Cellulose-Based Irreversible Hydrogels Used for CO₂ Sequestration

CO2-switchable hydrogels have been well documented during the past decade; however, the reversible response makes them unable to sequestrate CO2 owing to the gas release and viscosity reduction under high temperatures, weakening their capacity to absorb CO2. To address this issue, a series of copolymers based on grafting poly(dimethylaminopropyl methacrylamide) onto the backbone of sodium carboxymethyl cellulose (NaCMC) were prepared, characterized, and examined rheologically. In the semidilute entangled regime, the copolymer aqueous solutions can be gelled in the presence of CO2, but they cannot revert to the solution phase after bubbling N2 at 60 °C. With such irreversibility, 1 wt % aqueous solution of the copolymer with 24.88 mol % DMAPMAm can absorb CO2 up to 12.1 mg·g–1, whereas only 18.2% of the absorbed CO2 is released after heating at 60 °C. This work paves a new way to develop irreversible hydrogels for CO2 sequestration

The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main protease (SCM) and its inhibitors have been reported, they provide only static snapshots and fail to capture the dynamic nature of SCM/inhibitor interactions. Herein, we conducted molecular dynamics simulations for five SCM complexes: ritonavir (SCM/RTV), lopinavir (SCM/LPV), the identified inhibitor N3 (SCM/N3), the approved inhibitor ensitrelvir (SCM/ESV), and the approved drug nirmatrelvir (SCM/NMV). Additionally, we explored the potential for covalent bond formation in the N3 and NMV inhibitors through QM/MM calculations using Umbrella sampling. The results show that the binding site is highly flexible to fit those five different inhibitors and each compound has its unique binding mode at the same binding site. Moreover, the binding affinities of positive and negative inhibitors to SCM exhibit significant differences. By gaining insights into the dynamics, we can potentially elucidate why lopinavir/ritonavir, initially considered promising, failed to effectively treat COVID-19. Furthermore, understanding the mechanistic aspects of N3 and NMV inhibition on SCM not only contributes to rational drug discovery against COVID-19 but also aids future studies on the catalytic mechanisms of main proteases in other novel coronaviruses. Communicated by Ramaswamy H. Sarma</p

Fabrication of Active Surfaces with Metastable Microgel Layers Formed during Breath Figure Templating

Patterned porous surfaces with responsive functionalities are fabricated by a thermoresponsive microgel-assisted breath figure (BF) process. When water droplets submerge into a polystyrene (PS) solution during formation of a porous surface by the bottom-up BF process, poly­(<i>N</i>-isopropylacrylamide)-<i>co</i>-acrylic acid (PNIPAm-<i>co</i>-AA) microgels dispersed in the solution spontaneously assemble at the water–organic interfaces like “Pickering emulsions”, reinforced by capillary flow. The conformal layer of PNIPAm-<i>co</i>-AA microgels lining the pores appears in images from a scanning electron microscope (SEM) either as a smooth surface layer (L) or as an array of domelike protrusions (D), depending on the conditions at which the sample was dried for SEM. The change between L and D morphology correlates with the volume phase transition behavior of the microgels freely suspended: drying at a temperature below the volume phase transition temperature (VPTT) gives L, and the D morphology is formed by drying at a temperature greater than the VPTT of PNIPAm-<i>co</i>-AA microgels. The morphological transition is shown to accompany a significant change in surface contact angle (CA) relative to a corresponding pore layer made of PS, with L having a CA that is reduced by 85° relative to PS, while the decrease is only 22° for D. Porous structures with morphologically responsive surfaces could find application in biocatalysis or tissue engineering, for example, with functional enzymes sequestered when microgels are collaped and accessible when the microgels are swollen

Additional file 2: of Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection

Figure S2. Ex-vivo adhesion of MSCs suspended in col. I solution. BLIS analysis of MSCs suspended in 10 ng/ml, 500 ng/ml, and 10μg/ml col. I solution on cartilage slices. MSCs pretransfected by luciferase and the total adhered MSC number calculated by luminescent intensity (n = 5 in each group). (JPG 86 kb

Image_1_CD64 plays a key role in diabetic wound healing.tif

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.</p

Additional file 1: of Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection

Figure S1. Concentration of residual collagen I in MSC suspension after PCC. Concentration of col. I detected (n = 5) by Rat Collagen I ELISA Kit (LSBio, USA). (JPG 133 kb

Additional file 3: of Pericellular collagen I coating for enhanced homing and chondrogenic differentiation of mesenchymal stem cells in direct intra-articular injection

Figure S3. In-vivo homing suspended in col. I solution. a, b BLIS analysis of luminescent distribution within left knees of New Zealand rabbits at 2 days after DIAI of luciferase-labeled MSCs or MSCs suspended in 10 ng/ml col. I solution. Red frames indicate cartilage defect (a, n = 3 in each group). Luminescent intensity of total ROI radiance within cartilage defect (red frame) calculated to reveal homing of MSCs (b). a Sagittal frozen sections of cartilage lesion site, red particles are CM-DiI-labeled MSCs (scale bar, 400 μm). (TIF 1614 kb

Image_3_CD64 plays a key role in diabetic wound healing.tif

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.</p

Image_2_CD64 plays a key role in diabetic wound healing.tif

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.</p

DataSheet1_Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study.xlsx

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes.Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates.Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)–mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028–1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094–4.516). Both analyses yielded no consistent evidence of other associations.Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.</p