.

Association of C-reactive protein/albumin ratio with mortality in patients with Traumatic Brain Injury: A systematic review and meta-analysis.

Objective: This study examines the C-reactive protein (CRP)/albumin ratio (CAR) as an inflammation-based prognostic score for predicting mortality in patients with Traumatic Brain Injury (TBI). Methods: We systematically searched the electronic databases PubMed, Embase, and Cochrane up to February 2024. Our inclusion criteria encompassed studies investigating CAR-predicted mortality in patients with TBI. We calculated the Odds Ratio (OR) and associated 95 % confidence intervals (95 % CI) using a random-effects model. Quality assessment of the included studies was appraised using a Newcastle-Ottawa scale. Results: A total of five studies comprising 1040 patients were included in this meta-analysis. The pooled results indicated that CAR was associated with mortality in patients with TBI (OR = 1.88, 95 % CI: 1.05-3.36, P < 0.0001). The findings of subgroup analysis indicated that the relationship between CAR and mortality in patients with TBI did not vary with the severity of the condition. Conclusions: CAR emerges as a valuable prognostic tool for mortality in patients with TBI, underscoring its potential role in early risk stratification and management strategies.

Intracellular Gelation-Mediated Living Bacteria for Advanced Biotherapeutics in Mouse Models.

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

Accurate Structural Elucidation of Samoquasine A and an Unknown Homologue Using a Computation-Based Machine Learning Protocol.

The structure of samoquasine A has long been a subject of controversy, which was resolved only upon its successful total synthesis. We examined the structures of the associated compounds using the state-of-the-art SVM-M protocol. The method accurately discriminated all putative structures historically attributed to samoquasine A from a pool of 48 isomeric structures, confirming that samoquasine A is indeed identical to perlolidine. Furthermore, by applying the SVM-M protocol to an additional pool of 67 isomeric structures, we successfully assigned a yet unknown natural product, initially misidentified as perlolidine, as a novel oxime, (E)-3H-cyclopenta[c]quinolin-3-one oxime, representing the first reported cyclone oxime-quinoline natural product.

Impact of Online Video Game-Based Dichoptic Training on Binocular Vision Rehabilitation in Post-surgical Patients with Intermittent Exotropia.

INTRODUCTION: Dichoptic training has emerged as a promising rehabilitation approach for improving binocular visual function in patients with strabismus. A prospective observational study design was employed to assess the effectiveness of online video game-based dichoptic training in rehabilitating binocular visual function in patients who had undergone an operation for intermittent exotropia. METHODS: A total of 64 patients who had undergone an operation for intermittent exotropia were recruited and divided into the training group and the control group based on whether they would receive the dichoptic training. The dichoptic training was conducted for 3 months in the training group and the control group would not accept any form of orthoptic therapy. Assessments of binocular visual functions and deviation were conducted at baseline, 3-month and 6-month follow-up. RESULTS: Twenty-nine participants in the training group (mean 9.69 ± 2.66 years old) and 26 participants in the control group (mean 8.41 ± 2.64 years old) completed follow-up. At both 3- and 6-month follow-ups, the training group showed superior distance stereopsis compared to the control group, with near stereopsis only showing significant difference at the 6-month follow-up. Additionally, the training group exhibited significantly less distance exo-deviation drift than the control group at these times, and no significant difference was observed in near exo-deviation drift between the groups. The control group had a significantly higher rate of suboptimal surgical outcomes at both the 3- and 6-month follow-up. However, no significant differences were observed in simultaneous perception and fusion functions between the two groups. CONCLUSIONS: Online video game-based dichoptic training has the potential to become a novel postoperative rehabilitation strategy for patients with intermittent exotropia.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross-Presentation Through Gap Junction.

Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors.

Dental caries status and related factors among 5-year-old children in Shanghai.

BACKGROUND: Dental caries in young children is a difficult global oral health problem. In the last decade, China has put a great deal of effort into reducing the prevalence of dental caries. This study, which is part of the China Population Chronic Disease and Nutrition Surveillance 2021, aimed to investigate the prevalence of dental caries among children aged 5 in Shanghai, China, and its associated factors. METHODS: A total of 1281 children aged 5 years from 6 districts in Shanghai were selected by a stratified sampling method. The survey consisted of an oral health questionnaire and an oral health examination. The questionnaire included questions on oral health knowledge, attitudes, and behaviours. The oral health examination used WHO standards. After screening, the data were input and analysed. Chi-square tests and logistic regression analyses were used to study the relevant factors affecting dental caries. RESULTS: The prevalence of dental caries among 1281 children was 51.0%, the dmft index score was 2.46, the Significant Caries Index (SiC) score was 6.39, and the SiC10 score was 10.35. Dental caries experience was related to the frequency of sweet drink consumption, the age of starting tooth brushing, eating habits after brushing, whether the children had received an oral examination provided by the government (p < 0.05), and the mother's education level but was not related to sex, the use of fluoride toothpaste, the frequency of brushing, whether the parents assisted brushing, or the frequency of flossing (p > 0.05). Logistic regression analysis showed that the region of residence, eating after brushing and the age of starting brushing were associated with dental caries. CONCLUSIONS: Dental caries remained prevalent among 5-year-old children in Shanghai, China. Prevention strategies that target the associated factors including region of residence, eating after brushing, and the age of starting brushing should be considered.

