ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis.

Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3ß/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.

Diallyl Trisulfide Acts as a Soil Disinfestation Against the Ilyonectria destructans through Inducing the Burst of Reactive Oxygen Species.

Soil-borne diseases represent an impediment to the sustainable development of agriculture. A soil-borne disease caused by Ilyonectria destructans severely impacts Panax species, and soil disinfestation has proven to be an effective management approach. Here, diallyl trisulfide (DATS), derived from garlic, exhibited pronounced inhibitory effects on the growth of I. destructans in vitro tests and contributed to the alleviation of soil-borne diseases in the field. A comprehensive analysis demonstrated that DATS inhibits the growth of I. destructans by activating detoxifying enzymes, such as GSTs, disrupting the equilibrium of redox reactions. A series of antioxidant amino acids were suppressed by DATS. Particularly noteworthy is the substantial depletion of glutathione by DATS, resulting in the accumulation of ROS, ultimately culminating in the inhibition of I. destructans growth. Briefly, DATS could effectively suppress soil-borne diseases by inhibiting pathogen growth through the activation of ROS, and it holds promise as a potential environmentally friendly soil disinfestation.

Preparation, characterization of basil essential oil liposomes unidirectional single-conducting water sustained-release pads and their preservation properties to Lateolabrax japonicus fillets.

The juice exudation of aquatic products oozes out during storage can influence storage quality. Herein, a novel basil essential oil liposome unidirectional water-conducting sustained-release preservation pads (BEOL/UCSP) were prepared with nylon mesh as water-conducting layer, basil essential oil liposome (BEOL) as sustained-release preservation layer, and diatomite and absorbent-cotton as water-absorbing layer. EL/UCSP, ß-CL/UCSP, and BEO/UCSP were prepared after BEOL was replaced by eugenol liposome, ß-caryophyllene liposome, and BEO. BEOL are microspheres with bilayer structure, had good storage stability, centrifugal stability, thermal stability, embedding capacity, sustained-release, and oxidation resistance, and the main components of preservatives had a synergistic effect on antibacterial properties. The pads without preservative can initially slow down quality deterioration. BEOL/UCSP can directionally absorb exudate and realize long-term sustained-release of preservative, has excellent antibacterial and antioxidant effect, and extended shelf life of Lateolabrax japonicus fillets from 6.0 days to 12.8 days. The BEOL/UCSP can provide technical theoretical support for preservation materials.

A Novel Fluorescence Sensor for Iodide Detection Based on the 1,3-Diaryl Pyrazole Unit with AIE and Mechanochromic Fluorescence Behavior.

A D-A type of luminophore, TPA-CDP, was designed and synthesized by using triphenylamine (TPA) as D (electron donor), 1,3-diaryl pyrazole with cyano groups (CDP) as A (electron acceptor) and employing a cyanovinyl segment as a recognition group. Firstly, TPA-CDP demonstrates effective fluorescence quenching as a sensor for I- by the nucleophilic addition reaction of the cyanovinyl segment with a high level of sensitivity, selectivity and a low determination limit of 4.43 µM. Interestingly, TPA-CDP exhibited an AIE phenomenon with the fw value reaching 50%. In addition, TPA-CDP displayed distinct mechanochromic fluorescence behavior with 70 nm red shift, which was observed over four repeated cycles. Furthermore, the mechanochromic fluorescence behavior of TPA-CDP, as observed in powder XRD experiments, was found to be associated with the morphological transition from a crystalline state to an amorphous state. These results confirm the significant potential of CDP as a powerful electron-deficient component in the creation of D-A-type mechanochromic fluorescence materials and biosensors for detecting I-.

Functionalized Metal-Organic Framework-Modified Hydrogel That Breaks the Vicious Cycle of Inflammation and ROS for Repairing of Diabetic Bone Defects.

The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during bone regeneration period. These two effects reinforce one another and create an endless loop that is also accompanied by mitochondrial dysfunction. However, there is still no effective and inclusive method targeting at the two aspects and breaking the vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel that is capable of releasing metformin and Zn elements are constructed. This hydrogel treats hyperglycemia while also controlling mitochondrial function, reducing inflammation, and restoring homeostasis. In addition, the synergetic effect from metformin and Zn ions inhibits ROS-inflammation cascade generation and destroys the continuous progress by taking effects in both ROS and inflammation and further keeping organelles' homeostasis. Furthermore, with the recovery of mitochondria and breakdown of the ROS-inflammation cascade cycle, osteogenesis under a diabetic microenvironment is enhanced in vivo and in vitro. In conclusion, the study provides critical insight into the biological mechanism and potential therapy for diabetic bone regeneration.

