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Enterococcus faecalis (E. faecalis) biofilm-associated persistent endodontic infections (PEIs) are one of the most common tooth lesions, causing chronic periapical periodontitis, root resorption, and even tooth loss. Clinical root canal disinfectants have the risk of damaging soft tissues (e.g., mucosa and tongue) and teeth in the oral cavity, unsatisfactory to the therapy of PEIs. Nanomaterials with remarkable antibacterial properties and good biocompatibility have been developed as a promising strategy for removing pathogenic bacteria and related biofilm. Herein, carbon dots (CDs) derived from fucoidan (FD) are prepared through a one-pot hydrothermal method for the treatment of PEIs. The prepared FDCDs (7.15 nm) with sulfate groups and fluorescence property are well dispersed and stable in water. Further, it is found that in vitro FDCDs display excellent inhibiting effects on E. faecalis and its biofilm by inducing the formation of intracellular and extracellular reactive oxygen species and altering bacterial permeability. Importantly, the FDCDs penetrated the root canals and dentinal tubules, removing located E. faecalis biofilm. Moreover, the cellular assays show that the developed FDCDs have satisfactory cytocompatibility and promote macrophage recruitment. Thus, the developed FDCDs hold great potential for the management of PEIs. [ABSTRACT FROM AUTHOR]

Tooth removal, particularly for patients with severe periodontitis, can frequently cause massive bleeding, postoperative infection, and bone resorption, resulting in a dry socket. Thus, developing bio-multifunctional materials with excellent antibacterial, hemostatic, and osteogenic characteristics for the prevention of dry sockets after tooth removal is highly desirable in clinical applications. Herein, chitosan-CaP microflowers (CM) and metronidazole (MD) loaded calcium alginate (CA) sponges (CA@CM/MD) with enhanced antibacterial, hemostatic, and osteogenic properties were developed via Ca2+ crosslinking, lyophilization, and electrostatic interaction for the prevention of dry socket after tooth removal. The fabricated CM particles display 3-dimensional, relatively homogeneous, and flower-shaped architectures. The CA@CM/MD composite sponges were facilely shaped into the tooth root as well as exhibit interconnected porous and lamellar structures with remarkable porosity, suitable maximum swelling ratio, as well as excellent compressive and hemostatic performance. Besides, the in vitro cellular assessment demonstrates that the prepared CA@CM/MD composite sponges possess satisfactory cytocompatibility. Importantly, the designed sponges significantly suppress the growth of S. aureus and E. coli , as well as promote cellular osteogenic differentiation by upregulating the formation of alkaline phosphatase. Our findings indicate that the tooth root-shaped composite sponges hold great promise for wound management after tooth removal. [ABSTRACT FROM AUTHOR]

Inorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is one of the most common diseases that threaten millions of lives annually. Evidence supports that bile acid (BA) affects HCC through inflammation, DNA damage, or other mechanisms. Methods. A total of 127 BA-associated genes were analyzed in HCC tumor and nontumor samples using The Cancer Genome Atlas data. Genes correlated to the prognosis of patients with HCC were identified using univariate and multivariate Cox regression analyses. Furthermore, a prediction model with identified genes was constructed to evaluate the risk of patients with HCC for prognosis. Results. Out of 26 genes with differential expressions between the HCC and nontumor samples, 19 and 7 genes showed upregulated and downregulated expressions, respectively. Three genes, NPC1, ABCC1, and SLC51B, were extrapolated to construct a prediction model for the prognosis of patients with HCC. Conclusion. The three-gene prediction model was more reliable than the pathological staging characters of the tumor for the prognosis and survival of patients with HCC. In addition, the upregulated genes facilitating the transport of BAs are associated with poor prognosis of patients with HCC, and genes of de novo synthesis of BAs benefit patients with HCC. [ABSTRACT FROM AUTHOR]

Developing biomaterials with high osteogenic properties is crucial for achieving rapid bone repair and regeneration. This study focuses on the application of nanocrystal hydroxyapatite (nHAp) as a drug carrier to load Fu Yuan Huo Xue Decoction (FYHXD), a traditional Chinese medicine derived from Angelica sinensis, aiming to achieve improved efficacy in treating bone diseases such as osteoporosis. Through a facile physical adsorption approach, the FTIR result emerges new characteristic absorption peaks in the range of 1200–950 cm−1, proving the successful absorption of FYHXD onto the nHAp with a loading efficiency of 39.76 %. The modified nHAp exhibits a similar shape to the bone-derived hydroxyapatite nanocrystals, and their diameter increases slightly after modification. The drug release assay implies the rapid release of FYHXD in the first 10 h, followed by a continuously slow release within 70 h. The developed nHAp effectively enhances the adhesion, spreading, and proliferation of MC3T3-E1 cells in vitro, and significantly promotes their osteogenic differentiation, as indicated by increased alkaline phosphatase activity. Overall, the biocomposites hold great promise as active ingredients for integration into bone-associated biomaterials, offering the potential to stimulate spontaneous osteogenesis without requiring exogenous osteogenic factors. • FYHXD was loaded onto nHAp in one step using physical adsorption under mild conditions. • nHAp@FYHXD achieved drug sustained-release to promote MC3T3-E1 cell adhesion and proliferation. • The combination of nHAp and FYHXD significantly promoted MC3T3-E1 cell differentiation. [ABSTRACT FROM AUTHOR]

The recent use of PARP inhibitors (PARPi) in the maintenance treatment of ovarian tumor has significantly improved the survival rates of cancer patients. However, the current oral administration of PARP inhibitors fails to realize optimal therapeutic effects due to the low bioavailability in cancerous tissues, and often leads to a range of systemic adverse effects including hematologic toxicities, digestive system reactions, and neurotoxicities. Therefore, the demand for an advanced drug delivery system that can ensure effective drug administration while minimizing these unfavorable reactions is pressing. Injectable hydrogel emerges as a promising solution for local administration with the capability of sustainable drug release. In this study, we developed an injectable hydrogel made from aminated hyaluronic acid and aldehyde-functionalized pluronic127 via Schiff base reaction. This hydrogel exhibits excellent injectability with short gelation time and remarkable self-healing ability, and is applied to load niraparib. The drug-loaded hydrogel (HP@Nir hydrogel) releases drugs sustainably as tested in vitro as well as displays significant anti-proliferation and anti-migratory properties on human epithelial ovarian cancer cell line. Notably, HP@Nir hydrogel effectively suppresses the growth of ovarian cancer, without significant adverse reactions as demonstrated in animal studies. Additionally, the developed hydrogel is gradually degraded in vivo for around 20 d, while maintaining good biocompatibility. Overall, the injectable hydrogel loaded with niraparib provides a secure and efficient strategy for the treatment and management of ovarian cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

