A novel functionally graded bilayer membrane with excellent barrier function and in vivo osteogenesis promotion for guided bone regeneration.

Introduction: Guided bone regeneration (GBR) technology has been widely used as a reliable method to address alveolar bone defects. To improve the clinical effects of GBR approach, there have been attempts to develop barrier membranes with enhanced regenerative properties. However, modifying the material and structure of GBR membranes to integrate physicochemical properties and biological activity remains challenging. The aim of this study was to develop a novel functionally graded bilayer membrane (FGBM) with a gradient structure and composition, and to evaluate its osteogenesis promotion effect for GBR. Methods: By combining the phase inversion method and electrospinning method, functionally graded bilayer membranes (FGBM) with gradient structure and composition of poly(lactic-co-glycolic acid) (PLGA), nano-hydroxyapatite (nHA), and gelatin were fabricated in this study. The physicochemical and biological properties of the prepared FGBM, including structural and morphological characterization, mechanical properties, in vitro biodegradation, cell behaviors, and in vivo osteogenic bioactivity, were comprehensively evaluated. Results: The findings demonstrated the successful fabrication of PLGA/nHA/gelatin FGBM with an asymmetric structure, exhibiting enhanced hydrophilic, mechanical, and degradation properties. The incorporation of gelatin not only improved the biological integration, but also enhanced the binding affinity between electrospun fiber layer and phase inversion layer. The FGBM with a 30% nHA mass fraction and a PLGA/gelatin mass ratio of 1:1 exhibited excellent barrier function and osteogenic bioactivities in vitro and in vivo. Discussion: This work demonstrated the potential of PLGA/nHA/gelatin FGBM in bone regeneration and provided valuable insight for the development of barrier membrane.

USP18 Is Associated with PD-L1 Antitumor Immunity and Improved Prognosis in Colorectal Cancer.

BACKGROUND: Compared with conventional chemotherapy and targeted therapy, immunotherapy has improved the treatment outlook for a variety of solid tumors, including lung cancer, colorectal cancer (CRC), and melanoma. However, it is effective only in certain patients, necessitating the search for alternative strategies to targeted immunotherapy. The deubiquitinating enzyme USP18 is known to play an important role in various aspects of the immune response, but its role in tumor immunity in CRC remains unclear. METHODS: In this study, multiple online datasets were used to systematically analyze the expression, prognosis, and immunomodulatory role of USP18 in CRC. The effect of USP18 on CRC was assessed via shRNA-mediated knockdown of USP18 expression in combination with CCK-8 and colony formation assays. Finally, molecular docking analysis of USP18/ISG15 and programmed death-ligand 1 (PD-L1) was performed via HDOCK, and an ELISA was used to verify the potential of USP18 to regulate PD-L1. RESULTS: Our study revealed that USP18 expression was significantly elevated in CRC patients and closely related to clinicopathological characteristics. The experimental data indicated that silencing USP18 significantly promoted the proliferation and population-dependent growth of CRC cells. In addition, high USP18 expression was positively correlated with the CRC survival rate and closely associated with tumor-infiltrating CD8+ T cells and natural killer (NK) cells. Interestingly, USP18 was correlated with the expression of various chemokines and immune checkpoint genes. The results of molecular docking simulations suggest that USP18 may act as a novel regulator of PD-L1 and that its deficiency may potentiate the antitumor immune response to PD-L1 blockade immunotherapy in CRC. CONCLUSIONS: In summary, USP18 shows great promise for research and clinical application as a potential target for CRC immunotherapy.

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Effect of co-infection with Newcastle disease virus on Mycoplasma gallisepticum pathogenesis in vivo and in vitro.

The co-infection of Newcastle disease virus (NDV) and Mycoplasma gallisepticum (MG) has a detrimental effect on chicken production performance, exerts a deleterious impact on poultry production performance, resulting in substantial economic losses. However, the exact impact and underlying mechanisms remain ambiguous. In this study, co-infection models were established both in vivo and in vitro. Through these models, it was found that the co-infection facilitated the replication of MG and NDV, as well as MG induced pathogenesis. The administration of lentogenic NDV resulted in the suppression of the innate immune response in vivo. At cellular level, co-infection promoted MG induced apoptosis through caspase-dependent mitochondrial endogenous pathway and suppressed the inflammatory secretion. This research contributes novel insights in co-infection.

