A heterologous expression platform in Aspergillus nidulans for the elucidation of cryptic secondary metabolism biosynthetic gene clusters: discovery of the Aspergillus fumigatus sartorypyrone biosynthetic pathway.

Aspergillus fumigatus is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have developed a heterologous expression platform in Aspergillus nidulans, using a newly created genetic dereplication strain, to express a previously unknown BGC from A. fumigatus and determine its products. The BGC produces sartorypyrones, and we have named it the spy BGC. Analysis of targeted gene deletions by HRESIMS, NMR, and microcrystal electron diffraction (MicroED) enabled us to identify 12 products from the spy BGC. Seven of the compounds have not been isolated previously. We also individually expressed the polyketide synthase (PKS) gene spyA and demonstrated that it produces the polyketide triacetic acid lactone (TAL), a potentially important biorenewable platform chemical. Our data have allowed us to propose a biosynthetic pathway for sartorypyrones and related natural products. This work highlights the potential of using the A. nidulans heterologous expression platform to uncover cryptic BGCs from A. fumigatus and other species, despite the complexity of their secondary metabolomes.

Real-Time Observation for Dynamic Oscillation during Self-Assembly and Clearance of Aß42.

The dynamic oscillation implicated in structural heterogeneity during the self-assembly of amyloid peptide 1-42 (Aß42) may play a crucial role in eliciting cellular responses. We developed a real-time monitoring platform to observe an oscillatory non-equilibrium interaction that dominated the Aß42 clearance by neuronal cells during interplay with an oscillator (lipopolysaccharide, LPS). Molecular dynamics studies indicated that the electrostatic and hydrophobic segments of LPS involved in the temporary heteromolecular association and slightly decelerated the intrinsic thermally-induced protein dynamics of Aß42. A bait-specific intervention strategy could temporarily slow down the self-propagation of Aß42 to extend the lifetime of autonomous oscillation and augment Aß42 clearance of neuronal cells. The lifetime increment of oscillation shows a bait concentration-dependent manner to reflect the non-equilibrium binding strength. This relationship may serve as a predictor for Alzheimer's disease drug discovery.

Polystyrene Upcycling into Fungal Natural Products and a Biocontrol Agent.

Polystyrene (PS) is one of the most used yet infrequently recycled plastics. Although manufactured on the scale of 300 million tons per year globally, current approaches toward PS degradation are energy- and carbon-inefficient, slow, and/or limited in the value that they reclaim. We recently reported a scalable process to degrade post-consumer polyethylene-containing waste streams into carboxylic diacids. Engineered fungal strains then upgrade these diacids biosynthetically to synthesize pharmacologically active secondary metabolites. Herein, we apply a similar reaction to rapidly convert PS to benzoic acid in high yield. Engineered strains of the filamentous fungus Aspergillus nidulans then biosynthetically upgrade PS-derived crude benzoic acid to the structurally diverse secondary metabolites ergothioneine, pleuromutilin, and mutilin. Further, we expand the catalog of plastic-derived products to include spores of the industrially relevant biocontrol agent Aspergillus flavus Af36 from crude PS-derived benzoic acid.

Chinese Herbal Fumigation Steam Therapy and Acupuncture in the Treatment of Knee Osteoarthritis: A Three-armed, Randomized, Controlled Trial.

Context: Knee osteoarthritis is a common form of joint disease found in humans and one of the leading causes of disability globally. Knee osteoarthritis (KOA) is responsible for a higher number of disabilities than any other medical condition affecting activities of daily living (ADL). To date no definitive, conventional medical protocol is available to deal with KOA. Objectives: The study intended to clinically investigate whether the benefits of acupuncture in the treatment of KOA) could be augmented by the addition of Chinese herbal fumigation steam therapy (CHFST) to the treatment protocol and to what degree it had benefits. Design: The research team designed a three-armed, randomized, controlled trial. The sample size was determined by analysis of power; for a sample size of 42, the power was 83.5%; the effect size was 0.5; and the α was 0.05. Setting: The setting was the traumatology department in the Chinese Medicine Branch of Taipei City Joint Hospital in Kun Ming, Taiwan. Participants: Participants were 45 males and females between the ages of 35 and 75, who were patients in the traumatology department and who were suffering from bilateral knee osteoarthritis. Three participants were lost to follow-up. Interventions: Participants were randomly assigned to one of three groups, each with 15 participants; (1) the control group, who received acupuncture only; (2) the normal CHFST group, an intervention group who received acupuncture plus a normal dose of CHFST; and (3) the one-sixteenth CHFST group, an intervention group who received acupuncture plus one-sixteenth of a normal dose of CHFST. Participants underwent biweekly treatments for four consecutive weeks. Outcomes Measures: The primary outcome measures included a visual analog scale (VAS) to assess variations in pain intensity and a goniometer measure for range of motion (ROM). Results: The addition of CHFST to acupuncture in the treatment of KOA significantly reduced pain (P = .0017) for the normal CHFST group compared to the control group and the one-sixteenth CHFST group. Chinese medical interventions overall for all groups showed a decrease in pain and increases in ROM, and health related quality of life (HrQoL). Conclusions: CHFST, in conjunction with acupuncture, showed promise in the treatment of KOA in reducing pain, increasing ROM, and improving quality of life (QoL).