• A glycerol@H 3 PO 4 based PVP nanofiber membrane was prepared by electrospun. • The capacitive pressure sensor exhibits enhanced detection range and sensitivity. • A human posture recognition integrated system was developed by a CNN algorithm. • The movement of the human body can be monitored in 3D real-time on computers. Flexible pressure sensors are widely used in wearable devices, especially in the field of human–computer interaction. Hence, the development of flexible pressure sensors with excellent sensitivity and detection range is essential. This paper introduces a flexible capacitive pressure sensor based on glycerol@phosphoric acid nanofibers, showcasing remarkable properties, including high sensitivity (53.97 kPa−1 at 300–1200 kPa), exceptionally wide detection range (1800 kPa), faster response/recovery time than human skin (14.4/9.6 ms), extremely low detection limit (5 Pa), outstanding stability (>10,000 fatigue tests), and excellent biocompatibility. In addition, the sensor was seamlessly integrated with deep learning algorithms, embedded systems, and internet technologies to develop a comprehensive human posture recognition system, which can adeptly capture and identify intricate human movements with an accuracy rate over 98 %. This system establishes a diagnostic channel between home patients and rehabilitation experts. Owing to its excellent sensitivity and detection range, the developed sensor presents promising prospects for future advancements in human–computer interaction. [ABSTRACT FROM AUTHOR]

[Display omitted] • The prepared PL-CQDs had uniform particle size, fluorescent properties, and positive charge. • Biocompatible PL-CQDs enhanced T cell viability with increasing concentration and inhibit T cell differentiation to CD4 + T cells in mice. • PL-CQDs, together with T cells, promoted osteogenic differentiation of MC3T3-E1 cells and promoted alkaline phosphatase expression and calcium nodule formation in MC3T3-E1 cells. • In vivo, PL-CQDs promoted periodontal bone formation, reduced periodontal tissue inflammation, and had good therapeutic effects in animal models. Periodontitis, a common chronic inflammatory disease, is characterized by T cell responses leading to gradual alveolar bone loss and eventual tooth mobility or loss. Herein, polylysine-derived carbon quantum dots (PLL-CQDs) are synthesized via the pyrolysis method to facilitate the recovery of periodontal bone loss induced by periodontitis by modulating T cell phenotype. The PLL-CQDs, characterized by small particle size (2.31 ± 0.70 nm) and fluorescence properties, preserved the positive charge of PLL, affirming successful preparation. In vitro studies revealed that PLL-CQDs significantly increased T cell proliferation in a concentration-dependent manner, while effectively suppressing differentiation into CD4+ phenotype. Furthermore, they promoted alkaline phosphatase expression and calcium nodule formation in MC3T3-E1 cells, indicating potential for periodontal bone regeneration. In viv o experiments demonstrated that PLL-CQDs mitigated alveolar bone resorption and modulated periodontal tissue inflammation. Overall, PLL-CQDs exhibited the ability to regulate T cell differentiation and expedite periodontal bone healing, offering promising implications for periodontitis treatment and suggesting novel strategies for addressing immune-associated bone diseases using CQDs. [ABSTRACT FROM AUTHOR]

Unintended pregnancy is a global issue with serious ramifications for women, their families, and society, including abortion, infertility, and maternal death. Although existing contraceptive strategies have been widely used in people's lives, there have not been satisfactory feedbacks due to low contraceptive efficacy and related side effects (e.g., decreased sexuality, menstrual cycle disorder, and even lifelong infertility). In recent years, biomaterials-based long-acting reversible contraception has received increasing attention from the viewpoint of fundamental research and practical applications mainly owing to improved delivery routes and controlled drug delivery. This review summarizes recent progress in advanced biomaterials for long-acting reversible contraception via various delivery routes, including subcutaneous implant, transdermal patch, oral administration, vaginal ring, intrauterine device, fallopian tube occlusion, vas deferens contraception, and Intravenous administration. In addition, biomaterials, especially nanomaterials, still need to be improved and prospects for the future in contraception are mentioned. [ABSTRACT FROM AUTHOR]

Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed. [ABSTRACT FROM AUTHOR]

Developing bio‐multifunctional patches with natural extracellular matrix‐like structures, excellent high adhesion in the wet state, self‐healing ability, antibacterial activity, and favorable cell responses for accelerating tissue healing is highly desirable in clinical applications. Herein, bio‐multifunctional composite hydrogels are developed by coupling carboxymethyl chitosan and 4‐arm poly (ethylene glycol) aldehyde for full‐thickness abdominal wall defect repair. The prepared hydrogels exhibit excellent self‐healing and mechanical properties, high adhesion in the wet state, and significant antibacterial ability. In vitro cellular experiments show that the hydrogels combined with recombinant bovine basic fibroblast growth factor remarkably promote cell proliferation and then accelerate full‐thickness abdominal wall defect repair in a rat model. The histomorphological evaluation shows that compared to the commercial polypropylene mesh used clinically, the designed hydrogel patches facilitate an increase in the thickness and integrity of the abdominal wall tissue by upregulating the production of Ki67, enhancing the formation of collagen, inducing neovascularization, and inhibiting inflammation by reducing the expression of IL‐6, TNF‐α, and IL‐1β. The results demonstrate that this novel bio‐multifunctional hydrogel patch holds great potential for the treatment of full‐thickness abdominal wall defects. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most significant public health threat worldwide. Patients with severe COVID-19 usually have pneumonia concomitant with local inflammation and sometimes a cytokine storm. Specific components of the SARS-CoV-2 virus trigger lung inflammation, and recruitment of immune cells to the lungs exacerbates this process, although much remains unknown about the pathogenesis of COVID-19. Our study of lung type II pneumocyte cells (A549) demonstrated that ORF7, an open reading frame (ORF) in the genome of SARS-CoV-2, induced the production of CCL2, a chemokine that promotes the chemotaxis of monocytes, and decreased the expression of IL-8, a chemokine that recruits neutrophils. A549 cells also had an increased level of IL-6. The results of our chemotaxis Transwell assay suggested that ORF7 augmented monocyte infiltration and reduced the number of neutrophils. We conclude that the ORF7 of SARS-CoV-2 may have specific effects on the immunological changes in tissues after infection. These results suggest that the functions of other ORFs of SARS-CoV-2 should also be comprehensively examined. [ABSTRACT FROM AUTHOR]

