A Green Environmental Protection Photocatalytic Molecular Reactor for Aerobic Oxidation of Sulfide to Sulfoxide.

The design and synthesis of metal-organic frameworks (MOFs) as photocatalytic molecular reactors for varied reactions have drawn great attention. In this work, we designed a novel photoactive perylenediimides-based (PDI) carboxylate ligand N,N'-di(3',3",5',5"-tetrakis(4-carboxyphenyl))-1,2,6,7-tetrachloroperylene-3,4,9,10-tetracarboxylic acid diimide (Cl-PDI-TA) and use it to successfully synthesize a novel Zr(IV)-based MOF 1 constructed from [Zr6 O8 (H2 O)8 ]8+ clusters bridged by Cl-PDI-TA ligands. Structural analysis revealed that Zr-MOF 1 manifests a 3D framework with (4,8)-connected csq topology and possesses triangular channels of ~17 Šand mesoporous hexagonal channels of ~26 Šalong c-axis. Moreover, the synthesized Zr-MOF 1 exhibits visible-light absorption and efficient photoinduced free radical generation property, making it a promising photocatalytic molecular reactor. When Zr-MOF 1 was used as a photocatalyst for the aerobic oxidation of sulfides under irradiation of visible light, it could afford the corresponding sulfoxides with high yield and selectivity. Experimental results demonstrated that the substrate sulfides could be fixed in the pores of 1 and directly transformed to the products sulfoxides in the solid state. Furthermore, the mechanism for the photocatalytic transformation was also investigated and the results revealed that the singlet oxygen (1 O2 ) and superoxide radical (O2 ⋅- ) generated by the energy transfer and electron transfer from the photoexcited Zr-MOF to oxidants were the main active species for the catalytic reactions. This work offers a perceptive comprehension of the mechanism in PDI-based MOFs for further study on photocatalytic reactions.

P2X7 receptor of microglia in olfactory bulb mediates the pathogenesis of olfactory dysfunction in a mouse model of allergic rhinitis.

The pathogenesis of allergic rhinitis (AR)-related olfactory dysfunction (OD) remains unknown. Inhibiting microglial response in olfactory bulb (OB) can ameliorate AR-related OD, but no precise targets have been available. In this study, we established a mouse model of ovalbumin (OVA)-induced AR and combined with the application of P2X7 receptor (P2X7R)-specific antagonists and cell culture in conditioned medium to investigate the role and mechanism of OB microglial P2X7R in AR-related OD. Serum IgE and IL-5 levels determined via ELISA and federated the number of nose-scratching to affirm the success of OVA-induced AR mouse model. Buried food pellet test was used to evaluate the olfactory function of mice. The changes of IBA1, GFAP, P2X7R, IL-1ß, IL-1Ra, and CASPASE 1 were detected by quantitative polymerase chain reaction and western blotting. The levels of adenosine triphosphate (ATP) were determined by the commercialized kit. The morphological changes of microglia were assessed using immunofluorescence staining and Sholl analysis. Findings showed that AR-related OD was associated with OB microglia-mediated imbalance between IL-1ß and IL-1Ra. Treatment with BBG improved the olfactory function in AR mice with restoring the balance between IL-1ß and IL-1Ra. In vitro, the conditioned medium obtained after HNEpC treatment with Der p1 could activate HMC3 to arise inflammatory reaction basing on "ATP-P2X7R-Caspase 1" axis, while inhibition of its P2X7R suppressed the reaction. In brief, microglial P2X7R in OB is a direct effector molecule in AR-related OD and inhibition of it may be a new strategy for the treatment of AR-related OD.

Atomically Dispersed Ni-N4 Sites Assist Pt3 Ni Nanocages with Pt Skin to Synergistically Enhance Oxygen Reduction Activity and Stability.