Transdermal Delivery of Succinate Accelerates Energy Dissipation of Brown Adipocytes to Reduce Remote Fat Accumulation.

Weight loss by increasing energy consumption of thermogenic adipocytes to overcome obesity remains a challenge. Herein, we established a transdermal device that was based on the local and temporarily controlled delivery of succinate (SC), a tricarboxylic acid cycle metabolic intermediate to stimulate the thermogenesis pathway of uncoupling protein 1 (UCP1) and accelerate energy dissipation of brown adipose tissue (BAT) under the dorsal interscapular skin, further initiating the consumption of fatty acids by systemic metabolism. SC microneedle patches significantly suppressed weight gain and fat accumulation of remote organs, including liver and peripheral white adipose tissue (WAT) in high-fat diet-induced obese mice. mRNA expression levels of Ucp1 in BAT and other browning markers in WAT were significantly elevated in the mice that were treated with SC microneedle. Thus, the energy dissipation of BAT using UCP1-mediated thermogenesis accelerated by the transdermal delivery of SC may become a potential and effective strategy for preventing obesity.

Factors associated with having home care physicians as an integrated source of medications for chronic conditions among homebound patients.

BACKGROUND: Inappropriate management of medications is a major threat to homebound patients with chronic conditions. Despite many efforts in improving medication reconciliation in ambulatory and inpatient settings, little research has focused on home care settings. In 2016, Taiwan initiated the Integrated Home Health Care programme, which was intended to reduce potentially inappropriate medication management and risks of uncontrolled polypharmacy through the integration of different medication sources for chronic conditions among homebound patients. This study investigated factors associated with having home care physicians as an integrated source of medications for chronic conditions among homebound patients. METHOD: This retrospective cohort study enrolled 3142 community-dwelling homebound patients from Taipei City Hospital. Homebound patients' adherence to using home care physicians as an integrated source of chronic condition medications was defined as having all prescriptions for their chronic conditions prescribed by a single home care physician for at least 6 months. Both patient and home care physician characteristics were analysed. Multivariable logistic regression was applied. RESULTS: Of the 3142 patients with chronic conditions, 1002 (31.9%) had consistently obtained all medications for their chronic illnesses from their home care physicians for 6 months and 2140 (68.1%) had not. The most common chronic diseases among homebound patients were hypertension, diabetes mellitus, dementia, cerebrovascular disease and constipation. Oldest-old patients with poor functional status, fewer daily medications, no co-payment exemption and no recent inpatient experience were more likely to adhere to this medication integration system. In addition, patients whose outpatient physicians were also their home care physicians were more likely to adhere to the system. CONCLUSIONS: The finding suggests that building trust and enhancing communication among homebound patients, caregivers and home care physicians are critical. Patient and provider variations highlight the need for further improvement and policy modification for medication reconciliation and management in home care settings. The improvement in medication management and care integration in home care settings may reduce misuse and polypharmacy and improve homebound patients' safety.

Retrospective study of the differences in patient characteristics and revenue between male and female surgeons in Taiwan.