Marine polysaccharide-based hydrogels have drawn much attention for diversified biomedical applications owing to their excellent (bio)physicochemical properties. In the present work, a series of marine polysaccharide-based hydrogels composed of chitosan, alginate, or fucoidan are prepared via a facile chemical cross-linking approach in an alkali/urea aqueous system. The prepared hydrogels possess tunable microporous architecture, swelling, and biodegradable properties by changing the components and proportions of marine polysaccharides. Importantly, the developed hydrogels are mechanically robust and the maximum compressive stress is up to 28.37 ± 4.63 kPa. Furthermore, the composite hydrogels exhibit excellent cytocompatibility, blood compatibility, and histocompatibility. When implanted subcutaneously in rats, the hydrogels containing fucoidan inhibit the inflammatory response of surrounding tissue. Thus, the designed composite hydrogels are promising bio-scaffolds in biomedical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Fucoidan has received much attention in healthy food and biomedicine owing to their unique (bio)physicochemical properties, particularly antibacterial and antiviral. Pathogenic microorganisms and probiotics are coexisting in many tissues (e.g., gut, oral, and vagina). However, the effect of fucoidan on probiotics has not been examined. Herein, fucoidan sterilized by different methods (i.e., 0.22 μm filter and high-temperature autoclave) is applied to explore its effect on the responses of Lactobacillus rhamnosus. It is found that high-temperature autoclave treatment causes the depolymerization of fucoidan. Further, the proliferation, morphology, and metabolism of probiotics are greatly dependent on the concentrations of fucoidan. The formation of probiotic biofilm is reduced with an increased concentration of fucoidan. Moreover, the antibacterial ability of probiotics initially increases and then decreases with an increased concentration of fucoidan. Thus, fucoidan could serve as a new marine-origin prebiotic, offering new insight into probiotic modulation and its application in inhibiting bacterial infections. • Depolymerized fucoidan with appropriate concentration promotes the growth of L. rhamnosus. • Depolymerized fucoidan affects the morphology and metabolism of L. rhamnosus. • Depolymerized fucoidan inhibits the formation of probiotic biofilm. • Depolymerized fucoidan enhances the antibacterial ability of L. rhamnosus. • Depolymerized fucoidan serves as a marine-origin prebiotic. [ABSTRACT FROM AUTHOR]

Fluorescence resonance energy transfer, a promising method for in situ imaging of miRNA in living cells, has intrinsic limitation on sensitivity and selectivity. Herein, a fluorescent amplification strategy based on catalyzed hairpin assembly indirectly covalent on Fe 3 O 4 @C nanoparticles via short single-stranded DNA was investigated for cellular miRNA detection in living cells, integrating non-enzyme target-active releasing for amplifying the signal output, highly quenching efficiency of Fe 3 O 4 @C nanoparticles with low background, ssDNA assisted fluorescent group-fueled chain releasing from Fe 3 O 4 @C nanoparticles with enhanced fluorescence response. The designed platform exhibits highly sensitive in a wide linear concentration range of 0.450 pM–190 pM and is highly specific for miRNA-20a detection with the ability of discriminating one mistake base. Additionally, the CHA-Fe 3 O 4 @C was successfully applied in imaging visualization of miRNA-20a in the living cell. The strategy provides a promising bioassay approach for clinical research. Image 1 • An indirectly covalent strategy based on catalytic hairpin assembly coupling Fe 3 O 4 @C nanoparticles was proposed. • The biosensor with high sensitivity displayed a linear response in the range of 0.450–190 pM for miRNA-20a. • The method possessed high selectivity with the ability of discriminating one mistake base. • The biosensor was successfully used for imaging of miRNAs in living cells. [ABSTRACT FROM AUTHOR]

Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients. [ABSTRACT FROM AUTHOR]

Abstract In this paper, a novel design of metamaterial absorber (MA) with multi modes and tunability characteristics in terahertz (THz) range is presented. The MA consists of patterned gold-graphene on the top layer, graphene sheet and gold ground separated by SiO 2. The chemical potential of patterned graphene and graphene sheet can be tuned independently. Thus, the regulation flexibility of MA is greatly enhanced. For demonstration, the proposed MA is investigated using circuit analogy method and the distributions of the electric field are also discussed in detail to explore underlying mechanism. Numerical calculations are stimulated in a commercial full-wave solver and indicate that the proposed MA possesses excellent absorption properties. There are three perfect absorption (≥ 99.2 %) modes at 2.4 THz, 4.2 THz and 7.2 THz respectively. Under the regulation of chemical potential, the proposed MA could serve as single-frequency or dual-frequency absorber without change of physical structure. When working as single-frequency absorber, the MA could be regulated between different modes during a large frequency range and the absorption peaks could also be regulated within the same mode during a relative smaller frequency range. Furthermore, the MA has two absorption peaks at 2.4 THz and 7.2 THz (≥ 95 %) simultaneously as dual-frequency absorber. The proposed MA shows promising application potentials due to the flexible modulation and functions and this work provides a new perspective for the design of tunable THz absorbers based on graphene. Highlights • Multi perfect absorption modes. • Could be regulated from single-frequency absorber to dual-frequency absorber though chemical potential. • Absorption modes can be regulated. • The absorption frequency could be modulated within the same mode. [ABSTRACT FROM AUTHOR]

Particle shape is an essential aspect of granular soils that affects their mechanical properties. It is challenging to isolate the effect of particle shape from other mechanical properties such as inter-particle friction coefficient and particle shear modulus in laboratory tests. The discrete element method (DEM) makes it feasible to investigate the effect of macroscopic and mesoscopic particle morphologies including sphericity and roundness. This study provides a systematical DEM investigation of the particle shape effect on the dynamic properties of granular soils by simulating cyclic undrained triaxial tests at various initial confining pressures and void ratios. The results indicate that specimen consisting of angular particles generally exhibit a higher secant shear modulus G than that of rounded particles. Additionally, particle shape has no significant effect on modulus ratio G / G 0 but a noticeable impact on damping ratio D at relatively large strains due to dilatancy. A weighted coordination number CN' was proposed to reveal the microscopic effect of particle shape on G 0. Contact sliding was found to be the main cause of modulus degradation and damping increase with increasing shear strain. The tangential shear modulus ratio G tan / G 0 is inversely correlated to the weighted contact sliding ratio f s '. [ABSTRACT FROM AUTHOR]

BK polyomavirus (BKPyV) is an opportunistic infectious pathogen that is associated with hemorrhagic cystitis and nephropathy, mainly in transplant recipients and human immunodeficiency virus 1 (HIV-1) infected patients. However, molecular characterization studies of BKPyV in China are rare. This study was designed to elucidate the prevalence and to determine the main subtypes of BKPyV among HIV-1-infected patients in southeastern China. In addition, the increased incidences for BKPyV reactivation were analyzed. The isolated BKPyV DNA was amplified by polymerase chain reaction (PCR) and the specimen sequences were aligned with the reference sequences for phylogenetic analysis. In this study, BKPyV viruria was detected in 64.2% (88/137) of HIV-1-infected patients. Patients in the BKPyV-positive group were more diverse with respect to gender (P = 0.039) and age (P = 0.023) than their counterparts in the BKPyV-negative group, and they had a higher rate of co-infection with tuberculosis (TB) (P = 0.026). Viruria was more commonly found in patients with CD4 counts <200 cells/mm (72.7%) than in those with CD4 counts ≥200 cells/mm (58.5%) (not significant). All sequenced BKPyV isolates belonged to subtype I (13/32) and IV (19/32). A high prevalence of BKPyV reactivation was discovered in patients with HIV-1 infection. Females and elderly individuals, as well as those with a TB co-infection, appeared more susceptible to BKPyV reactivation in this study. BKPyV viruria was found more often and was associated with lower CD4 counts. [ABSTRACT FROM AUTHOR]

