Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

The Multiple Promoting Effects of Suaeda glauca Root Exudates on the Growth of Alfalfa under NaCl Stress.

Under abiotic stress, plant root exudates can improve plant growth performance. However, studies on the effect of root exudates on the stress resistance of another plant are insufficient. In this study, root exudates (REs) were extracted from Suaeda glauca to explore their effect on alfalfa seedlings under salt stress. The results showed that the plant height and fresh weight of alfalfa significantly increased by 47.72% and 53.39% after 7 days of RE treatment at a 0.4% NaCl concentration. Under 1.2% salt stress, REs reduced the Malondialdehyde content in alfalfa by 30.14% and increased the activity of its antioxidant enzymes (peroxidase and catalase) and the content of its osmotic regulators (soluble sugar and proline) by 60.68%, 52%, 45.67%, and 38.67%, respectively. Soil enzyme activity and the abundance of soil-beneficial bacteria were increased by REs. Spearman analysis showed that urease and neutral phosphatase were related to the richness of beneficial bacteria. Redundancy analysis confirmed that urease affected the composition of the soil bacterial community. The partial least squares structural equation model (PLS-SEM) revealed that REs had a direct positive effect on alfalfa growth under salt stress by regulating the plant's injury and antioxidant systems, and the soil bacterial community had an indirect positive effect on alfalfa growth through soil enzyme activity.

Application of extracellular matrix cross-linked by microbial transglutaminase to promote wound healing.

One primary focus of skin tissue engineering has been the creation of innovative biomaterials to facilitate rapid wound healing. Extracellular matrix (ECM), an essential biofunctional substance, has recently been discovered to play a crucial role in wound healing. Consequently, we endeavored to decellularize ECM from pig achilles tendon and refine its mechanical and biological properties through modification by utilizing cross-linking agents. Glutaraldehyde (GA), 1-ethyl-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), double aldol starch (DAS), and microbial transglutaminase (MTG) were utilized to produce crosslinked ECM variants (GA-ECM, EDC/NHS-ECM, DAS-ECM, and MTG-ECM). Comprehensive assessments were conducted to evaluate the physical properties, biocompatibility, and wound healing efficacy of each material. The results indicated that MTG-ECM exhibited superior tensile strength, excellent hydrophilicity, minimal cytotoxicity, and the best pro-healing impact among the four modified scaffolds. Staining analysis of tissue sections further revealed that MTG-ECM impeded the transition from type III collagen to type I collagen in the wound area, potentially reducing the development of wound scar. Therefore, MTG-ECM is expected to be a potential pro-skin repair scaffold material to prevent scar formation.

Oxidation of emerging contaminants by S(IV) activated ferrate: Identification of reactive species.

Studies on the Fe(VI)/S(IV) process have focused on improving the efficiency of emerging contaminants (ECs) degradation under alkaline conditions. However, the performance and mechanisms under varying pH levels remain insufficiently investigated. This tudy delved into the efficiency and mechanism of Fe(VI)/S(IV) process using sulfamethoxazole (SMX) and ibuprofen (IBU) as model contaminants. We found that pH was crucial in governing the generation of reactive species, and both Fe(V/IV) and SO4•- were identified in the reaction system. Specifically, an increase in pH favored the formation of SO4•-, while the formation of Fe(VI) to Fe(V/IV) became more significant at lower pH. At pH 3.2, Fe(III) resulting from the Fe(VI) self-decay reactedwith HSO3-to produce SO4•-and •OH. Under near-neutral conditions, the coexistance of Fe(V/IV) and SO4•- in abundance contributed to the optimal oxidation of both pollutants in the Fe(VI)/S(IV) process, with the removal exceeding 74% in 5 min. Competitive quenching experiments showed that the contributions of Fe(V/IV) to SMX and IBU destruction dimished, while the contributions of radicals increased with an increase in pH. However, this evolution was slower during SMX degradation compared to IBU degradation. A comprehensive understnding of pH as the key factor is essential for the optimization of the sulfite-activated Fe(VI) oxidation process in water treatment.

