A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis.

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.

Modulatory effects of fermented Polygonatum cyrtonema Hua on immune homeostasis and gut integrity in a dextran-sulfate-sodium-induced colitis model.

The gut health-promoting properties of saponin-rich Polygonatum cyrtonema Hua (FP) fermented with Lactobacillus plantarum P9 were explored in a dextran sulfate sodium (DSS)-induced colitis mouse model. FP supplementation effectively inhibited DSS-induced physiological alteration and impaired immune responses by reducing the disease activity index (DAI) score and restoring the T helper (Th) 1/Th2 and regulatory T (Treg)/Th17 ratios. In addition, FP supplementation protected the gut barrier function against DSS-induced damage via upregulation of zonula occludens (ZO)-1 and occludin and downregulation of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-18, and the granulocyte-macrophage colony-stimulating factor (GM-CSF). This study further elucidated the potential mechanisms underlying the FP-mediated suppression of the plasticity of type 3 innate lymphoid cells (ILC3) and subsequent macrophage polarization. Therefore, the FP supplementation effectively restored mucosal immune homeostasis and enhanced gut integrity. In addition, it suppressed the growth of Escherichia-Shigella and Enterococcus and promoted the enrichment of probiotics and short-chain fatty acid-producing microbes, such as Romboutsia, Faecalibaculum, and Blautia. In conclusion, P. cyrtonema Hua fermented with L. plantarum P9 might be a promising dietary intervention to improve gut health by sustaining overall gut homeostasis and related gut integrity.

Systematic review and meta-analysis of cardiac neurosis for development of clinical practice guidelines of Korean medicine.

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

The application of nanoparticles based on ferroptosis in cancer therapy.

Ferroptosis is a new form of non-apoptotic programmed cell death. Due to its effectiveness in cancer treatment, there are increasing studies on the application of nanoparticles based on ferroptosis in cancer therapy. In this paper, we present a summary of the latest progress in nanoparticles based on ferroptosis for effective tumor therapy. We also describe the combined treatment of ferroptosis with other therapies, including chemotherapy, radiotherapy, phototherapy, immunotherapy, and gene therapy. This summary of drug delivery systems based on ferroptosis aims to provide a basis and inspire opinions for researchers concentrating on exploring this field. Finally, we present some prospects and challenges for the application of nanotherapies to clinical treatment by promoting ferroptosis in cancer cells.

Neuropsychiatric disorders associated with recreational nitrous oxide use.

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

"Closed-Loop" O2-Economizer Induced In Situ Therapeutic Vaccine against Hypoxic Tumors.

Therapeutic tumor vaccines, which use tumor antigens to stimulate a cancer patient's immune system to eventually kill the tumor tissues, have emerged as one of the most attractive strategies in anticancer research. Especially, exploring in situ vaccines has become a potential field in cancer immunotherapy. However, due to the hypoxic tumor microenvironment, the generation of tumor antigens is always mild and not sufficient. Hence, in this study, we designed a closed-loop mitochondrial oxygen-economizer (TPCA) to induce enhanced phototherapy-driven in situ vaccines. The O2-economizer was developed by the integration of the photosensitizer CyI and the mitochondrial inhibitor atovaquone into the PAMAM dendrimer. In vitro and in vivo studies showed that TPCA could enter the mitochondria through (3-propylcarboxyl) triphenylphosphine bromide (TPP) and effectively restrict the respiration of tumor cells to reduce tumor hypoxia, thus providing continuous oxygen for enhanced iodinated cyanine dye mediated photodynamic therapy, which could further induce in situ vaccines for ablating the primary tumor directly and inhibiting the tumor metastasis and recurrence. Furthermore, the antitumor mechanism revealed that O2-economizer-based oxygen-boosted PDT elicited immunogenic cancer cell death with enhanced exposure and release of DAMPs and altered the immunosuppressive tumor microenvironment with increased recruitment of T cells in tumors, thereby inducing in situ vaccines and provoking the systematic antitumor responses against CT26 tumors. This study will provide innovative approaches for local, abscopal, and metastatic tumor treatment.