Inhibition of ACSF2 protects against renal ischemia/reperfusion injury via mediating mitophagy in proximal tubular cells.

Acute kidney injury (AKI) is a prevalent clinical condition caused by sepsis and ischemia reperfusion (IR) injury. The principal driver of IR-induced AKI involves renal tubular structural changes triggered by the impairment of function in renal tubular cells. The target gene, Acyl-CoA Synthetase Family Member 2 (ACSF2), was retrieved from the GEO database based on high specific expression in renal tubular cells and location in mitochondria. Here, we substantiate that ACSF2 is specifically localized in the mitochondria of the renal tubular epithelium. Functionally silencing ACSF2 in HK2 cells enhanced hypoxia-reoxygenation (HR)-induced mitophagy, restored mitochondrial function and decreased the production of mitochondrial superoxide. Our study demonstrated that these effects were reversed by silencing Bcl-2 19-kDa interacting protein 3 (BNIP3), a receptor regulating mitophagy. In vivo, ACSF2 knockdown significantly enhanced IR-induced mitophagy and improved renal function in mice with IR injury. Conversely, BNIP3 knockdown inhibited mitophagy and exacerbated renal damage in ACSF2-knockdown mice with IR injury. In conclusion, our study demonstrated that inhibition of ACSF2 enhances mitophagy, restoring mitochondrial function and protects against IR-induced AKI, providing a new target and potential strategy for therapy.

A sustained-release PDGF-BB nanocomposite hydrogel for DM-associated bone regeneration.

Regeneration of bone tissue in the environment of diabetes mellitus (DM) remains one of the clinical challenges, with malfunction of stem cells in a high-glucose microenvironment being the primary obstacle. We designed an injectable sustained-release PDGF-BB nanocomposite hydrogel. PDGF-BB, a star molecule for treating various complications of DM, was used for the first time for DM-associated bone regeneration, and we showed that it restored stem cell proliferation and migration and facilitated osteogenesis inhibition under high glucose stimulation by activating ERK and AKT pathways. To address the requirements for continuous PDGF-BB release in GelMA while also increasing mechanical strength, nanoclay LAPONITE® was added, which may still exhibit pro-osteogenic activity in diabetic environments by releasing bioactive ions (Si4+, Mg2+, and Li+). This injectable hydrogel heals calvarial lesions successfully in diabetic rats and has the potential to be used as a direct and effective tool for treating diabetic patients.

Comparison of the Three Sets of Diagnostic Criteria for Vogt-Koyanagi-Harada Disease in Southeast China - A Retrospective Case-Control Study.

PURPOSE: To compare the utility of the Chinese diagnostic criteria for Vogt-Koyanagi-Harada (VKH) disease (CDCV), the revised diagnostic criteria (RDC) and the classification criteria by SUN (SUN-C). METHODS: Two groups of patients (VKH group and non-VKH group) were assessed in this retrospective case-control study. Sensitivity, specificity and area under receiver operating characteristic curve (AUC) were evaluated among these criteria. RESULTS: 258 patients were included after propensity score matching. The sensitivities were 92.2% in CDCV, 66.7% in RDC, and 54.3% in SUN-C. In different disease stages (early and late), similar sensitivity results were observed. The specificities were 96.1% in CDCV, 97.7% in RDC, and 99.2% in SUN-C. The AUCs were 0.942 in CDCV, 0.822 in RDC and 0.767 in SUN-C. CONCLUSION: A higher sensitivity value and larger AUC in CDCV were found. CDCV are highly useful in the diagnosis and classification of VKH disease in Chinese patients.

Regenerative Peripheral Nerve Interfaces Effectively Prevent Neuroma Formation After Sciatic Nerve Transection in Rats.