CuS@TA-Fe Nanoparticle-Doped Multifunctional Hydrogel with Peroxide-Like Properties and Photothermal Properties for Synergistic Antimicrobial Repair of Infected Wounds.

Bacterial infection is a critical factor in wound healing. Due to the abuse of antibiotics, some pathogenic bacteria have developed resistance. Thus, there is an urgent need to develop a non-antibiotic-dependent multifunctional wound dressing for the treatment of bacteria-infected wounds. In this work, a multifunctional AOCuT hydrogel embedded with CuS@TA-Fe nanoparticles (NPs) through Schiff base reaction between gelatin quaternary ammonium salt - gallic acid (O-Gel-Ga) and sodium dialdehyde alginate (ADA) along with electrostatic interactions with CuS@TA-Fe NPs is prepared. These composite hydrogels possess favorable injectability, rapid shape adaptation, electrical conductivity, photothermal antimicrobial activity, and biocompatibility. Additionally, the doped NPs not only impart fast self-healing properties and excellent adhesion performance to the hydrogels, but also provide excellent peroxide-like properties, enabling them to scavenge free radicals and exhibit anti-inflammatory and antioxidant capabilities via photothermal (PTT) and photodynamic (PDT) effects. In an S. aureus infected wound model, the composite hydrogel effectively reduces the expression level of wound inflammatory factors and accelerates collagen deposition, epithelial tissue, and vascular regeneration, thereby promoting wound healing. This safe and synergistic therapeutic system holds great promise for clinical applications in the treatment of infectious wounds.

Ultrasonication-Tailored Graphene Oxide of Varying Sizes in Multiple-Equilibrium-Route-Enhanced Adsorption for Aqueous Removal of Acridine Orange.

Graphene oxide (GO) has shown remarkable performance in the multiple-equilibrium-route adsorption (MER) process, which is characterized by further activation of GO through an in-situ reduction process based on single-equilibrium-route adsorption (SER), generating new adsorption sites and achieving an adsorption capacity increase. However, the effect of GO on MER adsorption in lateral size and thickness is still unclear. Here, GO sheets were sonicated for different lengths of time, and the adsorption of MER and SER was investigated at three temperatures to remove the typical cationic dye, acridine orange (AO). After sonication, we found that freshly prepared GO was greatly reduced in lateral size and thickness. In about 30 min, the thickness of GO decreased dramatically from several atomic layers to fewer atomic layers to a single atomic layer, which was completely stripped off; after that, the monolayer lateral size reduction dominated until it remained constant. Surface functional sites, such as hydroxyl groups, showed little change in the experiments. However, GO mainly reduces the C=O and C-O bonds in MER, except for the conjugated carbon backbone (C-C). The SER adsorption kinetics of all temperatures fitted the pseudo-first-order and pseudo-second-order models, yet room temperature preferred the latter. An overall adsorption enhancement appeared as sonication time, but the equilibrium capacity of SER GO generally increased with thickness and decreased with the single-layer lateral size, while MER GO conversed concerning the thickness. The escalated temperature facilitated the exfoliation of GO regarding the adsorption mechanism. Thus, the isotherm behaviors of the SER GO changed from the Freundlich model to Langmuir as size and temperature changed, while the MER GO were all of the Freundlich. A record capacity of ~4.3 g of AO per gram of GO was obtained from the MER adsorption with a sixty-minute ultrasonicated GO at 313.15 K. This work promises a cornerstone for MER adsorption with GO as an adsorbent.

Antibacterial and osteoconductive polycaprolactone/polylactic acid/nano-hydroxyapatite/Cu@ZIF-8 GBR membrane with asymmetric porous structure.

