1,3,5-2,4,6-Functionalized Benzene Molecular Cage: An Environmentally Responsive Scaffold that Supports Hierarchical Superstructures.

New stimulus responsive scaffolds are of interest as constituents of hierarchical supramolecular ensembles. 1,3,5-2,4,6-Functionalized, facially segregated benzene moieties have a time-honored role as building blocks for host molecules. However, their user as switchable motifs in the construction of multi-component supramolecular structures remains poorly explored. Here, we report a molecular cage 1, which consists of a bent anthracene dimer 3 paired with 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene 2. As the result of the pH-induced ababab ↔ bababa isomerization of the constituent functionalized benzene units derived from 2, this cage can reversibly convert between an open state and a closed form, both in solution and in the solid state. Cage 1 was used to create stimuli-responsive hierarchical superstructures, viz. Russian doll-like complexes with [K⊂18-crown-6⊂1]+ and [K⊂cryptand-222⊂1]+. The reversible assembly and disassembly of these superstructures could be induced by switching cage 1 from its open to closed form. The present study thus provides an unusual example where pH-triggered conformation motion within a cage-like scaffold is used to control the formation and disassociation of hierarchical ensembles.

Enhanced brain-targeting and efficacy of cannabidiol via RVG-Exo/CBD nanodelivery system.

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.

Self-Thermal Management in Filtered Selenium-Terminated MXene Films for Flexible Safe Batteries.

Li-ion batteries with superior interior thermal management are crucial to prevent thermal runaway and ensure safe, long-lasting operation at high temperatures or during rapid discharging and charging. Typically, such thermal management is achieved by focusing on the separator and electrolyte. Here, the study introduces a Se-terminated MXene free-standing electrode with exceptional electrical conductivity and low infrared emissivity, synergistically combining high-rate capacity with reduced heat radiation for safe, large, and fast Li+ storage. This is achieved through a one-step organic Lewis acid-assisted gas-phase reaction and vacuum filtration. The Se-terminated Nb2Se2C outperformed conventional disordered O/OH/F-terminated materials, enhancing Li+-storage capacity by ≈1.5 times in the fifth cycle (221 mAh·g-1 at 1 A·g-1) and improving mid-infrared adsorption with low thermal radiation. These benefits result from its superior electrical conductivity, excellent structural stability, and high permittivity in the infrared region. Calculations further reveal that increased permittivity and conductivity along the z-direction can reduce heat radiation from electrodes. This work highlights the potential of surface groups-terminated layered material-based free-standing flexible electrodes with self-thermal management ability for safe, fast energy storage.

Water and Air Stable Copper(I) Complexes of Tetracationic Catenane Ligands for Oxidative C-C Cross-Coupling.

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

Development and validation of machine learning models for diagnosis and prognosis of cancer by urinary proteomics, based on the FLEMENGHO cohort.

The current study aims to develop and validate machine learning (ML) models for the prediction of cancer status by the non-invasive urinary proteomic in a population-based cohort. In this retrospective study, urinary proteome profiles in 804 cases from the FLEMENGHO cohort were measured by mass spectrometry. After feature selection by LASSO on both clinical variables and urinary proteome profile, benchmark models by clinical variables were built with six different ML algorithms. Proteome-based models and combined models were built and compared with the benchmark models. The models' performance, i.e. area under the curve (AUC) was compared by Delong method. The 95% confidence interval was estimated by the bootstrapping method. The best-performing model was explained by Shapley Additive Explanations (SHAP) method. The predictive role of proteome biomarkers in longitudinal cancer diagnosis was also explored. A clinical model, based on age, blood sugar and blood lipid profile, yielded the best AUC of 0.75 (0.68-0.82), with 0.80 (0.72-0.91) for the proteome model based on 13 selected biomarkers and 0.83 (0.77-0.90) for the combined model (P=0.01 for comparison with clinical model). SHAP on the support vector machine in the combined setting showed that except for age, proteome biomarkers contribute to the final prediction of the model. After adjusting with clinical factors, three proteome biomarkers are independent risk factors for longitudinal cancer development. Urinary proteome profiling, together with fine-tuned machine learning algorithms, demonstrates the predictive potential for cancer diagnosis transparently.

Genetic Association Studies in Restless Legs Syndrome: Risk Variants & Ethnic Differences.