Surgery is traditionally a male-dominated field, and gender differences exist despite the growing numbers of female surgeons. A handful of studies have evaluated the condition in Asian societies. We aimed to examine the difference between female and male surgeons in urology, general surgery, and gynecology by analyzing a nationwide, population-based database. We identified surgeons with a clinical experience of six to thirteen years between 1995 to 2013 from the National Health Insurance Research Database. We collected patient numbers and revenue per month in outpatient and inpatient care, as well as monthly numbers of surgeries conducted by female and male surgeons in urology, general surgery, and gynecology, for analysis. Original student's t-test and wilcoxon rank sum test was used to compare the differences between female and male surgeons, and p values less than 0.05 were considered statistically significant. Female urologists and general surgeons had a significantly higher ratio of female patients in Taiwan. Female urologists had patient numbers, revenues, and numbers of surgeries comparable to male urologists. In contrast, female general surgeons had significantly less involvement in outpatient and inpatient care and had low monthly revenues. Female general surgeons contradictorily performed more oncological surgeries per month than males. However, the difference in numbers of oncological surgeries was not significant after excluding breast cancer surgeries. Female gynecologists had a similar amount of outpatients and outpatient revenue but significantly less inpatient care and numbers of surgeries per month. A gender-based gap exists among surgeons in Taiwan. The gap between females and males appeared narrower in urology than in general surgery and gynecology. Management of diseases related to female sex organs, including breast, were more common among female surgeons. Efforts should be made to decrease gender stereotypes, to ensure that patients receive the best care regardless of the sex of the surgeons.

Atrial Fibrillation Is Not Associated With Sudden Sensorineural Hearing Loss.

OBJECTIVES: The aim of this study is to assess the association between atrial fibrillation (AF) and sudden sensorineural hearing loss (SSNHL). METHODS: This study was conducted by searching the longitudinal health insurance database of the Taiwan National Health Insurance Program for relevant information from January 1, 2000, to December 31, 2011. Patients with AF were matched with non-AF controls with a 1:1 strategy according to propensity scores. Multiple logistic regression analyses were performed to determine the risk of SSNHL. RESULTS: In total, 14 698 patients with AF were matched with the same number of non-AF patients as controls. After propensity score matching, the use of antiplatelet or anticoagulation medications and the occurrence of SSNHL were found to have a significant difference between AF and non-AF patients. The occurrence of SSNHL was found to be higher in men, those of 45 to 74 years old, and patients with hypertension in both AF and non-AF groups. Multiple logistic regression analyses revealed that male gender, age between 45 and 74 years, hyperlipidemia, and hypertension are risk factors for SSNHL. The use of aspirin was found to reduce the rate of SSNHL (odds ratio [OR]: 0.67, 95% CI: 0.49-0.94, P = .019), but AF was not found to be a risk factor for SSNHL (OR: 0.89, 95% CI: 0.64-1.23, P = .467). CONCLUSION: The association between AF and SSNHL is not significant.

Pseudostellariawuyishanensis, a new species of Caryophyllaceae from Fujian, China.

Pseudostellariawuyishanensis, a new species from the Wuyishan National Park, Fujian, China, is described and illustrated. Morphologically, Pseudostellariawuyishanensis resembles P.heterantha. However, the new species can be distinguished by presence of stolons, 1 line of hairs on the stem, smaller leaf blades, shorter pedicels, and ovary with 2 styles.

Prevalence and Factors Associated with the Reuse of Mask during the COVID-19 Pandemic: A Nationwide Survey in Taiwan.

Mask usage is an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection; however, mask reuse is not recommended. Studies examining the factors associated with mask reuse during the coronavirus disease (COVID-19) pandemic are limited. This nationwide survey aimed to determine the prevalence and factors associated with mask reuse among Taiwanese citizens during the pandemic. From 18 May through 31 May 2020, a computer-assisted telephone interview system was used to randomly select Taiwanese citizens for interview regarding COVID-19-preventive behaviors and knowledge on mask usage. For a total of 1075 participants, the overall mean age was 57.4 years, and 82.2% of participants reported mask reuse during the COVID-19 pandemic. After controlling for other covariates, participants who had a greater knowledge of mask usage or had a high supply of masks were less likely to reuse masks during the pandemic. Moreover, generalized estimating equations (GEE) analysis showed that, compared with the participants' mask-wearing behaviors before the COVID-19 pandemic, they were more likely to reuse masks during the pandemic. Thus, it is imperative to educate people on the correct usage of masks. Furthermore, the government should provide sufficient masks to the general population to reduce mask reuse.

Type I Interferon Signaling Accelerates Liver Regeneration by Metabolic Modulation in Noninfectious Conditions.