Currently, the rarity and high cost of platinum (Pt)-based electrocatalysts seriously limit their commercial application in fuel cells cathode. Decorating Pt with atomically dispersed metal-nitrogen sites possibly offers an effective pathway to synergy tailor their catalytic activity and stability. Here active and stable oxygen reduction reaction (ORR) electrocatalysts (Pt3 Ni@Ni-N4 -C) by in situ loading Pt3 Ni nanocages with Pt skin on single-atom nickel-nitrogen (Ni-N4 ) embedded carbon supports are designed and constructed. The Pt3 Ni@Ni-N4 -C exhibits excellent mass activity (MA) of 1.92 A mgPt -1 and specific activity of 2.65 mA cmPt -2 , together with superior durability of 10 mV decay in half-wave potential and only 2.1% loss in MA after 30 000 cycles. Theoretical calculations demonstrate that Ni-N4 sites significant redistribute of electrons and make them transfer from both the adjacent carbon and Pt atoms to the Ni-N4 . The resultant electron accumulation region successfully anchored Pt3 Ni, that not only improves structural stability of the Pt3 Ni, but importantly makes the surface Pt more positive to weaken the adsorption of *OH to enhance ORR activity. This strategy lays the groundwork for the development of super effective and durable Pt-based ORR catalysts.

Brain response in allergic rhinitis: Profile and proposal.

In addition to typical nasal symptoms, patients with allergic rhinitis (AR) will further lead to symptoms related to brain function such as hyposmia, anxiety, depression, cognitive impairment, memory loss, etc., which seriously affect the quality of life of patients and bring a heavy burden to the patient's family and society. Some scholars have speculated that there may be potential "nose-brain communication" mechanism in AR that rely on neuro-immunity. This mechanism plays an important role in AR-associated brain response process. However, no study has directly demonstrated which neural circuits will change in the connection between the nose and brain during the onset of AR, and the mechanism which underlines this question is also lack. Focusing on the topic of "nose-brain communication", this paper systematically summarizes the latest research progress between AR and related brain responses and discusses the mechanism of AR-related neurological phenotypes. Hope new diagnostic and therapeutic targets to ameliorate the brain function-related symptoms and improve the quality of life of AR patients will be developed.

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

IL-1ß and Allergy: Focusing on Its Role in Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic upper airway immune-inflammation response mediated by immunoglobulin E (IgE) to allergens and can seriously affect the quality of life and work efficiency. Previous studies have shown that interleukin-1ß (IL-1ß) acts as a key cytokine to participate in and promote the occurrence and development of allergic diseases. It has been proposed that IL-1ß may be a potential biomarker of AR. However, its definitive role and potential mechanism in AR have not been fully elucidated, and the clinical sample collection and detection methods were inconsistent among different studies, which have limited the use of IL-1ß as a clinical diagnosis and treatment marker for AR. This article systematically summarizes the research advances in the roles of IL-1ß in allergic diseases, focusing on the changes of IL-1ß in AR and the possible interventions. In addition, based on the findings by our team, we provided new insights into the use of IL-1ß in AR diagnosis and treatment, in an attempt to further promote the clinical application of IL-1ß in AR and other allergic diseases.

BMAL1 regulation of microglia-mediated neuroinflammation in MPTP-induced Parkinson's disease mouse model.

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.

Fe(III)EDTA and Fe(II)EDTA-NO reduction by a sulfate reducing bacterium in NO and SO2 scrubbing liquor.

A viable process concept, based on NO and SO2 absorption into an alkaline Fe(II)EDTA (EDTA: ethylenediaminetetraacetic acid) solution in a scrubber combined with biological reduction of the absorbed SO2 utilizing sulfate reducing bacteria (SRB) and regeneration of the scrubbing liquor in a single bioreactor, was developed. The SRB, Desulfovibrio sp. CMX, was used and its sulfate reduction performances in FeEDTA solutions and Fe(II)EDTA-NO had been investigated. In this study, the detailed regeneration process of Fe(II)EDTA solution, which contained Fe(III)EDTA and Fe(II)EDTA-NO reduction processes in presence of D. sp. CMX and sulfate, was evaluated. Fe(III)EDTA and Fe(II)EDTA-NO reduction processes were primarily biological, even if Fe(III)EDTA and Fe(II)EDTA-NO could also be chemically convert to Fe(II)EDTA by biogenic sulfide. Regardless presence or absence of sulfate, more than 87 % Fe(III)EDTA and 98 % Fe(II)EDTA-NO were reduced in 46 h, respectively. Sulfate and Fe(III)EDTA had no affection on Fe(II)EDTA-NO reduction. Sulfate enhanced final Fe(III)EDTA reduction. Effect of Fe(III)EDTA on Fe(II)EDTA-NO reduction rate was more obvious than effect of sulfate on Fe(II)EDTA-NO reduction rate before 8 h. To overcome toxicity of Fe(II)EDTA-NO on SRB, Fe(II)EDTA-NO was reduced first and the reduction of Fe(III)EDTA and sulfate occurred after 2 h. First-order Fe(II)EDTA-NO reduction rate and zero-order Fe(III)EDTA reduction rate were detected respectively before 8 h.

