Assessing the effects of air pollution and residential greenness on frailty in older adults: a prospective cohort study from China.

Many studies have established a correlation between air pollution and green space with age-related diseases, yet the relationship between air pollution, green space, and frailty among older adults is not fully understood. The primary objective of this investigation is to examine the longitudinal association among air pollution, green space, and frailty in older adults, as well as the potential interaction and mediating effect. Analyzed data were obtained from the multi-wave CLHLS investigation (2008-2018). The participants' environmental exposure was evaluated using six air pollutants (PM1, PM2.5, PM10, PM10-2.5, O3, and NO2), and normalized difference vegetation index (NDVI). Annual ambient air pollutants were estimated using satellite-based spatiotemporal models. Time-varying Cox proportional risk models were employed to investigate the longitudinal relationships between air pollutants, greenness, and the onset of frailty in the elderly population. We conducted a variety of subgroup analyses, sensitivity analyses, and assessed potential interaction and causal mediating effects. A total of 6953 eligible elderly individuals were enrolled in our study. In the fully adjusted model, per IQR uptick in levels of PM1, PM2.5, PM10, PM10-2.5, O3, and NO2 corresponded to a 17% (95% CI 1.10-1.24), 25% (95% CI 1.17-1.34), 29% (95% CI 1.20-1.39), 35% (95% CI 1.24-1.47), 12% (95% CI 1.04-1.20), and 11% (95% CI 1.05-1.18) increase in frailty risk, respectively. For NDVI, increased IQR was significantly negatively associated with the risk of frailty (aHR 0.82, 95% CI 0.77-0.87). Our results revealed a significant interaction effect among O3, NO2, and residential greenness. PM1, PM2.5, PM10, and PM10-2.5 play a mediating role in the estimated relationship between residential greenness and frailty. In summary, our study reveals that PM1, PM2.5, PM10, PM10-2.5, O3, and NO2 correspond to elevated risks of frailty in the elderly. Residential greenness is associated with a lower risk of frailty in the elderly. Residential greenness can exert a positive impact on frailty by reducing particulate matter concentrations.

In vitro research of oral microscope-assisted implant surface decontamination.

OBJECTIVES: To investigate the effect of oral microscope-assisted surface decontamination on implants in vitro. METHODS: Twelve implants that fell off because of severe peri-implantitis were collected, and decontamination was carried out on the surfaces of implants through curetting, ultrasound, titanium brushing, and sandblasting at 1×, 8×, or 12.8× magnifications. The number and sizes of residues on the implants' surfaces after decontamination were determined, and the decontamination effect was analyzed according to the thread spacing in the different parts of the thread. RESULTS: 1) The 8× and 12.8× groups scored lower for implant surface residues than the 1× group (P<0.000 1), and the 12.8× group scored lower than the 8× group (P<0.001); 2) no difference in residue score was found between the wide and narrow thread pitch (P>0.05), and the 8× and 12.8× groups had lower scores than the 1× group (P<0.001); 3) the lowest number of contaminants was observed at the tip of the thread, whereas the highest was observed below the thread, and the difference was significant (P<0.001). However, the thread pitch had no effect on the number of contaminants in different areas (P>0.05); 4) the residue scores of the 8× and 12.8× groups were lower than those of the 1× group at the thread tip and above, sag, and below the thread of the implants (P<0.05). CONCLUSIONS: Residues on the surfaces of contaminated implants can be effectively removed by using an oral microscope. After decontamination, the residues of pollutants were mainly concentrated below the thread of the implants, and the thread pitch of the implants had no significant effect on the residues.

Association of a mixture of phthalates and phenols with frailty among middle-aged and older adults: A population-based cross-sectional study.