Type I interferon (IFN-I) has a well-known function in controlling viral infections, but its contribution in hepatocyte proliferation and hepatocellular carcinoma (HCC) formation remains unclear. Mice deficient in IFN-α receptor expression in whole mice or only in hepatocytes (Ifnar-/- and IfnarΔliver) were used to investigate the role of IFN-I signaling in cell proliferation and cancer formation in the liver. Ifnar-/- mice were resistant to chemical-induced HCC formation in the absence of infection. The results show that low grade of IFN-I and interferon-stimulated gene were expressed substantially in naïve mouse liver. The low level of IFN-I activation is constantly present in mouse liver after weaning and negatively modulates forkhead box O hepatic expression. The IFN-I signaling can be partially blocked by the clearance of lipopolysaccharide. Mice lacking IFN-I signaling have lower basal proliferation activity and delayed liver regeneration processes after two-thirds partial hepatectomy. The activation of IFN-I signaling on hepatocyte controls glucose homeostasis and lipid metabolism to support proliferation potency and long-term tumorigenesis. Our results reveal a positive role of low-grade IFN-I singling to hepatocyte proliferation and HCC formation by modulating glucose homeostasis and lipid metabolism.

Ultra-Small Platinum Nanoparticle-Enabled Catalysis and Corrosion Susceptibility Reverse Tumor Hypoxia for Cancer Chemoimmunotherapy.

A major challenge in the use of chemotherapy and immunotherapy is hypoxia-induced progression of tumor cells. We aim to curb hypoxia using metal-based O2-producing nanomedicine. The key focus is therapeutic targeting of hypoxia-inducible factor 1α (HIF-1α), a major reactive oxygen species (ROS)-activated player that drives hypoxia-dependent tumor progression. Inhibition of tumor growth by blocking both HIF-1α and immune checkpoint molecules via ROS removal is a promising new strategy to avoid ROS-induced hypoxia signaling and boost antitumor immunity. Here, we investigated the synergistic effect of ultra-small platinum nanoparticles (Pt-nano) with dual functions of enzyme-mimicking catalysis and corrosion susceptibility to block hypoxia signaling of tumors. Ultra-small Pt-nano with highly corrosive susceptibility can efficiently catalyze ROS scavenging and promote oxygen accumulation for hypoxia reversal, leading to reduced HIF-1α expression. The unique corrosion susceptibility allows ultra-small Pt-nano to effectively exert platinum cytotoxicity, induce reversal of hypoxia-mediated immune suppression by promoting cytotoxic T-cell infiltration of tumors, and reduce the levels of tumoral immune checkpoint molecules and immunosuppressive cytokines. In combination with immune checkpoint blockade using monoclonal antibodies, nanoparticle-enabled enzyme-mimicking is a promising strategy for the enhancement of chemoimmunotherapeutic efficacy through the reversal of tumor hypoxia.

Supramolecular Bait to Trigger Non-Equilibrium Co-Assembly and Clearance of Aß42.

In living systems, non-equilibrium states that control the assembly-disassembly of cellular components underlie the gradual complexification of life, whereas in nonliving systems, most molecules follow the laws of thermodynamic equilibrium to sustain dynamic consistency. Little is known about the roles of non-equilibrium states of interactions between supramolecules in living systems. Here, a non-equilibrium state of interaction between supramolecular lipopolysaccharide (LPS) and Aß42, an aggregate-prone protein that causes Alzheimer's disease (AD), was identified. Structurally, Aß42 presents a specific groove that is recognized by the amphiphilicity of LPS bait in a non-equilibrium manner. Functionally, the transient complex elicits a cellular response to clear extracellular Aß42 deposits in neuronal cells. Since the impaired clearance of toxic Aß42 deposits correlates with AD pathology, the non-equilibrium LPS and Aß42 could represent a useful target for developing AD therapeutics.

Primary Amine Modified Gold Nanodots Regulate Macrophage Function and Antioxidant Response: Potential Therapeutics Targeting of Nrf2.

BACKGROUND: Gold nanoparticles with high biocompatibility and immunomodulatory properties have potential applications in the development of new diagnostic and therapeutic strategies for nanomedicine. Nanoparticles targeting macrophages can manipulate or control immunological diseases. This study assessed the activity of dendrimer-encapsulated gold nanodots (AuNDs) with three surface modifications [ie, outfacing groups with primary amine (AuNDs-NH2), hydroxyl (AuNDs-OH), and quaternary ammonium ions (AuNDs-CH3)] regulated macrophage function and antioxidant response through Nrf2-dependent pathway. METHODS: AuNDs were prepared and characterized. Intracellular distribution of AuNDs in human macrophages was observed through confocal microscopy. The activity of AuNDs was evaluated using macrophage functions and antioxidant response in the human macrophage cell line THP-1. RESULTS: AuNDs-NH2 and AuNDs-CH3, but not AuNDs-OH, drove the obvious Nrf2-antioxidant response element pathway in THP-1 cells. Of the three, AuNDs-NH2 considerably increased mRNA levels and antioxidant activities of heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in THP-1 cells. IL-6 mRNA and protein expression was mediated through Nrf2 activation in AuNDs-NH2-treated macrophages. Furthermore, Nrf2 activation by AuNDs-NH2 increased the phagocytic ability of THP-1 macrophages. CONCLUSION: AuNDs-NH2 had immunomodulatory activities in macrophages. The findings of the present work suggested that AuNDs have potential effects against chronic inflammatory diseases via the Nrf2 pathway.