The relationship between depression severity and heart rate variability in children and adolescents: A meta-analysis.

OBJECTIVE: Depression in children and adolescents has gradually attracted social attention. Heart rate variability (HRV) has been found to be influenced by depression severity, but results have not been uniformed in children and adolescents. This study investigated the relationship between depression severity and heart rate variability in children and adolescents, aiming to provide additional evidence for an objective, effective, and convenient depression screening tool in this population. METHODS: Literature searching was conducted in China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, ScienceDirect, and EBSCO. Relevant studies investigating the relationship between depression severity and HRV in children and adolescents were selected for meta-analysis. RESULTS: 31 articles were included in this meta-analysis, involving 4534 participants. Depression severity in children and adolescents was significantly negatively correlated with high frequency (HF) and root mean square of successive differences (RMSSD) in HRV (HF: r = -0.10, 95% CI: -0.17 to -0.04, p = 0.001; RMSSD: r = -0.18, 95% CI: -0.30 to -0.05, p = 0.01). The relationship between HF and depression severity was moderated by age, higher among those aged >12 than among those aged <12 (r = -0.17, -0.02, Q = 7.32, p = 0.007). CONCLUSION: Heart rate variability is associated with depression severity in children and adolescents.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

Mineralogical transformation of arsenic at different copper smelting workshops: The impact on arsenic bioaccessibility.

Soil arsenic (As) contamination associated with the demolition of smelting plants has received increasing attention. Soil As can source from different industrial processes, and also participate in soil weathering, making its speciation rather complex. This study combined the usage of chemical sequential extraction and advanced spectroscopic techniques, e.g., time of flight secondary ion mass spectrometry (ToF-SIMS), to investigate the mineralogical transformation of soil As at different processing sites from a typical copper smelting plant in China. Results showed that the stability of arsenic species decreased following the processes of storage, smelting, and flue gas treatment. Arsenic in the warehouse area was incorporated into pyrite (FeS2) as well as its secondary minerals such as jarosite (KFe3(SO4)2(OH)6). At the smelting area, a large proportion of As was adsorbed by iron oxides from smelting slags, while some As existed in stable forms like orpiment (As2S3). At the acid-making area, more than half of As was adsorbed on amorphous iron oxides, and some were adsorbed on the flue gas desulfurization gypsum. More importantly, over 86% of the As belonged to non-specifically and specifically adsorbed fractions was found to be bioaccessible, highlighting the gypsum-adsorbed As one of the most hazardous species in smelting plant soils. Our findings indicated the importance of iron oxides in As retention and suggested the potential health risk of gypsum-adsorbed As. Such detailed knowledge of As speciation and bioaccessibility is vital for the management and remediation of As-contaminated soils in smelting plants.

NDV inhibited IFN-ß secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation.

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-ß) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-ß, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-ß. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-ß production through the activation of IRF3 and NF-κB.

Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes.

Newcastle disease (ND) is a disease that threatens the world's poultry industry, which is caused by virulent Newcastle disease virus (NDV). As its pathogenic mechanism remains not fully clear, the proteomics of NDV-infected cells were analyzed. The results revealed that coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) protein displayed a significant decrease at the late stage of NDV infection. To investigate the function of CHCHD10 in NDV infection, its expression after NDV infection was detected both in vivo and in vitro. Besides, the tissue viral loads and pathological damage of C57BL/6 mice with CHCHD10 differently expressed were also investigated. The results showed that the CHCHD10 expression was significantly decreased both in vivo and in vitro at the late stage of NDV infection. The viral loads were significantly higher in CHCHD10 silenced C57BL/6 mice, along with more severe pathological damage and vice versa.

Protective effects of a novel chimeric virus-like particle vaccine against virulent NDV and IBDV challenge.