BACKGROUND: Frailty is a complex geriatric syndrome caused by degenerative changes in the body or various chronic diseases. The use of personal care and consumer products is associated with a wide range of health outcomes, but its relationship with frailty remains unknown. Therefore, our primary aim was to explore the potential links between exposure to phenols and phthalates, either separately or in combination, and frailty. METHODS: The exposure levels of phthalates and phenols were evaluated through the measurement of metabolites in urine samples. Frailty state was assessed by a 36-item frailty index with values ≥ 0.25 indicating frailty. Weighted logistic regression was used to explore the relationship between individual chemical exposure and frailty. In addition, multi-pollutant strategies (WQS, Qgcomp, BKMR) were used to examine the joint effect of chemical mixture on frailty. A series of subgroup analyses and sensitivity analyses were conducted as well. RESULTS: In the multivariate logistic regression model, each unit increase in natural log-transformed BPA (OR: 1.21; 95%CI: 1.04, 1.40), MBP (OR: 1.25; 95%CI: 1.07, 1.46), MBzP (OR: 1.18; 95%CI: 1.03, 1.36), and MiBP (OR: 1.19; 95%CI: 1.03, 1.37) were significantly associated with higher odds of frailty. The results of the WQS and Qgcomp indicated that increasing quartiles of chemical mixture was associated with odds of frailty with ORs of 1.29 (95%CI: 1.01, 1.66) and 1.37 (95%CI: 1.06, 1.76). The weight of MBzP is dominant in both the WQS index and the positive weight of Qgcomp. In the BKMR model, the cumulative effect of chemical mixture was positively correlated with the prevalence of frailty. CONCLUSIONS: In summary, higher levels of BPA, MBP, MBzP, and MiBP are significantly associated with higher odds of frailty. Our study provides preliminary evidence that phenol and phthalate biomarker mixture is positively associated with frailty, with MBzP contributing most to the positive association.

Associations of perchlorate, nitrate, and thiocyanate with metabolic syndrome and its components among US adults: A cross-sectional study from NHANES.

Perchlorate, nitrate and thiocyanate are common endocrine disruptors. Herein, this study was undertaken to evaluate the associations between perchlorate, nitrate, and thiocyanate exposures (alone or in combination) and risk of metabolic syndrome (MetS) among adults, which has not been explored so far. Analytical data were extracted from different datasets in the National Health and Nutrition Examination Survey (NHANES) database. Multivariate logistic regression models were constructed to investigate the associations between perchlorate, nitrate, and thiocyanate exposures, and the prevalence of MetS. Subsequently, odds ratios (OR) and their corresponding 95 % confidence intervals (CIs) were adopted to represent the magnitude of the effect size. We performed a series of subgroup analyses and sensitivity analyses as well. Moreover, three commonly used mixture modeling strategies [Weighted quantile sum (WQS) regression, quantile-based g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR)] were utilized to evaluate the joint mixture effect on MetS. This study included 12,007 participants in the subsequent analyses. After adjustment for confounding factors, higher levels of perchlorate, and thiocyanate concentrations were significantly associated with the risk of MetS (OR = 1.15, 95%CI:1.00, 1.32; OR = 1.21, 95%CI:1.04, 1.41, respectively). Analyses of WQS and Qgcomp showed that a quartile increase in chemical mixture was correlated with the occurrence of MetS with ORs of 1.07 (95%CI: 0.99, 1.16) and 1.07 (95%CI: 1.00, 1.14), respectively. This positive association was mainly driven by perchlorate and thiocyanate. Analysis of BKMR revealed that perchlorate, nitrate, and thiocyanate mixture was positively associated with the risk of MetS while perchlorate, and thiocyanate were major predictors in the mixture. In summary, our study reveals positive relationships between perchlorate, thiocyanate and MetS. Co-exposure to perchlorate, nitrate and thiocyanate is positively associated with the risk of MetS, with perchlorate and thiocyanate contributing the most to the overall mixture effect.

Association between screen time and developmental and behavioral problems among children in the United States: evidence from 2018 to 2020 NSCH.