Repair of periodontal and maxillofacial bone defects is a major challenge in clinical. Guided bone regeneration (GBR) is considered one of the most effective methods. However, the efficacy of currently available GBR membranes for repair is frequently limited by their poor osteogenic potential and lack of antibacterial activity. The first step in this investigation was to construct a zinc-based zeolite-imidazolate framework loaded with copper ions (Cu@ZIF-8). Following that, a novel polycaprolactone/polylactic acid/nano-hydroxyapatite/Cu@ZIF-8 (PCL/PLA/n-HA/Cu@ZIF-8) GBR membrane was developed using a simple porogen with nonsolvent-induced phase separation (NIPS) approach. The produced membrane with asymmetric porous structure (one smooth side and one rough side) possesses hydrophilicity corresponding to the roughness of its two sides. The superior mechanical property, stability of degradation, and ion release capability of the membrane all contribute to the clinical feasibility. Additionally, in vitro biological experiments demonstrated that the PCL/PLA/n-HA/Cu@ZIF-8 membrane had favorable osteogenic and antibacterial properties, which suggests the high potential for application in the GBR procedure.

Acceleration of Oral Wound Healing under Diabetes Mellitus Conditions Using Bioadhesive Hydrogel.

Oral wounds under diabetic conditions display a significant delay during the healing process, mainly due to oxidative stress-induced inflammatory status and abnormal immune responses. Besides, the wet and complicated dynamic environment of the oral cavity impedes stable treatment of oral wounds. To overcome these, a biomimetic hydrogel adhesive was innovatively developed based on a mussel-inspired multifunctional structure. The adhesive displays efficient adhesion and mechanical harmony on the oral mucosa through enhanced bonding in an acidic proinflammatory environment. The bioadhesive hydrogel exhibits excellent antioxidative properties by mimicking antioxidative enzymatic activities to reverse reactive oxygen species (ROS)-mediated immune disorders. Experiments on oral wounds of diabetic rats showed that this hydrogel adhesive could effectively protect against mucosal wounds and obviously shorten the inflammatory phase, thus promoting the wound-healing process. Therefore, this study offers a promising therapeutic choice with the potential to advance the clinical treatment of diabetic oral wounds.

nHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair.

Critical-sized maxillofacial bone defects have been a tough clinical challenge considering their requirements for functional and structural repair. In this study, an injectable in-situ forming double cross-linked hydrogel was prepared from gelatin (Gel), 20 mg/mL alginate dialdehyde (ADA), 4.5 mg/mL Ca2+ and borax. Improved properties of composite hydrogel might well fit and cover irregular geometric shape of facial bone defects, support facial structures and conduct masticatory force. We innovatively constructed a bioactive poly-porous structure by decoration with nano-sized hydroxyapatite (nHA). The highly ordered, homogeneous and size-confined porous surface served as an interactive osteogenic platform for communication and interplay between macrophages and bone marrow derived stem cells (BMSCs). Effective macrophage-BMSC crosstalk well explained the remarkable efficiency of nHA-loaded gelatin/alginate hydrogel (nHA@Gel/ADA) in the repair of critical-size skull bone defect. Collectively, the composite hydrogel constructed here might serve as a promising alternative in repair process of complex maxillofacial bone defects.

Liver tumor segmentation using 2.5D UV-Net with multi-scale convolution.

Liver tumor segmentation networks are generally based on U-shaped encoder-decoder network with 2D or 3D structure. However, 2D networks lose the inter-layer information of continuous slices and 3D networks might introduce unacceptable parameters for GPU memory. As a result, 2.5D networks were proposed to balance the memory consumption and 3D context. Different from the canonical 2.5D design, which utilizes a 2D network combined with RNN, we propose a new 2.5D design called UV-Net to encode the inter-layer information in the context of 3D convolution, and reconstruct the high-resolution results with 2D deconvolution. At the same time, the multi-scale convolution structure enables multi-scale feature extraction without extra computational cost, which effectively mines structured information, reduces information redundancy, strengthens independent features, and makes feature dimension sparse, to enhance network capacity and efficiency. Combined with the proposed preprocessing method of removing mean energy, UV-Net significantly outperforms the existing methods in liver tumor segmentation and especially improves the segmentation accuracy of small objects on the LiTS2017 dataset.