A Quantum Dot Fluorescence Sensor System Design for Hg²âº Trace Detection.

The detection of Hg²âº ions usually requires large laboratory equipment, which encounters difficulties for rapid field test in most applications. In this paper, we design a reflective sensor for trace Hg²âº analysis based on the fluorescent quenching of Quantum dots, which contains two major modules, i. e. the fluorescent sensing module and the signal processing module. The fluorescence sensing module is composed of a laser source, a light collimated system and a photo-detector, which enables the realization of the fluorescence excitation as well as its detection. The signal processing module realized the further amplification of the detected signal and hereafter the filtering of noises. Furthermore, the Hg²âº concentration will displayed on the QT interface using a Linux embedded system. The sensor system is low cost and small, which makes it available for rapid field test or portable applications. Experimental results show that the sensor has a good linear relationship for the Hg²âº concentration range from 15.0 x 10⁻9 to 1.8 x 10⁻6 mol · L⁻¹. The regression equation is V0/V = 1.309 13 + 3.37c, where c is Hg²âº concentration, and V0 is the voltage value for the blank case. In our work, the linearity is determined as 0. 989 26. The experiments exhibit that Ca²âº, Mn²âº and Pb²âº ions have small influence on the Hg²âº detection, and the interfere of other common ions can be neglected, which indicates a good selectivity of the sensor. Finally, it shows that our sensor has a rapid response time of 35 s and a good repeatability, thus it is potential for field test of trace Hg²âº.

Crystalline metal phosphide-coated amorphous iron oxide-hydroxide (FeOOH) with oxygen vacancies as highly active and stable oxygen evolution catalyst in alkaline seawater at high current density.

In this study, we employed a straightforward phosphorylation approach to achieve a dual objective: constructing c-a heterostructures consisting of crystalline Ni12P5 and amorphous FeOOH, while simultaneously enhancing oxygen vacancies. The resulting oxygen evolution reaction (OER) catalyst, Ni12P5/FeOOH/NF, exhibited remarkable performance with current densities of 500 mA cm-2 in both 1 M KOH and 1 M KOH + seawater, requiring low overpotentials of only 288 and 365 mV, respectively. Furthermore, Ni12P5/FeOOH/NF exhibited only a slight increase in overpotential, with increments of 18 mV and 70 mV in 1 M KOH after 15 and 150 h, and 32 mV and 108 mV in 1 M KOH + seawater at 500 mA cm-2 after 15 and 150 h, respectively. This minimal change can be attributed to the stabilized c-a structure, the protective coating of Ni12P5, and superhydrophilic. Through in-situ Raman and ex-situ XPS analysis, we discovered that Ni12P5/FeOOH/NF can undergo a reconfiguration into an oxygen vacancy-rich (Fe/Ni)OOH phase during OER process. The elevated OER activity is mainly due to the contribution of the oxygen vacancy-rich (Fe/Ni)OOH phase from the reconfigure of the Ni12P5/FeOOH/NF. This finding emphasizes the critical role of oxygen vacancies in facilitating the production of OO species and overcoming the limitations associated with OOH formation, ultimately enhancing the kinetics of the OER.

Chitosan thermogelation and cascade mineralization via sequential CaCO3 incorporations for wound care.

Physically crosslinked hydrogels have shown great potential as excellent and eco-friendly matrices for wound management. Herein, we demonstrate the development of a thermosensitive chitosan hydrogel system using CaCO3 as a gelling agent, followed by CaCO3 mineralization to fine-tune its properties. The chitosan hydrogel effectively gelled at 37 °C and above after an incubation period of at least 2 h, facilitated by the CaCO3-mediated slow deprotonation of primary amine groups on chitosan polymers. Through synthesizing and characterizing various chitosan hydrogel compositions, we found that mineralization played a key role in enhancing the hydrogels' mechanical strength, viscosity, and thermal inertia. Moreover, thorough in vitro and in vivo assessments of the chitosan-based hydrogels, whether modified with mineralization or not, demonstrated their outstanding hemostatic activity (reducing coagulation time by >41 %), biocompatibility with minimal inflammation, and biodegradability. Importantly, in vivo evaluations using a rat burn wound model unveiled a clear wound healing promotion property of the chitosan hydrogels, and the mineralized form outperformed its precursor, with a reduction of >7 days in wound closure time. This study presents the first-time utilization of chitosan/CaCO3 as a thermogelation formulation, offering a promising prototype for a new family of thermosensitive hydrogels highly suited for wound care applications.