A metamaterial analogy of tunable electromagnetically induced transparency (EIT) is theoretically investigated in terahertz regime. The proposed metamaterial consists of vertical gold strips and horizontal graphene wires, which perform as bright elements and dark elements, respectively. The EIT-like phenomenon can be induced by bright–dark mode coupling on condition of structural lateral displacement. Numerical result reveals that the EIT-like effect remains noticeable with a wide range of incidence polarization angles. Most importantly, by manipulating gate voltages, the EIT window can be dynamically controlled without refabricating the structure. The amplitude modulation depth can reach 81%, 79%, and 68% respectively at three characteristic frequencies as Fermi energy changes in the scope of 0.8–1.0 eV. Furthermore, a sensitivity of 0.95 THz per refractive index unit (RIU) is realized varying the refractive index in the surrounding medium. This structure provides potential applications for detectors, sensors, and modulators. [ABSTRACT FROM AUTHOR]

Through applying gate voltage to tune the chemical potential of graphene, the relative permittivity of multilayer graphene/Al 2 O 3 stack can be dynamically adjusted over a wide range. In this paper, we mainly design novel photonic-crystal waveguides based on graphene stacks including a side-coupled waveguide with two defect cavities as well as a two-channel multiport waveguide, and aim to modulate the propagation of incident light wave via controlling the permittivity of graphene stack. It is demonstrated according to simulations that tunable switching property can be achieved in our proposed structures, such as blue shift of resonant stopband, adjustable coupled-resonator-induced transparency, and tunability of output quantity. These results could be very instructive for the potential applications in high-density integrated optical devices, photoelectric transducer, and laser pulse limiters. [ABSTRACT FROM AUTHOR]

With the ability of tuning chemical potential via gate voltage, the permittivity of graphene stack can be dynamically adjusted over a wide range. In this paper, we design electrically tunable metamaterials based on the graphene/Al 2 O 3 stacks array, which can achieve a good modulation of resonant frequency and peak value in terahertz region. Due to the enlargement of plasmonic resonance response and the broaden distribution of electric field, our proposed structures perform a better tunability compared with traditional metamaterials loaded monolayer graphene. Since the dipole-dipole coupling between adjacent stacks strengthens immensely as reduces the filling factor of array, the modulated capacity could be further improved. It is found that for oblique incidence, the transmission property is also sensitive to the chemical potential of graphene as well as the polarization direction of incident terahertz wave. These results could be very instructive for the potential applications in voltage-sensitive devices, tunable sensors and photovoltaic switches. [ABSTRACT FROM AUTHOR]

Probiotics are beneficial bacteria located in the oral cavity which exhibit antimicrobial properties and contribute to the regulation of immune function and the modulation of tissue repair. Fucoidan (FD), a marine prebiotic, may further enhance the ability of probiotics to promote ulcer healing. However, neither FD nor probiotics are attached to the oral cavity and neither are well-suited for oral ulcer healing owing to the wet and highly dynamic environment. In this study, probiotic-loaded calcium alginate/fucoidan composite hydrogels were developed for use as bioactive oral ulcer patches. The well-shaped hydrogels exhibited remarkable wet-tissue adhesion, suitable swelling and mechanical properties, sustained probiotic release, and excellent storage durability. Moreover, in vitro biological assays demonstrated that the composite hydrogel exhibited excellent cyto/hemocompatibility and antimicrobial effects. Importantly, compared to commercial oral ulcer patches, bioactive hydrogels show superior therapeutic capability for promoting ulcer healing in vivo by enhancing cell migration, inducing epithelial formation and orderly collagen fiber deposition, as well as facilitating neovascularization. These results demonstrate that this novel composite hydrogel patch demonstrates great potential for the treatment of oral ulcerations. [ABSTRACT FROM AUTHOR]

Intelligent delivery systems, stimuli-responsive nanocarriers, targeting PD-1/PD-L1 pathway hold the promise of controlling and adjusting the position and schedule of immunomodulator release in the selected tumor sites for enhanced cancer immunotherapy and have aroused enormous interests. [Display omitted] The drugs targeting the PD-1/PD-L1 pathway have gained abundant clinical applications for cancer immunotherapy. However, only a part of patients benefit from such immunotherapy. Thus, brilliant novel tactic to increase the response rate of patients is on the agenda. Nanocarriers, particularly the rationally designed intelligent delivery systems with controllable therapeutic agent release ability and improved tumor targeting capacity, are firmly recommended. In light of this, state-of-the-art nanocarriers that are responsive to tumor-specific microenvironments (internal stimuli, including tumor acidic microenvironment, high level of GSH and ROS, specifically upregulated enzymes) or external stimuli (e.g., light, ultrasound, radiation) and release the target immunomodulators at tumor sites feature the advantages of increased anti-tumor potency but decreased off-target toxicity. Given the fantastic past achievements and the rapid developments in this field, the future is promising. In this review, intelligent delivery platforms targeting the PD-1/PD-L1 axis are attentively appraised. Specifically, mechanisms of the action of these stimuli-responsive drug release platforms are summarized to raise some guidelines for prior PD-1/PD-L1-based nanocarrier designs. Finally, the conclusion and outlook in intelligent delivery system targeting PD-1/PD-L1 pathway for cancer immunotherapy are outlined. [ABSTRACT FROM AUTHOR]

Translation of the expanded (ggggcc) repeat in C9orf72 patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA inclusions. To elucidate their role in pathogenesis, we generated transgenic mice expressing codon-modified (GA) conjugated with cyan fluorescent protein (CFP). Transgenic mice progressively developed poly-GA inclusions predominantly in motoneurons and interneurons of the spinal cord and brain stem and in deep cerebellar nuclei. Poly-GA co-aggregated with p62, Rad23b and the newly identified Mlf2, in both mouse and patient samples. Consistent with the expression pattern, 4-month-old transgenic mice showed abnormal gait and progressive balance impairment, but showed normal hippocampus-dependent learning and memory. Apart from microglia activation we detected phosphorylated TDP-43 but no neuronal loss. Thus, poly-GA triggers behavioral deficits through inflammation and protein sequestration that likely contribute to the prodromal symptoms and disease progression of C9orf72 patients. [ABSTRACT FROM AUTHOR]