BACKGROUND: Genetic association studies have not produced consistent results in restless legs syndrome (RLS). OBJECTIVES: To conduct a systematic review on genetic association studies in RLS to highlight the common gene variants and ethnic differences. METHODOLOGY: We conducted Pubmed, Embase, and Cochrane search using terms "Genetic association studies" and "restless legs syndrome" for candidate gene-based studies. Out of the initial 43 studies, 18 case control studies (from 2012 to 2022) were included. Thirteen studies including 10794 Caucasian subjects (4984 RLS cases and 5810 controls) and five studies involving 2009 Asian subjects (796 RLS cases and 1213 controls) were tabulated and analyzed. In addition, three Genome-Wide Association Studies (GWAS) in Asians and Europeans/Caucasians were included for comparisons. RESULTS: In the Asian population, gene variants in BST1, SNCA Rep1, IL1B, BTBD9, and MAP2K5/SKOR1 increased the risk of RLS (odds ratio range 1.2-2.8). In Caucasian populations, examples of variants that were associated with an increased risk of RLS (odds ratio range 1.1-1.9) include those in GABRR3 TOX3, ADH1B, HMOX1, GLO1, DCDC2C, BTBD9, SKOR1, and SETBP1. Based on the meta-analysis of GWAS studies, the rs9390170 variant in UTRN gene was identified to be a novel genetic marker for RLS in Asian cohorts, whereas rs113851554 in MEIS1 gene was a strong genetic factor among the >20 identified gene variants for RLS in Caucasian populations. CONCLUSION: Our systemic review demonstrates that multiple genetic variants modulate risk of RLS in Caucasians (such as MEIS1 BTBD9, MAP2K5) and in Asians (such as BTBD9, MAP2K5, and UTRN).

The structural and functional properties of hemp protein isolate-epigallocatechin-3-gallate biopolymer covalent complex during heating.

BACKGROUND: It is well known that hemp proteins have the disadvantages of poor solubility and poor emulsification. To improve these shortcomings, an alkali covalent cross-linking method was used to prepare hemp protein isolate-epigallocatechin-3-gallate biopolymer (HPI-EGCG) and the effects of different heat treatment conditions on the structure and emulsifying properties of the HPI-EGCG covalent complex were studied. RESULTS: The secondary and tertiary structures, solubility, and emulsification ability of the HPI-EGCG complexes were evaluated using particle size, zeta potential, circular dichroism (CD), and fluorescence spectroscopy indices. The results showed that the absolute value of zeta potential of HPI-EGCG covalent complex was the largest, 18.6 mV, and the maximum binding amount of HPI to EGCG was 29.18 µmol g-1 . Under heat treatment at 25-35 °C, the α-helix content was reduced from 1.87% to 0%, and the ß-helix content was reduced from 82.79% to 0% after the covalent binding of HPI and EGCG. The solubility and emulsification properties of the HPI-EGCG covalent complexes were improved significantly, and the emulsification activity index (EAI) and emulsion stability index (ESI) were increased by 2.77-fold and 1.21-fold, respectively. CONCLUSION: A new HPI-EGCG covalent complex was developed in this study to provide a theoretical basis for the application of HPI-EGCG in food industry. © 2023 Society of Chemical Industry.

Nanotheranostic Trojan Horse for visualization and photo-immunotherapy of multidrug-resistant bacterial infection.

Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient imaging diagnosis of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate bacteria, both extracellularly and intracellularly. Further combined with photothermal therapy-induced immunogenic cell death and MP-MENP-mediated macrophage reprogramming, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrates dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promises a new way for complete eradication of MDR bacterial infection.

M1 macrophages induce PD-L1hi cell-led collective invasion in HPV-positive head and neck squamous cell carcinoma via TNF-α/CDK4/UPS14.