Objective: The disordered growth of nerve stumps after amputation leading to the formation of neuromas is an important cause of postoperative pain in amputees. This severely affects the patients' quality of life. Regenerative peripheral nerve interfaces (RPNIs) are an emerging method for neuroma prevention, but its postoperative nerve growth and pathological changes are yet to be studied. Methods: The rat sciatic nerve transection model was used to study the effectiveness of RPNI in this experiment. The RPNI (experimental) group (n = 11) underwent RPNI implantation after sciatic nerve transection, while the control group (n = 11) only underwent sciatic nerve transection. Autotomy behavior, ultrasonography, and histopathology were observed for 2 months postoperatively. Results: Compared to the control group, the incidence and size of the neuromas formed and the incidence and extent of autotomy were significantly reduced in the RPNI group. The axon density in the stump and degree of stump fibrosis were also significantly reduced in the RPNI group. Conclusion: RPNI effectively prevented the formation of neuromas.

Contrast Sensitivity Deficits and Its Structural Correlates in Fuchs Uveitis Syndrome.

Purpose: To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure. Methods: In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE). Results: The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes. Conclusions: We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.

Antimicrobial Terpenes Suppressed the Infection Process of Phytophthora in Fennel-Pepper Intercropping System.

The interactions between non-host roots and pathogens may be key to the inhibition of soilborne pathogens in intercropping systems. Fennel (Foeniculum vulgare) can be intercropped with a wide range of other plants to inhibit soilborne pathogens in biodiversity cultivation. However, the key compounds of fennel root exudates involved in the interactions between fennel roots and pathogens are still unknown. Here, a greenhouse experiment confirmed that intercropping with fennel suppressed pepper (Capsicum annuum) blight disease caused by Phytophthora capsici. Experimentally, the roots and root exudates of fennel can effectively interfere with the infection process of P. capsici at rhizosphere soil concentrations by attracting zoospores and inhibiting the motility of the zoospores and germination of the cystospores. Five terpene compounds (D-limonene, estragole, anethole, gamma-terpenes, and beta-myrcene) that were identified in the fennel rhizosphere soil and root exudates were found to interfere with P. capsica infection. D-limonene was associated with positive chemotaxis with zoospores, and a mixture of the five terpene compounds showed a strong synergistic effect on the infection process of P. capsici, especially for zoospore rupture. Furthermore, the five terpene compounds can induce the accumulation of reactive oxygen species (ROS), especially anethole, in hyphae. ROS accumulation may be one of the antimicrobial mechanisms of terpene compounds. Above all, we proposed that terpene compounds secreted from fennel root play a key role in Phytophthora disease suppression in this intercropping system.

Application of the Adverse Outcome Pathway Concept to In Vitro Nephrotoxicity Assessment: Kidney Injury due to Receptor-Mediated Endocytosis and Lysosomal Overload as a Case Study.

Application of adverse outcome pathways (AOP) and integration of quantitative in vitro to in vivo extrapolation (QIVIVE) may support the paradigm shift in toxicity testing to move from apical endpoints in test animals to more mechanism-based in vitro assays. Here, we developed an AOP of proximal tubule injury linking a molecular initiating event (MIE) to a cascade of key events (KEs) leading to lysosomal overload and ultimately to cell death. This AOP was used as a case study to adopt the AOP concept for systemic toxicity testing and risk assessment based on in vitro data. In this AOP, nephrotoxicity is thought to result from receptor-mediated endocytosis (MIE) of the chemical stressor, disturbance of lysosomal function (KE1), and lysosomal disruption (KE2) associated with release of reactive oxygen species and cytotoxic lysosomal enzymes that induce cell death (KE3). Based on this mechanistic framework, in vitro readouts reflecting each KE were identified. Utilizing polymyxin antibiotics as chemical stressors for this AOP, the dose-response for each in vitro endpoint was recorded in proximal tubule cells from rat (NRK-52E) and human (RPTEC/TERT1) in order to (1) experimentally support the sequence of key events (KEs), to (2) establish quantitative relationships between KEs as a basis for prediction of downstream KEs based on in vitro data reflecting early KEs and to (3) derive suitable in vitro points of departure for human risk assessment. Time-resolved analysis was used to support the temporal sequence of events within this AOP. Quantitative response-response relationships between KEs established from in vitro data on polymyxin B were successfully used to predict in vitro toxicity of other polymyxin derivatives. Finally, a physiologically based kinetic (PBK) model was utilized to transform in vitro effect concentrations to a human equivalent dose for polymyxin B. The predicted in vivo effective doses were in the range of therapeutic doses known to be associated with a risk for nephrotoxicity. Taken together, these data provide proof-of-concept for the feasibility of in vitro based risk assessment through integration of mechanistic endpoints and reverse toxicokinetic modelling.