Modularization of Regional Electronic Structure over Defect-Rich CeO2 Rods for Enhancing Photogenerated Charge Transfer and CO2 Activation.

Oxygen vacancy (OV) engineering has been widely applied in different types of metal oxide-based photocatalytic reactions. Our study has shown that the redistributed OVs resulting from voids in CeO2 rods lead to significant differences in the band structure in space. The flat energy band within the highly crystallized bulk region hinders the recombination of photogenerated carrier pairs during the transfer process. The downward curved energy band in the surface region enhances the activation of the absorbents. Therefore, the localization of the band structure through crystal structure regionalization renders V-CeO2 capable of achieving efficient utilization of photogenerated carriers. Practically, the V-CeO2 rod shows a remarkable turnover number of 190.58 µmol g-1 h-1 in CO2 photoreduction, which is ∼9.4 times higher than that of D-CeO2 (20.46 µmol g-1 h-1). The designed modularization structure in our work is expected to provide important inspiration and guidance in coordinating the kinetic behavior of carriers in OV defect-rich photocatalysts.

The RAS-signaling-pathway-mutation-related prognosis in B-cell acute lymphoblastic leukemia: A report from South China children's leukemia group.

The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of RAS signaling pathway mutations are different significantly between T-ALL and B-ALL. In B-ALL, the RAS pathway is mostly involved, and NRAS (17.6%), KRAS (22.7%), and PTPN11 (7.7%) were the three most frequently mutated genes. Co-occurring mutations of CREBBP and NRAS, FLT3, or PTPN11 (p = 0.002, p = 0.009, and p = 0.003, respectively) were found in this cohort. The 3-year RFS rates for the RAS signaling pathway mutation-positive and negative cases was 76.5 % versus 89.7 % (p = 0.012). Four cases relapsed in the lately 3 years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.

LINC01977 promotes colorectal cancer growth and metastasis by enhancing aerobic glycolysis via the ERK/c-Myc axis.

Background: How colorectal cancer (CRC) gain the ability to growth and metastasis remains largely unknown. Findings from preceding studies have revealed the participation of long non-coding RNAs (lncRNAs) in CRC progression. However, the role of LINC01977 in CRC remains unexplored. This study aims to explore the function and underlying mechanism of LINC01977 in CRC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the expression of LINC01977 in CRC and its correlation with CRC prognosis. In our research, we explored the influence of LINC01977 on CRC progression such as cell proliferation, migration, invasion, and aerobic glycolysis, and identified its fundamental molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models. Results: LINC01977 exhibited significantly elevated expression in CRC tissues and cell lines, and its level was significantly correlated with malignant clinicopathological characteristics and negative prognosis. Furthermore, both in vivo and in vitro tests revealed LINC01977's role in facilitating CRC cell proliferation and metastasis. LINC01977's significant part in CRC aerobic glycolysis was also discovered. With an aim to uncover the underlying mechanism, we investigated LINC01977's effect on c-Myc, a key gene in glycolysis. The results showed that LINC01977 regulated c-Myc stability via extracellular signal-regulated kinase (ERK)-mediated phosphorylation, and LINC01977-mediated c-Myc activated the level of vital glycolysis-related genes such as HK2, PGK1, LDHA, and GLUT1. Rescue experiments further confirmed that LINC01977 promoted CRC proliferation, metastasis, and aerobic glycolysis via c-Myc. Conclusions: This study is the first to report that LINC01977 facilitates CRC proliferation, metastasis, and aerobic glycolysis through c-Myc, suggesting its potential as a therapeutic target for CRC treatment.

