Polyelectrolyte-Mediated Modulation of Spatial Internal Stresses of Hydrogels for Complex 3D Actuators.

Hydrogel actuators with complex 3D initial shapes show numerous important applications, but it remains challenging to fabricate such actuators. This article describes a polyelectrolyte-based strategy for modulating small-scale internal stresses within hydrogels to construct complex actuators with tailored 3D initial shapes. Introducing polyelectrolytes into precursor solutions significantly enhances the volume shrinkage of hydrogel networks during polymerization, allowing us to modulate internal stresses. Photopolymerization of these polyelectrolyte-containing solutions through a mask produces mechanically strong hydrogel sheets with large patterned internal stresses. Consequently, these hydrogel sheets attain complex 3D initial shapes at equilibrium, in contrast to the planar initial configuration of 2D actuators. We demonstrate that these 3D actuators can reversibly transform into other 3D shapes (i.e., 3D-to-3D shape transformations) in response to external stimuli. Additionally, we develop a predictive model based on the Flory-Rehner theory to analyze the polyelectrolyte-mediated shrinking behaviors of hydrogel networks during polymerization, allowing precise modulation of shrinkage and internal stress. This polyelectrolyte-boosted shrinking mechanism paves a route to the fabrication of high-performance 3D hydrogel actuators.

Engineered Bio-Heterojunction with Infection-Primed H2 S Liberation for Boosted Angiogenesis and Infectious Cutaneous Regeneration.

Photodynamic therapy (PDT) acts as a powerful weapon against infectious diseases for its enormous antimicrobial activity that quickly elicits storms of reactive oxygen species (ROS). Nevertheless, redundant ROS during treatment inevitably bring detriments in revascularization. To address this dilemma, an innovative P-N bio-heterojunction (bio-HJ) material consisting of p-type copper sulfide (p-CuS), n-type bismuth sulfide (n-Bi2 S3 ), and lactate oxidase (LOx) for effective treatment of recalcitrant infectious wounds by promoting angiogenesis is devised. LOx exhausts lactic acid accumulated in infection environment and converts it to hydrogen peroxide (H2 O2 ), which subsequently yields bactericidal hydroxyl radicals (·OH) via Fenton-like reactions. Ultimately, the P-N bio-HJs exert synergistic photothermal, photodynamic, and chemodynamic effects for rapid bacterial annihilation. Moreover, in vitro and RNA-seq analyses reveal that the crafted bio-HJs dramatically expedite the proliferation of L929 cells and promote angiogenesis by up-regulating angiogenic gene expression in hypoxia-inducible factor-1 (HIF-1) signaling pathway, which may ascribe to the evolution of H2 S in response to the infection microenvironment. Critically, results of in vivo experiments have authenticated that the bio-HJs significantly boost healing rates of full-thickness wounds by slaughtering bacteria, elevating angiogenesis, and promoting cytothesis. As envisioned, this work furnishes a novel tactic for the effective treatment of bacteria-invaded wound using H2 S-liberating P-N bio-HJs.

Photo-Activated Nanofibrous Membrane with Self-Rechargeable Antibacterial Function for Stubborn Infected Cutaneous Regeneration.

For quick disinfection treatment, phototherapy, including photothermal therapy and photodynamic therapy, has emerged as a promising alternative to conventional methods. However, the bactericidal effect of phototherapy, which only works upon light, is short-lived. The remaining bacteria in situ may repopulate when the irradiation of light is withdrawn. To address this refractory concern, an antibacterial fibrous membrane consisting of electrospun poly (polycaprolactone) scaffolds and polydopamine (pDA) coated MXene/Ag3 PO4 bioheterojunctions (MX@AgP bio-HJs) is devised and developed. Upon near-infrared (NIR) illumination, the MX@AgP nanoparticle (NP) in nanofibrous electrospun membranes exert the excellent bactericidal effect of phototherapy and release Ag+ ions which stop the remaining bacteria from multiplying in the dark state. When removing NIR light, pDA in situ reduces Ag+ ions to Ag0 NPs to realize the self-rechargeability of Ag+ ions and provides enough Ag+ ions for the second phototherapy. In vivo results show that photoactivated nanofibrous membranes can re-shape an infected wound microenvironment to the regenerative microenvironment through killing bacteria, ceasing bleeding, increasing epithelialization, and collagen deposition on the wound bed, as well as promoting angiogenesis. As predicted, the proposal work offers potential prospects for nanofibrous membranes with NIR-assisted "self-rechargeable" antibacterial properties to treat bacteria-infected full-thickness wounds.