Development of alginate macroporous hydrogels using sacrificial CaCO3 particles for enhanced hemostasis.

Polymeric hydrogels have increasingly garnered attention in the field of hemostasis. However, there remains a lack of targeted development and evaluation of non-dense polymeric hydrogels with physically incorporated pores to enhance hemostasis. Here, we present a facile route to macroporous alginate hydrogels using acid-induced CaCO3 dissolution to provide Ca2+ for alginate gelation and CO2 bubbles for subsequent macropore formation. The as-prepared pore structure in the hydrogels and its formation mechanisms were characterized through microscopic imaging and nitrogen adsorption/desorption tests. Functional analyses revealed that the macroporous hydrogels exhibited improved rheology, blood absorption, coagulation factor delivery, and platelet aggregation. Ultimately, the introduction of pores significantly enhanced the hemostatic effectiveness of alginate hydrogels in vivo, as demonstrated in rat tail amputation and liver injury models, leading to a reduction in blood loss of up to 77 % or a decrease in bleeding time of up to 88 %. Notably, hydrogels with higher porosity achieved with a CaCO3 to alginate ratio of 40 % outperformed those with lower porosity in the aforementioned properties. Furthermore, these improvements were found to be biocompatible and elicited minimal inflammation. Our findings underscore the potential of a simple porous hydrogel design to enhance hemostasis efficacy by physically incorporating macropores.

Thermo-assisted fabrication of a novel shape-memory hyaluronic acid sponge for non-compressible hemorrhage control.

Hyaluronic acid (HA), a major component of skin extracellular matrix, provides an excellent framework for hemostatic design; however, there still lacks HA materials tailored with superior mechanical properties to address non-compressible hemorrhages. Here, we present a solvent-free thermal approach for constructing a shape-memory HA sponge for this application. Following facile thermal incubation around 130 °C, HA underwent cross-linking via esterification with poly(acrylic acid) within the sponge pre-shaped through a prior freeze-drying process. The resulting sponge system exhibited extensively interconnected macropores with a high fluid absorption capacity, excellent shape-memory property, and robust mechanical elasticity. When introduced to whole blood in vitro, the HA sponges demonstrated remarkable hemostatic properties, yielding a shorter coagulation time and lower blood clotting index compared to the commercial gelatin sponge (GS). Furthermore, in vivo hemostatic studies involving two non-compressible hemorrhage models (rat liver volume defect injury or femoral artery injury) achieved a significant reduction of approximately 64% (or 56%) and 73% (or 70%) in bleeding time and blood loss, respectively, which also outperformed GS. Additionally, comprehensive in vitro and in vivo evaluations suggested the good biocompatibility and biodegradability of HA sponges. This study highlights the substantial potential for utilizing the designed HA sponges in massive bleeding management.

IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets.

The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological function of PDGF-CC and the underlying cellular and molecular mechanisms remain largely unexplored. Here, using different animal models, we report that PDGF-CC inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed both choroidal and retinal neovascularization. Importantly, we revealed that PDGF-CC targeting acted not only on multiple cell types important for pathological angiogenesis, such as vascular mural and endothelial cells, macrophages, choroidal fibroblasts and retinal pigment epithelial cells, but also on the expression of other important angiogenic genes, such as PDGF-BB and PDGF receptors. At a molecular level, we found that PDGF-CC regulated glycogen synthase kinase (GSK)-3beta phosphorylation and expression both in vitro and in vivo. Activation of GSK3beta impaired PDGF-CC-induced angiogenesis, and inhibition of GSK3beta abolished the antiangiogenic effect of PDGF-CC blockade. Thus, we identified PDGF-CC as an important candidate target gene for antiangiogenic therapy, and PDGF-CC inhibition may be of therapeutic value in treating neovascular diseases.

