Dual-Polymer Functionalized Melanin-AgNPs Nanocomposite with Hydroxyapatite Binding Ability to Penetrate and Retain in Biofilm Sequentially Treating Periodontitis.

Periodontitis is the leading cause of adult tooth missing. Thorny bacterial biofilm and high reactive oxygen species (ROS) levels in tissue are key elements for the periodontitis process. It is meaningful to develop an advanced therapeutic system with sequential antibacterial/ antioxidant ability to meet the overall goals of periodontitis therapy. Herein, a dual-polymer functionalized melanin-AgNPs (P/D-MNP-Ag) with biofilm penetration, hydroxyapatite binding, and sequentially treatment ability are fabricated. Polymer enriched with 2-(Dimethylamino)ethyl methacrylate (D), can be protonated in an acid environment with enhanced positive charge, promoting penetration in biofilm. The other polymer is rich in phosphate group (P) and can chelate Ca2+, promoting the polymer to adhere to the hydroxyapatite surface. Melanin has good ROS scavenging and photothermal abilities, after in situ reduction Ag, melanin-AgNPs composite has sequentially transitioned between antibacterial and antioxidative ability due to heat and acid accelerated Ag+ release. The released Ag+ and heat have synergistic antibacterial effects for bacterial killing. With Ag+ consumption, the antioxidant ability of MNP recovers to scavenge ROS in the inflammatory area. When applied in the periodontitis model, P/D-MNP-Ag has good therapeutical effects to ablate biofilm, relieve inflammation state, and reduce alveolar bone loss. P/D-MNP-Ag with sequential treatment ability provides a reference for developing advanced oral biofilm eradication systems.

Comparison of the surgical outcomes of endoscopic dacryocystorhinostomy in chronic dacryocystitis with or without previous bicanalicular silicone tube intubation.

AIMS: To compare the outcomes of endoscopic dacryocystorhinostomy (En-DCR) in chronic dacryocystitis (CD) with or without previous bicanalicular silicone tube intubation (BSTI), and investigate whether previous BSTI influenced postoperative outcomes. METHODS: We conducted a retrospective review of medical records of CD patients (group A) who had previously undergone BSTI for nasolacrimal duct stenosis and an age- and sex-matched control group of CD patients (group B) without previous intubation receiving En-DCR from November 2017 to January 2022. Sixty-one patients (61 eyes) were included in group A and age- and sex-matched 122 patients (122 eyes) in group B. Dacryocystic parameters were measured by computed tomography-dacryocystography and surgical findings were recorded during surgeries. The surgical success rates of the two groups were compared at 12 months post-operation. RESULTS: The mean horizontal, sagittal, and vertical lengths were 6.06 ± 1.24, 6.03 ± 1.44, and 8.05 ± 2.00 mm, respectively, in group A and 6.33 ± 1.25, 6.26 ± 1.19, and 10.40 ± 2.45 mm, respectively, in group B. There were no differences in the horizontal or sagittal parameters between the two groups. The vertical parameter in group A was significantly lower than that in group B. Scar formation in the sac was observed in 54 patients in group A but was absent in group B. At 12 months postoperatively, the anatomical and functional success rates were 88.52 % and 85.25 %, respectively, in group A and 92.62 % and 89.34 %, respectively, in group B, with no difference between the two groups. CONCLUSION: Previous BSTI reduced dacryocyst vertical parameter and caused dacryocyst scar formation but did not affect postoperative En-DCR efficacy.

Implications of Low-concentration Polymer on the Physical Stability of Glassy Griseofulvin: Role of the Segmental Mobility.

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.

Novel Strategy to Rapidly Profile and Identify Oxidized Species of Polysorbate 80 Using Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

Polysorbate 80 (PS80) is widely used as an excipient in vaccines and biopharmaceuticals. The oxidized species of PS80 have raised concern because of their potential to compromise product stability and pose a clinical risk. Analytical methods to profile and identify the oxidized species are hard to develop owing to their complexity and low abundance. Herein, a novel strategy was demonstrated to comprehensively profile and identify the oxidized species of PS80 using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The characteristic fragmentation patterns of the oxidized species were obtained under the "all ions" scan mode. Then, 10 types of distinct fragments from oxidized oleates were identified and confirmed using two purified oxidized species (polyoxyethylene (POE) sorbitan mono-hydroxy oleate and POE mono-keto oleate) whose structures were elucidated via nuclear magnetic resonance. A total of 348 (32 types) oxidized species were profiled and identified in the oxidized PS80 samples, including 119 (10 types) species found for the first time to our knowledge. Mathematical models were established and validated based on the good logarithmic relation between the POE degree of polymerization and the relative retention time and used to rapidly discover and identify the oxidized species. A novel strategy was established to profile and identify the PS80 oxidized species based on their retention time, HRMS, and HRMS2 data of the detected peaks using an in-house dataset. Using this strategy, 104 (14 types) and 97 (13 types) oxidized species were identified for the first time in PS80 and its preparations, respectively.

PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3ß/ß-catenin axis.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. METHODS: To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3ß/ß-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. RESULTS: The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3ß/ß-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. CONCLUSION: PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3ß/ß-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.

Marine biomaterials in biomedical nano/micro-systems.

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications.

Effect of Dialdehyde Carboxymethyl Cellulose Cross-Linking on the Porous Structure of the Collagen Matrix.

Porous structures are essential for some collagen-based biomaterials and can be regulated by crosslinkers. Herein, dialdehyde carboxymethyl cellulose (DCMC) crosslinkers with similar size but different aldehyde group contents were prepared through periodate oxidation of sodium carboxymethyl cellulose with varying degrees of substitution (DS). They can penetrate into the hierarchy of fibril and form inter-molecular and intra-fibril cross-linking within the collagen matrix due to their nanoscale sizes and reactive aldehyde groups. The collagen matrices possessed higher porosity, significantly greater proportion of large pores (Φ > 10 µm), and shorter D-periodicity after cross-linking, showing greater potential for biomedical applications. In addition, the crosslinked collagen matrices showed satisfactory biocompatibility and biodegradation. The decreased DS of carboxymethyl cellulose, which led to the increased aldehyde content of corresponding DCMC, brought about an enhanced cross-linking degree, porosity, and proportion of large pores of the crosslinked collagen matrix. DCMC dosage of 6% was sufficient for cross-linking and pore formation. Excess DCMC would physically deposit in the matrix and decrease the porosity instead. Therefore, the desired pore properties of the collagen matrix could be obtained by regulating the structure of DCMC and thereby achieving the required functions of the biomaterial.

Clinical evaluation of fenestration decompression combined with secondary curettage for ameloblastoma of the jaw: retrospective radiographic analysis.

BACKGROUND: Ameloblastoma is a benign odontogenic epithelial tumor with local infiltration and a high recurrence rate that occurs most frequently in the jawbone. The aim of this study was to investigate the outcomes of fenestration decompression combined with secondary curettage (FDSC) in the surgical treatment of jaw ameloblastoma, and clarify the possibility of FDSC to become an appropriate therapeutic method for ameloblastoma with large lesion. METHODS: A retrospective analysis was carried out in 145 patients diagnosed with multicystic ameloblastoma (MA) and 88 patients with unicystic ameloblastoma (UA). These patients were divided into two groups based on the therapeutic regimen: the FDSC group and the local curettage (LC) group. Panoramic radiography was taken 2 years after curettage to evaluate the change in lesion area in each case, and the therapeutic effects of different treatment methods were further assessed by the chi square test. RESULTS: For MA, the effective rate of cystic cavity area reduction in the FDSC group (71.19%) was higher than that in the LC group (30.23%) (P < 0.001). For UA patients, the effective rate of lesion area reduction after FDSC was 93.02%, which was higher than that after LC (53.33%) (P < 0.001). Moreover, the recurrence rate of the FDSC group in the MA was 30.51%, which was significantly different from that of the LC group (P < 0.001). Regarding UA, the recurrence rates were 13.95% and 28.89%, after FDSC and LC, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSIONS: FDSC exhibits a much better curative effect than LC in both MA and UA, whereas the recurrence rate of these two therapeutic strategies did not significantly differ in UA. The above data demonstrated that FDSC may serve as a routine, safe, effective and appropriate surgical treatment plan for MA or UA patients with large lesions.

ROS Responsive Nanoplatform with Two-Photon AIE Imaging for Atherosclerosis Diagnosis and "Two-Pronged" Therapy.

