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1.
Int Immunopharmacol ; 135: 112299, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38776853

ABSTRACT

OBJECTIVE: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches. METHODS: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components. RESULTS: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 µg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 µg/ mL, 10 µg/ mL, and 100 µg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 µg/mL. Network pharmacology results revealed the network relationship between Cd's components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds. CONCLUSION: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.

2.
Sci Total Environ ; 932: 172878, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38697541

ABSTRACT

Excessive phosphorus (P) in eutrophic water induces cyanobacterial blooms that aggravate the burden of in-situ remediation measures. In order to ensure better ecological recovery, Flock & Lock technique has been developed to simultaneously sink cyanobacteria and immobilize P but requires a combination of flocculent and P inactivation agent. Here we synthesized a novel lanthanum-modified pyroaurite (LMP), as an alternative for Flock & Lock of cyanobacteria and phosphorus at the background of rich humic acid and suspended solids. LMP shows a P adsorption capacity of 36.0 mg/g and nearly 100 % removal of chlorophyll-a (Chl-a), turbidity, UV254 and P at a dosage (0.3 g/L) much lower than the commercial analogue (0.5 g/L). The resultant sediment (98.2 % as immobile P) exhibits sound stability without observable release of P or re-growth of cyanobacteria over a 50-day incubation period. The use of LMP also constrains the release of toxic microcystins to 1.4 µg/L from the sunk cyanobacterial cells, outperforming the commonly used polyaluminum chloride (PAC). Similar Flock & Lock efficiency could also be achieved in real eutrophic water. The outstanding Flock & Lock performance of LMP is attributable to the designed La modification. During LMP treatment, La acts as not only a P binder by formation of LaPO4, but also a coagulant to create a synergistic effect with pyroaurite. The controlled hydrolysis of surface La(III) over pyroaurite aided the possible formation of La(III)-pyroaurite networking structure, which significantly enhanced the Flock & Lock process through adsorption, charge neutralization, sweep flocculation and entrapment. In the end, the preliminary economic analysis is performed. The results demonstrate that LMP is a versatile and cost-effective agent for in-situ remediation of eutrophic waters.


Subject(s)
Eutrophication , Lanthanum , Microcystis , Phosphorus , Lanthanum/chemistry , Water Pollutants, Chemical/analysis , Aluminum Hydroxide/chemistry , Adsorption , Environmental Restoration and Remediation/methods
3.
Water Res ; 255: 121484, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38518413

ABSTRACT

Dynamic feedback of the removal performance of trace organic contaminants (TrOCs) is essential towards economical advanced oxidation processes (AOPs), whereas the corresponding quick-response feedback methods have long been desired. Herein, machine learning (ML) multi-target regression random forest (MORF) models were developed based on the fluorescence spectra to predict the removal of TrOCs during UV/H2O2 treatment of municipal secondary effluent as a typical AOP. The predictive performance of the developed MORF model (R2 = 0.83-0.95) exhibited higher accuracy over the traditional linear regression models with R2 increased by ∼0.15. Furthermore, through feature importance analysis, the spectral regions of high importance were identified for different groups of TrOCs, thus enabling faster data acquisition due to remarkably reduced size of required fluorescence spectral scanning region. Specifically, the fluorescence regions Ex(235-275 nm)/Em(325-400 nm) and Ex(240-360 nm)/Em(325-450 nm) were found highly correlated with the removal of the TrOCs susceptible to both photodegradation and •OH degradation and those primarily subject to •OH degradation, respectively. In addition, the spectral regions of high importance were also individually identified for the investigated TrOCs during the AOP. Through providing an efficient ML-based feedback method to monitor TrOC removal during AOP, this study sheds light on the development of dynamic feedback-based strategies for precise and economical advanced treatment of wastewater.

4.
Emerg Microbes Infect ; 13(1): 2321994, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38377136

ABSTRACT

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Cricetinae , Humans , Mice , Rats , Animals , Vaccines, Combined , SARS-CoV-2/genetics , mRNA Vaccines , COVID-19 Vaccines/genetics , COVID-19/prevention & control , Broadly Neutralizing Antibodies , Mice, Inbred BALB C , RNA, Messenger/genetics
5.
J Med Virol ; 96(1): e29382, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235833

ABSTRACT

Japanese encephalitis (JE) caused by JE virus (JEV), remains a global public health concern. Currently, there is no specific antiviral drug approved for the treatment of JE. While vaccines are available for prevention, they may not cover all at-risk populations. This underscores the urgent need for prophylaxis and potent anti-JEV drugs. In this context, a high-content JEV reporter system expressing Nanoluciferase (Nluc) was developed and utilized for a high-throughput screening (HTS) of a commercial antiviral library to identify potential JEV drug candidates. Remarkably, this screening process led to the discovery of five drugs with outstanding antiviral activity. Further mechanism of action analysis revealed that cepharanthine, an old clinically approved drug, directly inhibited virus replication by blocking GTP binding to the JEV RNA-dependent RNA polymerase. Additionally, treatment with cepharanthine in mice models alleviated JEV infection. These findings warrant further investigation into the potential anti-JEV activity of cepharanthine as a new therapeutic approach for the treatment of JEV infection. The HTS method employed here proves to be an accurate and convenient approach that facilitates the rapid development of antiviral drugs.