Multi-omics reveals that green pea (Pisum sativum L.) hull supplementation ameliorates non-alcoholic fatty liver disease via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway.

Diets rich in various active ingredients may be an effective intervention strategy for non-alcoholic fatty liver disease (NAFLD). The green pea hull (GPH) is a processing by-product of green peas rich in dietary fiber and polyphenols. Here, a mouse model of NAFLD induced by DSS + high-fat diet (HFD) was established to explore the intervention effect of the GPH. The results showed that dietary supplements with the GPH can inhibit obesity and reduce lipid accumulation in the mouse liver to prevent liver fibrosis. GPH intervention can improve liver antioxidant capacity, reduce blood lipid deposition and maintain glucose homeostasis. DSS-induced disruption of the intestinal barrier aggravates NAFLD, which may be caused by the influx of large amounts of LPS. A multi-omics approach combining metabolomics and transcriptomic analysis indicated that glycine was the key target and its content was decreased in the liver after GPH intervention, and that dietary supplements with the GPH can relieve NAFLD via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway, which was further supported by liver-associated protein expression. In conclusion, our study demonstrated that dietary GPH can significantly ameliorate NAFLD, and the future development of related food products can enhance the economic value of the GPH.

Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity.

Introduction: Here, based on oxygen-dependent photodynamic therapy (PDT) and oxygen-consumed oxidative phosphorylation of cancer tissues, we designed and developed a nanosystem (named CyI&Met-Liposome, LCM) to co-encapsulate the photosensitizer CyI and mitochondrial respiration inhibitor metformin (Met) as a PDT enhancer. Methods: We synthesized nanoliposomes encapsulating Met and CyI with excellent photodynamic/photothermal and anti-tumor immune properties using a thin film dispersion method. Confocal microscopy and flow cytometry were used to assess the cellular uptake, PDT, photothermal therapy (PTT) and immunogenicity of nanosystem in vitro. Finally, two tumor models in mice were constructed to investigate the tumor suppression and immunity in vivo. Results: The resulting nanosystem relieved hypoxia in tumor tissues, enhanced PDT efficiency, and amplified antitumor immunity induced by phototherapy. As a photosensitizer, CyI effectively killed the tumor by generating toxic singlet reactive oxygen species (ROS), while the addition of Met reduced oxygen consumption in tumor tissues, thereby evoking an immune response via oxygen-boosted PDT. Both in vitro and in vivo results illustrated that LCM effectively restricted the respiration of tumor cells to reduce tumor hypoxia, thus providing continuous oxygen for enhanced CyI-mediated PDT. Furthermore, T cells were recruited and activated at high levels, providing a promising platform to eliminate the primary tumors and synchronously realize effective inhibition of distant tumors.

Triboelectric Nanogenerators-Based Therapeutic Electrical Stimulation on Skin: from Fundamentals to Advanced Applications.

Discovery of the amazing and vital therapeutic roles of electrical stimulation (ES) on skin has sparked tremendous efforts to investigate ES suppliers. Among them, triboelectric nanogenerators (TENGs), as a self-sustainable bioelectronic system, can generate self-powered and biocompatible ES for achieving superior therapeutic effects on skin applications. Here, a brief review of the application of TENGs-based ES on skin is presented, with specific discussions of the fundamentals of TENGs-based ES and its feasibility to be applied for adjusting physiological and pathological processes of skin. Then, a comprehensive and in-depth depiction of emerging representative skin applications of TENGs-based ES is categorized and reviewed, with particular descriptions about its therapeutic effects on achieving antibacterial therapy, promoting wound healing, and facilitating transdermal drug delivery. Finally, the challenges and perspectives for further advancing TENGs-based ES toward a more powerful and versatile therapeutic strategy are discussed, particularly regarding opportunities in fundamental multidisciplinary research and biomedical applications.