Atherosclerosis, characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause cardiovascular diseases. Although conventional anti-inflammatory drugs reveal a certain amount of therapeutic effect, more reasonable design on plaque targeting, local anti-inflammation, and lipid removal are still required for comprehensive atherosclerosis therapy. In this work, a theranostic nanoplatform is developed for atherosclerosis recognition and inhibition. A two-photon aggregation-induced emission (AIE) active fluorophore (TP) developed is linked to ß-cyclodextrin (CD) with a ROS responsive bond, which can carry prednisolone (Pred) in its entocoele via supramolecular interaction to build a diagnosis-therapy compound two-photon fluorophore-cyclodextrin/prednisolone complexes (TPCDP). With TPCDP packaged by nanosized micelles based on a ROS sensitive copolymer poly (2-methylthio ethanol methacrylate)-poly (2-methacryloyloxyethyl phosphorylcholine), the TPCDP@PMM can accumulate in atherosclerotic tissue through the damaged vascular endothelium. Activated by the local overexpressed ROS and rich lipid, the micelles are interrupted and TPCDP is further disintegrated with Pred release due to the relatively stronger interaction of lipid with CD, resulting in anti-inflammatory activity and lipid removal for atherosclerosis inhibition. Besides, labeled with the TP, TPCDP@PMM indicates a distinct two-photon AIE imaging on atherosclerosis recognition. The "two-pronged" therapeutic effect and plaque location ability has been confirmed in vivo on ApoE-/- mice, holding TPCDP@PMM a great promise for atherosclerosis theranostics.

A Biodegradable and Stretchable Protein-Based Sensor as Artificial Electronic Skin for Human Motion Detection.

Due to the natural biodegradability and biocompatibility, silk fibroin (SF) is one of the ideal platforms for on-skin and implantable electronic devices. However, the development of SF-based electronics is still at a preliminary stage due to the SF film intrinsic brittleness as well as the solubility in water, which prevent the fabrication of SF-based electronics through traditional techniques. In this article, a flexible and stretchable silver nanofibers (Ag NFs)/SF based electrode is synthesized through water-free procedures, which demonstrates outstanding performance, i.e., low sheet resistance (10.5 Ω sq-1 ), high transmittance (>90%), excellent stability even after bending cycles >2200 times, and good extensibility (>60% stretching). In addition, on the basis of such advanced (Ag NFs)/SF electrode, a flexible and tactile sensor is further fabricated, which can simultaneously detect pressure and strain signals with a large monitoring window (35 Pa-700 kPa). Besides, this sensor is air-permeable and inflammation-free, so that it can be directly laminated onto human skins for long-term health monitoring. Considering the biodegradable and skin-comfortable features, this sensor may become promising to find potential applications in on-skin or implantable health-monitoring devices.

Introduction of heterologous transcription factors and their target genes into Penicillium oxalicum leads to increased lignocellulolytic enzyme production.

Genetic engineering of transcription factors is an efficient strategy to improve lignocellulolytic enzyme production in fungi. In this study, the xylanase transcriptional regulators of Trichoderma reesei (Xyr1) and Neurospora crassa (XLR-1), as well as their constitutively active mutants (Xyr1A824V and XLR-1A828V), were heterologously expressed in Penicillium oxalicum. The two heterologous regulators were identified to be able to activate lignocellulolytic enzyme gene expression in P. oxalicum. Particularly, expression of T. reesei Xyr1 resulted in a higher cellulase production level compared with the expression of native xylanase transcriptional regulator XlnR using the same promoter. Xyr1A824V and XLR-1A828V were found to be able to confer P. oxalicum more enhanced lignocellulolytic abilities than wild-type regulators Xyr1 and XLR-1. Furthermore, introduction of regulatory modules containing Xyr1A824V/XLR-1A828V and their target cellulase genes resulted in greater increases in cellulase production than alone expression of transcriptional regulators. Through the cumulative introduction of three regulatory modules containing regulator mutants and their corresponding target cellulase genes from P. oxalicum, T. reesei, and N. crassa, a 2.8-fold increase in cellulase production was achieved in P. oxalicum.

Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish.