Subject(s)
Encephalitis Virus, Japanese , Encephalitis, Japanese , Animals , Mice , Encephalitis Virus, Japanese/genetics , Encephalitis, Japanese/drug therapy , High-Throughput Screening Assays , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Virus Replication
6.
RSC Adv ; 14(4): 2673-2677, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38226147

ABSTRACT

A ß-naphthol library has been efficiently constructed utilizing a mild continuous flow procedure, relying on a tandem Friedel-Crafts reaction and starting from readily available arylacetyl chloride and alkynes. Multiple functionalized ß-naphthols can be acquired within 160 s in generally high yields (up to 83%). Using an electron-rich phenylacetyl chloride derivative (4-OH- or 4-MeO-) provides spirofused triene dione as the primary product. A scale-up preparation affords a throughput of 4.70 g h-1, indicating potential large-scale application. Herein, we present a rapid, reliable, and scalable method to obtain various ß-naphthols in the compound library.

7.
Aging (Albany NY) ; 16(2): 1581-1604, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38240702

ABSTRACT

Basement membrane plays an important role in tumor invasion and metastasis, which is closely related to prognosis. However, the prognostic value and biology of basement membrane genes (BMGs) in prostate cancer (PCa) remain unknown. In the TCGA training set, we used differentially expressed gene analysis, protein-protein interaction networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator regression to construct a basement membrane-related risk model (BMRM) and validated its effectiveness in the MSKCC validation set. Furthermore, the accurate nomogram was constructed to improve clinical applicability. Patients with PCa were divided into high-risk and low-risk groups according to the optimal cut-off value of the basement membrane-related risk score (BMRS). It was found that BMRS was significantly associated with RFS, T-stage, Gleason score, and tumor microenvironmental characteristics in PCa patients. Further analysis showed that the model grouping was closely related to tumor immune microenvironment characteristics, immune checkpoint inhibitors, and chemotherapeutic drug sensitivity. In this study, we developed a new BMGs-based prognostic model to determine the prognostic value of BMGs in PCa. Finally, we confirmed that THBS2, a key gene in BMRM, may be an important link in the occurrence and progression of PCa. This study provides a novel perspective to assess the prognosis of PCa patients and provides clues for the selection of future personalized treatment regimens.


Subject(s)
Prostatic Neoplasms , Tumor Microenvironment , Male , Humans , Basement Membrane , Tumor Microenvironment/genetics , Prognosis , Prostatic Neoplasms/genetics , Nomograms
8.
Bioresour Technol ; 395: 130335, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38242237

ABSTRACT

This study presented the effects of hydrochar on humification, heavy metals (HMs) bioavailability and bacterial community succession during composting. Results indicated that hydrochar addition led to elevated composting temperature, 7.3% increase in humic acid (HA), and 52.9% increase in ratio of humic acid to fulvic acid. The diethylene triamine pentacetic acid extractable Zn, Cu, Pb, and Ni were reduced by 19.2%, 36.3%, 37.8%, and 27.1%, respectively, in hydrochar-involved composting system. Furthermore, main mechanisms driving the reduced HMs bioavailability by hydrochar addition were revealed. The addition of hydrochar significantly modified the microbial community structure. Correlation analysis and microbial analysis demonstrated that relative abundance of bacterial groups connected with humification and HMs passivation were increased. Consequently, the HA formation was promoted and the HMs bioavailability were reduced through bacterial bioremediation and HA complexation. This study demonstrates the addition of hydrochar as a promising strategy to mitigate the HMs bioavailability during composting.


Subject(s)
Composting , Metals, Heavy , Microbiota , Humic Substances , Soil/chemistry , Biological Availability , Manure , Metals, Heavy/analysis
9.
Cancer Commun (Lond) ; 44(2): 205-225, 2024 02.
Article in English | MEDLINE | ID: mdl-38155418

ABSTRACT

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.