Risks of forgotten double-J ureteric stents after ureterorenoscopic lithotripsy in Taiwan: a nationwide population-based study.

Delayed double-J ureteric stent (DJ) removal may cause severe morbidity. We aimed to identify high-risk patients for forgotten DJs to prevent iatrogenic injury and improve safety. Data of patients with DJs placed after ureterorenoscopic lithotripsy (URSL) between 2000 and 2013 from the National Health Insurance Database in Taiwan were included. Forgotten DJs were defined as indwelling DJs for > 6 months after URSL, which is approximately two times longer than the expiratory duration. Age at stenting, sex, socioeconomic status, specialty of stenting physician, comorbidities, postoperative emergency room visiting and abdominal plain x-ray filming frequencies, and alpha blocker use for > 7 days after stenting were analysed. Of 13,058 patients, 12,969 (99.31%) had timely removed DJs while 89 (0.68%) had forgotten DJs. Per a univariate analysis, patients with forgotten DJs were older, female, and of low socioeconomic status, and the use of more than one DJ for one URSL, placement by non-urologists, and less frequent postoperative abdominal plain x-ray filming and postoperative alpha blocker use were risk factors. Per a multivariate analysis, elderly patients (Odds ratio [OR] = 3.37, 95% confidence interval (CI) 1.36-8.32, p = 0.0085), DJ placement by non-urologists (OR = 9.63, 95% CI 6.09-15.24, p < 0.0001), more than two DJs for one URSL (OR = 2.93, 95% CI 1.58-5.42, p = 0.0006), and less frequent postoperative abdominal plain x-ray filming (OR = 0.66, 95% CI 0.51-0.86, p = 0.0016) were significantly associated with forgotten DJs. Forgotten URSL-related DJs are infrequent in Taiwan. Old age, complicated DJ insertion requiring more than two stents for one URSL, and stent placement by non-urologists are risk factors. Physicians should be aware of these high-risk patients.

Association between obesity and education level among the elderly in Taipei, Taiwan between 2013 and 2015: a cross-sectional study.

The inverse association between obesity and education level has been demonstrated in many developed countries; however, few studies have investigated obesity in geriatric populations. This cross-sectional analysis explored the association between geriatric obesity and education level, along with other demographic characteristics in Taipei, Taiwan between 2013 and 2015. Taipei citizens ≥ 65 years (aborigines ≥ 55 years) were recruited to participate in the elderly health examination programme. Logistic regression was applied to analyse the relationship between obesity (defined as body mass index ≥ 27 kg/m2 in Taiwan) and education level among men and women after controlling for age, race, income status, and smoking status. A total of 28,092 men and 31,835 women were included in the final analysis. Compared to those with education years ≥ 16, older men and women with education years ≤ 12 had higher odds of being obese. The odds ratios increase as years of education decrease, and the trend is more pronounced among women. Aborigines had much higher chances of being obese among men and women, while there were no differences by income status. The results clarified the factors related to obesity in the elderly, and will be useful for authorities working to improve health outcomes among this population.

Anti-Influenza Protective Efficacy of a H6 Virus-Like Particle in Chickens.