Excessive digital media use has become the common phenomenon among children's lifestyle, and its influences on the plausible accompanying psychological and behavioral problems are gradually investigated. This study aimed to examine the association between screen time and developmental and behavioral problems of children in the United States (US). A secondary analysis based on the data from the 2018 to 2020 National Survey of Children's Health (NSCH) was conducted. Seven types of developmental and behavioral problems and screen time on weekdays of children were collected through parents/caregivers' recall. Logistic regression models were constructed to determine the associations. Overall, 101,350 children aged between 0 and 17 years old were included in this study and 70.3% of preschoolers aged 0-5 years old and 80.2% of children and adolescents aged 6-17 years old had excessive screen time. Excessive screen time was positively associated with behavioral and conduct problem, developmental delay, speech disorder, learning disability, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD) and there were significant dose-response relationships. The association between excessive screen time and developmental and behavioral problems was stronger among preschoolers than among children and adolescents. Boys with excessive screen time showed high odds of most types of developmental and behavioral problems. It can be concluded that children with excessive screen time are at high odds of developmental and behavioral problems, especially for preschoolers and boys. Early intervention of digital media use is urgent and essential for children in the US.

Hexokinase 2-mediated glycolysis supports inflammatory responses to Porphyromonas gingivalis in gingival fibroblasts.

BACKGROUND: When infected with Porphyromonas gingivalis, gingival fibroblasts undergo metabolic reprogramming, and rely on aerobic glycolysis rather than oxidative phosphorylation for rapid energy replenishment. Hexokinases (HKs) are catalysts for glucose metabolism, and HK2 constitutes the major HK inducible isoform. The objective of this study is to determine whether HK2-mediated glycolysis promotes inflammatory responses in inflamed gingiva. METHODS: Levels of glycolysis-related genes were assessed in normal and inflamed gingiva. Human gingival fibroblasts were harvested and infected with Porphyromonas gingivalis in order to mimic periodontal inflammation. 2-deoxy-d-glucose, an analogue of glucose, was used to block HK2-mediated glycolysis, while small interfering RNA was used to knock down HK2 expression. The mRNA and protein levels of genes were analyzed by real-time quantitative PCR and western blotting, respectively. HK2 activity and lactate production were assessed by ELISA. Cell proliferation was assessed by confocal microscopy. The generation of reactive oxygen species was assessed by flow cytometry. RESULTS: Elevated expression of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was observed in the inflamed gingiva. P. gingivalis infection was shown to promote glycolysis in human gingival fibroblasts, as evidenced by increased gene transcription of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, cell glucose consumption, and HK2 activity. Inhibition and knockdown of HK2 resulted in reduced cytokine production, cell proliferation, and reactive oxygen species generation. Furthermore, P. gingivalis infection activated the hypoxia-inducible factor-1α signaling pathway, thus promoting HK2-mediated glycolysis and proinflammatory responses. CONCLUSIONS: HK2-mediated glycolysis promotes inflammatory responses in gingival tissues, and therefore glycolysis can be targeted in order to inhibit the progression of periodontal inflammation.

Ocular Drug Delivery: Advancements and Innovations.

Ocular drug delivery has been significantly advanced for not only pharmaceutical compounds, such as steroids, nonsteroidal anti-inflammatory drugs, immune modulators, antibiotics, and so forth, but also for the rapidly progressed gene therapy products. For conventional non-gene therapy drugs, appropriate surgical approaches and releasing systems are the main deliberation to achieve adequate treatment outcomes, whereas the scope of "drug delivery" for gene therapy drugs further expands to transgene construct optimization, vector selection, and vector engineering. The eye is the particularly well-suited organ as the gene therapy target, owing to multiple advantages. In this review, we will delve into three main aspects of ocular drug delivery for both conventional drugs and adeno-associated virus (AAV)-based gene therapy products: (1) the development of AAV vector systems for ocular gene therapy, (2) the innovative carriers of medication, and (3) administration routes progression.

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure-activity relationship, and mechanisms of action (2019-2021).