Newcastle disease (ND) and infectious bursal disease (IBD) pose significant threats to the chicken industry, causing substantial economic losses. Currently, immunization through vaccination is the most effective strategy to prevent ND and IBD but currently used traditional vaccines, including inactivated or attenuated vaccines, face challenges in achieving a balance between immunogenicity and safety. To develop a green and efficient novel vaccine for ND and IBD, we developed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein based on the ND VLPs carrier platform and insect baculovirus expression system. This study aimed to evaluate the immunogenicity and protective efficacy of ND-IBD cVLPs in specific pathogen-free chickens. Chickens were immunized with 50 µg of purified ND-IBD cVLPs at 7 days old, boosted at 21 days old, and challenged at 42 days old. The results demonstrated that ND-IBD cVLPs stimulated highly effective hemagglutination inhibition antibody levels against NDV HN protein and enzyme-linked immunosorbent assay antibody levels against the IBDV VP2 protein. Furthermore, ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and mitigated pathological damage to the lung caused by NDV infection and the bursa of Fabricius caused by IBDV infection. These findings suggest that ND-IBD cVLPs hold promise as a safe and efficient novel vaccine candidate for the effective prevention of ND and IBD, extending the development of a foreign protein delivery platform of ND VLPs.

Preparation of photothermal responsive, antibacterial hydrogel by using PVA-Alg and silver nanofibers as building blocks.

Introduction: Photothermal responsive, antimicrobial hydrogels are very attractive and have great potential in the field of tissue engineering. The defective wound environment and metabolic abnormalities in diabetic skin would lead to bacterial infections. Therefore, multifunctional composites with antimicrobial properties are urgently needed to improve the current therapeutic outcomes of diabetic wounds. We prepared an injectable hydrogel loaded with silver nanofibers for efficient and sustained bactericidal activity. Methods: To construct this hydrogel with good antimicrobial activity, homogeneous silver nanofibers were first prepared by solvothermal method and then dispersed in PVA-lg solution. After homogeneous mixing and gelation, injectable hydrogels (Ag@H) wrapped with silver nanofibers were obtained. Results: By virtue of Ag nanofibers, Ag@H exhibited good photothermal conversion efficiency and good antibacterial activity against drug-resistant bacteria, while the in vivo antibacterial also showed excellent performance. The results of antibacterial experiments showed that Ag@H had significant bactericidal effects on MRSA and E. coli with 88.4% and 90.3% inhibition rates, respectively. Discussion: The above results indicate that Ag@H with photothermal reactivity and antibacterial activity is very promising for biomedical applications, such as wound healing and tissue engineering.

Characterization of dental dust particles and their pathogenicity to respiratory system: a narrative review.

OBJECTIVES: Dental professionals are exposed to large amounts of dust particles during routine treatment and denture processing. This article provides a narrative review to investigate the most prevalent dust-related respiratory diseases among dental professionals and to discuss the effects of dental dust on human respiratory health. MATERIALS AND METHODS: A literature search was performed in PubMed/Medline, Web of Science, and Embase for articles published between 1990 and 2022. Any articles on the occupational respiratory health effects of dental dust were included. RESULTS: The characterization and toxicity evaluation of dental dust show a correlation between dust exposure and respiratory system injury, and the possible pathogenic mechanism of dust is to cause lung injury and abnormal repair processes. The combination use of personal protective equipment and particle removal devices can effectively reduce the adverse health effects of dust exposure. CONCLUSIONS: Dental dust should be considered an additional occupational hazard in dental practice. However, clinical data and scientific evidence on this topic are still scarce. Further research is required to quantify dust in the dental work environment and clarify its pathogenicity and potential toxicological pathways. Nonetheless, the prevention of dust exposure should become a consensus among dental practitioners. CLINICAL RELEVANCE: This review provides dental practitioners with a comprehensive understanding and preventive advice on respiratory health problems associated with dust exposure.

Quantifying knowledge from the perspective of information structurization.

