In-situ treatment of gaseous benzene in fixed-bed biofilter with polyurethane foam: Functional population response and benzene transformation pathway.

Volatile organic compounds emitted from landfills posed adverse effect on health. In this study, gaseous benzene was biologically treated using an in-situ biofilter without an air pump. Its performance was investigated and the removal efficiency of benzene reached over 90 %. The decrease in the average benzene concentration was consistent with first-order reaction kinetics. Mycolicibacterium dominated the bacterial consortium (41-57 %) throughout the degradation. Annotation of genes by metagenomic analysis helps to deduce the degradation pathways (benzene degradation, catechol ortho-cleavage and meta-cleavage) and to reveal the contribution of different species to the degradation process. In total, 21 kinds of key genes and 13 enzymes were involved in the three modules of benzene transformation. Mycolicibacter icosiumassiliensis and Sphingobium sp. SCG-1 carry multiple functional genes critically involved in benzene biodegradation. These findings provide technical and theoretical support for the in-situ bioremediation of benzene-contaminated soil and waste gas reduction in landfills.

A biomechanical analysis of novel endovascular implants for aortic valve replacement and ascending aortic repair.

Advances in medical technology have enabled minimally invasive treatment of type A aortic dissection with accompanying aortic regurgitation. Implants include endovascular stent grafts (ESG) and heart valve substitute (HVS) modules. Traditional implants can be divided into two types based on the assembly relationship between ESG and HVS: separated z-shaped implants (SZ) and separated diamond-shaped implants (SD). This study proposes a novel linked diamond-shaped implant (LD). To evaluate the safety and effectiveness of this new implant, finite element simulation models were created to assess the risks of endoleak, migration, and vascular wall rupture under annulus displacement load. After the SZ, SD, and LD implants were grafted in virtual release method, all the implants can cover tear-entry located in the ascending aorta, but space distance (δ) which exposed to blood was 14.5, 13.1, and 7.4 mm, respectively; the maximum areas of contact gap was 76.5, 51.5 and 6.3 mm2; the maximum migration distance (ΔL1) were 1.27, 1.06, and 0.1 mm; the maximum stress on ascending aorta was 0.19, 0.24, and 0.51 MPa, which were lower than failure stress (0.9 MPa). This study showed that both SZ and SD implants had minimal effects on the ascending aorta; however, higher risks were associated with implant migration and proximal endoleak. In contrast, the LD implant can simplify the surgical procedure, has a lower risk of endoleak and migration, and limited stress stimulation of the aorta. This study validated the feasibility and effectiveness of this novel implant using the finite element method, indicating its potential as a secure and reliable treatment option.

Influence of Zr Microalloying on the Microstructure and Room-/High-Temperature Mechanical Properties of an Al-Cu-Mn-Fe Alloy.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

The CsmiR397a-CsLAC17 module regulates lignin biosynthesis to balance the tenderness and gray blight resistance in young tea shoots.

Lignin accumulation can enhance the disease resistance of young tea shoots (Camellia sinensis). It also greatly reduces their tenderness, which indirectly affects the quality and yield of tea. Therefore, the regulation of lignin biosynthesis appears to be an effective way to balance tenderness and disease resistance in young tea shoots. In this study, we identified a laccase gene, CsLAC17, that is induced during tenderness reduction and gray blight infection in young tea shoots. Overexpression of CsLAC17 significantly increased the lignin content in transgenic Arabidopsis, enhancing their resistance to gray blight and decreasing stem tenderness. In addition, we found that CsLAC17 was negatively regulated by the upstream CsmiR397a by 5'-RLM-RACE, dual-luciferase assay, and transient expression in young tea shoots. Interestingly, the expression of CsmiR397a was inhibited during tenderness reduction and gray blight infection of young tea shoots. Overexpression of CsmiR397a reduced lignin accumulation, resulting in decreased resistance to gray blight and increased stem tenderness in transgenic Arabidopsis. Furthermore, the transient overexpression of CsmiR397a and CsLAC17 in tea leaves directly confirms the function of the CsmiR397a-CsLAC17 module in lignin biosynthesis and its effect on disease resistance. These results suggest that the CsmiR397a-CsLAC17 module is involved in balancing tenderness and gray blight resistance in young tea shoots by regulating lignin biosynthesis.

Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.

Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10+TNF-α- M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.

In Situ Hydrogel Modulates cDC1-Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.

The low expression of miR-155 promotes the expression of SHP2 by inhibiting the activation of the ERK1/2 pathway and improves cell pyroptosis induced by I/R in mice.

This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway.

Allicin treats myocardial infarction in I/R through the promotion of the SHP2 axis to inhibit p-PERK-mediated oxidative stress.

OBJECTIVE: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice. METHODS: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3. RESULTS: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3. CONCLUSIONS: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

Remote photoplethysmography based on reflected light angle estimation.

Objective. In previous studies, the factors affecting the accuracy of imaging photoplethysmography (iPPG) heart rate (HR) measurement have been focused on the light intensity, facial reflection angle, and motion artifacts. However, the factor of specularly reflected light has not been studied in detail. We explored the effect of specularly reflected light on the accuracy of HR estimation and proposed an estimation method for the direction of specularly radiated light.Approach. To study the HR measurement accuracy influenced by specularly reflected light, we control the component of specularly reflected light by controlling its angle. A total of 100 videos from four different reflected light angles were collected, and 25 subjects participated in the dataset collection. We extracted angles and illuminations for 71 facial regions, fitting sample points through interpolation, and selecting the angle corresponding to the maximum weight in the fitted curve as the estimated reflected angle.Main results. The experimental results show that higher specularly reflected light compromises HR estimation accuracy under the same value of light intensity. Notably, at a 60° angle, the HR accuracy (ACC) increased by 0.7%, while the signal-to-noise ratio and Pearson correlation coefficient increased by 0.8 dB and 0.035, respectively, compared to 0°. The overall root mean squared error, standard deviation, and mean error of our proposed reflected light angle estimation method on the illumination multi-angle incidence (IMAI) dataset are 1.173°, 0.978°, and 0.773°. The average Pearson value is 0.8 in the PURE rotation dataset. In addition, the average ACC of HR measurements in the PURE dataset is improved by 1.73% in our method compared to the state-of-the-art traditional methods.Significance. Our method has great potential for clinical applications, especially in bright light environments such as during surgery, to improve accuracy and monitor blood volume changes in blood vessels.