Efficient destruction of emerging contaminants in water by UV/S(IV) process with natural reoxygenation: Effect of pH on reactive species.

UV/sulfite systems with oxygen have recently been considered as advanced oxidation processes in view of the participation of oxysulfur radicals. However, the contribution of •OH and the efficiency of destructing emerging contaminants (ECs) in water remain largely unclear. Here, the UV/S(IV) process was applied with natural reoxygenation to degrade two typical ECs, diethyl phthalate (DEP) and bisphenol A (BPA) showing different properties. Solution pH played the key role in determining the reactive species, and both DEP and BPA were more favorably degraded at more alkaline conditions with higher utilization efficiency of SO32-. Specifically, the H•, O2•-, •OH and SO3•- were identified at acidic condition, but the amount of •OH accumulated significantly with the elevation of pH. Competitive quenching experiments showed that eaq- and •OH dominated the degradation of DEP and BPA at alkaline condition, respectively. Besides, DEP showed higher quantum efficiency for the indirect photolysis and mineralization degree than that of BPA at pH 9.2 mainly due to the direct use of the primary photoproduct. The possible transformation mechanisms of S(IV) and mineralization routes of both pollutants were proposed. This study may provide new insights into the mechanisms involved in UV/S(IV) process and a promising alternative for efficient removal of ECs in water.

Discrete and Stereospecific Oligomers Prepared by Sequential and Alternating Single Unit Monomer Insertion.

Natural biopolymers, such as DNA and proteins, have uniform microstructures with defined molecular weight, precise monomer sequence, and stereoregularity along the polymer main chain that affords them unique biological functions. To reproduce such structurally perfect polymers and understand the mechanism of specific functions through chemical approaches, researchers have proposed using synthetic polymers as an alternative due to their broad chemical diversity and relatively simple manipulation. Herein, we report a new methodology to prepare sequence-controlled and stereospecific oligomers using alternating radical chain growth and sequential photoinduced RAFT single unit monomer insertion (photo-RAFT SUMI). Two families of cyclic monomers, the indenes and the N-substituted maleimides, can be alternatively inserted into RAFT agents, one unit at a time, allowing the monomer sequence to be controlled through sequential and alternating monomer addition. Importantly, the stereochemistry of cyclic monomer insertion into the RAFT agents is found to be trans-selective along the main chains due to steric hindrance from the repeating monomer units. All investigated cyclic monomers provide such trans-selectivity, but analogous acyclic monomers give a mixed cis- and trans-insertion.

PET-RAFT polymerisation: towards green and precision polymer manufacturing.

The necessity of sustainable development in the chemical industry has continuously drawn attention to find safe, environmentally friendly and atom-economic chemical processes, which is defined in the 12 principles of green chemistry. Merging photoredox catalysis and reversible addition-fragmentation chain transfer (RAFT) polymerisation, the photoinduced electron/energy transfer (PET)-RAFT process has opened up a new way of performing reversible deactivation radical polymerisation for well-defined polymer synthesis using light as an external stimulus. While providing an increased level of control (spatiotemporal, wavelength, and intensity control) over the polymerisation, PET-RAFT has many attractive attributes (abundant catalyst availability, catalyst recyclability, selectivity and oxygen tolerance) to be green and sustainable, which is intriguing for precision polymer manufacturing in industry.

Adsorption Kinetics of 137Cs+/90Sr2+ on Ca-Bentonite.