Scientific literature, as the major medium that carries knowledge between scientists, exhibits explosive growth in the last century. Despite the frequent use of many tangible measures, to quantify the influence of literature from different perspectives, it remains unclear how knowledge is embodied and measured among tremendous scientific productivity, as knowledge underlying scientific literature is abstract and difficult to concretize. In this regard, there has laid a vacancy in the theoretical embodiment of knowledge for their evaluation and excavation. Here, for the first time, we quantify the knowledge from the perspective of information structurization and define a new measure of knowledge quantification index (KQI) that leverages the extent of disorder difference caused by hierarchical structure in the citation network to represent knowledge production in the literature. Built upon 214 million articles, published from 1800 to 2021, KQI is demonstrated for mining influential classics and laureates that are omitted by traditional metrics, thanks to in-depth utilization of structure. Due to the additivity of entropy and the interconnectivity of the network, KQI assembles numerous scientific impact metrics into one and gains interpretability and resistance to manipulation. In addition, KQI explores a new perspective regarding knowledge measurement through entropy and structure, utilizing structure rather than semantics to avoid ambiguity and attain applicability.

Transcriptome-wide N6-methyladenosine modification profiling of mRNAs during infection of Newcastle disease virus in chicken macrophages.

N6-methyladenosine (m6A) modification, the most prevalent post-transcriptional modification of eukaryotic mRNAs, is reported to play a crucial role in viral infection. However, the role of m6A modification during Newcastle disease virus (NDV) infection has remained unclear. In this study, we performed MeRIP-seq to investigate the transcriptome-wide m6A methylome and m6A-modified genes in NDV-infected chicken macrophages. A total of 9496 altered peaks were identified, of which 7015 peaks were significantly upregulated across 3320 genes, and 2481 peaks were significantly down-regulated across 1264 genes. Combined analysis of m6A peaks and mRNA expression showed that 1234 mRNAs had significantly altered levels of methylation and expression after NDV infection, and m6A modification tended to have a negative relationship with mRNA expression, suggesting that m6A modification may regulate the process of NDV infection by regulating gene expression, particularly of the genes important in the innate immune response. To the best of our knowledge, this is the first comprehensive characterization of m6A patterns in chicken macrophage mRNA after NDV infection, providing a valuable basis for further exploring the role of m6A modification mechanisms during the course of NDV infection.

Perfluoroalkyl Mixture Exposure in Relation to Fetal Growth: Potential Roles of Maternal Characteristics and Associations with Birth Outcomes.

Perfluoroalkyl substances (PFASs) exposure is suggested to interfere with fetal growth. However, limited investigations considered the roles of parity and delivery on PFASs distributions and the joint effects of PFASs mixture on birth outcomes. In this study, 506 birth cohorts were investigated in Hangzhou, China with 14 PFASs measured in maternal serum. Mothers with higher maternal ages who underwent cesarean section were associated with elevated PFASs burden, while parity showed a significant but diverse influence. A logarithmic unit increment in perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononane sulfonate (PFNS) was significantly associated with a reduced birth weight of 0.153 kg (95% confidence interval (CI): -0.274, -0.031, p = 0.014), 0.217 kg (95% CI: -0.385, -0.049, p = 0.012), and 0.137 kg (95% CI: -0.270, -0.003, p = 0.044), respectively. Higher perfluoroheptanoic acid (PFHpA) and perfluoroheptane sulphonate (PFHpS) were associated with increased Apgar-1 scores. PFOA (Odds ratio (OR): 2.17, 95% CI: 1.27, 3.71, p = 0.004) and PFNS (OR:1.59, 95% CI: 1.01, 2.50, p = 0.043) were also risk factors to preterm birth. In addition, the quantile-based g-computation showed that PFASs mixture exposure was significantly associated with Apgar-1 (OR: 0.324, 95%CI: 0.068, 0.579, p = 0.013) and preterm birth (OR: 0.356, 95% CI: 0.149, 0.845, p = 0.019). In conclusion, PFASs were widely distributed in the maternal serum, which was influenced by maternal characteristics and significantly associated with several birth outcomes. Further investigation should focus on the placenta transfer and toxicities of PFASs.

Isolation of a Novel Thermophilic Methanogen and the Evolutionary History of the Class Methanobacteria.

