Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect.

Delays in infected wound healing are usually a result of bacterial infection and local inflammation, which imposes a significant and often underappreciated burden on patients and society. Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration, owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs. Here, we report the design of a biocompatible probiotic-based microneedle (MN) patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency. The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol, thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects. Additionally, the beneficial bacteria can remain highly viable (>80 %) inside MNs for as long as 60 days at 4 °C. In a mouse model of Staphylococcus aureus-infected wounds, a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups, indicating great potential for accelerating infected wound closure. Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.

Self-Implantable Core-Shell Microneedle Patch for Long-Acting Treatment of Keratitis via Programmed Drug Release.

Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.

Silver Nanoparticle-Loaded Titanium-Based Metal-Organic Framework for Promoting Antibacterial Performance by Synergistic Chemical-Photodynamic Therapy.

The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.

A self-monitoring microneedle patch for light-controlled synergistic treatment of melanoma.

Melanoma is the most aggressive and malignant form of skin cancer. Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release. Here, a self-monitoring microneedle (MN)-based drug delivery system, which integrates a dissolving MN patch with aggregation-induced emission (AIE)-active PATC microparticles, is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma. The PATC polymeric particles, termed D/I@PATC, encapsulate both of chemotherapeutic drug doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon light illumination, PATC gradually dissociates into smaller particles, causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles, thereby not only enabling direct observation of the drug release process under light stimuli, but also facilitating verification of drug release by fluorescence recovery after light trigger. Moreover, encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo. In a tumor-bearing mouse, the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited ∼97% melanoma inhibition rate without inducing any evident systemic toxicity, suggesting a great potential for skin cancer treatment in clinics.

Multifunctional MOF-Based Microneedle Patch With Synergistic Chemo-Photodynamic Antibacterial Effect and Sustained Release of Growth Factor for Chronic Wound Healing.

Chronic wound healing is a major challenge in biomedicine. Conventional therapies are usually associated with poor drug permeability, low bioavailability, risk of antimicrobial resistance, and require frequent administration. Therefore, a novel formulation with reduced antibiotic dosage, improved drug delivery efficiency, and low application frequency is of remarkable interest for chronic wound healing. Herein, a multifunctional microneedle (MN) patch is presented to achieve rapid wound healing via efficient chemo-photodynamic antibacterial effect and sustained release of growth factors at the wound bed. When the MN patch pierces the skin, MN tips carrying both low dosage of antibiotics and bioactive small molecule-encapsulated metal-organic frameworks (MOFs) rapidly dissolve and subsequently deliver the payloads to the wound. Upon light irradiation, MOF-based nanoparticles robustly convert O2 into 1 O2 , which acts synergistically with chemotherapy to remove pathogenic bacteria from the wound, exhibiting excellent chemo-photodynamic antibacterial performance with a tenfold reduction in the required antibiotic amount. The nanoparticles can achieve a continuous release of growth factors in the wound tissue, promoting the formation of epithelial tissue and neovascularization, thereby further accelerating chronic wound healing. Collectively, the designed multifunctional MOF-based MN patches offer a simple, safe, and effective alternative for chronic wound management.

Dissolving Microneedle Patch Integrated with Microspheres for Long-Acting Hair Regrowth Therapy.

Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients' self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.

Dual-emissive metal-organic framework: a novel turn-on and ratiometric fluorescent sensor for highly efficient and specific detection of hypochlorite.

Hypochlorite (ClO-) is widely used as a disinfectant, whose residue content in water should be strictly controlled due to the potential threat to human health in an inappropriate concentration. Herein, dual-emissive metal-organic frameworks with a UiO-66 prototype structure, PDA/Eu/PDA-UiO-66-NH2(x), were elegantly designed and prepared by a mixed ligand assembly and sequential post-synthesis strategy. Since blue emission is sensitive to ClO-, PDA/Eu/PDA-UiO-66-NH2(40) was selected as a model nanosensor for ratiometric and turn-on sensing of ClO- while red emission acts as a reference signal. Remarkably, PDA/Eu/PDA-UiO-66-NH2(40) shows high efficiency and specificity toward ClO- detection, as verified by a very short response time of 15 s, a wide linear range of 0.1-60 µM, a low detection limit of 0.10 µM, and excellent selectivity toward common competing ions. The recovery experiments show that the recoveries of spiking ClO- in tap water range from 96 to 103%. The rigidification of the coordinated H2N-BDC2- ligands should be responsible for the turn-on fluorescence of PDA/Eu/PDA-UiO-66-NH2(40). This work not only shows a highly efficient and specific fluorescent nanosensor for ClO- detection but also presents the first MOF-based fluorescent probe for turn-on and ratiometric sensing of ClO-.

Dual-Emissive Metal-Organic Framework as a Fluorescent "Switch" for Ratiometric Sensing of Hypochlorite and Ascorbic Acid.