Cancer, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth, remains a prominent cause of death across the world. Almost all currently available anticancer agents used in clinical practice have developed multidrug resistance, creating an urgent need to develop novel chemotherapeutics. Benzimidazole derivatives could exert anticancer properties through diverse mechanisms, inclusive of the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, antiangiogenesis, and blockage of glucose transport. Moreover, several benzimidazole-based agents have already been approved for the treatment of cancers. Hence, benzimidazole derivatives are useful scaffolds for the development of novel anticancer agents. In particular, benzimidazole hybrids could exert dual or multiple antiproliferative activities and had the potential to overcome drug resistance, demonstrating the potential of benzimidazole hybrids as potential prototypes for clinical deployment in the control and eradication of cancers. The purpose of the present review article is to provide a comprehensive landscape of benzimidazole hybrids as potential anticancer agents, and the structure-activity relationship as well as mechanisms of action are also discussed to facilitate the further rational design of more effective candidates, covering articles published from 2019 to 2021.

Cinnamic acid hybrids as anticancer agents: A mini-review.

Cancer, as a long-lasting and dramatic disease, affects almost one-third of human beings globally. Chemotherapeutics play an important role in cancer treatment, but multidrug resistance and severe adverse effects have already become the main causes of failure in tumor chemotherapy. Therefore, it is an urgent need to develop novel chemotherapeutics. Cinnamic acid contains a ubiquitous α,ß-unsaturated acid moiety presenting potential therapeutic effects in the treatment of cancer as these derivatives could act on cancer cells by diverse mechanisms of action. Accordingly, cinnamic acid derivatives are critical scaffolds in discovering novel anticancer agents. This review provides a comprehensive overview of cinnamic acid hybrids as anticancer agents. The structure-activity relationship, as well as the mechanisms of action, are also discussed, covering articles published from 2012 to 2021.

Efficacious, safe, and stable inhibition of corneal neovascularization by AAV-vectored anti-VEGF therapeutics.

Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8-KH902 far exceeded that of rAAV2-KH902. A single-dose rAAV8-KH902 treatment at 8 × 108 genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10-14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8-KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV.

Periodontal treatment of furcation involvement at the mandibular first molar with a follow-up of 27 years.

Due to the complicated anatomical structures in the furcation area of multirooted mandibular first molars, dental hygiene is greatly compromised once the furcation is involved in the periodontitis, leading to the unfavorable prognosis of teeth with furcation involvement. A patient came to a dental office with the chief complaint of "mobile mandibular posterior tooth" 27 years ago. The periapical film showed alveolar bone resorption at the root furcation of the right mandibular first molar. Flap surgery and fine supportive therapy were conducted. The patient was diagnosed with "furcation involvement Class Ⅲ" during a revisit three years ago. Satisfactory and healthy periodontal statuses were observed 2, 9, 24, and 33 months after the periodontal flap surgery plus tunneling procedures. A follow-up of 27 years in the present case demonstrated that a favorable prognosis of furcation involvement can be achieved after adequate periodontal treatment.

Gingival fibroblasts dynamically reprogram cellular metabolism during infection of Porphyromonas gingivalis.

OBJECTIVE: The purpose of the present study was to explore the sequential changes in the cellular metabolism in gingival fibroblasts (GFs) in response toPorphyromonas gingvalis (P. gingivalis) ATCC33277 infection. DESIGN: GFs were treated withP. gingivalis at the MOI of 50 for 4, 24 and 48 h to mimic the early, medium, and late phase in the bacterial infection. LDH assay and cell counting kit-8 were utilized to explore cell death and proliferation. Real-time PCR was utilized to explore the gene transcription of pro-inflammatory genes. The relative levels of biomolecules in GFs were measured by gas chromatography-mass spectrometry. Principal component analysis and orthogonal partial least-squares-discriminant analysis were performed to visualize the metabolic difference among experimental groups. In addition, pathway analysis was conducted regarding differential metabolites in GFs. RESULTS: P. gingivalis infection triggered significant gene transcription of IL-1ß, IL 6, MCP 1, and MMP 1 in GFs. In addition, P. gingivalis stimulated cell proliferation of GFs at MOI of 10, 50 and 250. Moreover, P. gingivalis triggered significant cell death at higher MOI. 69, 173 and 148 metabolites were qualitatively detected at 4, 24 and 48 h after P. gingivalis infection respectively in GFs, showing a sequential change of different phase. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that ATP-binding cassette transporters, glutathione, purine and pyrimidine metabolism was significantly altered in different phase. CONCLUSIONS: Human GFs may sequentially rewire metabolomics to shape the inflammatory responses and support the proliferation of host cells during P. gingivalis infection.