Information flow dynamics between geopolitical risk and major asset returns.

We quantify information flows between geopolitical risk (GPR) and global financial assets such as equity, bonds, and commodities, with a focus on the Russian-Ukrainian conflict. We combine transfer entropy and the I-CEEMDAN framework to measure information flows at multi-term scales. Our empirical results indicate that (i) in the short term, crude oil and Russian equity show opposite responses to GPR; (ii) in the medium and long term, GPR information increases the risk in the financial market; and (iii) the efficiency of the financial asset markets can be confirmed on a long-term scale. These findings have important implications for market participants, such as investors, portfolio managers, and policymakers.

Tetrastigma hemsleyanum leaf extracts ameliorate NAFLD in mice with low-grade colitis via the gut-liver axis.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder, manifested as oxidative stress, lipid accumulation, and inflammation of the liver. Tetrastigma hemsleyanum leaves (THL), which are rich in flavonoids and phenolic acids, have good anti-inflammatory, antioxidant, and hepatoprotective effects. However, it is unknown whether THL extracts can improve NAFLD and the underlying mechanisms are unknown. Hence, this study was designed to investigate the effects of THL extracts on NAFLD and perform a preliminary inquiry into the underlying mechanism based on the gut-liver axis. The results showed that THL extracts could reverse NAFLD-related oxidative stress, lipid accumulation, and inflammation. Additionally, the protective effect of THL extracts on the gut includes the maintenance of the intestinal barrier and the regulation of gut microbiota, which may be one of the mechanisms by which THL improves NAFLD. To be specific, in our study, THL extracts alleviated hepatic lipid accumulation and oxidative stress by regulating the expression of lipid synthesis/catabolism and the oxidative stress genes (SREBP-1c/ACC-1/PPAR-α/PPAR-γ/Keap1/Nrf2). In addition, THL extracts reduced damage to the intestinal barrier (ZO-1/Mucin2/occludin) and increased the relative abundance of Lactobacillales, Ruminococcaceae, and Bifidobacteriales in NAFLD mice. In short, THL extracts alleviated NAFLD-related oxidative stress, lipid accumulation, and inflammation in NAFLD mice which may be via the gut-liver axis (gut barrier integrity and gut microbiota).

Enhanced photothermal-ferroptosis effects based on RBCm-coated PDA nanoparticles for effective cancer therapy.

Ferroptosis, a type of programmed cell death induced by the iron-dependent lipid hydroperoxide pathway, has attracted widespread attention. However, Fenton response-dependent ferroptosis has many limitations, such as insufficient reaction conditions in the tumor micro-environment. Here, we propose an all-in-one phototherapy nanoplatform consisting of iron-polydopamine (Fe-PDA), a folic acid-modified red blood cell membrane (FA-RBCm), and epirubicin (EPI), namely, Fe-PDA-EPI@FA-RBCm NPs, to achieve enhanced photothermal-ferroptosis effects via overcoming the limitations of the Fenton-like reaction. The results showed that the synthesized biomimetic nanoparticles could decompose hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH), and further induce the non-apoptotic ferroptosis pathway. After irradiation with near-infrared (NIR) light, the uptake of Fe-PDA-EPI@FA-RBCm NPs by cells could be effectively promoted, and it presented impressive in vitro and in vivo photothermal properties. In vitro and in vivo results showed that laser irradiation could enhance ferroptosis by promoting the production of reactive oxygen species (ROS) and lipid peroxides, down-regulating the expression of glutathione peroxidase 4 (GPX4), and reducing the mitochondrial membrane potential. Furthermore, the photothermal-promoted ferroptosis and apoptosis pathways (photothermal therapy and chemotherapy) exhibited outstanding synergistic antitumor efficacy in vitro and in vivo, with an in vivo tumor inhibition rate as high as 76.95%. In conclusion, the construction of tumor-targeted biomimetic nanocarriers utilizing the advantageous properties of RBCm has been investigated as a potential anticancer strategy.