[Quantitative detection of ethyl paraoxon based on SERS and PCA-SLR].

In the present paper, the surface-enhanced Raman spectroscopy (SERS) was used to build the model for the quantitative detection of ethyl paraoxon by the principal component analysis and segmented linear regression (PCA-SLR). Firstly, SERS in 820-1630 cm(-1) of ethyl paraoxon solution were measured and the spectra in 820-1630 cm(-1)(complete range) and 845-875 cm(-1) (characteristic range) of ethyl paraoxon solution were preprocessed by standard normal transformation (SNV), multiplicative scatter correction (MSC), the absolute values of first derivative and the second derivative respectively. Additionally, the number of dimensions of the spectra was reduced by PCA. Finally, the models were established by SLR It was found that the model developed with MSC preprocessed spectroscopy of characteristic range performed best (RMSEP: 0.33) by comparing the predictive accuracy of the different models. The result could meet with the needs in the quantitative detection of ethyl paraoxon.

Trojan-horse mineralization of trigger factor to impregnate non-woven alginate fabrics for enhanced hemostatic efficacy.

Uncontrolled hemorrhage remains a leading cause of mortality after trauma. This work describes a facile mineralization strategy for enhancing hemostatic efficacy of alginate non-woven fabrics, involving the precipitation of amorphous CaCO3 induced by alginate fibers, along with Trojan-horse-like tissue factor (TF) encapsulation. The amorphous CaCO3 served as a transient carrier, capable of releasing Ca2+ and TF upon contact with blood. Coagulation test and rat tail cut and hemorrhaging liver models all revealed superior hemostatic capability of mineralized TF-in-alginate fabrics compared to bare fabrics, solely mineralized form, or commercial zeolite-modified gauze, benefiting from the combined hemostatic properties of alginate matrix and released Ca2+ and TF. Meanwhile, comprehensive biocompatibility and mechanical stability evaluations demonstrate the ternary composite's good biosafety. These results along with the extension study with chitosan- and cellulose-based dressings underline the great potential and versatility of polysaccharide-hemostat-mediated CaCO3 mineralization with TF integration for achieving rapid hemorrhage control.

Injectable thermogelling bioadhesive chitosan-based hydrogels for efficient hemostasis.

Development of an injectable hemostatic for treating noncompressible or irregularly shaped bleeding wounds remains a pressing medical need. Herein, we report an injectable thermogelling chitosan/glycerophosphate formulation that enhances gel-forming capacity and wet tissue adherence by incorporation of dihydrocaffeic acid (DHCA). This was found to decrease gelation time by >2 times around 37 °C while increasing hydrogel internal network structure, with its tissue adhesive strength >2 times greater than that of the non-composite hydrogel or previously reported. The thermosensitive hydrogels significantly reduce whole blood coagulation time in vitro and both hemostasis time and blood loss in vivo using rat hepatic hemorrhage and tail amputation models. These improvements are biocompatible, without adversely affecting cell viability, blood components, biodegradability, or introducing notable inflammation, thus enabling injury healing. Moreover, our results displayed the potential of a facile approach to enhance thermogelling and bioadhesion of chitosan-based hydrogels via noncovalent supramolecular mechanisms.

A peptide-engineered alginate aerogel with synergistic blood-absorbing and platelet-binding capabilities to rapidly stop bleeding.

Polysaccharide matrix infused with hemostasis-stimulating chemistry represents a critical medical need of bleeding management. Herein, we describe the development of a polysaccharide-peptide conjugate platform, an alginate engineered with fibrinogen-derived platelet-binding peptides (APE). The alginate backbone was found to allow for multivalent grafting of the peptides. Processing APE conjugate into crosslinked aerogels promoted platelet accumulation, leading to a significant reduction in the coagulation time of whole rabbit blood and improving the stability of the formed clot. The APE aerogels also exhibited a high porosity and fluid uptake capacity (>90 in weight ratio) as well as good biocompatibility in hemostasis. Furthermore, in vivo studies conducted in rat models of tail cut and hepatic hemorrhage showed that APE aerogels reduced bleeding time by >58 % and blood loss by >61 %. The platelet-enrichment capacity of the APE construct synergized by high absorbency in its aerogel form offers a prototype for customized polysaccharide hemostats.