H6 avian influenza viruses (AIVs) have a worldwide distribution, and they pose a potential concern for public health. In Taiwan, H6 AIVs have circulated in domestic chickens for more than 40 years, and certain strains have crossed the species barrier to infect mammals. With the goal of containing the disease, there is a pressing need to develop a safe and effective vaccine for pandemic preparedness. In this study, we prepared a virus-like particle (VLP) that consisted of the hemagglutinin (HA) and matrix protein 1 (M1) derived from a H6 AIV as a vaccine antigen, and we examined the immunogenicity and protective efficacy when combined with an adjuvant in a chicken model. Full-length HA and M1 protein genes were cloned and expressed using a baculovirus expression system, and VLPs were purified from the supernatant of insect cell cultures. We performed nanoparticle-tracking analysis and transmission electron microscopy to validate that the particle structure and properties resembled the native virions. In animal experiments, specific-pathogen-free chickens that received the H6 VLPs in combination with an adjuvant showed superior H6N1 virus-specific serum IgG and hemagglutination-inhibition antibody responses, which lasted more than 112 days. Following the H6N1 viral challenge, the vaccinated chickens showed reduced viral replication in the lungs, kidneys and conjunctival/cloacal shedding. The antibodies induced in the chickens by the vaccine were able to cross-react with the H6N1 human isolate and drifted avian H6N1 isolates. In summary, the H6 VLP vaccine elicited superb immunogenicity in vivo, and the use of an adjuvant further enhanced the antiviral protective efficacy. This vaccine formulation could potentially be used to manage H6 influenza virus infections in chickens.

Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens.

BACKGROUND: Poultry vaccine has limited choices of adjuvants and is facing severe threat of infectious diseases due to ineffective of widely used commercial vaccines. Thus, development of novel adjuvant that offers safe and effective immunity is of urgent need. MATERIALS AND METHODS: The present research engineers a novel chicken adjuvant with potent immune-potentiating capability by incorporating avian toll-like receptor 21 (TLR21) agonist CpG ODN 2007 with a poly(lactic-co-glycolic acid) (PLGA)-based hollow nanoparticle platform (CpG-NP), which subsequently assessed ex vivo and in vivo. RESULTS: CpG-NPs with an average diameter of 164 nm capable of sustained release of CpG for up to 96 hours were successfully prepared. With the ex vivo model of chicken bone marrow-derived dendritic cells (chBMDCs), CpG-NP was engulfed effectively and found to induce DC maturation, promoting dendrite formation and upregulation of CD40, CD80 and CCR7. In addition to enhanced expression of IL-1ß, IL-6, IL-12 and IFN-γ, 53/84 immune-related genes were found to be stimulated in CpG-NP-treated chBMDCs, whereas only 39 of such genes were stimulated in free CpG-treated cells. These upregulated genes suggest immune skewing toward T helper cell 1 bias and evidence of improved mucosal immunity upon vaccination with the CpG-NP. The CpG-NP-treated chBMDCs showed protective effects to DF-1 cells against avian influenza virus H6N1 infection. Upon subsequent coupling with infectious bronchitis virus subunit antigen administration, chickens were immunostimulated to acquire higher humoral immune response and protective response against viral challenge. CONCLUSTION: This work presents a novel hollow CpG-NP formulation, demonstrating effective and long-lasting immunostimulatory ability ex vivo and in vivo for chickens, as systemically compared to free CpG. This enhanced immune stimulation benefits from high stability and controlled release of internal component of nanoparticles that improve cellular delivery, lymphoid organ targeting and sustainable DC activation. CpG-NP has broad application potential in antiviral and vaccine development.

The Bioactive Core and Corona Synergism of Quantized Gold Enables Slowed Inflammation and Increased Tissue Regeneration in Wound Hypoxia.

The progress of wound regeneration relies on inflammation management, while neovascular angiogenesis is a critical aspect of wound healing. In this study, the bioactive core and corona synergism of quantized gold (QG) were developed to simultaneously address these complicated issues, combining the abilities to eliminate endotoxins and provide oxygen. The QG was constructed from ultrasmall nanogold and a loosely packed amine-based corona via a simple process, but it could nonetheless eliminate endotoxins (a vital factor in inflammation also called lipopolysaccharides) and provide oxygen in situ for the remodeling of wound sites. Even while capturing endotoxins through electrostatic interactions, the catalytic active sites inside the nanogold could maintain its surface accessibility to automatically transform the overexpressed hydrogen peroxide in hypoxic wound regions into oxygen. Since the inflammatory stage is an essential stage of wound healing, the provision of endotoxin clearance by the outer organic corona of the QG could slow inflammation in a way that subsequently promoted two other important stages of wound bed healing, namely proliferation and remodeling. Relatedly, the efficacy of two forms of the QG, a liquid form and a dressing form, was demonstrated at wound sites in this study, with both forms promoting the development of granulation, including angiogenesis and collagen deposition. Thus, the simply fabricated dual function nanocomposite presented herein not only offers reduced batch-to-batch variation but also increased options for homecare treatments.