A Dentin Biomimetic Remineralization Material with an Ability to Stabilize Collagen.

The integrity of collagen matrix structure is a prerequisite for effectively inducing biomimetic remineralization. Repeated low pH stimulation activates matrix metalloproteinases (MMPs) in dental caries. Activated MMPs cause the breakdown of collagen fibrils. Collagen stabilization is a major obstacle to the clinical application of remineralization templates. Here, galardin-loaded poly(amido amine) (PAMAM)-NGV (PAMAM-NGV@galardin, PNG) is constructed to induce collagen stabilization and dentin biomimetic remineralization simultaneously, in order to combat early caries in dentin. PAMAM acts in the role of nucleation template for dentin remineralization, while galardin acts as the role of MMPs inhibitor. NGV peptides modified on the surface of dendrimer core can form small clusters with synergistic movement in short range, and those short-range clusters can form domain areas with different properties on the surface of PAMAM core and restrict the movement of collagen, favoring collagen crosslinking, which can be explained through the computational simulation analysis results. NGV peptides and galardin show a dual collagen-protective effect, laying the foundation for the dentin remineralization effect induced by PAMAM. PNG induces dentin remineralization in an environment with collagenase, meanwhile showsing anti-dentin caries efficacy in vivo. These findings indicate that PNG has great potential to combat early dentin caries for future clinical application.

Glabridin arrests cell cycle and inhibits proliferation of hepatocellular carcinoma by suppressing braf/MEK signaling pathway.

Glabridin, an isoflavone isolated from licorice, owns a variety of pharmacological effects. Several reports have demonstrated that glabridin could regulate multiple cellular signaling pathways to inhibit the progression of cancer. However, the target proteins have not been elucidated yet. We used shape screening and induced fit docking to screen the protein data bank against glabridin. Braf and MEK1/2, important intermediate molecules of the braf/MEK cascade, were identified as the potential targets of glabridin. The experimental data showed that glabridin could inhibit the phosphorylation of MEK1/2 and the phosphorylation levels of downstream molecules including ERK1/2 and transcription factors ATF1 and CREB, but had no effect on the phosphorylation of braf. In particular, the in vitro pull-down assay indicated that glabridin selectively bound to braf and MEK1/2. What is more, exposure to glabridin significantly suppressed the proliferation of hepatocellular carcinoma HepG2 cell line. In addition, glabridin might arrest cell cycle in G1 through downregulation of cyclinD3, CDK2, and CDK4. In conclusion, glabridin is a potential multi-molecule-targeting inhibitor in the field of clinical prevention or treatment of cancer.

Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer's disease: a meta-analysis.

We preformed this meta-analysis to investigate the influence of ABCA1 (ATP-binding cassette sub-family A member 1) rs2422493 (C-477T), rs1800977 (C-14T), rs2066718 (V771M), and PTGS2 (Prostaglandin-endoperoxide synthase 2) rs20417 (G-765C) polymorphisms on the risk of Alzheimer's disease (AD). Seventeen eligible case-control studies were acquired from PubMed, Embase, Alzgene, Chinese National Knowledge Infrastructure and Wanfang databases. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association under five genetic models. Combined data indicated that ABCA1 rs2422493 polymorphism was statistically significant associated with increasing AD risk in three genetic models (allelic T vs C: OR = 1.12, 95 % CI: 1.01-1.24; homozygous TT vs CC: OR = 1.26, 95 % CI: 1.03-1.55; and recessive TT vs TC + CC: OR = 1.33, 95 % CI: 1.12-1.58) while no association was found between two other ABCA1 polymorphisms and AD susceptibility. Nevertheless, a further risk-stratification analysis showed that ApoE-ε4 carriers with any ABCA1 polymorphism suffered a much higher probability to be AD patients. Meanwhile, PTGS2 rs20417 polymorphism was linked to decreasing AD risk with a P < 0.0001 in five genetic models (e.g., allelic C vs G: OR = 0.59, 95 % CI: 0.50-0.70; homozygous CC vs GG: OR = 0.31, 95 % CI: 0.18-0.52; and heterozygous CG vs GG: OR = 0.64, 95 % CI: 0.52-0.78). In summary, our meta-analysis results showed that ABCA1 rs2422493 polymorphism was a risk factor for AD while PTGS2 rs20417 variant showed a protective effect on AD risk. In addition, ABCA1 rs2066718 and rs1800977 polymorphisms might not contribute to AD susceptibility in general population, but they should play a role on AD development when interacted with ApoE-ε4.

