Micro and nano plastics release from a single absorbable suture into simulated body fluid.

Synthetic polymers are widely used in medical devices and implants where biocompatibility and mechanical strength are key enablers of emerging technologies. One concern that has not been widely studied is the potential of their microplastics (MPs) release. Here we studied the levels of MP debris released following 8-week in vitro tests on three typical polyglycolic acid (PGA) based absorbable sutures (PGA 100, PGA 90 and PGA 75) and two nonabsorbable sutures (polypropylene-PP and polyamide-PA) in simulated body fluid. The MP release levels ranked from PGA 100 > > PGA 90 > PGA 75 > > PP ∼ PA. A typical PGA 100 suture released 0.63 ± 0.087 million micro (MPs > 1 µm) and 1.96 ± 0.04 million nano (NPs, 200-1000 nm) plastic particles per centimeter. In contrast, no MPs were released from the nonabsorbable sutures under the same conditions. PGA that was co-blended with 10-25% L-lactide or epsilon-caprolactone resulted in a two orders of magnitude lower level of MP release. These results underscore the need to assess the release of nano- and microplastics from medical polymers while applied in the human body and to evaluate possible risks to human health.

The association between plain water intake and periodontitis in the population aged over 45: a cross-sectional study based on NHANES 2009-2014.

BACKGROUND: Numerous studies have demonstrated the impact of beverage consumption on overall health and oral health. Specifically, high consumption of sugar-sweetened beverages and coffee has been associated with an increased risk of metabolic disorders and periodontitis. Conversely, high intake of plain water has been linked to various health benefits, including weight management and reduced energy intake. However, no previous studies have explored the potential association between plain water intake and the risk of periodontitis. OBJECTIVES: Our objective was to investigate the relationship between plain water consumption and periodontitis in a middle-aged and elderly population. METHODS: The present cross-sectional study was conducted among participants aged ≥ 45 in the 2009-2014 National Health and Nutrition Examination Surveys. Multivariable regression analysis, subgroup analysis and smooth fitting tests were conducted to explore the independent relationship between plain water intake and periodontitis. RESULTS: A total of 5,882 participants were enrolled,62.02% have periodontitis. Periodontitis patients have lower plain water intake. The multivariable regression tests showed that the risk of periodontitis decreased with increased plain water intake quartiles (Q4 OR = 0.78; 95%CI 0.62-0.96) after fully adjustment. Subgroup analysis and interaction tests showed that gender, age, smoking, diabetes, hypertension or BMI does not significantly interact with the association. However, the relation was significant in males (Q4 OR = 0.64; 95%CI 0.47-0.86) but not in females (Q4 OR = 0.97;95% CI 0.71-1.31). In the smoothed curve fits stratified by gender, the curve for male participants displayed as a U-shape, with an optimal plain water intake at 1200 ml/day. For males drinking plain water less than 1200 ml/day, the risk of periodontitis decreased by 24% with each increase of 500 ml plain water intake (OR = 0.76, 95%CI 0.66-0.87, p < 0.001). CONCLUSIONS: Together, the results showed that plain water intake is negatively associated with periodontitis risk in US middle aged and elderly population. Further studies are needed to investigate the mechanism unites this association. Attention should be given to adequate plain water intake when considering dietary suggestions to the population at high risk of developing periodontitis, especially for men.

Genome-wide identification of the melon (Cucumis melo L.) response regulator gene family and functional analysis of CmRR6 and CmPRR3 in response to cold stress.

The response regulator (RR) gene family play crucial roles in cytokinin signal transduction, plant development, and resistance to abiotic stress. However, there are no reports on the identification and functional characterization of RR genes in melon. In this study, a total of 18 CmRRs were identified and classified into type A, type B, and clock PRRs, based on phylogenetic analysis. Most of the CmRRs displayed tissue-specific expression patterns, and some were induced by cold stress according to two RNA-seq datasets. The expression patterns of CmRR2/6/11/15 and CmPRR2/3 under cold treatment were confirmed by qRT-PCR. Subcellular localization assays indicated that CmRR6 and CmPRR3 were primarily localized in the nucleus and chloroplast. Furthermore, when either CmRR6 or CmPRR3 were silenced using tobacco ringspot virus (TRSV), the cold tolerance of the virus-induced gene silencing (VIGS) melon plants were significantly enhanced, as evidenced by measurements of chlorophyll fluorescence, ion leakage, reactive oxygen, proline, and malondialdehyde levels. Additionally, the expression levels of CmCBF1, CmCBF2, and CmCBF3 were significantly increased in CmRR6-silenced and CmPRR3-silenced plants under cold treatment. Our findings suggest that CmRRs contribute to cold stress responses and provide new insights for further pursuing the molecular mechanisms underlying CmRRs-mediated cold tolerance in melon.