Fibroblast Growth Factor 21 Relieves Lipopolysaccharide-Induced Acute Lung Injury by Suppressing JAK2/STAT3 Signaling Pathway.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening disease without an effective drug at present. Fibroblast growth factor 21 (FGF21) was reported to be protective against inflammation in metabolic disease in recent studies. However, the role of FGF21 in ALI has been rarely investigated. In this study, it was found that the expression of FGF21 was markedly increased in lung tissue under lipopolysaccharide (LPS) stimulation in vivo, whereas it was decreased in lung epithelial cells under LPS stimulation in vitro. Therefore, our research aimed to elucidate the potential role of FGF21 in LPS-induced ALI and to detect possible underlying mechanisms. The results revealed that the deficiency of FGF21 aggravated pathological damage, inflammatory infiltration, and pulmonary function in LPS-induced ALI, while exogenous administration of FGF21 improved these manifestations. Moreover, through RNA sequencing and enrichment analysis, it was unveiled that FGF21 might play a protective role in LPS-induced ALI via JAK2/STAT3 signaling pathway. The therapeutic effect of FGF21 was weakened after additional usage of JAK2 activator in vivo. Further investigation revealed that FGF21 significantly inhibited STAT3 phosphorylation and impaired the nuclear translocation of STAT3 in vitro. In addition, the aggravation of inflammation caused by silencing FGF21 can be alleviated by JAK2 inhibitor in vitro. Collectively, these findings unveil a potent protective effect of FGF21 against LPS-induced ALI by inhibiting the JAK2/STAT3 pathway, implying that FGF21 might be a novel and effective therapy for ALI.

Covalent conjugation with polyphenol reduced the sensitization of walnut and ameliorated allergy by enhancing intestinal epithelial barrier in mice.

In order to reduce the sensitization of walnut protein (WP), the effects of the interaction between WP and (-)-Epigallocatechin gallate (EGCG), quercetin, trans-ferulic acid, and resveratrol were investigated. Covalent and non-covalent conjugations were compared. The results suggested that covalent conjugation reduced the free amino acid content, sulfhydryl content, and surface hydrophobicity. When compared to non-covalent conjugation, covalent modification showed a lower IgE binding capacity, accompanied by changes in protein conformation. Moreover, animal experiments revealed that there were up-regulation of transforming growth factor-ß, T-box expressed in t cells, and forkhead transcription factor Foxp3 mRNA expression, and down-regulation of IL-4, IL-17, GATA binding protein 3 and retinoid-related orphan nuclear receptor γt mRNA expression in the conjugate groups. These results suggested that covalent conjugation of polyphenols, especially EGCG, likely ameliorated allergy by promoting Th1/Th2 and Treg/Th17 balance and alleviating allergy-induced intestinal barrier damage, which might be a support in reducing the allergenicity of WP.

Sensitive and Selective Dual-Mode Responses to Reactive Oxygen Species by Chiral Manganese Dioxide Nanoparticles for Antiaging Skin.

Excessive accumulation of reactive oxygen species (ROS) can lead to oxidative stress and oxidative damage, which is one of the important factors for aging and age-related diseases. Therefore, real-time monitoring and the moderate elimination of ROS is extremely important. In this study, a ROS-responsive circular dichroic (CD) at 553 nm and magnetic resonance imaging (MRI) dual-signals chiral manganese oxide (MnO2 ) nanoparticles (NPs) are designed and synthesized. Both the CD and MRI signals show excellent linear ranges for intracellular hydrogen peroxide (H2 O2 ) concentrations, with limits of detection (LOD) of 0.0027 nmol/106 cells and 0.016 nmol/106 cells, respectively. The lower LOD achieved with CD detection may be attributable to its higher anti-interference capability from the intracellular matrix. Importantly, ROS-induced cell aging is intervened by chiral MnO2 NPs via redox reactions with excessive intracellular ROS. In vivo experiments confirm that chiral MnO2 NPs effectively eliminate ROS in skin tissue, reduce oxidative stress levels, and alleviate skin aging. This approach provides a new strategy for the diagnosis and treatment of age-related diseases.

Immunoadjuvant-Modified Rhodobacter sphaeroides Potentiate Cancer Photothermal Immunotherapy.

Photothermal immunotherapy has become a promising strategy for tumor treatment. However, the intrinsic drawbacks like light instability, poor immunoadjuvant effect, and poor accumulation of conventional inorganic or organic photothermal agents limit their further applications. Based on the superior carrying capacity and active tumor targeting property of living bacteria, an immunoadjuvant-intensified and engineered tumor-targeting bacterium was constructed to achieve effective photothermal immunotherapy. Specifically, immunoadjuvant imiquimod (R837)-loaded thermosensitive liposomes (R837@TSL) were covalently decorated onto Rhodobacter sphaeroides (R.S) to obtain nanoimmunoadjuvant-armed bacteria (R.S-R837@TSL). The intrinsic photothermal property of R.S combined R837@TSL to achieve in situ near-infrared (NIR) laser-controlled release of R837. Meanwhile, tumor immunogenic cell death (ICD) caused by photothermal effect of R.S-R837@TSL, synergizes with released immunoadjuvants to promote maturation of dendritic cells (DCs), which enhance cytotoxic T lymphocytes (CTLs) infiltration for further tumor eradication. The photosynthetic bacteria armed with immunoadjuvant-loaded liposomes provide a strategy for immunoadjuvant-enhanced cancer photothermal immunotherapy.