Dibenzylideneacetone Overcomes Botrytis cinerea Infection in Cherry Tomatoes by Inhibiting Chitinase Activity.

Chitinase, a crucial component of the fungal cell wall and septa, plays an important role in fungal germination by hydrolyzing chitin to provide carbon and energy for fungal growth and reproduction. In this study, we initially screened dibenzylideneacetone (DBA), a small molecule with inhibitory activity against Botrytis cinerea Chitinase, exhibiting an IC50 of 13.10 µg/mL. By constructing a three-dimensional (3D) model of the B. cinerea Chitinase and utilizing computational biology approaches, we found DBA bound to the active site pocket and formed strong π-π interactions and hydrophobic interactions with Chitinase, indicative of its competitive inhibitory mode. Site-directed mutagenesis also revealed that TRP-382, TRP-135, and ALA-215 were key amino acid residues involved in DBA binding. Subsequent antifungal assays showed that DBA had an MIC of 32 µg/mL against B. cinerea and EC50 values of 16.29 and 14.64 µg/mL in inhibiting mycelial growth and spore germination, respectively. Importantly, in vivo experiments demonstrated that DBA treatment significantly extended the shelf life of cherry tomatoes by 2-fold. Therefore, DBA represents a promising antifungal agent for fruit preservation applications.

A simulation study of the decomposition, biotoxicity, and transfer of LCMs in LCD panels after being in contact with sulfuric acid and extraction/stripping agents.

For indium recycling from LCD panels, the decomposition of 9 commonly used liquid crystal monomers (LCMs) that were in contact with sulfuric acid (i.e., leaching agent) and extraction/stripping agents, has been investigated in the present study. Also their biological toxicity changes and transfer have been studied. The results showed that 7 of the 9 LCMs were decomposed in the sulfuric acid agent, while the reaction time and temperature had no effect on the types of the decomposition products. The maximum decomposition rate was 96% when the concentration of the sulfuric acid was increased to 12 M. The time required for a 100% decomposition of the various LCMs in a 5 M sulfuric acid ranged from 41 h to 150 h. Also, Estimation Programs Interface (EPI) and ECOSAR calculations were used to compare the biotoxicity of the LCMs and the decomposition products. The results from the EPI calculations showed that the biological half-lives of the decomposition products were significantly reduced as compared with the LCMs, from the original highest value of 329.2 days-92.71 days. Furthermore, the ECOSAR calculations showed that the biological toxicity of the decomposition products for aquatic organisms was lower than for the LCMs, but they were still toxic and harmful substances. In addition, the transfer rates of the undecomposed LCMs and decomposition products in different extractants remained above 90%, and reached 100% at most. After stripping with hydrochloric acid, more than 70% of the undecomposed LCMs became enriched in the aqueous solution, while the products were enriched in the extractant.

Assessment of radiation exposure and public health before and after the operation of Sanmen nuclear power plant.