Methanogens can produce methane in anaerobic environments via the methanogenesis pathway, and are regarded as one of the most ancient life forms on Earth. They are ubiquitously distributed across distinct ecosystems and are considered to have a thermophilic origin. In this study, we isolated, pure cultured, and completely sequenced a single methanogen strain DL9LZB001, from a hot spring at Tengchong in Southwest China. DL9LZB001 is a thermophilic and hydrogenotrophic methanogen with an optimum growth temperature of 65 °C. It is a putative novel species, which has been named Methanothermobacter tengchongensis-a Class I methanogen belonging to the class Methanobacteria. Comparative genomic and ancestral analyses indicate that the class Methanobacteria originated in a hyperthermal environment and then evolved to adapt to ambient temperatures. This study extends the understanding of methanogens living in geothermal niches, as well as the origin and evolutionary history of these organisms in ecosystems with different temperatures.

Exposure to per- and polyfluoroalkyl substances as a risk factor for gestational diabetes mellitus through interference with glucose homeostasis.

Per- and polyfluoroalkyl substances (PFASs) are hypothesized to trigger gestational diabetes mellitus (GDM) through modulation of glucose metabolism. However, studies investigating links between joint PFASs to GDM are limited and led to discrepant conclusions. This study included 171 women with GDM development in pregnancy and 169 healthy controls from Hangzhou, China between October 2020 and September 2021. By using the solid-phase extraction (SPE)-ultra performance liquid chromatography-tandem-mass-spectrometry (UPLC/MS-MS), 15 PFASs were detected to be widely distributed in maternal serum, with highest median concentrations of 7.43, 4.23, and 3.64 ng/mL for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonates (6:2 Cl-PFESA). Multivariable logistic regressions suggested that the adjusted odds ratios (ORs) with 95% confidence intervals (CI) of GDM for second and highest tertiles of PFOA were 2.57 (1.24, 4.86), p = 0.001 and 1.98 (1.06, 3.65), p = 0.023. Compared with the reference tertile, the ORs of GDM were also significantly increased at the highest tertile of perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoA), PFOS and 6:2Cl-PFESA. Multiple linear regressions further indicated that exposure to these PFASs congeners were positively associated with continuous glycemic outcomes of fasting blood glucose (FBG), 1-h, and 2-h glucose after 75 g oral glucose tolerance (OGTT) test as well as glycohemoglobin (HbA1c). Nevertheless, perfluorohexane sulfonic acid (PFHxS), 4:2 fluorotelomer sulfonates (FTSs), and 3H-perfluoro-3-[(3-methoxy-propoxy) propanoic acid] (ADONA) exhibited protective effects on some of these glycemic outcomes. When assessing the PFASs as mixtures by conducting the Bayesian kernel machine regression (BKMR), the risks of GDM and values of glycemic outcomes increased significantly as the concentrations of the PFASs mixture increased, with PFOA being the largest contributor. We therefore propose that although the effects on glucose homeostasis varied between different PFAS congeners, the elevated combined exposures to PFASs may be associated with substantially increased GDM risks by altering glucose metabolism.

Chrysin Protects Against Titanium Particle-Induced Osteolysis by Attenuating Osteoclast Formation and Function by Inhibiting NF-κB and MAPK Signaling.

Bone homeostasis only exists when the physical function of osteoblast and osteoclast stays in the balance between bone formation and resorption. Bone resorption occurs when the two processes are uncoupled, shifting the balance in favour of bone resorption. Excessive activation of osteoclasts leads to a range of osteolytic bone diseases including osteoporosis, aseptic prosthesis loosening, rheumatoid arthritis, and osteoarthritis. Receptor activator of nuclear factor kappa-B ligand (RANKL) and its downstream signaling pathways are recognized as key mediators that drive the formation and activation of osteoclastic function. Hence, osteoclast formation and/or its function remain as dominant targets for research and development of agents reaching the treatment towards osteolytic diseases. Chrysin (CHR) is a flavonoid with a wide range of anti-inflammatory and anti-tumor effects. However, its effect on osteoclasts remains unknown. In this study, we found the effects of CHR on inhibiting osteoclast differentiation which were assessed in terms of the number and size of TRAcP positive multinucleated osteoclasts (OCs). Further, the inhibitory effects of CHR on bone resorption and osteoclast fusion of pre-OC were assessed by hydroxyapatite resorption pit assay and F-actin belts staining; respectively. Western blotting analysis of RANKL-induced signaling pathways and immunofluorescence analysis for p65 nuclear translocation in response to RANKL-induced osteoclasts were used to analyze the mechanism of action of CHR affecting osteoclasts. Lastly, the murine calvarial osteolysis model revealed that CHR could protect against particle-induced bone destruction in vivo. Collectively, our data strongly suggested that CHR with its promising anti-tumor effects would also be a potential therapeutic agent for osteolytic diseases.