Self-Assembled CuCo2S4 Nanoparticles for Efficient Chemo-Photothermal Therapy of Arterial Inflammation.

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.

Erratum: Withdrawal notice to: Electroacupuncture plus moxibustion for major depressive disorder: A randomized, sham-controlled, pilot clinical trial.

[This corrects the article DOI: 10.1016/j.imr.2021.100802.].

Holocene seasonal temperature evolution and spatial variability over the Northern Hemisphere landmass.

The origin of the temperature divergence between Holocene proxy reconstructions and model simulations remains controversial, but it possibly results from potential biases in the seasonality of reconstructions or in the climate sensitivity of models. Here we present an extensive dataset of Holocene seasonal temperatures reconstructed using 1310 pollen records covering the Northern Hemisphere landmass. Our results indicate that both summer and winter temperatures warmed from the early to mid-Holocene (~11-7 ka BP) and then cooled thereafter, but with significant spatial variability. Strong early Holocene warming trend occurred mainly in Europe, eastern North America and northern Asia, which can be generally captured by model simulations and is likely associated with the retreat of continental ice sheets. The subsequent cooling trend is pervasively recorded except for northern Asia and southeastern North America, which may reflect the cross-seasonal impact of the decreasing summer insolation through climatic feedbacks, but the cooling in winter season is not well reproduced by climate models. Our results challenge the proposal that seasonal biases in proxies are the main origin of model-data discrepancies and highlight the critical impact of insolation and associated feedbacks on temperature changes, which warrant closer attention in future climate modelling.

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1-Nrf2 Signaling Pathway and Regulating Gut Microbiota.

Inflammatory bowel disease (IBD), with increasing incidence, causes a range of gastrointestinal symptoms and brings distress and impact on the health and lives of patients. The aim of this study was to explore the protective effects of industrially produced rice protein peptides (RPP) on dextran sulfate sodium (DSS)-induced acute colitis in mice and the potential mechanisms. The results showed that RPP treatment alleviated the symptoms of colitis in mice, including weight loss, colon shortening, and injury, decreased the level of disease activity index (DAI), regulated the balance of inflammatory factors and oxidation, activated Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, regulated the expression of related antioxidant proteases, and promoted the expression of intestinal tight junction proteins. In addition, RPP maintained intestinal mucosal barrier function and alleviated acute colitis caused by DSS treatment in mice by increasing the value of F/B, increasing the relative abundance of beneficial bacteria such as Akkermansia, and regulating the level of short-chain fatty acids. In conclusion, RPP alleviated colitis symptoms through the Keap1-Nrf2 signaling pathway and regulating gut microbiota, which had the potential as dietary supplements or functional foods.

Effects of mobile mindfulness training on mental health of employees: A CONSORT-compliant pilot randomized controlled trial.

BACKGROUND: Employee stress and well-being affect organizational efficiency and productivity, as well as physical and psychological health of employees. Mindfulness is believed to reduce stress, prevent diseases, and promote well-being. Mindfulness has been used as the main component of various smartphone-based healthcare applications. Previous studies have suggested that mindfulness applications have a positive effect on employee stress and mental health. However, relatively few randomized controlled trials have examined the effectiveness of mindfulness applications on employees. This study aims to evaluate whether mobile mindfulness training (MMT) as a stress self-management tool improves employees' perceived stress, subjective well-being, and Mibyeong, a condition that is not a disease but shows obvious health abnormalities. METHODS: Participants were recruited through advertisements displayed at 3 workplaces, including a patent attorney's office, a construction company, and a public relations firm. A total of 45 employees were randomly assigned to 1 of 2 groups: the MMT group (Group A) receiving smartphone application-based mindfulness training, and a wait-list control (WLC) group (Group B), who received no intervention. Group A employees conducted MMT following daily and event guidelines for 4 weeks. In contrast, Group B employees did not receive any intervention in that time. The outcome variables were perceived stress, subjective well-being, and Mibyeong. Surveys were conducted at baseline, post-intervention, and follow-up (fourth week post-intervention). RESULTS: Demographic characteristics and baseline assessments were not significantly different between the 2 groups. The results of this study revealed that subjective well-being and Mibyeong were significantly improved in the MMT group compared with the WLC group. Moreover, this improvement was maintained up to at least 4 weeks later. However, perceived stress was not significantly reduced in the MMT group compared to the WLC group. CONCLUSION: Four weeks of MMT improved the subjective well-being and Mibyeong of employees. However, further studies are required to investigate the effect of MMT on other areas of mental health.

