Candida albicans CHK1 gene regulates its cross-kingdom interactions with Streptococcus mutans to promote caries.

The cross-kingdom interactions between Candida albicans and Streptococcus mutans have played important roles in early childhood caries (ECC). However, the key pathways of C. albicans promoting the cariogenicity of S. mutans are still unclear. Here, we found that C. albicans CHK1 gene was highly upregulated in their dual-species biofilms. C. albicans chk1Δ/Δ significantly reduced the synergistical growth promotion, biofilm formation, and exopolysaccharides (EPS) production of S. mutans, the key cariogenic agent, compared to C. albicans wild type (WT) and CHK1 complementary strains. C. albicans WT upregulated the expressions of S. mutans EPS biosynthesis genes gtfB, gtfC, and gtfD, and their regulatory genes vicR and vicK, but chk1Δ/Δ had no effects. Both C. albicans WT and chk1Δ/Δ failed to promote the biofilm formation and EPS production of S. mutans ΔvicK and antisense-vicR strains, indicating that C. albicans CHK1 upregulated S. mutans vicR and vicK to increase the EPS biosynthesis gene expression, then enhanced the EPS production and biofilm formation to promote the cariogenicity. In rat caries model, the coinfection with chk1Δ/Δ and S. mutans decreased the colonization of S. mutans and developed less caries especially the severe caries compared to that from the combinations of S. mutans with C. albicans WT, indicating the essential role of C. albicans CHK1 gene in the development of dental caries. Our study for the first time demonstrated the key roles of C. albicans CHK1 gene in dental caries and suggested that it may be a practical target to reduce or treat ECC. KEY POINTS: • C. albicans CHK1 gene is important for its interaction with S. mutans. • CHK1 regulates S. mutans two-component system to promote its cariogenicity. • CHK1 gene regulates the cariogenicity of S. mutans in rat dental caries.

The resistance change and stress response mechanisms of chlorine-resistant bacteria under microplastic stress in drinking water distribution system.

The presence of both chlorine-resistant bacteria (CRB) and microplastics (MPs) in drinking water distribution systems (DWDS) poses a threat to water quality and human health. However, the risk of CRB bio evolution under the stress of MPs remains unclear. In this study, polypropylene (PP) and polyethylene (PE) were selected to study the adsorption and desorption behavior of sulfamethoxazole (SMX), and it was clear that MPs had the risk of carrying pollutants into DWDS and releasing them. The results of the antibiotic susceptibility test and disinfection experiment confirmed that MPs could enhance the resistance of CRB to antibiotics and disinfectants. Bacteria epigenetic resistance mechanisms were approached from multiple perspectives, including physiological and biochemical characteristics, as well as molecular regulatory networks. When MPs enter DWDS, CRB could attach to the surface of MPs and directly interact with both MPs and the antibiotics they release. This attachment process promoted changes in the composition and content of extracellular polymers (EPS) within cells, enhanced surface hydrophobicity, stimulated oxidative stress function, and notably elevated the relative abundance of certain antibiotic resistance genes (ARGs). This study elucidates the mechanism by which MPs alter the intrinsic properties of CRB, providing valuable insights into the effective avoidance of biological risks to water quality during CRB evolution.

Methacrylated Carboxymethyl Chitosan Scaffold Containing Icariin-Loaded Short Fibers for Antibacterial, Hemostasis, and Bone Regeneration.

Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

A Horn Peptide-Thermoresponsive Hydrogel for Angiogenesis and Bone Regeneration.

The management of critical-sized bone defects presents a formidable clinical challenge, especially given the increasing incidence of bone diseases in the aging population. Consequently, there is an increased demand for minimally invasive bone repair materials that can effectively address this challenge, particularly in outpatient settings. In this study, the goal is to develop an injectable and biodegradable biomaterial that adheres to and fills bone-defect sites to support bone regeneration. The osteogenic and angiogenic activities of animal horn peptides are investigated by incorporating them into biologically active moieties, in combination with a novel thermosensitive hydrogel. The resulting thermosensitive hydrogel exhibited essential biological functionalities, allowing precise modulation of its physical and chemical properties. Notably, the hydrogel incorporating the horn peptide rapidly filled the bone defect site, promoting both angiogenesis and bone induction. Consequently, this approach significantly accelerates new bone regeneration. In summary, the findings of this study present a promising, minimally invasive solution for addressing critical-sized bone defects.

