3D printing redefines microneedle fabrication for transdermal drug delivery.

Microneedles (MNs) have emerged as an innovative, virtually painless technique for intradermal drug delivery. However, the complex and costly fabrication process has limited their widespread accessibility, especially for individuals requiring frequent drug administration. This study introduces a groundbreaking and cost-effective method for producing MNs utilizing fused deposition modeling (FDM) 3D printing technology to enhance transdermal drug delivery. The proposed fabrication process involves the elongation of molten polylactic acid (PLA) filaments to create meticulously designed conoid and neiloid MNs with smooth surfaces. This study underscores the critical role of printing parameters, particularly extrusion length and printing speed, in determining the shape of the MNs. Notably, the conoid-shaped MNs exhibit exceptional skin-penetrating capabilities. In order to evaluate their effectiveness, the MNs were tested on a polydimethylsiloxane (PDMS) skin model for skin penetration. The results highlight the high potential of 3D-printed MNs for transdermal drug administration. This novel approach capitalizes on the benefits of 3D printing technology to fabricate MNs that hold the promise of transforming painless drug administration for a variety of medical applications.

A review on the enantioselective distribution and toxicity of chiral pesticides in aquatic environment.

Chiral pesticides account for about 40% of the total pesticides. In the process of using pesticides, it will inevitably flow into the surface water and even penetrate into the groundwater through surface runoff and other means, as a consequence, it affects the water environment. Although the enantiomers of chiral pesticides have the same physical and chemical properties, their distribution, ratio, metabolism, toxicity, etc. in the organism are often different, and sometimes even show completely opposite biological activities. In this article, the selective fate of different types of chiral pesticides such as organochlorine, organophosphorus, triazole, pyrethroid and other chiral pesticides in natural water bodies and sediments, acute toxicity to aquatic organisms, chronic toxicity and other aspects are summarized to further reflect the risks between the enantiomers of chiral pesticides to non-target organisms in the water environment. In this review, we hope to further explore its harm to human society through the study of the toxicity of chiral pesticide enantiomers, so as to provide data support and theoretical basis for the development and production of biochemical pesticides.

Combined effect and mechanism of microplastic with different particle sizes and levofloxacin on developing Rana nigromaculata: Insights from thyroid axis regulation and immune system.

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants with other environmental pollutants, such as levofloxacin (LVFX). After 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, we measured the weight, snout-to-vent length (SVL), and development stages of Rana nigromaculata. Furthermore, we analyzed proteins and genes related to immune system and thyroid axis regulation, intestinal histological, and bioaccumulation of LVFX and MPs in the intestine and brain to further explore the toxic mechanism of co-exposure. We found MPs exacerbated the effect of LVFX on growth and development, and the order of inhibitory effects is as follows: LVFX-MP3>LVFX-MP1>LVFX-MP2. 0.1 and 1 µm MP could penetrate the blood-brain barrier, interact with LVFX in the brain, and affect growth and development by regulating thyroid axis. Besides, LVFX with MPs caused severer interference on thyroid axis compared with LVFX alone. However, 10 µm MP was prone to accumulating in the intestine, causing severe histopathological changes, interfering with the intestinal immune system and influencing growth and development through immune enzyme activity. Thus, we concluded that MPs could regulate the thyroid axis by interfering with the intestinal immune system.

A rare combination of correct transposition of the great arteries and isolated levocardia: Imaging characterization.

Congenitally correct transposition of the great arteries (cc-TGA) is an extremely rare congenital cardiac malposition. It can be detected antenatally by echocardiography. This case report describes a 58-year-old female patient who presented with tachycardia. The combination of cc-TGA and isolated levocardia is incidentally diagnosed by transthoracic echocardiography and cardiac magnetic resonance imaging.

Fe/Cu MOFs of Fe2+-rich and Cu-doping via in situ reduction as nanozyme for peroxidase-like catalycity enhancement.

Fe-MOFs of mixed valence was synthesized by a solvothermal method via the in-situ reduction of ethylene glycol (EG) pre-coordination with the proper ratio of Fe2+/Fe3+ between 0.83 and 2.46. Synchronously with copper introduction, the Fe/Cu MOFs of mixed valence (Fe/Cu-MVMOFs) was then one pot acquired to remarkably improve the affinity of Fe2+ and Cu+ to H2O2 and promote the conversion efficiency of Fe2+/Fe3+ via the electron transfer among Fe-Cu bimetal clusters (XPS and XRD). Hence, the maximum reaction rate of H2O2 with Fe/Cu-MVMOFs reached 16.65 M·s-1, along with Km as low as 0.0479 mM. H2O2 and glutathione (GSH) were efficiently detected, ranging from 0.25 to 60 µM and from 0.2 to 40 µM, respectively. The investigation of catalyzation selectivity and practical serum detection by Fe/Cu-MVMOFs illustrated the efficacy and efficiency, denoting Fe/Cu-MVMOFs as the promising peroxidase candidate.