The detection of hypochlorite (ClO-) content in tap water is extremely important because excess amounts of hypochlorite can convert into highly toxic species and inadequate amounts of hypochlorite cannot fully kill bacteria and viruses. Although several metal-organic frameworks (MOFs) have been successfully employed as fluorescent sensors for hypochlorite detection, all these sensors are based on single emission that responds to the dose of hypochlorite. Ratiometric sensors are highly desirable, which can improve the sensitivity, accuracy, and reliability via self-calibration. Herein, a nanoscale dual-emission multivariate 5-5-Eu/BPyDC@MOF-253-NH2 was synthesized by sequential mixed-ligand self-assembly and postsynthesis method. Among the two emission bands of 5-5-Eu/BPyDC@MOF-253-NH2, the strong blue emitting derived from ligands is sensitive to hypochlorite, while the red emitting derived from Eu(III) almost keeps invariable. Therefore, 5-5-Eu/BPyDC@MOF-253-NH2 was exploited as a fluorescent ratiometric nanosensor for "on-off" sensing of hypochlorite. Notably, the proposed sensing system showed an excellent performance including fast response (within 15 s), relative high specificity, wide linear range (0.1-30 µM), and low detection limit (0.094 µM). Besides, the suppressed blue emitting was recovered after the addition of ascorbic acid (AA) that consumes ClO- via the redox reaction. Therefore, 5-5-Eu/BPyDC@MOF-253-NH2 was further employed as a fluorescent ratiometric nanosensor for the "on-off-on" sensing of AA. This work represents the first MOF-based fluorescent "switch" for the ratiometric sensing of hypochlorite and the second for ratiometric sensing of AA.

An Improved Spatiotemporal Fusion Approach Based on Multiple Endmember Spectral Mixture Analysis.

High spatial and temporal resolution remotely sensed data is of great significance for the extraction of land use/cover information and the quantitative inversion of biophysical parameters. However, due to the limitation of sensor performance and the influence of rain cloud weather, it is difficult to obtain remote sensing images with both high spatial and temporal resolution. The spatiotemporal fusion model is a crucial method to solve this problem. The spatial and temporal adaptive reflectivity fusion model (STARFM) and its improved models are the most widely used spatiotemporal adaptive fusion models. However, the existing spatiotemporal adaptive reflectivity fusion model and its improved models have great uncertainty in selecting neighboring similar pixels, especially in spatially heterogeneous areas. Therefore, it is difficult to effectively search and determine neighboring spectrally similar pixels in STARFM-like models, resulting in a decrease of imagery fusion accuracy. In this research, we modify the procedure of neighboring similar pixel selection of ESTARFM method and propose an improved ESTARFM method (I-ESTARFM). Based on the land cover endmember types and its fraction values obtained by spectral mixing analysis, the neighboring similar pixels can be effectively selected. The experimental results indicate that the I-ESTARFM method selects neighboring spectrally similar pixels more accurately than STARFM and ESTARFM models. Compared with the STARFM and ESTARFM, the correlation coefficients of the image fused by the I-ESTARFM with that of the actual image are increased and the mean square error is decreased, especially in spatially heterogeneous areas. The uncertainty of spectral similar neighborhood pixel selection is reduced and the precision of spatial-temporal fusion is improved.

Zr-Based Metal-Organic Frameworks with Intrinsic Peroxidase-Like Activity for Ultradeep Oxidative Desulfurization: Mechanism of H2O2 Decomposition.

The restriction of sulfur content in fuels has become increasingly stringent as a result of the growing environmental concerns. Although several MOF-derived materials like POM@MOF composites have shown the ability to catalyze oxidative desulfurization (ODS), their catalytic activities inevitably obstructed by the encapsulated catalytic sites like POM due to the blockage of cavities. Therefore, MOFs with intrinsic and accessible catalytic sites are highly desirable for their applications in ultradeep ODS. Herein, four representative Zr-based MOFs (Zr-MOFs), namely, UiO-66, UiO-67, NU-1000, and MOF-808, were assessed for catalytic ODS. These MOFs were confirmed that they have peroxidase-like activity and can catalyze ODS with H2O2 as oxidant. Among them, MOF-808 showed the highest catalytic activity and it can fully desulfurize dibenzothiophene (DBT) in a model gasoline with a S concentration of 1000 ppm under 40 °C within 5 min. An extremely low apparent Arrhenius activation energy (22.0 KJ·mol-1) and an extraordinarily high TOF value (42.7 h-1) were obtained, ranking MOF-808 among the best catalysts for the catalytic DBT oxidation. Further studies confirmed that the excellent catalytic activity is mainly responsible for the high concentration of the accessible Zr-OH(H2O) catalytic sites decorated in MOF-808. The superoxide radicals (•O2-) and hydroxyl radicals (•OH) were identified and were proved to involve in the DBT oxidation. Besides, the effects of Brönsted and lewis acidity to the catalytic efficiency were also discussed. Based on the experimental results, a plausible mechanism concerning on Zr-OH(H2O) groups promoting the H2O2 decomposion in to both •O2- and •OH was first proposed. Moreover, MOF-808 can be facilely reused for at least eight runs without significant loss of its catalytic activity. By the integration of facile synthesis, high catalytic efficiency, and good stability, MOF-808 thus represents a new benchmark catalyst for catalytic oxidative desulfurization.