Novel High-Performance Glyoxylate Derivative-Based Photoinitiators for Free Radical Photopolymerization and 3D Printing with Visible LED.

Investigations concerning the glyoxylate moiety as a photocleavable functional group for visible light photoinitiators, particularly in the initiation of free radical photopolymerization remain limited. This study introduces nine innovative carbazole-based ethyl glyoxylate derivatives (CEGs), which are synthesized and found to exhibit excellent photoinitiation abilities as monocomponent photoinitiating systems. Notably, these structures demonstrate robust absorption in the near-UV/visible range, surpassing the commercial photoinitiators. Moreover, the newly developed glyoxylate derivatives show higher acrylate function conversions compared to a benchmark photoinitiator (MBF) in free radical photopolymerization. Elucidation of the photoinitiation mechanism of CEGs is achieved through a comprehensive analysis involving the decarboxylation reaction and electron spin resonance spin trapping. Furthermore, their practical utility is confirmed during direct laser writing and 3D printing processes, enabling the successful fabrication of 3D printed objects. This study introduces pioneering concepts and effective strategies in the molecular design of novel photoinitiators, showcasing their potential for highly advantageous applications in 3D printing.

PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice.

Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

Experimental investigation of freeze injury temperatures in trees and their contributing factors based on electrical impedance spectroscopy.

In trees, injuries resulting from subfreezing temperatures can cause damage to the cellular biofilm system, metabolic functions, and fibrous reticulum, and even cell death. Investigating the occurrence of freezing damage and its contributing factors could help understand the mechanisms underlying freezing injury and prevent the subsequent damage in trees. To achieve this, a laboratory experiment was conducted using cut wood samples from Korean pine (Pinus koraiensis Siebold & Zucc) and Simon poplar (Populus simonii Carr.), and the effects of environmental freezing factors, including freezing temperatures, freezing duration, and cooling rate, on the temperature at which freezing injuries occur were examined using the electrical impedance spectroscopy (EIS) method. The semi-lethal temperature (LT50), as an indicator of freezing injury in wood tissue, was theoretically deduced based on the measured extracellular resistance (r e) using EIS. The contributory factors to changes in LT50 were determined and their relationship was established. The results revealed that all freezing factors exhibited significant effects on electrical impedance characteristics (r e, r i, and τ), significantly influencing the LT50 of the wood. Random forest (RF) and support vector machine (SVM) models were used to assess the contribution of the freezing factors and moisture content (MC). Among the factors examined, freezing duration had the greatest impact on LT50, followed by the MC, whereas the contribution of the cooling rate was minimal. The model accuracies were 0.89 and 0.86 for Korean pine and Simon poplar, respectively. The findings of our study illustrate that the occurrence of freezing injury in trees is primarily influenced by the duration of freezing at specific subzero temperatures. Slow cooling combined with prolonged freezing at low subzero temperatures leads to earlier and more severe freezing damage.

Protocol for reconstituting peptides/peptidomimetics from DMSO to aqueous buffers for circular dichroism analyses.

Circular dichroism (CD) spectrometry is a rapid technique for detecting protein secondary structure, particularly helicity. DMSO is used to ensure optimal solubility of peptides/peptidomimetics; however, its background absorbance hinders effective CD analysis. Here, we present a protocol for reconstituting peptides/peptidomimetics from DMSO to aqueous buffers for CD analyses. We describe steps for identifying chemicals that induce DMSO evaporation, extracting peptides/peptidomimetics from DMSO, and CD spectrometer setup and analysis. We then detail procedures for secondary structure analyses of reconstituted peptides/peptidomimetics. For complete details on the use and execution of this protocol, please refer to Gao et al. (2023).1.

Hydrogen bond unlocking-driven pore structure control for shifting multi-component gas separation function.

Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.

Nano-Regulator Inhibits Tumor Immune Escape via the "Two-Way Regulation" Epigenetic Therapy Strategy.

Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint-dependent suppression limits the immunotherapeutic effect. Herein, a "two-way regulation" epigenetic therapeutic strategy is proposed using a novel nano-regulator that inhibits tumor immune escape by upregulating expression of tumor-associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD-L1) expression to block programmed death-1 (PD-1)/PD-L1. To engineer the nano-regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 are co-loaded into the cationic liposomes with condensing the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine (CpG) via electrostatic interactions to obtain G-J/ZL. Then, asparagine-glycine-arginine (NGR) modified material carboxymethyl-chitosan (CMCS) is coated on the surface of G-J/ZL to construct CG-J/ZL. CG-J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD-L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour-associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano-regulator CG-J/ZL can upregulate TAAs expression to enhance T-cell infiltration and downregulate PD-L1 expression to improve the recognition of tumor cells by T-cells, representing a promising strategy to improve antitumor immune response.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). RESULTS: Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I² = 0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I² = 0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I² = 0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I² = 44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I² = 0%, P = 0.65) exhibited no significant differences between the groups. CONCLUSIONS: DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.