A Novel Hybrid Reactor of Pressure-Retarded Osmosis Coupling with Activated Sludge Process for Simultaneously Treating Concentrated Seawater Brine and Wastewater and Recovering Energy.

As an attractive way to deal with fresh water shortage, membrane-based desalination technologies are receiving increased interest. However, concentrated seawater brine, in needing further treatment, remains a main obstacle for desalination via membrane technology. Here, a hybrid technology integrating pressure-retarded osmosis with activated sludge process (PRO-MBR) was applied for simultaneously treating concentrated seawater brine and municipal wastewater. Performance of the PRO-MBR, including water flux, power density, contaminants removal, and membrane fouling was evaluated and compared at two different membrane orientations (i.e., active layer facing feed solution (AL-FS) mode and active layer facing draw solution (AL-DS) mode). During the PRO-MBR process, the municipal wastewater was completely treated regardless of the membrane orientation, which means that there was no concentrated sewage needing further treatment, owing to the biodegradation of microorganisms in the bioreactor. In the meantime, the concentrated brine of seawater desalination was diluted into the salinity level of seawater, which met the standard of seawater discharge. Owing to the high rejection of forward osmosis (FO) membrane, the removal efficiency of total organic carbon (TOC), total phosphorus (TP), ammonia nitrogen (NH4+-N), and total nitrogen (TN) was higher than 90% at both modes in the PRO-MBR. In addition, the PRO-MBR can simultaneously recover the existing osmotic energy between the municipal wastewater and the seawater brine at both modes. Compared with the AL-DS mode, the AL-FS mode took a shorter time and achieved a bigger power density to reach the same terminal point of the PRO-MBR owing to a better water flux performance. Furthermore, the membrane fouling was much more severe in the AL-DS mode. In conclusion, the current study demonstrated that the PRO-MBR at the AL-FS mode can be a promising and sustainable brine concentrate and municipal wastewater treatment technology for its simultaneous energy and water recovery.

An NIR-Triggered Au Nanocage Used for Photo-Thermo Therapy of Chronic Wound in Diabetic Rats Through Bacterial Membrane Destruction and Skin Cell Mitochondrial Protection.

Bacterial infection and its severe oxidative stress reaction will cause damage to skin cell mitochondria, resulting in long-lasting wound healing and great pain to patients. Thus, delayed wound healing in diabetic patients with Staphylococcus aureus infection is a principal challenge worldwide. Therefore, novel biomaterials with multifunction of bacterial membrane destruction and skin cell mitochondrial protection are urgently needed to be developed to address this challenge. In this work, novel gold cage (AuNCs) modified with epigallocatechin gallate (EGCG) were prepared to treat delayed diabetic wounds. The results showed that Au-EGCG had a high and stable photothermal conversion efficiency under near-infrared irradiation, and the scavenging rate of Au-EGCG for S. aureus could reach 95%. The production of large amounts of reactive oxygen species (ROS) leads to the disruption of bacterial membranes, inducing bacterial lysis and apoptosis. Meanwhile, Au-EGCG fused into hydrogel (Au-EGCG@H) promoted the migration and proliferation of human umbilical cord endothelial cells, reduced cellular mitochondrial damage and oxidative stress in the presence of infection, and significantly increased the basic fibroblast growth factor expression and vascular endothelial growth factor. In addition, animal studies showed that wound closure was 97.2% after 12 days of treatment, and the healing of chronic diabetic wounds was significantly accelerated. Au-EGCG nanoplatforms were successfully prepared to promote cell migration and angiogenesis in diabetic rats while removing S. aureus, reducing oxidative stress in cells, and restoring impaired mitochondrial function. Au-EGCG provides an effective, biocompatible, and multifunctional therapeutic strategy for chronic diabetic wounds.