COVID-19: the novel coronavirus disease and its manifestations and management in ophthalmology.

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.

Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase-HIF-1α axis.

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis.

HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration.

Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is considered a major cause of RPE dysfunction and senescence in age-related macular degeneration (AMD), and N-retinylidene-N-retinylethanolamine (A2E) is the main fluorophore identified in lipofuscin from aged human eyes. Here, human-induced pluripotent stem cell (iPSC)-RPE was generated from healthy individuals to reveal proteomic changes associated with A2E-related RPE cell senescence. A novel RPE cell senescence-related protein, high-mobility group box 1 (HMGB1), was identified based on proteomic mass spectrometry measurements on iPSC-RPE with A2E treatment. Furthermore, HMGB1 upregulated Caveolin-1, which also was related RPE cell senescence. To investigate whether changes in HMGB1 and Caveolin-1 expression under A2E exposure contribute to RPE cell senescence, human ARPE-19 cells were stimulated with A2E; expression of HMGB1, Caveolin-1, tight junction proteins and senescent phenotypes were verified. HMGB1 inhibition alleviated A2E induced cell senescence. Migration of RPE cells was evaluated. Notably, A2E less than or equal to 10µM induced both HMGB1 and Caveolin-1 protein upregulation and HMGB1 translocation, while Caveolin-1 expression was downregulated when there was more than 10µM A2E. Our data indicate that A2E-induced upregulation of HMGB1、Caveolin-1 and HMGB1 release may relate to RPE cell senescence and play a role in the pathogenesis of AMD.

A novel in situ bone elevation method to achieve vertical periodontal augmentation in dogs: A pilot study.

OBJECTIVES: The purpose of this study was to investigate whether a novel in situ interdental bone elevation method could achieve vertical bone augmentation around natural teeth. METHODS: Horizontal periodontal bone defects were created at nine quadrants of mandibles in five dogs. Six weeks later, one of the nine quadrants was randomly chosen as the model control. The remaining mandibles were allocated into two experimental groups: cortical bone removing (CBR) or interdental bone elevation (IBE). For the IBE group, four millimetres of interdental bone blocks were separated and elevated from the base of alveolar bone. Then bone xenografts were implanted beneath the elevated alveolar blocks. Animals were euthanised 12 weeks post-operation. Cone beam computed tomography (CBCT) examination and histological analysis were performed to evaluate the surgical outcomes. RESULTS: Enhanced soft tissue profiles were observed in the two experimental groups as compared to the model control group. CBCT images showed that the height of alveolar bone was significantly higher in the IBE group with bone blocks seated near the cementoenamel junction. Significantly larger area of bone tissues with the highest coronal level of new bone was observed in the IBE group. New bone was observed around the elevated bone blocks with bone remodelling and neovascularisation inside the elevated blocks. CONCLUSIONS: Vertical bone augmentation at interdental sites may be performed through in situ interdental bone elevation for patients with horizontal alveolar bone resorption.

Dual-Color imaging of nuclear division and mitotic spindle elongation in live cells of Aspergillus nidulans.

We have developed a dual-color imaging system based on cyan fluorescent protein-labeled histone H2A and green fluorescent protein-labeled alpha tubulin to visualize DNA and spindles simultaneously in the same living cell of Aspergillus nidulans. This system allows new details of mitosis and nuclear movement to be revealed.