This paper presents the design, simulation and measurement of a sextuple-band ultra-thin metamaterial absorber (MA). The unit cell of this proposed structure is composed of triangular spiral-shaped complementary structures imprinted on the dielectric substrate backed by a metal ground. The measured results are in good agreement with simulations with high absorptivities of more than 90% at all six absorption frequencies. In addition, this proposed absorber has good performances of ultra-thin, polarization insensitivity and a wide-angle oblique incidence, which can easily be used in many potential applications such as detection, imaging and sensing. [ABSTRACT FROM AUTHOR]

Radical pelvic surgery is commonly accompanied by the risk of postoperative erectile dysfunction induced by cavernous nerve injury (CNI-ED). The strategy of using adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) to treat neurodegenerative diseases has shown promising results. However, it remains challenging to prolong the retention of unbound ADSC-Exo in damaged tissues to exert therapeutic effects. Herein, we develop a novel injectable thermo-sensitive hydroxyethyl chitosan/sodium β-glycerophosphate hydrogel (HG) encapsulating ADSC-Exo (HG@Exo) to manage CNI-ED. The HG exhibits excellent injectability, structural stability, and body temperature sensitivity. In vivo assessment demonstrates that the designed ADSC-Exo-loaded HG hydrogel enhances the retention of ADSC-Exo and displays a slow release. Furthermore, when HG@Exo is applied to the site of nerve injury, erectile function in the bilateral cavernous nerve injury rat model is significantly improved. Thus, our finding indicates that the developed bioactive hydrogel presents a promising strategy for the effective management of CNI-ED. [Display omitted] [ABSTRACT FROM AUTHOR]

Tooth extraction commonly causes uncontrolled bleeding, loss of blood clots, and bacterial infection, leading to the dry socket and bone resorption. Thus, it is highly attractive to design a bio-multifunctional scaffold with outstanding antimicrobial, hemostatic, and osteogenic performances for avoiding dry sockets in clinical applications. Herein, alginate (AG)/quaternized chitosan (Qch)/diatomite (Di) sponges were fabricated via electrostatic interaction, Ca2+ cross-linking, as well as lyophilization methods. The composite sponges are facilely made into the shape of the tooth root, which could be well integrated into the alveolar fossa. The sponge shows a highly interconnected and hierarchical porous structure at the macro/micro/nano levels. The prepared sponges also possess enhanced hemostatic and antibacterial abilities. Moreover, in vitro cellular assessment indicates that the developed sponges have favorable cytocompatibility and significantly facilitate osteogenesis by upregulating the formation of alkaline phosphatase and calcium nodules. The designed bio-multifunctional sponges display great potential for trauma treatment after tooth extraction. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Astaxanthin-loaded Janus nanofiber patches were prepared via electrospinning. • The saliva-insoluble PCL backing prevented drug loss in the oral cavity. • The patches showed a suitable astaxanthin release rate and permeated into buccal mucosa. • The patches greatly promoted the recovery of oral premalignant lesions. • The patches showed great potential for managing oral premalignant lesions. Oral premalignant lesions (OPL) are one of the most common oral diseases, affecting the quality of life and even leading to oral cancer. Current treatments commonly use steroids/retinoids in mouthwashes, films, or ointments. However, conventional drugs/formulations have significant side effects/limitations. Herein, astaxanthin-loaded polycaprolactone (PCL)/gelatin (GT) nanofiber-based mucoadhesive patches (PGA) with the water‐insoluble PCL nanofiber backing (PCL/PGA) are developed via electrospinning for the management of OPL. The saliva-insoluble PCL backing could greatly prevent drug loss after application in the oral cavity. The prepared PCL/PGA patches exhibit a suitable astaxanthin release rate for achieving high local drug concentration, which permeated into buccal mucosa. In addition, the developed thin patches display excellent wet tissue adhesion and great air permeability due to their high porosity. Notably, the in vivo experiment shows that the bioactive mucoadhesive patches significantly promote the recovery of OPL by suppressing the expression of Ki67 and cyclooxygenase-2 (COX-2), comparable to clinical tretinoin cream formulation. Also, the patches did not induce any side effects (i.e., hair loss and oral ulcers) compared to clinical tretinoin cream formulation. The results demonstrate that this novel electrospun mucoadhesive bilayer patch holds great potential for the treatment of OPL. [ABSTRACT FROM AUTHOR]

Triggering the repair process of diabetic wounds is a huge clinical challenge due to microbial infection, the reduced migration and proliferation of fibroblasts, decreased angiogenesis and collagen formation caused by the long-term negative stimulation of high blood glucose levels. Herein, bio-multifunctional benzaldehyde-terminated 4-arm PEG (4-arm-PEG-CHO)/carboxymethyl chitosan (CMCS)/basic fibroblast growth factor (bFGF) hydrogels (BP/CS-bFGF) are prepared via the dynamic Schiff base reaction for diabetic wound treatment. BP/CS-bFGF hydrogel dressing shows strong wet-tissue adhesion, self-mending, and antibacterial property. Biological assessments display that the BP/CS-bFGF hydrogel has excellent biocompatibility and fast hemostasis capacity. Importantly, BP/CS-bFGF hydrogel dressing significantly accelerates full-thickness diabetic wound repair by increasing the production of Ki67, promotes the generation of epithelialization and collagen, induces the formation of hair follicles, and enhances neovascularization by upregulating the production of CD31 and CD34. Thus, our work demonstrates that BP/CS-bFGF hydrogel dressing displays great potential for diabetic chronic wound management. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • All organic PC 71 BM/g-C 3 N 4 photocatalysts were constructed by in situ self-assembly. • The heterostructures possess satisfactory biocompatibility. • The PC 71 BM served as the electron acceptor and photosensitizer. • · O 2 - acted as the main active species in the degradation process. Photocatalysis has been reported as a potential water purification technology for combating the pathogenic bacteria and degrading the hazardous chemicals. The photoactive organic semiconductors as the emerging class of an alternative to the traditional developed inorganic semiconductors are being widely pursued due to their tunable structures and low toxicity. Herein, the all-organic [6,6] -phenyl C 71 butyric acid methyl ester (PC 71 BM)/g-C 3 N 4 heterostructure have been created by introducing self-assembled n-type fullerene small molecule to the g-C 3 N 4 surface in situ. The absorption edge of the heterostructures with PC 71 BM as the photosensitizer extend from 450 to 650 nm. Moreover, the charge separation and transfer efficiencies of the photocatalysts are greatly promoted even with 1.0% amount of PC 71 BM because of its low reorganization energy and high reduction potential. All of these superiorities endow the heterostructures with over 99.7% antibacterial rates toward E. coli and S. aureus and excellent performance against their biofilms after irradiation for 135 and 180 min, respectively. Additionally, the heterostructures achieve excellent photocatalytic degradation ability for Rhodamine B and tetracycline. Importantly, the in vitro experiments reveal that the as-prepared heterostructures possess satisfactory biocompatibility and their toxicity is negligible. This study provides a new perspective for designing ecofriendly all-organic heterostructures with high photocatalytic activity. [ABSTRACT FROM AUTHOR]