Application of cell transplantation in the treatment of neuropathic pain.

Nerve injury can not only lead to sensory and motor dysfunction, but also be complicated with neuropathic pain (NPP), which brings great psychosomatic injury to patients. At present, there is no effective treatment for NPP. Based on the functional characteristics of cell transplantation in nerve regeneration and injury repair, cell therapy has been used in the exploratory treatment of NPP and has become a promising treatment of NPP. In this article, we discuss the current mainstream cell types for the treatment of NPP, including Schwann cells, olfactory ensheathing cells, neural stem cells and mesenchymal stem cells in the treatment of NPP. These bioactive cells transplanted into the host have pharmacological properties of decreasing pain threshold and relieving NPP by exerting nutritional support, neuroprotection, immune regulation, promoting axonal regeneration, and remyelination. Cell transplantation can also change the microenvironment around the nerve injury, which is conducive to the survival of neurons. It can effectively relieve pain by repairing the injured nerve and rebuilding the nerve function. At present, some preclinical and clinical studies have shown that some encouraging results have been achieved in NPP treatment based on cell transplantation. Therefore, we discussed the feasible strategy of cell transplantation as a treatment of NPP and the problems and challenges that need to be solved in the current application of cell transplantation in NPP therapy.

Ultrafast Dual-Shock Chemistry Synthesis of Ordered/Disordered Hybrid Carbon Anodes: High-Rate Performance of Li-Ion Batteries.

Graphite exhibits crystal anisotropy, which impedes the mass transfer of ion intercalation and extraction processes in Li-ion batteries. Herein, a dual-shock chemical strategy has been developed to synthesize the carbon anode. This approach comprised two key phases: (1) a thermal shock utilizing ultrahigh temperature (3228 K) can thermodynamically facilitate graphitization; (2) a mechanical shock (21.64 MPa) disrupting the π-π interactions in the aromatic chains of carbon can result in hybrid-structured carbon composed of crystalline and amorphous carbon. The optimized carbon (DSC-200-0.3) demonstrates a capacity of 208.61 mAh/g at a 10C rate, with a significant enhancement comparing with 15 mAh/g of the original graphite. Impressively, it maintains 81.06% capacity even after 3000 charge-discharge cycles. Dynamic process analysis reveals that this superior rate performance is attributed to a larger interlayer spacing facilitating ion transport comparing with the original graphite, disordered amorphous carbon for additional lithium storage sites, and crystallized carbon for enhanced charge transfer. The dual-shock chemical approach offers a cost-effective and efficient method to rapidly produce hybrid-structured carbon anodes, enabling 10C fast charging capabilities in lithium-ion batteries.

DCBLD2 deletion increases hyperglycemia and induces vascular remodeling by inhibiting insulin receptor recycling in endothelial cells.

Discoidin, CUB, LCCL domain-containing 2 (DCBLD2) is a type I transmembrane protein with a similar structure to neuropilin, which acts as a co-receptor for certain receptor tyrosine kinases (RTKs). The insulin receptor is an RTK and plays a critical role in endothelial cell function and glycolysis. However, how and whether DCBLD2 regulates insulin receptor activity in endothelial cells is poorly understood. Diabetes was induced through treatment of Dcbld2 global-genome knockout mice and endothelium-specific knockout mice with streptozotocin. Vascular ultrasound, vascular tension test, and hematoxylin and eosin staining were performed to assess endothelial function and aortic remodeling. Glycolytic rate assays, real-time PCR and western blotting were used to investigate the effects of DCBLD2 on glycolytic activity and insulin receptor (InsR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in endothelial cells. Co-immunoprecipitation was used to assess the effects of DCBLD2 on insulin receptor endocytosis and recycling. Membrane and cytoplasmic proteins were isolated to determine whether DCBLD2 could affect the localization of the insulin receptor. We found that Dcbld2 deletion exacerbated endothelial dysfunction and vascular remodeling in diabetic mice. Both Dcbld2 knockdown and Dcbld2 deletion inhibited glycolysis and the InsR/PI3K/Akt signaling pathway in endothelial cells. Furthermore, Dcbld2 deletion inhibited insulin receptor recycling. Taken together, Dcbld2 deficiency exacerbated diabetic endothelial dysfunction and vascular remodeling by inhibiting the InsR/PI3K/Akt pathway in endothelial cells through the inhibition of Rab11-dependent insulin receptor recycling. Our data suggest that DCBLD2 is a potential therapeutic target for diabetes and cardiovascular diseases.