BACKGROUND: Although the roles of PD-L1 in promoting tumor escape from immunosurveillance have been extensively addressed, its non-immune effects on tumor cells remain unclear. METHODS: The spatial heterogeneity of PD-L1 staining in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) tissues was identified by immunohistochemistry. Three-dimensional (3D) specific cell-led invasion assay and 3D cancer spheroid model were used to investigate the roles of PD-L1hileader cells in collective invasion. The impact of M1 macrophages on specific PD-L1 expression in leader cells and its mechanisms were further studied. Finally, the effect of combination therapy of anti-PD-L1 and CDK4 inhibitor on HPV-positive tumors were evaluated on a mice model. RESULTS: Here, we observed a distinctive marginal pattern of PD-L1 expression in HPV-positive HNSCC tissues. By mimicking this spatial pattern of PD-L1 expression in the 3D invasion assay, we found that PD-L1hi cells led the tumor collective invasion. M1 macrophages induced specific PD-L1 expression in leader cells, and depletion of macrophages in tumor-bearing mice abrogated PD-L1hileader cells and collective invasion. Mechanistically, TNF-α secreted by M1 macrophages markedly increased the abundance of PD-L1 via CDK4/ubiquitin-specific peptidase 14-mediated deubiquitination of PD-L1. We also found that suppression of CDK4 enhanced the efficacy of anti-PD-L1 therapy in an E6/E7 murine model. CONCLUSIONS: Our study identified TNF-α/CDK4/ubiquitin-specific peptidase 14-mediated PD-L1 stability as a novel mechanism underlying M1 macrophage-induced PD-L1hileader cells and collective tumor invasion, and highlighted the potential of the combination therapy of anti-PD-L1 and CDK4 inhibitor for HPV-positive HNSCC.

Integrated metabolomics and network pharmacology to reveal the mechanism of areca nut addiction.

As a chewing hobby, areca nut (Areca catechu L.) has become the most common psychoactive substance in the world, besides tobacco, alcohol and caffeinated beverages. Moreover, as a first-class carcinogen designated by International Agency for Research on Cancer, long-term chewing areca nut can result in oral mucosal diseases and even oral cancer. To clarify the potential mechanism of areca nut addiction, an integrated strategy of metabolomics and network pharmacology was adopted in this study. Network pharmacology study indicated that all the key targets related to areca nut addiction could be regulated by arecoline and pointed out the importance of G-protein coupled receptor signalling pathway. Analysis results of mice plasma metabolome and faeces metabolome intervened by arecoline suggested that the component may affect the dopamine system and 5-HT system by regulating phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and intestinal flora structure. Moreover, the potential importance of bile acids in formation of addictive behaviour of chewing areca nut was investigated by integrative analysis of the relationships between metabolites and intestinal flora. The study can provide scientific basis for the addiction intervention and treatment of areca nut chewers.

Peptide-drug co-assembling: A potent armament against cancer.

Cancer is still one of the major problems threatening human health and the therapeutical efficacies of available treatment choices are often rather low. Due to their favorable biocompatibility, simplicity of modification, and improved therapeutic efficacy, peptide-based self-assembled delivery systems have undergone significant evolution. Physical encapsulation and covalent conjugation are two common approaches to load drugs for peptide assembly-based delivery, which are always associated with drug leaks in the blood circulation system or changed pharmacological activities, respectively. To overcome these difficulties, a more elegant peptide-based assembly strategy is desired. Notably, peptide-mediated co-assembly with drug molecules provides a new method for constructing nanomaterials with improved versatility and structural stability. The co-assembly strategy can be used to design various nanostructures for cancer therapy, such as nanotubes, nanofibrils, hydrogels, and nanovesicles. Recently, these co-assembled nanostructures have gained tremendous attention for their unique superiorities in tumor therapy. This article describes the classification of assembled peptides, driving forces for co-assembly, and specifically, the design methodologies for various drug molecules in co-assembly. It also highlights recent research on peptide-mediated co-assembled delivery systems for cancer therapy. Finally, it summarizes the pros and cons of co-assembly in cancer therapy and offers some suggestions for conquering the challenges in this field.

Gene knockout of glutathione reductase results in increased sensitivity to heavy metals in Acidithiobacillus caldus.