Allyl Isothiocyanate in the Volatiles of Brassica juncea Inhibits the Growth of Root Rot Pathogens of Panax notoginseng by Inducing the Accumulation of ROS.

The cultivation of Panax notoginseng is often seriously hindered by root rot disease caused by the accumulation of soil-borne pathogens. Here, the inhibitory activity of Brassica juncea volatiles on P. notoginseng root rot pathogens was assessed and compounds in volatiles were identified. Furthermore, the antimicrobial activity and mechanism of allyl isothiocyanate (AITC) were deciphered by integrated transcriptome and metabolome analyses. The volatiles of B. juncea showed dose-dependent antimicrobial activity against root rot pathogens. AITC, identified as the main volatile compound, not only significantly inhibited pathogen growth in vitro but also suppressed root rot disease in the field. Integrated transcriptomic and metabolomics analysis revealed that AITC inhibited Fusarium solani by interfering with energy production and induced the accumulation of ROS by decreasing the content of glutathione (GSH). In summary, B. juncea releases AITC to inhibit soil-borne pathogens and could be used as a rotation crop or soil fumigant to alleviate root rot disease.

[Clinical Characteristics, Prognostic Factors and Misdiagnosis of Bone Marrow Necrosis Patients].

OBJECTIVE: To analyze the clinical characteristics, diagnosis and prognostic factors of bone marrow necrosis (BMN) patients, aim to avoid misdiagnosis, missed diagnosis or delayed treatment. METHODS: The clinical data of 51 BMN patients treated in the Affiliated Hospital of Xuzhou Medical University from January 2010 to December 2017 were retrospectively analyzed. The types of primary disease, etiology, clinical manifestations, laboratory tests, radiological findings, treatment outcomes and prognostic factors were summrized, and the reasons for misdiagnosis were analyzed. RESULTS: Among 51 BMN patients, the hematologic tumor was detected out in 32 patients; solid tumors caused- BMN was detected out in 14 patients, benign lesions for 5 patients. The time of interval from the appearance of symptoms to the confirmation of BMN was 7 days to 6 months, with a median of 35 days. Misdiagnosis and missed diagnosis occurred in 25.5% of the BMN patients. Anemia was found in all of the 51 BMN patients, fever accounted for 58.8%, systemic bone pain for 52.9%, bleeding for 29.4%, lymphadenectasis for 37.3%, and hepatosplenomegaly for 19.6%. Leukoerythroblastic anemia accounted for 84.3%, bicytopenia for 51.0%, pancytopenia for 25.5%, and monocytopenia for 23.5%. The serologic test revealed no specific results. The first bone marrow aspiration were 38 patients and multi-site puncture were 7 patients. The diagnostic coincidence rate of bone marrow smear was 88.2%. Among 51 BMN patients, 41 patients received bone marrow biopsy, and the diagnostic coincidence rate of bone marrow biopsy was 75.6%. The abnormal signals were found in multiple vertebral bodies by spinal/pelvic MRI scan in 13 BMN patients; PET-CT scan revealed a diffuse pattern of low FDG uptake in the bone marrow in 16 patients, with a local increase in FDG uptake accompanied by bone marrow involvement. For 46 patients with BMN combined with malignancies, among which 35 patients died (76.1%) and the median survival time was 25 days. Among the 32 patients with hematologic tumors, early death occurred in 12 patients, BMN disappeared in 11 out of 20 patients received active chemotherapy for the primary disease, 9 patients died within 1 week to 3 months. Fourteen patients combined with bone marrow metastatic carcinoma died within 2 weeks to 3 months. Focal necrosis disappeared in 4 out of 5 BMN patients secondary to non-malignant diseases after symptomatic supportive treatment and still alived. Multiple logistic regression was performed to analyze factors affecting the prognosis of BMN patients, the result showed that the prognosis of BMN was closely related to the factors of primary disease (benign and malignant). The reasons for misdiagnosis and missed diagnosis were as follows: hidden onset of the primary disease, nonspecific symptoms, insufficient understanding and alertness of the physicians regarding the primary clinical characteristics and hematological abnormalities, and failure to receive multiple sites bone marrow punctures or bone marrow biopsies. CONCLUSION: BMN usually occurs concomitantly to hematologic tumors and bone marrow metastases from solid tumors. Its prognosis is closely related to the nature and severity of the primary disease and its own severity. In the clinic, BMN should be suspected in patients with severe bone pain, fever, hepatosplenomegaly, hemocytopenia, lymphadenectasis and leukoerythroblastic anemia. Bone marrow puncture at multiple positions and bone marrow biopsy can compensate for each other in the diagnosis of BMN. The combined use of the two methods can improve the diagnostic coincidence rate of BMN, and the positive rate of the etiological diagnosis of BMN.