Update on the mechanism of microglia involvement in post-stroke cognitive impairment.

Post-stroke cognitive impairment (PSCI) is a clinical syndrome characterized by cognitive deficits that manifest following a stroke and persist for up to 6 months post-event. This condition is grave, severely compromising patient quality of life and longevity, while also imposing substantial economic burdens on societies worldwide. Despite significant advancements in identifying risk factors for PSCI, research into its underlying mechanisms and therapeutic interventions remains inadequate. Microglia, the brain's primary immune effector cells, are pivotal in maintaining, nurturing, defending, and repairing neuronal function, a process intrinsically linked to PSCI's progression. Thus, investigating microglial activation and mechanisms in PSCI is crucial. This paper aims to foster new preventive and therapeutic approaches for PSCI by elucidating the roles, mechanisms, and characteristics of microglia in the condition.

Nanoengineering of Cathode Catalysts for Li-O2 Batteries.

Lithium-oxygen (Li-O2) batteries have obtained widespread attention as next-generation energy storage systems due to their extremely high energy density. However, the high charge overpotential, attributed to the insulating property of Li2O2, significantly limits the energy efficiency and triggers solvent degradation. The high electrochemical activities of oxygen reduction reactions (ORR) and oxygen evolution reactions (OER) on the cathode are crucial for alleviating the high charging polarizations and enhancing the lifetime of Li-O2 batteries, which are also top challenges of state-of-art research. In this review, the scientific challenges and the proposed solutions in the development of cathode catalysts have been summarized. The recent research advancements on the nanoengineering of cathode catalysts for Li-O2 batteries have been comprehensively discussed, and the perspectives on the structure optimization are presented. Meanwhile, we have elucidated the structure-performance relationship between the electronic state and performance of the cathode catalysts at the nanoscale level. This review intends to provide guidelines for the design and construction of cathode catalysts in advanced Li-O2 batteries.

Recent Developments in Nickel-Based Layered Double Hydroxides for Photo(-/)electrocatalytic Water Oxidation.

Layered double hydroxides (LDHs), especially those containing nickel (Ni), are increasingly recognized for their potential in photo(-/)electrocatalytic water oxidation due to the abundant availability of Ni, their corrosion resistance, and their minimal toxicity. This review provides a comprehensive examination of Ni-based LDHs in electrocatalytic (EC), photocatalytic (PC), and photoelectrocatalytic (PEC) water oxidation processes. The review delves into the operational principles, highlighting similarities and distinctions as well as the benefits and limitations associated with each method of water oxidation. It includes a detailed discussion on the synthesis of monolayer, ultrathin, and bulk Ni-based LDHs, focusing on the merits and drawbacks inherent to each synthesis approach. Regarding the EC oxygen evolution reaction (OER), strategies to improve catalytic performance and insights into the structural evolution of Ni-based LDHs during the electrocatalytic process are summarized. Furthermore, the review extensively covers the advancements in Ni-based LDHs for PEC OER, including an analysis of semiconductors paired with Ni-based LDHs to form photoanodes, with a focus on their enhanced activity, stability, and underlying mechanisms facilitated by LDHs. The review concludes by addressing the challenges and prospects in the development of innovative Ni-based LDH catalysts for practical applications. The comprehensive insights provided in this paper will not only stimulate further research but also engage the scientific community, thus driving the field of photo(-/)electrocatalytic water oxidation forward.

Aluminum substitution stabilizes organic matter in ferrihydrite transforming into hematite: A molecular analysis.