Characterization of an (R)-specific enoyl-CoA hydratase from Streptomyces sp. strain CFMR 7: A metabolic tool for enhancing the production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate).

Poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] [P(3HB-co-3HHx)] has a high potential to serve as a commercial bioplastic due to its biodegradability, thermoplastic and mechanical properties. The properties of this copolymer are greatly affected by the composition of 3HHx monomer. One of the most efficient ways to modulate the composition of 3HHx monomer in P(3HB-co-3HHx) is by manipulating the (R)-3HHx-CoA monomer supply. In this study, a new (R)-specific enoyl-CoA hydratase originating from a non-PHA producer, Streptomyces sp. strain CFMR 7 (PhaJSs), was characterized and found to be effective in supplying 3HHx monomer during in vivo production of P(3HB-co-3HHx) copolymer. The P(3HB-co-3HHx) copolymer produced from the Cupriavidus necator transformant that harbors phaJSs, PHB-4/pBBR1-CBP-M-CPF4JSs, showed enhanced 3HHx incorporation of up to 11 mol% without affecting the P(3HB-co-3HHx) production when palm oil was used as the carbon source. In addition, both kcat and kcat/Km of PhaJSs were higher toward the C6 than the shorter C4 substrates, underscoring the preference for 3-hydroxyhexanoyl-CoA. These results suggest that PhaJSs has a significant ability to supply 3HHx monomers for PHA biosynthesis via ß-oxidation and can be applied for metabolic engineering of robust PHA-producing strains.

Efficient epidermal delivery of antibiotics by self-assembled lecithin/chitosan nanoparticles for enhanced therapy on epidermal bacterial infections.

The treatment for epidermal bacterial infections has become a primary healthy concern, producing a significant therapeutic challenge. Here we present a facile strategy to fabricate lecithin/chitosan nanoparticles (LCNPs) for efficient epidermal drug delivery over epidermal bacterial infections. The central rotatable composite design method was used for the optimization of the preparation, and that the optimal size (212.63 ± 1.95 nm) was obtained via analysis of variance (ANOVA). The prepared CIP-LCNPs show an average diameter of 325.9 ± 7.4 nm and a zeta potential of 26.6 ± 1.2 mV. Antibiotics can be well encapsulated in LCNPs and its release kinetics is studied with cumulative release of 93.81 ± 2.05 % for 48 h. The hemolytic activity, cytotoxicity, and skin irritation are further investigated. The zones of inhibition are 2.16 ± 0.04 cm and 2.92 ± 0.03 cm for Escherichia coli and Staphylococcus aureus, respectively. Moreover, in vitro permeation studies demonstrate that LCNPs can increase the accumulation of antibiotics in the epidermis with retention ratio 2-3 fold higher than commercial formulations. The in vivo result over epidermal-infected wound demonstrates the superior therapeutic effects of LCNPs. The developed LCNPs represent an important advance in fabricating therapeutic materials for enhanced therapy over epidermal bacterial infections.

Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome.

Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals-gut microbiota-intestinal metabolites-low-grade inflammation-metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.