Fabrication and design of poly(l-lactic acid) membrane for passive MAP packaging of Brassica chinensis L.

PLDx L copolymers were synthesized from physically stable rigid poly(l-lactic acid) (PLLA) and a few different molecular weights of polydimethylsiloxane (PDMS) to increase the O2 and CO2 permeabilities of PLLA films and make them acceptable for packaging highly respirable products. The effect of PDMS on the morphology, mechanical properties, and gas permeability of PLDx L was investigated. Copolymers showed approximately 10 times the fracture strain and 1.7 times the CO2 and O2 permeabilities of neat PLLA. Additionally, PLDx L maintained an increased CO2 /O2 perm-selectivity consistent between 5 and 40°C. Passive modified atmosphere packaging of Brassica chinensis L was developed to assess the membrane's impact on headspace gas inside the package. The results showed that poly(amide)/poly(ethylene) packaging with 48 cm2 PLD1.8 L membrane as a breathing window can provide 50 g B. chinensis L. with a healthy atmosphere of 3%-8% O2 and 5%-8% CO2 between 6 and 22 days. Vegetables packaged in PLD1.8 L had the lower respiration rate, lower nitrite contents, and less proliferation of microorganisms. Moreover, a suitable atmosphere kept vegetables with higher ascorbic acid and a good appearance after more than 2 weeks of storage at 5°C. PRACTICAL APPLICATION: The permeability of the PLLA-based membrane can be adjusted for the breathable window membrane of sealed fresh products. In the future, several types of film could be developed to match the respiratory and metabolic characteristics of different kinds of products. Such PLLA-based specialized membranes can refine the fresh-keeping function and be more attractive to the customer.

Icy core-shell composite nanofibers with cooling, antibacterial and healing properties for outdoor burns.

Burns are usually difficult to treat because their susceptibe to bacterial infections. When burns is accompanied by hyperthermia, the heat accumulated on the skin will causes extensive tissue damage. Most dressings focus on the treatment process, while ignoring the first-aid treatment to remove hyperthermia. To make matters worse, when outdoors, it is hard to find clean water to wash and cool the burned area. A dressing which can simultaneously realize first-time cooling and repairing treatment of the burned area can shorten treatment time, and is especially beneficial for outdoor use. In this study, a handheld coaxial electrospinning device is developed for preparing platelet-rich plasma @Polycaprolactone-epsilon polylysine (PRP@PCL/ε-PL) core-shell nanofibers. The nanofibers can be synchronously transformed into ice fibers during the spinning process, and directly deposited on the skin. The whole process is convenient to use outdoor. Via dual cooling mechanisms, first aid can take away the excessive heat in the burn area by nanofibers. These core-shell nanofibers also show its excellent antimicrobial and tissue regeneration-promoting properties. Therefore, it achieves first-time cooling and repair treatment of the burned area at the same time. Moreover, due to direct in-situ deposition of this handheld coaxial electrospinning, better antimicrobial properties, and faster healing performance are achieved. By using this integrated strategy that combines cooling, antibacterial and healing promotion, the burn recovery time is shortened from 21 days to 14 days.

Manipulating electrostatic field to control the distribution of bioactive proteins or polymeric microparticles on planar surfaces for guiding cell migration.

We report a general strategy to generate linear and circular gradients of active proteins or polymeric microparticles on planar surfaces by controlling the distribution of electrostatic field during electrohydrodynamic jet printing or electrospray process. Taking fibronectin as an example, we generated a circular gradient of fibronectin and investigated its effect on accelerating the migration of fibroblasts to suit for use in wound closure. In another demonstration, we created linear gradients of laminin in unidirectional and bidirectional patterns, respectively. We showed that such gradations significantly promoted the migration of human neuroblastoma cells with the increase of laminin content. When we changed fibronectin/laminin to electrosprayed poly(lactic-co-glycolic acid) (PLGA) microparticles, we found similar results in terms of guiding cell migration, except that the guidance cues varied from biological signal to topographic structure. Taken together, this method for generating linear/circular gradients of fibronectin/laminin and PLGA microparticles can be readily extended to different types of bioactive proteins and polymeric microparticles to suit wound closure, nerve repair, and related applications involving cell migration.