Subject(s)
Antineoplastic Agents , Extracellular Vesicles , Neoplasms , Humans , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Drug Resistance
10.
Acta Pharmaceutica Sinica ; (12): 532-542, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016612

ABSTRACT

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

11.
NPJ Vaccines ; 8(1): 170, 2023 Nov 04.
Article in English | MEDLINE | ID: mdl-37925490

ABSTRACT

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that poses a severe threat to humans due to its high morbidity and the lack of viable countermeasures. Vaccines are the most crucial defense against NiV infections. Here, a recombinant chimpanzee adenovirus-based vaccine (AdC68-G) and a DNA vaccine (DNA-G) were developed by expressing the codon-optimized full-length glycoprotein (G) of NiV. Strong and sustained neutralizing antibody production, accompanied by an effective T-cell response, was induced in BALB/c mice by intranasal or intramuscular administration of one or two doses of AdC68-G, as well as by priming with DNA-G and boosting with intramuscularly administered AdC68-G. Importantly, the neutralizing antibody titers were maintained for up to 68 weeks in the mice that received intramuscularly administered AdC68-G and the prime DNA-G/boost AdC68-G regimen, without a significant decline. Additionally, Syrian golden hamsters immunized with AdC68-G and DNA-G via homologous or heterologous prime/boost immunization were completely protected against a lethal NiV virus challenge, without any apparent weight loss, clinical signs, or pathological tissue damage. There was a significant reduction in but not a complete absence of the viral load and number of infectious particles in the lungs and spleen tissue following NiV challenge. These findings suggest that the AdC68-G and DNA-G vaccines against NiV infection are promising candidates for further development.

12.
Sci Bull (Beijing) ; 68(24): 3192-3206, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-37993332

ABSTRACT

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants.


Subject(s)
COVID-19 Vaccines , COVID-19 , mRNA Vaccines , Animals , Cricetinae , Mice , COVID-19/prevention & control , COVID-19 Vaccines/immunology , mRNA Vaccines/immunology , SARS-CoV-2/genetics , Primates , Immunogenicity, Vaccine , Broadly Neutralizing Antibodies , Antibodies, Viral
13.
J Nanobiotechnology ; 21(1): 442, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37993888

ABSTRACT

Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.


Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Humans , Photothermal Therapy , Phototherapy/methods , Theranostic Nanomedicine/methods , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Coloring Agents , Photoacoustic Techniques/methods , Cell Line, Tumor
14.
JCI Insight ; 8(23)2023 Dec 08.
Article in English | MEDLINE | ID: mdl-37917215

ABSTRACT

Nipah virus (NiV), a bat-borne paramyxovirus, results in neurological and respiratory diseases with high mortality in humans and animals. Developing vaccines is crucial for fighting these diseases. Previously, only a few studies focused on the fusion (F) protein alone as the immunogen. Numerous NiV strains have been identified, including 2 representative strains from Malaysia (NiV-M) and Bangladesh (NiV-B), which differ significantly from each other. In this study, an F protein sequence with the potential to prevent different NiV strain infections was designed by bioinformatics analysis after an in-depth study of NiV sequences in GenBank. Then, a chimpanzee adenoviral vector vaccine and a DNA vaccine were developed. High levels of immune responses were detected after AdC68-F, pVAX1-F, and a prime-boost strategy (pVAX1-F/AdC68-F) in mice. After high titers of humoral responses were induced, the hamsters were challenged by the lethal NiV-M and NiV-B strains separately. The vaccinated hamsters did not show any clinical signs and survived 21 days after infection with either strain of NiV, and no virus was detected in different tissues. These results indicate that the vaccines provided complete protection against representative strains of NiV infection and have the potential to be developed as a broad-spectrum vaccine for human use.


Subject(s)
Henipavirus Infections , Nipah Virus , Viral Vaccines , Cricetinae , Animals , Humans , Mice , Mesocricetus , Henipavirus Infections/prevention & control
15.
Int J Biol Sci ; 19(15): 4726-4743, 2023.
Article in English | MEDLINE | ID: mdl-37781511

ABSTRACT

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.


Subject(s)
Glycolysis , Prostatic Neoplasms , Male , Humans , Glycine Dehydrogenase (Decarboxylating)/genetics , Glycine Dehydrogenase (Decarboxylating)/metabolism , Glycolysis/genetics , Prostatic Neoplasms/genetics
17.
Cancer Lett ; 579: 216464, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37879429

ABSTRACT

The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.