Introduction: Sanmen nuclear power plant (SNPP) operates the first advanced passive (AP1000) nuclear power unit in China. Methods: To assess the radiological impacts of SNPP operation on the surrounding environment and the public health, annual effective dose (AED) and excess risk (ER) were estimated based on continuous radioactivity monitoring in drinking water and ambient dose before and after its operation during 2014-2021. In addition, the residents' cancer incidence was further analyzed through authorized health data collection. Results: The results showed that the gross α and gross ß radioactivity in all types of drinking water were ranged from 0.008 to 0.017 Bq/L and 0.032 to 0.112 Bq/L, respectively. The cumulative ambient dose in Sanmen county ranged from 0.254 to 0.460 mSv/y, with an average of 0.354 ± 0.075 mSv/y. There is no statistical difference in drinking water radioactivity and ambient dose before and after the operation of SNPP according to Mann-Whitney U test. The Mann-Kendall test also indicates there is neither increasing nor decreasing trend during the period from 2014 to 2021. The age-dependent annual effective doses due to the ingestion of drinking water or exposure to the outdoor ambient environment are lower than the recommended threshold of 0.1 mSv/y. The incidence of cancer (include leukemia and thyroid cancer) in the population around SNPP is slightly higher than that in other areas, while it is still in a stable state characterized by annual percentage changes. Discussion: The current comprehensive results show that the operation of SNPP has so far no evident radiological impact on the surrounding environment and public health, but continued monitoring is still needed in the future.

Lack of association between MTHFR A1298C variant and Alzheimer's disease: evidence from a systematic review and cumulative meta-analysis.

OBJECTIVES: Previous studies have investigated the association between MTHFR A1298C (rs1801131) polymorphism and susceptibility to Alzheimer's disease (AD). Nevertheless, an ultimate conclusion remains obscure. We then executed this meta-analysis to estimate this association more precisely. METHODS: Related studies were systematically searched on PubMed, Embase, China National Knowledge Infrastructure, Google scholar, and AlzGene databases. The association was evaluated by reviewing the odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Publication bias, sensitivity analysis, and cumulative meta-analysis were performed to help draw a more definite conclusion. RESULTS: Ten eligible studies were finally enrolled in this meta-analysis. Lack of association between MTHFR A1298C polymorphism and AD risk was observed in five genetic models (allelic: OR = 1.17, 95% CI: 0.88-1.56; homozygous: OR = 1.15, 95% CI: 0.87-1.53; heterozygous: OR = 1.19, 95% CI: 0.76-1.86; dominant: OR = 1.23, 95% CI: 0.81-1.87; recessive: OR = 1.16, 95% CI: 0.89-1.52). The result of cumulative meta-analysis sorted by publication year was also detected a dynamic tendency of no correlation between MTHFR A1298C polymorphism and AD. CONCLUSION: This meta-analysis reveals that MTHFR A1298C polymorphism may not be associated with AD risk.

Tumor suppressor BLU promotes TRAIL-induced apoptosis by downregulating NF-κB signaling in nasopharyngeal carcinoma.

A putative tumor suppressor BLU mapped on the chromosomal 3p21 region, is frequently lost in human tumors including nasopharyngeal carcinoma (NPC). To explore the underlying mechanism of tumor suppression by BLU, its potential to promote apoptosis induced by TRAIL, an effector molecule elaborated by natural killer-T (NKT) cells was investigated. BLU was re-expressed in NPC-derived HNE1 cells by recombinant adenoviral infection and the cells were challenged with recombinant TRAIL. The growth inhibition of BLU was assayed and apoptosis was examined by flow cytometry-based tetramethylrhodamine ethyl ester (TMRE) and annexin V staining, cleavage of pro-caspase-8 and poly ADP ribose polymerase (PARP). The modulation of NF-κB pathway by BLU was evaluated by the reporter activity and estimation of the level of the molecules involved such as IKKalpha, p65 NF-κB, as well as NF-κB induced anti-apoptotic factors cFLIPL and cIAP2. The expression of BLU exerted in vitro and in vivo growth inhibitory effect and promoted TRAIL-induced apoptosis. This phenomenon was validated by FACS-based assays of mitochondrial membrane potential (BLU vs. Vector 87.8% ± 7.7% and 72.1%±6.7% at 6h exposure to TRAIL) and phosphatidylserine turnover (BLU vs. vector: 28.7%±2.9% and 22.6%±2.5%), as well as, enhanced caspapse-8 cleavage. Similar with the findings that BLU promotes chemotherapeutic agent-induced apoptosis, it also augmented death receptor-induced pathway through NF-κB pathway inhibition. In conclusion, BLU suppressed tumor formation by strengthening the antitumor immunity.