137Cs+/90Sr2+ adsorption kinetics on natural Ca-bentonite under the impact of different adsorption conditions was examined in detail. The results indicate that natural Ca-bentonite shows a strong adsorption capacity for Cs+/Sr2+. The adsorption reached at equilibrium after 2 hours for Cs+. Cs+/Sr2+removal efficiency reaches the highest when the pH value is 5 to 8 and increases with the increase of Ca-bentonite adding amount. Cs+ removal efficiency increases with the increase of Cs+ initial concentration, while Sr2+ removal efficiency slightly varies around 70%. The adsorption of Cs+/Sr2+ by Ca-bentonite follows the pseudo-second-order model and is controlled by chemical adsorption. Meanwhile, the results of intraparticle diffusion modelling indicate that intraparticle diffusion is a kinetics controlling step, besides surface adsorption and liquid film diffusion.

Are protein hubs faster folders? Exploration based on Escherichia coli proteome.

Protein hubs in protein-protein interaction network are especially important due to their central roles in the entire network. Despite of their importance, the folding kinetics of hub proteins in comparison with non-hubs is still unknown. In this work, the folding rates for protein hubs and non-hubs were predicted and compared for the interactome of Escherichia coli K12, and the results showed that hub proteins fold faster than non-hub proteins. A possible explanation might be that protein hubs have more and fast-folding structural conformations than non-hubs, which leads to the notion of "hub of hubs" in the protein conformation space. It was found that the sequence and structure features relevant to protein folding rates are also different between hub and non-hub proteins. Moreover, the interacting proteins tend to have similar folding rates. These results gave insightful implications for understanding the interplay between the mechanisms of protein folding and interaction.

Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity.

The therapeutic utility of exenatide (Ex-4) is limited due to short plasma half-life of 2.4h and thus numerous approaches have been used to obtain a longer action time. However, such strategies often attend to one thing and lose another. The study aimed to identify a candidate with balanced glucoregulatory activity and prolonged in vivo activity. A series of fatty chain conjugates of Ex-4 were designed and synthesized. First, thirteen cysteine modified peptides (1-13) were prepared. Peptides 1, 10, and 13 showed improved glucagon-like peptide-1 (GLP-1) receptor activate potency and were thus selected for second step modifications to yield conjugates I-1-I-9. All conjugates retained significant GLP-1 receptor activate potency and more importantly exerted enhanced albumin-binding properties and in vitro plasma stability. The protracted antidiabetic effects of the most stable I-3 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of I-3 to streptozotocin (STZ) induced diabetic mice achieved long-term beneficial effects on hemoglobin A1C (HbA1C) lowering and glucose tolerance. Once daily injection of I-3 to diet induced obesity (DIO) mice also achieved favorable effects on food intake, body weight, and blood chemistry. Our results suggested that I-3 was a promising agent deserving further investigation to treat obesity patients with diabetes.

Coumaglutide, a novel long-acting GLP-1 analog, inhibits ß-cell apoptosis in vitro and invokes sustained glycemic control in vivo.

Glucagon-like peptide-1 (GLP-1) is a potential candidate for the treatment of type 2 diabetes. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2=2 min). Our recent discovery of the novel long-acting GLP-1 analog, coumaglutide, elicits favorable hypoglycemic effects. The present study was aimed at determining the protection effect of ß-cell from apoptosis and in vivo pharmacologic properties of coumaglutide in diabetic mice. To determine the protective effect of coumaglutide on INS-1 cell viability and apoptosis, cells were exposed to 1 µM streptozotocin (STZ) and coumaglutide for 24 h. Moreover, STZ-induced diabetic mice were treated daily with coumaglutide for 20 days and a range of pharmacologic parameters, including hemoglobin A1c (HbA1C), intraperitoneal glucose tolerance, food intake and body weight were assessed before and after the treatment. As with other glucagon-like peptide-1 receptor agonizts, coumaglutide was able to protect ß-cell from apoptosis in vitro and induce a durable restoration of glycemic control (normalization of both HbA1C and improvement of intraperitoneal glucose tolerance) in diabetic mice. It can be concluded that coumaglutide retains native GLP-1 activities and thus may serve as a promising hypoglycemic drug candidate.

Novel Pentapeptide GLP-1 (32-36) Amide Inhibits ß-Cell Apoptosis In Vitro and Improves Glucose Disposal in Streptozotocin-Induced Diabetic Mice.