Subject(s)
Histones , Prostatic Neoplasms , Humans , Male , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation , Histones/genetics , Histones/metabolism , Lysine/metabolism , Methyltransferases/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism
18.
Prog Biophys Mol Biol ; 184: 50-78, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37769974

ABSTRACT

Periodontitis, the sixth most prevalent epidemic disease globally, profoundly impacts oral aesthetics and masticatory functionality. Hypoxia-inducible factor-1α (HIF-1α), an oxygen-dependent transcriptional activator, has emerged as a pivotal regulator in periodontal tissue and alveolar bone metabolism, exerts critical functions in angiogenesis, erythropoiesis, energy metabolism, and cell fate determination. Numerous essential phenotypes regulated by HIF are intricately associated with bone metabolism in periodontal tissues. Extensive investigations have highlighted the central role of HIF and its downstream target genes and pathways in the coupling of angiogenesis and osteogenesis. Within this concise perspective, we comprehensively review the cellular phenotypic alterations and microenvironmental dynamics linking HIF to periodontitis. We analyze current research on the HIF pathway, elucidating its impact on bone repair and regeneration, while unraveling the involved cellular and molecular mechanisms. Furthermore, we briefly discuss the potential application of targeted interventions aimed at HIF in the field of bone tissue regeneration engineering. This review expands our biological understanding of the intricate relationship between the HIF gene and bone angiogenesis in periodontitis and offers valuable insights for the development of innovative therapies to expedite bone repair and regeneration.

19.
Proc Natl Acad Sci U S A ; 120(35): e2305255120, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37603736

ABSTRACT

As a classic strategy to maximize catalytic activity, modulation of the electronic structure of central metal using organic ligands encounters great challenge in radical reactions exemplified by advanced oxidation processes (AOPs) due to operando destruction of employed ligands. Herein, we provide a paradigm achieving in situ ligand-modulated activation of the originally inert Ce(III/IV) for catalytic ozonation as a representative AOP widely applied in full-scale water treatment. Among the small-molecule carboxylates typically produced from pollutant degradation during ozonation, we find oxalate (OA) is a potent ligand to activate Ce(III/IV), inducing 11.5- and 5.8-fold elevation in rate constants of O3 decomposition and atrazine degradation, respectively. The Ce(III)-OA complex is proved the catalytic active species to boost pollutant degradation, while the catalytic ozonation unusually involves both •OH-dependent and •OH-independent pathways with comparable contributions. Both experiment and density functional theory calculation results show the pronounced electron donating effect of OA as evidenced by the substantial decreases in the charge residing on Ce, the ionization potential, and the Ce(III/IV) electrode potential, affords the activation of the Ce center for efficient ozonation. A comprehensive kinetic model involving 67 reactions is established to verify and elaborate the catalytic mechanism. Moreover, with in situ OA production, trace Ce3+ enables autocatalytic mineralization and codegradation of typical contaminants, which are not observed in case of Fe2+ or Cu2+. In addition, Ce3+ outperforms numerous state-of-the-art ozonation catalysts in terms of mass activity. This study sheds light on sustainable activation of the metal center harnessing operando ligands produced from the catalyzed reaction.

20.
Water Res ; 242: 120289, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37413748

ABSTRACT

Industrial wastewater is a substantial source of per- and polyfluoroalkyl substances (PFASs) in the environment. However, very limited information is available on the occurrences and fates of PFASs along industrial wastewater treatment processes, particularly for the textile dyeing industry where PFASs occur extensively. Herein, the occurrences and fates of 27 legacy and emerging PFASs were investigated along the processes of three full-scale textile dyeing wastewater treatment plants (WWTPs) based on UHPLC-MS/MS in combination with self-developed solid extraction protocol featuring selective enrichment for ultrasensitive analysis. The total PFASs ranged at 630-4268 ng L-1 in influents, 436-755 ng L-1 in effluents, and 91.5-1182 µg kg-1 in the resultant sludge. PFAS species distribution varied among WWTPs, with one WWTP dominated by legacy perfluorocarboxylic acids while the other two dominated by emerging PFASs. Perfluorooctane sulfonate (PFOS) was trivial in the effluents from all the three WWTPs, indicating its diminished use in textile industry. Various emerging PFASs were detected at different abundances, demonstrating their use as alternatives to legacy PFASs. Most conventional processes of the WWTPs were inefficient in removing PFASs, especially for the legacy PFASs. The microbial processes could remove the emerging PFASs to different extents, whereas commonly elevated the concentrations of legacy PFASs. Over 90% of most PFASs could be removed by reverse osmosis (RO) and was enriched into the RO concentrate accordingly. The total oxidizable precursors (TOP) assay revealed that the total concentration of PFASs was increased by 2.3-4.1 times after oxidation, accompanied by formation of terminal perfluoroalkyl acids (PFAAs) and degradation of emerging alternatives to various extents. This study is believed to shed new light on the monitoring and management of PFASs in industries.

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