Carbamylated erythropoietin regulates immune responses and promotes long-term kidney allograft survival through activation of PI3K/AKT signaling.

Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival. To determine mechanisms by which a nonhematopoietic erythropoietin (EPO) derivative, carbamylated EPO (CEPO), regulates innate and adaptive immune cells and affects renal allograft survival, we utilized a rat model of fully MHC-mismatched kidney transplantation. CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group. This therapeutic effect was inhibited when the recipients were given LY294002, a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or anti-EPO receptor (EPOR) antibody, in addition to CEPO. In vitro, CEPO inhibited the differentiation and function of dendritic cells and modulated their production of pro-inflammatory and anti-inflammatory cytokines, along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells. Moreover, after CD4+ T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell (Treg)/Th17 ratio increased. These effects were abolished by LY294002 or anti-EPOR antibody, suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner. The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.

Inhibitory mechanism of 6-Pentyl-2H-pyran-2-one secreted by Trichoderma atroviride T2 against Cylindrocarpon destructans.

Root rot caused by Cylindrocarpon destructans is one of the most devastating diseases of Panax notoginseng, and Trichoderma species are potential agents for the biocontrol of fungal diseases. Thus, we screened a total of 10 Trichoderma isolates against C. destructans and selected Trichoderma atroviride T2 as an antagonistic strain for further research. 6-Pentyl-2H-pyran-2-one (6PP) was identified as an important active metabolite in the fermentation broth of the strain and exhibited antifungal activity against C. destructans. Transcriptome and metabolome analyses showed that 6PP significantly disturbed the metabolic homeostasis of C. destructans, particularly the metabolism of amino acids. By constructing a gene coexpression network, ECHS1 was identified as the hub gene correlated with 6PP stress. 6PP significantly downregulated the expression of ECHS1 at the transcriptional level and combined with the ECHS1 protein. Autophagy occurred in C. destructans cells under 6PP stress. In conclusion, 6PP may induce autophagy in C. destructans by downregulating ECHS1 at the transcriptional level and inhibiting ECHS1 protein activity. 6PP is a potential candidate for the development of new fungicides against C. destructans.

Alveolar Bone Loss, Tooth Loss and Oral Cancer Mortality in Older Patients: A Retrospective Cohort Study.

PURPOSE: There has been growing interest in the association between periodontitis and systemic disease. In recent years, however, inconsistent results have also been found by case-control studies for the role of periodontitis in the development of oral cancer. This study aimed to examine whether periodontitis was an independent risk factor for oral cancer with a ≥75-year age group cohort. MATERIALS AND METHODS: Between January 2010 and December 2014, 1385 patients aged ≥75 years who underwent radiographic examination were included in this retrospective cohort study. We collected demographic information and comorbid health conditions from local health authorities. Participants were followed up until either the occurrence of mortality, or the end of the study on December 31, 2018. Cox proportional hazards regression and competing risk hazard models were used to examine the association between periodontitis and oral cancer mortality. RESULTS: Periodontitis and loss of teeth were significantly associated with oral cancer mortality. Compared to oral cancer mortality in healthy subjects, the HR and 95% CI in patients with mild, moderate, and severe periodontitis were 4.46 (0.94-21.06), 5.16 (1.14-23.39), and 6.65 (1.51-29.36), respectively. The HR (95% CI) was 1.05 (1.01-1.09) for tooth loss after controlling for potential confounding factors. All the increases in risk persisted in patients aged ≥80 years. CONCLUSION: The present study provides substantial evidence that poor periodontal health is associated with oral cancer mortality. It is necessary to underline the importance of considering periodontitis in the prevention of oral cancer, particularly in the older patients.