A Ubiquitin-Dependent Switch on MEF2D Senses Pro-Metastatic Niche Signals to Facilitate Intrahepatic Metastasis of Liver Cancer.

Effective treatment for metastasis, a leading cause of cancer-associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro-metastatic niche signals. Here, systemic motif-enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding ß1-integrin) and Itgb4 (coding ß4-integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps-DNA (NETs-DNA) for subsequent chemotaxis and colonization. In turn, an integrin-FAK circuit promotes a phosphorylation-dependent USP14-orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3-ubiquitin-ligase MDM2. Clinically, the USP14(pS432)-MEF2D-ITGB1/4 feedback loop is often hyper-active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination-dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro-metastatic integrin-FAK signaling. Disruption of this feedback loop is clinically applicable with fast-track potential to block microenvironmental cues driving metastasis.

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound transporters, key metabolic enzymes, and sensors such as mTOR and GCN2 play critical roles in controlling immune cell differentiation and function. As such, anti-cancer immune responses could be enhanced by supplement of specific essential amino acids, or targeting the metabolic enzymes or their sensors, thereby developing novel adjuvant immune therapeutic modalities. To further dissect metabolic regulation of anti-tumor immunity, this review summarizes the regulatory mechanisms governing reprogramming of amino acid metabolism and their effects on the phenotypes and functions of tumor-infiltrating immune cells to propose novel approaches that could be exploited to rewire amino acid metabolism and enhance cancer immunotherapy.

Alcohol Pretreatment to Eliminate the Interference of Micro Additive Particles in the Identification of Microplastics Using Raman Spectroscopy.

Raman spectroscopy is an indispensable tool in the analysis of microplastics smaller than 20 µm. However, due to its limitation, Raman spectroscopy may be incapable of effectively distinguishing microplastics from micro additive particles. To validate this hypothesis, we characterized and compared the Raman spectra of six typical slip additives with polyethylene and found that their hit quality index values (0.93-0.96) are much higher than the accepted threshold value (0.70) used to identify microplastics. To prevent this interference, a new protocol involving an alcohol treatment step was introduced to successfully eliminate additive particles and accurately identify microplastics. Tests using the new protocol showed that three typical plastic products (polyethylene pellets, polyethylene bottle caps, and polypropylene food containers) can simultaneously release microplastic-like additive particles and microplastics regardless of the plastic type, daily-use scenario, or service duration. Micro additive particles can also adsorb onto and modify the surfaces of microplastics in a manner that may potentially increase their health risks. This study not only reveals the hidden problem associated with the substantial interference of additive particles in microplastic detection but also provides a cost-effective method to eliminate this interference and a rigorous basis to quantify the risks associated with microplastic exposure.

Strong magnetic exchange coupling in a radical-bridged trinuclear nickel complex.

Reaction of 2,3,6,7,10,11-hexaaminotriphenylene hexahydrochloride (HATP·6HCl) and (TpPhNi)Cl (TpPh = tris(3,5-diphenyl-1-pyrazolyl)borate) produces the radical-bridged trinickel complex [(TpPhNi)3(HITP)] (HITP3-˙ = 2,3,6,7,10,11-hexaiminotriphenylene). Magnetic measurements and broken-symmetry density functional theory calculations reveal strong exchange coupling persisting at room temperature between HITP3-˙ and two of the three Ni2+ centers, a rare example of strong radical-mediated magnetic coupling in multimetallic complexes. These results demonstrate the potential of radical-bearing tritopic HITP ligands as building blocks for extended molecule-based magnetic materials.

Effect of lathyrol derivatives on non-small cell lung cancer and the possible mechanism. / 千金子二萜醇衍生物抗非小细胞肺癌的作用及机制.