Acidithiobacillus caldus plays an important role in bioleaching of low-grade metal ore. It can promote the release of heavy metals in mining-associated habitats and survive in high concentrations of heavy metals. Functions of glutathione reductase (GR) in cell defense against reactive oxygen species caused by heavy metals have been elucidated in some eukaryotic cells and bacteria; however, no information is available in A. caldus. In this research, the methods of bioinformatics, gene expression, GR activity assays were used to detect and characterize the glutathione reductase gene from the A. caldus MTH-04 strain. Then, A. caldus gr knockout mutant and gr overexpression strain were constructed, and the heavy metal tolerant properties and transcriptional levels of ROS related genes of them were compared to study the function of GR. The results showed that, a putative gr gene F0726_RS04210 was detected in the genome of A. caldus MTH-04. The purified recombinant protein of F0726_RS04210 showed remarkable GR activity at optimal pH 7.0 and 30°C using in vitro assay. The evolutionary relationship of GR from A. caldus MTH-04 was close to that from Escherichia coli K12. Gene knockout or overexpression of gr in A. caldus did not affect the growth rate on S0 medium, suggesting that GR did not play a key role in the activation of sulfur. Deletion of gr resulted in increased sensitivity to heavy metals (Cu2+ and Zn2+) in A. caldus, and the gr overexpression strain showed enhanced tolerance to heavy metals. Furthermore, transcription analysis also revealed strong correlations between GR and the antioxidant pathway. The above results suggest that GR can play an important role in heavy metal tolerance in A. caldus.

Sonoactivated Nanomaterials: A potent armament for wastewater treatment.

The world is currently facing a critical issue of water pollution, with wastewater being a major contributor. It comes from different types of pollutants, including industrial, medical, agricultural, and domestic. Effective treatment of wastewater requires efficient degradation of pollutants and carcinogens prior to discharge. Commonly used methods for wastewater treatment include filtration, adsorption, biodegradation, advanced oxidation processes, and Fenton oxidation, among others.The sonochemical effect refers to the decomposition, oxidation, reduction, and other reactions of pollutant molecules in wastewater upon ultrasound activation, achieving pollutants removal. Furthermore, the micro-flow effect generated by ultrasonic waves creates tiny bubbles and eddies. This significantly increases the contact area and exchange speed of pollutants and dissolved oxygen, thereby accelerating pollutant degradation. Currently, ultrasonic-assisted technology has emerged as a promising approach due to its strong oxidation ability, simple and cheap equipments, and minimal secondary pollution. However, the use of ultrasound in wastewater treatment has some limitations, such as high energy consumption, lengthy treatment time, limited water treatment capacity, stringent water quality requirements, and unstable treatment effects. To address these issues, the combination of enhanced ultrasound with nanotechnology is proposed and has shown great potential in wastewater treatment. Such a combination can greatly improve the efficiency of ultrasonic oxidation, resulting in an improved performance of wastewater purification. This article presents recent progress in the development of sonoactivated nanomaterials for enhanced wastewater disposal. Such nanomaterials are systematically classified and discussed. Potential challenges and future prospects of this emerging technology are also highlighted.

The spatial distribution of interleukin-4 (IL-4) reference values in China based on a back propagation (BP) neural network.

This study aimed to investigate the geospatial distribution of normal reference values of Interleukin 4 (IL-4) in healthy Chinese adults and to provide a basis for the development of standard references. IL-4 values of 5,221 healthy adults from 64 cities in China were collected and analyzed for a potential correlation with 24 topographical, climatic and soil factors. Seven of these factors were extracted and used to build a back propagation (BP) neural network model that was used to predict IL-4 reference values in healthy individuals from 2,317 observation sites nationwide. The predicted values were tested for normality and geographic distribution by analytic Kriging interpolation to map the geographic distribution of IL-4 reference values in healthy Chinese subjects. The results showed that IL-4 values generally decreased and then increased from the South to the North. We concluded that the BP neural network model applies to this approach, where certain geographical factors determine levels of various biochemical and immunological standards in healthy adults in regions with different topography, climate and soil indices.

GAD1-mediated GABA elicits aggressive characteristics of human oral cancer cells.

Studies suggest that the expression of glutamate decarboxylase 1 (GAD1), γ-aminobutyric acid (GABA), and GABA receptors are involved in tumor progression. However, the underlying mechanisms of high expression and potential functions of GAD1 and GABA in oral squamous cell carcinoma (OSCC) are not known. In this study, we found that the expressions of GAD1 and GABA were considerably increased in OSCC samples, which were closely associated with clinical stage and lymph node metastasis. The knockdown of GAD1 expression significantly inhibited the proliferation, migration and invasion abilities of OSCC cells by reducing the expression of GABA-mediated GABAB receptors, which could be reversed by exogenous GABA, but did not cause excessive OSCC cell proliferation. And GABA secreted by OSCC cells promoted M2 macrophage polarization for inhibiting anti-tumor immunity by activating GABBR1/ERK/Ca2+. In addition, GABA/GABABR promoted the proliferation and progression of OSCC xenograft tumor. Altogether, our results showed that GAD1 synthetized GABA to promote the malignant progression of OSCC and limits the anti-tumor immunity of macrophages, thereby targeting GABA can be a novel strategy for treating OSCC.