A TIE2 mutation causing arginine-to-tryptophan substitution at residue 849 (TIE2-R849W) is commonly identified in heredofamilial venous malformation. However, there is no in vivo model to confirm the pathogenic role of TIE2-R849W. Humanized TIE2-R849W plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, TIE2-R849W significantly induces multiple malformations in zebrafish: caudal vein plexus (CVP) defect, eye abnormalities, forebrain formation perturbations, and mandibular malformation. Histologically, these phenotypes accompany aphakia, confused retina plexiform layer, abnormal mandibular cartilage, ectopic myelencephalon proliferation and aberrant location of neurogliocytes. According to qRT-PCR, except for high expression of egfl7, the other CVP-related genes cd146, nr2f1a, and s1pr1 are not significantly different from control. TIE2-R849W also induced upregulation of the wnt signaling pathway. Gene array in vitro shows that under the effect of TIE2-R849W, consistent with high expression of pik3 and foxo1, high levels of egfl7, wnt9a, lrp5 and dkk1 were partly confirmed. This in vivo model directly identifies the venous-related pathogenic role of TIE2-R849W. Under up-regulation of TIE2-R849W, egfl7 could be considered a potential reason for venous defects. Moreover, the wnt pathway may perform an important role as a key trigger for head multi-malformations.

Enterovibrio pacificus sp. nov., isolated from seawater, and emended descriptions of Enterovibrio coralii and the genus Enterovibrio.

A Gram-stain-negative, elliptical and facultatively anaerobic strain, designated SW014T, motile by means of a single polar flagellum and positive for poly-ß-hydroxybutyrate accumulation, was isolated from surface seawater of the South Pacific Gyre, during the Integrated Ocean Drilling Program Expedition 329. The strain was able to grow at 10-37 °C (optimum 28 °C). Growth was observed at NaCl concentrations (w/v) of 1-7 % (optimum 3-4 %). The pH range for growth was 7.0-9.0 (optimum pH 8.0). Phylogenetic analysis based on 16S rRNA gene sequences and multilocus sequence analysis indicated that strain SW014T belongs to the genus Enterovibrio within the family Vibrionaceae and is related most closely to Enterovibrio coralii LMG 22228T with 96.3, 83.7, 95.0, 77.1, 84.1 and 85.8 % sequence similarity based on 16S rRNA, recA, rpoA, rpoD, pyrH and ftsZ genes, respectively. The predominant cellular fatty acids were C16 : 1ω7c and/or C16 : 1ω6c, C16 : 0, and C18 : 1ω7c and/or C18 : 1ω6c. The respiratory quinone was ubiquinone-8 (Q-8). The polar lipids of strain SW014T comprised phosphatidylethanolamine, glycolipid, two unidentified aminolipids, two unidentified phospholipids and two unidentified polar lipids. The DNA G+C content was 44.8 mol%. Combining phylogenetic analysis, phenotypic characteristics and chemotaxonomic studies, strain SW014T represents a novel species of the genus Enterovibrio, for which the name Enterovibrio pacificus sp. nov. is proposed. The type strain is SW014T ( = KCTC 42425T = MCCC 1K00500T). Emended descriptions of Enterovibrio coralii and of the genus Enterovibrio are also provided.

Determining the optimal transmembrane gas pressure for nitrification in membrane-aerated biofilm reactors based on oxygen profile analysis.

The goal of this study was to investigate the effect of transmembrane gas pressure (P g) on the specific ammonium removal rate in a membrane-aerated biofilm reactor (MABR). Our experimental results show that the specific ammonium removal rate increased from 4.98 to 9.26 gN m(-2) day(-1) when P g increased from 2 to 20 kPa in an MABR with a biofilm thickness of approximately 600 µm. However, this improvement was not linear; there was a threshold of P g separating the stronger and weaker effects of P g. The ammonium removal rate was improved less significantly when P g was over the threshold, indicating that there is an optimal threshold of P g for maximizing ammonium removal in an MABR. The change in oxygen penetration depth (d p) is less sensitive to P g in the ammonia-oxidizing active layer than in the inactive layer in membrane-aerated biofilm. The location of the P g threshold is at the same point as the thickness of the active layer on the curve of d p versus P g; thus, the active layer thickness and the optimal P g can be determined on the basis of the changes in the slope of d p to P g.

Anti-freezing hydrogel regulated by ice-structuring proteins/cellulose nanofibers system as flexible sensor for winter sports.