We proposed that a pentapeptide, LVKGR amide, GLP-1 (32-36) amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), might possess favorable actions against diabetes. Therefore, GLP-1 (32-36) amide was synthesized and the effects of it were examined in INS-1 cell and streptozotocin-induced diabetic mice model. To determine the protective effects of GLP-1 (32-36) amide on INS-1 cell viability and apoptosis, cells were exposed to 1 µm streptozotocin (STZ) and GLP-1 (32-36) amide for 24 h. Results showed that GLP-1 (32-36) amide treatment decreased apoptosis rate and significantly retained cell viability compared with saline-treated controls. Then, GLP-1 (32-36) amide was administered intraperitoneally to streptozotocin-induced diabetic mice with normal mice used as control. Body weight, energy intake, plasma glucose, and histopathology of the pancreas were assessed. Results showed that GLP-1 (32-36) amide protected ß-cell viability and apoptosis against STZ-induced toxicity, inhibited weight gain, and relieved symptoms of polydipsia. Moreover, GLP-1 pentapeptide-treated mice showed a slight trend toward reduced glucose excursions in intraperitoneal glucose tolerance test at the end of the experiment. GLP-1 (32-36) amide exerted favorable protective actions in streptozotocin-induced diabetic mice. The peptide curtailed weight gain and alleviates symptoms of polydipsia. These findings suggested the probable utility of GLP-1 (32-36) amide, a peptide mimetic derived there from GLP-1, for adjuvant treatment of diabetes.

Preliminary study on removing Cs⁺/Sr²âº by activated porous calcium silicate-A by-product from high-alumina fly ash recycling industry.

¹³7Cs⁺/9°Sr²âº-containing radioactive wastewater is one of the most important problems that the world has been facing with. A by-product, activated porous calcium silicate, is generated at high levels by the pre-desiliconizing and soda-lime-sintering processes for producing Al2O3from high-alumina fly ash. In order to examine if this by-product could be used as an absorbent for removal of ¹³7Cs⁺/9°Sr²âº from radioactive wastewater, various parameters, such as pH, adsorbent dose, contact time, and initial concentration, were discussed. Results indicated that the equilibrium reached in about 2 hr. Activated porous calcium silicate was highly pH sensitive and able to remove Cs(+)/Sr²âº in a near-neutral environment. The adsorption equilibrium was best described by Freundlich isotherm equations, and the adsorption of Cs⁺/Sr²âº was a physical process. The adsorption kinetic data could be better fitted by the pseudo-second-order model, and the adsorption was controlled by multidiffusion. Current study showed that activated porous calcium silicate has a good adsorption of Cs⁺/Sr²âº for their removal. However, other characteristics, such as selectivity because of coexisting cations, elution and regeneration, thermal stability, and acid resistance, should be discussed carefully before using it in an actual field.

Design, synthesis, and biological activity of novel dicoumarol glucagon-like peptide 1 conjugates.

Twelve novel dicoumarol glucagon-like peptide 1 (GLP-1) conjugates were designed, synthesized, and tested for biological activity. All derivatives retained receptor activation efficacy, and exhibited improved albumin affinity and in vitro stability in rat plasma. The in vivo elimination half-lives of 13c and 13 l (22.07 and 18.78 h, respectively) were much longer than those of the GLP-1 receptor agonists exendin-4 (2.82 h) and liraglutide (12.53 h). The prolonged in vivo antidiabetic effects of 13c and 13 l on db/db mice were confirmed by the hypoglycemic efficacy test and the multiple intraperitoneal glucose tolerance test. Importantly, a once daily administration of 13c to db/db mice for 7 weeks provided long-term beneficial effects by lowering glycated hemoglobin (HbA1c) levels to 5.05%, which was lower than with liraglutide treatment (5.41%). These results suggest that 13c is a promising long-lasting GLP-1 mimetic that may be suitable for clinical use following further research.