Oral inflammatory diseases (OIDs) are among the most common lesions in the oral cavity, affecting the quality of human life and even causing oral cancer. However, most of the current oral mucosa patches still have some limitations, particularly instant, poor mechanical strength and conformability, low adhesion to tissue, and foreign body sensation. Herein, triamcinolone acetonide (TA)-loaded chitosan/fucoidan (CF) composite hydrogels were prepared via chemical crosslinking. The macro/microscopic morphologies and (bio)physicochemical properties of composite hydrogels were investigated. Incorporating fucoidan in chitosan hydrogels greatly enhanced their swelling behavior, mechanical strength, and adhesion properties. Further, the addition of TA in CF hydrogels improved their elastic feature, inhibited inflammatory response, and promoted the formation of mature and well-organized collagen fibers. The developed composite hydrogels displayed not only good antibacterial properties but also good cytocompatibility and histocompatibility. Thus, the designed hydrogels allow the development of oral mucosa patches as a potential treatment for OIDs. [Display omitted] • Chitosan/fucoidan/triamcinolone acetonide (CFT) hydrogels are developed. • CFT hydrogels possess excellent elastic, flexible, and adhesive properties. • CFT hydrogels have great antibacterial ability. • CFT hydrogels show good cytocompatibility and histocompatibility. • CFT hydrogels display great potential as oral mucosa patches. [ABSTRACT FROM AUTHOR]

[Display omitted] • The preparation of biomaterial-based encapsulated probiotics (BEP) is summarized. • The BEP in diversified biomedical applications are highlighted. • The challenges and perspectives for the BEP are proposed. Probiotics have recently received increasing attention in a range of biomedical applications, such as antimicrobial agents, tissue repair and regeneration, as well as disease treatment. However, the activity and viability of probiotics are significantly affected by complicated tissue/organ environment and thus the probiotics can not stay steady at the target location. Probiotic encapsulation is developed as a biotechnological tool to cope with the technological issues derived from the handling and application of probiotics. Encapsulating living probiotics within appropriate biomaterials is a crucial extension of the functions of probiotics and further development. Biomaterials-based probiotic encapsulation not only protects the vitality of the probiotics but also is a better way to make them delivered to their target location. This review summarizes recent advances of biomaterial-based encapsulated probiotics, including encapsulation methods, encapsulation materials, and encapsulation effects. Further, we highlight biomaterial-based encapsulated probiotics in diversified biomedical applications, including the gastrointestinal tract, oral cavity, vagina, and skin. In the final section, current challenges faced by biomaterial-based encapsulated probiotics are outlined and future perspectives for advancing this research are proposed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hierarchically hybrid CS/nHA-nZnO-PDA coating on Ti implants is successfully developed. • The developed Ti-based implants exhibit enhanced antibacterial efficacy. • The developed Ti-based implants improve cytocompatibility and the osteogenic differentiation of cells. • The designed CS/nHA-nZnO-PTi surfaces display great potential for dental/orthopedic applications. Titanium (Ti) is widely applied as bone-anchoring implants in dental and orthopedic applications owing to its superior mechanical characteristics, high corrosion resistance, and excellent biocompatibility. Nevertheless, Ti-based implants with the deficiencies of insufficient osteoinduction and associated infections can result in implant failure, which significantly limits its applications in some cases. In this work, hierarchically hybrid biocoatings on Ti implants are developed by gradual incorporation of polydopamine (PDA), ZnO nanoparticles (nZnO), and chitosan (CS)/nanocrystal hydroxyapatite (nHA) via oxidative self-polymerization, nanoparticle deposition, solvent casting and evaporation methods for enhancing their antibacterial activity and osteogenesis. The modification of PDA on porous reticular Ti substrates greatly reduces the surface roughness, wettability, protein adsorption, and provides high adhesion to the deposited nZnO. Further, incorporating nZnO on PDA-coated Ti surfaces affects the surface structure and wettability, significantly inhibits the growth of both Staphylococcus aureus and Escherichia coli. Moreover, the CS/nHA-doped coating on the nZnO-modified Ti surfaces remarkably improves cytocompatibility and enhances the osteogenic differentiation of MC3T3-E1 cells by upregulating the protein expression of alkaline phosphatase. This work offers a promising alternative for developing Ti implants with long-lifetime bioactivity to achieve strong antibacterial ability and enhanced bone formation for potential dental/orthopedic applications. [ABSTRACT FROM AUTHOR]

Developing bio-multifunctional wound dressings with excellent hemostasis, antibacterial, anti-inflammatory, enhanced angiogenesis and hair follicle regeneration for promoting full-thickness wound healing is highly valuable in clinical application. Herein, bio-multifunctional composite sponges were prepared by coupling alginate and chitosan with fucoidan through electrostatic interaction, Ca2+ crosslinking, and lyophilization processes. The prepared alginate/chitosan/fucoidan (ACF) sponges display excellent elastic properties, preserving their shape even after bending and compressive strain without failure. The ACF sponge containing 10% fucoidan (ACF-1) shows better hemostatic and antibacterial performances, and significantly promotes wound closure in a rat full-thickness wounds model compared to the alginate/chitosan group and ACF sponge containing 30% fucoidan. Furthermore, the ACF-1 sponge greatly facilitates the epithelialization and the formation of collagen in the dermis, promotes the hair follicle regeneration, enhances vascularization by upregulating the protein expression of CD31, and reduces inflammation by downregulating the protein expression of TNF-α. This work suggests that ACF sponges with a certain amount of fucoidan display great potential for the treatment of full-thickness skin repair. Unlabelled Image • Bio-multifunctional ACF sponges were successfully prepared through a facile, efficient, green cross-linked, and freeze-drying processes. • The ACF sponges possessed excellent hemostatic and antibacterial performances as well as greatly promoted full-thickness wound healing. • The ACF sponges reduced inflammation, facilitated the epithelialization, as well as enhanced angiogenesis and hair follicle regeneration. [ABSTRACT FROM AUTHOR]