The association of soil organic matter (SOM) with iron (Fe) oxyhydroxides, particularly ferrihydrite, plays a pivotal role in the biogeochemical cycling of carbon (C) in both terrestrial and aquatic environment. The aging of ferrihydrite to more crystalline phases can impact the stability of associated organic C, a process potentially influenced by aluminum (Al) substitution due to its abundance. However, the molecular mechanisms governing the temporal and spatial distribution of SOM during the aging process of Al-substituted Fe oxyhydroxides remain unclear. This study aims to bridge this knowledge gap through a comprehensive approach, utilizing batch experiments, solid characterization techniques, and atomic force microscopy (AFM) based peak-force quantitative nanomechanical mapping (PF-QNM). Batch experiments revealed that humic acid (HA) was released into the aqueous phase during aging, with Al inhibiting this release. Various solid characterization methods collectively suggested that Al hindered the crystalline transformation of ferrihydrite and significantly preserved HA on the surface of newly formed hematite, rather than it being occluded within the interior of the new minerals. Results from 3-Dimensional fluorescence spectroscopy (3D-EEM) and Fourier-transform infrared spectroscopy (FTIR) indicated that the structure of HA remained constant, with the carboxyl-rich and hydroxyl-rich portions of HA fixed at the mineral interface during the aging period. Furthermore, we developed AFM-based PF-QNM to both quantify and visualize the interactions between Fe oxyhydroxides and HA, demonstrating variations in HA affinity among different Fe oxyhydroxides and highlighting the influence of the Al substitution rate.

Cell Migration Assays and Their Application to Wound Healing Assays-A Critical Review.

In recent years, cell migration assays (CMAs) have emerged as a tool to study the migration of cells along with their physiological responses under various stimuli, including both mechanical and bio-chemical properties. CMAs are a generic system in that they support various biological applications, such as wound healing assays. In this paper, we review the development of the CMA in the context of its application to wound healing assays. As such, the wound healing assay will be used to derive the requirements on CMAs. This paper will provide a comprehensive and critical review of the development of CMAs along with their application to wound healing assays. One salient feature of our methodology in this paper is the application of the so-called design thinking; namely we define the requirements of CMAs first and then take them as a benchmark for various developments of CMAs in the literature. The state-of-the-art CMAs are compared with this benchmark to derive the knowledge and technological gap with CMAs in the literature. We will also discuss future research directions for the CMA together with its application to wound healing assays.

Three-Dimensional Bioprinted Skin Microrelief and Its Role in Skin Aging.

Skin aging is a complex physiological process, in which cells and the extracellular matrix (ECM) interreact, which leads to a change in the mechanical properties of skin, which in turn affects the cell secretion and ECM deposition. The natural skin microrelief that exists from birth has rarely been taken into account when evaluating skin aging, apart from the common knowledge that microreliefs might serve as the starting point or initialize micro-wrinkles. In fact, microrelief itself also changes with aging. Does the microrelief have other, better uses? In this paper, owing to the fast-developing 3D printing technology, skin wrinkles with microrelief of different age groups were successfully manufactured using the Digital light processing (DLP) technology. The mechanical properties of skin samples with and without microrelief were tested. It was found that microrelief has a big impact on the elastic modulus of skin samples. In order to explore the role of microrelief in skin aging, the wrinkle formation was numerically analyzed. The microrelief models of different age groups were created using the modified Voronoi algorithm for the first time, which offers fast and flexible mesh formation. We found that skin microrelief plays an important role in regulating the modulus of the epidermis, which is the dominant factor in wrinkle formation. The wrinkle length and depth were also analyzed numerically for the first time, owing to the additional dimension offered by microrelief. The results showed that wrinkles are mainly caused by the modulus change of the epidermis in the aging process, and compared with the dermis, the hypodermis is irrelevant to wrinkling. Hereby, we developed a hypothesis that microrelief makes the skin adaptive to the mechanical property changes from aging by adjusting its shape and size. The native-like skin samples with microrelief might shed a light on the mechanism of wrinkling and also help with understanding the complex physiological processes associated with human skin.

Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model.

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

Molecular mechanisms of gut microbiota in diabetic nephropathy.

Diabetic nephropathy is a common complication of diabetes and a considerable contributor to end-stage renal disease. Evidence indicates that glucose dysregulation and lipid metabolism comprise a pivotal pathogenic mechanism in diabetic nephropathy. However, current treatment outcomes are limited, as they only provide symptomatic relief without preventing disease progression. The gut microbiota is a group of microorganisms that inhabit the human intestinal tract and play a crucial role in maintaining host energy balance, metabolism, and immune activity. Patients with diabetic nephropathy exhibit altered gut microbiota, suggesting its potential involvement in the onset and progression of the disease. However, how a perturbed microbiota induces and promotes diabetic nephropathy remains unelucidated. This article summarizes the evidence of the impact of gut microbiota on the progression of diabetic nephropathy, with a particular focus on the molecular mechanisms involved, aiming to provide new insights into the treatment of diabetic nephropathy.