Effect of stepwise psychological intervention on improving adverse mood and quality of life after colon cancer surgery.

OBJECTIVE: To explore the effect of stepwise psychological intervention on adverse mood and quality of life of patients after colon cancer surgery. METHODS: The clinical data from 102 patients with colon cancer admitted to the Second Hospital of Baoding from January 2018 to June 2022 were collected and analyzed retrospectively. Based on the intervention measures, 51 patients with the general intervention were regarded as the general group, and 51 patients with the stepwise psychological intervention were considered as the intervention group. Piper Fatigue Scale (PFS) was used to scale the degree of Cancer-related fatigue (CRF); Self-rating anxiety scale (SAS) and Self-rating depression scale (SDS) were applied to measure the negative emotion; Positive and negative emotion scale (PANAS) was used to evaluate the degree of positive negative emotions. In addition, Symptom Checklist 90 (SCL-90), Connor-Davidson Resilience Scale (CD-RISC) self-assessment scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were applied to evaluate the mental state, mental resilience, and quality of life, respectively. The adverse reactions, prognosis, and intervention satisfaction after intervention were compared between the two groups. RESULTS: After intervention, the PFS scores, SAS score, SDS score, and PANAS score in the general group and intervention groups were decreased (all P < 0.05), and these scores decreased more obviously in the intervention group compared with the general group (all P < 0.05); The scores of each dimension in SCL-90 scale were decreased in both groups (P < 0.05), and the SCL-90 scores in the intervention group were lower than those in the general group (P < 0.05); The scores of each dimension in CD-RISC scale improved in both groups (P < 0.05), and the scores were higher in the intervention group compared with the general group (P < 0.05); The scores of EORTC QLQ-C30 scale improved in both groups (P < 0.05), and these scores were higher in the intervention groups compared with the general group (P < 0.05). In addition, the adverse reaction rate was lower, while the prognosis and nursing satisfaction were better in the intervention group than those in the general group (all P < 0.05). Logistic regression analysis showed that the poor emotion and poor life quality were the risk factors of the poor prognosis (all P < 0.05). CONCLUSIONS: The stepwise psychological intervention can improve the psychological wellbeing and quality of life in the patients after colon cancer surgery.

Bio-inspired self-assembled bacteriochlorin nanoparticles for superior visualization and photothermal ablation of tumors.

BACKGROUND: Although hyperthermia-based photothermal therapy (PTT) has achieved great success in the battle against malignant tumors, various commonly used photothermal sensitizers still suffer from non-selective tumor accumulation, limited photothermal conversion efficiency, potential toxicity and side effects, as well as complex and low cost-effective preparation process. Therefore, novel photothermal sensitizers are urgently required. The well-organized self-assembling of natural bacteriochlorophylls with superior photothermal property may provide an interesting option for the engineering of ideal PTS. METHODS: Inspired by the self-assembly peripheral light-harvesting antennas of natural bacteriochlorin in microorganisms, a biomimetic light-harvesting nanosystem (Nano-Bc) was developed via bacteriochlorophylls self-arranging in aqueous phase. The characterization of Nano-Bc were measured using DLS, TEM, UV-vis-near-infrared spectroscopy and preclinical PA imaging system. The cytotoxicity of Nano-Bc was quantitatively evaluated via a standard MTT assay using mouse breast cancer 4T1 cells, and the in vivo photothermal eradication of tumor was investigated in the 4T1 breast tumor-bearing mouse model. RESULTS: The obtained bacteriochlorin nanoparticles (Nano-Bc) exhibited ultra-high photothermal performance within the biological transparent window, showing superior heating capacity compared to commonly used photothermal sensitizers of organic dye indocyanine green and inorganic gold nanorods. Guiding by the inherent photoacoustic imaging of Nano-Bc, complete tumor elimination in vitro and vivo was evidenced upon laser irradiation. CONCLUSION: The green and facile preparation, ultra-high photothermal effect in the transparent window, excellent photoacoustic imaging capacity, and great biosafety prompt, the bio-inspired Nano-Bc as a promising theranostic platform against cancer in the areas of healthcare.