Phenolic Acids Released in Maize Rhizosphere During Maize-Soybean Intercropping Inhibit Phytophthora Blight of Soybean.

Interspecies interactions play a key role in soil-borne disease suppression in intercropping systems. However, there are limited data on the underlying mechanisms of soil-borne Phytophthora disease suppression. Here, a field experiment confirmed the effects of maize and soybean intercropping on Phytophthora blight of soybean caused by Phytophthora sojae. Experimentally, the roots and root exudates of maize were found to attract P. sojae zoospores and inhibit their motility and the germination of cystospores. Furthermore, five phenolic acids (p-coumaric acid, cinnamic acid, p-hydroxybenzoic acid, vanillic acid, and ferulic acid) that were consistently identified in the root exudates and rhizosphere soil of maize were found to interfere with the infection behavior of P. sojae. Among them, cinnamic acid was associated with significant chemotaxis in zoospores, and p-coumaric acid and cinnamic acid showed strong antimicrobial activity against P. sojae. However, in the rhizosphere soil of soybean, only p-hydroxybenzoic acid, low concentrations of vanillic acid, and ferulic acid were identified. Importantly, the coexistence of five phenolic acids in the maize rhizosphere compared with three phenolic acids in the soybean rhizosphere showed strong synergistic antimicrobial activity against the infection behavior of P. sojae. In summary, the types and concentrations of phenolic acids in maize and soybean rhizosphere soils were found to be crucial factors for Phytophthora disease suppression in this intercropping system.

Microfluidic chip for culturing intestinal epithelial cell layers: Characterization and comparison of drug transport between dynamic and static models.

Dynamic flow in vitro models are currently widely explored for their applicability in drug development research. The application of gut-on-chip models in toxicology is lagging behind. Here we report the application of a gut-on-chip model for biokinetic studies and compare the observed biokinetics of reference compounds with those obtained using a conventional static in vitro model. Intestinal epithelial Caco-2 cells were cultured on a porous membrane assembled between two glass flow chambers for the dynamic model, or on a porous membrane in a Transwell model. Confocal microscopy, lucifer yellow translocation, and alkaline phosphatase activity evaluation revealed that cells cultured in the gut-on-chip model formed tight, differentiated, polarized monolayers like in the static cultures. In the dynamic gut-on-chip model the transport of the high permeability compounds antipyrine, ketoprofen and digoxin was lower (i.e. 4.2-, 2.7- and 1.9-fold respectively) compared to the transport in the static Transwell model. The transport of the low permeability compound, amoxicillin, was similar in both the dynamic and static in vitro model. The obtained transport values of the compounds are in line with the compound Biopharmaceuticals Classification System. It is concluded that the gut-on-chip provides an adequate model for transport studies of chemicals.

Periodontitis increases the risk of respiratory disease mortality in older patients.

Evidence for an association between periodontitis and respiratory disease in the older patients is limited. Additionally, little information exists regarding the role of potential effect modifiers. The aim of this study is to examine whether periodontitis increases the risk of respiratory disease mortality in older patients. Between January 2010 and December 2014, 1385 patients aged 75 years and above who underwent radiographic examination in the largest dental hospital in Shanghai, China were included in this retrospective cohort study. The dental examination was made with the panoramic radiographs. Demographic information and comorbid health conditions were collected from local health authorities. Participant follow up was continued until either the occurrence of mortality, or the end of the study on December 31, 2018. Cox proportional hazards regression and competing risk hazard models were performed to examine the association between periodontitis and respiratory disease mortality. We found that periodontitis was associated with total respiratory disease mortality. Compared with healthy participants, the hazards ratio and 95% confidence interval for total respiratory disease mortality in patients with severe periodontitis was 2.72(1.04,7.11) after adjusting for relevant confounding variables. With increasing severity of periodontitis, risks for chronic obstructive pulmonary disease (COPD) mortality also increased significantly (P = .038). Smokers and participants with body mass index (BMI) < 25 kg/m2 were at increased risk. Loss of teeth was not associated with either total respiratory disease or COPD mortality. Although the present study cannot ascertain causal association, it provides substantial evidence that poor periodontal health is associated with respiratory disease in the older patients, particularly in smokers and patients with BMI < 25 kg/m2.