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells. METHODS: Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, ß-catenin, and MMP2 in A549 cells, respectively. RESULTS: Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin ß1, MMP2, MMP9, ß-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, ß-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05). CONCLUSIONS: The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.

Sampling, Identification and Characterization of Microplastics Release from Polypropylene Baby Feeding Bottle during Daily Use.

Microplastics (MPs) are becoming a global concern due to the potential risk to human health. Case studies of plastic products (i.e., plastic single-use cups and kettles) indicate that MP release during daily use can be extremely high. Precisely determining the MP release level is a crucial step to identify and quantify the exposure source and assess/control the corresponding risks stemming from this exposure. Though protocols for measuring MP levels in marine or freshwater has been well developed, the conditions experienced by household plastic products can vary widely. Many plastic products are exposed to frequent high temperatures (up to 100 °C) and are cooled back to room temperature during daily use. It is therefore crucial to develop a sampling protocol that mimics the actual daily-use scenario for each particular product. This study focused on widely used polypropylene-based baby feeding bottles to develop a cost-effective protocol for MP release studies of many plastic products. The protocol developed here enables: 1) prevention of the potential contamination during sampling and detection; 2) realistic implementation of daily-use scenarios and accurate collection of the MPs released from baby feeding bottles based on WHO guidelines; and 3) cost-effective chemical determination and physical topography mapping of MPs released from baby feeding bottles. Based on this protocol, the recovery percentage using standard polystyrene MP (diameter of 2 µm) was 92.4-101.2% while the detected size was around 102.2% of the designed size. The protocol detailed here provides a reliable and cost-effective method for MP sample preparation and detection, which can substantially benefit future studies of MP release from plastic products.

Microplastic release from the degradation of polypropylene feeding bottles during infant formula preparation.

Polypropylene-based products are commonly used for food preparation and storage, but their capacity to release microplastics is poorly understood. We investigated the potential exposure of infants to microplastics from consuming formula prepared in polypropylene (PP) infant feeding bottles (IFBs). Here, we show that PP IFBs release microplastics with values as high as 16,200,000 particles per litre. Scenario studies showed that PP IFB sterilization and exposure to high-temperature water significantly increase microplastic release. A 21-d test of PP IFBs showed periodic fluctuations in microplastic release. To estimate the potential global exposure to infants up to 12 months old, we surveyed 48 regions, finding values ranging from 14,600-4,550,000 particles per capita per day, depending on the region. We demonstrate that infant exposure to microplastics is higher than was previously recognized due to the prevalence of PP-based products used in formula preparation and highlight an urgent need to assess whether exposure to microplastics at these levels poses a risk to infant health.

Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

BACKGROUND: Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//ß-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/ß-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. METHODS: In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. RESULTS: Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/ß-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/ß-catenin signaling. The P1427Q mutation dramatically increased WNT/ß-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. CONCLUSION: Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/ß-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research 110:63-71, 2018. © 2017 Wiley Periodicals, Inc.

The effect of semaphorin 3A on fracture healing in osteoporotic rats.

BACKGROUNDS: Semaphorin 3A (Sema3A) was demonstrated to exert an osteoprotective effect by both inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation. The effect of Sema3A on fracture healing of osteoporotic rats was investigated in this study. METHODS: Twelve weeks after bilateral ovariectomy, all animals underwent unilateral transverse osteotomy on the proximal tibiae, and were then randomly divided into two groups. Rats received vehicle (control) or weekly local injection of Sema3A (500 µg/kg) into the injury site (group Sema3A) after fracture surgery until sacrifice at 4 and 8 weeks. Specimens were harvested and examined by radiography, iDXA, histology, micro-CT, and three-point bending test. RESULTS: Compared to control, Sema3A treatment significantly increased bone mineral density, percent bone volume and biomechanical strength of the callus at 4 and 8 weeks post-fracture. At 8 weeks after fracture, the bone volume of callus showed no difference between groups, while the average cross-sectional area of callus in the control group was 43.8 % higher than that of Sema3A group. Histological images showed increased callus formation at 4 weeks post-fracture and better callus ossification in the Sema3A group, while callus remodeling in the control group seemed to be delayed and not well bridged. CONCLUSIONS: Results in this study indicated that Sema3A treatment increased callus volume and density at 4 weeks post-fracture, and induced promoted callus ossification and remodeling at 8 weeks post-fracture compared to control.