Genetic association of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection: a meta-analysis.

Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization in infants worldwide. It is recognized by Toll-like receptor 4 (TLR 4) and cluster of differentiation 14 (CD14) in the innate immune response. Previous case-control studies reported the influence of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms on the risk of severe RSV infection. However, a decisive conclusion has not been achieved. Therefore, we performed this meta-analysis to examine the association between these three polymorphisms and the development of RSV bronchiolitis. A systematic literature search was performed using the PubMed, EMbase, Google Scholar Search, China National Knowledge Infrastructure, China Biological Medicine, and Wanfang Databases. The data were extracted and pooled odds ratios with 95% confidence intervals were calculated under six genetic models. A total of six studies with 1009 cases and 1348 controls, three studies with 473 cases and 481 controls, or four studies with 325 cases and 650 controls relating to each of the three polymorphisms were included in this meta-analysis. The analyzed data indicated that all of these polymorphisms were not associated with the risk of severe RSV infection. This is the first meta-analysis to investigate the relationship of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection. Although the results of this retrospective analysis indicated a lack of the association, more extensive multicentric studies with large sample sizes are necessary to provide a more reliable estimation of the association between these three polymorphisms and RSV bronchiolitis susceptibility.

Eriocitrin from lemon suppresses the proliferation of human hepatocellular carcinoma cells through inducing apoptosis and arresting cell cycle.

Hepatocellular carcinoma is a lethal cancer with high recurrence ratio and lacks effective therapeutics. In the past few years, it has been reported that increased intake of vegetables and fruits could reduce the cancer incidence, which suggests dietary agents might possess anticancer effects. Eriocitrin is a flavonoid isolated from lemon, which is known as a strong antioxidant agent. We here for the first time demonstrated that eriocitrin could inhibit the proliferation of hepatocellular carcinoma cell lines by arresting cell cycle in S phase through up-regulation of p53, cyclin A, cyclin D3 and CDK6. Furthermore, we found that eriocitrin could trigger apoptosis by activating mitochondria-involved intrinsic signaling pathway. Thus, eriocitrin might be regarded as a potential chemopreventive natural product to inhibit the early malignant transformation of hepatocellular carcinoma.

Niflumic acid exhibits anti-tumor activity in nasopharyngeal carcinoma cells through affecting the expression of ERK1/2 and the activity of MMP2 and MMP9.

Niflumic acid (NFA) was known to inhibit cell proliferation or migration in several types of cancer. However, the function of NFA in human nasopharyngeal carcinoma (NPC) cells was not clarified. The proliferation of NPC cell line CNE-2Z cells with NFA treatment was detected using the cell counting kit-8 method and transwell assay was employed to assess the effect of NFA on the CNE-2Z cell migration and invasion. The activity of MMP2 and MMP9 was detected by Gelatin Zymography. Cell cycle distribution and apoptosis were detected using flow cytometry. In vitro pull-down assay, western blot, and computational technique were applied to investigate the NFA regulating signaling pathway. Our results indicated that the growth capacity and colony formation potential of CNE-2Z cells in soft agar were significantly suppressed by treatment with NFA. NFA inhibited the proliferation of CNE-2Z cells in a concentration and time-dependent manner. NFA exerted an S phase arrest on the CNE-2Z cells in a concentration-dependent manner, while promoting apoptosis in a dose-dependent manner. Migration and invasion potential of CNE-2Z cells were decreased by NFA treatment in vitro. In vitro pull-down assay and molecular modeling indicated that NFA directly bound with early respond kinase 1 (ERK1). Finally, the anti-tumor effect of NFA was suggested to be mediated by inhibiting early respond kinases (ERK) expression and the MMP2 and MMP9 activities. NFA has proliferation-inhibiting, invasion-suppressing, cell cycle-blocking and apoptosis-promoting effects on CNE-2Z cells through regulation of ERK/MAPK and our results indicates that NFA may serve as a candidate of anticancer drug for NPC.