The GGGGCC hexanucleotide repeat expansion (HRE) of the C9orf72 gene is the most frequent cause of amyotrophic lateral sclerosis (ALS), a devastative neurodegenerative disease characterized by motor neuron degeneration. C9orf72 HRE is associated with lowered levels of C9orf72 expression and its translation results in the production of dipeptide-repeats (DPRs). To recapitulate C9orf72 -related ALS disease in vivo , we developed a zebrafish model where we expressed glycine-proline (GP) DPR in a c9orf72 knockdown context. We report that C9orf72 gain- and loss-of-function properties act synergistically to induce motor neuron degeneration and paralysis with poly(GP) accumulating preferentially within motor neurons along with Sqstm1/p62 aggregation indicating macroautophagy/autophagy deficits. Poly(GP) levels were shown to accumulate upon c9orf72 downregulation and were comparable to levels assessed in autopsy samples of patients carrying C9orf72 HRE. Chemical boosting of autophagy using rapamycin or apilimod, is able to rescue motor deficits. Proteomics analysis of zebrafish-purified motor neurons unravels mitochondria dysfunction confirmed through a comparative analysis of previously published C9orf72 iPSC-derived motor neurons. Consistently, 3D-reconstructions of motor neuron demonstrate that poly(GP) aggregates colocalize to mitochondria, thus inducing their elongation and swelling and the failure of their processing by mitophagy, with mitophagy activation through urolithin A preventing locomotor deficits. Finally, we report apoptotic-related increased amounts of cleaved Casp3 (caspase 3, apoptosis-related cysteine peptidase) and rescue of motor neuron degeneration by constitutive inhibition of Casp9 or treatment with decylubiquinone. Here we provide evidence of key pathogenic steps in C9ALS-FTD that can be targeted through pharmacological avenues, thus raising new therapeutic perspectives for ALS patients.

Introduction: One of the methods for pain management involves the use of local anesthesia, which numbs sensations in specific body regions while maintaining consciousness., Objectives: Considering the certain limitations (e.g., pain, the requirement of skilled professionals, or slow passive diffusion) of conventional delivery methods of local anesthetics, developing alternative strategies that offer minimally invasive yet therapeutically effective delivery systems is of great concern for ophthalmic regional anesthesia., Methods and Results: In this study, a rapidly dissolving cambered microneedle (MNs) patch, composed of poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) and served as a delivery system for lidocaine (Lido) in local anesthesia, was developed taking inspiration from the mosquito proboscis's ability to extract blood unnoticed. The lidocaine-containing MNs patch (MNs@Lido) consisted of 25 microneedles with a four-pronged cone structure (height: 500 μm, base width: 275 μm), arranged in a concentric circle pattern on the patch, and displays excellent dissolubility for effective drug delivery of Lido. After confirming good cytocompatibility, MNs@Lido was found to possess adequate rigidity to penetrate the cornea without causing any subsequent injury, and the created corneal pinhole channels completely self-healed within 24 h. Interestingly, MNs@Lido exhibited effective analgesic effects for local anesthesia on both heel skin and eyeball, with the sustained anesthetic effect lasting for at least 30 min., Conclusions: These findings indicate that the mosquito proboscis-inspired cambered MNs patch provides rapid and painless local anesthesia, overcoming the limitations of conventional delivery methods of local anesthetics, thus opening up new possibilities in the treatment of ophthalmic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Small extracellular vesicles (sEVs) hold considerable promise for drug delivery due to their natural origin and inherent qualities. However, their clinical application is impeded by two main challenges: low yield and potential side effects. Therefore, it is crucial to obtain substantial quantities of sEVs that adhere to rigorous biosafety standards to ensure successful translation into clinical practice. To address this need, we propose exploring optimized methods for sourcing and separating sEVs, taking inspiration from clinical blood transfusion. In particular, we have identified blood sEVs as a viable alternative and developed a novel separation technique for their isolation. Our approach involves incubating dopamine solution with serum, resulting in the formation of polydopamine (PDA) nanoparticles on the surface of blood sEVs. These nanoparticles have minimal impact on blood sEVs, facilitating their easy separation under standard centrifugal conditions with high purity. This innovative technique enables the development of nanocarriers using blood sEVs with efficient drug-loading capabilities and enhanced pharmacokinetics. Additionally, the incorporation of PDA nanoparticles imparts a photothermal effect to the nanomedicines, enabling the integration of chemotherapy and photothermal therapy. Moreover, the photothermal effect holds the potential to facilitate the membrane fusion of sEVs and cells. In summary, our straightforward surface functionalization technique utilizing PDA effectively isolates blood sEVs and enables chemo-thermal tumor therapy. This approach significantly enhances the feasibility of translating sEV-based nanomedicines into clinical applications.

Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed., Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms., Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis ( E. faecalis ), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo., Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis -associated PEIs., Competing Interests: The authors declare no competing financial interest., (© 2024 Xu et al.)

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments., (© 2024. The Author(s).)

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu 2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu 2+ -induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum , thereby suppressing bacteria growth and biofilm formation in vitro , but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Introduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species., Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools., Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, ε-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction., Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation., Competing Interests: The authors declare no competing financial interest., (© 2024 Bian et al.)

Aggregating poly(glycine-alanine) (poly-GA) is derived from the unconventional translation of the pathogenic intronic hexanucleotide repeat expansion in the C9orf72 gene, which is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly-GA accumulates predominantly in neuronal cytoplasmic inclusions unique to C9orf72 ALS/FTD patients. Poly-GA is, therefore, a promising target for PET/CT imaging of FTD/ALS to monitor disease progression and therapeutic interventions. A novel 64 Cu-labeled anti-GA antibody (mAb1A12) targeting the poly-GA protein was developed and evaluated in a transgenic mouse model. It was obtained with high radiochemical purity (RCP), radiochemical yield (RCY), and specific activity, and showed high stability in vitro and ex vivo and specifically bound to poly-GA. The affinity of NODAGA-mAb1A12 for poly-GA was not affected by this modification. [ 64 Cu]Cu-NODAGA-mAb1A12 was injected into transgenic mice expressing GFP-(GA) 175 in excitatory neurons driven by Camk2a-Cre and in control littermates. PET/CT imaging was performed at 2, 20, and 40 h post-injection (p.i.) and revealed a higher accumulation in the cortex in transgenic mice than in wild-type mice, as reflected by higher standardized uptake value ratios (SUVR) using the cerebellum as the reference region. The organs were isolated for biodistribution and ex vivo autoradiography. Autoradiography revealed a higher cortex-to-cerebellum ratio in the transgenic mice than in the controls. Results from autoradiography were validated by immunohistochemistry and poly-GA immunoassays. Moreover, we confirmed antibody uptake in the CNS in a pharmacokinetic study of the perfused tissues. In summary, [ 64 Cu]Cu-NODAGA-mAb1A12 demonstrated favorable in vitro characteristics and an increased relative binding in poly-GA transgenic mice compared to wild-type mice in vivo . Our results with this first-in-class radiotracer suggested that targeting poly-GA is a promising approach for PET/CT imaging in FTD/ALS., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The application of orthopedic implants for bone tissue reconstruction and functional restoration is crucial for patients with severe bone fractures and defects. However, the abiotic nature of orthopedic implants allows bacterial adhesion and colonization, leading to the formation of bacterial biofilms on the implant surface. This can result in implant failure and severe complications such as osteomyelitis and septic arthritis. The emergence of antibiotic-resistant bacteria and the limited efficacy of drugs against biofilms have increased the risk of orthopedic implant-associated infections (OIAI), necessitating the development of alternative therapeutics. In this regard, antibacterial hydrogels based on bacteria repelling, contact killing, drug delivery, or external assistance strategies have been extensively investigated for coating orthopedic implants through surface modification, offering a promising approach to target biofilm formation and prevent OIAI. This review provides an overview of recent advancements in the application of antibacterial hydrogel coatings for preventing OIAI by targeting biofilm formation. The topics covered include: (1) the mechanisms underlying OIAI occurrence and the role of biofilms in exacerbating OIAI development; (2) current strategies to impart anti-biofilm properties to hydrogel coatings and the mechanisms involved in treating OIAI. This article aims to summarize the progress in antibacterial hydrogel coatings for OIAI prevention, providing valuable insights and facilitating the development of prognostic markers for the design of effective antibacterial orthopedic implants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zheng, Yin, Dai, Fan, Jiang, Liu, Fang, Yi, Zhou and Wang.)