Hydrothermal synthesis of nitrogen and copper co-doped carbon dots with intrinsic peroxidase-like activity for colorimetric discrimination of phenylenediamine isomers.

Carbon dots doped with nitrogen and copper have been synthesized via a hydrothermal method. They possess favorable peroxidase-like catalytic activity over a wide range of pH values and temperatures. Specifically, they were used to catalyze the oxidation of ortho- and para-phenylenediamine (OPD and PPD) by H2O2. The resulting products possess different colors (yellow for OPD and brown for PPD), which can be visually discriminated. The corresponding typical absorption peaks of oxidized products for OPD and PPD are at 413 nm and 500 nm, respectively. The method displays excellent discrimination ability and selectivity over potential interferents. The detection limits are 1.1 µM for OPD and 1.9 µM for PPD. The respective linear ranges are from 5 to 200 µM for OPD and from 2.5 to 700 µM for PPD. The method was applied to the quantification of OPD and PPD in spiked natural waters. Graphical abstract Schematic presentation of the synthesis of nitrogen and copper co-doped carbon dots (N,Cu-CDs) and their application as an enzyme mimic for colorimetric discrimination of ortho-, meta- and para-phenylenediamine (OPD, MPD and PPD).

[Maternal sulfur dioxide exposure and the risk of low birth-weight babies].

The relationship between maternal exposure to sulfur dioxide (SO2) and the risk of low birth-weight (LBW) babies which has been reported in literatures remained inconclusive. In this study, the data on SO2 emission, meteorology, topography as well as LBW and control babies in the Dallas-Fort Worth area of the United States in 1997 were collected to re-examine the associations between maternal SO2 exposure and the risk of LBW in babies. A combination of air dispersion modeling, Geographic Information System (GIS) spatial interpolation and geo-statistical analysis, as well as logistic regression was used for analyses. Results showed that the risk of LBW was not significantly increased with the exposure of pregnant mothers to higher level of SO2 when all data were considered together as one group. However, for mothers at the age 35 or older, the risk of LBW babies was higher in exposure to SO2 (OR = 2.31, 95% CI 1.01 - 5.30). Therefore, the potential risk of LBW baby might be higher in elder women in exposure to SO2 during pregnancy.

An emission-weighted proximity model for air pollution exposure assessment.

BACKGROUND: Among the most common spatial models for estimating personal exposure are Traditional Proximity Models (TPMs). Though TPMs are straightforward to configure and interpret, they are prone to extensive errors in exposure estimates and do not provide prospective estimates. METHOD: To resolve these inherent problems with TPMs, we introduce here a novel Emission Weighted Proximity Model (EWPM) to improve the TPM, which takes into consideration the emissions from all sources potentially influencing the receptors. EWPM performance was evaluated by comparing the normalized exposure risk values of sulfur dioxide (SO(2)) calculated by EWPM with those calculated by TPM and monitored observations over a one-year period in two large Texas counties. In order to investigate whether the limitations of TPM in potential exposure risk prediction without recorded incidence can be overcome, we also introduce a hybrid framework, a 'Geo-statistical EWPM'. Geo-statistical EWPM is a synthesis of Ordinary Kriging Geo-statistical interpolation and EWPM. The prediction results are presented as two potential exposure risk prediction maps. The performance of these two exposure maps in predicting individual SO(2) exposure risk was validated with 10 virtual cases in prospective exposure scenarios. RESULTS: Risk values for EWPM were clearly more agreeable with the observed concentrations than those from TPM. Over the entire study area, the mean SO(2) exposure risk from EWPM was higher relative to TPM (1.00 vs. 0.91). The mean bias of the exposure risk values of 10 virtual cases between EWPM and 'Geo-statistical EWPM' are much smaller than those between TPM and 'Geo-statistical TPM' (5.12 vs. 24.63). CONCLUSION: EWPM appears to more accurately portray individual exposure relative to TPM. The 'Geo-statistical EWPM' effectively augments the role of the standard proximity model and makes it possible to predict individual risk in future exposure scenarios resulting in adverse health effects from environmental pollution.

Air pollution exposure assessment methods utilized in epidemiological studies.

The assessment of personal exposure to air pollution is a critical component of epidemiological studies associating air pollution and health effects. This paper critically reviewed 157 studies over 29 years that utilized one of five categories of exposure methods (proximity, air dispersion, hybrid, human inhalation, and biomarkers). Proximity models were found to be a questionable technique as they assume that closer proximity equates to greater exposure. Inhalation models and biomarker estimates were the most effective in assessing personal exposure, but are often cost prohibitive for large study populations. This review suggests that: (i) factors such as uncertainty, validity, data availability, and transferability related to exposure assessment methods should be considered when selecting a model; and (ii) although an entirely discreet new class of approach is not necessary, significant progress could be made through the development of a 'hybrid' model utilizing the strengths of several existing methods. Future work should systematically evaluate the performance of hybrid models compared to other individual exposure assessment methods utilizing geospatial information technologies (e.g. geographic information systems (GIS) and remote sensing (RS)) to more robustly refine estimates of ambient exposure and quantify the linkages and differences between outdoor, indoor and personal exposure estimates.