Cell-membrane-coated nanoparticles for the fight against pathogenic bacteria, toxins, and inflammatory cytokines associated with sepsis.

Sepsis is the main cause of death in patients suffering from serious illness. Yet, there is still no specific treatment for sepsis, and management relies on infection control. Cell membrane-coated nanoparticles (MNPs) are a new class of biomimetic nanoparticles based on covering the surface of synthetic nanoparticles (NPs) with natural cell membranes. They retain the physicochemical properties of synthetic nanomaterials and inherit the specific properties of cellular membranes, showing excellent biological compatibility, enhanced biointerfacing capabilities, capacity to hold cellular functions and characteristics, immunological escape, and longer half-life when in circulation. Additionally, they prevent the decomposition of the encapsulated drug and active targeting. Over the years, studies on MNPs have multiplied and a breakthrough has been achieved for cancer therapy. Nevertheless, the use of "bio"-related approaches is still rare for treating sepsis. Herein, we discussed current state-of-the-art on MNPs for the treatment of bacterial sepsis by combining the pathophysiology and therapeutic benefits of sepsis, i.e., pathogenic bacteria, bacteria-producing toxins, and inflammatory cytokines produced in the dysregulated inflammatory response associated with sepsis.

Pigment Biosynthesis and Molecular Genetics of Fruit Color in Pepper.

Pepper, as a vegetable crop with a wide cultivation area worldwide, besides being a significant condiment and food, also has a momentous use for chemistry, medicine, and other industries. Pepper fruits are rich in various pigments, such as chlorophyll, carotenoids, anthocyanins, and capsanthin, which have important healthcare and economic value. Since various pigments are continuously metabolized during the development of pepper fruits, peppers exhibit an abundant fruit-colored phenotype in both the mature and immature periods. In recent years, great progress has been made in the study of pepper fruit color development, but the developmental mechanisms are still unclear systematically dissected in terms of pigment, biosynthesis, and regulatory genes. The article outlines the biosynthetic pathways of three important pigments: chlorophyll, anthocyanin, and carotenoid in pepper and the various enzymes involved in these pathways. The genetics and molecular regulation mechanisms of different fruit colors in immature and mature peppers were also systematically described. The objective of this review is to provide insights into the molecular mechanisms of pigments biosynthesis in pepper. This information will provide theoretical basis for the breeding of high-quality colored pepper varieties in the future.

LncRNA SELL/L-selectin promotes HPV-positive HNSCC progression and drives fucoidan-mediated therapeutic strategies.

Positive human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) presents a higher risk of lymph node metastasis and poor prognosis. Here, advanced microarray analysis of clinically collected HNSCC tissues revealed significant upregulation of the lncRNA SELL in HPV+ HNSCC, and its overexpression was obviously associated with lymph node metastasis. The lncRNA SELL could function as a promigratory and proinvasive mediator as well as an inducer of M1-like tumour-associated macrophages (TAM) by increasing the level of L-selectin. Furthermore, fucoidan, as an L-selectin inhibitor, obviously weakened the formation of tongue lesions induced by 4-Nitroquinoline N-oxide (4-NQO) in HPV16 E6/E7 transgenic mice. This result drove us to synchronously develop a nanodelivery platform to verify fucoidan-mediated anti-growth and anti-metastasis effects. This work highlighted the important influence of the lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposed a potential fucoidan-mediated therapeutic strategy. STATEMENT OF SIGNIFICANCE: Head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) involvement present a greater risk of lymph node metastasis than HPV negative HNSCC patients. However, treatment protocols, including surgery and platinum-based chemo- and radiotherapy, have not improved the 5-year overall survival due to the high tendency of lymphatic metastasis. Here, microarray of clinical HNSCC samples confirms the oncogenic significance of lncRNA SELL, which acts as an M1-like TAM inducer and promotes tumorigenesis by upregulating L-selectin. Fucoidan, as an L-selectin inhibitor, suppresses tongue lesions in transgenic mice, and a fucoidan-mediated nanodelivery platform inhibits HPV+ HNSCC growth. The present study highlights lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposes a potential fucoidan-mediated therapeutic.