Oral ulcer can be treated with diverse biomaterials loading drugs or cytokines. However, most patients do not benefit from these materials because of poor adhesion, short-time retention in oral cavity and low drug therapeutic efficacy. Here we report a self-stabilized and water-responsive deliverable coenzyme salt polymer poly(sodium α-lipoate) (PolyLA-Na)/coenzyme polymer poly(α-lipoic acid) (PolyLA) binary synergistic elastomer adhesive patch, where hydrogen bonding cross-links between PolyLA and PolyLA-Na prevents PolyLA depolymerization and slow down the dissociation of PolyLA-Na, thus allowing water-responsive sustainable delivery of bioactive LA-based small molecules and durable adhesion to oral mucosal wound due to the adhesive action of PolyLA. In the model of mice and mini-pig oral ulcer, the adhesive patch accelerates the healing of the ulcer by regulating the damaged tissue inflammatory environment, maintaining the stability of oral microbiota, and promoting faster re-epithelialization and angiogenesis. This binary synergistic patch provided a therapeutic strategy to treat oral ulcer., (© 2023. The Author(s).)

Herein, a flexible pressure sensor with high sensitivity was created using a dielectric layer featuring a hierarchical pyramid microstructure, both in simulation and fabrication. The capacitive pressure sensor comprises a hierarchically arranged dielectric layer made of polydimethylsiloxane (PDMS) with pyramid microstructures, positioned between copper electrodes at the top and bottom. The achievement of superior sensing performance is highly contingent upon the thickness of the dielectric layer, as indicated by both empirical findings and finite-element analysis. Specifically, the capacitive pressure sensor, featuring a dielectric layer thickness of 0.5 mm, exhibits a remarkable sensitivity of 0.77 kPa -1 within the pressure range below 1 kPa. It also demonstrates an impressive response time of 55 ms and recovery time of 42 ms, along with a low detection limit of 8 Pa. Furthermore, this sensor showcases exceptional stability and reproducibility with up to 1,000 cycles. Considering its exceptional achievements, the pressure sensor has been effectively utilized for monitoring physiological signals, sign language gestures, and vertical mechanical force exerted on objects. Additionally, a 5 × 5 sensor array was fabricated to accurately and precisely map the shape and position of objects. The pressure sensor with advanced performance shows broad potential in electronic skin applications., Competing Interests: Author XL was employed by Hisense Visual Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Liu, Jiang, Li, Zhang, Zhou, Dhakal, Li, Li and Yao.)

Background: Oral microbial infections are one of the most common diseases. Their progress not only results in the irreversible destruction of teeth and other oral tissues but also closely links to oral cancers and systemic diseases. However, traditional treatment against oral infections by antibiotics is not effective enough due to microbial resistance and drug blocking by oral biofilms, along with the passive dilution of the drug on the infection site in the oral environment., Aim of Review: Besides the traditional antibiotic treatment, carbon dots (CDs) recently became an emerging antimicrobial and microbial imaging agent because of their excellent (bio)physicochemical performance. Their application in treating oral infections has received widespread attention, as witnessed by increasing publication in this field. However, to date, there is no comprehensive review available yet to analyze their effectiveness and mechanism. Herein, as a step toward addressing the present gap, this review aims to discuss the recent advances in CDs against diverse oral pathogens and thus propose novel strategies in the treatment of oral microbial infections., Key Scientific Concepts of Review: In this manuscript, the recent progress of CDs against oral pathogens is summarized for the first time. We highlighted the antimicrobial abilities of CDs in terms of oral planktonic bacteria, intracellular bacteria, oral pathogenic biofilms, and fungi. Next, we introduced their microbial imaging and detection capabilities and proposed the prospects of CDs in early diagnosis of oral infection and pathogen microbiological examination. Lastly, we discussed the perspectives on clinical transformation and the current limitations of CDs in the treatment of oral microbial infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Yin, Mo, Wang, Wang, Li and Zhou.)

Periodontitis is a chronic inflammatory disease induced by a plaque biofilm, which can lead to the destruction of the periodontal support tissue and even teeth loss. The common strategies of periodontitis treatment are to eliminate bacterial/biofilm-related inflammation and subsequently inhibit alveolar bone resorption, for which antibiotic therapy is the most traditional one. However, impenetrable polymeric substances on bacterial biofilms make it difficult for traditional antimicrobial agents to take effect. In this study, a novel nanoparticle protease-loaded CuS NPs was developed, combining the advances of photodynamic and photothermal therapy from CuS and enzymatic degradation of the biofilm by a protease. The photothermal activity and the reactive oxygen generation capacity of the designed nanoparticles were verified by the experimental results, constituting the basis of antibacterial function. Next, the high antimicrobial activity of CuS@A NPs on Fusobacterium nucleatum and its biofilm was demonstrated. The proper hemo/cytocompatibility of CuS-based NPs was demonstrated by in vitro assays. Last, effective treatment against periodontitis was achieved in a rat periodontitis model through the significant efficacy of inhibiting bone resorption and alleviating inflammation. Thus, the developed CuS@A NPs prove a promising material for the management of periodontitis.

Background: Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management., Methods: We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively., Results: Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®)., Conclusions: Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment., (© 2023. The Author(s).)