Conductive hydrogels are widely used as sensors in wearable devices. However, hydrogels cannot endure harsh low-temperature environments. Herein, a new regulatory system based on natural ice-structuring proteins (ISPs) and cellulose nanofibers (CNFs) is introduced into hydrogel network consisting of chemically crosslinked network of copolymerized acrylamide and 2-acrylamide-2-methylpropanesulfonic acid, and physically crosslinked polyvinyl alcohol chains, affording an anti-freezing hydrogel with high conductivity (2.63 S/m). These hydrogels show excellent adhesion behavior to various matrices (including aluminum, glass, pigskin, and plastic). Their mechanical properties are significantly improved with the increase in CNF content (tensile strength of 106.4 kPa, elastic modulus of 133.8 kPa). In addition, ISPs inhibit the growth of ice. This endows the hydrogels with anti-freezing property and allows them to maintain satisfactory mechanical properties, conductivity and sensing properties below zero degrees. Moreover, this hydrogel shows high sensitivity to tensile and compressive deformation (GF = 5.07 at 600-800 % strain). Therefore, it can be utilized to develop strain-type pressure sensors that can be attached directly to human skin for detecting various body motions accurately, reliably, and stably. This study proposes a simple strategy to improve the anti-freezing property of hydrogels, which provides new insights for developing flexible hydrogel electronic devices for application in winter sports.

Oxygen self-sufficient nanodroplet composed of fluorinated polymer for high-efficiently PDT eradicating oral biofilm.

Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H2O2, while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.

Aqueous-phase dual-functional chiral perovskites for hydrogen sulfide (H2S) detection and antibacterial applications in Escherichia coli.

Perovskite nanocrystals (PNCs) have attracted extensive attention for their potential applications in biology. However, only a handful of PNCs have been scrutinized in the biological domain due to issues such as instability, poor dispersion, and size inhomogeneity in polar solvents. The development of dual-functional perovskite nanomaterials with hydrogen sulfide (H2S) sensing and antibacterial capabilities is particularly intriguing. In this study, we prepared chiral quasi-two-dimensional (quasi-2D) perovskite nanomaterials, Bio(S-PEA)2CsPb2Br7 and Bio(R-PEA)2CsPb2Br7, that were uniformly dispersed in aqueous media. The effective encapsulation of methoxypolyethylene glycol amine (mPEG-NH2) improved water stability and uniformity of particle size. Circular dichroism (CD) signals were created by the successful insertion of chiral cations. These perovskites as probes showed a rapid and sensitive fluorescence quenching response to H2S, and the effect of imaging detection was observed at the Escherichia coli (E. coli) level. As antibacterial agents, their pronounced positive charge properties facilitated membrane lysis and subsequent E. coli death, indicating a significant antibacterial effect. This work has preliminary explored the application of chiral perovskites in biology and provides insight into the development of bifunctional perovskite nanomaterials for biological applications.

Synthetic Cells and Molecules in Cellular Immunotherapy.

Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

Fabrication and properties of multi-functional polydopamine coated Cu/F-codoped hydroxyapatite hollow microspheres as drug carriers.

Due to its excellent bone conductivity and drug adsorption as well as pH-responsive drug release property, hydroxyapatite (HAp) is widely used as a drug carrier in bone repair field. Here, we report for the first time a novel multi-functional polydopamine (PDA) coated Cu/F-codoped HAp (Cu/F-HAp-PDA) hollow microspheres. Both Cu2+ and F- were successfully doped into the lattice of HAp and uniformly distributed in the shell of hollow microspheres through a one-step hydrothermal synthesis. Then PDA was coated homogeneously on the outer layer of Cu/F-HAp hollow microspheres. Both Cu/F-HAp and Cu/F-HAp-PDA samples displayed high drug loading efficiency and pH responsive drug release behavior. Moreover, the obtained Cu/F-HAp-PDA hollow microspheres exhibited excellent photothermal conversion efficiency and photothermal stability. The molecular dynamics simulations showed that PDA and HAp can form mutual binding mainly through Ca-O bonding, while doxorubicin (DOX) is mainly bound to PDA molecules through hydrogen bonding and π-π stacking interaction.

A Rare Strain Actinomadura geliboluensis Was First Isolated from the Bronchoalveolar Lavage Fluid of a Patient with Pneumonia.

Background: Actinomadura geliboluensis was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that Actinomadura geliboluensis has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis. Case Description: The patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. Actinomadura geliboluensis was isolated from the patient's BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that Actinomadura geliboluensis was easy to be mistakenly identified as Actinomyces dental caries by using the Merieux ANC identification card. Based on the MIC test, Actinomadura geliboluensis was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed Actinomadura geliboluensis was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the Actinomadura geliboluensis belongs to Planobispora rosea EF-Tu mutants conferring resistance to inhibitor GE2270A, AAC(3)-VIIa, vanRO, chrB, and mexY. Conclusion: Actinomycetes is generally sensitive to Penicillin but Actinomadura geliboluensis is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.