Discovery of Kebanmycins with Antibacterial and Cytotoxic Activities from the Mangrove-Derived Streptomyces sp. SCSIO 40068.

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain Streptomyces sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A-D (1-4) and two known analogues FD-594 (5) and the aglycon (6). The structures of 1-6 were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. 1-3 featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster (keb) was identified in Streptomyces sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar-O-methyltransferase, leading to a proposed biosynthetic route to 1-6. This study paves the way to further investigate 1 as a potential lead compound.

Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors.

Carrier-free nanomedicines offer advantages of extremely high drug loading capacity (>80%), minimal non-drug constituent burden, and facile preparation processes. Numerous studies have proved that multimodal cancer therapy can enhance chemotherapy efficiency and mitigate multi-drug resistance (MDR) through synergistic therapeutic effects. Upon penetration into the tumor matrix, nanoparticles (NPs) are anticipated to be uptaken by cancer cells, primarily through clathrin-meditated endocytosis pathways, leading to their accumulation in endosomes/lysosomes within cells. However, endo/lysosomes exhibit a highly degradative environment for organic NPs and drug molecules, often resulting in treatment failure. Hence, this study designed a lysosomal escape mechanism with carrier-free nanomedicine, combining the chemotherapeutic drug, curcumin (Cur), and the photothermal/photodynamic therapeutic drug, indocyanine green (ICG), for synergistic cancer treatment (ICG-Cur NPs) via a facile preparation process. To facilitate endo/lysosomal escape, ICG-Cur NPs were modified with metal-phenolic networks (MPNs) of different thickness. The results indicate that a thick MPN coating promotes rapid endo/lysosomal escape of ICG-Cur NPs within 4 h and enhances the photothermal conversion efficiency of ICG-Cur NPs by 55.8%, significantly improving anticancer efficacy in both chemo- and photo-therapies within 3D solid tumor models. This finding underscores the critical role of endo/lysosomal escape capacity in carrier-free drug NPs for therapeutic outcomes and offers a facile solution to achieve it.

An efficient rare-earth free deep red-emitting GdGeSbO6:Mn4+ phosphor for white light-emitting diodes.

Red phosphors play an important role in improving the light quality and color rendering index of white light-emitting diodes (WLEDs) for lighting. In this paper, we report the transition ion Mn4+-activated deep red phosphor GdGeSbO6:x%Mn4+ and analyze its crystal structure, composition and luminescence behavior in detail. Its optimal doping concentration of Mn4+ is 0.3%. Under ultraviolet (UV) excitation, GdGeSbO6:0.3%Mn4+ produces a narrow emission peak centred at 682 nm in the range of 650-800 nm with a full width at half maximum (FWHM) of 25 nm, which is attributed to the spin-prohibited 2Eg → 4A2g transition of Mn4+ ions. Notably, the optimal phosphor GdGeSbO6:0.3%Mn4+ has a high internal quantum efficiency (IQE ≈ 65%) and excellent thermal stability performance (I423 K/I303 K ≈ 62%). The synthesis of high-performance warm WLEDs and full-spectrum WLEDs was achieved by combining and coating GdGeSbO6:0.3%Mn4+ phosphors with commercial phosphors on the surface of a 365 nm UV chip.

Functional analysis of the key BrSWEET genes for sugar transport involved in the Brassica rapa-Plasmodiophora brassicae interaction.

Plasmodiophora brassicae, the causative agent of clubroot disease, establishes a long-lasting parasitic relationship with its host by inducing the expression of sugar transporters. Previous studies have indicated that most BrSWEET genes in Chinese cabbage are up-regulated upon infection with P. brassicae. However, the key BrSWEET genes responsive to P. brassicae have not been definitively identified. In this study, we selected five BrSWEET genes and conducted a functional analysis of them. These five BrSWEET genes showed a notable up-regulation in roots after P. brassicae inoculation. Furthermore, these BrSWEET proteins were localized to the plasma membrane. Yeast functional complementation assays confirmed transport activity for glucose, fructose, or sucrose in four BrSWEETs, with the exception of BrSWEET2a. Mutants and silenced plants of BrSWEET1a, -11a, and -12a showed lower clubroot disease severity compared to wild-type plants, while gain-of-function Arabidopsis thaliana plants overexpressing these three BrSWEET genes exhibited significantly higher disease incidence and severity. Our findings suggested that BrSWEET1a, BrSWEET11a, and BrSWEET12a play pivotal roles in P. brassicae-induced gall formation, shedding light on the role of sugar transporters in host-pathogen interactions.